Lipid hydroperoxides permit deformation-dependent leak of monovalent cation from erythrocytes

Subtle peroxidative perturbation of normal red blood cells (RBC) using t-butylhydroperoxide creates a leak pathway for monovalent cations that is reversibly activated by cell deformation. To determine what factor promotes expression of this unique membrane defect, we have dissected "peroxidation" into components that can be evaluated separately by comparing K leak from suitably modified RBC during elliptical deformation and parallel control incubation. Selective introduction of phospholipid hydroperoxides into normal RBC membranes successfully induces a deformation-dependent leak pathway having the same phenomenology as that previously documented for cells treated with t- butylhydroperoxide itself (fully recoverable; calcium-independent; inhibited at lower pH; K efflux balanced by Na influx). This leak pathway occurs in the absence of detectable secondary peroxidative change and appears to reflect a direct influence of lipid hydroperoxide. Using micropipette examination of vesicular bilayers reconstituted from RBC lipid extracts, we find that lipid from peroxidized RBC exhibits only a slight tendency to be less cohesive than normal lipid, apparently precluding isolated lipid properties as an explanation for altered permeability barrier function. However, addition of a hydrophobic membrane-spanning peptide to these same lipids significantly diminishes bilayer cohesion, an effect that is exacerbated further by the presence of peroxidized lipid. These observations suggest that lipid hydroperoxide is a necessary, but perhaps not sufficient, factor for induction of this unique leak pathway. Our results may be relevant to the abnormal cation homeostasis of sickle RBC in which deformation of an oxidatively perturbed membrane occurs during the sickling phenomenon.     

Falling through the cracks: the gap between evidence and policy in responding to depression in gay, lesbian and other homosexually active people in Australia

Objective: To examine the evidence for a national policy response to depression among gay, lesbian and other homosexually active people in Australia. Methods: A literature review using database searches on depression among non‐heterosexual people then a web‐based search of national policy investigating how mental health needs in this population are addressed in Australia. Results: The literature review found that non‐heterosexual people experience depression at higher rates, but the literature on interventions was sparse. The policy analysis found no mention of depression or the broader mental health needs of non‐heterosexual people in key national mental health policy documents. These documents outline a policy approach for population groups with a higher prevalence of mental health problems, and stigma and discrimination are relevant associated factors, but only the National Suicide Strategy considers non‐heterosexual people an ‘at‐risk group’. Conclusions: The results suggest that the evidence on higher rates of depression in non‐heterosexual people is strong, but that this is not recognised in current national policy. Implications: Defining non‐heterosexual people as an ‘at‐risk’ group is appropriate, as is prioritising access to mental health services that are socially and culturally appropriate. Addressing homophobia as an associated factor would require a strategic policy approach across a range of sectors.     

Anti-Jka, -C, and -E in a single patient, initially demonstrable only by the manual hexadimethrine bromide (Polybrene) test, with incompatibilities confirmed by 51Cr-labeled red cell studies

Published reports have confirmed the superior sensitivity of the manual hexadimethrine bromide (Polybrene) test (MPT) for demonstrating many alloantibodies in vitro; however, the clinical significance of alloantibodies demonstrable exclusively by MPT has not been shown conclusively. A patient with macroglobulinemia experienced chills, fever, hemoglobinemia, and hemoglobinuria following the transfusion of 1 unit of red cells (RBCs) shown to be compatible by the low-ionic-strength antiglobulin (LIS-AG) method. Serologic investigation was negative. Intravascular hemolysis occurred with a second "compatible" unit. Serologic studies were again negative by LIS-AG and ficin-AG methods, but revealed anti-Jka by MPT. Both donors were Jk(a+b-), and 51Cr studies of the second donor's RBCs revealed a t1/2 of less than 30 minutes, with marked intravascular hemolysis. A LIS-AG-compatible Jk(a-) unit was transfused uneventfully, but with no rise in hematocrit. MPT next revealed anti-C; subsequent 51Cr studies with the Jk(a-), Cc donor's RBCs showed a 51Cr t1/2 of 100 minutes with slight intravascular lysis. Four transfusions of Jk(a-), C- blood were uneventful, but 5 days later the patient's hemoglobin declined. The following day, anti-E was demonstrable exclusively by MPT. 51Cr-labeled Jk(a-), C-, E- RBCs had normal 24-hour survival. The patient's hemoglobin rose to 11 g per dl following transfusions of Jk(a-), C-, E- RBCs, and he was discharged. In vitro studies employing the patient's purified IgM paraprotein revealed no interference with alloantibody binding or detection.     

Studies of rhinovirus resistant to an antiviral chalcone

During studies of the antiviral activity of chalcone Ro-09-0410 on human rhinovirus type 9 (RV9) chalcone-resistant strains of RV9 were isolated and appeared with a frequency of about 10(-5) in chalcone sensitive stock. Chalcone-dependent viruses were found after further passage. Some characteristics of the resistant viruses were studied and compared with those of the wild type virus; a number of differences were detected. They produced smaller plaques and grew to lower titre; they were no longer protected by chalcone from inactivation by heat and low pH. The event responsible for drug dependence apparently took place after that responsible for drug resistance. Drug-resistant viruses were still sensitive to dichloroflavan and enviroxime.     

精子释放时精子质量的检测方法

评价新修订的《世界卫生组织人类精液分析实验室技术手册》(简称手册)中涉及精子释放(精子脱离支持细胞从睾丸中排出)时的精子特征。修订手册的目的是在不影响临床应用的情况下改善"精液分析的质量"。手册指出,精液分析还有助于①研究男性生殖状态。②在男性生殖调节期间和之后监测精子的发生状态。但是,如果对射精精液精子的分析是用于上述②的目的,那么就必须识别出精子释放时的异常精子。手册未提出精子释放时精子质量的检测方法。相反,采用了精子穿过宫颈黏液或到达受精位置这一"金标准"。这个标准虽然适合于判断个体使其伴侣妊娠的可能性,但却不适用于研究睾丸本身的疾病。因此,手册介绍的测定精子质量的方法无法鉴别精子异常是发生在精子释放同时还是之后。基于活动或"活"精子的百分率评价精子释放时的精子质量是没有意义的。介绍了能反映精子释放时精子质量的其他特征,基于射出精液中单个精子的质量特征评价精子释放时精子质量可采用以下方法:①采用新的精子质量形态评估体系。②采用现代技术评价一定样本中单个精子的几个合适和独立的特征,以便更准确地确定异常精子的比例。     

A large cohort study of the effects of Lewis,ABO, 13 other blood groups,and secretor status on COVID-19 susceptibility,severity, and long COVID-19

Background

Previous studies have reported Blood type O to confer a lower risk of SARS-CoV-2 infection, while secretor status and other blood groups have been suspected to have a similar effect as well.

Study design and methods

To determine whether any other blood groups influence testing positive for SARS-CoV-2, COVID-19 severity, or prolonged COVID-19, we used a large cohort of 650,156 Danish blood donors with varying available data for secretor status and blood groups ABO, Rh, Colton, Duffy, Diego, Dombrock, Kell, Kidd, Knops, Lewis, Lutheran, MNS, P1PK, Vel, and Yt. Of these, 36,068 tested positive for SARS-CoV-2 whereas 614,088 tested negative between 2020-02-17 and 2021-08-04. Associations between infection and blood groups were assessed using logistic regression models with sex and age as covariates.

Results

The Lewis blood group antigen Le^a displayed strongly reduced SARS-CoV-2 susceptibility OR 0.85 CI[0.79–0.93] p < .001. Compared to blood type O, the blood types B, A, and AB were found more susceptible toward infection with ORs 1.1 CI[1.06–1.14] p < .001, 1.17 CI[1.14–1.2] p < .001, and 1.2 CI[1.14–1.26] p < .001, respectively. No susceptibility associations were found for the other 13 blood groups investigated. There was no association between any blood groups and COVID-19 hospitalization or long COVID-19. No secretor status associations were found.

Discussion

This study uncovers a new association to reduced SARS-CoV-2 susceptibility for Lewis type Le^a and confirms the previous link to blood group O. The new association to Le^a could be explained by a link between mucosal microbiome and SARS-CoV-2.