Platelet glycoproteins IIb and IIIa as a calcium channel in liposomes

Human platelet membrane glycoproteins IIb and IIIa (GPIIb and IIIa) were incorporated into phospholipid vesicles by the reverse-phase technique to assess the ability of GPIIb and IIIa to function as a Ca2+ channel. Movement of Ca2+ across the lipid bilayer was quantitated by injection of proteoliposomes with encapsulated Fura-2 into Ca2+ buffers and measurement of Fura-2 fluorescence as an indicator of Ca2+ influx. Reciprocally, to assess the function of proteins in an inside-out orientation, Ca2+-loaded vesicles were injected into Ca2+-free buffer and Ca2+ efflux monitored by a calcium electrode. Incorporation of the IIb-IIIa complex produced significant facilitation of Ca2+ movement across the lipid bilayer. No net transmembrane Ca2+ movement was seen with dissociated IIb and IIIa. Movement of Ca2+ was proportional to the transmembrane Ca2+ gradient. Ca2+ movement into the vesicles was inversely proportional to extravesicular NaCl from 25 to 150 mmol/L, analogous to several studies in the intact platelet. Adenosine triphosphate had no effect on Ca2+ movement into or out of the vesicles. Specific inhibition of a Ca2+ shift into the vesicles was seen with M148, a monoclonal antibody to IIb/IIIa, while no inhibition was observed with a panel of other anti-IIb/IIIa monoclonal antibodies. This suggests that a specific site on the complex or orientation of the complex is essential for calcium channel function. These data demonstrate that the GPIIb/IIIa complex can serve as a passive Ca2+ channel across a phospholipid bilayer and has the potential to play a role in Ca2+ flux across the platelet plasma membrane.     

Sexual Risk Behavior,Alcohol Use,and Social Media Use Among Secondary School Students in Informal Settlements in Cape Town and Port Elizabeth,South Africa

South Africa’s HIV prevalence among young people remains among the highest in the world. A cross-sectional study was carried out in 2012 to estimate prevalences of sexual risk behavior and hazardous alcohol use (HAU) (via the Alcohol Use Disorder Identification Test) as well as to investigate potential associations between these outcomes and social media use. In all, 4485 students (mean age 15.66 years, SD 1.39) at 46 secondary schools in informal settlements in Cape Town and Port Elizabeth completed mobile-phone-assisted, self-administered baseline questionnaires within a cluster-randomized trial. In all, 312 females (12.5 %) and 468 males (23.5 %) screened positive for HAU (AOR = 1.98, 95 % CI 1.69–2.34). 730 males (39.9 %) and 268 females (11.8 %) reported having had two or more partners in the last year (AOR = 3.46, 95 % CI 2.87–4.16). Among females, having a Facebook account was associated with reported multiple partnerships in the last year (AOR = 1.81, 95 % CI 1.19–2.74), age-disparate sex in the last year (AOR = 1.96, 95 % CI 1.16–3.32) and HAU (AOR = 1.97, 95 % CI 1.41–2.74). Using Mxit—a popular mobile instant messaging application—was associated with higher odds of reported multiple partnerships in the last year among both males (AOR = 1.70, 95 % CI 1.35–2.14) and females (AOR = 1.45, 95 % CI 1.07–1.96) and with HAU among both males (AOR = 1.47, 95 % CI 1.14–1.90) and females (AOR = 1.50, 95 % CI 1.18–1.90). Further longitudinal and qualitative research should explore in more depth the observed links between social media and risk behavior.     

《英国非酒精性脂肪性肝炎肝移植指南》导读

非酒精性脂肪性肝炎（non—alcoholicsteatohepatitis,NASH）现已成为肝移植愈来愈重要的基础肝病。鉴于晚期NASH患者常并存多种影响肝移植转归的临床问题,而至今尚无针对NASH患者进行肝移植的评估和治疗指南,为此英国移植学会（British Transplant Society,BTS）邀请相关专家制定了指南,以指导肝移植前后NASH患者的处理。     

Diagnosis and management for urosepsis

Urosepsis is defined as sepsis caused by a urogenital tract infection. Urosepsis in adults comprises approximately 25% of all sepsis cases, and is in most cases due to complicated urinary tract infections. The urinary tract is the infection site of severe sepsis or septic shock in approximately 10–30% of cases. Severe sepsis and septic shock is a critical situation, with a reported mortality rate nowadays still ranging from 30% to 40%. Urosepsis is mainly a result of obstructed uropathy of the upper urinary tract, with ureterolithiasis being the most common cause. The complex pathogenesis of sepsis is initiated when pathogen or damage‐associated molecular patterns recognized by pattern recognition receptors of the host innate immune system generate pro‐inflammatory cytokines. A transition from the innate to the adaptive immune system follows until a T_H2 anti‐inflammatory response takes over, leading to immunosuppression. Treatment of urosepsis comprises four major aspects: (i) early diagnosis; (ii) early goal‐directed therapy including optimal pharmacodynamic exposure to antimicrobials both in the plasma and in the urinary tract; (iii) identification and control of the complicating factor in the urinary tract; and (iv) specific sepsis therapy. Early adequate tissue oxygenation, adequate initial antibiotic therapy, and rapid identification and control of the septic focus in the urinary tract are critical steps in the successful management of a patient with urosepsis, which includes early imaging, and an optimal interdisciplinary approach encompassing emergency unit, urological and intensive‐care medicine specialists.     

COVID-19 manifestations in people with Parkinson’s disease: a USA cohort

Journal of Neurology - With the explosion of COVID-19 globally, it was unclear if people with Parkinson’s disease (PD) were at increased risk for severe manifestations or negative outcomes....     

Personalized mailed feedback for college drinking prevention: a randomized clinical trial

The current study was designed to evaluate the efficacy of a mailed feedback and tips intervention as a universal prevention strategy for college drinking. Participants (N = 1,488) were randomly assigned to feedback or assessment-only control conditions. Results indicated that the mailed feedback intervention had a preventive effect on drinking rates overall, with participants in the feedback condition consuming less alcohol at follow-up in comparison with controls. In addition, abstainers in the feedback condition were twice as likely to remain abstinent from alcohol at follow-up in comparison with control participants (odds ratio = 2.02), and feedback participants were significantly more likely to refrain from heavy episodic drinking (odds ratio = 1.43). Neither gender nor severity of baseline drinking moderated the efficacy of the intervention in these analyses, but more conservative analyses utilizing last-observation carryforward suggested women and abstainers benefited more from this prevention approach. Protective behaviors mediated intervention efficacy, with participants who received the intervention being more likely to use strategies such as setting limits and alternating alcohol with nonalcoholic beverages. Implications of these findings for universal prevention of college drinking are discussed.     

Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels

To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL- 3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c- kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL- 3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL- 3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells.