Notes

Seniors Utilised Fewer Home Care Companies Through the COVID-19 Widespread: Results From A Supplementary Investigation Of the Important Questionnaire Within Asia.
The presence of periprocedural asymptomatic ipsilateral DW-MRI lesions was higher in patients in the noncalcified plaque group (45 [16.8%]) than in patients in the calcified plaque group (31 [10.3%]; P = 0.02).

This study demonstrated that the rate of ipsilateral asymptomatic cerebral embolism detected on cerebral DW-MRI was higher in the CAS procedures performed for noncalcified carotid artery plaques than in those performed for calcified plaques.
This study demonstrated that the rate of ipsilateral asymptomatic cerebral embolism detected on cerebral DW-MRI was higher in the CAS procedures performed for noncalcified carotid artery plaques than in those performed for calcified plaques.Chemical read-across is commonly evaluated without specific knowledge of the biological mechanisms leading to observed adverse outcomes in vivo. Integrating data that indicate shared modes of action in humans will strengthen read-across cases. Here we studied transcriptomic responses of primary human hepatocytes (PHH) to a large panel of carboxylic acids to include detailed mode-of-action data as a proof-of-concept for read-across in risk assessment. In rodents, some carboxylic acids, including valproic acid (VPA), are known to cause hepatic steatosis, whereas others do not. We investigated transcriptomics responses of PHHs exposed for 24 h to 18 structurally different VPA analogues in a concentration range to determine biological similarity in relation to in vivo steatotic potential. Using a targeted high-throughput screening assay, we assessed the differential expression of ~3,000 genes covering relevant biological pathways. Differentially expressed gene analysis revealed differences in potency of carboxylic acids, and expression patterns were highly similar for structurally similar compounds. Strong clustering occurred for steatosis-positive versus steatosis-negative carboxylic acids. To quantitatively define biological read-across, we combined pathway analysis and weighted gene co-expression network analysis. Active carboxylic acids displayed high similarity in gene network modulation. Importantly, free fatty acid synthesis modulation and stress pathway responses are affected by active carboxylic acids, providing coherent mechanistic underpinning for our findings. Our work shows that transcriptomic analysis of cultured human hepatocytes can reinforce the prediction of liver injury outcome based on quantitative and mechanistic biological data and support its application in read-across.Adipose tissue (AT) expands by a combination of two fundamental cellular mechanisms hypertrophic growth of existing adipocytes or through generation of new adipocytes, also known as hyperplastic growth. Multiple lines of evidence suggest a limited capacity for hyperplastic growth of AT in adulthood and that adipocyte number is relatively stable, even with fluctuations in AT mass. If the adipocyte number is stable in adulthood, despite well-documented birth and death of adipocytes, then this would suggest that birth may be coupled to death in a regenerative cycle. To test this hypothesis, we examined the dynamics of birth of new fat cells in relationship to adipocyte death by using high-fidelity stable isotope tracer methods in C57Bl6 mice. We discovered birth of new adipocytes at higher frequency in histological proximity to dead adipocytes. In diet-induced obesity, adipogenesis surged after an adipocyte death peak beyond 8 weeks of high-fat feeding. Through transcriptional analyses of AT and fractionated adipocytes, we found that the dominant cell death signals were inflammasome related. Proinflammatory signals were particularly evident in hypertrophied adipocytes or with deletion of a constitutive oxygen sensor and inhibitor of hypoxia-inducible factor, Egln1. We leveraged the potential role for the inflammasome in adipocyte death to test the adipocyte death-birth hypothesis, finding that caspase 1 loss of function attenuated adipocyte death and birth in murine visceral AT. These data collectively point to a regenerative cycle of adipocyte death and birth as a driver of adipogenesis in adult murine AT.Information about how the risk of death varies with age within the 0-5 age range represents critical evidence for guiding health policy. This study proposes a new model for summarizing regularities about how under-5 mortality is distributed by detailed age. The model is based on a newly compiled database that contains under-5 mortality information by detailed age in countries with high-quality vital registration systems, covering a wide array of mortality levels and patterns. It uses a log-quadratic approach in predicting a full mortality schedule between ages 0 and 5 on the basis of only one or two parameters. With its larger number of age-groups, the proposed model offers greater flexibility than existing models in terms of both entry parameters and model outcomes. We present applications of this model for evaluating and correcting under-5 mortality information by detailed age in countries with problematic mortality data.The prevention of unplanned or unintended pregnancies continues to be a cornerstone of U.S. reproductive health policy, but the evidence that such pregnancies cause adverse maternal and child outcomes is limited. In this research note, we examine these relationships using recent large-scale data and inverse propensity weights estimated from generalized boosted models. We find that pregnancy timing is related to maternal experience during pregnancy, but not to infant outcomes at birth-both of which are consistent with prior research. In an addition to the literature, we show that pregnancy timing is relevant for a number of maternal outcomes, such as the onset of depression and intimate partner violence, changes in smoking behavior, and receipt of medical care. These findings suggest that policy intended to improve infant welfare by preventing unintended pregnancies has little empirical support, but that policy focused on increasing reproductive autonomy and maternal well-being has the potential to improve outcomes.Chronic pain is the most common neurological disorder of HIV patients. Multiple neuropathologies were identified in the pain pathway. Among them is the prominent astrocytic reaction (a.k.a. astrogliosis). However, the pathogenic role and mechanism of the astrogliosis are unclear. Here, we show that the astrogliosis is crucial for the pain development induced by a key neurotoxic HIV protein gp120 and that a neuron-to-astrocyte Wnt5a signal controls the astrogliosis. Ablation of astrogliosis blocked the development of gp120-induced mechanical hyperalgesia, and concomitantly the expression of neural circuit polarization (NCP) in the spinal dorsal horn (SDH). We demonstrated that conditional knockout (CKO) of either Wnt5a in neurons or its receptor ROR2 in astrocytes abolished not only gp120-induced astrogliosis but also hyperalgesia and NCP. Furthermore, we found that the astrogliosis promoted expression of hyperalgesia and NCP via IL-1β regulated by a Wnt5a-ROR2-MMP2 axis. Our results shed light on the role and mechanism of astrogliosis in the pathogenesis of HIV-associated pain.Colorectal cancer (CRC) and diabetes are two of the most prevalent chronic diseases worldwide with dysregulated receptor tyrosine kinase signaling and strong co-occurrence correlation. Plasma autoantibodies represent a promising early diagnostic marker for both diseases before symptoms appear. In this study, we explore the value of autoantibodies against receptor-type tyrosine-protein phosphatase-like N (PTPRN; full-length or selected domains) as diagnostic markers using a cohort of individuals with type 2 diabetes (T2D), CRC, or both diseases or healthy individuals. We show that PTPRN autoantibody levels in plasma discriminated between patients with T2D with and without CRC. Consistently, high PTPRN expression correlated with decreased survival of patients with CRC. Mechanistically, PTPRN depletion significantly reduced invasiveness of CRC cells in vitro and liver homing and metastasis in vivo by means of a dysregulation of the epithelial-mesenchymal transition and a decrease of the insulin receptor signaling pathway. Therefore, PTPRN autoantibodies may represent a particularly helpful marker for the stratification of patients with T2D at high risk of developing CRC. Consistent with the critical role played by tyrosine kinases in diabetes and tumor biology, we provide evidence that tyrosine phosphatases such as PTPRN may hold potential as therapeutic targets in patients with CRC.Do neighborhood conditions affect wealth accumulation? This study uses the National Longitudinal Survey of Youth 1979 cohort and a counterfactual estimation strategy to analyze the effect of prolonged exposure to neighborhood (dis)advantage from emerging adulthood through middle adulthood. RZ-2994 Neighborhoods have sizable, plausibly causal effects on wealth, but these effects vary significantly by race/ethnicity and homeownership. White homeowners receive the largest payoff to reductions in neighborhood disadvantage. Black adults, regardless of homeownership, are doubly disadvantaged in the neighborhood-wealth relationship. They live in more-disadvantaged neighborhoods and receive little return to reductions in neighborhood disadvantage. Findings indicate that disparities in neighborhood (dis)advantage figure prominently in wealth inequality and the racial wealth gap.We previously showed that treating NOD mice with an agonistic monoclonal anti-TLR4/MD2 antibody (TLR4-Ab) reversed acute type 1 diabetes (T1D). Here, we show that TLR4-Ab reverses T1D by induction of myeloid-derived suppressor cells (MDSCs). Unbiased gene expression analysis after TLR4-Ab treatment demonstrated upregulation of genes associated with CD11b+Ly6G+ myeloid cells and downregulation of T-cell genes. Further RNA sequencing of purified, TLR4-Ab-treated CD11b+ cells showed significant upregulation of genes associated with bone marrow-derived CD11b+ cells and innate immune system genes. TLR4-Ab significantly increased percentages and numbers of CD11b+ cells. TLR4-Ab-induced CD11b+ cells, derived ex vivo from TLR4-Ab-treated mice, suppress T cells, and TLR4-Ab-conditioned bone marrow cells suppress acute T1D when transferred into acutely diabetic mice. Thus, the TLR4-Ab-induced CD11b+ cells, by the currently accepted definition, are MDSCs able to reverse T1D. To understand the TLR4-Ab mechanism, we compared TLR4-Ab with TLR4 agonist lipopolysaccharide (LPS), which cannot reverse T1D. TLR4-Ab remains sequestered at least 48 times longer than LPS within early endosomes, alters TLR4 signaling, and downregulates inflammatory genes and proteins, including nuclear factor-κB. TLR4-Ab in the endosome, therefore, induces a sustained, attenuated inflammatory response, providing an ideal "second signal" for the activation/maturation of MDSCs that can reverse acute T1D.
Etiological diagnosis of febrile illnesses in returning travelers is a great challenge, particularly when presenting with no focal symptoms [acute undifferentiated febrile illnesses (AUFI)], but is crucial to guide clinical decisions and public health policies. In this study, we describe the frequencies and predictors of the main causes of fever in travelers.

Prospective European multicenter cohort study of febrile international travelers (November 2017-November 2019). A predefined diagnostic algorithm was used ensuring a systematic evaluation of all participants. After ruling out malaria, PCRs and serologies for dengue, chikungunya and Zika viruses were performed in all patients presenting with AUFI ≤ 14days after return. Clinical suspicion guided further microbiological investigations.

Among 765 enrolled participants, 310/765 (40.5%) had a clear source of infection (mainly traveler's diarrhea or respiratory infections), and 455/765 (59.5%) were categorized as AUFI. AUFI presented longer duration of fever (p < 0.
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