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In addition, the oxidative stress level was increased in PM2.5-treated paternal rats. Administration with tempol in paternal rats restored the increased blood pressure and decreased urine volume and sodium excretion in the offspring of PM2.5-exposed paternal rats. Treatment with tempol in paternal rats also reversed the increased expressions of AT1R and GRK4 in the kidney of their offspring. We suggest that paternal PM2.5 exposure causes hypertension in offspring. The mechanism may be involved that paternal PM2.5 exposure-associated oxidative stress induces the elevated renal GRK4 level, leading to the enhanced AT1R expression and its-mediated sodium retention, consequently causes hypertension in male offspring.The γ-tubulin complex acts as the predominant microtubule (MT) nucleator that initiates MT formation and is therefore an essential factor for cell proliferation. Nonetheless, cellular MTs are formed after experimental depletion of the γ-tubulin complex, suggesting that cells possess other factors that drive MT nucleation. Here, by combining gene knockout, auxin-inducible degron, RNA interference, MT depolymerization/regrowth assay, and live microscopy, we identified four microtubule-associated proteins (MAPs), ch-TOG, CLASP1, CAMSAPs, and TPX2, which are involved in γ-tubulin-independent MT generation in human colon cancer cells. In the mitotic MT regrowth assay, nucleated MTs organized noncentriolar MT organizing centers (ncMTOCs) in the absence of γ-tubulin. Depletion of CLASP1 or TPX2 substantially delayed ncMTOC formation, suggesting that these proteins might promote MT nucleation in the absence of γ-tubulin. In contrast, depletion of ch-TOG or CAMSAPs did not affect the timing of ncMTOC appearance. CLASP1 also accelerates γ-tubulin-independent MT regrowth during interphase. Thus, MT generation can be promoted by MAPs without the γ-tubulin template.Vaishnavi Ananthanarayanan investigates the regulation of motor proteins and cytoskeleton-organelle interactions using single-molecule microscopy.Visceral adipose tissue shows remarkable plasticity, constantly replacing mature adipocytes from an inherent pool of adipocyte precursors. The number of precursors is set in the juvenile organism and remains constant in adult life. Which signals drive precursor pool expansion in juveniles and why they operate in visceral but not in subcutaneous white adipose tissue (WAT) are unclear. Using mouse models, we identified the insulin-sensitizing receptor SORLA as a molecular factor explaining the distinct proliferative capacity of visceral WAT. High levels of SORLA activity in precursors of juvenile visceral WAT prime these cells for nutritional stimuli provided through insulin, promoting mitotic expansion of the visceral precursor cell pool in overfed juvenile mice. SORLA activity is low in subcutaneous precursors, blunting their response to insulin and preventing diet-induced proliferation of this cell type. Our findings provide a molecular explanation for the unique proliferative properties of juvenile visceral WAT, and for the genetic association of SORLA with visceral obesity in humans.Hu et al. (2021. J. Cell Biol.https//doi.org/10.1083/jcb.202009082) show that Glypican 4 participates in filopodia-mediated Wnt transport from endoderm to mesoderm in zebrafish embryos to facilitate intercellular communication between germ layers.
A slow or incomplete civil registry makes it impossible to determine excess mortality due to COVID-19 and difficult to inform policy.
To quantify the association of the COVID-19 pandemic with excess mortality and household income in rural Bangladesh in 2020.
This repeated survey study is based on an in-person census followed by 2 rounds of telephone calls. Data were collected from a sample of 135 villages within a densely populated 350-km2 rural area of Bangladesh. Household data were obtained first in person and subsequently over the telephone. For the analysis, mortality data were stratified by month, age, sex, and household education. Mortality rates were modeled by bayesian multilevel regression, and the strata were aggregated to the population by poststratification. Data analysis was performed from February to April 2021.
Date and cause of any changes in household composition, as well as changes in income and food availability.
Mortality rates were compared for 2019 and 2020, both without adjus 2020, salaried primary income earners reported a 40% decrease in monthly income (from 17 485 to 10 835 Bangladeshi Taka), and self-employed earners reported a 60% decrease in monthly income (23 083 to 8521 Bangladeshi Taka), with only a small recovery observed by November 2020.
In this study of households in rural Bangladesh, all-cause mortality was lower in 2020 compared with 2019. Restrictions imposed by the government may have limited the scale of the COVID-19 pandemic in rural areas, although economic data suggest that these restrictions need to be accompanied by expanded welfare programs.
In this study of households in rural Bangladesh, all-cause mortality was lower in 2020 compared with 2019. Restrictions imposed by the government may have limited the scale of the COVID-19 pandemic in rural areas, although economic data suggest that these restrictions need to be accompanied by expanded welfare programs.
Seroprevalence studies inform the extent of infection and assist evaluation of mitigation strategies for the COVID-19 pandemic.
To estimate the prevalence of unidentified SARS-CoV-2 infection in the general population of Hong Kong.
A prospective cross-sectional study was conducted in Hong Kong after each major wave of the COVID-19 pandemic (April 21 to July 7, 2020; September 29 to November 23, 2020; and January 15 to April 18, 2021). Adults (age ≥18 years) who had not been diagnosed with COVID-19 were recruited during each period, and their sociodemographic information, symptoms, travel, contact, quarantine, and COVID-19 testing history were collected.
The main outcome was prevalence of SARS-CoV-2 infection. Raf inhibitor SARS-CoV-2 IgG antibodies were detected by an enzyme-linked immunosorbent assay based on spike (S1/S2) protein, followed by confirmation with a commercial electrochemiluminescence immunoassay based on the receptor binding domain of spike protein.
The study enrolled 4198 participants (2539 [60%]on of Hong Kong remain naive to SARS-CoV-2, highlighting the urgent need to achieve high vaccine coverage.
Antidepressant use may be associated with reduced levels of several proinflammatory cytokines suggested to be involved with the development of severe COVID-19. An association between the use of selective serotonin reuptake inhibitors (SSRIs)-specifically fluoxetine hydrochloride and fluvoxamine maleate-with decreased mortality among patients with COVID-19 has been reported in recent studies; however, these studies had limited power due to their small size.
To investigate the association of SSRIs with outcomes in patients with COVID-19 by analyzing electronic health records (EHRs).
This retrospective cohort study used propensity score matching by demographic characteristics, comorbidities, and medication indication to compare SSRI-treated patients with matched control patients not treated with SSRIs within a large EHR database representing a diverse population of 83 584 patients diagnosed with COVID-19 from January to September 2020 and with a duration of follow-up of as long as 8 months in 87 health car215 [13.3%]; RR, 0.74 [95% CI, 0.55-0.99]; adjusted P = .04). The association between receiving any SSRI that is not fluoxetine or fluvoxamine and risk of death was not statistically significant (447 of 2898 [15.4%] vs 1474 of 8694 [17.0%]; RR, 0.92 [95% CI, 0.84-1.00]; adjusted P = .06).
These results support evidence that SSRIs may be associated with reduced severity of COVID-19 reflected in the reduced RR of mortality. Further research and randomized clinical trials are needed to elucidate the effect of SSRIs generally, or more specifically of fluoxetine and fluvoxamine, on the severity of COVID-19 outcomes.
These results support evidence that SSRIs may be associated with reduced severity of COVID-19 reflected in the reduced RR of mortality. Further research and randomized clinical trials are needed to elucidate the effect of SSRIs generally, or more specifically of fluoxetine and fluvoxamine, on the severity of COVID-19 outcomes.
Gemcitabine-nab-paclitaxel (GEMNAB) and fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) both improve survival of patients with advanced pancreatic cancer when compared with single-agent gemcitabine in clinical trials.
To describe changes in the survival of patients with advanced pancreatic cancer associated with sequential drug-funding approvals and to determine if there exist distinct patient populations for whom GEMNAB and FOLFIRINOX are associated with survival benefit.
This population-based, retrospective cohort study examined all incident cases of advanced pancreatic cancer treated with first-line chemotherapy in Ontario, Canada (2008-2018) that were identified from the Cancer Care Ontario (Ontario Health) New Drug Funding Program database. Statistical analysis was performed from October 2020 to January 2021.
First-line chemotherapy for advanced pancreatic cancer.
The main outcomes were the proportion of patients treated with each chemotherapy regimen over time and overall sue and improved survival. Both FOLFIRINOX and GEMNAB were associated with survival benefits in distinct patient populations.
The use of intercostal nerve block (ICNB) analgesia with local anesthesia is common in thoracic surgery. However, the benefits and safety of ICNB among adult patients undergoing surgery is unknown.
To evaluate the analgesic benefits and safety of ICNB among adults undergoing thoracic surgery.
A systematic search was performed in Ovid MEDLINE, Ovid Embase, Scopus, and the Cochrane Library databases using terms for ICNB and thoracic surgery (including thoracic surgery, thoracoscopy, thoracotomy, nerve block, intercostal nerves). The search and results were not limited by date, with the last search conducted on July 24, 2020.
Selected studies were experimental or observational and included adult patients undergoing cardiothoracic surgery in which ICNB was administered with local anesthesia via single injection, continuous infusion, or a combination of both techniques in at least 1 group of patients. For comparison with ICNB, studies that examined systemic analgesia and different forms of regional analges (eg, 48 hours after surgery mean difference, 48.31 MMEs; 95% CI, 36.11-60.52 MMEs) and PVB (eg, 48 hours after surgery mean difference, 3.87 MMEs; 95% CI, 2.59-5.15 MMEs).
In this study, single-injection ICNB was associated with a reduction in pain during the first 24 hours after thoracic surgery and was clinically noninferior to TEA or PVB. Intercostal nerve block analgesia had opioid-sparing effects; however, TEA and PVB were associated with larger decreases in postoperative MMEs, suggesting that ICNB may be most beneficial for cases in which TEA and PVB are not indicated.
In this study, single-injection ICNB was associated with a reduction in pain during the first 24 hours after thoracic surgery and was clinically noninferior to TEA or PVB. Intercostal nerve block analgesia had opioid-sparing effects; however, TEA and PVB were associated with larger decreases in postoperative MMEs, suggesting that ICNB may be most beneficial for cases in which TEA and PVB are not indicated.
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