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The release of interleukin (IL)-1β from primary human monocytes in response to extracellular LPS occurs through the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome. In primary monocytes, in response to LPS, NLRP3 inflammasome activation is characterized by an independence of K+ efflux and ASC speck formation and has been termed the 'alternative' pathway. Here, we report that pharmacological inhibition of V-ATPase with bafilomycin A1 exacerbated LPS-induced NLRP3 inflammasome activation in primary human monocytes. Inhibition of V-ATPase in the presence of extracellular LPS led to NLRP3-dependent, K+ efflux-independent, ASC oligomerization and caspase-1 activation. Although V-ATPases are required for lysosomal acidification, we found that acidic lysosomal pH and protease activity were dispensable for this altered response, suggesting that V-ATPase inhibition triggered alternative signalling events. Therefore, V-ATPases may serve additional roles during NLRP3 inflammasome activation in primary human monocytes.

To determine the prevalence, risk factors and impact of non-disclosure of HIV serostatus to sexual partners among HIV-positive patients at Siriraj Hospital, Bangkok.

We conducted a prospective observational study to enrol HIV-positive adults with one or more regular sexual partners during the past 3months. We obtained personal information via anonymous questionnaire and clinical data of those receiving antiretroviral therapy (ART) for ≥12months via chart-review.

A total of 328 HIV-positive participants were enrolled. Approximately half were female and in the symptomatic HIV stage at diagnosis, with an average age 44.08±8.59years. Approximately one-third of participants (35.7%) reported that they had not disclosed their HIV serostatus to their sexual partners. The non-disclosure group had a higher rate of poor ART adherence owing to fear of revealing their HIV serostatus to their partner (12.0% vs. 1.9%; P<0.001), as compared with the disclosure group. Rates of immunological and virological failure dippropriately focusing interventions on high-risk populations with aforementioned risk factors is important for improved HIV care.The Mental Toughness Questionnaire-48 (MTQ48) is a 48-item self-report instrument to measure one's level of mental toughness. Despite its wide popularity in psychological studies, the questionnaire has been criticized due to its factorial validity. The present study aimed to re-assess the factorial validity of the instrument and propose alternative models to provide researchers with theoretically and practically useful instruments to measure mental toughness. Tofacitinib price Two studies were conducted using large samples of university students (Study 1 n = 2186; Study 2 n = 3209). In Study 1, none of one-, four- and six-factor models with 48 items satisfactorily fit the data set. Instead, two refined 18- and 6-item versions of the questionnaire, covering six aspects of mental toughness, were proposed the Short MTQ and Very Short MTQ. Both measures demonstrated excellent fit to the data. These results were replicated with a larger independent sample in Study 2. With the Short MTQ, it is possible to represent mental toughness as a multidimensional construct consisting of a global mental toughness factor and six specific factors. The Very Short MTQ is a practical tool for occasions where constraints prevent use of the Short MTQ. The refined questionnaires are promising options to measure and understand individuals' mental toughness with the MTQ.

Hypercalcemia of malignancy (HCM) is a serious metabolic complication, and the highest rates are in multiple myeloma (MM). The cause of hypercalcemia in newly diagnosed multiple myeloma (NDMM) remains unknown. We sought to evaluate the prognostic impact and mechanism of hypercalcemia in patients with symptomatic NDMM.

We studied all consecutive MM patients who were initially diagnosed and followed up at Beijing Jishuitan Hospital between February 2013 and December 2019; 357 patients were included in the retrospective analysis.

A total of 16.8% of MM patients presented with hypercalcemia at the time of MM diagnosis. The presence of hypercalcemia was associated with higher serum levels of β2 microglobulin, creatinine, phosphorus, uric acid, procollagen I N-terminal peptide, β-carboxy-terminal cross-linking telopeptide of type I collagen and osteocalcin, lower serum levels of hemoglobin, parathyroid hormone (PTH), and advanced ISS and R-ISS stages. Multivariate analysis showed that serum PTH, hemoglobin, creatinine, and uric acid levels were the main factors affecting hypercalcemia. The presence of hypercalcemia was associated with significantly inferior survival (40months vs 57months, p<0.05) based on univariate analysis, and it remained an independent poor prognostic factor (HR 1.854, 95% CI 1.006-3.415, adjusted p=0.048) in a multivariate model that included age and R-ISS stage.

This study shows that hypercalcemia is associated with poor survival and is caused by manifold factors with humoral effects and local bone destruction.

This study shows that hypercalcemia is associated with poor survival and is caused by manifold factors with humoral effects and local bone destruction.The inappropriate marketing and aggressive promotion of breastmilk substitutes (BMS) undermines breastfeeding and harms child and maternal health in all country contexts. Although a global milk formula 'sales boom' is reportedly underway, few studies have investigated its dynamics and determinants. This study takes two steps. First, it describes trends and patterns in global formula sales volumes (apparent consumption), by country income and region. Data are reported for 77 countries, for the years 2005-19, and for the standard (0-6 months), follow-up (7-12 m), toddler (13-36 m), and special (0-6 m) categories. Second, it draws from the literature to understand how transformations underway in first-food systems - those that provision foods for children aged 0-36 months - explain the global transition to higher formula diets. Total world formula sales grew by 115% between 2005 and 2019, from 3.5 to 7.4 kg/child, led by highly-populated middle-income countries. Growth was rapid in South East and East Asia, especially in China, which now accounts for one third of world sales.