Academic literature on the topic '791/.01/4'

<p>The aim of this study was to systematically review the literature to assess static fracture strength tests applied for FDPs and analyze the impact of periodontal ligament (PDL) simulation on the fracture strength. Original scientific papers published in MEDLINE (PubMed) database between 01/01/1981 and 01/06/2010 were included in this systematic review. Data were analyzed considering the test method (static loading), material type (metal-ceramic-MC, oxide all-ceramic-AC, fiber reinforced composite resin-FRC, composite resin-C), PDL (without or with) and restoration type (single crowns, 3-unit, 4-unit, inlay-retained and cantilever FDPs). The selection process resulted in the 72 studies. In total, 377 subgroups revealed results from static load-bearing capacity of different materials. Fourteen metal-ceramic, 190 AC, 121 FRC, 45 C resin groups were identified as subgroups. Slightly decreased results were observed with the presence of PDL for single crowns (without PDL=1117±215 N; with PDL=876±69 N), 3-unit FDPs (without PDL=791±116 N; with PDL=675±91 N) made of AC, 3-unit FDP (without PDL=1244±270 N; with PDL=930±76 N) and inlay-retained FDP (without PDL=848±104 N; with PDL=820±91 N) made of FRC and 4-unit FDPs (without PDL=548±26 N; with PDL=393±67 N) made of C. Overall, for single crowns, fracture strength of FRC was higher than that of AC and MC; for 3-unit FDPs FRC=C&gt;AC=MC; for 4-unit FDPs AC&gt;FRC&gt;C and for inlay-retained FDPs, FRC=AC. An inclination for decreased static fracture strength could be observed with the simulation of PDL but due to insufficient data this could not be generalized for all materials used for FDPs.</p>

565 Background: SET2,3 index measures hormone receptor-related transcriptional activity (SETER/PR) adjusted for a baseline prognosis index (BPI) derived from tumor size, nodes involved and a 4-gene molecular subtype (RNA4). SET2,3 added prognostic information to the 21-gene Breast Recurrence Score (RS) in the SWOG 8814 trial (1). To confirm this, we independently evaluated both tests performed on node-positive, hormone receptor-positive (HR+) cancers from the PACS-01 trial (Roche et al, JCO 2006, PMID: 17116941) that evaluated the addition of adjuvant docetaxel to anthracycline-based chemotherapy. Adjuvant endocrine therapy became standard for premenopausal patients during PACS-01, justifying a sensitivity analysis in the population who received adjuvant endocrine therapy. Methods: SET2,3 was measured with the QuantiGene Plex bead-based hybridization assay (ThermoFisher) using an aliquot of residual RNA from prior RS testing in 791 HR+ tumor samples. Pre-defined cut points defined higher risk if RS >25 or SET2,3 <2.10. SETER/PR index and BPI, individual components of SET2,3 index, were evaluated as continuous variables. The primary endpoint was distant recurrence-free interval (DRFI). Multivariable Cox proportional hazards models were used to calculate hazard ratios with 95% confidence interval (HR, 95%CI) adjusted for treatment arm, and the likelihood ratio (LR) of benefit from addition of SET2,3 to RS with LR test for significance at p <0.05. Results: Of 791 tumor samples, 760 (96.1%) passed quality control (QC) for the SET assay; 724 had pathologic information to calculate SET2,3 index; and 659 had results for RS and SET2,3. At a median follow-up of 8 years, distant recurrence occurred in 144 of 659 (21.9%) patients overall, and 94 of 490 (19.2%) patients in the sensitivity population. Overall, high RS status (HR 2.33, 1.60-3.39) and high SET2,3 (HR 0.43, 0.30-0.62) were independently prognostic. SET2,3 was high in 303/377 (80.4%) patients with RS ≤25, with 5-year DRFI of 93.7% [95%CI 90.2;95.9]; and SET2,3 was low in 171/282 (60.6%) patients with RS >25, with 5-year DRFI 64.6% [95%CI 56.9;71.3]. SETER/PR index of endocrine transcriptional activity and the BPI, each contributed additional prognostic information to RS status in the sensitivity population (Table). Conclusions: SET2,3 index added prognostic information to the Recurrence Score in this independent blinded validation study of the PACS-01 trial for node-positive breast cancer. 1. Speers et al, JCO 2023, PMID: 36649570. [Table: see text]

PURPOSE To provide fludarabine to physicians for the management of patients with advanced refractory chronic lymphocytic leukemia (CLL) and to determine the response rate and duration, toxicity, and survival with this agent. PATIENTS AND METHODS This phase II protocol was open to all eligible patients whose local physicians obtained written permission from the National Cancer Institute (NCI) to register patients onto this protocol. Of 791 national and international enrolled patients, 724 with a median age of 65 years received fludarabine, of which 703 were assessable for response. RESULTS Thirty-two percent of assessable patients responded (95% confidence interval [CI], 29% to 36%), with 21 patients (3%) obtaining a complete response and 205 (29%) a partial response. The median duration of response was 13.1 months and the median survival time from registration was 12.6 months. Age, performance status (PS), and Rai stage correlated with survival (P < .01). Grade 4 hematologic toxicity was reported in 43% and was associated with infection in 22%. Neurotoxicity (primarily grade 1 motor dysfunction) was reported in 14% patients and correlated with age. CONCLUSION This study describes the toxicity and activity of fludarabine in refractory CLL in a setting that more closely resembles clinical practice than most published trials. The low response rate may be related to advanced stage (89% Rai high-risk), disease-related symptoms (63% had B symptoms), and/or degree of prior treatment. Other contributing factors inherent in a group C treatment protocol included lack of central pathology review, variable supportive care, and a tendency to use this mechanism at a later stage in the disease.

SUMMARYWildlife reservoir hosts of bovine tuberculosis (bTB) include Eurasian badgers (Meles meles) and brushtail possum (Trichosurus vulpecula) in the UK and New Zealand, respectively. Similar species warrant further investigation in the northern lower peninsula of Michigan, USA due to the continued presence of bTB on cattle farms. Most research in Michigan, USA has focused on interactions between white-tailed deer (Odocoileus virginianus) and cattle (Bos taurus) for the transmission of the infectious agent of bTB, Mycobacterium bovis, due to high deer densities and feeding practices. However, limited data are available on medium-sized mammals such as Virginia opossum (Didelphis virginiana; hereafter referred to as opossum) and their movements and home range in Michigan near cattle farms. We conducted surveillance of medium-sized mammals on previously depopulated cattle farms for presence of M. bovis infections and equipped opossum with Global Positioning System (GPS) technology to assess potential differences in home range between farms inside and outside the bTB core area that has had cattle test positive for M. bovis. On farms inside the bTB core area, prevalence in opossum was comparable [6%, 95% confidence interval (CI) 2·0–11·0] to prevalence in raccoon (Procyon lotor; 4%, 95% CI 1·0–9·0, P = 0·439) whereas only a single opossum tested positive for M. bovis on farms outside the bTB core area. The prevalence in opossum occupying farms that had cattle test positive for M. bovis was higher (6·4%) than for opossum occupying farms that never had cattle test positive for M. bovis (0·9%, P = 0·01). Mean size of home range for 50% and 95% estimates were similar by sex (P = 0·791) both inside or outside the bTB core area (P = 0·218). Although surveillance efforts and home range were not assessed on the same farms, opossum use of farms near structures was apparent as was selection for farms over surrounding forested habitats. The use of farms, stored feed, and structures by opossum, their ability to serve as vectors of M. bovis, and their propensity to ingest contaminated sources of M. bovis requires additional research in Michigan, USA.

ABSTRACT Despite causing marked inhibition of somatic growth, glucocorticoids enhance both the response to GH-releasing hormone (GHRH) and the amplitude of naturally occurring GH secretory pulses in the male rat. The relative contribution of the two major hypothalamic regulatory factors for GH (somatostatin and GHRH) to these observed effects remains speculative. In the present studies, we have investigated endogenous and stimulated GH release in rats pretreated with glucocorticoid or vehicle, and the effects of passive immunoneutralization of somatostatin or GHRH. In an initial study, four groups of eight rats were treated with either saline or various doses of a depot preparation of betamethasone: low dose, 0·85 mg; medium dose, 1·7 mg; high dose, 3·4 mg. All doses significantly suppressed body weight gain, total adrenal weight and concentrations of both plasma corticosterone and pituitary ACTH. Seven days after betamethasone treatment, GH responses to an i.v. injection of 1 μg human GHRH(1–29) were evaluated during pentobarbitone anaesthesia. Compared with saline-treated controls (peak GH concentration of 506·0±68·5 μg/l), peak GH levels were enhanced by the low dose (704·4±47·8 μg/l, P<0·05), unaltered by the medium dose (543±65·8 μg/l) and suppressed by the high dose (312·7±55·2 μg/l, P<0·05) of betamethasone. Similarly, the area under the secretory curves was increased by 46% following the low dose (P<0·01), unaltered by the medium dose and reduced by 33% after the high dose of betamethasone. In a second study, rats were pretreated for 7 days before blood sampling with either the medium dose of betamethasone or saline. On day 5, 48 h before blood sampling, an indwelling venous catheter was fitted enabling sampling of conscious rats. On the day of study, blood samples were taken at 30-min intervals over an initial 2-h period (10.00–12.00 h). Following the sample at 12.00 h, rats were given the reconstituted and dialysed immunoglobulin fraction from either control sheep serum (NSIgG), sheep anti-rat GHRH serum (GHRHab) or sheep anti-somatostatin serum (SRIHab), and samples were taken for a further 90 min (12.30–14.00 h). Directly after the sample at 14.00 h, GH stimulation was effected in all rats using 1 μg human GHRH(1–29) with samples taken at 5, 10, 20 and 40 min following stimulation. During the initial sampling period, mean GH levels were significantly (P<0·005) higher in steroidpretreated animals than in saline-pretreated controls (29·3±5·8 vs 13·2±1·6 μg/l), with a higher amplitude secretory pulse occurring at 11.30 h (80·7±18·6 vs 26·4±4·1 μg/l, P < 0·01). Administration of GHRHab to saline-pretreated animals did not alter mean GH levels when compared with animals receiving control NSIgG (saline plus NSIgG, 9·3±1·1; saline plus GHRHab, 8±1·1 μg/l, P = NS). In contrast, the raised mean GH levels seen in betamethasone-pretreated rats receiving NSIgG (12·3 ±1·1 μg/l) were reduced by GHRHab administration (7·6±1·1 μg/l); these levels were not different from those of the saline-pretreated group suggesting that the observed permissive effect of glucocorticoids on GH secretion is mediated through enhanced GHRH activity. SRIHab increased mean basal GH levels to a similar extent in both saline- and betamethasone-pretreated groups (17·4±1·2 μg/l and 19·3 ±1·1 μg/l respectively, P<0·01 vs comparable NSIgG group). Administration of the various immunoglobulin fractions had no effect on GHRH-stimulated GH secretion except when SRIHab was given to betamethasone-pretreated animals, resulting in a significantly increased peak response (1467±93 μg GH/l, P<0·001) when compared with either saline- or betamethasone-pretreated rats given NSIgG (643±95 and 791±92 μg/l respectively). This enhancement following SRIHab administration was not seen in saline-pretreated animals (893±180 μg GH/l). These results imply that glucocorticoid treatment increases basal GH levels through a GHRH-dependent mechanism and also increases pituitary sensitivity to exogenous GHRH when inhibitory somatostatin tone is blocked. Journal of Endocrinology (1991) 131, 75–86

Background: Superiority of Axicabtagene Ciloleucel (Axi-Cel) in relapsed/refractory (R/R) large B cell lymphomas (LBCL) compared with standard of care was shown in both the 3 rd and 2 nd line setting. However, optimal timing for incorporation of CAR-T is not well established. We aimed to compare efficacy, toxicity profile, and product kinetics of Axi-Cel as 2 nd vs 3 rd line of treatment. Methods: we performed a national real world retrospective study of consecutive patients treated with Axi-Cel as 2 nd line with propensity score-matched patients treated with 3 rd line treatment. Patients were matched for age (±2 years), Eastern Cooperative Oncology Group (ECOG) performance status, and disease status at lymphodepletion. Disease status and response were defined by the Lugano criteria, cytokine release syndrome (CRS) and immune effector cells-associated neurotoxicity syndrome (ICANS) were defined by ASTCT Consensus (2019) and progression-free survival (PFS) was calculated from infusion to index event. Immunophenotyping from peripheral blood at day 7+ was used to analyze expansion of CAR-T cells. Results: Between 01/2019and 06/2023, 44 patients treated with Axi-Cel fulfilled the inclusion criteria, 22 in each cohort. Groups were well matched in the propensity score domains (mean difference 2, p=.65 for age, mean square .32, p=.57 for ECOG, and mean square .26, p=.61 for disease status at lymphodepletion). Median follow up was 2.2 (range, 1-28.8) months in 2 nd line group and 10.8 (range, 1-39) months in the 3 rd group. Median age was 68 (range, 39 - 84) and 66 (range, 32 - 80) years in the 2 nd and 3 rd line groups, respectively. There were no differences between gender (p=.76), LBCL subtypes (p=.16), % of patients receiving bridging therapy (p=.55), % of patients with elevated LDH levels prior to lymphodepletion (p=.98), and n days from collection to treatment (p=.29) between the 2 groups. There was a lower % of patients with primary refractory disease in the 2 nd, compared to 3 rd line therapy group (63% vs. 36%, respectively, p=.09) and a higher % of patients with transformed disease (42% vs. 14%, respectively, p=.04). Both overall and grade 3-4 incidences of CRS were similar between the 2 nd line and the 3 rd line groups (86% vs. 95%, p=.16 and 18% in both groups, p=1, respectively). Median days to CRS onset was also similar (1, range 0 - 5 and 2, range 0 - 7, p=.1, respectively). Both overall and grade 3-4 incidences of ICANS) were similar between the 2 nd line and the 3 rd line groups (41% vs. 64%, p=.48 and 14% vs. 18%, p=.73, respectively. Median days to ICANS onset was lower in the 2 nd line compared to the 3 rd line group (4, range 0 - 8 and 6, range 0 - 7, p=.06, respectively). There were no differences between the groups in the median tocilizumab doses (p=.21), % of patients receiving steroids (p=.12), cumulative steroids dose (p=.17), % of patients receiving growth factors (p=1), and duration of admission (p=.51). Median day +7 CAR-T blood levels were higher in the 2 nd line compared to the 3 rd line group (126 (range,1-791) vs. 18.1 (range, 0-988) cells/microL, p=.05, respectively). 1-month overall response rate (ORR) was 86% (CR=77%) in the 2nd line group vs 64% (CR=45%), in the 3rd line group, p=.081 Figure 1a. Three-months progression-free survival was 88% (95%, CI 64%-100%) vs. 59% (45%-73%), respectively, Figure 1b. Cox regression identified 2 nd line treatment associated with better progression-free survival (HR=.15, p=.007) and progressive disease at lymphodepletion associated with worse progression-free (HR=8.5, p=.007), while age, gender, and ECOG performance status did not impact progression. Conclusions: This matched comparison showed favorable ORR and PFS rates when Axi-Cel is utilized as a 2nd line treatment vs 3rd line. Toxicity profile is similar. Higher CAR-T expansion in the 2nd line might provide insight regarding product quality and exhaustion phenotype when manufactured earlier in the LBCL treatment course. A longer follow-up is needed to test whether these findings translate to durable remission and cure.

Kikuyugrass (Pennisetum clandestinum) is a C4 grass and invasive weed adopted for use as a primary turf species in some golf course fairways and roughs in southern California. In September 2008, a new Rhizoctonia-like fungus was isolated from a diseased kikuyugrass sample received from a golf course fairway in Oceanside, CA. The kikuyugrass was from a mature stand (>20 years old) that was maintained at a height of approximately 1.25 cm. Symptoms on kikyuygrass developed initially as irregular, blighted, chlorotic patches, several centimeters to one meter, which occurred during a period of warm, humid weather (27 to 29°C maximum daytime temperature, 75 to 85% average relative humidity) on a small part of one fairway. Affected areas became brown and necrotic as the disease progressed. Leaf chlorosis and stem rot were observed on affected plants. The organism was isolated by placing symptomatic leaves on acidified one-quarter-strength potato dextrose agar (PDA) (600 μl of 85% lactic acid per liter of medium) in a petri dish (1). A colony of a Rhizoctonia-like fungus with yellow aerial hyphae, multinucleate hyphal cells, and irregularly shaped, golden brown sclerotia (4 to 7 mm) developed within 30 days at 28°C. The rDNA internal transcribed spacer (ITS) sequence was obtained (GenBank Accession No. HQ850254) using PCR amplification with primers ITS1F and ITS4 (1,2), and a BLAST search showed 100% similarity with Waitea circinata var. prodigus (GenBank Accession No. HM597145), which had recently been described as the cause of basal leaf blight of seashore paspalum (Paspalum vaginatum), another C4 grass (3), in Florida. Colony morphology and other physical characteristics were similar but not completely identical to those from Florida, reflecting the reported morphological variation inherent in the pathogen (3). Koch's postulates were performed by growing this isolate on PDA in a petri dish for 7 days, homogenizing the culture with 100 ml of sterilized water, filtering the suspension through two layers of cheesecloth, and pipetting 10 ml of the mycelial suspension onto the foliage and stems of 4-week-old AZ-1 kikuyugrass plants grown in UC-soilless-mix in 7.5-cm-diameter pots (4). Control plants were treated with a homogenized and filtered dish of PDA only. There were three replicate pots for inoculated and noninoculated treatments and the experiment was repeated independently three times. All of the pots were incubated in a moist chamber with a 12-h light period at 28°C. Yellow lesions were observed on leaves and stems of inoculated plants 4 days postinoculation and necrosis developed 8 days later in all experiments. The same organism was isolated from symptomatic plants. The control plants did not exhibit any symptoms. To our knowledge, this is the first report of basal leaf blight caused by W. circinata var. prodigus on kikuyugrass in California and the first report of this pathogen affecting turfgrass in the western United States. References: (1) C. M. Chen et al. Plant Dis. 93:906, 2009 (2) K. de la Cerda et al. Plant Dis. 91:791, 2007. (3) S. J. Kammerer et al. Plant Dis. 95:515, 2011. (4) T. Toda et al. J. Gen. Plant Pathol. 73:379, 2007.

The pandemic of COVID-19 has afflicted every individual and has initiated a cascade of directly or indirectly involved events in precipitating mental health issues. The human species is a wanderer and hunter-gatherer by nature, and physical social distancing and nationwide lockdown have confined an individual to physical isolation. The present review article was conceived to address psychosocial and other issues and their aetiology related to the current pandemic of COVID-19. The elderly age group has most suffered the wrath of SARS-CoV-2, and social isolation as a preventive measure may further induce mental health issues. Animal model studies have demonstrated an inappropriate interacting endogenous neurotransmitter milieu of dopamine, serotonin, glutamate, and opioids, induced by social isolation that could probably lead to observable phenomena of deviant psychosocial behavior. Conflicting and manipulated information related to COVID-19 on social media has also been recognized as a global threat. Psychological stress during the current pandemic in frontline health care workers, migrant workers, children, and adolescents is also a serious concern. Mental health issues in the current situation could also be induced by being quarantined, uncertainty in business, jobs, economy, hampered academic activities, increased screen time on social media, and domestic violence incidences. The gravity of mental health issues associated with the pandemic of COVID-19 should be identified at the earliest. Mental health organization dedicated to current and future pandemics should be established along with Government policies addressing psychological issues to prevent and treat mental health issues need to be developed. References World Health Organization (WHO) Coronavirus Disease (COVID-19) Dashboard. 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Abstract Background Previous studies have suggested that recurrent heart failure hospitalizations (HFh) are a predictor of cardiovascular (CV) and all-cause mortality. Patients with atrial fibrillation (AF) or type 2 diabetes mellitus (T2DM) may be at increased risk. Purpose This real-world study examined the impact of recurrent HFh on CV mortality in subgroups of patients with (i) AF or (ii) T2DM in the UK. Methods Adult HF patients identified in the CPRD database with a first (index) hospitalization due to HF recorded in the HES dataset from 01/01/2010 to 31/12/2014 and with a claim for AF or T2DM (not mutually exclusive) within the year prior to the index hospitalization were included. Patients were followed until death, transfer out or end of study period (31/12/2017). CV death as primary cause and death due to any cause were evaluated. An extended Cox regression model was used for reporting adjusted relative CV mortality rates for time dependent recurrent HFh. Results 4585 (53.30%) HF patients with AF and 2344 (27.25%) HF patients with T2DM were included, providing 7846 and 4269 patient-years follow-up, respectively. Patients were relatively old (median [IQR] age of 81 [74–87] and 78 [70–84]) and majority were male (54.2% and 59.1%, respectively). All-cause and CV mortality rates are provided in the table. Compared with those without recurrent HFh, the adjusted hazard ratios (95% CI) for CV death for the AF group were 2.6 (2.3–3.1), 3.2 (2.5–4.1), 5.8 (4.1–8.1) and 6.9 (4.6–10.5) for 1, 2, 3 and ≥4 recurrent HFh, and for the T2DM group were 2.2 (1.7–2.8), 3.3 (2.3–4.7), 5.1 (3.3–8.1) and 3.9 (2.3–6.6), respectively. All-cause and CV mortality rates 0 Recurrent HFh 1 Recurrent HFh 2 Recurrent HFh 3 Recurrent HFh 4+ Recurrent HFh All patients AF n=3294 (71.8%) n=817 (17.8%) n=282 (6.2%) n=116 (2.5%) n=76 (1.2%) n=4585 (100.0%) Follow-up time (days) from respective recurrent HF hospitalization (median [IQR]) 345 [57–906] 118 [27–522] 80 [19–367] 54 [19–240] 126 [50–379] 254 [42–793] All-cause death (n (%)) 1755 (53.3%) 483 (59.1%) 159 (56.4%) 80 (69.0%) 46 (60.5%) 2523 (55.0%) CV death- primary cause (n (%)) 1059 (32.2%) 325 (39.8%) 109 (38.7%) 56 (48.3%) 34 (44.7%) 1583 (34.5%) T2DM n=1573 (67.1%) n=456 (19.5%) n=170 (7.3%) n=85 (3.6%) n=60 (2.6%) n=2344 (100.0%) Follow-up time (days) from respective recurrent HF hospitalization (median [IQR]) 360 [63–933] 198 [43–545] 68 [17–292] 106 [26–251] 160 [68–389] 267 [49–771] All-cause death (n (%)) 824 (52.4%) 248 (54.4%) 99 (58.2%) 51 (60.0%) 40 (66.7%) 1262 (53.8%) CV death – primary cause (n (%)) 501 (31.9%) 159 (34.9%) 69 (40.6%) 36 (42.4%) 26 (43.3%) 791 (33.8%) Conclusion Recurrent HFh are a strong predictor of CV death in the HF population with AF or with T2DM. The risk of CV and all-cause death increases with recurrent HFh in these subpopulations, highlighting the relevance of reducing hospitalizations in the management of HF patients with such comorbid conditions.