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Cellular Immune Response after Vaccination with an Adjuvanted, Recombinant Zoster Vaccine in Allogeneic Hematopoietic Stem Cell Transplant Recipients
Hematopoietic stem cell transplant (HSCT) recipients have a high risk of developing primary varicella-zoster virus (VZV) infection and reactivation. VZV vaccination may prevent infection and reactivation. In the current study, recipients of allogeneic HSCT (34 females, 45 males) were vaccinated with adjuvanted, recombinant zoster vaccine Shingrix™, which contains the VZV glycoprotein E. Cellular immunity against various VZV antigens was analyzed by interferon-gamma ELISpot. Peripheral blood mononuclear cells (PBMC) of recipients with versus without prior shingles (n = 36 and n = 43, respectively) showed approximately twofold higher VZV-specific responses prior to and post vaccination. After the first and second vaccination, ELISpot responses towards the glycoprotein E were significantly higher in males versus females (median of spots increment 18 versus 1 and 17 versus 4, respectively, p ≤ 0.02 each). Multivariate analysis showed that shingles and sex both impacts significantly on VZV immunity. Whereas vaccination-induced changes could hardly be detected after stimulation with a whole VZV antigen, there was a significant increase in responses towards glycoprotein E after vaccination (p < 0.005). These data indicate that vaccination with Shingrix™ augmented cellular, VZV-specific immunity in HSCT recipients. Shingles and male sex could both be identified as factors leading to increased immunit
Effect of Sleep Intervention Programs during Cardiac Rehabilitation on the Sleep Quality of Heart Patients
ackground and Objective. Patients with cardiovascular problems experience sleep disorders. Due to the importance of adequate sleep and rest for the growth and repair of damaged cells, it is necessary to use appropriate interventions to improve it. This study determined the effect of sleep intervention programs during cardiac rehabilitation on patients’ sleep quality. Materials and Methods. In this quasi-experimental study with unequal control group design, 35 individuals participated in the cardiac rehabilitation program as the experimental group and 35 served as the control group. The program included 12 weeks of exercise, 3 sessions per week, 3 sessions of training programs each lasting for 45 minutes, and a special two-session sleep improvement program. Data were collected using the Pittsburgh Sleep Quality Index and analysed with descriptive and inferential statistical methods. Results. There were not any significant differences between the two groups in age, sex, marital status, smoking, and indication for cardiac rehabilitation (). The scores of sleep quality of patients were before and after intervention in the experimental group and before and after intervention in the control group. There was no significant difference between the two groups before intervention (). yet there was a significant difference after intervention (). In addition, scores of sleep quality of patients were significantly different in the experimental and control groups before and after intervention (). Conclusion. Findings indicated that the quality of sleep of cardiac patients improved after the sleep intervention program during the cardiac rehabilitation program. Therefore, it is suggested to implement sleep improvement programs for cardiac patient care as an effective, easy, and feasible technique. In addition, it is necessary to pay more attention to the sleep improvement program in cardiac rehabilitation. Trial Registration. The trial was retrospectively registered on https://en.irct.ir/trial/50799 on 14 September 2020 (14.09.2020) with registration number IRCT20140307016870N6
Report on the 9th National Congress AICPE (Associazione Italiana di Chirurgia Plastica Estetica) Held in Sorrento, Italy, 22–24 April 2022
The annual congress of the Italian Association of Plastic Aesthetic Surgery (AICPE) is one of the most relevant conference meetings in Europe concerning aesthetic plastic surgery due to the number of participants and as parterre of invited speakers chosen for their renowned scientific valu
Confluent Small Bowel Lipomatosis: A Rare Cause of Recurrent Abdominal Pain
Small intestine lipomatosis is rare but may be associated with pain, intussusception, and gastrointestinal bleeding. In this report, we examine the case of a 41-year-old man who had recurrent presentations to the emergency department with non-specific abdominal pain. Preoperative imaging suggested extensive infiltration of small intestine with macroscopic fat. At surgery, extensive and confluent small bowel lipomatosis were seen. The affected ileal segment was resected, and the patient remained symptom-free after surgery. Abdominal lipomatosis is a rare condition which can be completely treated by resection of the affected gut segment but is often unsuspected and difficult to diagnose. In this report, we describe a case with the most extensive lipomatosis on record with more than 70 cm of gut with confluent lipomatosis. Magnetic resonance Enterography (MRE) is a useful non-invasive diagnostic modality, although laparoscopy/laparotomy may be necessary for assessment of the extent of disease. Symptomatic cases should be treated with segmental small bowel resection, which is curative.
Determinants of the Hesitancy toward COVID-19 Vaccination in Eastern European Countries and the Relationship with Health and Vaccine Literacy: A Literature Review
Herd immunity is necessary to control the coronavirus disease 2019 (COVID-19) pandemic. However, a low proportion of vaccinated people and low levels of vaccine acceptance have been noted in Eastern Europe. Our paper aimed to review the central attitudes associated with the hesitancy toward COVID-19 vaccination specific to Eastern European countries. The main Eastern European determinants of COVID-19 vaccine acceptance identified from the included studies are: public confidence in the vaccines’ safety and efficacy, vaccine literacy, and public trust in the government and the medical system. Each of these determinants is discussed along with possible improvement measures. Variables specific to Eastern Europe that predict the willingness to vaccinate have also been highlighted. The specific attitudes and their context as identified by our review should be incorporated into local public health programs, with the ultimate goal of reducing viral spreading, mutation emergence, and COVID-19 morbidity and mortality both within the borders of Eastern Europe and beyon
Pleiotropic constraints promote the evolution of cooperation in cellular groups
The evolution of cooperation in cellular groups is threatened by lineages of cheaters that proliferate at the expense of the group. These cell lineages occur within microbial communities, and multicellular organisms in the form of tumours and cancer. In contrast to an earlier study, here we show how the evolution of pleiotropic genetic architectures—which link the expression of cooperative and private traits—can protect against cheater lineages and allow cooperation to evolve. We develop an age-structured model of cellular groups and show that cooperation breaks down more slowly within groups that tie expression to a private trait than in groups that do not. We then show that this results in group selection for pleiotropy, which strongly promotes cooperation by limiting the emergence of cheater lineages. These results predict that pleiotropy will rapidly evolve, so long as groups persist long enough for cheater lineages to threaten cooperation. Our results hold when pleiotropic links can be undermined by mutations, when pleiotropy is itself costly, and in mixed-genotype groups such as those that occur in microbes. Finally, we consider features of multicellular organisms—a germ line and delayed reproductive maturity—and show that pleiotropy is again predicted to be important for maintaining cooperation. The study of cancer in multicellular organisms provides the best evidence for pleiotropic constraints, where abberant cell proliferation is linked to apoptosis, senescence, and terminal differentiation. Alongside development from a single cell, we propose that the evolution of pleiotropic constraints has been critical for cooperation in many cellular groups
Risk factors associated with SARS-CoV-2 infection in a multiethnic cohort of United Kingdom healthcare workers (UK-REACH): A cross-sectional analysis
Healthcare workers (HCWs), particularly those from ethnic minority groups, have been shown to be at disproportionately higher risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) compared to the general population. However, there is insufficient evidence on how demographic and occupational factors influence infection risk among ethnic minority HCWs.
Methods and findings
We conducted a cross-sectional analysis using data from the baseline questionnaire of the United Kingdom Research study into Ethnicity and Coronavirus Disease 2019 (COVID-19) Outcomes in Healthcare workers (UK-REACH) cohort study, administered between December 2020 and March 2021. We used logistic regression to examine associations of demographic, household, and occupational risk factors with SARS-CoV-2 infection (defined by polymerase chain reaction (PCR), serology, or suspected COVID-19) in a diverse group of HCWs. The primary exposure of interest was self-reported ethnicity.
Among 10,772 HCWs who worked during the first UK national lockdown in March 2020, the median age was 45 (interquartile range [IQR] 35 to 54), 75.1% were female and 29.6% were from ethnic minority groups. A total of 2,496 (23.2%) reported previous SARS-CoV-2 infection. The fully adjusted model contained the following dependent variables: demographic factors (age, sex, ethnicity, migration status, deprivation, religiosity), household factors (living with key workers, shared spaces in accommodation, number of people in household), health factors (presence/absence of diabetes or immunosuppression, smoking history, shielding status, SARS-CoV-2 vaccination status), the extent of social mixing outside of the household, and occupational factors (job role, the area in which a participant worked, use of public transport to work, exposure to confirmed suspected COVID-19 patients, personal protective equipment [PPE] access, aerosol generating procedure exposure, night shift pattern, and the UK region of workplace). After adjustment, demographic and household factors associated with increased odds of infection included younger age, living with other key workers, and higher religiosity. Important occupational risk factors associated with increased odds of infection included attending to a higher number of COVID-19 positive patients (aOR 2.59, 95% CI 2.11 to 3.18 for ≥21 patients per week versus none), working in a nursing or midwifery role (1.30, 1.11 to 1.53, compared to doctors), reporting a lack of access to PPE (1.29, 1.17 to 1.43), and working in an ambulance (2.00, 1.56 to 2.58) or hospital inpatient setting (1.55, 1.38 to 1.75). Those who worked in intensive care units were less likely to have been infected (0.76, 0.64 to 0.92) than those who did not. Black HCWs were more likely to have been infected than their White colleagues, an effect which attenuated after adjustment for other known risk factors. This study is limited by self-selection bias and the cross sectional nature of the study means we cannot infer the direction of causality
Blind demixing methods for recovering dense neuronal morphology from barcode imaging data
Cellular barcoding methods offer the exciting possibility of ‘infinite-pseudocolor’ anatomical reconstruction—i.e., assigning each neuron its own random unique barcoded ‘pseudocolor,’ and then using these pseudocolors to trace the microanatomy of each neuron. Here we use simulations, based on densely-reconstructed electron microscopy microanatomy, with signal structure matched to real barcoding data, to quantify the feasibility of this procedure. We develop a new blind demixing approach to recover the barcodes that label each neuron, and validate this method on real data with known barcodes. We also develop a neural network which uses the recovered barcodes to reconstruct the neuronal morphology from the observed fluorescence imaging data, ‘connecting the dots’ between discontiguous barcode amplicon signals. We find that accurate recovery should be feasible, provided that the barcode signal density is sufficiently high. This study suggests the possibility of mapping the morphology and projection pattern of many individual neurons simultaneously, at high resolution and at large scale, via conventional light microscopy.
Author summary
In situ barcode sequencing allows us to simultaneously locate many neurons in intact brain tissues, albeit at modest spatial resolution. By increasing the barcode density, high-resolution neuronal morphology reconstruction from such data might be possible. Here we use simulations to study this possibility, while addressing the computational challenges in analyzing such data. We developed a novel blind demixing method that uses fluorescent images and identifies the unknown barcodes used to label the neurons with high accuracy. Further, we developed a neural network which can reconstruct the morphology for these labeled neurons from the observed ‘pointilistic’ imaging data. We show that under both high- and low-resolution optical settings, our methods can successfully extract the morphologies for many labeled neurons. The results from this theoretical study suggest that it may be feasible to map the morphology and projection pattern of many individual neurons simultaneously, at high resolution and at large scale, via conventional light microscopy
Effectiveness of GnRH Antagonists and Agonists in Patients with Hormone-Sensitive Prostate Cancer: A Retrospective Study
Objective. To assess the effectiveness of gonadotropin-releasing hormone (GnRH) antagonists and agonists in the treatment of patients with hormone-sensitive prostate cancer (HSPC), thus providing valid data support for their clinical treatment. Methods. We collected 52 and 65 HSPC patients treated with GnRH antagonists and agonists, respectively, in Tongji Hospital, Tongji Medical College of HUST between May 2019 and April 2021. Prostate-specific antigen (PSA) levels before and after treatment were recorded and analyzed. Further, univariate and multivariate logistic regressions were used to analyze the influencing factors of PSA control rate in HSPC patients. Results. In patients receiving antagonist, the control rate of prostate-specific antigen (PSA) was 54.28% and 88% without and with abiraterone, respectively, and 47.91% and 72% in patients treated using agonist without and with abiraterone. In 32 pairs of patients obtained via propensity score matching, the PSA control rates were 84.38% and 53.13% for those receiving antagonists and agonists, respectively, and 66.67% and 50% for those without abiraterone, respectively. In addition, univariate logistic regression analysis showed that the type of androgen deprivation therapy (ADT) drugs and combined use of abiraterone had a significant effect on the control rate of PSA. Further multivariate logistic regression revealed that GnRH antagonists in ADT drugs were risk factors for PSA control rate. Conclusion. The PSA control rate of HSPC patients treated with GnRH antagonist is significantly higher than that of the agonist group, and the use of GnRH antagonist is an independent predictor of PSA control rate
Comparative molecular genomic analyses of a spontaneous rhesus macaque model of mismatch repair-deficient colorectal cancer
Colorectal cancer (CRC) remains the third most common cancer in the US with 15% of cases displaying Microsatellite Instability (MSI) secondary to Lynch Syndrome (LS) or somatic hypermethylation of the MLH1 promoter. A cohort of rhesus macaques from our institution developed spontaneous mismatch repair deficient (MMRd) CRC with a notable fraction harboring a pathogenic germline mutation in MLH1 (c.1029C<G, p.Tyr343Ter). Our study aimed to provide a detailed molecular characterization of rhesus CRC for cross-comparison with human MMRd CRC. We performed PCR-based MSI testing (n = 41), transcriptomics analysis (n = 35), reduced-representation bisulfite sequencing (RRBS) (n = 28), and MLH1 DNA methylation (n = 10) using next-generation sequencing (NGS) of rhesus CRC. Systems biology tools were used to perform gene set enrichment analysis (GSEA) for pathway discovery, consensus molecular subtyping (CMS), and somatic mutation profiling. Overall, the majority of rhesus tumors displayed high levels of MSI (MSI-H) and differential gene expression profiles that were consistent with known deregulated pathways in human CRC. DNA methylation analysis exposed differentially methylated patterns among MSI-H, MSI-L (MSI-low)/MSS (MS-stable) and LS tumors with MLH1 predominantly inactivated among sporadic MSI-H CRCs. The findings from this study support the use of rhesus macaques as an alternative animal model to mice to study carcinogenesis, develop immunotherapies and vaccines, and implement chemoprevention approaches relevant to sporadic MSI-H and LS CRC in humans