The effect of host structure on the selectivity and mechanism of supramolecular catalysis of Prins cyclizations.

The effect of host structure on the selectivity and mechanism of intramolecular Prins reactions is evaluated using K12Ga4L6 tetrahedral catalysts. The host structure was varied by modifying the structure of the chelating moieties and the size of the aromatic spacers. While variation in chelator substituents was generally observed to affect changes in rate but not selectivity, changing the host spacer afforded differences in efficiency and product diastereoselectivity. An extremely high number of turnovers (up to 840) was observed. Maximum rate accelerations were measured to be on the order of 105, which numbers among the largest magnitudes of transition state stabilization measured with a synthetic host-catalyst. Host/guest size effects were observed to play an important role in host-mediated enantioselectivity

Attenuated Expression of DFFB is a Hallmark of Oligodendrogliomas with 1p-Allelic Loss

Allelic loss of chromosome 1p is frequently observed in oligodendroglioma. We screened 177 oligodendroglial tumors for 1p deletions and found 6 tumors with localized 1p36 deletions. Several apoptosis regulation genes have been mapped to this region, including Tumor Protein 73 (p73), DNA Fragmentation Factor subunits alpha (DFFA) and beta (DFFB), and Tumor Necrosis Factor Receptor Superfamily Members 9 and 25 (TNFRSF9, TNFRSF25). We compared expression levels of these 5 genes in pairs of 1p-loss and 1p-intact tumors using quantitative reverse-transcriptase PCR (QRTPCR) to test if 1p deletions had an effect on expression. Only the DFFB gene demonstrated decreased expression in all tumor pairs tested. Mutational analysis did not reveal DFFB mutations in 12 tested samples. However, it is possible that DFFB haploinsufficiency from 1p allelic loss is a contributing factor in oligodendroglioma development

Impact of coronavirus disease 2019 (COVID-19) outbreak quarantine, isolation, and lockdown policies on mental health and suicide

The novel coronavirus disease (COVID-19) pandemic has made a huge impact on people\u27s physical and mental health, and it remains a cause of death for many all over the world. To prevent the spread of coronavirus infection, different types of public health measures (social isolation, quarantine, lockdowns, and curfews) have been imposed by governments. However, mental health experts warn that the prolonged lockdown, quarantine, or isolation will create a “second pandemic” with severe mental health issues and suicides. The quarantined or isolated people may suffer from various issues such as physical inactivity, mental health, economic and social problems. As with the SARS outbreak in 2003, many suicide cases have been reported in connection with this current COVID-19 pandemic lockdown due to various factors such as social stigma, alcohol withdrawal syndrome, fear of COVID infection, loneliness, and other mental health issues. This paper provides an overview of risk factors that can cause suicide and outlines possible solutions to prevent suicide in this current COVID-19 pandemic

High-Relaxivity MRI Contrast Agents: Where Coordination Chemistry Meets Medical Imaging

The desire to improve and expand the scope of clinical magnetic resonance imaging (MRI) has prompted the search for contrast agents of higher efficiency. The development of better agents requires consideration of the fundamental coordination chemistry of the gadolinium(III) ion and the parameters that affect its efficacy as a proton relaxation agent. In optimizing each parameter, other practical issues such as solubility and in vivo toxicity must also be addressed, making the attainment of safe, high-relaxivity agents a challenging goal. Here we present recent advances in the field, with an emphasis on the hydroxypyridinone family of Gd{sup III} chelates

Secondary Sex Ratio among Women Exposed to Diethylstilbestrol in Utero

BACKGROUND. Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the mid-1900s, is a potent endocrine disruptor. Previous studies have suggested an association between endocrine-disrupting compounds and secondary sex ratio. METHODS. Data were provided by women participating in the National Cancer Institute (NCI) DES Combined Cohort Study. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relation of in utero DES exposure to sex ratio (proportion of male births). Models were adjusted for maternal age, child's birth year, parity, and cohort, and accounted for clustering among women with multiple pregnancies. RESULTS. The OR for having a male birth comparing DES-exposed to unexposed women was 1.05 (95% CI, 0.95-1.17). For exposed women with complete data on cumulative DES dose and timing (33%), those first exposed to DES earlier in gestation and to higher doses had the highest odds of having a male birth. The ORs were 0.91 (95% C, 0.65-1.27) for first exposure at ≥ 13 weeks gestation to < 5 g DES; 0.95 (95% CI, 0.71-1.27) for first exposure at ≥ 13 weeks to ≥ 5 g; 1.16 (95% CI, 0.96-1.41) for first exposure at < 13 weeks to < 5 g; and 1.24 (95% CI, 1.04-1.48) for first exposure at < 13 weeks to ≥ 5 g compared with no exposure. Results did not vary appreciably by maternal age, parity, cohort, or infertility history. CONCLUSIONS. Overall, no association was observed between in utero DES exposure and secondary sex ratio, but a significant increase in the proportion of male births was found among women first exposed to DES earlier in gestation and to a higher cumulative dose.National Cancer Institute (N01-CP-21168, N01-CP-51017, N01-CP-01289

Can Transcranial Direct-Current Stimulation Alone or Combined With Cognitive Training Be Used as a Clinical Intervention to Improve Cognitive Functioning in Persons With Mild Cognitive Impairment and Dementia? A Systematic Review and Meta-Analysis

Background: Transcranial direct-current stimulation (tDCS) facilitates cognitive improvement in healthy and pathological populations. It has been increasingly used in cases of mild cognitive impairment (MCI) and dementia. Our research question is: Can tDCS serve as a clinical intervention for improving the cognitive functions of persons with MCI (PwMCI) and dementia (PwD)?Objective: This systematic review evaluated the evidence to determine the efficacy of tDCS in improving cognitive outcomes in PwD and PwMCI.Methods: A systematic review was conducted of studies published up to November 2017 involving tDCS in cases of MCI and dementia. Studies were ranked according to the level of evidence (Oxford Center for Evidence-Based Medicine) and assessed for methodological quality (Risk of Bias Tool in the Cochrane Handbook for Systematic Reviews of Interventions). Data was extracted on all protocol variables to establish a reference framework for clinical interventions. Different modalities, tDCS alone or combined with cognitive training, compared with sham tDCS were examined in both short and long-term effects. Four randomized control trials (RCTs) with memory outcomes were pooled using the fixed-effect model for the meta-analysis.Results: Twelve studies with 195 PwD and four with 53 PwMCI met the inclusion criteria. Eleven articles were ranked as Level 1b. The results on the meta-analysis on pooled effects of memory indicated a statistically significant medium effect size of 0.39 (p = 0.04) for immediate effects. This improvement was not maintained in the long term 0.15 (p = 0.44).Conclusion: tDCS improves memory in PwD in the short term, it also seems to have a mild positive effect on memory and language in PwMCI. However, there is no conclusive advantage in coupling tDCS with cognitive training. More rigorous evidence is needed to establish whether tDCS can serve as an evidence-based intervention for both populations