Effects of Coronavirus Disease Pandemic on Tuberculosis Notifications,Malawi

The coronavirus disease (COVID-19) pandemic might affect tuberculosis (TB) diagnosis and patient care. We analyzed a citywide electronic TB register in Blantyre, Malawi and interviewed TB officers. Malawi did not have an official COVID-19 lockdown but closed schools and borders on March 23, 2020. In an interrupted time series analysis, we noted an immediate 35.9% reduction in TB notifications in April 2020; notifications recovered to near prepandemic numbers by December 2020. However, 333 fewer cumulative TB notifications were received than anticipated. Women and girls were affected more (30.7% fewer cases) than men and boys (20.9% fewer cases). Fear of COVID-19 infection, temporary facility closures, inadequate personal protective equipment, and COVID-19 stigma because of similar symptoms to TB were mentioned as reasons for fewer people being diagnosed with TB. Public health measures could benefit control of both TB and COVID-19, but only if TB diagnostic services remain accessible and are considered safe to attend.     

妊娠合并登革热35例临床分析

目的 探讨登革热对妊娠的影响。方法 对35例妊娠合并登革热进行回顾性分析。结果 35例患有27例出现不正常分娩及产后大出血,有22例出现流产、死胎、早产及畸胎。结论 妊娠合并登革热在妊娠早期可出现流产或死胎,中期可引起早产,晚期可出现产后大出血。     

Comparison of efficacy and safety of daily oral L-arginine and PDE5Is alone or combination in treating erectile dysfunction: A systematic review and meta-analysis of randomised controlled trials

The meta-analysis was performed to assess the efficacy and safety of daily oral L-arginine and phosphodiesterase type 5 inhibitors (PDE5Is) alone or combination in treating patients with erectile dysfunction (ED). We performed a search of randomised controlled trials in the following databases: PubMed, EMBASE and Cochrane Library databases. Four articles including 373 patients were studied. Erectile functions were significantly improved in three therapy groups compared with baseline. Patients who received the combination of L-arginine and PDE5Is showed significant improvement compared to those treated with L-arginine and PDE5Is alone, as assessed by sexual function index (p <0.00001 and p =0.005, respectively) and total testosterone (p <0.00001 and p =0.0007, respectively). Furthermore, patients who treated with PDE5Is alone exhibited the better efficacy than those treated with L-arginine alone in respects of sexual function index (p <0.00001) and total testosterone (p =0.0001). However, the combination of L-arginine and PDE5Is had no obvious difference relative to PDE5Is alone in terms of various adverse events (AEs). Conclusively, compared with monotherapy, the combination of L-arginine and PDE5Is showed a greater improvement of sexual function and total testosterone, and did not significantly increase the AEs. Besides, PDE5Is alone revealed a better effect than those treated with L-arginine alone for patients with ED.     

Intercellular Interactions of an Adipogenic CXCL12-Expressing Stromal Cell Subset in Murine Bone Marrow

Bone marrow houses a multifunctional stromal cell population expressing C-X-C motif chemokine ligand 12 (CXCL12), termed CXCL12-abundant reticular (CAR) cells, that regulates osteogenesis and adipogenesis. The quiescent pre-adipocyte-like subset of CXCL12⁺ stromal cells (“Adipo-CAR” cells) is localized to sinusoidal surfaces and particularly enriched for hematopoiesis-supporting cytokines. However, detailed characteristics of these CXCL12⁺ pre-adipocyte-like stromal cells and how they contribute to marrow adipogenesis remain largely unknown. Here we highlight CXCL12-dependent physical coupling with hematopoietic cells as a potential mechanism regulating the adipogenic potential of CXCL12⁺ stromal cells. Single-cell computational analyses of RNA velocity and cell signaling reveal that Adipo-CAR cells exuberantly communicate with hematopoietic cells through CXCL12-CXCR4 ligand-receptor interactions but do not interconvert with Osteo-CAR cells. Consistent with this computational prediction, a substantial fraction of Cxcl12-creER⁺ pre-adipocyte-like cells intertwines with hematopoietic cells in vivo and in single-cell preparation in a protease-sensitive manner. Deletion of CXCL12 in these cells using Col2a1-cre leads to a reduction of stromal-hematopoietic coupling and extensive marrow adipogenesis in adult bone marrow, which appears to involve direct conversion of CXCL12⁺ cells to lipid-laden marrow adipocytes without altering mesenchymal progenitor cell fates. Therefore, these findings suggest that CXCL12⁺ pre-adipocyte-like marrow stromal cells prevent their premature differentiation by maintaining physical coupling with hematopoietic cells in a CXCL12-dependent manner, highlighting a possible cell-non-autonomous mechanism that regulates marrow adipogenesis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection

BackgroundDeveloping a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells’ proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection.MethodsUsing 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets.ResultsAn exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature’s negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell–mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature’s negative predictive value was 90.6% and its positive predictive value was 77.8%.ConclusionsOur findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.     

Exploration of the association between serum uric acid and testosterone in adult males: NHANES 2011–2016

BackgroundPrevious studies have suggested that the possible relationship between serum uric acid (SUA) and testosterone. However, the results of previous studies are controversial and there is limited evidence examining the relationship between SUA and testosterone in a general US population of men. The objective of this study is to explore the correlation of SUA and testosterone among adult males from the US.MethodsData from the National Health and Nutrition Examination Survey 2011–2016 were used, including a total of 7,796 male participants aged 18 years or older and excluding those lacking serum testosterone and uric acid data. Clinical characteristics of the participants among different SUA groups and testosterone groups are compared. Univariate and multivariate linear regression analyses were applied to evaluate the association between SUA and testosterone.ResultsWe found an inverse association between SUA and testosterone after fully adjusted the potential confounding factors in general US adult males. In the multivariate linear regression analysis, we found that increasing age (estimate testosterone percent difference: −0.20% per year, P<0.01), uric acid (estimate testosterone percent difference: −4.40% per md/dL, P<0.01) and BMI (estimate testosterone percent difference: −2.86% per kg/m2, P<0.01) were associated with declining serum testosterone. This association remained significant in sensitivity analysis, while in the stratified analysis, above association was not significant in men with diabetes or aged 65 and over.ConclusionsSUA levels might be negatively associated with serum testosterone in adult males.     

Improvement of surface bioactivity on titanium by water and hydrogen plasma immersion ion implantation

We have investigated the surface bioactivity of titanium after water and hydrogen plasma immersion ion implantation. Plasma immersion ion implantation (PIII) excels in the surface treatment of components possessing a complicated shape such as medical implants. In addition, water and hydrogen PIII has been extensively studied as a method to fabricate silicon-on-insulator (SOI) substrates in the semiconductor industry and so it is relatively straightforward to transfer the technology to the biomedical field. In our investigation, water and hydrogen were plasma-implanted into titanium sequentially. Our objective is that water PIII introduces near-surface damages that trap hydrogen implanted in the subsequent step to improve the surface bioactivity while the desirable bulk properties of the materials are not compromised. Ti-OH functional groups can be detected on the (H(2)O+H(2))-implanted titanium surface by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy. After incubation in simulated body fluids (SBF) for cytocompatibililty evaluation in vitro, bone-like hydroxyapatite was found to precipitate on the (H(2)O+H(2)) implanted samples while no apatite was found on titanium samples plasma implanted with water or hydrogen alone. Human osteoblast cells were cultured on the (H(2)O+H(2))-implanted titanium surface and they exhibited good adhesion and growth. Our results suggest a practical means to improve the surface bioactivity and cytocompatibility of medical implants made of titanium.