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Abstract Spike glycoprotein of SARS-CoV-2 variants plays a critical role in infection and transmission through its interaction with human angiotensin converting enzyme 2 (hACE2) receptors. Prior findings using molecular docking and biomolecular studies reported varied findings on the difference in the interactions among the spike variants with the hACE2 receptors. Hence, it is a prerequisite to understand these interactions in a more precise manner. To this end, firstly, we performed ELISA with trimeric spike glycoproteins of SARS-CoV-2 variants including Wuhan Hu-1(Wild), Delta, C.1.2 and Omicron. Further, to study the interactions in a more specific manner by mimicking the natural infection, we developed hACE2 receptors expressing HEK-293T cell line, evaluated their binding efficiencies and competitive binding of spike variants with D614G spike pseudotyped virus. In line with the existing findings, we observed that Omicron had higher binding efficiency compared to Delta in both ELISA and Cellular models. Intriguingly, we found that cellular models could differentiate the subtle differences between the closely related C.1.2 and Delta in their binding to hACE2 receptors. Our study using the cellular model provides a precise method to evaluate the binding interactions between spike sub-lineages to hACE2 receptors.

Summary: Human pluripotent stem cell (hPSC) technology has offered nearly infinite opportunities to model all kinds of human diseases in vitro. Cardiomyocytes derived from hPSCs have proved to be efficient tools for cardiac disease modeling, drug screening and pathological mechanism studies. In this review, we discuss the advantages and limitations of 2D hPSC-cardiomyocyte (hPSC-CM) system, and introduce the recent development of three-dimensional (3D) culture platforms derived from hPSCs. Although the development of bioengineering technologies has greatly improved 3D platform construction, there are certainly challenges and room for development for further in-depth research.

Naturally occurring point mutations in the HBG promoter switch hemoglobin synthesis from defective adult beta-globin to fetal gamma-globin in sickle cell patients with hereditary persistence of fetal hemoglobin (HPFH) and ameliorate the clinical severity. Inspired by this natural phenomenon, we tiled the highly homologous HBG proximal promoters using adenine and cytosine base editors that avoid the generation of large deletions and identified novel regulatory regions including a cluster at the –123 region. Base editing at –123 and –124 bp of HBG promoter induced fetal hemoglobin (HbF) to a higher level than disruption of well-known BCL11A binding site in erythroblasts derived from human CD34+ hematopoietic stem and progenitor cells (HSPC). We further demonstrated in vitro that the introduction of –123T > C and –124T > C HPFH-like mutations drives gamma-globin expression by creating a de novo binding site for KLF1. Overall, our findings shed light on so far unknown regulatory elements within the HBG promoter and identified additional targets for therapeutic upregulation of fetal hemoglobin.

To study the perceived illness intrusion of continuous ambulatory peritoneal dialysis (CAPD) patients, to examine their demographics, and to find out the association among demographics, duration of illness as well as illness intrusion, 40 chronic kidney disease stage V patients on CAPD during 2006-2007 were studied. Inclusion criteria were patients′ above 18 years, willing, stable, and completed at least two months of dialysis. Those with psychiatric co-morbidity were excluded. Sociodemographics were collected using a semi-structured interview schedule. A 14-item illness intrusion checklist covering various aspects of life was administered. The subjects had to rate the illness intrusion in their daily life and the extent of intrusion. The data was analyzed using descriptive statistics and chi square test of association. The mean age of the subjects was 56.05 ± 10.05 years. There was near equal distribution of gender. 82.5% were married, 70.0% belonged to Hindu religion, 45.0% were pre-degree, 25.0% were employed, 37.5% were housewives and 30.0% had retired. 77.5% belonged to the upper socioeconomic strata, 95.0% were from an urban background and 65.0% were from nuclear families. The mean duration of dialysis was 19.0 ± 16.49 months. Fifty-eight percent of the respondents were performing the dialysis exchanges by themselves. More than 95.0%were on three or four exchanges per day. All the 40 subjects reported illness intrusion in their daily life. Intrusion was perceived to some extent in the following areas: health 47.5%, work 25.0%, finance 37.5%, diet 40.0%, and psychological 50.0%. Illness had not intruded in the areas of relationship with spouse 52.5%, sexual life 30.0%, with friends 92.5%, with family 85.5%, social functions 52.5%, and religious functions 75.0%. Statistically significant association was not noted between illness intrusion and other variables. CAPD patients perceived illness intrusion to some extent in their daily life. Elderly, educated married subjects were predominant. There was no statistically significant association between illness intrusion and other variables.

Organ transplantation is the most preferred treatment modality for patients with end-stage organ disease. There is an inadequate supply of cadaver organs commensurate with need. Health-care professionals are the critical link in augmenting public awareness about organ donation. Their attitudes and beliefs can influence the public opinion. This study aims at understanding the awareness, attitudes, and beliefs among the medical postgraduate students. A total of 123 post-graduates of a medical college hospital in South India participated in the study. A specially de-signed questionnaire was used in assessment. Data were statistically analyzed using SPSS Windows version 10.0. The mean age of the postgraduate students was 28.32 ± 3.5 years, 54% were males, 62% belonged to Christian religion, 69% were single, 77% were from nuclear families, 87% had urban background, and 54% were from upper socio-economic strata. About 97% said they were aware of organ donation through media, 23 unders-tood the concept of "cadaver" as "brain-death" and 93% were able to distinguish between brain-death and persistent vegetative state. Eighty-nine percent wished to donate their organs, 77% did not believe in body disfigurement and 87% did not believe in rebirth without the donated organs, if they pledged their organs. Sixty-nine percent were willing to donate the organs of their family members. Eighty percent were willing to receive organs from family and cadaver, 40% were willing to donate a child′s organs, 95% did not believe that organ donation is against their religion, 87% disagreed with the notion that doctors would not impart adequate care if they were pledged organ donors and 79% agreed that doctors would not declare death prematurely, if they had pledged their organs during life. There was a statis-tically significant correlation between attitudes, beliefs and demographics. In conclusion, the concept of brain-death was clearly understood by only a small number of medical postgraduate students. They how-ever, had positive attitudes and beliefs towards organ donation.

Dialysis therapy is extremely stressful as it interferes with all spheres of daily acti-vities of the patients. This study is aimed at understanding the perceived illness intrusion among pa-tients on hemodialysis (HD) and to find the association between illness intrusion and patient demo-graphics as well as duration of dialysis. A cross sectional study involving 90 patients with chronic kidney disease (CKD) stage V, on HD was performed during the period from 2005 to 2006. The subjects included were above 18 years of age, willing, stable and on dialysis for at least two months. Patients with psychiatric co-morbidity were excluded. A semi-structured interview schedule covering socio-demographics and a 13 item illness intrusion checklist covering the various aspects of life was ca-rried out. The study patients were asked to rate the illness intrusion and the extent. The data were ana-lyzed statistically. The mean age of the subjects was 50.28 ± 13.69 years, males were predominant (85%), 73% were married, 50% belonged to Hindu religion, 25% had pre-degree education, 25% were employed and 22% were housewives. About 40% and 38% of the study patients belonged to middle and upper socio-economic strata respectively; 86% had urban background and lived in nuclear fami-lies. The mean duration on dialysis was 24 ± 29.6 months. All the subjects reported illness intrusion to a lesser or greater extent in various areas including: health (44%), work (70%) finance (55%), diet (50%) sexual life (38%) and psychological status (25%). Illness had not intruded in areas of rela-tionship with spouse (67%), friends (76%), family (79%), social (40%) and religious functions (72%). Statistically significant association was noted between illness intrusion and occupation (P= 0.02).

Urinary tract infections (UTI) are the most common bacterial infections after renal transplantation and are associated with significant morbidity and mortality. Recurrent or relapsing infections are not uncommon in the early post-transplant period and superadded fungal UTI can occur in these patients, posing a difficult therapeutic problem. Literature on recurrent UTI after transplant as well as the ideal approach to such patients is scanty. We present the case of a renal al-lograft recipient who presented with relapsing bacterial UTI complicated by systemic fungemia; also, a brief review of fungal UTI is attempted.

The aim of this work is to propose a method to establish trust at bootload level in cloud computing environment. This work proposes a game theoretic based approach for achieving trust at bootload level of both resources and users perception. Nash equilibrium (NE) enhances the trust evaluation of the first-time users and providers. It also restricts the service providers and the users to violate service level agreement (SLA). Significantly, the problem of cold start and whitewashing issues are addressed by the proposed method. In addition appropriate mapping of cloud user’s application to cloud service provider for segregating trust level is achieved as a part of mapping. Thus, time complexity and space complexity are handled efficiently. Experiments were carried out to compare and contrast the performance of the conventional methods and the proposed method. Several metrics like execution time, accuracy, error identification, and undecidability of the resources were considered.