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Enantioselective Syntheses involving C2-Symmetric Pyrazolones along with Diones via One-Pot Organo-/Iodine Consecutive Catalysis.
We evaluated the impact of Samata, a 3-year multilayered intervention among scheduled caste/scheduled tribe (SC/ST) adolescent girls in rural northern Karnataka, on family-level (parents or guardian) attitudes and direct and indirect norms related to child marriage and girl's education. Endline data from 1840 family members were used to assess the effect of Samata on attitudes and norms related to schooling and child marriage, while data from 4097 family members (including 2257 family members at baseline) were used to understand the shifts in attitudes and norms over the period 2014-2017. Overall, we found that the programme had little impact on family-level attitudes and norms. However, there were shifts in some attitudes, norms and perceived sanctions between baseline (when girls were aged 13-14 years) and endline (when girls were aged 15-16 years), with some becoming more progressive (e.g. direct norms related to child marriage) and others more restrictive (e.g. norms around girls completing secondary eductration number NCT01996241.
Technosphere
Insulin (TI), a human insulin powder for inhalation (Afrezza
; MannKind Corporation, Westlake Village, CA, USA), is an ultra-rapid-acting inhaled insulin indicated to improve postprandial glycemic control in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). Because TI is absorbed across the alveolar membrane, the objective of this analysis was to characterize its pulmonary safety.

Pooled data from 13 phase 2/3 clinical studies in 5505 patients with T1DM or T2DM treated with TI, Technosphere inhalation powder without insulin (TP; placebo), or active-comparator treatment were analyzed for incidences of respiratory treatment-emergent adverse events (TEAEs), changes in pulmonary function, and lung malignancies. Radiographic changes in the lungs were monitored in a subset of 229 patients.

Among 3017 patients receiving TI, the median duration of TI exposure was 168days; median active-comparator and TP exposure durations were 363 and 149days for 2198 and 290 patients, respectively. Respiratory TEAEs were comparable across treatments, except for a higher incidence of mildcoughwith TI in active-comparator studies (28.0% vs. 5.2%). Slight reversible declines in pulmonary function from baseline were observed for TI versus TP and active-comparator treatments, including in a subpopulation of patients with retrospectively identified lung dysfunction. Lung malignancies were reported in two patients on active TI therapy with a smoking history. No clinically significant changes from baseline were observed in radiographic images.

Pulmonary safety assessment of the TI inhalation system did not identify any safety issues in individuals with either T1DM or T2DM.
Pulmonary safety assessment of the TI inhalation system did not identify any safety issues in individuals with either T1DM or T2DM.Adolescent girls and young women (AGYW) are at high risk of HIV and other sexually transmitted infections (STIs), including at first sexual intercourse. The literature is scarce on factors influencing use of protective strategies at this critical time. We conducted 20 in-depth interviews and five focus group discussions with purposively sampled AGYW aged 16-20 years who reported first sex while enrolled in a larger cohort study and willing to participate. All AGYW were counseled on HIV prevention and had access to reproductive health information and services. Data collected were transcribed, translated and analyzed thematically. We identified two approaches to first sex. In one approach, the AGYW facilitated protection use, and those AGYW reported intention and preparation to initiate sexual activity and ability to request condom use, as well as their male partner's willingness to use and provide condoms. In another approach, AGYW experienced first sexual intercourse without agency (the feeling of control over actions and their consequences [Moore, 2016]) and described lack of prior intentions and planning, discomfort with discussions about sex and condom use, and desire to experience sexual pleasure as reported by peers. No AGYW mentioned parents/adults as playing any role as facilitators of protection use at first sex, highlighting the need for further research on the missing gap. The AGYW were trusting of verbal reports by male partners describing themselves as having never engaged in sex, HIV negative, and free of STIs. We found that some AGYW were empowered to plan, discuss, and request protection at first sex, and others did not take agency. First sex is a time of vulnerability where innovative strategies are needed to strengthen AGYW's agency and promote condom use and other HIV/STI prevention methods.
Neuroendocrine differentiation (NED) may serve as a prognostic factor in colorectal cancer; however, the prognostic relevance of NED remains controversial. The aim of the present study was to determine whether NED influenced the survival of patients in colorectal cancer while exploring its potential interactions with other clinicopathological features.

Patients with primary stage I to IV colorectal adenocarcinoma ranging between 2010 and 2015 were identified using the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier technique, Cox proportional hazards model, propensity score matching, and stratification analyses were employed in this study.

A total of 94,291 patients (including 101 patients with NED and 94,190 patients without NED) were included. In the univariable analyses, NED was found to be correlated with a significantly poorer overall survival (hazard ratio (HR) of death = 3.09, 95% CI 2.42-3.95, P < 0.001) and cancer-specific survival (HR of death = 3.77, 95% CI 2.94-4.83, P < 0.001). Moreover, NED remained independently correlated with overall survival (HR of death = 1.84, 95% CI 1.34-2.51, P < 0.001) and cancer-specific survival (HR of death = 2.01, 95% CI 1.45-2.79, P < 0.001) after adjusting in multivariable and propensity score analyses. Furthermore, further stratification analyses indicated that the influence of NED on survival was not affected by tumor location, differentiation, T stage, and distant metastasis status; however, it was found to be associated with lymph node metastasis.

NED is associated with poor survival outcomes among colorectal cancer patients, especially in those with positive lymph nodes.
NED is associated with poor survival outcomes among colorectal cancer patients, especially in those with positive lymph nodes.
At present, there are many studies on metformin and the risk of colorectal cancer in patients with diabetes, but the conclusions are contradictory. Our aim is to comprehensively collect the published literature and systematically evaluate the relationship between metformin and the risk of colorectal cancer in patients with diabetes.

We systematically searched the MEDLINE, EMBASE, and CENTRAL databases up to March 2020. We adopted adjusted estimates and their 95% confidence intervals (CI) to calculate summary effect estimates using either a fixed-effects or a random-effects model.

A total of 17 articles were included in this study, with a total of 1,092,074 patients with diabetes. Meta-analysis of observational studies showed that metformin treatment could significantly reduce the incidence of colorectal cancer in diabetic patients (adjusted RR = 0.884, 95%CI = 0.829-0.943), and there was heterogeneity between studies (p = 0.013, I
= 47.9%). Subgroup analysis showed that metformin treatment was significantly associated with a significantly reduced risk of colorectal cancer in diabetics in America and Europe (adjusted RR = 0.852, 95%CI = 0.786-0.924; adjusted RR = 0.900, 95%CI = 0.845-0.958). Patients with diabetes treated with metformin had a significantly lower risk of colorectal cancer compared with patients who had never been treated with metformin or sulfonamide monotherapy (adjusted RR = 0.863, 95%CI = 0.776-0.960; adjusted RR = 0.911, 95%CI = 0.882-0.941).

Metformin therapy is associated with a significantly reduced risk of colorectal disease in patients with diabetes, and it is necessary to conduct larger, more standardized clinical studies to verify this conclusion.
Metformin therapy is associated with a significantly reduced risk of colorectal disease in patients with diabetes, and it is necessary to conduct larger, more standardized clinical studies to verify this conclusion.The author found a mistake in their published article. They observed that Fig. 2 presented some mistakes as follow.Self-reported experiences of discrimination are associated with a number of negative health outcomes. However, the neurobiological correlates of discrimination remain elusive. Recent neuroimaging work suggests that the amygdala is sensitive to forms of social adversity and the insula is involved in assessments of trust. We hypothesized that functional connectivity (FC) of these brain regions may be associated with discrimination in older Black adults. One-hundred and twenty-four nondemented older Black adults participating in the Minority Aging Research Study or the Clinical Core study of the Rush Alzheimer's Disease Center completed a measure of self-reported experiences of discrimination and a 3T MRI brain scan including structural T1 and resting-state fMRI EPIBOLD sequences. The right and left amygdala and insula regions were anatomically delineated as ROIs according to the Harvard-Oxford Brain Atlas and whole-brain voxelwise FC analyses were conducted using default parameters in the CONN toolbox. In regression analyses controlling for demographics and global cognition, self-reported experiences of discrimination were associated with greater FC between the left insula and the bilateral intracalcarine cortex, weaker FC between the left insula and the left dorsolateral prefrontal cortex, and weaker FC between the right insula and the left supplementary motor area. Amygdala analyses yielded no significant findings. Greater self-reported experiences of discrimination are associated with differential insula functional connectivity in older adults. read more More specifically, results suggest that discrimination is associated with differential connectivity of a key region (the insula) involved in trust perception.Insomnia disorder (ID) is reclassified into short-term and chronic subtypes based on recent etiological advances, however, neural mechanisms underlying the subtypes are rarely examined. In this study, we investigated gray matter volume and resting-state functional connectivity (RSFC) alterations of hippocampal subregions in short-term and chronic ID using multimodal MRI. We found convergent and divergent alterations between both ID groups in specific hippocampal subregions [right cornu ammonis 1 (CA1), subicular complex (Subc), and caudal hippocampus, (cHipp)] with prefrontal cortex [bilateral medial prefrontal cortex (MPFC), and right middle frontal gyrus] and limbic/paralimbic regions (bilateral middle cingulate cortex and left parahippocampal gyrus). Intriguingly, the RSFC of the right CA1/cHipp, particularly the intersection between these two subregions, with bilateral MPFC exhibited gradual increases from healthy controls to short-term ID and from short-term ID to chronic ID. Moreover, a negative correlation between the right CA1-left parahippocampal gyrus RSFC and Epworth Sleepiness Scale scores, and a positive correlation between the right CA1-bilateral MPFC RSFC and Insomnia Severity Index scores were found in the chronic ID group (P  less then  0.
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