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This model was tested on an independent sample of 83 subjects providing a median error of 4.5 years. In the present study, an epigenetic model for age prediction was validated in a sample of the Italian population. However, its applicability to advanced ages still represents the main limitation in forensic caseworks.Background Regorafenib is an oral multikinase inhibitor targeting angiogenesis, oncogenesis, and cancer proliferation/metastasis. This study evaluated the efficacy of regorafenib in refractory biliary tract cancer (BTC) in a multi-institutional phase 2 study. Methods Patients with BTC who progressed on at least 1 line of systemic therapy received regorafenib at 160 mg daily for 21 days on and 7 days off. The primary endpoint was 6-month overall survival (OS), and the secondary endpoints were median OS, progression-free survival (PFS), and objective response rates. Pretreatment plasma was collected for cytokine evaluation. Results A total of 39 patients were enrolled, and 33 were evaluable for efficacy. The median PFS and OS were 3.7 and 5.4 months, respectively, with survival rates of 46.2% at 6 months, 35.9% at 12 months, and 25.6% at 18 months for the intention-to-treat population. For the 33 evaluable patients who received regorafenib for at least 3 weeks, the median PFS and OS were 3.9 and 6.7 months, respectively, with survival rates of 51.5% at 6 months, 39.4% at 12 months, and 27.3% at 18 months. The objective response rate was 9.1%, and the disease control rate was 63.6%. Twenty-eight patients (71.8%) experienced grade 3/4 adverse events. Among the 23 cytokines analyzed, elevated baseline vascular endothelial growth factor D (VEGF-D) was associated with shorter PFS, whereas elevated baseline interleukin 6 (IL-6) and glycoprotein 130 (GP130) were associated with shorter OS. Conclusions Regorafenib demonstrated modest clinical efficacy in heavily pretreated patients with BTC. Further exploration of biomarkers is warranted to identify a group of patients with BTC who may benefit from regorafenib.Objectives CD8+ (or CD4+ ) CD25+ fork-head box transcription factor (Foxp3)+ regulatory T cells (CD8+ or CD4+ Tregs) all play a significant role in immune homeostasis and tolerance. However, the role of CD8+ Tregs in allergic rhinitis (AR) have not been clearly elucidated. The present study was aimed to assess the influence of CD8+ Tregs on peripheral blood mononuclear cells (PBMCs) from AR patients. Study design Prospective cross-sectional study. Methods Patients with AR were enrolled. PBMCs were obtained, and CD4+ and CD8+ Tregs were separated from PBMCs and cultured in vitro. We examined percentages of these Tregs in total CD4+ or CD8+ T cells, respectively. After that, we evaluated levels of interleukin (IL)-10 and transforming growth factor (TGF)-β in Tregs cultures. Finally, we administered CD4+ and CD8+ Tregs from AR patients into PBMCs cultures and examined contents of IL-4 and IL-5. Results The percentages of CD4+ or CD8+ Tregs in the total CD4+ or CD8+ T cells from PBMCs in AR patients were reduced compared to normal subjects. However, IL-10 and TGF-β and their mRNAs were increased in CD4+ and CD8+ Tregs cultures from AR patients, and there were no significant differences in their levels between these two Tregs cultures. IL-4 and IL-5 were increased in AR subjects' PBMCs compared to normal ones and decreased after the AR CD4+ or CD8+ Tregs administration. However, there were no statistical differences in IL-4 and IL-5 concentrations between these two Tregs treatments. Conclusions The findings demonstrate that CD8+ Tregs may alleviate inflammatory responses in AR condition. Level of evidence 3 Laryngoscope, 2020.Although prenatal diagnosis and prenatal and neonatal therapy of congenital toxoplasmosis are available, there is controversy concerning the effectiveness of prophylaxis to prevent placental transmission. Experimental, parasitological and clinical data suggest a "window of opportunity" following maternal infection. Among medications active against T. gondii, mainly spiramycin (Spy) and pyrimethamine + sulfonamide combinations (P-S) have been evaluated. Results from observational studies suffered treatment bias, since prescriptions differed according to the gestational age at seroconversion, which is the major risk factor for transmission, and many lacked precise timing. Some large retrospective studies found no difference in transmission according to prophylactic treatment, but transmission was lower when treatment started promptly after maternal seroconversion. A few recent studies adjusting for timing of infection observed lower transmission in case of P-S than other or no prophylaxis. selleck products In the only randomized controlled trial, transmission was lower with P-S than S (18.5% vs. 30%, p = 0.147) ; this association was strengthened when the treatment was started within 3 weeks of seroconversion, and the incidence of fetal cerebral ultrasound signs was significantly reduced in the P-S group. Rapid initiation of prophylactic therapy following maternal infection, which is usually asymptomatic, requires systematic screening for maternal seroconversion during pregnancy. This article is protected by copyright. All rights reserved.Objective To investigate whether intensive blood pressure treatment is associated with less hematoma growth and better outcome in ICH patients who received intravenous nicardipine treatment within 2 hrs after onset of symptoms. Methods A post-hoc exploratory analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial was performed. This was a multicenter, international, open-label randomized clinical trial in which patients with primary ICH were allocated to intensive versus standard blood pressure treatment with nicardipine within 4.5 hours of symptom onset. We have included 913 patients with complete imaging and follow-up data in the present analysis. Results Among the 913 included patients, 354 (38.7%) had intravenous nicardipine treatment initiated within 2 hours. In this subgroup of patients treated within 2 hours, the frequency of ICH expansion was significantly lower in the intensive blood pressure reduction group as compared with standard treatment group (P = 0.02). Multivariable analysis showed that ultra-early intensive blood pressure treatment was associated with a decreased risk of hematoma growth (odds ratio, 0.56; 95% CI, 0.34-0.92; P = 0.02), higher rate of functional independence (odds ratio, 2.17; 95% CI, 1.28-3.68; P = 0.004) and good outcome (OR, 1.68; 95% CI, 1.01-2.83; P = 0.048) at 90 days. Ultra-early intensive blood pressure reduction was associated with a favorable shift in modified Rankin Scale score distribution at 3 months (p = 0.04). Interpretation In a subgroup of ICH patients with elevated blood pressure given intravenous nicardipine within 2 hours of symptom onset, intensive blood pressure reduction was associated with reduced hematoma growth and improved functional outcome. This article is protected by copyright. All rights reserved.The present study was designed to compare gender differences in psychiatric diagnosis with the dimension of psychopathy in women and men who had attempted or committed homicide. The study samples consisted of 39 homicidal females and 48 homicidal males who were confined in one of Italy's REMS or prison facilities in two southern provinces of Italy (Puglia and Basilicata). Assessment instruments included the SCID-5, the PID-5 IRF, and the PCL-R. Each gender group was stratified according to the level of criminal responsibility for the homicidal offense (full, partial, absent), and after assessments, according to the degree of the psychopathic dimension. There were clear gender differences in homicidal individuals. Female offenders were less likely to have had a record of criminal charges/convictions or imprisonment, and their homicides were more often intrafamilial, victimizing especially of their children, whereas males targeted intimate partners and extrafamilial victims. In the entire group, there was an inverse relationship between the level of psychopathy and the personality disorder on one side, and the psychotic disturbance on the other. Factor 2 (lifestyle/antisocial dimension) of the PCL-R was higher among the homicidal males, whereas females tended to score higher on Factor 1 (the interpersonal/affective dimension). Finally, if the psychopathic dimension is a qualifier for antisocial personality disorder, as indicated in DSM-5, this appears to be less true for females who tend to have other personality disorders.Since December 2019, the novel SARS-CoV-2 outbreak has resulted in millions of cases and more than 200,000 deaths worldwide. The clinical course among non-pregnant women has been described but data about potential risks for women and their fetus remain scarce. The SARS and MERS epidemics were responsible for miscarriages, adverse fetal and neonatal outcomes and maternal deaths. For COVID-19 infection, only 9 cases of maternal death have been reported as of April 22, 2020 and pregnant women seem to develop the same clinical presentation as the general population. However, severe maternal cases, as well as prematurity, fetal distress and stillbirth among newborns have been reported. The SARS-CoV-2 pandemic greatly impacts prenatal management and surveillance and raise the need for clear unanimous guidelines. In this narrative review, we describe the current knowledge about coronaviruses (SARS, MERS and SARS-CoV-2) risks and consequences on pregnancies and we summarize available current candidate therapeutic options for pregnant women. Finally, we compare current guidance proposed by RCOG, ACOG and the WHO to give an overview of prenatal management which should be utilized until future data appear. This article is protected by copyright. All rights reserved.Plastin 3 (PLS3), encoded by PLS3, is a newly recognized regulator of bone metabolism and mutations in the encoding gene result in severe childhood-onset osteoporosis. Since an X chromosomal gene, PLS3 mutation-positive males are typically more severely affected while females portray normal to increased skeletal fragility. Despite the severe skeletal pathology, conventional metabolic bone markers tend to be normal and are thus insufficient in diagnosing or monitoring patients. Our study aimed to explore serum microRNA (miRNA) concentrations in subjects with defective PLS3 function to identify novel markers that could differentiate subjects according to mutation status and give insight into the molecular mechanisms by which PLS3 regulates skeletal health. We analyzed fasting serum samples for a custom-designed panel comprising 192 miRNAs in 15 mutation-positive (5 males, age range 8-76 years, median 41 years) and 14 mutation-negative (6 males, 8-69 years, 40 years) subjects from four Finnish families with diff disease and may provide novel avenues for exploring miRNAs as biomarkers in PLS3 osteoporosis or as target molecules in future therapeutic applications.Background The effectiveness and portability of the collaborative care model in the primary care treatment of depression has not been demonstrated in many randomized controlled trials in healthcare settings across the world. We determined the effectiveness of collaborative care management of elderly depression in the primary care setting in Singapore. Method Eligible participants with depressive symptoms were randomized to 6-month duration usual care (UC, N = 112) or collaborative care (CC, N = 102). Outcome measures were HDRS-17, GDS, BDI and SF-12 MCS QOL measured at 3, 6, and 12-month, care satisfaction at 6-month, and also measured on 120 participants who refused referral (non-receipt of care, NC). Primary outcome was HDRS-17 measure of depression severity, response and remission at 6-month. Results HDRS scores in CC group compared to UC group were reduced more at 6-month (1.5 points difference in change from baseline), and also at 3 and 12-month, with similar observations of differences for GDS and BDI. There was significantly greater improvement for both CC and UC groups compared to NC group.
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