Artículos de revistas sobre el tema "821/.92"

The antimicrobial susceptibility testing was conducted on 174 single isolates from poultry farms in Serbia and it was determined that seven Salmonella spp. were multidrug resistant. Sixteen serotypes were detected, but only serotype Infantis confirmed reduced susceptibility to colistin. Seven colistin resistant Salmonella Infantis were studied in detail using the WGS approach. Three sequence types were identified corresponding to different epizootiology region. The isolate from the Province of Vojvodina 3842 and isolates from Jagodina (92 and 821) are represented by the sequence type ST413 and ST11, respectively. Four isolates from Kraljevo are ST32, a common S. Infantis sequence type in humans, poultry and food. The fosfomycin resistance gene fosA7 in isolate 3842 and the vgaA gene in isolate 8418/2948 encoding resistance to pleuromutilins were reported for the first time in serovar Infantis. The changes in relative expression of the phoP/Q, mgrB and pmrA/B genes were detected. Single nucleotide polymorphisms of the pmrB gene, including transitions Val164Gly or Val164Met, and Arg92Pro are described. Analyses of quinolone resistance determining region revealed substitutions Ser83Tyr in GyrA protein and Thr57Ser and Ser80Arg in ParC protein. Based on WGS data, there are two major clusters among analyzed Salmonella Infantis isolates from central Serbia.

Despite catastrophic ash (Fraxinus spp.) mortality observed by the mid-2000s in the epicenter of the emerald ash borer (EAB) (Agrilus planipennis Fairmaire) invasion in southeast Michigan, we noticed numerous live white ash (Fraxinus americana L.) in some forests in this region. In 2015, we inventoried overstory trees and regeneration in 28 white ash sites spanning 11 counties. White ash survival ranged from 0% to 100% of stems. Overall, 75% of 821 white ash trees, ranging from 10.0 to 44.0 cm diameter at breast height, and 66% of the white ash basal area, ranging from 0.3 to 3.5 m2·ha–1, were alive. Nearly all live white ash had signs of previous EAB colonization, but 83% had healthy canopies (≤10% canopy dieback). Green ash trees were recorded in 27 sites, but 92% were killed by EAB. Model selection indicated that variation in white ash survival was related to white ash abundance and distance of sites from the original EAB epicenter but not to green ash related variables or to the distance of sites from the Asian parasitoid release or recovery locations. Regeneration strata were dominated by white ash, suggesting that some white ash populations may persist in post-invasion areas.

The objective of this study was to measure the effect of supplementation with molasses blocks compared with conventional mineral supplementation (with specific formulations for the rainy and dry season) in 92 7-month-old Nellore heifers (Experiment 1) and 40 primiparous 31-month-old Nellore cows (Experiment 2) in Marandu grazing areas. The following measurements were obtained: weight, supplement intake, blood urea and glucose in heifers (Experiment 1), supplement intake, cow weight, body score, calf weight and ruminal temperature and drinking events in primiparous females (Experiment 2). The average molasses block intake was 242 g day-1 per heifer, with an average weight gain of 0.290 kg day-1; the heifers who consumed the molasses blocks were heavier during the rainy season (P < 0.05; Experiment 1). In Experiment 2, molasses block intake varied from 77 to 821 g day-1 per primiparous female, and the average intake in the control group was between 100 and 370 g day-1. The primiparous females given molasses blocks displayed lower weight loss due to calving (P < 0.05) and retained higher body scores at 150 days postpartum (P < 0.05). Ruminal temperature (P < 0.05) and drinking events (P < 0.05) were higher in primiparous Nellore females given molasses blocks. Overall, molasses blocks effectively increased Nellore female performance during the rainy season in Marandu grass pastures.

Object Surgery on the pituitary gland is increasingly being performed through an endoscopic approach. However, there is little published data on its safety and relative advantages over traditional microscope-based approaches. Published reports are limited by small sample size and nonrandomized study design. A meta-analysis allows for a description of the impact of endoscopic surgery on short-term outcomes. Methods The authors performed retrospective review of data from their institution as well as a systematic review of the literature. The pooled data were analyzed for descriptive statistics on short-term outcomes. Results Nine studies (821 patients) met inclusion criteria. Overall, the pooled rate of gross tumor removal was 78% (95% CI 67–89%). Hormone resolution was achieved in 81% (95% CI 71–91%) of adrenocorticotropic hormone secreting tumors, 84% (95% CI 76–92%) of growth hormone secreting tumors, and 82% (95% CI 70–94%) of prolactin secreting tumors. The pooled complication rates were 2% (95% CI 0–4%) for CSF leak and 1% (95% CI 0–2%) for permanent diabetes insipidus. There were 2 deaths reported in the literature that were both related to vascular injury, giving an overall mortality rate of 0.24%. Conclusions The results of this meta-analysis support the safety and short-term efficacy of endoscopic pituitary surgery. Future studies with long-term follow-up are required to determine tumor control.

A total of 821 gray whales were seen during aerial surveys in the northeastern Chukchi Sea from July through October 1982–1987. Gray whale distribution extended from south of Point Hope to northeast of Point Barrow, Alaska, between 0.5 and 166 km offshore. Monthly abundance estimates (number of whales/survey hour) were highest in July (6.81) and lowest in October (0.40). Gray whales were usually in open water (82%, n = 670) or in light ice (16%, n = 134) and were seldom associated with heavy ice (2%, n = 17). Most whales were feeding (63%, n = 514), with the majority of the others swimming and diving (24%, n = 193) or forming part of a cow–calf association (9%, n = 72). One group of three whales was involved in sexual activity. Feeding whales were seen most often within 40 km of the shore, but also occurred offshore. Thirty-six gray whale calves were seen. Calf abundance (number of calves/survey hour) was significantly higher (p < 0.001) in July, when 92% (n = 33) of all calves were seen, than in any other month. Most cow–calf pairs were seen nearshore between Point Hope and Point Barrow. Monthly calf ratios (number of calves/number of whales) ranged from 0.09 in July to 0.00 in October, with an overall rate of 0.04.

ObjectivesTo provide a formative educational test of knowledge that allows clinicians to measure themselves against their peers.DesignAnnual Neurosurgery and Neurology knowledge tests, supported by the ABN & SBNS, have been available since 2014 (NSurg) and 2017 (Neurol). The NSurg test requires all candidates to participate over 3 days, answers are available after the test whereas the Neurol formative questions are available over 6 weeks, answers are available immediately.SubjectsThere have been 821 first attempts at the formative questions; NSurg; 44, 63,187,143,164 and Neurol; 74, 146. Candidates are mostly from UK (NSurg 92%, Neurol 69%) and mostly specialty trainees (NSurg 98%, Neurol 63%).MethodsThe formative questions are delivered through the ebrain virtual learning platform, statistics are generated automatically. Proposed questions are written by candidates as ‘payment’ for doing the formative test.ResultsMean Cronbach’s alpha was 87.3%. The mean score for the tests was 60.4% (Range 55.9%–77.9%). Feedback is voluntary: In 2018 17 feedback comments were received, 10 were unambiguously positive, 5 were mixed including criticism of one or more questions, 2 were judged to be neutral. Examples of feedback comments received this year included ‘Comprehensive exam that covers a wide range of topics’ and ‘This is of great value’.ConclusionsThis formative educational initiative has high internal consistency and solid feedback. Although set up differently, it is proving both valuable and popular in both specialties.

Objetivo Estimar la carga de enfermedad por lesiones de causa externa (LCE) en el departamento de Casanare durante 2008-2012.Métodos Estudio descriptivo retrospectivo desde los registros de la notificación al Sivigila de los eventos agrupados como LCE y los eventos reportados al Sistema de Vigilancia Epidemiológica de Lesiones de Causa Externa (SIVELCE). Análisis de variables en tiempo-lugar-persona mediante estadística descriptiva, con plantillas disponibles vía OMS en Microsoft Office® Excel 2013 y Epi-Info® 7.1.3.Resultados Entre 2008-2012 fueron notificados al Sistema de Salud Pública (SIVIGILA) 5 829 casos agrupados como LCE: accidente ofídico 751(12,9%), agresiones por rabia 3 774(64,7%), intoxicaciones 1 231(21,1%), lesiones por pólvora 32(0,5%) y violencia 41(0,7%), razón hombre/mujer 1:1, edad promedio 25±19,3(r=0,01-92) años, años de vida ajustados por discapacidad (AVAD) 821(2,5 años por 1 000 habitantes); y, al SIVELCE 15 539 reportes: lesiones intencionales 12 834(82,6%) y lesiones no intencionales 2 704(17,4%), razón hombre/mujer 1:1, edad promedio 28±14,1(r=0,03-90) años, relación entre morir por lesiones intencionales vs lesiones no intencionales tuvo una razón de disparidad OR=0,12 (X²=1 060,56 1 g.l, valor-p=0,0), AVAD 18 179(55,8/1 000).Conclusiones Las LCE afectan por igual a hombres y mujeres, los AVAD ocurren a expensas de la morbilidad. Todas las LCE son prevenibles, por tanto, es necesario fortalecer las respectivas acciones de vigilancia, prevención y control.

SummaryField experiments made in 1984 and 1985 compared the effects of ammonium chloride with those of other nitrogen fertilizers applied to winter wheat in spring. The dressing was divided, 40 kg N/ha in March and 160 kg N/ha in April. In both years take-all in July was at levels which usually decrease yield, and take-all ratings were greatest in plots treated with ‘Nitro-Chalk’ (calcium ammonium nitrate) and least in plots treated with ammonium sulphate, but the differences were not statistically significant. Ammonium chloride and the other treatments, urea and ‘Nitro-Chalk’ with potassium chloride, had intermediate effects and the ranking of treatments according to disease was consistent in both years. In 1984 the mean yield was 8·27 t/ha, range 7·92 t/ha (with ammonium chloride) to 859 t/ha (with ‘Nitro-Chalk’) and in 1985, 821 t/ha, range 7·;42 t/ha (with ‘Nitro-Chalk’) to 8·55 t/ha (with ammonium sulphate). In both years treatments had no significant effects on yields and the relationship between yield and disease was obscured in 1985 because of highly correlated disease and block effects.Whereas applying spring nitrogen all in the ammonium form seemed to decrease take-all slightly, the effects on yields of winter wheat were inconsistent. There is no evidence of extra benefit to be gained from applying the ammonium as ammonium chloride to crops at risk from take-all in this country, but there may be some benefit in applying KCl with ‘Nitro-Chalk’ top-dressings in the spring.

AbstractDivergent breeding lines of Romney sheep, selected as lambs for consistently low or high faecal worm egg count (FEC) following natural multispecific challenge by nematode parasites, have been maintained at Wallaceville Animal Research Centre since 1979. From the start of the trial until 1992, 821 and 736 experimental lambs in lines selected for increased resistance (R) and increased susceptibility (S), respectively, were generated, with the use of 44 different sires. In order to assess genetic responses to selection, FEC and productivity data were analysed using restricted maximum likelihood procedures. By 1988 the two lines had diverged in average loge (FEC+100) by 0·67 log units, and by 1992 divergence had increased to 1·48 log units, representing 2·90 genetic standard deviations of divergence. No significant correlated responses were observed in live weights. However, by 1992 the mean score for breech soiling (dags) in the R line was proportionally 0·41 greater than in the S line (F < 0·001). Yearling fleece weight was proportionally 0·15 greater in S-line than in R-line animals when grazed together under identical levels of challenge (P < 0·001) but the lines did not differ significantly in fleece weight when they were grazed apart. The R line had significantly higher reproductive success than the S line (P < 0·05), as measured by lambs weaned per ewe mated (1·01 v. 0·92, respectively). It is concluded that selective breeding can change the degree of resistance or susceptibility to nematode infection in Romney sheep, and selection for productivity needs to be continued at the same time in any practical breeding programme.

Abstract Background: During the smoking of crack cocaine (COC), methyl ecgonidine (MED) is formed as one of the pyrolysis products. Once in the body, MED is converted to ecgonidine (ED) through several processes that include spontaneous hydrolysis and enzymatic hydrolysis. The presence of MED and/or ED could provide valuable information to help determine antemortem conditions in cases where COC is involved. Our goal was to examine postmortem tissues and fluids for the presence of MED, ED, COC, and benzoylecgonine (BZ). Methods: Liver, brain, blood, and urine specimens obtained from 15 postmortem cases were extracted using solid-phase extraction, derivatized, and analyzed using gas chromatography–mass spectrometry with selective-ion monitoring. Results: Median concentrations (range) of drugs observed in postmortem liver, brain, blood, and urine were 0 (0–10) ng/g, 7 (0–92) ng/g, 0 (0–42) μg/L, and 62 (0–2030) μg/L, respectively, for MED; 655 (90–3274) ng/g, 22 (0–52) ng/g, 119 (13–773) μg/L, and 456 (109–7452) μg/L, respectively, for ED; 57 (0–503) ng/g, 187 (0–1403) ng/g, 12 (0–88) μg/L, and 1208 (37–28 062) μg/L, respectively, for COC; and 821 (45–4980) ng/g, 524 (46–5153) ng/g, 458 (30–2071) μg/L, and 6768 (917–116 430) μg/L, respectively, for BZ. MED was detected in 12 of 15 postmortem cases. The concentrations were highest in urine compared with liver, brain, and blood. The hydrolysis product ED was detected in all postmortem cases, and the concentrations were substantially higher than MED in all liver, blood, and urine specimens. Conclusion: ED may be a more useful indicator of crack COC smoking.

Abstract Abstract 680 Cytogenetics play an essential role in determining the prognosis of patients with AML. However, there is still no validated cytogenetics grouping scheme that specifically applies to patients undergoing allogeneic stem cell transplantation, which hampers accurate prognostication and risk stratification. We studied 821 adult patients (median age 41, range 18–74) who underwent SCT between 1999 and 2004 for AML (excluding APL) in CR1 or CR2 and who were reported to the CIBMTR from centers with >20 patients meeting study criteria. 75% of patients received a myeloablative conditioning. 496 patients had a normal karyotype. The primary cytogenetics reports were manually reviewed for 92% of the patients with an abnormal karyotype. We compared the ability of the 6 existing grouping schemes (MRC, CALGB, EORTC/GIMEMA, SWOG/ECOG, DFCI, and Monosomal Karyotype (MK) classifications) to stratify patients, using both the Akaike Information Criterion in multivariable models and the C-statistic. Among all existing schemes, the DFCI system provided a marginally superior stratification for overall and leukemia-free survival. We also built a new classification using individual cytogenetic abnormalities in a Cox model that included other significant covariates (performance status, therapy-related disease, conditioning intensity, graft source, donor match, duration of CR1, and gender match). This CIBMTR scheme (see Table), which is similar to the DFCI scheme except for the inclusion of patients with t(8;21) in the intermediate group, could stratify patients into 3 groups with similar treatment-related mortality but significantly different overall survival, leukemia-free survival, and incidence of relapse. This scheme appeared to apply to both patients in CR1 and in CR2 (see FiguresF2). This transplant-specific scheme could be adopted for prognostication purposes and to stratify patients with karyotypic abnormalities entering transplantation clinical trials. Future studies may clarify the relative outcome of patients with t(8;21) and refine this scheme with the inclusion of molecular abnormalities. Disclosures: No relevant conflicts of interest to declare.

BackgroundLive, interactive patient cases have shown to be a valuable resource in medical education. Although a few studies have shown that using patients as teachers helps students develop clinical reasoning, motivates students to learn, and has important educational benefits, there is little research understanding medical student feedback during these interactive patient cases.[1,2]ObjectivesTo evaluate second year medical students’ perceptions on interactive patient encounters during the teaching of the skin and rheumatology course (BMS 6635) based on surveys collected from 2016-2022.MethodsSecond year medical students completed a survey on their experience from four to five interactive patient cases at University of Central Florida College of Medicine. The interactive cases, involving patients with diagnoses of systemic lupus erythematosus, psoriatic arthritis, dermatomyositis, scleroderma, and pyoderma gangrenosum. Second year medical students enrolled in BMS 6635 from 2016-2022 were included. Students who did not respond to the survey questions were excluded. Chi Square test was performed on survey responses. Regression analysis was performed on significantly different survey responses.ResultsA total of 700 surveys were completed after the interactive patient encounters. 90% of participants answered that they enjoyed the interactive patient cases with 92% of students agreeing that the interactive patient cases were an appropriate learning experience for their education. 76% of students agreed that the patient encounters helped them retain knowledge of the disease processes. However, only 36% agreed that the number of patients in the interactive patient cases should be increased (Table 1). From 2016 to 2022 there has been a slight decrease in enjoyment in the interactive patient cases over time (97%, 88%, 93%, 94%, 86%, 81%,p<.001, respectively per year). From 2016 to 2022, there was a slight decrease in students agreeing that the interactive patient cases were an appropriate learning experience in their education (98%, 92%, 94%, 95%, 93%, 84%,p=.001, respectively per year) (Figure 1).Table 1.Medical student survey responses of agreement to live patient cases comparing those who agree to those who disagreeStudent ResponsesValuesAgreeDisagreeTotalI enjoyed the live patient cases62890%7210%700The live patient cases were an appropriate learning experience at this stage in my education64692%548%700We should increase the number of patients in the live patient cases12336%21964%342The live patient cases helped me remember the diseases well for the exam26176%8124%342Figure 1.Agreement trend in medical student’s response to survey questions from 2016 to 2022ConclusionInteractive patient cases are a valuable resource in medical education and should be integrated in medical curricula. Overall, students enjoyed the interactive patient cases, believed they were an appropriate learning addition to their medical education even with a minimal number of cases, and aided in retention of material. However, from 2016 to 2022 a slight decrease in positive feedback regarding this approach was noted, which could be attributed to technological advancements and the increasing use of third-party resources among students. The decrease, while minimal, is an important consideration for academic institutions.References[1]Spencer J, Blackmore D, Heard S, et al. Patient-oriented learning: a review of the role of the patient in the education of medical students.Med Educ.2000;34(10):851-857. doi: 10.1046/j.1365-2923.2000.00779.x.[2]Wykurz G, Kelly D. Developing the role of patients as teachers: literature review.BMJ.2002;325(7368):818-821. doi: 10.1136/bmj.325.7368.818.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Study Objective: To assess the efficiency and safety of intraarticular combination therapy with sodium hyaluronate and chondroitin sulfate (Hyalurom СS) in patients with knee osteoarthritis (OS). Materials and Methods. The 6-month study enrolled 79 patients with primary knee OA stage II–III (Kellgren и Lawrence), with pain intensity of at least 40 mm, using a visual analogue scale. Mean age was 60.3 ± 8.7 years; mean body mass index was 29.2 ± 4.7 kg/m2, and duration of disease of 6 (3–10) years. Therapy efficiency and safety were assessed on the basis of pain dynamics, constrained movements, joint functionality, patient health, quality of life, and daily need in non-steroidal anti-inflammatory drugs. Study Results. Initial pain was 62 (55–72) mm. After intraarticular injection of the drug, knee pain was statistically less severe, and in a week, it was 41 (32–51) mm, in a month — 28 (20–42) mm, in 3 months — 22 (14–37) mm, and in 6 months — 20 (14–42) mm (р < 0.0001). The same pattern was identified when the total knee functionality points were determined: 1,125 (899–1540) mm — initial value, 821 (556–1119) mm — in a week, 627 (401–874) mm — in a month, 554 (310–750) mm — in 3 months, and 552 (309–837) mm — in 6 months of follow-up (p < 0.0001). The same pattern was true for the assessment of all components of the index. Pain: 268 (189–312) mm, 161 (91–206) mm, 121 (63–165) mm, 102 (48–163) mm, 91 (48–171) mm, respectively (p < 0.0001); constrained movements: 101 (59–130) mm, 66 (30–92) mm, 51 (24-68) mm, 41 (18-60) mm, 40 (20-61) mm, respectively (p < 0.0001); impaired functionality: 802 (647–1095) mm, 587 (405-798) mm, 457 (277-683) mm, 396 (220-586) mm, 402 (191-638) mm, respectively (p < 0.0001). Statistically significant improvement in the quality of life and overall health condition was noted throughout the entire follow-up period: 0.52 (-0.02–0.59) mm and 0.69 (0.59–0.80) mm, р < 0.0001; 48 (30–60) mm and 72 (60–80) mm, р < 0.0001. The therapy led to reduction in the need for non-steroidal anti-inflammatory drugs: in a week, they were discontinued by 39.2% of patients; in a month — by 72.2% of patients, in 3 months — 73.4%, and in 6 months — 54.4% of patients. When the therapy efficiency was assessed by the patient and physician, “significant improvement” and “improvement” were recorded in a majority of cases. Adverse events associated with increased pain and/or swollen knee were noted in 8 (10.1%) patients. Conclusion. The results show good long-term effect from Hyalurom СS therapy. We recorded statistically significant reduction in pain, less constrained movements, rarer need in non-steroidal anti-inflammatory drugs, improved quality of life and joint functionality. The drug possesses a good safety profile and can be recommended for wide clinical application. Keywords: knee osteoarthritis, hyaluronic acid, chondroitin sulfate.

Abstract Abstract 4570 RIC AlloHCT can provide a curative option for patients with hematologic diseases who are not candidates for myeloablative AlloHCT. However, this approach is limited by high relapse rates, especially with aggressive myeloid malignancies. We hypothesized that achieving greater cytoreduction by increasing conditioning intensity would increase the efficacy of a RIC regimen. Therefore, we utilized fludarabine (40 mg/m2/day × 4 days on days -5 to -2), melphalan 50 mg/m2 (day -2) and TBI (total of 400 cGy in 2 fractions on day -1) (FluMelTBI) in a pilot trial of RIC for hematologic disorders. Forty-nine patients who were not eligible for myeloablative transplantation accrued between March 2009 and June 2011. Tacrolimus (0.015 mg/kg oral every 12 hours, starting on day -1, titrated to 5–15 ng/ml), mycophenolate mofetil (1000 mg oral every 8 hours, starting on day -1) and methotrexate (2.5 mg/m2 IV on days 1, 3 and 6) were used for Graft-versus-Host Disease (GvHD) prophylaxis in all patients. Patient and donor characteristics are presented in Table A. All 49 patients engrafted neutrophils at a median 16 days (range 10–39). One patient did not nadir platelets <20 × 109/L; of the remaining 48 patients, two died before platelet recovery on days +14 and +50, while 46 achieved platelet recovery at a median 17 days (range, 11–73). At day +100 post-RIC AlloHCT, 71% were in CR, with 2 patients too early to evaluate. The transplant related mortality (TRM) was 10% at day +100 and 22% at 1 yr. The incidence of acute GvHD grade 2–4 was 49% and grade 3–4 was 23%. Chimerism data are presented in Table B. At a median follow-up of 364 days (range 17–821), the 1 yr OS and PFS are 58% (95% CI: 42–72%) and 50% (95% CI: 34–64%), respectively. Factors that were significantly related to lower OS were older age (p=0.02) and gender mismatch (p=0.03). In conclusion, FluMelTBI is a well-tolerated RIC regimen with low TRM, achieves early complete donor chimerism and a good early disease response. Longer follow-up is needed to determine long term survival and disease control.Table A:Patient and donor characteristicsAge: median (range)N=4958 yrs (5-72)Gender: male female45% 55%Disease: AML or ALL MDS or MPD NHL other51% 20% 14% 10%Disease status prior to transplant: CR1 CR>1 No prior CR Untreated MDS/MPD/SAA 1st relapse or CML blast crisis27% 12% 27% 20% 14%Related Unrelated33% 67%HLA matched 10/10 HLA mismatched (<10/10)75% 25%ABO compatible incompatible49% 51%Gender matched mismatched61% 39%Peripheral blood hematopoietic cells Bone marrow hematopoietic cells84% 16%CD 34+ cell dose: median (range) × 106/kg5.24 (0.82-40.72)Table B:Chimerism results post AlloHCTN evaluableDay+30Day+100Day+365383614N (%) complete (>95% donor) myeloid chimerism36 (95%)34 (94%)13 (93%)N (%) complete (>95% donor) lymphoid chimerism34 (89%)33 (92%)14 (100%) Disclosures: Hahn: Novartis

Abstract Abstract 821 Introduction: Sickle cell disease (SCD) is characterized by recurrent acute vaso-occlusive painful crisis frequently leading to SCD related complications such as acute chest syndrome, stroke, multi-organ failure and even sudden death. The complex pathophysiology of the vaso-occlusive painful crisis is mediated by activation of endothelial cells, adhesion of sickled erythrocytes and neutrophils, oxidative stress, coagulation activation and increased release of inflammatory mediators, resulting in ischemic organ damage. Recently, neutrophils have been demonstrated to form neutrophil extracellular traps (NETs) upon activation. Nucleosomes and histones exposed together with neutrophil proteases, such as elastase on these NETs have been shown to kill efficiently bacteria. NET formation has been shown to propagate coagulation in sepsis and in deep venous thrombosis. In addition, nucleosomes and histones exposed on NETs have been shown to be strongly cytotoxic to endothelial cells. Beside the exposure on NETs, nucleosomes can be actively released into the circulation from dead cells. Circulating nucleosomes detected in sepsis have been reported to correlate with severity of inflammation, organ dysfunction and mortality. However, no studies are available yet on the dynamics of nucleosomes and NETs in sickle cell patients suffering from painful crisis. The aim of this case-control study was to assess plasma levels of circulating nucleosomes and human neutrophil elastase–α1-antitrypsin (EA) complexes as measure of systemic neutrophil activation, in sickle cell patients during steady state and painful crisis. Methods: Plasma levels of nucleosomes and EA as a measure of neutrophil activation were measured in 74 patients in asymptomatic state (49 HbSS/HbSβ0-thalassemia, and 25 HbSC/HbSβ+-thalassemia), 70 painful crises (53 HbSS/HbSβ°-thalassemia and 17 HbSC/HbSβ+-thalassemia) in 49 patients and in 24 HbAA healthy controls using Enzyme-Linked Immunosorbent Assay (ELISA). Results: Plasma levels of nucleosomes in both HbSS/HbSβ°-thalassemia and HbSC/HbSβ+-thalassemia patients were significantly higher during painful crisis (median; interquartile range, 20.2; 8.9 – 129.0 U/ml, P < 0.0001 and 11.7; 5.1 – 67.7 U/ml, P = 0.045 respectively) as compared to patients in steady state (6.0; 3.0 – 9.8 U/ml and 7.1; 4.6 – 9.6 U/ml respectively). Nucleosomes levels in healthy controls were just above the detection limit of the assay (5.0; 5.0 – 6.5) U/ml). Plasma levels of EA in HbSS/HbSβ°-thalassemia patients were significantly increased during painful crisis as compared to steady state (75.1; 56.5 – 102.4 vs. 45.7; 34.7 – 59.7 ng/ml, P < 0.0001). Also in HbSC/HbSβ+-thalassemia patients, EA levels were higher during painful crisis than in steady state, though the difference did not reach statistical significance (62.0; 48.0 – 96.7 vs. 50.2; 33.3 – 67.7, P = 0.051). Plasma levels of EA in healthy controls (39.9; 31.5 – 62.2 ng/ml) were comparable with those in steady state patients. In a paired analysis of 36 patients, included both during steady state and painful crisis, significant increments were observed during painful crisis in levels of both nucleosomes (from 5.0; 3.0 – 10.8 to 20.2; 6.8 – 94.3 U/ml, P < 0.0001) and EA (from 47.9; 36.0 – 67.6 to 70.6; 55.9 – 101.4 ng/ml, P < 0.0001), as compared to steady state. During painful crisis, EA levels were strongly correlated with levels of nucleosomes in both HbSS/HbSβ°-thalassemia (Spearman's rank (Sr)=0.55, P<0.0001) and HbSC/HbSβ+-thalassemia patients (Sr=0.90, P=<0.0001). In steady state the correlation was significant only in HbSC/HbSβ+-thalassemia patients (Sr=0.63, P=0.001) Four patients who developed an acute chest syndrome during painful crisis were among the patients with the highest nucleosome (359, 130, 128 and 100 U/ml) and EA levels (121, 87, 92 and 64 ng/ml respectively). Conclusion: Sickle cell painful crisis is associated with increased levels of nucleosome and stronger neutrophil activation. This might point to a crucial role of NET formation in the pathogenesis of painful crisis. Disclosures: No relevant conflicts of interest to declare.

Abstract Bombycidae, Saturniidae, mtDNA RFLP, Cytochrome Oxidase I Gene The phylogenetic relationships between Bombyx mori and Bombyx mandarina species of Bombycidae, and Antheraea yamamai and Antheraea pernyi species of Saturniidae were investigated based on mtDNA RFLP and cytochrome oxidase I gene. The sizes of the mtDNA of all the species were estimated at approximately 16 kbp ± 500 bp by total length of all the restricted fragments and no variation in size was recognized. Of the fourteen different restriction endonucleases used, BamHl, Hindlll, Pstl, EcoRl and Xbal showed RFLP. Among these, only Hindlll showed RFLP between B. mori and B. mandarina. A comparative analysis of sequences was also conducted with the mitochondrial cytochrome oxidase I genes of each species. The results indicated that B. mori shared a 97% , 85% and 87% sequence identity with B. mandarina, A. yamamai and A. pernyi, respectively. B. mandarina shared a 87% and 88% sequence identity with A. yamamai and A. penyi, respectively. A. yamamai shared 92% sequence identity with A. pernyi. The results of the phylogenetic analysis exhib­ited monophyly and confidence limits of more than 99% in all trees for both Bombycidae and Saturniidae.

Abstract The enzyme ribulose-1,5-bisphosphate carboxylase-oxygenase (rubisco) and its functional subunits from barley (Hordeum vulgare L.) leaves were purified to homogeneity by activitydirected sequencial steps of chromatography. Based on the molecular mass estimation by SDS-PAGE, the large subunit (LS) had an apparent molecular weight of ca. 55 kDa, whereas the small subunit (SS) was ca. a 14 kDa polypeptide chain. The N-terminal sequences, established by automated Edman degradation analysis of the purified subunits, showed very close sequence homologies (52-92%) with the subunits of other rubisco enzymes reported from several photosynthetic species. In order to establish the chemical heterogeneity in the rubisco from barley, the amino acid composition of purified native enzyme was analyzed and the results systematically compared with other known type-I rubisco enzymes from spinach, maize, tobacco and pea. Major differences have been observed in the amino acid composition of barley rubisco, the concentration of cysteine, serine, threonine, isoleucine, leucine, arginine and tryptophan residues were found quite variable as compared to other higher plants. The thermostability of the native rubisco was also investigated using circular dichroism and fluorescence spectroscopy. The critical ( Tc) and melting ( Tm) temperatures were determined to be 60 °C and 57 °C, respectively, and at this temperature the enzyme not only retains its structural integrity but also its enzymatic activity. Results of these studies were discussed in the light of structural and functional adaptation of this bifunctional enzvme in C3 and C4 plants to their environments.

<p><span style="font-family: ArabicTypesetting; font-size: 16pt;">Tafsir is the main instrument in an attempt to answer the problems of the <span style="font-size: 16pt;">people, who must soon discovered the concept or theory. This departs from the <span style="font-size: 16pt;">question that is often uttered by Hassan Hanafi: " hal ladainā naẓariyah fi ’lTafsīr?" This is an Islamic thinker anxiety on the theory and methodology of <span style="font-size: 16pt;">interpretation that is less classical touches many social problems. From here <span style="font-size: 16pt;">arises the methods, including taḥlīlī (analysis). Taḥlīlī method (analysis) is to <span style="font-size: 16pt;">interpret the verses of the Qur'an to describe all aspects contained in the verses<br /><span style="font-size: 16pt;">that are interpreted and explained the meanings contained therein in accordance <span style="font-size: 16pt;">with the expertise and inclination commentators interpret these verses. The <span style="font-size: 16pt;">main purpose taḥlīlī method is to lay the foundations for a rational understanding of the miracle of the Qur'an, something which is not considered an urgent <span style="font-size: 16pt;">need for Muslims today. Because it is necessary to develop a method of interpretation because this method produces the idea that diverse and fragmented.<br /></span></span></span></span></span></span></span></span></span></span></p><p><span style="font-family: ArabicTypesetting; font-size: 16pt;"><span style="font-size: 16pt;"><span style="font-size: 16pt;"><span style="font-size: 16pt;"><span style="font-size: 16pt;"><span style="font-size: 16pt;"><span style="font-size: 16pt;"><span style="font-size: 16pt;"><span style="font-size: 16pt;"><span style="font-size: 16pt;"><span style="font-size: 16pt;">Keywoard: al-Qur’an, manhaj, taḥlīlī, tafsir, analisis</span></span></span></span></span></span></span></span></span></span><br style="orphans: 2; text-align: -webkit-auto; widows: 2;" /></span></p><span style="font-family: ArabicTypesetting; font-size: 16pt; color: #231f20;">=1*18&amp;('18*$'(888('?8821B(*8&amp;(?*2&gt;7('12=8&amp;(<br /><span style="font-size: 16pt;">?(2?7(B&amp;2'$18122192k(*(8&amp;(929(?82*8&amp;(2*E&amp;1(?*81=*2'8&amp;(<br /><span style="font-size: 16pt;">c$(1828&amp;812=8($88(*(&gt;11=6}&amp;77oN*&amp;=07.<br /><span style="font-size: 16pt;">=1r*†}&amp;1117'98&amp;%(*•(828&amp;(8&amp;(2*'(8&amp;2272)2=<br /><span style="font-size: 16pt;">8(*?*(8828&amp;8 17(11 97119782$9&amp;(1'1297 ?*2&gt;7('1E*2'&amp;(*(<br /><span style="font-size: 16pt;">*1(18&amp;('(8&amp;2197$)8Z7r7r711EZ7r7r'(8&amp;2711182<br /><span style="font-size: 16pt;">8(*?*(88&amp;(k(*1(12=8&amp;(/$*•82(19*&gt;(771?(981928(8&amp;(k(*1(1<br /><span style="font-size: 16pt;">8&amp;8*(8(*?*(8((•?7(8&amp;('()1928(8&amp;(*(992*9(<br /><span style="font-size: 16pt;">B8&amp; 8&amp;( (•?(*81( 9782 92''(882*1 8(*?*(8 8&amp;(1( k(*1(1E &amp;(<br /><span style="font-size: 16pt;">'?$*?21(8Z7r7r'(8&amp;218278&amp;(=2$821=2**827$(*18.<br /><span style="font-size: 16pt;">)2=8&amp;('*97(2=8&amp;(/$*•12'(8&amp;)B&amp;9&amp;128921(*($*)(8<br /><span style="font-size: 16pt;">((=2* $17'182E(9$1(81(9(11*82(k(72?'(8&amp;22=8(*.<br /><span style="font-size: 16pt;">?*(882&gt;(9$1(8&amp;1'(8&amp;2?*2$9(18&amp;((8&amp;8k(*1(=*)'(8(E<br /><span style="font-size: 16pt;">8$968$96 7./$*0'&amp;@8Z7r7r8=1*711</span></span></span></span></span></span></span></span></span></span></span></span></span><br style="orphans: 2; text-align: -webkit-auto; widows: 2;" /></span>

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e4176066In this paper we present a discussion about the implications of the theory of mental models in the teaching and learning process in Chemistry, with the purpose of discussing the use of stop motion animation as a data collection instrument to investigate the students' mental representations about chemical concepts, especially about their dynamic character. To achieve the objectives mentioned in the present work, we seek to relate the theory of mental models and their implications for the teaching and learning processes in chemistry, with the proposal of the triangulation of the three different representational levels of Chemistry (submicroscopic, symbolic and macroscopic), which are necessary to understand this Science. It is also noteworthy that this articulation was based on the main difficulties associated with the teaching and learning processes in Chemistry and was thought of the particularity involving the dynamics of the atomic-molecular level. The discussions carried out involving the different references used allowed us to discuss the potentialities associated with the use of stop motion as an instrument for investigating mental models on chemical concepts, highlighting the fact that it is a technique that is easy to apply, low cost and that allows the dynamic representation of chemical phenomena considering the submicroscopic level.ResumoNo presente trabalho apresentamos uma discussão acerca das implicações da teoria dos modelos mentais nos processos de ensino e aprendizagem em Química, com a finalidade de discorrer sobre o uso de animação em stop motion como um instrumento de coleta de dados para se investigar as representações mentais dos sujeitos sobre conceitos químicos, em especial sobre seu caráter dinâmico. Para atingir os objetivos mencionados no presente trabalho, buscamos relacionar a teoria dos modelos mentais e suas implicações para os processos de ensino e aprendizagem em Química, com a proposta da triangulação dos três diferentes níveis representacionais da Química (submicroscópico, simbólico e macroscópico), que são necessários para a compreensão dessa Ciência. Destacamos também, que tal articulação foi pautada nas principais dificuldades associadas aos processos de ensino e aprendizagem em Química e pensada na particularidade envolvendo a dinamicidade do nível atômico-molecular. 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RESUMEN:El objetivo del artículo es aproximarnos a la controvertida biografía del comisario Manuel Brabo Portillo. El trabajo está basado en fuentes primarias y secundarias. El método utilizado es empírico. En el imaginario del mundo sindicalista revolucionario, Brabo Portillo era el policía más odiado, la reencarnación de la cara más turbia del Estado. Fue, así mismo, un espía alemán relacionado con el hundimiento de barcos españoles, el asesinato del empresario e ingeniero Barret y el primer jefe de los terroristas vinculados a la patronal barcelonesa. La conflictividad que afectó a España en el período de la Primera Guerra Mundial es fundamental para entender los orígenes del terrorismo vinculado al pistolerismo, que marcó la historia político social española del primer tercio del siglo XX.PALABRAS CLAVE: Brabo Portillo, pistolerismo, espionaje, sindicalismo, Primera Guerra Mundial.ABSTRACT:The objective of the article is an approach to the controversial biography of Police Chief Manuel Brabo Portillo. The work is based on primary and secondary sources. The method used is empirical. In the imagery of the revolutionary syndicalist world, Brabo Portillo was the most hated policeman, the reincarnation of the murkiest face of the state. He was also a German spy connected with the sinking of Spanish ships, the murder of businessman and engineer Josep Barret and the first head of the terrorists linked to Barcelona employers. 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Abstract Background Seizures commonly occur in patients with cryptococcal meningitis, yet risk factors and outcomes related to seizures are not well described. Methods We performed post hoc analyses on participants prospectively enrolled in 3 separate human immunodeficiency virus (HIV)-associated cryptococcal meningitis clinical trials during 2010–2017. Documentation of seizures at presentation or during hospitalization and antiseizure medication receipt identified participants with seizures. We summarized participant characteristics by seizure status via Kruskal-Wallis and χ 2 tests. Cox proportional hazards models analyzed the relationship between seizures and mortality. We compared mean quantitative neurocognitive performance Z (QNPZ-8) scores, and individual domain z-scores, at 3-months using independent t tests. Results Among 821 HIV-infected cryptococcal meningitis participants, 28% (231 of 821) experienced seizures: 15.5% (127 of 821) experienced seizures at presentation, and 12.7% (104 of 821) experienced incident seizures. Participants with seizures at presentation had a significantly lower Glasgow coma scale ([GCS] &lt;15; P &lt; .001), CD4 count (&lt;50 cells/mcL; P = .02), and higher cerebrospinal fluid (CSF) opening pressure (&gt;25 cm H2O; P = .004) when compared with participants who never experienced seizures. Cerebrospinal fluid fungal burden was higher among those with seizures at presentation (125 000 Cryptococcus colony-forming units [CFU]/mL CSF) and with seizures during follow-up (92 000 CFU/mL) compared with those who never experienced seizures (36 000 CFU/mL, P &lt; .001). Seizures were associated with increased 10-week mortality (adjusted hazard ratio = 1.45; 95% confidence interval, 1.11–1.89). Participants with seizures had lower neurocognitive function at 3 months (QNPZ-8 = −1.87) compared with those without seizures (QNPZ-8 = −1.36; P &lt; .001). Conclusions Seizures were common in this HIV-associated cryptococcal meningitis cohort and were associated with decreased survival and neurocognitive function.

<p>En el presente estudio se analizan las propiedades psicométricas de la Escala de Florecimiento en Puerto Rico. Se realizaron tres estudios. En el primero, con 665 participantes, se analizaron la confiabilidad y la estructura factorial de la escala. En el segundo, con 821 participantes, se efectuó un análisis factorial confirmatorio. En el tercero, con 342 mujeres puertorriqueñas, se calculó la validez convergente y divergente de las escalas con otras medidas de bienestar y depresión. Los resultados de los estudios mostraron propiedades psicométricas adecuadas en la escala. El índice de confiabilidad Alfa de Cronbach de la escala fue de .92. La varianza explicada en el análisis factorial exploratorio fue de un 65.35%. Los resultados confirmaron que la escala posee una estructura unidimensional. Los ocho ítems de la escala cumplieron con los criterios de discriminación. Se realizaron análisis de validez convergente y discriminante mediante la evaluación de correlación entre el florecimiento, la satisfacción con la vida y la depresión. Se obtuvieron valores estadísticamente significativos. Estos resultados sugieren que la Escala de Florecimiento tiene el potencial para medir este constructo en adultos puertorriqueños.</p>

Abstract Aims During the COVID-19 pandemic in-person visits for patients with cardiac implantable electronic devices should be replaced by remote monitoring (RM), in order to prevent viral transmission. A direct home-delivery service of the RM communicator has been implemented at 49 Italian arrhythmia centres. Methods and results According to individual patient preference or the organizational decision of the centre, patients were assigned to the home-delivery group or the standard in-clinic delivery group. In the former case, patients received telephone training on the activation process and use of the communicator. In June 2020, the centres were asked to reply to an ad hoc questionnaire to describe and evaluate their experience in the previous 3 months. RM was activated in 1324 patients: 821 (62%) received the communicator at home and the communicator was activated remotely. Activation required one additional call in 49% of cases, and the median time needed to complete the activation process was 15 min (25th–75th percentile: 10–20). 753 (92%) patients were able to complete the correct activation of the system. At the time when the questionnaire was completed, 743 (90%) communicators were regularly transmitting data. The service was generally deemed useful (96% of respondents) in facilitating the activation of RM during the COVID-19 pandemic and possibly beyond. Conclusions Home delivery of the communicator proved to be a successful approach to system activation, and received positive feedback from clinicians. The increased use of a RM protocol will reduce risks for both providers and patients, while maintaining high-quality care.

Abstract Objective: To examine whether the association between women’s origin and early pregnancy overweight and obesity (OW/OB) varies by length of residence in Sweden. Design: This cross-sectional observational study used pooled Swedish population register data from 1992 to 2012. Logistic regression models were run to estimate odds ratios (OR) of early pregnancy OW/OB and 95 % confidence intervals (95 % CI), comparing Swedish-born and immigrants by length-of-residence categories while adjusting for covariates. Setting: Sweden. Participants: In total, 1 771 821 pregnant women, 315 992 of whom were immigrants. Results: With longer residence in Sweden, more immigrant women from various origins exhibited higher odds of experiencing early OW/OB compared with Swedish-born women. Findings specifically showed increased odds of early pregnancy OW/OB with increasing length of residence for women born in Latin America, Europe-27 and Southeast Asia. For example, immigrant women from Latin America residing in Sweden for < 6 years showed similar odds as Swedish-born (OR≤ 5 years 0·92, 95 % CI 0·87, 0·98), while their longer residing counterparts showed higher odds than Swedish-born women (OR6–15 years1·21, 95 % CI 1·14, 1·28 and OR≥ 16 years 1·68, 95 % CI 1·59, 1·78). Mixed results were found for other origins. Conclusions: The current study suggests that host country conditions might play an important role in explaining OW/OB among some groups of immigrant women. Although further studies are needed to disentangle the mechanisms that generate these health inequalities, policy efforts should focus on immigrant reception and early integration to prevent pregnancy-related OW/OB.

BackgroundCryptophthalmos is characterized by congenital ocular dysplasia with eyelid malformation. The pathogenicity of mutations in genes encoding components of the FRAS1/FREM protein complex is well established, but the underlying pathomechanisms of this disease are still unclear. In the previous study, we generated mice carrying Frem2R725X/R2156W compound heterozygous mutations using CRISPR/Cas9 and showed that these mice recapitulated the human cryptophthalmos phenotype.MethodsIn this study, we tracked changes in the metabolic profile of embryos and expression of metabolism-related genes in Frem2 mutant mice on E13.5 compared with wild-type mice. RNA sequencing (RNA-seq) was utilized to decipher the differentiated expression of genes associated with metabolism. Untargeted metabolomics and targeted metabolomics analyses were performed to detect and verify the shifts in the composition of the embryonic metabolome.ResultsDifferentially expressed genes participating in amino acid metabolism and energy metabolism were observed by RNA-seq. Transcriptomic analysis suggests that 821 (39.89%) up-regulated genes and 320 (32.99%) down-regulated genes were involved in the metabolic process in the enriched GO terms. A total of 92 significantly different metabolites were identified including creatine, guanosine 5′-monophosphate, cytosine, cytidine 5′-monophosphate, adenine, and L-serine. Interestingly, major shifts related to ATP binding cassette transporters (ABC transporters) and the biosynthesis of amino acids in the composition of the embryonic metabolome were observed by KEGG metabolic analysis, indicating that these pathways could also be involved in the pathogenesis of cryptophthalmos.ConclusionWe demonstrate that Frem2 mutant fetal mice have increased susceptibility to the disruption of eye morphogenesis in association with distinct transcriptomic and metabolomic signatures. Our findings suggest that the metabolomic signature established before birth may play a role in mediating cryptophthalmos in Frem2 mutant mice, which may have important implications for the pathogenesis of cryptophthalmos.

BackgroundCryptophthalmos is characterized by congenital ocular dysplasia with eyelid malformation. The pathogenicity of mutations in genes encoding components of the FRAS1/FREM protein complex is well established, but the underlying pathomechanisms of this disease are still unclear. In the previous study, we generated mice carrying Frem2R725X/R2156W compound heterozygous mutations using CRISPR/Cas9 and showed that these mice recapitulated the human cryptophthalmos phenotype.MethodsIn this study, we tracked changes in the metabolic profile of embryos and expression of metabolism-related genes in Frem2 mutant mice on E13.5 compared with wild-type mice. RNA sequencing (RNA-seq) was utilized to decipher the differentiated expression of genes associated with metabolism. Untargeted metabolomics and targeted metabolomics analyses were performed to detect and verify the shifts in the composition of the embryonic metabolome.ResultsDifferentially expressed genes participating in amino acid metabolism and energy metabolism were observed by RNA-seq. Transcriptomic analysis suggests that 821 (39.89%) up-regulated genes and 320 (32.99%) down-regulated genes were involved in the metabolic process in the enriched GO terms. A total of 92 significantly different metabolites were identified including creatine, guanosine 5′-monophosphate, cytosine, cytidine 5′-monophosphate, adenine, and L-serine. Interestingly, major shifts related to ATP binding cassette transporters (ABC transporters) and the biosynthesis of amino acids in the composition of the embryonic metabolome were observed by KEGG metabolic analysis, indicating that these pathways could also be involved in the pathogenesis of cryptophthalmos.ConclusionWe demonstrate that Frem2 mutant fetal mice have increased susceptibility to the disruption of eye morphogenesis in association with distinct transcriptomic and metabolomic signatures. Our findings suggest that the metabolomic signature established before birth may play a role in mediating cryptophthalmos in Frem2 mutant mice, which may have important implications for the pathogenesis of cryptophthalmos.

Summary In an ideal hydraulic fracturing project, the viscosity of hydraulic fracturing fluid (HFF) should drop to facilitate an efficient and quick fracture cleanup once proppants have been placed. Ammonium persulfate (APS) is widely used as an oxidizer breaker to degrade the insoluble residue of the HFF. However, a complex network of artificial fractures with sizes ranging from millimeters to micrometers restricts the transportation application and reaction time of standard breakers and current millimeter-sized capsule breakers. In this study, we introduce an APS nanocapsule (APS-NC) breaker, fabricated via a simple miniemulsion technique, that is capable of addressing the degradation of insoluble residue of the HFF in deep fractures. The nanocapsules are produced through precise control of the nanoprecipitation of poly(methyl methacrylate) (PMMA) onto aqueous APS nanodroplets. Stable aqueous nanodroplets are generated by means of an inverse miniemulsion using Pluronic P-123 as a specific surfactant to form a large and stable water-oil internal surface referring to the long chain and amphipathic property of Pluronic P-123 molecule. Pluronic P-123 is included in the process not only to stabilize the miniemulsion and increase the precipitation efficiency of PMMA but also to function as a thermo-responsive switch for the delayed burst release of APS. The size of the resulting nanocapsules can be controlled within the 207 and 821 nm range, yielding APS up to 92%. The release rate of APS can be controlled by the initial amount of PMMA (150–300 mg), environmental temperature (40–80°C), and environmental pH (3.4–7). When the temperature was 80℃, the initial amount of Pluronic P-123 dominated the release dynamic of APS. Compared with the APS breaker in a dynamic degradation experiment, the APS-NC had a more controllable degradation profile that could cause hydrolyzed polyacrylamide (HPAM) to burst degrade after 6 hours of heating at 80°C.

Abstract Background The electronic Personal Health Record (ePHR) is a health information system that registers health data on newly arriving migrants and was implemented in eight European countries (Bulgaria, Croatia, Cyprus, Greece, Italy, Romania, Serbia and Slovenia). This is a cross-sectional study aimed to describe the health problems and health status of all migrants attended at health clinics as part of the health assessment programme established in the reception centres (2016–2019). Methods Data were collected on demographics, clinical and laboratory findings and diagnostics performed, including medical records. We classified all diseases using pre-specified algorithms according to information on pre-specified variables from the ePHR questionnaire, ICD-10 codes, positive laboratory findings or review of medical records. Crude proportions were calculated and odds ratios (OR) estimated using logistic regression modelling. Results The ePHR dataset contained a total of 19 564 clinical episodes in 14 436 individuals, recorded between January 2016 and October 2019. Most individuals (75%) were refugees or asylum seekers (22%) from 92 different nationalities. There were 2531/19 564 (12.9%) infectious diseases episodes reported during the study period, being 1283/2531 (50.7%) of them pharyngo-tonsillitis, 529 (20.9%) scabies, 158 (6.2%) viral hepatitis and 156(6.1%) lower respiratory infections. There were 2462 (17.1%) individuals with non-communicable diseases reported; including 821 (5.7%) cardiovascular diseases, 1183 (8.2%) neurological condition, 644 (4.5%) Diabetes mellitus and 212 (1.5%) kidney disease cases. Having Diabetes Mellitus (adjusted OR, aOR 3.3, [95% confidence interval, CI 2.7–4.1], P &lt; 0.001), and neurological disorders (aOR 1.8, [95% CI 1.4–2.2], P &lt; 0.001) were associated with cardiovascular disorders in the multivariable logistic regression model. Mental health problems were reported in 641/14 436 (4.4%) individuals and were associated with increasing age. Furthermore, 610 episodes of acute injuries were reported among 585/14 436 (4.1%) people, 517 (88.4%) of them in men (P &lt; 0.001). Conclusions The ePHR is a valuable tool to efficiently collect health-related data to better address migrant health issues. We described a mostly healthy population with many acute infectious disease episodes particularly in children, but also with significant number of chronic conditions and less frequent injuries or mental health problems.

Abstract Background Pleiotropic effects have been implicated in clinical benefits of ticagrelor compared to thienopyridine P2Y12 antagonists. There are conflicting data regarding effects of ticagrelor vs. thienopyridine P2Y12 blockers on endothelial function. Our aim was to compare endothelial biomarkers and their relations with platelet reactivity in real-world patients after acute coronary syndrome (ACS) on maintenance dual antiplatelet therapy (DAPT) with ticagrelor or clopidogrel stratified by diabetes status. Methods Biochemical indices of endothelial dysfunction/activation and platelet reactivity by multiple electrode aggregometry were compared in 126 stable post-ACS subjects (mean age: 65 ± 10 years, 92 men and 34 women), including patients with (n = 61) or without (n = 65) coexistent type 2 diabetes (T2DM) on uneventful maintenance DAPT with either ticagrelor (90 mg b.d.) or clopidogrel (75 mg o.d.) in addition to low-dose aspirin. Exclusion criteria included a complicated in-hospital course, symptomatic heart failure, left ventricular ejection fraction < 40% and relevant coexistent diseases except for well-controlled diabetes, mild renal insufficiency or hypertension. Results Clinical characteristics were similar in patients on ticagrelor (n = 62) and clopidogrel (n = 64). The adenosine diphosphate-induced platelet aggregation and circulating soluble P-selectin (sP-selectin) were decreased in ticagrelor users irrespective of T2DM status (p < 0.001 and p < 0.01 for platelet reactivity and sP-selectin, respectively). Plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) were lower in T2DM subjects on ticagrelor vs. clopidogrel (758 ± 162 vs. 913 ± 217 µg/L, p < 0.01). In contrast, plasma sVCAM-1 was similar in non-diabetic patients on ticagrelor and clopidogrel (872 ± 203 vs. 821 ± 210 µg/L, p > 0.7). The concentrations of sE-selectin, monocyte chemoattractant protein-1 and asymmetric dimethylarginine did not differ according to the type of P2Y12 antagonist regardless of T2DM status. Platelet reactivity was unrelated to any endothelial biomarker in subjects with or without T2DM. Conclusions Our preliminary findings may suggest an association of ticagrelor-based maintenance DAPT with favorable endothelial effects compared to clopidogrel users in stable post-ACS patients with T2DM. If proven, this could contribute to more pronounced clinical benefits of ticagrelor in diabetic subjects.

The TRP superfamily of channels (nomenclature as agreed by NC-IUPHAR [159, 999]), whose founder member is the Drosophila Trp channel, exists in mammals as six families; TRPC, TRPM, TRPV, TRPA, TRPP and TRPML based on amino acid homologies. TRP subunits contain six putative TM domains and assemble as homo- or hetero-tetramers to form cation selective channels with diverse modes of activation and varied permeation properties (reviewed by [679]). Established, or potential, physiological functions of the individual members of the TRP families are discussed in detail in the recommended reviews and in a number of books [371, 635, 1066, 236]. The established, or potential, involvement of TRP channels in disease is reviewed in [412, 634] and [637], together with a special edition of Biochemica et Biophysica Acta on the subject [634]. Additional disease related reviews, for pain [585], stroke [1052], sensation and inflammation [921], itch [117], and airway disease [284, 979], are available. The pharmacology of most TRP channels has been advanced in recent years. Broad spectrum agents are listed in the tables along with more selective, or recently recognised, ligands that are flagged by the inclusion of a primary reference. See Rubaiy (2019) for a review of pharmacological tools for TRPC1/C4/C5 channels [751]. Most TRP channels are regulated by phosphoinostides such as PtIns(4,5)P2 although the effects reported are often complex, occasionally contradictory, and likely to be dependent upon experimental conditions, such as intracellular ATP levels (reviewed by [941, 638, 747]). Such regulation is generally not included in the tables.When thermosensitivity is mentioned, it refers specifically to a high Q10 of gating, often in the range of 10-30, but does not necessarily imply that the channel's function is to act as a 'hot' or 'cold' sensor. In general, the search for TRP activators has led to many claims for temperature sensing, mechanosensation, and lipid sensing. All proteins are of course sensitive to energies of binding, mechanical force, and temperature, but the issue is whether the proposed input is within a physiologically relevant range resulting in a response. TRPA (ankyrin) familyTRPA1 is the sole mammalian member of this group (reviewed by [268]). TRPA1 activation of sensory neurons contribute to nociception [382, 831, 555]. Pungent chemicals such as mustard oil (AITC), allicin, and cinnamaldehyde activate TRPA1 by modification of free thiol groups of cysteine side chains, especially those located in its amino terminus [529, 51, 336, 531]. Alkenals with α, β-unsaturated bonds, such as propenal (acrolein), butenal (crotylaldehyde), and 2-pentenal can react with free thiols via Michael addition and can activate TRPA1. However, potency appears to weaken as carbon chain length increases [23, 51]. Covalent modification leads to sustained activation of TRPA1. Chemicals including carvacrol, menthol, and local anesthetics reversibly activate TRPA1 by non-covalent binding [391, 470, 1007, 1006]. TRPA1 is not mechanosensitive under physiological conditions, but can be activated by cold temperatures [392, 193]. The electron cryo-EM structure of TRPA1 [688] indicates that it is a 6-TM homotetramer. Each subunit of the channel contains two short ‘pore helices’ pointing into the ion selectivity filter, which is big enough to allow permeation of partially hydrated Ca2+ ions. TRPC (canonical) familyMembers of the TRPC subfamily (reviewed by [261, 726, 15, 4, 84, 410, 687, 60]) fall into the subgroups outlined below. TRPC2 is a pseudogene in humans. It is generally accepted that all TRPC channels are activated downstream of Gq/11-coupled receptors, or receptor tyrosine kinases (reviewed by [713, 889, 999]). A comprehensive listing of G-protein coupled receptors that activate TRPC channels is given in [4]. Hetero-oligomeric complexes of TRPC channels and their association with proteins to form signalling complexes are detailed in [15] and [411]. TRPC channels have frequently been proposed to act as store-operated channels (SOCs) (or compenents of mulimeric complexes that form SOCs), activated by depletion of intracellular calcium stores (reviewed by [689, 15, 718, 765, 1039, 141, 675, 55, 142]). However, the weight of the evidence is that they are not directly gated by conventional store-operated mechanisms, as established for Stim-gated Orai channels. TRPC channels are not mechanically gated in physiologically relevant ranges of force. All members of the TRPC family are blocked by 2-APB and SKF96365 [319, 318]. Activation of TRPC channels by lipids is discussed by [60]. Important progress has been recently made in TRPC pharmacology [751, 571, 400, 92]. TRPC channels regulate a variety of physiological functions and are implicated in many human diseases [270, 61, 827, 960]. TRPC1/C4/C5 subgroup TRPC1 alone may not form a functional ion channel [210]. TRPC4/C5 may be distinguished from other TRP channels by their potentiation by micromolar concentrations of La3+. TRPC2 is a pseudogene in humans, but in other mammals appears to be an ion channel localized to microvilli of the vomeronasal organ. It is required for normal sexual behavior in response to pheromones in mice. It may also function in the main olfactory epithelia in mice [1036, 672, 673, 1037, 496, 1077, 1032].TRPC3/C6/C7 subgroup All members are activated by diacylglycerol independent of protein kinase C stimulation [319].TRPM (melastatin) familyMembers of the TRPM subfamily (reviewed by [252, 318, 689, 1064]) fall into the five subgroups outlined below. TRPM1/M3 subgroupIn darkness, glutamate released by the photoreceptors and ON-bipolar cells binds to the metabotropic glutamate receptor 6 , leading to activation of Go . This results in the closure of TRPM1. When the photoreceptors are stimulated by light, glutamate release is reduced, and TRPM1 channels are more active, resulting in cell membrane depolarization. Human TRPM1 mutations are associated with congenital stationary night blindness (CSNB), whose patients lack rod function. TRPM1 is also found melanocytes. Isoforms of TRPM1 may present in melanocytes, melanoma, brain, and retina. In melanoma cells, TRPM1 is prevalent in highly dynamic intracellular vesicular structures [368, 657]. TRPM3 (reviewed by [663]) exists as multiple splice variants which differ significantly in their biophysical properties. TRPM3 is expressed in somatosensory neurons and may be important in development of heat hyperalgesia during inflammation (see review [878]). TRPM3 is frequently coexpressed with TRPA1 and TRPV1 in these neurons. TRPM3 is expressed in pancreatic beta cells as well as brain, pituitary gland, eye, kidney, and adipose tissue [662, 877]. TRPM3 may contribute to the detection of noxious heat [949].TRPM2TRPM2 is activated under conditions of oxidative stress (respiratory burst of phagocytic cells) and ischemic conditions. However, the direct activators are ADPR(P) and calcium. As for many ion channels, PIP2 must also be present (reviewed by [1020]). Numerous splice variants of TRPM2 exist which differ in their activation mechanisms [219]. The C-terminal domain contains a TRP motif, a coiled-coil region, and an enzymatic NUDT9 homologous domain. TRPM2 appears not to be activated by NAD, NAAD, or NAADP, but is directly activated by ADPRP (adenosine-5'-O-disphosphoribose phosphate) [902]. TRPM2 is involved in warmth sensation [789], and contributes to neurological diseases [66]. Recent study shows that 2'-deoxy-ADPR is an endogenous TRPM2 superagonist [253]. TRPM4/5 subgroupTRPM4 and TRPM5 have the distinction within all TRP channels of being impermeable to Ca2+ [999]. A splice variant of TRPM4 (i.e.TRPM4b) and TRPM5 are molecular candidates for endogenous calcium-activated cation (CAN) channels [301]. TRPM4 is active in the late phase of repolarization of the cardiac ventricular action potential. TRPM4 deletion or knockout enhances beta adrenergic-mediated inotropy [546]. Mutations are associated with conduction defects [374, 546, 821]. TRPM4 has been shown to be an important regulator of Ca2+ entry in to mast cells [926] and dendritic cell migration [43]. TRPM5 in taste receptor cells of the tongue appears essential for the transduction of sweet, amino acid and bitter stimuli [494] TRPM5 contributes to the slow afterdepolarization of layer 5 neurons in mouse prefrontal cortex [471]. Both TRPM4 and TRPM5 are required transduction of taste stimuli [226].TRPM6/7 subgroupTRPM6 and 7 combine channel and enzymatic activities (‘chanzymes’). These channels have the unusual property of permeation by divalent (Ca2+, Mg2+, Zn2+) and monovalent cations, high single channel conductances, but overall extremely small inward conductance when expressed to the plasma membrane. They are inhibited by internal Mg2+ at ~0.6 mM, around the free level of Mg2+ in cells. Whether they contribute to Mg2+ homeostasis is a contentious issue. When either gene is deleted in mice, the result is embryonic lethality. The C-terminal kinase region is cleaved under unknown stimuli, and the kinase phosphorylates nuclear histones. TRPM7 is responsible for oxidant- induced Zn2+ release from intracellular vesicles [3] and contributes to intestinal mineral absorption essential for postnatal survival [574]. TRPM8Is a channel activated by cooling and pharmacological agents evoking a ‘cool’ sensation and participates in the thermosensation of cold temperatures [54, 161, 205] reviewed by [943, 516, 420, 599]. TRPML (mucolipin) familyThe TRPML family [729, 1049, 723, 1010, 173] consists of three mammalian members (TRPML1-3). TRPML channels are probably restricted to intracellular vesicles and mutations in the gene (MCOLN1) encoding TRPML1 (mucolipin-1) cause the neurodegenerative disorder mucolipidosis type IV (MLIV) in man. TRPML1 is a cation selective ion channel that is important for sorting/transport of endosomes in the late endocytotic pathway and specifically, fission from late endosome-lysosome hybrid vesicles and lysosomal exocytosis [766]. TRPML2 and TRPML3 show increased channel activity in low extracellular sodium and are activated by similar small molecules [293]. A naturally occurring gain of function mutation in TRPML3 (i.e. A419P) results in the varitint waddler (Va) mouse phenotype (reviewed by [729, 639]). TRPP (polycystin) familyThe TRPP family (reviewed by [197, 195, 275, 988, 345]) or PKD2 family is comprised of PKD2 (PC2), PKD2L1 (PC2L1), PKD2L2 (PC2L2), which have been renamed TRPP1, TRPP2 and TRPP3, respectively [999]. It should also be noted that the nomenclature of PC2 was TRPP2 in old literature. However, PC2 has been uniformed to be called TRPP2 [317]. PKD2 family channels are clearly distinct from the PKD1 family, whose function is unknown. PKD1 and PKD2 form a hetero-oligomeric complex with a 1:3 ratio. [845]. Although still being sorted out, TRPP family members appear to be 6TM spanning nonselective cation channels. TRPV (vanilloid) familyMembers of the TRPV family (reviewed by [928]) can broadly be divided into the non-selective cation channels, TRPV1-4 and the more calcium selective channels TRPV5 and TRPV6.TRPV1-V4 subfamilyTRPV1 is involved in the development of thermal hyperalgesia following inflammation and may contribute to the detection of noxius heat (reviewed by [710, 824, 860]). Numerous splice variants of TRPV1 have been described, some of which modulate the activity of TRPV1, or act in a dominant negative manner when co-expressed with TRPV1 [787]. The pharmacology of TRPV1 channels is discussed in detail in [303] and [947]. TRPV2 is probably not a thermosensor in man [684], but has recently been implicated in innate immunity [503]. TRPV3 and TRPV4 are both thermosensitive. There are claims that TRPV4 is also mechanosensitive, but this has not been established to be within a physiological range in a native environment [114, 488].TRPV5/V6 subfamily TRPV5 and TRPV6 are highly expressed in placenta, bone, and kidney. Under physiological conditions, TRPV5 and TRPV6 are calcium selective channels involved in the absorption and reabsorption of calcium across intestinal and kidney tubule epithelia (reviewed by [984, 185, 601, 248]).