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The availability of intensive care beds during the COVID-19 epidemic is crucial to guarantee the best possible treatment to severely affected patients. In this work we show a simple strategy for short-term prediction of COVID-19 intensive care unit (ICU) beds, that has proved very effective during the Italian outbreak in February to May 2020. Our approach is based on an optimal ensemble of two simple methods a generalized linear mixed regression model, which pools information over different areas, and an area-specific nonstationary integer autoregressive methodology. Optimal weights are estimated using a leave-last-out rationale. The approach has been set up and validated during the first epidemic wave in Italy. A report of its performance for predicting ICU occupancy at regional level is included.Various lines of evidence implicate oxidative stress in the pathogenic mechanism(s) underpinning tauopathies. Consequently, antioxidant therapies have been considered in clinical practice for the treatment of tauopathies such as Alzheimer's disease (AD), but with mixed results. We and others have previously reported increased protein oxidation upon expression of both human 0N3R (hTau0N3R ) and 0N4R (hTau0N4R ) tau in vivo. Building on these studies, we demonstrate here the suppression of hTau0N3R associated phenotypes in Drosophila melanogaster after treatment with vitamin C or vitamin E. Curiously the rescue of phenotype was seen without alteration in total tau level or alteration in phosphorylation at a number of disease-associated sites. Moreover, treatment with paraquat, a pro-oxidant drug, did not exacerbate the hTau0N3R phenotypes. This result following paraquat treatment is reminiscent of our previous findings with hTau0N4R which also causes greater oxidative stress when compared to hTau0N3R but has a milder phenotype. Collectively our data imply that the role of oxidative stress in tau-mediated toxicity is not straight forward and there may be isoform-specific effects as well as contribution of other factors. This may explain the ambiguous effects of anti-oxidant treatments on clinical outcome in dementia patients.Lithium-rich layered oxides (LLOs) are prospective cathode materials for next-generation lithium-ion batteries (LIBs), but severe voltage decay and energy attenuation with cycling still hinder their practical applications. Herein, a series of full concentration gradient-tailored agglomerated-sphere LLOs are designed with linearly decreasing Mn and linearly increasing Ni and Co from the particle center to the surface. The gradient-tailored LLOs exhibit noticeably reduced voltage decay, enhanced rate performance, improved cycle stability, and thermal stability. Without any material modifications or electrolyte optimizations, the gradient-tailored LLO with medium-slope shows the best electrochemical performance, with a very low average voltage decay of 0.8 mV per cycle as well as a capacity retention of 88.4% within 200 cycles at 200 mA g-1 . These excellent findings are due to spinel structure suppression, electrochemical stress optimization, and Jahn-Teller effect inhibition. Further investigation shows that the gradient-tailored LLO reduces the thermal release percentage by as much as about 41% when the battery is charged to 4.4 V. SL-327 This study provides an effective method to suppress the voltage decay of LLOs for further practical utilization in LIBs and also puts forward a bulk-structure design strategy to prepare better electrode materials for different rechargeable batteries.Atopic dermatitis (AD) is a common skin disease during infancy, which imposes a considerable burden on patients, their families, and the society, requiring effective treatment options that result in rapid and sustained symptom relief. Additionally, early treatment may prevent the development of atopic comorbidities by restoring the skin barrier. Currently, topical standard-of-care for AD in infants includes emollients and topical corticosteroids (TCS) to treat and reduce the risk of flares. However, only few have been approved for infants and long-term maintenance therapy with TCS is not indicated due to potential local and systemic side effects, including skin atrophy. Accordingly, the recently updated European guidelines for treatment of AD recommend topical calcineurin inhibitors (TCIs) for long-term use, treatment of sensitive skin areas, and for use in the pediatric population. Evidence on the use of TCIs for infants has almost been exclusively collected for pimecrolimus, with >4000 infants evaluated in clinical trials, consistently confirming that pimecrolimus is a safe and effective treatment for infants with AD. Nevertheless, its use is still restricted in most countries to children above the age of 2 years due to initial and mostly theoretical safety concerns. Based on a careful review of the available evidence of clinical trials, post-marketing surveillance, and epidemiological studies, an Expert Panel of European dermatologists and pediatric allergologists concluded that these safety concerns are no longer valid. Therefore, pimecrolimus offers a safe and effective alternative to TCS in infants aged 3 months and above, and labeling restrictions in this age group are no longer justified.Prostate cancer has high metastatic potential. Men with higher urinary levels of the sleep hormone melatonin are much less likely to develop advanced prostate cancer compared with men with lower levels of melatonin. Melatonin has shown anticancer activity in experimental investigations. Nevertheless, the therapeutic effect of melatonin in metastatic prostate cancer has largely remained a mystery. Analyses of Gene Expression Omnibus data and human tissue samples indicated that levels of matrix metallopeptidase 13 (MMP-13) expression are higher in prostate cancer patients than in healthy cancer-free individuals. Mechanistic investigations revealed that melatonin inhibits MMP-13 expression and the migratory and invasive capacities of prostate cancer cells via the MT1 receptor and the phospholipase C, p38, and c-Jun signaling cascades. Importantly, tumor growth rate and metastasis to distant organs were suppressed by melatonin in an orthotopic prostate cancer model. This is the first demonstration showing that melatonin impedes metastasis of prostate cancer by suppressing MMP-13 expression in both in vitro and in vivo models. Thus, melatonin is promising in the management of prostate cancer metastasis and deserves to undergo clinical investigations.

Data visualization techniques were used to ascertain (1) site-specific effects of cigarette smoking on the periodontium compared to never-smokers; (2) patterns of site-specific effects by age among current and never-smokers using contour maps.

Data from 10,713 dentate participants aged ≥30 years in NHANES 2009-2014 were used. Pocket depth (PD) and clinical attachment level (CAL) for six sites/tooth were ascertained by smoking status and plotted using contour maps to identify new patterns.

In the overall sample, 19% (n=2015) were current smokers and 56% (n=6013) were never-smokers. Contour maps of the overall sample showed teeth/sites most affected with mean PD>2.1mm were molars (2,3,15,18,19,30,31) in mesio-lingual (ML) and disto-lingual (DL) sites. Most affected sites for current smokers were interproximal sites of most posterior teeth. Among never-smokers, fewer teeth/sites were affected with PD>2.1mm, whereas among smokers, number of affected teeth/sites increased with age. Overall, teeth/siteserent contour pattern than never-smokers.Fibrosis is one of the largest sources of human morbidity. The skin is a complex organ where interplay between diverse cell types and signalling pathways is essential both in homeostasis and wound repair, which can result in fibrosis or regeneration. This makes skin a useful model to study fibrosis and regeneration. While fibrosis often occurs postinjury, both clinical and laboratory observations suggest skin regeneration, complete with reconstituted cell diversity and de novo hair follicles, is possible. Extensive research performed in pursuit of skin regeneration has elucidated the key players, both cellular and molecular. Interestingly, some cells known for their homeostatic function are not implicated in regeneration or wound-induced hair neogenesis (WIHN), suggesting regeneration harnesses separate functional pathways from embryogenesis or other non-homeostatic mechanisms. For example, classic bulge cells, noted for their role in normally cycling hair follicles, do not finally contribute to long-lived cells in the regenerated tissue. During healing, multiple populations of cells, among them specific epithelial lineages, mesenchymal cells, and immune cells promote regenerative outcomes in the wounded skin. Ultimately, targeting specific populations of cells will be essential in manipulating a postwound environment to favour regeneration in lieu of fibrosis.

Cutaneous tuberculosis (CTB) rarely involves the ear as the primary site, but while diagnosing and treating ear infections, it should be considered a differential diagnosis in a tropical country such as India. The present study reports the incidence and clinical presentation of auricular tuberculosis (TB) in a tertiary care hospital in New Delhi.

A retrospective, observational study was conducted from 2005 to 2019 whereby all cases of CTB confirmed by biopsy were retrieved from the database. The demographic details, clinical details, Mantoux results, and photographs were extracted and studied. The data were entered into MS Excel and analyzed.

In a retrospective analysis of 886 cases of CTB over a period of 15years, we found 20 cases (2.26%) of ear involvement (1 case with bilateral involvement). The median age of the patients with ear involvement was 29years with 42.11% men and 57.89% women. Morphological variants seen over pinna were predominantly classic plaque type (31.58%) and nodular (31.58%), with few ulcerative (21.05%) and tumoral forms (15.79%). CTB of the pinna showed predominant involvement of either helix or ear lobule (7 cases each). All cases were strongly positive to tuberculin and showed response to the empirical antitubercular treatment.

CTB can exclusively affect the pinna in varied presentations. The ear lobules and the helix are the usual sites of affection. It is rare for both ears to be affected with CTB, unlike bacilliferous leprosy. Regression following institution of antitubercular treatment is a reasonable way to confirm CTB.

CTB can exclusively affect the pinna in varied presentations. The ear lobules and the helix are the usual sites of affection. It is rare for both ears to be affected with CTB, unlike bacilliferous leprosy. Regression following institution of antitubercular treatment is a reasonable way to confirm CTB.

Long-term potentiation of glutamatergic transmission to hippocampal interneurons in stratum oriens does not require NMDA receptors and the induction mechanisms are incompletely understood. Extracellular stimulation, conventionally used to monitor synaptic strength and induce long-term potentiation (LTP), does not exclusively recruit glutamatergic axons. We used optogenetic stimulation of either glutamatergic or cholinergic afferents to probe the relative roles of different signalling mechanisms in LTP induction. Selective stimulation of cholinergic axons was sufficient to induce LTP, which was prevented by chelating postsynaptic Ca

or blocking nicotinic receptors. The present study adds nicotinic receptors to the list of sources of Ca

that induce NMDA receptor independent LTP in hippocampal oriens interneurons.

Many interneurons located in stratum oriens of the rodent hippocampus exhibit a form of long-term potentiation (LTP) of glutamatergic transmission that does not depend on NMDA receptors for its induction but, instead, requires Ca

-permeable AMPA receptors and group I metabotropic glutamate receptors.

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