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Investigation of the molecular mechanisms of aging in the human heart is challenging because of confounding factors, such as diet and medications, as well as limited access to tissues from healthy aging individuals. The laboratory mouse provides an ideal model to study aging in healthy individuals in a controlled environment. However, previous mouse studies have examined only a narrow range of the genetic variation that shapes individual differences during aging. Here, we analyze transcriptome and proteome data from 185 genetically diverse male and female mice at ages 6, 12, and 18 mo to characterize molecular changes that occur in the aging heart. Transcripts and proteins reveal activation of pathways related to exocytosis and cellular transport with age, whereas processes involved in protein folding decrease with age. Additional changes are apparent only in the protein data including reduced fatty acid oxidation and increased autophagy. For proteins that form complexes, we see a decline in correlation between their component subunits with age, suggesting age-related loss of stoichiometry. The most affected complexes are themselves involved in protein homeostasis, which potentially contributes to a cycle of progressive breakdown in protein quality control with age. Our findings highlight the important role of post-transcriptional regulation in aging. In addition, we identify genetic loci that modulate age-related changes in protein homeostasis, suggesting that genetic variation can alter the molecular aging process.
Health system strengthening (HSS) activities should accompany disease-targeting interventions in low/middle-income countries (LMICs). Economic evaluations provide information on how these types of investment might best be balanced but can be challenging. We conducted a systematic review to evaluate how researchers address these economic evaluation challenges.

We identified studies about economic evaluation of HSS activities in LMICs using a two-stage approach. First, we conducted a broad search to identify areas where economic evaluations of HSS activities were being conducted. Next, we selected specific interventions for more targeted literature review. We extracted study characteristics using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Finally, we summarised authors' modelling decisions using a framework that examines how models are developed to emphasise generalisability, precision, or realism.

Our searches produced 1978 studies, out of which we included 36. Mo precise) results. More research into how decision-makers would use economic evaluations to define the expansion path to strengthening health systems would allow for conceptualising impactful work on the economic value of HSS.
Migrants, especially those in temporary accommodations like camps and shelters, might be a vulnerable population during the COVID-19 pandemic, but little is known about the impact of the pandemic in these settings in low-income and middle-income countries. We assessed SARS-CoV-2 seropositivity and RNA prevalence, the correlates of seropositivity (emphasising socially determined conditions), and the socioeconomic impacts of the pandemic among migrants living in shelters in Tijuana, a city on the Mexico-US border.

We conducted a cross-sectional, non-probability survey of migrants living in shelters in Tijuana in November-December 2020 and February-April 2021. Participants completed a questionnaire and provided anterior nasal swab and blood samples for detection of SARS-CoV-2 RNA and antibodies (IgG and IgM), respectively. We explored whether SARS-CoV-2 infection was associated with sociodemographic and migration-related variables, access to sanitation, protective behaviours and health-related factors.

Ovepared with results from other studies conducted in the general population in Mexico at a similar time, migrants living in shelters were at increased risk of acquiring SARS-CoV-2, and they suffered considerable adverse socioeconomic impacts as a consequence of the pandemic. Expanded public health and other social support systems are needed to protect migrants from COVID-19 and reduce health inequities.The geographic and economic characteristics unique to island nations create a different set of conditions for, and responses to, the spread of a pandemic compared with those of mainland countries. Here, we aimed to describe the initial period of the COVID-19 pandemic, along with the potential conditions and responses affecting variation in the burden of infections and severe disease burden, across the six island nations of the WHO's Africa region Cabo Verde, Comoros, Madagascar, Mauritius, São Tomé e Príncipe and Seychelles. We analysed the publicly available COVID-19 data on confirmed cases and deaths from the beginning of the pandemic through 29 November 2020. To understand variation in the course of the pandemic in these nations, we explored differences in their economic statuses, healthcare expenditures and facilities, age and sex distributions, leading health risk factors, densities of the overall and urban populations and the main industries in these countries. We also reviewed the non-pharmaceutical response measures implemented nationally. We found that the burden of SARS-CoV-2 infection was reduced by strict early limitations on movement and biased towards nations where detection capacity was higher, while the burden of severe COVID-19 was skewed towards countries that invested less in healthcare and those that had older populations and greater prevalence of key underlying health risk factors. These findings highlight the need for Africa's island nations to invest more in healthcare and in local testing capacity to reduce the need for reliance on border closures that have dire consequences for their economies.
Pleural exudative effusions without diagnosis after initial work up are a frequent problem in any respiratory division. Several ways to obtain pleural biopsy exist. Thoracoscopy is one of the most frequently used. Differential diagnosis mainly exists out of malignant pleuritis, tuberculosis, nonspecific pleuritis and rarely systemic or autoimmune disease. We performed a retrospective data analysis of our almost 10-year period experience, the first Belgian data to be published.

We performed a retrospective data analysis of all patients with unexplained pleural exudates who underwent diagnostic medical thoracoscopy under general anaesthesia in our respiratory department during the period 2006-2015. We report on diagnoses made, sensitivity and specificity, safety of thoracoscopy and follow-up of patients after thoracoscopy.

131 patients underwent diagnostic medical thoracoscopy during the inclusion period. 44.3% (n=58) of the patients were diagnosed with malignant pleuritis, 45.0% (n=59) with nonspecific pn, benign or autoimmune disease related.A 54-year-old man, with history of undergoing deep anterior lamellar keratoplasty (DALK) 20 months ago, presented with mature senile cataract in the same eye. While undergoing phacoemulsification, a large, central Descemet membrane detachment (DMD) was noted, separating the donor cornea from the host predescemetic layer. No DM tears were noted. Stromal puncture was done at the graft host junction to reduce the extent of DMD. This was followed by a large intracameral air bubble insertion, which resulted in complete resolution of DMD on the first postoperative day. DMD during hydration of wound is a unique complication to be anticipated while doing cataract surgery in an operated DALK eye.Multiple sclerosis (MS) is a chronic inflammatory demyelinating autoimmune disease with chronic inflammatory demyelination of the CNS. Experimental autoimmune encephalomyelitis (EAE) is an important animal model to study MS, with many pathological phenomena similar to MS. Th17 cells are important regulators of EAE and MS pathogenesis. Most cytokines needed for Th cell development are secreted by APCs, such as dendritic cells (DCs). Consequently, MS could be improved by inhibiting cytokine secretion from DCs. In this study, we reported that chlorzoxazone could ameliorate EAE pathogenesis via inhibiting IL-6 production by DCs. The EAE signs in the chlorzoxazone-treated group of mice were relieved, which was mainly manifested as lower clinical scores, a decrease in the number of immune cells, and a reduction of demyelination in the CNS. https://www.selleckchem.com/products/LBH-589.html Moreover, the proportion of Th17 cells in the spleen and CNS decreased significantly. In vitro experiments showed that chlorzoxazone treatment significantly reduced DC-derived IL-6 production. In the DC-T cell coculture experiment, significantly decreased Th17 differentiation was observed after chlorzoxazone treatment. In addition, mass spectrometric analysis was performed to elucidate the mechanism by which chlorzoxazone affected EAE and DC function. We showed that the effect of chlorzoxazone on inhibiting the secretion of IL-6 by DCs may be mediated via the AMP-activated protein kinase pathway. Overall, our study elucidated the key role of chlorzoxazone in regulating EAE pathogenesis and suggested that it might be used as a new drug for MS patients.Recent evidence suggests interaction of platelets with dendritic cells (DCs), while the molecular mechanisms mediating this heterotypic cell cross-talk are largely unknown. We evaluated the role of integrin Mac-1 (αMβ2, CD11b/CD18) on DCs as a counterreceptor for platelet glycoprotein (GP) Ibα. In a dynamic coincubation model, we observed interaction of human platelets with monocyte-derived DCs, but also that platelet activation induced a sharp increase in heterotypic cell binding. Inhibition of CD11b or GPIbα led to significant reduction of DC adhesion to platelets in vitro independent of GPIIbIIIa, which we confirmed using platelets from Glanzmann thrombasthenia patients and transgenic mouse lines on C57BL/6 background (GPIbα-/-, IL4R-GPIbα-tg, and muMac1 mice). In vivo, inhibition or genetic deletion of CD11b and GPIbα induced a significant reduction of platelet-mediated DC adhesion to the injured arterial wall. Interestingly, only intravascular antiCD11b inhibited DC recruitment, suggesting a dynamic DC-platelet interaction. Indeed, we could show that activated platelets induced CD11b upregulation on Mg2+-preactivated DCs, which was related to protein kinase B (Akt) and dependent on P-selectin and P-selectin glycoprotein ligand 1. Importantly, specific pharmacological targeting of the GPIbα-Mac-1 interaction site blocked DC-platelet interaction in vitro and in vivo. These results demonstrate that cross-talk of platelets with DCs is mediated by GPIbα and Mac-1, which is upregulated on DCs by activated platelets in a P-selectin glycoprotein ligand 1-dependent manner.The immunoregulation of platelets and platelet-monocyte aggregates (PMAs) is increasingly recognized, but it roles in tuberculosis (TB) remain to be elucidated. In this study, we found that CD14+CD41+ PMAs were increased in peripheral blood of patients with active TB. CD14+CD41+ PMAs highly expressed triggering receptors expressed on myeloid cells (TREMs)-like transcript-1 (TLT-1), P-selectin (CD62P), and CD40L. Our in vitro study found that platelets from patients with active TB aggregate with monocytes to induce IL-1β and IL-6 production by monocytes. Importantly, we identified that TLT-1 was required for formation of PMAs. The potential TLT-1 ligand was expressed and increased on CD14+ monocytes of patients with TB determined by using TLT-1 fusion protein (TLT-1 Fc). Blocking of ligand-TLT-1 interaction with TLT-1 Fc reduced PMA formation and IL-1β and IL-6 production by monocytes. Further results demonstrated that PMAs induced IL-10 production by B cells (B10) dependent on IL-1β, IL-6, and CD40L signals in a coculture system.
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