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1
Burmistrova, A. L., M. N. Vavilov, D. S. Stashkevich, and T. A. Suslova. "Immunogenetic profile of MIC (A, B) HLA loci linked to MHC antigenic complex in Russians of the Chelyabinsk Region." Medical Immunology (Russia) 24, no. 1 (March 10, 2022): 41–52. http://dx.doi.org/10.15789/1563-0625-ipo-2324.
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The MIC genes are located on chromosome 6 in the class I major histocompatibility complex (MHC) region and encode a membrane-bound stress-inducible protein that acts as a ligand to stimulate the NKG2D activating receptor expressed on the surface of the most natural killer cells (NK). Currently, 7 MIC loci are known, of which only MICA and MICB encode proteins and show a significant allelic polymorphism. The MIC gene polymorphism and their location in the HLA region suggests presence of some ethnic and populational differences for the gene frequencies, linkage disequilibrium of distinct loci, and distribution of HLA-MIC haplotypes, thus making it possible to get information on genetic relationship of human populations. The aim of our study was to assess immunogenetic profile of Russian population in Chelyabinsk Region based on the non-classical HLA loci, i.e., MICA and MICB, in the context of worldwide population data. Methods of the study included immunogenetic typing of 100 donors identifying themselves as Russians, taken from the Registry of Stem Cell Donors at the Chelyabinsk Regional Blood Transfusion Station. The 2 loci (MICA and MICB) were typed at basic resolution, using PCR technique with sequence-specific primers (SSP-PCR). Gene frequencies (GF) were calculated using programs for immunogenetic research (Arlequin 3.5).Among Russian population from Chelyabinsk Region, the following characteristics of the MICA gene distributions were found: MICA *008, *002, *010, *009, frequency of > 7%; average frequencies, for MICA *004, *007, *018, *017; whereas MICA *027, *011, *006, *009:02, *049, *012, *016 was registered at a frequency of < 3.5%. MICB gene profile was as follows: MICB *005:02, *004, *002, *008 at a frequency of > 6%; at a frequency of 4% MICB *003, *005:03; MICB *005:01, * 005:04, * 009N, MICB *013, *014 at a frequency of0.5%. As based on calculated genetic distances (according to Ney) for the MICA locus, the dendrogram and scatter plot were designed by means of multidimensional scaling (MDS) method, presenting location of 30 world populations, including data on Russians in Chelyabinsk Region. The smallest genetic distances between the population of Russians from Chelyabinsk Region and other world populations were found between the population of Slovenia, as well as the USA population of European origin. As based on scatterplot obtained by the MDS approach for MICA gene frequencies, using the data of cluster analysis, we have found that the population of Russians from Chelyabinsk Region belongs to a cluster of typical European populations.The obtained patterns could be used for practical purposes to create a registry of stem cell donors in Russia. In addition, the data may be used as a control group for further research in the area of HLA-disease association, and could be also demanded by the specialists in population ethnogenesis.
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Tsimberidou, A. M., C. Tam, W. Wierda, S. O' Brien, S. Lerner, and M. J. Keating. "Beta-2 microglobulin (B2M) is an independent prognostic factor for clinical outcomes in patients with CLL treated with frontline fludarabine, cyclophosphamide, and rituximab (FCR) regardless of age, creatinine clearance (CrCl)." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 7034. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.7034.
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7034 Introduction: High β2M levels are a risk factor in CLL. PCR therapy has been reported to be better tolerated than FCR in older or with decrease renal function pts (Shanafelt, Blood 108:15a). We assessed the association between age, CrCl, PS, β2M and outcomes in pts treated with FCR. Methods: From 7/99 to 1/04, 300 pts received rituximab 375 mg/m2 D1; fludarabine 25 mg/m2/d D2–3; and cyclophosphamide 250 mg/m2/d D2–3. Serum β2M levels were measured by radioimmunoassay. CrCl was calculated (Cockcroft-Gault equation). Results: The median age was 57 yrs (≥70, 14%). Age ≥70 was associated with fewer FCR courses (p<.0001); lower rates of CR (p=.001), overall response (OR; p=.04), survival (OS; p<.0001), and FFS (p=.008); and higher rates of G3–4 thrombopenia (p<.0001) or anemia (p=.002) compared with age<70. The median CrCl was 90 mL/min (CrCl <70, 27%). Pts with CrCl <70 had higher rates of G3–4 thrombopenia (p=.006) or anemia (p=.01) than others. There were no differences between the 2 groups in the other outcomes. PS was 0 in 40%, 1 in 57%, and 2 in 3% of pts. Better PS was associated with higher rates of CR (p=.007) and FFS (p=.02) but did not affect OR or OS. The median β2M level was 3.7 mg/L (β2M ≥ 4, 43%). The rates of CR, survival, and FFS were lower in pts with β2M ≥ 4 compared with others (p<.0001 each). High β2M levels were associated with older age, lower CrCl levels, poorer PS (p<.0001 each), higher rates of G3–4 neutropenia (p=.005), thrombocytopenia (p=.01), and infections (p=.03), and fewer FCR courses (p=.004). The median follow-up was 5 yrs. The rates of CR, 3-yr OS and 3-yr FFS were 72%, 87% and 76%, respectively. Independent factors predicting response were lower β2M (p=.0004) and lower WBC counts (p=.02). Independent factors predicting longer OS were younger age (p=.001), lower β2M (p=.003) and lower WBC (p=.03). Independent factors predicting longer FFS were lower β2M levels (p=.0006), and lower WBC counts (p=.005). Conclusion: Age ≥70 yrs and poor PS, but not CrCl level were associated with poor clinical outcomes. High β2M levels are an independent adverse prognostic factor for CR, OS, and FFS in the context of other prognostic factors. No significant financial relationships to disclose.
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Beltrame, André B., and Sérgio Florentino Pascholati. "Cianobactérias e algas reduzem os sintomas causados por Tobacco vosaic virus (tmv) em plantas de fumo." Summa Phytopathologica 37, no. 2 (June 2011): 140–45. http://dx.doi.org/10.1590/s0100-54052011000200010.
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As algas e as cianobactérias produzem uma grande diversidade de compostos com atividade biológica direta sobre microrganismos ou agem como ativadores de mecanismos de resistência em plantas. Em vista disso, foi investigada a manifestação dos sintomas causados pelo Tobacco mosaic virus (TMV) em plantas de fumo previamente tratadas com cianobactérias ou algas. Quando as folhas plantas de fumo foram tratadas dois dias antes da inoculação, foi verificado que suspensões de células dos isolados de cianobactérias 004/02, 008/02, Anabaena sp. e Nostoc sp. 61; e do isolado de alga 061/02, bem como as preparações do conteúdo intracelular do isolado 004/02 (4 C) e do filtrado do meio de cultivo do isolado 061/02 (61 M) apresentaram efeito na redução do número de lesões locais provocadas por TMV em folhas de plantas fumo, cultivar TNN. Além disso, foi observado que os isolados Anabaena sp., Nostoc sp. 21 (cianobactéria), Nostoc sp. 61 e 090/02 (alga) mostraram efeito direto sobre o vírus semi-purificado. Em vista disso, pode-se sugerir que os isolados estudados sintetizam compostos que agem diretamente sobre o TMV e/ou ativam o mecanismo de defesa de plantas contra fitopatógenos.
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Finkenstedt, Gerd, Rudolf W. Gasser, Günter Höfle, Christine Watfah, and Leo Fridrich. "Effects of growth hormone (GH) replacement on bone metabolism and mineral density in adult onset of GH deficiency: results of a double-blind placebo-controlled study with open follow-up." European Journal of Endocrinology 136, no. 3 (March 1997): 282–89. http://dx.doi.org/10.1530/eje.0.1360282.
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Abstract It is known that GH stimulates bone turnover and that GH-deficient adults have a lower bone mass than healthy controls. In order to evaluate the influences of GH replacement therapy on markers of bone turnover and on bone mineral density (BMD) in patients with adult onset GH deficiency, a doubleblind placebo-controlled study of treatment with recombinant human GH (rhGH; mean dose 2·4 IU daily) in 20 patients for 6 months and an extended open study of 6 to 12 months were conducted. Eighteen patients, fourteen men and four women, with a mean age of 44 years with adult onset GH deficiency were evaluated in the study. Compared with placebo, after 6 months serum calcium (2·39±0·02 vs 2·32±0·02 mmol/l, P=0·037) and phosphate (0·97±0·06 vs 0·75±0·05 mmol/l, P=0·011) increased and the index of phosphate excretion (0·03±0·03 vs 0·19±0·02, P<0·001) decreased significantly, and there was a significant increase in the markers of bone formation (osteocalcin, 64·8±11·8 vs 17·4±1·8 ng/ml, P<0·001; procollagen type I carboxyterminal propeptide (PICP), 195·3±26·4 vs 124·0±15·5 ng/ml, P=0·026) as well as those of bone resorption (type I collagen carboxyterminal telopeptide (ICTP), 8·9±1·2 vs 3·3±0·5 ng/ml, P<0·001; urinary hydroxyproline, 0·035±0·006 vs 0·018±0·002 mg/100 ml glomerular filtration rate, P=0·009). BMD did not change during this period of time. IGF-I was significantly higher in treated patients (306·5±45·3 vs 88·7±22·5 ng/ml, P<0·001). An analysis of the data compiled from 18 patients treated with rhGH for 12 months revealed similar significant increases in serum calcium and phosphate, and the markers of bone turnover (osteocalcin, PICP, ICTP, urinary hydroxyproline). Dual energy x-ray absorptiometry (DXA)-measured BMD in the lumbar spine (1·194±0·058 vs 1·133±0·046 g/cm2, P=0·015), femoral neck (1·009±0·051 vs 0·936±0·034 g/cm2, P=0·004), Ward's triangle (0·801±0·055 vs 0·816±0·04 g/cm2, P=0·019) and the trochanteric region (0·869±0·046 vs 0·801±0·033 g/cm2, P=0·005) increased significantly linearly (compared with the individual baseline values). At 12 months, BMD in patients with low bone mass (T-score < −1·0 s.d.) increased more than in those with normal bone mass (lumbar spine 11·5 vs 2·1%, P=0·030, and femoral neck 9·7 vs 4·2%, P=0·055). IGF-I increased significantly in all treated patients. In conclusion, treatment of GH-deficient adults with rhGH increases bone turnover for at least 12 months. BMD in the lumbar spine and the proximal femur increases continuously in this time (open study) and the benefit is greater in patients with low bone mass. Therefore, GH-deficient patients exhibiting osteopenia or osteoporosis should be considered candidates for GH supplementation. However, long-term studies are needed to establish that the positive effects on BMD are persistent and are associated with a reduction in fracture risk. European Journal of Endocrinology 136 282–289
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Toledano, Bryan Rene F., Maria Johanna Jaluage-Villanueva, and Sharon Marisse Lacson. "Outcomes of Tricuspid Regurgitation after Percutaneous Mitral Commissurotomy." ASEAN Heart Journal 30, no. 2 (November 2021): 9–19. http://dx.doi.org/10.31762/ahj2130.0203.
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PURPOSE The gap in evidence in the management of multivalvular lesions can be addressed by providing more data on clinical and echocardiographic outcomes after Percutaneous Mitral commissurotomy (PMC). METHODS Participants were Filipinos aged >/= 19 years old, admitted due to severe mitral stenosis with moderate to severe tricuspid regurgitation (TR). The outcome of PMC was divided into 2 groups: Significant TR which included the progression of moderate to severe TR or persistence of severe TR and Insignificant TR group which included those with mild TR, regression to moderate to mild TR, severe to moderate, or persistence of moderate TR. These groups were compared from baseline, 24th hour, 1st month, and 6th month using the same echocardiographic parameters. The numerical data between significant and nonsignificant tricuspid regurgitation were compared using non-parametric Mann Whitney U test and categorical data using the Chi-Square test. RESULTS A total of 38 participants were analyzed. On the 24th-hour post- PTMC, the Significant TR group had significantly higher RAVI (42.3 vs 26.1, p=.004), RVD mid (3.81 vs 2.92, p=.001), SPAP (60.5 vs 38.5, p=.003), and RVOT (2.8 vs 2.2, p=.001) and lower MV planimetry (1.25 vs 1.58, p=.009); On the 1st-month RVD mid (3.4 vs 2.8, p=.02) and TV annulus (3.35 vs 2.76, p=0.10) were significantly higher in the Significant TR group; On the 6th month RAVI (59 vs 24.7, p=.001), RVD mid (4 vs 2.73, p=.006), and TV annulus (4.5 vs 2.67 p=.001) were significantly higher in the Significant TR group when compared to Insignificant TR group. CONCLUSION PMC improved baseline parameters of SPAP, MV planimetry, MV gradient, and functional class on short-term follow-up on both groups of TR. Majority of outcomes after the procedure had insignificant TR. However, those with significant TR had higher RVD mid and TV annulus from the 24th hour to 6 months when compared to the insignificant TR group.
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Marcucci, Guido, K. Mrózek, A. S. Ruppert, K. Maharry, J. E. Kolitz, R. J. Mayer, M. J. Pettenati, et al. "t(8;21) Acute Myeloid Leukemia (AML) Differs from inv(16) AML in Pretreatment Characteristics, Outcome and Prognostic Factors Predicting Outcome: A Cancer and Leukemia Group B (CALGB) Study." Blood 104, no. 11 (November 16, 2004): 2017. http://dx.doi.org/10.1182/blood.v104.11.2017.2017.
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Abstract Since t(8;21) and inv(16) disrupt core binding factor in AML and confer a favorable prognosis, these cytogenetic groups are often treated similarly, but hitherto have not been compared in a large study. We compared 144 adult AML patients (pts) with t(8;21) with 168 with inv(16) enrolled on the cytogenetic study CALGB 8461. t(8;21) pts were less frequently white (P=.01), had lower hemoglobin levels (P=.03), WBC (P<.001) and % blood (P<.001) and BM blasts (P=.005), and had more frequently secondary chromosome aberrations (P<.001) than inv(16) pts, who more often had extramedullary disease (P<.001). Pts were induced with cytarabine/daunorubicin (AD) or cytarabine/daunorubicin/etoposide ±PSC833(ADE±P). Complete remission (CR) was achieved by 89% of t(8;21) and 87% of inv(16) pts. Upon multivariable analysis (MVA), non-white race (P=.006), lower platelets (P=.01) and higher BM blasts (P=.004) predicted negatively for CR in t(8;21), and lower platelets (P=.009) and hepatomegaly (P=.04) in inv(16) pts. Non-whites with t(8;21) had 5.7 times the odds of not achieving CR as whites. For the entire group (median follow-up 6.4 yrs), the estimated 5-yr overall survival (OS) and cumulative incidence of relapse (CIR) were 51% and 53%, respectively. Pts with t(8;21) showed a trend for shorter OS (46% vs 54%; P=.17) but no difference in CIR compared with inv(16) pts. Upon MVA, t(8;21) pts had worse OS than inv(16) pts (HR 1.5; P=.04), once adjusting for age, platelets, and WBC. Following first relapse, the 5-yr survival of t(8;21) pts (n=58) was shorter than that of inv(16) pts (n=74) (14% vs 36%; P=.01); in an age-adjusted model, the risk of death was 1.8 times higher for t(8;21) pts (P=.005). In a subanalysis of pts <60 yrs, consolidation therapy with multi-course high-dose cytarabine (HDAC x3 or 4) significantly decreased CIR compared to single-course HDAC (x1) in t(8;21) (5-yr CIR, 35% vs 64%; P=.005) and inv(16) (5-yr CIR, 44% vs 70%; P =.03) pts. Upon MVA, consolidation with multi-course HDAC reduced CIR for both t(8;21) and inv(16), but other prognostic factors differed (see Table). For t(8;21), induction with ADE±P and higher platelets increased risk of relapse. However, relatively few pts received ADE±P so its prognostic impact requires confirmation. For inv(16), +22 and other secondary cytogenetic aberrations, and male sex were favorable prognostic factors. Multivariable analysis (MVA) for CIR in pts <60 yrs achieving CR on CALGB 8221, 8525, 9022, 9222, 9621 Variable t(8;21) HR (95% CI); P inv(16) HR (95% CI); P HR=Hazard Ratio, CI=confidence intervals —, not included in final model Consolidation:Single vs multi-course HDAC 4.5 (2.1-9.4); <.001 3.4 (1.7-6.6); <.001 Induction:ADE±P vs AD 2.6 (1.1-5.9); .02 1.4 (0.6-3.2); .41 log(platelets) 1.8 (1.2-2.9); .007 — Secondary cytogenetics — 0.2 (<0.1-0.5); .002 Male vs Female — 0.5 (0.3-0.9); .03 In summary, once pretreatment factors and therapy are considered, the outcome of t(8;21) AML appears inferior to that of inv(16). Although these data should be confirmed prospectively, our analysis suggests that future studies should report the outcomes of pts with t(8;21) and inv(16) separately, and seek to identify and target therapeutically leukemogenic mechanisms accountable for these clinical differences.
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Karnovsky, Sydney C., Andrew J. Rosenbaum, Bridget DeSandis, Christopher Johnson, Conor I. Murphy, Russell F. Warren, Samuel A. Taylor, and Mark C. Drakos. "Radiographic Analysis of National Football League Players’ Fifth Metatarsal Morphology Relationship to Proximal Fifth Metatarsal Fracture Risk." Foot & Ankle International 40, no. 3 (November 7, 2018): 318–22. http://dx.doi.org/10.1177/1071100718809357.
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Background: Fractures of the proximal fifth metatarsal are one of the most common foot injuries in athletes. Repetitive stresses endured by the fifth metatarsal can lead to stress fracture, delayed union, and refracture, making optimal treatment challenging. A radiographic analysis of fifth metatarsal morphology and foot type in National Football League (NFL) players was performed to investigate morphologic risk factors for these injuries. Methods: This was a case-control study that looked at NFL players treated between 1992 and 2012, as well as participants at the NFL Combine. Ninety-six feet (51 athletes) were included. Fractures were present in 15 feet. Two reviewers assessed fifth metatarsal morphology and foot type on anteroposterior, lateral, and oblique radiographs. Differences in foot type and metatarsal morphology between athletes with and without fractures were determined. Results: On anteroposterior radiographs, significant differences in apex medullary canal width, 4-5 intermetatarsal angle, fifth metatarsal angle, and talar head uncovering were observed between fractured and non-fractured feet ( P = .001, .003, .004, .008, respectively). On lateral radiographs, significant differences in the fifth metatarsal length, distance to apex, apex height, fifth metatarsal angle, and talocalcaneal angle were observed between fractured and nonfractured feet ( P = .04, .01, .02, .01, .01, respectively). On oblique radiographs, a significant difference was observed in apex height between fractured and nonfractured feet ( P = .002). Conclusion: Individuals with long, narrow, and straight fifth metatarsals with an adducted forefoot were most at risk for fifth metatarsal fractures. With this insight, attempts at fracture prevention can be implemented via footwear modifications, orthoses, and off-loading braces that account for those aforementioned morphologic attributes that place athletes at risk. Level of Evidence: Level III, retrospective comparative study.
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Cairo, M. S., C. Mallett, C. VandeVen, P. Kempert, G. A. Bennetts, and J. Katz. "Impaired in vitro polymorphonuclear function secondary to the chemotherapeutic effects of vincristine, adriamycin, cyclophosphamide, and actinomycin D." Journal of Clinical Oncology 4, no. 5 (May 1986): 798–804. http://dx.doi.org/10.1200/jco.1986.4.5.798.
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The present study investigated the in vitro effect of four different chemotherapeutic agents, namely, cyclophosphamide (CTX), vincristine (VCR), Adriamycin (Adria Laboratories, Columbus, Ohio) (ADR), and actinomycin D (ACT-D) on human polymorphonuclear leukocyte (PMN) function. Human PMNs suspended in phosphate-buffered saline (PBS) at 1 X 10(7) cells/mL were incubated with increasing concentrations of CTX (0, 10(-5), 10(-4), 10(-3) mol/L) or VCR (0, 10(-7), 10(-6), 10(-5), 10(-4) mol/L), ADR (0, 10(-6), 10(-5), 10(-4), 10(-3) mol/L), or ACT-D (0, 5 X 10(-8), 1 X 10(-7), 5 X 10(-7), and 10(-6) mol/L). The cells were then tested for bacterial killing against Staphylococcus aureus, chemotaxis activity stimulated by Escherichia coli endotoxin, N-formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated aggregation, and cytochalasin B (Cyto B)/FMLP-stimulated superoxide production and enzyme degranulation. High concentration of CTX, an alkylating agent, showed a significant depression of PMN superoxide production, (124 +/- 13 v 161 +/- 15 nmol/10(7) cells, 5 minutes, P less than or equal to .025). ADR, an intercalating agent and membrane inhibitor, showed a significant depression of PMN degranulation and lysozyme release at 10(-4) and 10(-3) mol/L (15.3% +/- 1.7% v 24% +/- 7%, P less than .01; and 15.0% +/- 2.5% v 24% +/- 7%, P less than or equal to .025). VCR, a microtubule inhibitor, showed a significant depression of PMN aggregation at 10(-6), 10(-5), and 10(-4) mol/L (P less than .05), lysozyme release at 10(-4) mol/L (P less than .004), and beta-glucuronidase release at 10(-4) mol/L (P less than .004). In addition, chemotaxis was inhibited by VCR in a dose-dependent manner at all concentrations (10(-7) mol/L, P less than .02; 10(-6) mol/L, P less than .007; 10(-5) mol/L, P less than .006, and 10(-4) mol/L, P less than .003). ACT-D showed no significant effect on the PMN functions tested. These studies conclude that chemotherapeutic agents have modulating in vitro effects on PMN function. Further in vivo studies are therefore needed to assess PMN abnormalities in patients receiving cancer chemotherapy to determine their role in infectious complications.
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Ottinger, HD, DW Beelen, B. Scheulen, UW Schaefer, and H. Grosse-Wilde. "Improved immune reconstitution after allotransplantation of peripheral blood stem cells instead of bone marrow." Blood 88, no. 7 (October 1, 1996): 2775–79. http://dx.doi.org/10.1182/blood.v88.7.2775.bloodjournal8872775.
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Clinical studies are evaluating possible advantages of allogeneic peripheral blood stem cell transplantation (PBSCT) over bone marrow transplantation (BMT). We compared immune reconstitution after PBSCT (n = 20) and BMT (n = 20) in terms of lymphocyte subset counts and proliferative in vitro responses to mitogens and recall antigens (follow-up: 5 to 11 months posttransplant). Additionally, 10 PBSC harvests and 10 marrow harvests were analyzed for their composition of immunocompetent cells. Compared with BMT patients, PBSCT recipients had PB counts of naive (CD4+CD45RA+) and memory (CD4+CD45RO+) helper T cells and of B cells (CD19+) that were elevated (P < .003, P < .001, and P < .004, respectively) and proliferative responses to phytohemagglutinin (P < .0001), pokeweed mitogen (P < .02), Tetanus toxoid (P < .0005), and Candida (P < .004) that were increased. PBSCT recipients received a mean of 188 (range, 44 to 280) x 10(6) naive helper T cells and 169 (range, 18 to 296) x 10(5) memory helper T cells per kilogram; the corresponding numbers for BMT recipients were 11 (range, 4 to 24) and 10 (range, 1 to 22) x 10(5) cells per kilogram, respectively. The question of whether the documented improved in vitro immune competence after PBSCT is associated with a lower incidence of infectious complications in vivo still needs further study.
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Ortiz, Johana, John Van Camp, Sylviana Wijaya, Silvana Donoso, and Lieven Huybregts. "Determinants of child malnutrition in rural and urban Ecuadorian highlands." Public Health Nutrition 17, no. 9 (September 30, 2013): 2122–30. http://dx.doi.org/10.1017/s1368980013002528.
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AbstractObjectiveTo identify and compare the sociodemographic determinants of stunting, wasting and overweight among infants of urban and rural areas in the Ecuadorian highlands.DesignCross-sectional study.SettingNabon (rural) and Cuenca (urban) cantons, Azuay Province, Ecuador.SubjectsA total of 703 children aged 0–24 months and their caregivers (227 rural and 476 urban) recruited during the period from June to September 2008.ResultsStunting prevalence was significantly higher in the rural area (37·4 %v. 17·7 %;P< 0·001) while wasting (7·1 %) and overweight (17·1 %) prevalence were more similar between areas. Determinants of stunting for the pooled sample were male gender (OR = 1·43; 95 % CI 1·06, 1·92;P= 0·02), preterm delivery (OR = 1·65; 95 % CI 1·14, 2·38;P= 0·008), child's age (OR = 1·04; 95 % CI 1·01, 1·07;P= 0·011), maternal education (OR = 0·95; 95 % CI 0·92, 0·99;P= 0·025) and facility-based delivery (OR = 0·57; 95 % CI 0·45, 0·74;P< 0·001). The latter was also a determinant of overweight (OR = 0·39; 95 % CI 0·25, 0·62;P< 0·001). Rural determinants of stunting were maternal height (OR = 0·004; 95 % CI 0·00004, 0·39;P= 0·018), diarrhoea prevalence (OR = 2·18; 95 % CI 1·13, 4·21;P= 0·02), socio-economic status (OR = 0·79; 95 % CI 0·64, 0·98;P= 0·030) and child's age (OR = 1·07; 95 % CI 1·02, 1·11;P= 0·005). Urban determinants were: maternal BMI for stunting (OR = 0·91; 95 % CI 0·84, 0·99;P= 0·027), cough prevalence (OR = 0·57; 95 % CI 0·34, 0·96;P= 0·036) and facility-based delivery (OR = 0·25; 95 % CI 0·09, 0·73;P= 0·011) for overweight, and hygiene for wasting (OR = 0·57; 95 % CI 0·36, 0·89;P= 0·013).ConclusionsInfant malnutrition was associated with different sociodemographic determinants between urban and rural areas in the Ecuadorian highlands, a finding which contributes to prioritize the determinants to be assessed in nutritional interventions.
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Crago, Elizabeth A., Paula R. Sherwood, Catherine Bender, Jeffrey Balzer, Dianxu Ren, and Samuel M. Poloyac. "Plasma Estrogen Levels Are Associated With Severity of Injury and Outcomes After Aneurysmal Subarachnoid Hemorrhage." Biological Research For Nursing 17, no. 5 (December 29, 2014): 558–66. http://dx.doi.org/10.1177/1099800414561632.
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Background:Biochemical mediators alter cerebral perfusion and have been implicated in delayed cerebral ischemia (DCI) and poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Estrogens (estrone [E1] and estradiol [E2]) are mediators with neuroprotective properties that could play a role in DCI. This study explored associations between plasma estrogen levels and outcomes following aSAH.Methods:Plasma samples from 1–4, 4–6, and 7–10 days after hemorrhage from 99 adult aSAH patients were analyzed for estrogen levels using liquid chromatography tandem mass spectrometry. DCI was operationalized as radiographic/ultrasonic evidence of impaired cerebral blood flow accompanied by neurological deterioration. Outcomes were assessed using the Modified Rankin Scale at 3 and 12 months after hemorrhage. Statistical analysis included correlation, regression, and group-based trajectory.Results:Higher E1 and E2 levels were associated with higher Hunt and Hess grade (E1, p = .01; E2, p = .03), the presence of DCI (E1, p = .02; E2, p = .02), and poor 3-month outcomes (E1, p = .002; E2, p = .002). Trajectory analysis identified distinct populations over time for E1 (61% E1 high) and E2 (68% E2 high). Patients in higher trajectory groups had higher Fisher grades (E1, p = .008; E2, p = .01), more frequent DCI (E1, p = .04; E2, p = .08), and worse 3-month outcomes (E1, p = .01; E2, p = .004) than low groups.Conclusions:These results provide the first clinical evidence that plasma E1 and E2 concentrations are associated with severity of injury and outcomes after aSAH.
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Boyer, Patricia M., Gabriela E. Compagnucci, María I. Olivera, Clarisa Bozzini, María C. Roig, Cecilia V. Compagnucci, and Rosa M. Alippi. "Bone status in an animal model of chronic sub-optimal nutrition: a morphometric, densitometric and mechanical study." British Journal of Nutrition 93, no. 5 (May 2005): 663–69. http://dx.doi.org/10.1079/bjn20041331.
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In children, inappropriate eating habits can induce a disease known as nutritional dwarfing (ND). Due to the link between nutritional condition and bone growth, the effects induced by a 20 % reduction of food intake on bone competence were assessed in an animal model of ND. Bone status during catch-up growth was also analysed. Male Wistar rats were divided into control (C) and ND groups. C rats were fed ad libitum. ND received 80 % of the diet consumed by C for 4 weeks (T4); thereafter, they were fed ad libitum for 8 weeks. Results, expressed as mean (sem) for ND v. C, were as follows. At T4, body weight (g) and length (cm) and femur weight (g) and length (mm) were 97·35 (sem 5·89) v. 199·07 (sem 9·24), 16·91 (sem 0·41) v. 20·26 (sem 0·31), 0·30 (sem 0·01) v. 0·46 (sem 0·01) and 23·09 (sem 0·29) v. 26·98 (sem 0·26), respectively (P<0·001); bone mineral content (g) and density (g/cm2) were 0·014 (sem 0·002) v. 0·030 (sem 0·002) and 0·061 (sem 0·004) v. 0·080 (sem 0·003), respectively (P<0·001); load-bearing capacity (N), yielding load (N) and elastic stiffness (N/mm) were 25·06 (sem 1·24) v. 50·34 (sem 2·94), 23·72 (sem 1·02) v. 46·97 (sem 1·75) and 65·98 (sem 4·42) v. 115·07 (sem 3·85), respectively (P<0·001); cross-sectional area (mm2) and moment of inertia (mm4) were 2·86 (sem 0·19) v. 4·54 (sem 0·17) and 1·27 (sem 0·08) v. 3·03 (sem 0·16), respectively (P<0·001). Significant effects were not evident in material properties. Parameters assessed normalized during re-feeding. These results suggest that the impaired mechanical femur competence in ND rats could be due to an altered bone mass and architectural distribution rather than to intrinsic quality. Re-feeding caused a reversal of the effects of food restriction on growth and bone parameters in ND rats.
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Shab-Bidar, Sakineh, Tirang R. Neyestani, and Abolghassem Djazayery. "Vitamin D receptor Cdx-2-dependent response of central obesity to vitamin D intake in the subjects with type 2 diabetes: a randomised clinical trial." British Journal of Nutrition 114, no. 9 (September 8, 2015): 1375–84. http://dx.doi.org/10.1017/s0007114515003049.
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AbstractThis study aimed to investigate the effects of daily intake of vitamin D-fortified yogurt drink (doogh) on central obesity indicators in subjects with type 2 diabetes (T2D) and the possible modulation of this effect by vitamin D receptor (VDR) Cdx-2 genotypes. A total of sixty T2D subjects were randomly allocated to two groups to receive either plain doogh (PD; n 29, containing 170 mg Ca and no vitamin D/250 ml) or vitamin D3-fortified doogh (FD; n 31, containing 170 mg Ca and 12·5 μg/250 ml) twice a day for 12 weeks. 25-hydroxyvitamin D (25(OH)D), glycaemic as well as adiposity indicators were evaluated before and after the intervention. VDR-Cdx-2 genotypes in extended number of T2D subjects in the FD group (n 60) were determined as AA, GA and GG. After 12 weeks, in FD compared with PD, serum 25(OH)D increased (+35·4 v. −4·8 nmol/l; P<0·001) and mean changes of waist circumference (WC; −1·3 v. +1·6 cm; P=0·02), body fat mass (FM; −1·9 v. +0·60 %; P=0·008), truncal fat (TF; −1·1 v. 0·13 %; P=0·003) and visceral adipose tissue (−0·80 v. +0·37 AU; P<0·001) decreased significantly. Circulating 25(OH)D was raised only in the AA group (34·8 nmo/l in AA group v. −6·4 nmol/l in AG and −1·6 nmol/l in GG groups; P<0·001), which was accompanied by a significant decrease in changes of WC (P=0·004), FM% (P=0·01) and TF% (P<0·001) in the AA genotype. Daily intake of vitamin D-FD for 12 weeks improved the central obesity indices in T2D subjects, and the improvement was more pronounced in the carriers of the AA genotype of VDR-Cdx-2.
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Rogers, Megan L., and Thomas E. Joiner. "Rumination, Suicidal Ideation, and Suicide Attempts: A Meta-Analytic Review." Review of General Psychology 21, no. 2 (June 2017): 132–42. http://dx.doi.org/10.1037/gpr0000101.
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Rumination has been implicated as a risk factor for suicidal ideation and attempts, yet the literature to date has not been synthesized. We conducted a meta-analysis of the association between rumination and both suicidal ideation and attempts to consolidate the existing literature ( k = 29). Results indicated that the relationships between global rumination ( k = 13; Hedge's g = .74, p < .001, 95% CI [.45, 1.04]), brooding ( k = 12; Hedge's g = .63, p < .001, 95% CI [.35, .90]), and reflection ( k = 12; Hedge's g = .38, p = .002, 95% CI [.10, .65]) with suicidal ideation were significant. Associations between global rumination ( k = 3; Hedge's g = .26, p < .001, 95% CI [.08, .44]) and brooding ( k = 4; Hedge's g = .47, p = .004, 95% CI [.02, .91]) and suicide attempts were significant, but reflection ( k = 4; Hedge's g = .09, p = .646, 95% CI [−.54, .72]) was unrelated. However, given the limited studies included in suicide attempt analyses—and the exclusive use of cross-sectional designs and heterogeneity with regard to samples and measures—these parameters should be taken with caution. Generally, age, gender, race/ethnicity, and year of publication were not moderators, and there was little evidence for publication bias across effects, with the exception of the effect of global rumination on suicidal ideation. Several future research directions are discussed.
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ARCHIMÈDE, H., C. PONCET, M. BOVAL, F. NIPEAU, L. PHILIBERT, A. XANDÉ, and G. AUMONT. "Comparison of fresh and dried Digitaria decumbens grass intake and digestion by Black-belly rams." Journal of Agricultural Science 133, no. 2 (September 1999): 235–40. http://dx.doi.org/10.1017/s0021859699006784.
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The intake and digestion of fresh and dried Digitaria decumbens grass by rams was compared using a 2×2 factorial design. The experiment took place in Guadeloupe (French West Indies) in 1996. Eight rams (mean liveweight: 45·7±3·1 kg) were maintained in metabolism cages. Digitaria decumbens grass was cut daily and distributed to four of them, the other four were fed the following day with the equivalent forage which had meanwhile been dried for 20 h at 60°C. Chemical composition (g/kg of dry matter (DM)) of the two diets based on neutral detergent fibre (NDF, 713, S.E. 18), acid detergent fibre (ADF, 361, S.E. 13) and crude protein (CP, 90, S.E. 4) was similar. The DM intake (61·0 and 53·2 g/W0·75, S.E. 2·0, P<0·05), the NDF (0·753 and 0·727, S.E. 0·004, P<0·011) and CP (0·588 and 0·544, S.E. 0·014, P<0·09) total tract digestibility of fresh and dried herbage were different. Nylon bag estimates of effective DM degradability and fractional degradation rates (per h) in the rumen were 0·436, 0·414 (S.E. 0·005, P<0·004) and 0·048, 0·038 (S.E. 0·002, P<0·02) for fresh and dried grass, respectively. Rumen digestibility of organic matter and NDF were 0·516, 0·541 (S.E. 0·021) and 0·763, 0·692 (S.E. 0·019), respectively. The rumen turnover rates of particles (per h) were 0·024 and 0·015 (S.E. 0·001, P<0·05) for fresh and dried forage respectively. The efficiency of microbial protein synthesis (g microbial nitrogen/kg organic matter apparently degraded in the rumen) was similar with the two diets : 33·5 and 33·0 (S.E. 3·3, P<0·9) for fresh and dried forage respectively. In conclusion, fresh Digitaria decumbens was nutritionally superior to dried. This is probably due to a faster degradation rate and a lower rumen retention time of the fresh forage.
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Langer, C., A. S. Ruppert, M. D. Radmacher, S. P. Whitman, P. Paschka, C. D. Baldus, K. Mrózek, J. E. Kolitz, G. Marcucci, and C. D. Bloomfield. "High BAALC expression associates with other molecular prognostic markers, poor outcome and a distinct gene expression signature in cytogenetically normal acute myeloid leukemia (CN AML): A Cancer and Leukemia Group B (CALGB) study." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 7013. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.7013.
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7013 Background: High BAALC expression predicts poor outcome in CN AML patients (pts). Yet, little is known about BAALC's function or its relation to other prognostic markers. We evaluated BAALC expression in the context of molecular markers and clinical outcome in 172 de novo CN AML adults, aged <60 years (y) treated on similar CALGB protocols (9621 and 19808). Methods: BAALC expression was measured by quantitative real-time RT-PCR in pretreatment blood samples. Pts were grouped as high (n=86) or low BAALC (n=86) expressers using the median expression value, by protocol, as a cutoff. Gene expression profiling (Affymetrix U133 plus 2.0 GeneChip) was performed on high (n=26) and low (n=24) pts. Results: BAALC expression was associated with several molecular markers ( Table ). Complete remission (CR) rate was lower in high BAALC pts (79% v 90%), for whom achieving CR was almost 4 times less likely than for low BAALC pts (P=.02; odds ratio=0.27), after adjusting for age (P=.004), ERG expression (P=.05) and white blood cell count (WBC; P=.04). With a median follow-up of 4.3 y, high BAALC pts had shorter overall survival (OS) (P=.002; 3-y OS: 42% v 59%). In a multivariable model, high BAALC provided further adverse prognostic information (P=.06; hazard ratio=1.66) independent of FLT3 ITD (P<.001), WBC (P=.007) and NPM1 (P=.02). A gene expression signature was identified consisting of 312 probe sets differentially expressed (P<.001) between BAALC groups. High BAALC was associated with overexpression of, among other genes, PROM1, CD34 and KIT indicating a less differentiated phenotype in these pts. Conclusions: Although associated with other prognostic markers, high BAALC expression independently predicts outcome and is associated with a distinct gene expression profile, potentially identifying new therapeutic targets in this pt subset. No significant financial relationships to disclose. [Table: see text]
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Safarinejad, Mohammad Reza, Nayyer Shafiei, and Shiva Safarinejad. "Effects of EPA, γ-linolenic acid or coenzyme Q10 on serum prostate-specific antigen levels: a randomised, double-blind trial." British Journal of Nutrition 110, no. 1 (November 30, 2012): 164–71. http://dx.doi.org/10.1017/s0007114512004783.
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The main objective of the present study was to determine the potential ofn-3 andn-6 fatty acids or coenzyme Q10(CoQ10) to alter serum prostate-specific antigen (PSA) levels in normal healthy men. A total of 504 healthy men with serum PSA level ≤ 2·5 ng/ml were recruited into the study. Serum PSA values were not segregated by decade of age. Participants were randomly assigned to a daily dietary supplement containingn-3 fatty acids (1·12 g of EPA and 0·72 g of DHA per capsule) (group 1,n126),n-6 fatty acid (600 mg γ-linolenic acid (GLA) each capsule) (group 2,n126), CoQ10(100 mg per capsule) (group 3,n126) or a similar regimen of placebo (group 4,n126) for 12 weeks. Study medication was administered as two capsules to be taken twice daily. Serum levels of PSA, EPA, DHA, GLA, lipid profile and reproductive hormones were also measured. EPA treatment significantly reduced serum PSA level by 30·0 (95 % CI 25, 36) % (P= 0·004) from baseline. In contrast, GLA therapy significantly increased serum PSA concentration by 15·0 (95 % CI 11, 20) % (P= 0·02). CoQ10therapy also significantly reduced serum PSA level by 33·0 (95 % CI 27, 40) % (P= 0·002). In multivariable analysis, serum values of PSA were strongly correlated with duration of EPA (r− 0·62; 95 % CI − 0·42, − 0·77;P= 0·003),n-6 (r0·42; 95 % CI 0·31, 0·58;P= 0·02) and CoQ10use (r− 0·77; 95 % CI − 0·56, − 0·87;P= 0·001). There were also significant correlations between serum values of DHA, EPA, GLA and CoQ10and serum PSA levels. The present study demonstrates that dietary supplements containing EPA, GLA or CoQ10may significantly affect serum PSA levels.
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Bruera, Eduardo, Sriram Yennurajalingam, J. Lynn Palmer, Pedro E. Perez-Cruz, Susan Frisbee-Hume, Julio A. Allo, Janet L. Williams, and Marlene Z. Cohen. "Methylphenidate and/or a Nursing Telephone Intervention for Fatigue in Patients With Advanced Cancer: A Randomized, Placebo-Controlled, Phase II Trial." Journal of Clinical Oncology 31, no. 19 (July 1, 2013): 2421–27. http://dx.doi.org/10.1200/jco.2012.45.3696.
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Purpose Cancer-related-fatigue (CRF) is common in advanced cancer. The primary objective of the study was to compare the effects of methylphenidate (MP) with those of placebo (PL) on CRF as measured using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) fatigue subscale. The effect of a combined intervention including MP plus a nursing telephone intervention (NTI) was also assessed. Patients and Methods Patients with advanced cancer with a fatigue score of ≥ 4 out of 10 on the Edmonton Symptom Assessment Scale (ESAS) were randomly assigned to one of the following four groups: MP+NTI, PL+NTI, MP + control telephone intervention (CTI), and PL+CTI. Methylphenidate dose was 5 mg every 2 hours as needed up to 20 mg per day. The primary end point was the median difference in FACIT-F fatigue at day 15. Secondary outcomes included anxiety, depression, and sleep. Results One hundred forty-one patients were evaluable. Median FACIT-F fatigue scores improved from baseline to day 15 in all groups: MP+NTI (median score, 4.5; P = .005), PL+NTI (median score, 8.0; P < .001), MP+CTI (median score, 7.0; P = .004), and PL+CTI (median score, 5.0; P = .03). However, there were no significant differences in the median improvement in FACIT-F fatigue between the MP and PL groups (5.5 v 6.0, respectively; P = .69) and among all four groups (P = .16). Fatigue (P < .001), nausea (P = .01), depression (P = .02), anxiety (P = .01), drowsiness (P < .001), appetite (P = .009), sleep (P < .001), and feeling of well-being (P < .001), as measured by the ESAS, significantly improved in patients who received NTI. Grade ≥ 3 adverse events did not differ between MP and PL (40 of 93 patients v 29 of 97 patients, respectively; P = .06). Conclusion MP and NTI alone or combined were not superior to placebo in improving CRF.
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Ozunlu, Nihan, Hatice Tekeli, and Gul Baltaci. "Lateral Scapular Slide Test and Scapular Mobility in Volleyball Players." Journal of Athletic Training 46, no. 4 (July 1, 2011): 438–44. http://dx.doi.org/10.4085/1062-6050-46.4.438.
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Context: The stability of the scapula in relation to the entire moving upper extremity is the key in the throwing sequence. The importance of scapular positioning in volleyball players has been well documented in the literature, but no one has compared scapular positioning between volleyball players and sedentary people. Objective: To compare measurements of scapular mobility obtained using the lateral scapular slide test between volleyball players and sedentary participants without shoulder impairments and to compare changes in scapular mobility in players according to the number of years of sport participation. Design: Cross-sectional study. Setting: University research laboratory. Patients or Other Participants: A total of 121 people at a single university volunteered. Of these, 67 were sedentary (age = 24.3 ± 2.34 years, height = 1.69 ± 0.09 m, mass = 65.1 ± 11.91 kg); 54 were volleyball players from 4 professional teams and were separated into 2 groups according to their years of sport participation. The first group was named young players (n = 31; age = 17.7 ± 2.58 years, height = 1.83 ± 0.10 m, mass = 68.3 ± 12.21 kg, sport participation ≤ 9 years), and the second group was named old players (n = 23; age = 26.9 ± 3.39 years, height = 1.95 ± 4.38 m, mass = 90.7 ± 5.75 kg, sport participation ≥ 10 years). Main Outcome Measure(s): Study participants completed a rating scale for pain and a questionnaire about demographic and shoulder problems. One assessor performed the lateral scapular slide test and additional flexibility measurements around the shoulder girdle. Flexibility (external rotation, internal rotation) and scapular position (1, 2, 3) were compared among groups (young players, old players, sedentary people) and between sides (dominant, nondominant). Results: In sedentary participants, we found differences for position 1 (t66 = 3.327, P = .002), position 2 (t66 = 2.491, P = .004), position 3 (t66 = 2.512, P = .006), and internal rotation (t66 = 2.592, P = .001) between the dominant and nondominant sides. In old players, we found differences for position 2 between the dominant and nondominant sides (t22 = 2.956, P = .004). For position 2 (F2,118 = 4.265, P = .02) and position 3 (F2,118 = 4.702, P = .01), we found differences between young and old players. For internal rotation, we found differences between sedentary and old players (F2,118 = 6.578, P = .002) and between young and old players (F2,118 = 3.723, P = .01). Conclusions: Clinicians evaluating overhead athletes need to remember that asymmetric scapular posture between the dominant and nondominant sides in unilateral overhead athletes might be normal and not necessarily related to injury.
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Rahman, Fahd, Roy N. Gay, Samir K. Ballas, Juan C. Zubieta, Zekarias Berhane, Saad Rahman, M. N. Athar, and N. Takawira. "Predictors of Adverse Outcomes in Hospitalized Adult Patients with Sickle Cell Disease." Blood 106, no. 11 (November 16, 2005): 3197. http://dx.doi.org/10.1182/blood.v106.11.3197.3197.
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Abstract The identification of patients with sickle cell disease at risk of serious complications at the time of hospital admission can help stratify patients who will need aggressive management. We identified predictors associated with adverse outcomes such as frequent hospitalizations, acute pain crises and acute chest syndromes. To that end, we retrospectively reviewed medical records of 265 adult sickle cell disease patients, hospitalized between 1/1/98 and 2/3/05 at Mercy Catholic Medical Center, with complete clinical and laboratory data. 195/73.6% had HbSS and the rest had HbSC, HbSβ-thal0,HbS-βthal+or HbSOarab disease. 59 variables were considered including demographic, hematological, biochemical, clinical and treatment data. Logistic regression models were used to obtain associations between variables, and to adjust for confounding effects. Analysis showed that adverse events during admission included acute pain crises in 249/94%, acute chest syndromes in 25/9.4% and strokes in 5/1.9% patients. Other outcomes were a greater than 2 hospitalizations per year 82/31.9%, more than 2 pain crises per year 145/54.7%, transfusion required during admission 72/27.2%, length of hospital stay more than 5 days 105/39.6% and death during hospitalization 13/4.9%. Multivariate logistic regression analysis revealed 21 factors with statistically significant associations. A reticulocyte count greater than 1.5 (OR 3.98, CI 1.48–10.69, P.006) and employment status (OR .31, CI .13-.75, P.009) were associated with more admissions per year. History of acute chest syndrome (OR 5.33, CI 1.7–16.77, P.004), reticulocyte count greater than 1.5 (OR 3.46, CI .91–13.11, P.067) and care provided by a nonhematologist (OR 5.04, CI 1.7–14.95, P.0035) were linked with more pain crises per year. Pain crises during admission were associated with HbSS disease (OR 9.31, CI 2.17–39.9, P.01) and out patient folate therapy(OR 6.23, CI 1.45–26.84, P.003). Patients with leukocytosis (OR 3.41, CI 1.2–9.67, P.02) and a higher serum glucose level (OR 7.54, CI 2.6–21.86, P.0002) were linked to more acute chest syndromes. Females (OR .1, CI .03–.37, P.0004) were at lower risk of having acute chest syndromes. Outpatient folate therapy (OR .07, CI .007–.69, P.02) was associated with lower numbers of acute neurological events. Patients with initial hemoglobin levels less than 7 g/dL (OR 1.99, CI 1–4, P.0007) and prolonged hospitalization (OR 7.06, CI 3.63–13.74, P.0001) frequently required transfusions. Variant diseases (OR .28, CI .13–.58, P.05) required fewer transfusions. Deaths during hospitalization were lower with folate therapy (OR .18, CI .05–.63, P.007) and a transfusion requirement during admission (OR 5.07, CI 1.45–17.64, P.01) predicted more deaths. HbSS patients (OR 2.52, CI 1.1–5.8, P.03), substance abusers (OR 2.93, CI 1.21–7.08, P.01), those requiring antihistamines during admission (OR 3.33, CI 1.38–8.03, P.007), or requiring more than 2 hospitalizations per year (OR 2.62, CI 1.26–5.43, P.009) had hospital stays longer than 5 days while in females odds were low for this outcome (OR .30, CI .15–.59, P.0005). In conclusion, simple tools like a complete history, physical examination, demographic and laboratory data can help clinicians and health care providers to gauge severity of the illness and deliver tailored management protocols targeting these “at risk” sickle cell disease patients.
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Jian, Zhi-Hong, Yi-Chen Chiang, Chia-Chi Lung, Chien-Chang Ho, Pei-Chieh Ko, Oswald Ndi Nfor, Hui-Chin Chang, Yi-Ching Liaw, Yu-Chiu Liang, and Yung-Po Liaw. "Vegetarian diet and cholesterol and TAG levels by gender." Public Health Nutrition 18, no. 4 (June 25, 2014): 721–26. http://dx.doi.org/10.1017/s1368980014000883.
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AbstractObjectiveThe present study assessed the effects of vegetarian and omnivorous diets on HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), TAG and the ratio of HDL-C to total cholesterol (TC) by gender.DesignHDL-C, LDL-C, TAG and HDL-C:TC were compared among three diet groups (vegan, ovo-lacto vegetarian and omnivorous). Multivariate linear regression analysis was performed to examine factors significantly and independently associated with vegetarian status and to estimate the β value of lipid profiles for the diet groups.SettingsA cross-sectional study. Data were obtained from the Taiwanese Survey on the Prevalence of Hyperglycemia, Hyperlipidemia and Hypertension (TwSHHH).SubjectsThe study comprised included 3257 men and 3551 women.ResultsAfter adjusting for confounders, vegan and ovo-lacto vegetarian diets lowered LDL-C levels (β=−10·98, P=0·005 and β=−7·12, P=0·025, respectively) in men compared with omnivorous diet. There was a significant association between HDL-C and vegan diet (β=−6·53, P=0·004). In females, the β values of HDL-C, TAG and HDL-C:TC were −5·72 (P<0·0001), 16·51 (P=0·011) and −0·02 (P=0·012) for vegan diet, and −4·86 (P=0·002), 15·09 (P=0·008) and −0·01 (P=0·026) for ovo-lacto vegetarian diet, when compared with omnivorous diet.ConclusionsVegan diet was associated with lower HDL-C concentrations in both males and females. Because the ovo-lacto vegetarian diet was effective in lowering LDL-C, it may be more appropriate for males.
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DiFranza, J. "Does the First Exposure to Addictive Substances Predict Future Dependence?" European Psychiatry 24, S1 (January 2009): 1. http://dx.doi.org/10.1016/s0924-9338(09)70323-2.
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Aims:The risk factors for trying a cigarette are well known, however we were interested in the factors that determine which youths become addicted to nicotine once they have tried it.Method:To investigate this we followed a cohort of 1246 students (mean baseline age of 12.2 years) over 4 years. Subjects underwent 11 interviews during which we assessed 45 risk factors, measured diminished autonomy over tobacco with the Hooked On Nicotine Checklist, and evaluated tobacco dependence using the International Classification of Diseases-10th revision. Cox proportional hazards models were used.Results:Among 217 youths who had inhaled from a cigarette, the loss of autonomy over tobacco was predicted by feeling relaxed the first time inhaling from a cigarette (adJusted Hazard Ratio (HR)=3.26; 95% CI, 1.95-5.46; P< .001) and depressed mood (HR=1.29; 1.09-1.54; P=.004). Tobacco dependence was predicted by feeling relaxed (HR=2.43; 1.27-4.65; P=.007), familiarity with Joe Camel (HR=2.19; 1.11-4.32; P=.02), novelty seeking (HR=1.56; 1.06-2.29; P=.02), and depressed mood (HR=1.17; 1.04-1.30; P=.007).Conclusion:Once exposure to nicotine had occurred, remarkably few risk factors for smoking consistently contributed to individual differences in susceptibility to the development of dependence. An experience of relaxation in response to the first dose of nicotine was the strongest predictor of both dependence and lost autonomy. This association was not explained by trait anxiety or many other psychosocial factors. These results are discussed in relation to the theory that addiction is initiated by the first dose of nicotine.
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Ali, Sharif, Jason D. Pimentel, Javier Munoz, Veena Shah, Rick McKinnon, George Divine, and Nalini Janakiraman. "Iron Overload in Allogeneic Hematopoietic Stem Cell Transplant Recipients." Archives of Pathology & Laboratory Medicine 136, no. 5 (May 1, 2012): 532–38. http://dx.doi.org/10.5858/arpa.2011-0190-oa.
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Context.—Patients who undergo hematopoietic stem cell transplant are at an increased risk of developing iron overload. Objectives.—To describe the effect of hepatic iron overload on hematopoietic stem cell transplant recipients and to validate the utility of histologic scoring system of iron granules in the liver. Design.—Records of 154 post allogeneic hematopoietic stem cell transplant patients were reviewed. Forty-nine patients underwent liver biopsy. Histologic hepatic iron overload was defined as a score of 2 or greater (scale, 0–4). Results.—Twenty-eight of 49 patients (57%) evaluated by liver biopsy had hepatic iron overload; 17 had moderate to severe hepatic iron overload (score, 3 or 4). In multivariate analysis, a significant correlation was discovered between hepatic iron overload and the number of transfusions (P < .001), posttransplant serum ferritin levels (P = .004), lactate dehydrogenase levels (P = .03), and the development of blood stream infections (P = .02). There was no correlation between hepatic iron overload and abnormal liver function test results. While 37 patients (76%) died after receiving a transplant, mortality was not influenced by hepatic iron overload but was significantly higher in older patients, in patients with lower serum albumin levels, higher serum bilirubin levels, and higher clinical grade of acute graft-versus-host disease (P = .04, P = .001, P = <.001, and P = .004, respectively). Conclusions.—Hepatic iron overload is commonly identified in hematopoietic stem cell transplant patients and can be accurately diagnosed by liver biopsy. In addition, hepatic iron overload has been identified in patients receiving as few as 25 units of packed red blood cells, with elevated posttransplant serum ferritin levels, and with blood stream infections.
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Tartour, E., J. Y. Blay, T. Dorval, B. Escudier, V. Mosseri, J. Y. Douillard, L. Deneux, et al. "Predictors of clinical response to interleukin-2--based immunotherapy in melanoma patients: a French multiinstitutional study." Journal of Clinical Oncology 14, no. 5 (May 1996): 1697–703. http://dx.doi.org/10.1200/jco.1996.14.5.1697.
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PURPOSE Various parameters have been reported to be correlated with response to interleukin-2 (IL-2) therapy. A multiinstitutional study was performed to assess by multivariate analysis the predictive value of known clinical and biologic melanoma prognostic markers recorded before the onset of IL-2 therapy on the likelihood of objective clinical response. PATIENTS AND METHODS Serum C-reactive protein (CRP), IL-6, and lactate dehydrogenase (LDH) levels were measured in 81 metastatic melanoma patients included in different IL-2-based regimens before the starting of IL-2-therapy. Clinically defined prognostic groups, i.e., patients with superficial or visceral metastases, were also analyzed for response correlates. Patients were evaluated for response to treatment 4 to 6 weeks after completion of one course of therapy. RESULTS On univariate analysis, the pretreatment values of CRP (P = .001), IL-6 (P = .007), and LDH (P = .02) and site of metastases (P = .0004) were correlated with clinical response. However, only CRP (P < .007) and clinically defined group (P < .004) were independent predictors on multifactorial analysis. Indeed, when adjusted to CRP, IL-6 tended to improve patient selection, but did not reach statistical significance (P = .07). Furthermore, using multivariate survival analysis based on the Cox proportional hazards model, only CRP was found to be an independent prognostic factor for survival (P < .0001). CONCLUSION In this study, patients with high serum levels of CRP and/or visceral organ involvement before therapy were unlikely to respond to IL-2 therapy. Therefore, clinical classification based on the site of metastases and serum CRP determination before the start of IL-2 therapy may help to improve selection of melanoma patients who may benefit from IL-2 and could prevent unnecessary morbidity.
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He, Zihao, Hua Wu, Fengyu Yu, Jinmei Fu, Shunli Sun, Ting Huang, Runze Wang, Delong Chen, Guanggao Zhao, and Minghui Quan. "Effects of Smartphone-Based Interventions on Physical Activity in Children and Adolescents: Systematic Review and Meta-analysis." JMIR mHealth and uHealth 9, no. 2 (February 1, 2021): e22601. http://dx.doi.org/10.2196/22601.
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Background About 70% of children and adolescents worldwide do not meet the recommended level of physical activity (PA), which is closely associated with physical, psychological, and cognitive well-being. Nowadays, the use of technologies to change PA is of interest due to the need for novel, more effective intervention approaches. The previous meta-analyses have examined smartphone-based interventions and their impact on PA in adults, but evidence in children and adolescents still needs further research. Objective This systematic review and meta-analysis aimed to determine the effectiveness of smartphone-based interventions for improving PA in children and adolescents. Methods Five electronic databases (PubMed, Web of Science, OVID, Scopus, and the China National Knowledge Infrastructure) were searched up to June 29, 2020. Randomized controlled trials with a control group that examine the effect of smartphone interventions on PA among children and adolescents were included. Bias risks were assessed using the Cochrane collaboration tool. Meta-analysis was performed to assess the pooled effect on PA using a random effects model. Subgroup analyses were conducted to examine the potential modifying effects of different factors (eg, types of intervention, intervention duration, age, measurement, study quality). Results A total of 9 studies were included in this review, including 4 mobile app interventions, 3 SMS text messaging interventions, and 2 app + SMS text messaging interventions. In general, the risk of bias of included studies was low. Compared with the control group, the use of smartphone intervention significantly improved PA (standardized mean difference [SMD] 0.44, 95% CI 0.11-0.77, P=.009), especially for total PA (TPA; weighted mean difference [WMD] 32.35, 95% CI 10.36-54.33, P=.004) and daily steps (WMD 1185, 95% CI 303-2068, P=.008), but not for moderate-to-vigorous PA (WMD 3.91, 95% CI –1.99 to 9.81, P=.19). High statistical heterogeneity was detected (I2=73.9%, P<.001) for PA. Meta-regression showed that duration (β=–.08, 95% CI –0.15 to –0.01, n=16) was a potential factor for high heterogeneity. The results of subgroup analyses indicated that app intervention (SMD 0.76, 95% CI 0.23-1.30, P=.005), children (SMD 0.64, 95% CI 0.10-1.18, P=.02), “≤8 weeks” (SMD 0.76, 95% CI 0.23-1.30, P=.005), objective measurement (SMD 0.50, 95% CI 0.09-0.91, P=.02), and low risk of bias (SMD 0.96, 95% CI 0.38-1.54, P=.001) can significantly improve PA. Conclusions The evidence of meta-analysis shows that smartphone-based intervention may be a promising strategy to increase TPA and steps in children and adolescents. Currently, app intervention may be a more effective strategy among smartphone intervention technologies. To extend the promise of smartphone intervention, the future needs to design comparative trials among different smartphone technologies. Trial Registration PROSPERO CRD42019148261; https://tinyurl.com/y5modsrd
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Lange, Beverly J., Patricia Dinndorf, Franklin O. Smith, Carola Arndt, Dorothy Barnard, Stephen Feig, James Feusner, et al. "Pilot Study of Idarubicin-Based Intensive-Timing Induction Therapy for Children With Previously Untreated Acute Myeloid Leukemia: Children's Cancer Group Study 2941." Journal of Clinical Oncology 22, no. 1 (January 1, 2004): 150–56. http://dx.doi.org/10.1200/jco.2004.04.016.
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Purpose Randomized comparisons of idarubicin (IDA) with daunorubicin (DNR) show that in adults with acute myeloid leukemia (AML), IDA achieves higher remission rates and longer remission durations. In Children's Cancer Group Pilot Study CCG-2941, we assessed toxicity and feasibility of substituting 4 mg of DNR with 1 mg of IDA in intensive-timing daunorubicin-based induction therapy (DNR/DNR) used in CCG-2891. Patients and Methods On days 1 through 3 and 10 through 14, patients received two courses of dexamethasone, cytarabine, 6-thioguanine, etoposide, and IDA (IDA/IDA). After enrollment of 65 patients, toxicity prompted replacement of IDA with DNR (IDA/DNR) on days 10 through 14 for the remaining 28 patients. Outcomes were compared with those of intensive timing in CCG-2891. Results Treatment-related mortality after two courses of induction was not significantly different among the three regimens: 14% with IDA/IDA, 7% with IDA/DNR, and 9% with DNR/DNR. In course 1 of CCG-2941 IDA/IDA, 11% of patients withdrew compared with 1.5% in CCG-2891 (P < .001) and 5% in CCG-2941 IDA/DNR (P = not significant). Compared with CCG-2891 DNR/DRN, CCG-2941 IDA/IDA increased days in hospital (43 v 36 days; P = .007), mean duration of course 1 by a week (P = .002), and risk of grade 3 or 4 hyperbilirubinemia (18% v 5%; P = .02). Toxicity of IDA/DNR was not different from that of DNR/DNR in CCG-2891. The mean day 7 marrow blast percentage was 11.4% in CCG-2941 versus 21.1% in CCG-2891 (P = .004). Remission induction, survival, and event-free survival rates were not significantly different from those of CCG-2891. Conclusion In CCG-2941, excessive toxicity and withdrawals outweighed potential benefits of early response with IDA.
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Senay, Sahin, Fevzi Toraman, Yasemin Akg�n, Ebuzer Aydin, Hasan Karabulut, Cem Alhan, and Tayyar Sarioglu. "Stroke After Coronary Bypass Surgery Is Mainly Related to Diffuse Atherosclerotic Disease." Heart Surgery Forum 14, no. 6 (December 13, 2011): 366. http://dx.doi.org/10.1532/hsf98.20111031.
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<p><b>Objective:</b> This study aims to investigate the risk factors for postoperative stroke and analysis of outcome after coronary bypass surgery with cardiopulmonary bypass.</p><p><b>Methods:</b> Between 1999 and 2008, 3248 consecutive patients who underwent isolated coronary surgery with cardiopulmonary bypass were prospectively enrolled in the study. Demographic and perioperative data were analyzed. Postoperative stroke was defined as severe adverse neurological events including permanent deficits or cerebral lesions with radiological demonstration of cerebral infarction within the first postoperative month.</p><p><b>Results:</b> In total, 32 patients (0.9%) were determined with stroke. Univariate risk factors for postoperative stroke were determined as preoperative unstable angina (<i>P</i> = .006), Canadian Class of Angina (CCA) ? 3 (<i>P</i> = .001), preoperative creatinin level >1.2 mg/dL (<i>P</i> = .001), left main coronary artery disease (<i>P</i> = .04), chronic obstructive lung disease (<i>P</i> = .04), peripheral arterial disease (<i>P</i> < .001), New York Heart Association (NYHA) Class ? 3 (<i>P</i> = .004), preoperative renal insufficiency (<i>P</i> = .001), age > 65 years (<i>P</i> = .04), preoperative hypothyroidism (<i>P</i> = .02), postoperative low cardiac output state (<i>P</i> < .001), severe coronary artery disease requiring distal anastomosis ? 4 (<i>P</i> = .05), non-elective operation (<i>P</i> = .02), and body mass index ? 25 (<i>P</i> = .02). Multivariate analysis revealed peripheral arterial disease (odds ratio [OR], 5.2; 95% confidence interval [CI], 1.9-14.0; <i>P</i> = .001), severe coronary artery disease (OR, 3.1; 95% CI, 1.1-8.5; <i>P</i> = .02), and postoperative low cardiac output state (OR, 5.1; 95% CI, 1.4-18.2; <i>P</i> = .01) as the independent risk factors.</p><p><b>Conclusions:</b> Stroke after coronary bypass surgery with cardiopulmonary bypass is mainly related to diffuse atherosclerotic disease.</p>
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Raygan, Fariba, Milad Behnejad, Vahidreza Ostadmohammadi, Fereshteh Bahmani, Mohammad A. Mansournia, Fatemeh Karamali, and Zatollah Asemi. "Selenium supplementation lowers insulin resistance and markers of cardio-metabolic risk in patients with congestive heart failure: a randomised, double-blind, placebo-controlled trial." British Journal of Nutrition 120, no. 1 (June 25, 2018): 33–40. http://dx.doi.org/10.1017/s0007114518001253.
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AbstractThis study was carried out to evaluate the effects of Se supplementation on metabolic profiles in patients with congestive heart failure (CHF). This randomised double-blind, placebo-controlled trial was performed among fifty-three subjects with CHF, aged 45–85 years old. Subjects were randomly allocated into two groups to take either 200 µg/d of Se as Se yeast (n 26) or placebo (n 27) for 12 weeks. Metabolic profiles were assessed at baseline and at the end of trial. Compared with the placebo, Se supplementation led to significant reductions in serum insulin (−18·41 (sd 27·53) v. +13·73 (sd 23·63) pmol/l, P<0·001), homoeostatic model of assessment for insulin resistance (−1·01 (sd 1·61) v. +0·55 (sd 1·20), P<0·001) and a significant increase in quantitative insulin sensitivity check index (QUICKI) (+0·007 (sd 0·03) v. −0·01 (sd 0·01), P=0·007). In addition, Se supplementation significantly decreased LDL-cholesterol (−0·23 (sd 0·29) v. −0·04 (sd 0·28) mmol/l, P=0·03) and total-:HDL-cholesterol ratio (−0·47 (sd 0·31) v. −0·06 (sd 0·42), P<0·001), and significantly increased HDL-cholesterol levels (+0·18 (sd 0·19) v. +0·02 (sd 0·13) mmol/l, P=0·001) compared with the placebo. In addition, taking Se supplements was associated with a significant reduction in high-sensitivity C-reactive protein (hs-CRP) (−1880·8 (sd 3437·5) v. +415·3 (sd 2116·5) ng/ml, P=0·01), and a significant elevation in plasma total antioxidant capacity (TAC) (+30·9 (sd 118·0) v. −187·9 (sd 412·7) mmol/l, P=0·004) and total glutathione levels (+33·7 (sd 130·4) v. −39·2 (sd 132·8) µmol/l, P=0·003) compared with the placebo. When we applied Bonferroni correction for multiple outcome testing, QUICKI (P=0·11), LDL-cholesterol (P=0·51), hs-CRP (P=0·17), TAC (P=0·06) and GSH (P=0·05) became non-significant, and other metabolic profiles did not alter. Overall, our study supported that Se supplementation for 12 weeks to patients with CHF had beneficial effects on insulin metabolism and few markers of cardio-metabolic risk.
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Khan, Faiz, Nora Granville, Raja Malkani, and Yash Chathampally. "Health-Related Quality of Life Improvements in Systemic Lupus Erythematosus Derived from a Digital Therapeutic Plus Tele-Health Coaching Intervention: Randomized Controlled Pilot Trial." Journal of Medical Internet Research 22, no. 10 (October 20, 2020): e23868. http://dx.doi.org/10.2196/23868.
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Background Systemic lupus erythematosus (SLE), a systemic autoimmune disease with no known cure, remains poorly understood and patients suffer from many gaps in care. Recent work has suggested that dietary and other lifestyle factors play an important role in triggering and propagating SLE in some susceptible individuals. However, the magnitude of influence of these triggers, how to identify pertinent triggers in individual patients, and whether removing these triggers confers clinical benefit is unknown. Objective To demonstrate that a digital therapeutic intervention, utilizing a mobile app that allows self-tracking of dietary, environmental, and lifestyle triggers, paired with telehealth coaching, added to usual care, improves quality of life in patients with SLE compared with usual care alone. Methods In this randomized controlled pilot study, adults with SLE were assigned to a 16-week digital therapeutic intervention plus usual care or usual care alone. Primary outcome measures were changes from baseline to 16 weeks on 3 validated health-related quality of life (HRQoL) tools: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Brief Pain Inventory-Short Form (BPI-SF), and Lupus Quality of Life (LupusQoL). Results A total of 50 patients were randomized (23 control, 27 intervention). In per-protocol analysis, the intervention group achieved significantly greater improvement than the control group in 9 of 11 domains: FACIT-F (34% absolute improvement for the intervention group vs –1% for the control group, P<.001), BPI-SF-Pain Interference (25% vs 0%, P=.02), LupusQoL-Planning (17% vs 0%, P=.004), LupusQoL-Pain (13% vs 0%, P=.004), LupusQoL-Emotional Health (21% vs 4%, P=.02), and LupusQoL-Fatigue (38% vs 13%, P<.001) were significant when controlling for multiple comparisons; BPI-SF-Pain Severity (13% vs –6%, P=.049), LupusQoL-Physical Health (17% vs 3%, P=.049), and LupusQoL-Burden to Others (33% vs 4%, P=.04) were significant at an unadjusted 5% significance level. Conclusions A digital therapeutic intervention that pairs self-tracking with telehealth coaching to identify and remove dietary, environmental, and lifestyle symptom triggers resulted in statistically significant, clinically meaningful improvements in HRQoL when added to usual care in patients with SLE. Trial Registration ClinicalTrials.gov NCT03426384; https://clinicaltrials.gov/ct2/show/NCT03426384
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Li, Xiaomin, You Yang, Shimin Liu, Jing Yang, Cheng Chen, and Zhihong Sun. "Grape seed extract supplementation attenuates the heat stress-induced responses of jejunum epithelial cells in Simmental × Qinchuan steers." British Journal of Nutrition 112, no. 3 (May 20, 2014): 347–57. http://dx.doi.org/10.1017/s0007114514001032.
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Grape seed extract (GSE), a rich source of polyphenols, is reported to possess antioxidant, anti-inflammatory and immunomodulatory properties. The objective of the present study was to determine whether GSE could attenuate the heat stress-induced responses of jejunum epithelial cells (JEC) in cattle. The JEC of a steer (Simmental × Qinchuan) were exposed to heat stress for 2 h in the absence (0 μg/ml) or presence (10, 20, 40 and 80 μg/ml) of GSE in the culture medium. When cultured at 40°C, JEC supplemented with GSE exhibited increased glutathione peroxidase activity (P= 0·04), viability (P= 0·004), and mRNA expression of epidermal growth factor (EGF; P= 0·03) and EGF receptor (EGFR; P= 0·01). Under the same conditions, the cells exhibited decreased mRNA expression of IL-8 (P= 0·01) and TNF-α (P= 0·03) and decreased protein concentrations of IL-1β (P= 0·02), Toll-like receptor 4 (TLR4; P= 0·04) and heat shock protein 70 (HSP70; P< 0·001). When cultured at 43°C, JEC supplemented with GSE exhibited increased catalase activity (P= 0·04), viability (P< 0·001), and mRNA expression of EGF (P< 0·001) and EGFR (P< 0·001) and decreased protein concentrations of IL-1β (P< 0·001), TLR4 (P= 0·03) and HSP70 (P< 0·001), as well as mRNA expression of IL-8 (P< 0·001), TLR4 (P= 0·002) and TNF-α (P< 0·001). Temperature × GSE concentration interactions were also observed for the concentrations of IL-1β (P< 0·001), IL-8 (P< 0·001), TNF-α (P= 0·01) and HSP70 (P= 0·04) and viability (P< 0·001) of JEC. The results of the present study indicate that GSE can attenuate the responses of JEC induced by heat stress within a certain range of temperatures.
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Goekkurt, Eray, Salah-Eddin Al-Batran, Jörg T. Hartmann, Ulrike Mogck, Gunter Schuch, Michael Kramer, Elke Jaeger, Carsten Bokemeyer, Gerhard Ehninger, and Jan Stoehlmacher. "Pharmacogenetic Analyses of a Phase III Trial in Metastatic Gastroesophageal Adenocarcinoma With Fluorouracil and Leucovorin Plus Either Oxaliplatin or Cisplatin: A Study of the Arbeitsgemeinschaft Internistische Onkologie." Journal of Clinical Oncology 27, no. 17 (June 10, 2009): 2863–73. http://dx.doi.org/10.1200/jco.2008.19.1718.
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PurposeTo evaluate the association of germ-line polymorphisms of genes that may impact treatment outcome of platinum and fluorouracil combination chemotherapy in advanced gastric cancer (AGC).Patients and MethodsBlood samples of 156 patients enrolled onto a phase III study comparing fluorouracil, leucovorin, and oxaliplatin with fluorouracil, leucovorin, and cisplatin were collected. Polymorphisms within genes of TS, MTHFR, MTR, OPRT, XPD, ERCC1, XRCC1, XPA, GSTP1, GSTT1, and GSTM1 were genotyped using polymerase chain reaction–based techniques.ResultsMedian overall survival (OS) was 11.8 months (95% CI, 9.75 to 13.79 months) and median progression-free survival (PFS) was 5.8 months (95% CI, 4.99 to 6.61 months). The TS-3R/+6 haplotype (P = .004), the GSTT1 deletion polymorphism (P = .015), and genotypes of OPRT-Gly213Ala (P = .003) and XRCC1-Arg399Gln (P = .023) could be identified as independent predictors of OS. For PFS analyses, the TS-3R/+6 haplotye (P = .003) and MTR-A2756G (P = .01) were identified as independent positive predictors. The association between the GSTT1 deletion polymorphism and PFS showed only borderline significance (P = .053). Treatment related hematotoxicity in terms of grade 3/4 leukopenia was lowest among TS-3R/+6 haplotype carriers (P = .037). Grade 3/4 neutropenia was directly associated with the MTR-2756G/G genotype (P = .011), GSTP1-105Ile/Ile genotype (P = .02), and with the ERCC1-118T/8092C-haplotype (P = .042). In addition, significant associations between GSTP1-105Ile/Ile genotype and neurotoxicity and between the XPD-Asn312/751Gln haplotype and nephrotoxicity could be identified (P = .028 and P = .005, respectively).ConclusionThese findings underline the hypothesis that germ-line polymorphisms may play an important role in individualizing chemotherapy in AGC and deserve further prospective evaluation in AGC patients.
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Brigido, Stephen A., Nicole M. Protzman, Melissa M. Galli, and Scott T. Bleazey. "The Role of Demineralized Allograft Subchondral Bone in the Treatment of Talar Cystic OCD Lesions That Have Failed Microfracture." Foot & Ankle Specialist 7, no. 5 (April 29, 2014): 377–86. http://dx.doi.org/10.1177/1938640014531984.
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Cystic talar shoulder defects are particularly challenging osteochondral lesions. A retrospective chart review was performed on 13 adults that previously failed microfracture, presented with medial cystic osteochondral lesions of the talus, and were treated with malleolar osteotomy and subchondral allograft reconstruction. The aim of the study was to evaluate the effect of a medial malleolar osteotomy and allograft subchondral bone plug on pain and function. We hypothesized that following surgery, pain and function would significantly improve. Compared with preoperative measures, pain (first step in the morning, during walking, at the end of the day) and function (descending the stairs, ascending the stairs, and ambulating up to 4 blocks) improved postoperatively at 6 and 12 months ( P ≤ .001). During each activity, pain improved postoperatively from 6 to 12 months ( P ≤ .006). Postoperatively, from 6 to 12 months, the level of disability improved while descending the stairs ( P = .004), and the level of disability experienced while ascending the stairs and ambulating up to 4 blocks was maintained ( P ≥ .02). Multiple regression analyses identified body mass index as a predictor of preoperative function ( R2 = .34, P = .04). No variables were identified as significant predictors of postoperative pain or function. With all osteotomies healing, no graft rejection, and a single deep venous thrombosis, allograft subchondral plugs appear to successfully treat osteochondral lesions of the talus with improvements in pain and function as well as an acceptable complication rate. Level of Evidence: Therapeutic, Level IV: Retrospective Case Series.
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Sekeres, Mikkael A., Jaroslaw P. Maciejewski, David W. Donley, David L. Grinblatt, Mohit Narang, James M. Malone, Rami S. Komrokji, et al. "A Study Comparing Dosing Regimens and Efficacy of Subcutaneous to Intravenous Azacitidine (AZA) for the Treatment of Myelodysplastic Syndromes (MDS)." Blood 114, no. 22 (November 20, 2009): 3797. http://dx.doi.org/10.1182/blood.v114.22.3797.3797.
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Abstract Abstract 3797 Poster Board III-733 Background AZA, the most commonly used disease-modifying therapy for MDS in the US, demonstrates a survival advantage in higher-risk (International Prognostic Scoring System [IPSS] Int-2, High, or excess blasts) MDS subtypes. It was approved by the US FDA in 2004 as a 7-day per 28-day, subcutaneous (SC) regimen, based on response rates, with the 7-day intravenous (IV) route approved in 2007 based on efficacy data from the CALGB 8421 study and pharmacokinetic data. This registry allows for the evaluation of community based practices for dosing and effectiveness of IV compared with SC administration in MDS. Methods AVIDA, a prospective, longitudinal, multicenter US patient (pt), registry collects data from community-based hematology clinics on the history and management of pts with MDS treated with AZA. Interim analyses were conducted on data collected from October 2006 – May 2009 with investigator chosen regimens according to the most commonly used per pt. Responses used 2006 International Working Group criteria, quantified as hematologic improvement (HI) or better and were assessed centrally. ANCOVA models were used for dose per cycle analyses and generalized estimating equations were used for analyses of cycle delay. Cox models incorporating survival were used for multivariate analyses. Results Of 380 registry pts (median age, 75 years [range, 29-91], 104 (31%), female), 331 had MDS or oligoblastic leukemia, of whom 190 (57%) most commonly received AZA via IV and 141 (43%) by SC (both for a median of 4 cycles). Median time since MDS diagnosis was 2 months (range, 0-207), and 10% of pts had secondary MDS. Baseline bone marrow blast % was: <5% (46%); 5-10% (26%); 11-20% (14%); 21-30% (3%); and unknown (11%); IPSS cytogenetic groups were: good (61%); intermediate (10%); poor (17%); unknown (11%), with 6% and 9% of pts having a chromosome 7 and 7q abnormalities, respectively. IPSS risk groups were: Low (11%); Int-1 (36%); Int-2 (15%); High (6%); unknown (33%). ECOG performance status was: 0 (25%); 1 (53%); 2 (16%); 3 (6%). Only 17% of pts received the FDA-approved continuous 7-day dosing schedule; 51% received <7 days; 30% 7 days with breaks; and 2% >7 days. There were no significant differences between SC and IV AZA recipients for any of the above baseline parameters. At the interim analysis time point of 600 days, there were 21 deaths (15%) in the SC group and 32 deaths (17%) in the IV group. In univariate analyses, the following predicted for worse survival: black race (versus white, P = .02); higher-risk MDS (P = .02); cytogenetic abnormalities (P = .004); IPSS poor risk cytogenetic group (P = .04); low body mass index (BMI, P = .03), high blast % (P = .01)and baseline low hemoglobin (hgb, P = .007), or low platelets (plt, P = .05), all analyzed continuously. SC vs. IV dosing had no differing effect on HI rate (24% overall). In multivariate analyses, significant variables included low hgb (P = .006), low plt (P = .05), high blast % (P = .04), cytogenetic abnormalities (P = .05), and low BMI (P = .002). Delays in cycle start times (>28 days from previous cycle start) were related in multivariate analyses to higher blast % (P = .004), male gender (P = .03), dosing schedule (P = .02), a trend with IV dosing (P = .1), cytogenetic risk score (P = .1) and del (5q) (P = .09). Lower AZA doses per cycle were related in multivariate analyses to IV dosing (P = .001, on average 12 mg lower); older age (P = .01, on average .6mg less per year); BMI (P < .001), female gender (P < .001), and, as expected, dosing schedule (P = .04). Conclusions In this interim analysis of the ongoing AVIDA Registry, IV AZA appears equi-efficacious to SC, although dose, schedule, and treatment differed between groups. Though the FDA-approved continuous dosing schedule of AZA was infrequently used, this has not negatively impacted efficacy to date. In multivariate analyses, traditional IPSS predictors of survival are still relevant in pts treated with AZA. These analyses also reveal other potentially significant factors, such as low BMI, the effect of gender, and age on treatment intensity and clinical outcomes in patients receiving AZA. Disclosures: Baker: Celgene: Employment, Equity Ownership. Sullivan:Celgene: Employment, Equity Ownership.
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Rahman, Sabuktagin, Ahmed Shafiqur Rahman, Nurul Alam, AM Shamsir Ahmed, Santhia Ireen, Ireen Akhter Chowdhury, Fatima Parveen Chowdhury, SM Mustafizur Rahman, and Tahmeed Ahmed. "Vitamin A deficiency and determinants of vitamin A status in Bangladeshi children and women: findings of a national survey." Public Health Nutrition 20, no. 6 (November 28, 2016): 1114–25. http://dx.doi.org/10.1017/s1368980016003049.
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AbstractObjectiveUsing data from the national micronutrients survey 2011–2012, the present study explored the status of subclinical vitamin A nutrition and the underlying determinants in the Bangladeshi population.DesignA nationwide cross-sectional study.SettingsThe survey covered 150 clusters; fifty in each of rural, urban and slum strata.SubjectsThree population groups: (i) pre-school age children (6–59 months; PSAC); (ii) school age children (6–14 years; SAC); and (iii) non-pregnant non-lactating women (15–49 years; NPNLW).ResultsNational prevalence of subclinical vitamin A deficiency was 20·5, 20·8 and 5·3 % in PSAC, SAC and NPNLW, respectively. Slum populations had higher prevalence compared with urban (PSAC: 38·1 v. 21·2 %, P<0·001; SAC: 27·1 v. 22·1 %, P=0·004; NPNLW: 6·8 v. 4·7 %, P=0·01). Dietary vitamin A met up to 27·1–46·0 % of daily needs; plant-source vitamin A constituted 73–87 % of the intakes. Multivariable regression analyses showed that higher consumption of animal foods was associated with higher retinol status in PSAC (β=0·27; P<0·001); and living in urban area was related to higher retinol status in NPNLW (β=0·08, P=0·004) and PSAC (β=0·11, P=0·04). Increased intake of leafy vegetables was associated with lower retinol status in SAC (β=−0·08, P=0·02). Vitamin A supplementation in PSAC did not significantly influence serum retinol within one year post-supplementation (P>0·05 for differences in β between <3 months v. 3–6 months, 6–9 months and 9–12 months).ConclusionsPrevalence of subclinical vitamin A deficiency was high in children in Bangladesh. Intakes of animal-source foods and leafy vegetables were associated with higher and lower retinol status, respectively. Increased food diversity through animal-source foods is required.
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Pomportes, Laura, Jeanick Brisswalter, Arnaud Hays, and Karen Davranche. "Effects of Carbohydrate, Caffeine, and Guarana on Cognitive Performance, Perceived Exertion, and Shooting Performance in High-Level Athletes." International Journal of Sports Physiology and Performance 14, no. 5 (May 1, 2019): 576–82. http://dx.doi.org/10.1123/ijspp.2017-0865.
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Purpose: To investigate the effect of ingesting carbohydrate (CHO), caffeine (CAF), and a guarana complex (GUAc) during a running exercise on cognitive performance, rating of perceived exertion (RPE), and shooting performance in high-level modern pentathlon athletes. Methods: A total of 10 athletes completed 4 counterbalanced sessions within a 2-wk period, corresponding to ingestions of CHO (30 g), GUAc (300 mg), CAF (200 mg), or placebo. The exercise involved a 40-min run on a treadmill at a steady speed, previously determined as a “somewhat hard” exercise (RPE 13). Shooting and cognitive performance (Simon task) were assessed in 3 phases: before exercise and ingestion, before exercise and after half ingestion, and after exercise and full ingestion. Drinks were consumed 40 min (250 mL) and 5 min (125 mL) prior to exercise and after 20 min of running (125 mL). RPE was assessed at 10-min intervals during exercise. Results: There was an interaction between drink and exercise on mean reaction time (P = .01, ) and a drink effect on RPE (P = .01, ). CHO, CAF, and GUAc enhanced the speed of information processing after exercise (P = .003, P = .004, and P = .04, respectively), but only CAF and GUAc decreased RPE (P = .002 and P = .02, respectively). Conclusion: The results highlight a beneficial effect of nutritional supplements on information processing and RPE. This finding is particularly interesting as decision-making processes are crucial in the performance of many sports.
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Tiu, Ramon V., Christine O'Keefe, Lukasz P. Gondek, Azim M. Mohamedali, Bartlomiej P. Przychodzen, Ghulam J. Mufti, Mikkael A. Sekeres, Anjali S. Advani, Michael A. McDevitt, and Jaroslaw P. Maciejewski. "Acquired Somatic Uniparental Disomy is a Chromosomal Defect Important in Predicting Treatment Responses and Survival Outcomes in MDS, MDS/MPN and Secondary AML." Blood 114, no. 22 (November 20, 2009): 2630. http://dx.doi.org/10.1182/blood.v114.22.2630.2630.
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Abstract Abstract 2630 Poster Board II-606 Single nucleotide polymorphism array (SNP-A) karyotyping improves detection of chromosomal defects in myeloid malignancies, including acquired somatic uniparental disomy (AS-UPD). AS-UPD comprises ∼30–35% of new lesions in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). To date, impact of AS-UPD on treatment responses and clinical outcomes has not been established. We hypothesized that AS-UPD is a clinically and prognostically important chromosomal lesion in MDS and associated myeloid neoplasms. To that end, we studied bone marrow (BM) from 403 patients using Affymetrix 250K and 6.0 SNP-A: 235 MDS, 80 MDS/ myeloproliferative neoplasms (MPN), 8 idiopathic myelofibrosis (IMF), and 80 AML that evolved from MDS (sAML). Median follow up was 23 months. All gains and deletions with >50% overlap with copy number variants (CNVs) in our internal control (N=1003) and publicly-available databases were excluded. We also excluded germ line, non-clonal regions of homozygosity (ROH) defined by criteria established through analysis of our control cohort. ROH were present in 12% of controls. Based on 95th percentile for interstitial and telomeric locations, ROH <24Mb and <7.4Mb, respectively, were excluded. Clinical parameters measured included survival outcomes (overall [OS], event free [EFS], and progression free [PFS] survival) analyzed using the Kaplan-Meier method. The two sided Fischer's-exact test were used for categorical comparisons. The Cox-proportional hazards model was used to assess univariate and multivariate analyses for OS, PFS, and EFS; factors assessed included age (≥60 vs. <60 years), BM blasts (≥5 vs. <5 %), number of cytopenias (≥2 vs. <1), metaphase cytogenetics (MC) risk groups using International Prognostic Scoring System (IPSS) criteria (good, intermediate, poor) and AS-UPD (with lesions vs. no lesions). Each variable was retained in the multivariate model regardless of its statistical significance or lack thereof. Only variables with p<.05 in multivariate analysis were considered significant. AS-UPD accounts for 30%, 32%, 31% of lesions in MDS, MDS/MPN and sAML, respectively. Sole AS-UPD was seen at >5% for chromosomes 1, 4, 6, 7, 9, 11, 17, 21, while 2 and ≥3 lesions occurred at 8.1% and 12.1%. Regardless of prior MC and type of myeloid neoplasm, patients with AS-UPD had worse OS [11 vs. 24 mo, p=.0004], PFS [15 vs. 33 mo, p=.0004], and EFS [13 vs. 21 mo, p=.003] compared to those with no AS-UPD. Patients with normal MC and AS-UPD had inferior survival outcomes (OS [13 vs. 45 mo, p=.002], EFS [13 vs. 28 mo; p=.004, PFS [14 vs. not reached {NR}; p=.01], as did those with AS-UPD and non-informative MC (OS [7 vs. 17 mo, p=.01], EFS [5 vs. 17 mo, p=.002], PFS [4 vs. 40 mo, p=<.0001]. When patients were stratified according to disease types, patients with AS-UPD had a worse OS [17 vs. 46 months; p=.02] in MDS; OS [3 vs. 5 mo, p=.01], PFS [3 vs. 7 mo, p=.0002], and EFS [3 vs. 6 mo, p=.03] in sAML. When patients were grouped according to WHO classification, the presence of AS-UPD conferred worse outcomes in low risk (OS [35 vs. 81 mo, p=0.05]) and high risk patients (OS [5 vs. 9 mo, p=.006], PFS [4 vs. 11 mo, p=.002], and EFS [4 vs. 8 mo, p=.004]). When individual AS-UPD lesions were analyzed, the worst OS was seen in patients with AS-UPD involving chromosomes 5(3 mo), 7(3 mo),13 (2 mo), 14 (3 mo), 16 (4 mo), 17 (3 mo) , 21(5 mo), and 22 (3 mo). AS-UPD also influences responses and outcomes related to treatment types. Overall response (CR + PR + HI) rates were worse in patients with AS-UPD (26% vs.42%, p=.003). Patients with AS-UPD treated with low intensity chemotherapy (LIC [lenalidomide, 5-azacitidine, decitabine, arsenic, thalidomide]) [6 vs. 16 mo, p=0.01] and allogeneic BM transplantation/intensive chemotherapy [6 vs. 14 mo, p=.09] have worse OS compared to those with no AS-UPD. In multivariate analyses, presence of AS-UPD (OS [HR=1.66, p=.01]; EFS [HR=1.5, p=.04]), BM blasts ≥5% (OS [HR=2.24, p=<.0001]; EFS [HR=2.04, p=.0001]), and poor risk cytogenetics by MC (OS [HR=1.57, p=.0002]; EFS [1.58, <.0001]) were poor predictors of both OS and EFS in MDS, MDS/MPN and sAML while age ≥60 remain a poor predictor of OS (HR=1.52, p=.01). In conclusion, AS-UPD is a chromosomal defect commonly seen in patients with MDS, MDS/MPN and sAML. The presence of AS-UPD influences treatment responses and outcomes to LIC and BMT/IC. More importantly, AS-UPD is an independent predictor of OS and EFS in myeloid malignancies. Disclosures: Advani: Cephalon: Research Funding.
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Malamitsi-Puchner, Ariadne, Theodora Boutsikou, Emmanuel Economou, Angeliki Sarandakou, Evangelos Makrakis, Dimitrios Hassiakos, and George Creatsas. "Vascular Endothelial Growth Factor and Placenta Growth Factor in Intrauterine Growth-Restricted Fetuses and Neonates." Mediators of Inflammation 2005, no. 5 (2005): 293–97. http://dx.doi.org/10.1155/mi.2005.293.
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The angiogenic factors vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) are respectively up- and downregulated by hypoxia. We aimed to study circulating levels of the above factors in intrauterine growth restriction (IUGR) and to correlate their levels with the customized centiles of the infants. The study included 25 IUGR and 25 appropriate for gestational age (AGA) full-term, singleton infants and their mothers. Maternal (MS), fetal (UC), and neonatal day 1 (N1) and 4 (N4) blood was examined. MS and N1 PlGF, as well as UC VEGF levels correlated with the customized centiles of the infants (r=0.39,P=.007,r=0.34,P=.01, andr=−0.41,P=.004, resp). Furthermore, UC, N1, and N4 VEGF levels were higher in girls (r=0.36,P=.01,r=0.33,P=.02, andr=0.41,P=.005resp). In conclusion, positive and negative correlations of examined factors with the customized centiles of the infant could rely on placental function and intrauterine oxygen concentrations—both being usually lower in IUGR cases—while higher VEGF levels in girls should possibly be attributed to the stimulating action of estrogens.
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Rossoni, Gilda, Vanesa Gregorc, Alessandra Bulotta, Maria Grazia Viganò, Gabriele Todisco, Antonio Lambiase, and Claudio Bordignon. "Infusion-related reactions (IRR) during NGR-hTNF therapy as potential predictors of clinical outcome." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e13593-e13593. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e13593.
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e13593 Background: NGR-hTNF, a selective antivascular agent, transiently modulates the systemic release of cytokines/chemokines. Intravenous infusion of NGR-hTNF is distinguished by an early on-target effect, IRR, which mostly consists of short-lived grade 1/2 chills. Methods: Incidence, predictors of development and relationships of IRR with treatment outcome were assessed in a pooled analysis of individual patient data from 5 phase II trials with NGR-hTNF. Global data set comprised 205 previously treated patients (pts) who had received NGR-hTNF 0.8 µg/m2 every 3 weeks (q3w) or weekly (q1w) alone in mesothelioma, colon and liver cancers or in combination with doxorubicin in small cell lung and ovarian cancers. In all trials, response to therapy (RECIST) was measured q6w until progression. Regression models estimated the effect size of IRR on response rate (RR; complete and partial response), disease control rate (DCR; RR plus stable disease) and progression free survival (PFS). Results: 137/205 pts (67%) experienced IRR on treatment, while 68 pts (33%) did not. In the IRR group, 63% of pts had grade 1 and 37% grade 2. By time to onset, 88% of pts developed IRR during first 6 weeks of therapy and 12% later. According to dosing schedule, IRR rates were higher with q1w than with q3w (85% vs 62%; p=.008). Baseline characteristics were (IRR vs non-IRR groups): median age: 66 vs 64; male: 50% vs 56%; PS ≥ 1: 34% vs 35%, range of prior lines: 1-4 vs 1-5. Among baseline characteristics, logistic regression analysis retained only a lower number of prior lines associated with higher IRR rates (OR=1.4; p=.02). Onset of IRR was related to better treatment outcome. RR was 12% in the IRR and 3% in the non-IRR group (OR=4.4; p=.05), while DCR was 50% in pts who had IRR and 34% in pts who did not (OR=2.0; p=.02). In pts with or without IRR, 6-month PFS was 21% vs 7% (HR=0.62; p=.001), respectively. Improvement in PFS time remained significant in a landmark analysis set at the 6-week time point (p=.004). On multivariate analyses adjusted for baseline variables, IRR independently predicted higher odds of tumor response (p=.05) and lower risk of progression or death (p=.009). Conclusions: Onset of IRR on NGR-hTNF treatment may predict subsequent clinical outcome. Clinical trial information: NCT00483080-NCT00483509-NCT00484211-NCT00484276-NCT00484432.
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Gluz, Oleg, Cornelia Liedtke, Aleix Prat, Matthias Christgen, Daniel Gebauer, Ronald E. Kates, Eva-Maria Grischke, et al. "Association of molecular subtype, proliferation, and immune genes with efficacy of carboplatin versus gemcitabine addition to taxane-based, anthracycline-free neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC): Results of the randomized WSG ADAPT-TN trial." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 573. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.573.
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573 Background: In the ADAPT-TN neoadjuvant trial, 12-week nab-paclitaxel (nab- pac)+carboplatin (carbo) was highly effective and superior to nab-pac+gemcitabine (gem). However, within TNBC, reliable predictive markers for carbo use have yet to be identified. Methods: Patients with early TNBC (centrally confirmed) were treated by nab-pac 125 mg/m2 with either carbo AUC2 or gem 1000 mg/m2 d 1,8 q21 given for 4 cycles. Genomic data (80 genes) and Prosigna (PAM-50) scores were available in 306 pre-therapeutic samples of 331 treated patients. Fisher’s exact test was performed for pCR differences; associations of continuous measurements or scores with pCR were analyzed by the Mann-Whitney statistic. Results: pCR was 44.5% to 28.4% (p=.004) in favor of nab-pac - carbo. Specifically within the carbo- containing arm, immunological (CD8, PD1, PFDL1) genes and proliferation markers (proliferation score and ROR scores, MKI67, CDC20, NUF2, KIF2C, CENPF, EMP3, TYMS) were positively associated with pCR (p<.05 for all). Specifically within the gem-arm, angiogenesis genes were negatively associated with pCR (ANGPTL4: p=.05; FGFR4: p=.02; VEGFA: p=.03). In the whole collective, basal-like (83.3%) was favorable for pCR (38% vs. 20%, p=.015) compared to other subtypes (HER: 6.4%; luminal-A: 1.7%; normal: 8.7%), as was lower HER-2 score (p<.001). Proliferation was positively associated with pCR: i.e., Pam50 proliferation score, ROR scores (all p<.004), and higher Ki67 by central IHC (p<.001) -- though not MKI67 RNA expression, despite their moderate correlation. Conclusions: In early TNBC, basal-like subtype, higher Ki67 (by IHC), and lower HER-2 score were associated with chemo-sensitivity for both neoadjuvant arms. Chemo-resistance pathways differed between the two taxane-based combinations (low proliferation and immune marker gene expression for carbo, high angiogenesis for gem). The positive predictive impact of immunological genes in the nab-pac - carbo arm could influence optimal patient selection for immune-modulative therapy. Clinical trial information: NCT01815242.
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Wattel, E., A. Guerci, B. Hecquet, T. Economopoulos, A. Copplestone, B. Mahe, ME Couteaux, et al. "A randomized trial of hydroxyurea versus VP16 in adult chronic myelomonocytic leukemia. Groupe Francais des Myelodysplasies and European CMML Group." Blood 88, no. 7 (October 1, 1996): 2480–87. http://dx.doi.org/10.1182/blood.v88.7.2480.bloodjournal8872480.
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We performed a randomized study of hydroxyurea (HY) versus VP16 in advanced chronic myelomonocytic leukemia (CMML) patients with CMML (according to French-American-British group criteria) and either documented visceral involvement (excluding liver and spleen infiltration) or at least 2 of the following: (1) neutrophils > 16 x 10(9)/I (2) Hemoglobin < 10 g/dL (3) platelets < 100 x 10(9)/L (4) marrow blasts > 5% (5) spleen > 5 cm below costal margin were eligible for this trial. Initial dosage was 1 g/d for HY and 150 mg/week for VP16, orally (doubled in case of visceral involvement). Doses were scheduled to be escalated up to HY 4 g/d and VP16 600 mg/week in the absence of response, and finally adjusted to maintain white blood cells (WBCs) between 5 and 10 x 10(9)/L. Crossing over was scheduled only in case of life threatening visceral involvement or major progression. The major endpoint of the study was survival. The study was closed on first interim analysis that showed a superiority of HY over VP16, after inclusion of 105 pts (HY arm: 53, VP16 arm: 52). Results of the second interim analysis, performed 7 months later, are presented here. Median age was 71 (range 38 to 91), median WBC count 20.10(9)/L (range 10 to 187). Thirteen pts had visceral involvement (3 serous effusions, 8 cutaneous infiltrations, 1 kidney, 1 bone infiltrations). Initial characteristics were similar in the HY and VP16 groups. Median follow up was 11 months in both groups (range 1 to 43+). Response to treatment was seen in 60% of the pts in the HY group, versus 36%, respectively, in the VP16 group (P = .02). Time to response was significantly shorter in the HY group (2.1 v 3.5 months, in the VP16 group, P = .003) and response duration was significantly longer in the HY group (median 24 v 9 months, in the VP16 group, P = .0004). The response rate of patients with visceral involvement was 3 out of 7 in the VP16 arm versus 5 out of 6 in the HY group. Three of the 10 pts crossed over from HY to VP16 responded as compared to 6 pts of the 11 pts crossed over from VP16 to HY. HY yielded better response on leukocytosis (P = .002). The effect on splenomegaly platelets, on hemoglobin level and transfusion requirement was similar in the 2 treatment groups. A significantly higher incidence of alopecia was noted in the VP16 arm (20% v 3%, P = .03). Fourteen (27%) and 20 (38%) patients in the HY and the VP16 group respectively, progressed to acute myeloid leukemia (difference NS). Twenty five (53%) and 44 (83%) patients in the HY and the VP16 group, respectively, had died (P = .002). Median actuarial survival was 20 months in the HY arm, versus 9 months in the VP16 arm (P < 10(-4)). Main factors associated with poor survival were allocation to the VP16 arm, “unfavorable” karyotype (ie, monosomy 7 or complex abnormalities) and anemia. In the HY group, unfavorable karyotype (P = .006), and low hemoglobin level (P = .004) were significantly associated with low response rates. Prognostic factors for poor survival in the HY group were also unfavorable karyotype (P = .001), and low hemoglobin level (P < 10(-4). In conclusion, we found that HY gave higher response rates and better survival than VP16 in advanced CMML. However, even with HY responses were only partial and survival was generally poor. This stresses the need for new agents in the treatment of CMML, that will have to be compared with HY in future randomized studies.
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Holowiecki, Jerzy, Sebastian Grosicki, Sebastian Giebel, Tadeusz Robak, Slawomira Kyrcz-Krzemien, Kazimierz Kuliczkowski, Aleksander B. Skotnicki, et al. "Cladribine, But Not Fludarabine, Added to Daunorubicin and Cytarabine During Induction Prolongs Survival of Patients With Acute Myeloid Leukemia: A Multicenter, Randomized Phase III Study." Journal of Clinical Oncology 30, no. 20 (July 10, 2012): 2441–48. http://dx.doi.org/10.1200/jco.2011.37.1286.
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Purpose The goal of this study was to evaluate whether the addition of a purine analog, cladribine or fludarabine, to the standard induction regimen affects the outcome of adult patients with acute myeloid leukemia (AML). Patients and Methods A cohort of 652 untreated AML patients with median age 47 years (range, 17 to 60 years) were randomly assigned to receive one of three induction regimens: DA (daunorubicin plus cytarabine), DAC (DA plus cladribine), or DAF (DA plus fludarabine). Postremission treatment was the same for all arms. Results Complete remission rate in the DAC arm was higher compared with the DA arm (67.5% v 56%; P = .01) as a consequence of reduced incidence of resistant disease (21% v 34%; P = .004). There was no significant difference in early outcome between the DAF and DA arms. The probability of overall survival was improved for the DAC arm (45% ± 4% at 3 years) compared with the DA arm (33% ± 4%; P = .02), and leukemia-free survival was comparable. Long-term outcome did not differ significantly for the comparison of the DAF and DA arms. A survival advantage of the DAC arm over the DA arm was observed among patients age 50 years or older (P = .005), those with initial leukocyte count above 50 × 109/L (P = .03), and those with unfavorable karyotype (P = .03). DAF revealed a significant advantage over DA in patients with adverse karyotype (P = .02). Conclusion The addition of cladribine to the standard induction regimen is associated with increased rate of complete remission and improved survival of adult patients with AML.
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Rocha, Vanderson, Myriam Labopin, Eliane Gluckman, Ray Powles, William Arcese, Andrea Bacigalupo, Josy Reiffers, et al. "Relevance of Bone Marrow Cell Dose on Allogeneic Transplantation Outcomes for Patients With Acute Myeloid Leukemia in First Complete Remission: Results of a European Survey." Journal of Clinical Oncology 20, no. 21 (November 1, 2002): 4324–30. http://dx.doi.org/10.1200/jco.2002.11.058.
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PURPOSE: Many attempts have been made to improve the results of allogeneic bone marrow transplantation (alloBMT) for patients with acute myeloid leukemia (AML) in first complete remission (CR1). Bone marrow cell dose has been reported to be an important factor in alloBMT; however, its true impact on relapse incidence (RI), leukemia-free survival (LFS), and nonrelapse mortality (NRM) in a large cohort of patients is unknown. PATIENTS AND METHODS: From January 1992 to December 1999, 572 bone marrow transplantation recipients reported to the European Blood and Marrow Transplantation (EBMT) registry underwent allografting from an HLA-identical sibling donor with an unmanipulated bone marrow for AML in CR1. RESULTS: The median number of nucleated cells (NCs) infused was 2.6 × 108/kg. Estimated 5-year NRM, LFS, and RI for patients receiving more or less than 2.6 × 108 NCs/kg were, respectively, 18% ± 5% v 30% ± 5% (P = .001), 68% ± 3% v 46% ± 3% (P < .00001), and 14% ± 4% v 24% ± 5% (P = .004). The association of cell dose with the above outcomes was confirmed in multivariate analyses for NRM (relative risk [RR], 0.53; P = .0007), for LFS (RR, 0.53; P = .00008), and for RI (RR, 0.57; P = .02). The cell dose was also an important factor for neutrophil (RR, 0.76; P = .009) and platelet (RR, 0.77; P = .03) recoveries; however, it did not statistically influence the incidence of acute graft-versus-host disease. CONCLUSION: This study shows that marrow cell dose is one of the most important factors influencing relapse, NRM, and LFS after alloBMT for patients with AML in CR1. Therefore, increasing the marrow cell dose should substantially improve the survival of these patients.
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Jung, Myungjin, Heontae Kim, Seungho Ryu, and Minsoo Kang. "Secular Trends in Physical Activity Among Immigrants in the United States, 2009–2018." Journal of Physical Activity and Health 18, no. 6 (June 1, 2021): 694–704. http://dx.doi.org/10.1123/jpah.2020-0812.
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Background: The objective of this study was to evaluate secular trends in domain-specific physical activity in the immigrant population in the US between 2009 and 2018. Method: A secondary data analysis from the 2009–2018 National Health and Nutrition Examination Survey; a total of 7282 immigrants in the US were included in this analysis. All domain-specific physical activity was assessed by a self-reported questionnaire. Tests for linear trends were performed to examine the trends of each physical activity time using orthogonal polynomial coefficients. Physical activity trends were assessed by the whole group and the various subgroups. Results: Total physical activity showed an upward linear trend in female (Ptrend = .04) and young adult (Ptrend = .009) immigrants. Work-related physical activity showed an upward linear trend in young adult immigrants (Ptrend = .01). Recreational physical activity showed an upward linear trend in young adult (Ptrend = .03) and Mexican American (Ptrend < .001) immigrants and in immigrants living in the US for 15–29 years (Ptrend = .02). In contrast, we observed downward linear trends in transit-related physical activity for immigrants across male (Ptrend = .04), middle-aged adult (Ptrend = .01), and non-Hispanic black groups (Ptrend = .004) and in immigrants living in the US for 15–29 years (Ptrend = .03). Conclusion: There were no significant linear trends in the 4 domains of physical activity in the overall US immigrant population; however, trends in domain-specific physical activity in the US immigrant population differed by gender, age, race/ethnicity, and length of residence. These findings may inform physical activity promotion strategies targeting US immigrant populations with diverse sociocultural backgrounds.
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Kampf, Anthony R., Jakub Plášil, Barbara P. Nash, Ivan Němec, and Joe Marty. "Uroxite and metauroxite, the first two uranyl oxalate minerals." Mineralogical Magazine 84, no. 1 (September 2, 2019): 131–41. http://dx.doi.org/10.1180/mgm.2019.57.
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AbstractUroxite (IMA2018-100), [(UO2)2(C2O4)(OH)2(H2O)2]⋅H2O, and metauroxite (IMA2019-030), (UO2)2(C2O4)(OH)2(H2O)2, are the first two uranyl oxalate minerals. Uroxite was found in the Markey mine, Red Canyon, San Juan County, Utah, USA and in the Burro mine, Slick Rock district, San Miguel County, Colorado, USA. Metauroxite was found only in the Burro mine. Both minerals are post-mining secondary phases found in efflorescent crusts on mine walls. Uroxite occurs as light yellow striated blades exhibiting moderate neon-green fluorescence, ca 2 Mohs hardness with good {101} and {010} cleavages. Calculated density = 4.187 g/cm3. Optics are: biaxial (–), α = 1.602(2), β = 1.660(2), γ = 1.680(2) (white light), 2Vmeas. = 59(1)°, 2Vcalc = 59.1°, moderate r > v dispersion, orientation Y = b, Z ∧ a = 35° in obtuse β and it is nonpleochroic. Metauroxite occurs as light yellow crude blades and tablets exhibiting weak green–grey fluorescence, ca 2 Mohs hardness with good {001} cleavage. Calculated density = 4.403 g/cm3. Approximate optics are: α′ = 1.615(5) and γ′ = 1.685(5). Electron probe microanalysis provided UO3 79.60, C2O3 10.02, H2O 10.03, total 99.65 wt.% for uroxite and UO3 82.66, C2O3 10.40, H2O 7.81, total 100.87 wt.% for metauroxite; C2O3 and H2O are based on the structures. Uroxite is monoclinic, P21/c, a = 5.5698(2), b = 15.2877(6), c = 13.3724(9) Å, β = 94.015(7)°, V = 1135.86(10) Å3 and Z = 4. Metauroxite is triclinic, P${\bar 1}$, a = 5.5635(3), b = 6.1152(4), c = 7.8283(4) Å, α = 85.572(5), β = 89.340(4), γ = 82.468°, V = 263.25(3) Å3 and Z = 1. The strongest reflections of the powder XRD pattern [d, Å (I, %)(hkl)] are for uroxite: 10.05(38)(011), 5.00(100)(022, ${\bar 1}$11), 4.75(23)(031), 4.43(51)(120, ${\bar 1}$02), 3.567(33)(131), 3.341(29)(033, ${\bar 1}$32, 004), 2.623(28)(${\bar 2}$02, 015, ${\bar 1}$43, 220) and for metauroxite: 6.06(45)(010), 5.52(33)(100), 4.97(34)(011), 4.52(100)(0${\bar 1}$1, 101), 3.888(80)(111, 002, ${\bar 1}$10), 3.180(51)(${\bar 1}$02, 0${\bar 1}$2), 2.604(32)(${\bar 2}$01, ${\bar 1}$${\bar 2}$1). In the structure of uroxite (R1 = 0.0333 for 2081 I > 2σI reflections), UO7 pentagonal bipyramids share corners forming [U4O24] tetramers, which are linked by C2O4 groups to form corrugated sheets. In the structure of metauroxite (R1 = 0.0648 for 1602 I > 2σI reflections) UO7 pentagonal bipyramids share edges forming [U2O12] dimers, which are linked by C2O4 groups to form zigzag chains.
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Stephens, Alastair, Hannah Rudd, Emilia Stephens, and Jayne Ward. "Secondary Prevention of Hip Fragility Fractures During the COVID-19 Pandemic: Service Evaluation of “MRS BAD BONES”." JMIR Aging 3, no. 2 (December 22, 2020): e25607. http://dx.doi.org/10.2196/25607.
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Background Management of osteoporosis is an important consideration for patients with femoral neck fractures due to the morbidity and mortality it poses. The input of orthogeriatric teams is invaluable in coordinating secondary fragility fracture prevention. The COVID-19 pandemic resulted in the rapid restructuring of health care teams and led to the redeployment of orthogeriatricians. Objective This study aimed to determine the impact COVID-19 had on the secondary prevention of fragility fractures among patients with femoral neck fractures, and to optimize management in this population. Methods A retrospective audit was conducted of patients with femoral neck fractures before and after the lockdown in response to the COVID-19 pandemic in the United Kingdom. A reaudit was conducted following the development of our new mnemonic, “MRS BAD BONES,” which addressed key factors in the assessment and management of osteoporosis: medication review, rheumatology/renal advice, smoking cessation; blood tests, alcohol limits, DEXA (dual energy X-ray absorptiometry) scan; bone-sparing medications, orthogeriatric review, nutrition, exercise, supplements. The Fisher exact test was used for comparison analyses between each phase. Results Data for 50 patients were available in each phase. The orthogeriatric team reviewed 88% (n=44) of patients prelockdown, which fell to 0% due to redeployment, before recovering to 38% (n=19) in the postintervention period. The lockdown brought a significant drop in the prescription of vitamin D/calcium supplements from 81.6% (n=40) to 58.0% (n=29) (P=.02); of bone-sparing medications from 60.7% (n=17) to 18.2% (n=4) (P=.004), and DEXA scan requests from 40.1% (n=9) to 3.6% (n=1) (P=.003). Following the implementation of our mnemonic, there was a significant increase in the prescription of vitamin D/calcium supplements to 85.7% (n=42) (P=.003), bone-sparing medications to 72.4% (n=21) (P<.001), and DEXA scan requests to 60% (n=12) (P<.001). Conclusions The redeployment of the orthogeriatric team, due to the COVID-19 pandemic, impacted the secondary prevention of fragility fractures in the study population. The “MRS BAD BONES” mnemonic significantly improved management and could be used in a wider setting.
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Gemming, Luke, Elaine Rush, Ralph Maddison, Aiden Doherty, Nicholas Gant, Jennifer Utter, and Cliona Ni Mhurchu. "Wearable cameras can reduce dietary under-reporting: doubly labelled water validation of a camera-assisted 24 h recall." British Journal of Nutrition 113, no. 2 (November 28, 2014): 284–91. http://dx.doi.org/10.1017/s0007114514003602.
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Preliminary research has suggested that wearable cameras may reduce under-reporting of energy intake (EI) in self-reported dietary assessment. The aim of the present study was to test the validity of a wearable camera-assisted 24 h dietary recall against the doubly labelled water (DLW) technique. Total energy expenditure (TEE) was assessed over 15 d using the DLW protocol among forty adults (n 20 males, age 35 (sd 17) years, BMI 27 (sd 4) kg/m2 and n 20 females, age 28 (sd 7) years, BMI 22 (sd 2) kg/m2). EI was assessed using three multiple-pass 24 h dietary recalls (MP24) on days 2–4, 8–10 and 13–15. On the days before each nutrition assessment, participants wore an automated wearable camera (SenseCam (SC)) in free-living conditions. The wearable camera images were viewed by the participants following the completion of the dietary recall, and their changes in self-reported intakes were recorded (MP24+SC). TEE and EI assessed by the MP24 and MP24+SC methods were compared. Among men, the MP24 and MP24+SC measures underestimated TEE by 17 and 9 %, respectively (P< 0·001 and P= 0·02). Among women, these measures underestimated TEE by 13 and 7 %, respectively (P< 0·001 and P= 0·004). The assistance of the wearable camera (MP24+SC) reduced the magnitude of under-reporting by 8 % for men and 6 % for women compared with the MP24 alone (P< 0·001 and P< 0·001). The increase in EI was predominantly from the addition of 265 unreported foods (often snacks) as revealed by the participants during the image review. Wearable cameras enhance the accuracy of self-report by providing passive and objective information regarding dietary intake. High-definition image sensors and increased imaging frequency may improve the accuracy further.
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Ahmadi, Shahnaz, Mehri Jamilian, Maryam Tajabadi-Ebrahimi, Parvaneh Jafari, and Zatollah Asemi. "The effects of synbiotic supplementation on markers of insulin metabolism and lipid profiles in gestational diabetes: a randomised, double-blind, placebo-controlled trial." British Journal of Nutrition 116, no. 8 (September 29, 2016): 1394–401. http://dx.doi.org/10.1017/s0007114516003457.
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AbstractTo the best of our knowledge, data on the effects of synbiotic supplementation on markers of insulin metabolism and lipid concentrations in patients with gestational diabetes mellitus (GDM) are scarce. The aim of the current study was to determine the effects of synbiotic supplementation on markers of insulin metabolism and lipid profiles in GDM patients. In total, seventy patients with GDM aged 18–40 years were assigned to two groups – the synbiotic group (n 35) and the placebo group (n 35) – in this randomised, double-blind, placebo-controlled trial. Patients in the synbiotic group received a daily capsule that contained three viable and freeze-dried strains: Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium bifidum (2×109 colony-forming units/g each) plus 800 mg inulin for 6 weeks. Fasting blood samples were collected at the beginning and week 6 to quantify related markers. After 6 weeks of intervention, compared with the placebo, synbiotic supplementation led to a significant decrease in serum insulin levels (−1·5 (sd 5·9) v. +4·8 (sd 11·5) µIU/ml, P=0·005), homoeostatic model assessment for insulin resistance (−0·4 (sd 1·3) v. +1·1 (sd 2·7), P=0·003) and homoeostatic model assessment for β cell function (−5·1 (sd 24·2) v. +18·9 (sd 45·6), P=0·008) and a significant increase in quantitative insulin sensitivity check index (+0·01 (sd 0·01) v. −0·007 (sd 0·02), P=0·02). In addition, synbiotic intake significantly decreased serum TAG (−14·8 (sd 56·5) v. +30·4 (sd 37·8) mg/dl, P<0·001) and VLDL-cholesterol concentrations (−3·0 (sd 11·3) v. +6·1 (sd 7·6) mg/dl, P<0·001) compared with the placebo. Overall, the results of this study demonstrate that taking synbiotic supplements for 6 weeks among patients with GDM had beneficial effects on markers of insulin metabolism, TAG and VLDL-cholesterol concentrations.
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Charmaraman, Linda, Rachel Hodes, and Amanda M. Richer. "Young Sexual Minority Adolescent Experiences of Self-expression and Isolation on Social Media: Cross-sectional Survey Study." JMIR Mental Health 8, no. 9 (September 15, 2021): e26207. http://dx.doi.org/10.2196/26207.
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Background Early adolescent years are marked by pervasive self- and peer-regulation regarding gender and sexuality norms, which can affect the mental well-being of sexual minority youth. During this developmental period, social media use is also emerging as a dominant mode of communication with peers, allowing for both risk and resilient behaviors that can impact well-being. Objective This exploratory study aims to examine how sexual minorities in middle school use social media, who they are connected to and for what purposes, and the associations between these behaviors and mental well-being compared with their heterosexual peers. Methods In our cross-sectional survey study of 1033 early adolescents aged between 10 and 16 years (average age 12.7, SD 1.21 years) from 4 middle school sites in the Northeastern United States, we conducted an exploratory study comparing sexual minorities (212/873, 24.3% of sample with known sexual orientation) with their heterosexual peers (n=661), obtaining an 84.46% (1033/1223; total possible) response rate. Results Sexual minorities reported having smaller networks on their favorite social media website (β=−.57; P<.001), less often responded positively when friends shared good news (β=−.35; P=.002), and less often tried to make friends feel better when they shared bad news (β=−.30; P=.01). However, sexual minorities more often reported joining a group or web-based community to make themselves feel less alone (β=.28; P=.003), unlike heterosexual youth. Sexual minorities had higher averages of loneliness and social isolation (β=.19; P<.001) than heterosexual students. Sexual minorities were also twice as likely to have tried to harm themselves in the past (β=.81; odds ratio [OR] 2.24, 95% CI 1.64-3.06; P<.001) and were more likely to have symptoms that reached the Center for Epidemiological Studies-Depression definition of depression (β=.15; OR 1.16, 95% CI 1.08-1.25; P<.001). About 39.1% (83/212) of sexual minorities had no one to talk to about their sexual orientation. Sexual minorities were 1.5 times more likely to have joined a social media website their parents would disapprove (β=.41; OR 1.50, 95% CI 1.14-1.97; P=.004) and more likely to report seeing videos related to self-harm (β=.33; OR 1.39, 95% CI 1.06-1.83; P=.02) on the web than heterosexual youth. Conclusions Given previous reports of supportive and safe web-based spaces for sexual minority youth, our findings demonstrated that sexual minority youth prefer to maintain small, close-knit web-based communities (apart from their families) to express themselves, particularly when reaching out to web-based communities to reduce loneliness. Future longitudinal studies could determine any bidirectional influences of mental well-being and social media use in sexual minorities during this difficult developmental period.
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Kampf, Anthony R., Jakub Plášil, Travis A. Olds, Barbara P. Nash, and Joe Marty. "Uranoclite, a new uranyl chloride mineral from the Blue Lizard mine, San Juan County, Utah, USA." Mineralogical Magazine 85, no. 3 (March 31, 2020): 438–43. http://dx.doi.org/10.1180/mgm.2021.33.
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AbstractThe new mineral uranoclite (IMA2020-074), (UO2)2(OH)2Cl2(H2O)4, was found in the Blue Lizard mine, San Juan County, Utah, USA, where it occurs as tightly intergrown aggregates of irregular yellow crystals in a secondary assemblage with gypsum. The streak is very pale yellow and the fluorescence is bright green–white under 405 nm ultraviolet light. Crystals are translucent with vitreous lustre. The tenacity is brittle, the Mohs hardness is ~1½, the fracture is irregular. The mineral is soluble in H2O and has a calculated density of 4.038 g⋅cm–3. Electron microprobe analyses provided (UO2)2(OH)2.19Cl1.81(H2O)4. The six strongest powder X-ray diffraction lines are [dobs Å(I)(hkl)]: 8.85(38)(002), 5.340(100)(200, 110), 5.051(63)($\bar{2}$02), 4.421(83)(112, 004, 202), 3.781(38)($\bar{2}$12) and 3.586(57)(014, $\bar{2}$04). Uranoclite is monoclinic, P21/n, a = 10.763(8), b = 6.156(8), c = 17.798(8) Å, β = 95.656(15)°, V = 1173.5(18) Å3 and Z = 4. The structure is the same as that of synthetic (UO2)2(OH)2Cl2(H2O)4 in which the structural unit is a dimer consisting of two pentagonal bipyramids that share an equatorial OH–OH edge. The dimers are linked to one another only by hydrogen bonding. This is the second known uranyl mineral containing essential Cl and the first in which Cl coordinates to U6+.
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Agteresch, Hendrik J., Trinet Rietveld, Leon G. M. Kerkhofs, J. Willem O. van den Berg, J. H. Paul Wilson, and Pieter C. Dagnelie. "Beneficial Effects of Adenosine Triphosphate on Nutritional Status in Advanced Lung Cancer Patients: A Randomized Clinical Trial." Journal of Clinical Oncology 20, no. 2 (January 15, 2002): 371–78. http://dx.doi.org/10.1200/jco.2002.20.2.371.
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PURPOSE: In a randomized clinical trial in patients with advanced non–small-cell lung cancer (NSCLC), infusion with adenosine 5′-triphosphate (ATP) inhibited loss of body weight and quality of life. In the present article, the effects of ATP on body composition, energy intake, and energy expenditure as secondary outcome measures in the same patients are reported. PATIENTS AND METHODS: Patients with NSCLC, stage IIIB or IV, were randomized to receive either 10 intravenous, 30-hour ATP infusions every 2 to 4 weeks or no ATP. Fat mass (FM), fat-free mass (FFM), and arm muscle area were assessed at 4-week intervals for 28 weeks. Food intake, body cell mass (BCM), and resting energy expenditure (REE) were assessed at 8-week intervals for 16 weeks. Between-group differences were tested for statistical significance by repeated-measures analysis of covariance. RESULTS: Fifty-eight patients were randomized (28 ATP, 30 control). No change in body composition over the 28-week follow-up period was found in the ATP group, whereas, per 4 weeks, the control group lost 0.6 kg of FM (P = .004), 0.5 kg of FFM (P = .02), 1.8% of arm muscle area (P = .02), and 0.6% of BCM/kg body weight (P = .054) and decreased 568 KJ/d in energy intake (P = .0001). Appetite also remained stable in the ATP group but decreased significantly in the control group (P = .0004). No significant differences in REE between the ATP and control groups were observed. CONCLUSION: The inhibition of weight loss by ATP infusions in patients with advanced NSCLC is attributed to counteracting the loss of both metabolically active and inactive tissues. These effects are partly ascribed to maintenance of energy intake.