Nevin Manimala

J Mol Med (Berl). 2022 Mar 5. doi: 10.1007/s00109-022-02182-7. Online ahead of print.

ABSTRACT

SARS-CoV-2 has evolved to enter the host via the ACE2 receptor which is part of the kinin-kallikrein pathway. This complex pathway is only poorly understood in context of immune regulation but critical to control infection. This study examines SARS-CoV-2-infection and epithelial mechanisms of the kinin-kallikrein-system at the kinin B₂ receptor level in SARS-CoV-2-infection that is of direct translational relevance. From acute SARS-CoV-2-positive study participants and -negative controls, transcriptomes of nasal curettages were analyzed. Primary airway epithelial cells (NHBEs) were infected with SARS-CoV-2 and treated with the approved B₂R-antagonist icatibant. SARS-CoV-2 RNA RT-qPCR, cytotoxicity assays, plaque assays, and transcriptome analyses were performed. The treatment effect was further studied in a murine airway inflammation model in vivo. Here, we report a broad and strong upregulation of kallikreins and the kinin B₂ receptor (B₂R) in the nasal mucosa of acutely symptomatic SARS-CoV-2-positive study participants. A B₂R-antagonist impeded SARS-CoV-2 replication and spread in NHBEs, as determined in plaque assays on Vero-E6 cells. B₂R-antagonism reduced the expression of SARS-CoV-2 entry receptor ACE2, G protein-coupled receptor signaling, and ion transport in vitro and in a murine airway inflammation in vivo model. In summary, this study provides evidence that treatment with B₂R-antagonists protects airway epithelial cells from SARS-CoV-2 by inhibiting its replication and spread, through the reduction of ACE2 levels and the interference with several cellular signaling processes. Future clinical studies need to shed light on the airway protection potential of approved B₂R-antagonists, like icatibant, in the treatment of early-stage COVID-19. KEY MESSAGES: Induction of kinin B₂ receptor in the nose of SARS-CoV-2-positive patients. Treatment with B₂R-antagonist protects airway epithelial cells from SARS-CoV-2. B₂R-antagonist reduces ACE2 levels in vivo and ex vivo. Protection by B₂R-antagonist is mediated by inhibiting viral replication and spread.

PMID:35247068 | DOI:10.1007/s00109-022-02182-7

Mil Med. 2022 Mar 5:usac044. doi: 10.1093/milmed/usac044. Online ahead of print.

ABSTRACT

INTRODUCTION: To compare the clinical outcomes of bilateral labia minora hypertrophy reduction using ultrasonic shears versus traditional methods.

MATERIALS AND METHODS: In this retrospective study, we evaluate the surgical outcomes of 11 women who underwent bilateral labia minora hypertrophy reduction using ultrasonic shears to 14 women who underwent the same procedure using various traditional methods between January 1, 2015 and February 29, 2020 in a single center. The primary outcomes evaluated are total operative time, estimated blood loss, and postoperative pain. Secondary outcomes include postoperative complications and total admission time. The statistical analyses used were exact Wilconxon Rank and Fisher’s exact test.

RESULTS: 25 total bilateral labiaplasty procedures were included in the analysis. 11 procedures were performed using ultrasonic shears and 14 were performed using traditional methods. The mean reduction operative time for the ultrasonic shears technique when compared with traditional methods was 43.25 minutes (22.82 minutes versus 66.07 minutes, P = .0002). A statistically significant but non-clinically significant difference in estimated blood loss was noted. No statistically significant differences existed with postoperative pain score, total admission time, or postoperative complications.

CONCLUSIONS: Ultrasonic shears significantly reduce the time needed for the reduction of bilateral labia minora hypertrophy and therefore should be considered by surgeons as a useful tool in increasing the efficiency of this procedure.

PMID:35247056 | DOI:10.1093/milmed/usac044

Clin Infect Dis. 2022 Mar 5:ciac185. doi: 10.1093/cid/ciac185. Online ahead of print.

ABSTRACT

BACKGROUND: Undiagnosed asymptomatic subclinical tuberculosis (TB) remains a significant threat to global TB control and accounts for a substantial proportion of cases among people living with HIV/AIDS (PLWHA). We determined the incidence, progression, and outcomes of subclinical TB in anti-retroviral therapy (ART) accessing PLWHA with known previous TB in South Africa.

METHODS: A total of 402 adult PLWHA previously treated for TB were enrolled in the prospective CAPRISA TRuTH (TB Recurrence Upon TB and HIV treatment) study. Participants were screened for TB with quarterly clinical and bacteriologic evaluation and bi-annual chest radiographs over 36 months. Those with suspected or confirmed TB were referred to the National TB Programme. Participants received HIV services, including ART. Incidence rate of TB was estimated by Poisson regression, and descriptive statistical analyses summarised data.

RESULTS: A total of 48/402 (11.9%) bacteriologically confirmed incident recurrent TB cases was identified, comprising 17/48 (35.4%) subclinical TB cases and 31/48 (64.5%) clinical TB cases. Age, sex, and body mass index (BMI) were similar among subclinical , clinical , and no TB groups. Incidence rates of recurrent TB overall; in clinical TB; and subclinical TB groups was 2.3 [95% CI: 1.7-3.0]; 1.5 [95% CI: 1.1-2.2]; and 0.9 [95% CI: 0.5-1.4] per 100 person-years, respectively. In the subclinical TB group, 14/17 (82.4%) was diagnosed by TB culture only, 11/17 (64.7%) received TB treatment, and 6/17 (35.3%) resolved TB spontaneously.

CONCLUSION: The high incidence rates of recurrent subclinical TB in PLWHA highlight inadequacies of symptom-based TB screening in high TB-HIV burden settings.

PMID:35247054 | DOI:10.1093/cid/ciac185

Plant Cell Physiol. 2022 Mar 5:pcac010. doi: 10.1093/pcp/pcac010. Online ahead of print.

ABSTRACT

Identifying the early predictive biomarkers or compounds represents a pivotal task for guiding a targeted agricultural practice. Despite the various available tools, it remains challenging to define the ideal compound combination and thereby elaborate an effective predictive model fitting that. Hence, we employed a stepwise feature selection approach followed by a maximum relevance and minimum redundancy (MRMR) on the untargeted metabolism in four mulberry genotypes at different fruit developmental stages (FDSs). Thus, we revealed that 7 out of 226 differentially abundant metabolites (DAMs) explained up to 80% variance of anthocyanin based on linear regression model and stepwise feature selection approach accompanied by an MRMR across the genotypes over the FDSs. Among them, the phosphoenolpyruvate, d-mannose and shikimate show the top 3 attribution indexes to the accumulation of anthocyanin in the fruits of these genotypes across the four FDSs. The obtained results were further validated by assessing the regulatory genes expression levels and the targeted metabolism approach. Taken together, our findings provide valuable evidences on the fact that the anthocyanin biosynthesis is somehow involved in the coordination between the carbon metabolism and secondary metabolic pathway. Our report highlights as well the importance of using the feature selection approach for the predictive biomarker identification issued from the untargeted metabolomics data.

PMID:35247053 | DOI:10.1093/pcp/pcac010

JMIR Res Protoc. 2022 Mar 5. doi: 10.2196/36928. Online ahead of print.

ABSTRACT

BACKGROUND: The world as we know it changed during the Covid-19 pandemic. Hope has emerged with the development of new vaccines against the disease. However, many factors hinder vaccine uptake and lead to vaccine hesitancy. Understanding the factors affecting vaccine hesitancy and how to assess its prevalence has become an imperative amidst the Covid-19 pandemic. The vaccine hesitancy scale (VHS), developed by the WHO Strategic Advisory Group of Experts on Immunization (SAGE), has been modified to the adult VHS (aVHS) and validated in English and Chinese. To our knowledge, no available aVHS have been designed or validated in Arabic or French.

OBJECTIVE: This research aim is to translate the aVHS from its original English language to Arabic and French and validate the translations in the WHO Eastern Mediterranean region.

METHODS: The study will follow a cross-sectional design divided into five phases inspired by the methodology proposed in the “Guidelines for developing, translating, and validating a questionnaire in perioperative and pain medicine.” By Tsang et al. Phase 1-The original aVHS will be forward translated to Arabic and French followed by backward translation to English. An expert committee will review and rate all versions of the translations. Expert agreement will then be measured using Cohen’s coefficient Kappa(K). Phase 2-The translated aVHS will be pilot tested on two samples of participants; a group that speaks both Arabic and English and another that speaks French and English, N=100. Participants’ responses to the English version will also be collected. Phase 3-Responses will then be compared. Descriptive statistics and paired t-test or one-way ANOVA and Pearson’s correlation coefficient (Rho) will be used in preliminary validation. Phase 4-Pre-final versions (Arabic and French) will be tested on a larger sample size, N=1000 for Arabic speakers and N=1000 for French speakers. Socio-demographic information and vaccination status will be collected and used for further analysis. Phase 5-The scale’s statistical reliability and internal consistency will be measured using Cronbach’s alpha. An Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) will be used to examine model fit resulting from EFA. ANOVA analyses and/or regression models will be constructed to control for confounders. All data will be electronically collected.

RESULTS: As of January 2022, the scale has been translated to Arabic and French and is undergoing the process of back translation. All data collection tools have been prepared (i.e., Socio-demographics, vaccination status and open-ended questions) and are ready to go into their electronic formats. We expect to reach the desired sample size in this phase by June 2022.

CONCLUSIONS: This study will provide researchers with a validated tool to assess adult vaccine hesitancy within populations that speak Arabic and/or French and provide a roadmap to scale translation and ensure cross-cultural adaptation.

PMID:35247043 | DOI:10.2196/36928

Anim Sci J. 2022 Jan;93(1):e13698. doi: 10.1111/asj.13698.

ABSTRACT

The Kumamoto sub-breed of Japanese Brown cattle has unique characteristics, such as great growth rate, and their contribution as future breeding materials is expected. To develop a DNA marker for their breeding, we investigated the effects of Leptin gene, controlling energy homeostasis, on carcass traits of the Kumamoto sub-breed. Sequence comparison identified five single nucleotide polymorphisms (SNPs): four linked synonymous mutations and one nonsynonymous mutation. Statistical analysis revealed that c.239C > T (p.A80V) had significant effects on the traits related with quality grade: beef marbling standard (p = 0.0132), meat brightness (p = 0.0383), and meat firmness (p = 0.0115). The C allele showed favorable effects; these scores of the C/C cattle were significantly higher than those of the C/T cattle. On the other hand, the effect of c.399T > C was observed on meat firmness (p = 0.0172) and beef fat standards (BFS) (p = 0.0129). The C/C cattle showed higher values of these traits than the T/T cattle. Our data suggested that these SNPs in Leptin gene could be used as a DNA marker for breeding of the Kumamoto sub-breed.

PMID:35247014 | DOI:10.1111/asj.13698

J Clin Pharm Ther. 2022 Mar 5. doi: 10.1111/jcpt.13637. Online ahead of print.

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: The Helicobacter pylori (H. pylori) eradication rate of proton pump inhibitor (PPI)-based regimen remains decreasing. Vonoprazan (VPZ), a stronger and longer-lasting acid blocker, has been proposed to treatment of H. pylori infection. However, previous reviews did not have a pre-established study protocol and did not conduct a comprehensive search of the database, so the results obtained were not robust. We aimed to perform a meta-analysis to assess the effectiveness and safety of VPZ-based regimens for treatment of H. pylori infection in comparison with other regimens.

METHODS: We conducted a systematic literature search on PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials and ChiCTR Register. Randomized clinical trials comparing VPZ-based regimens with similar eradication regimens without VPZ in the treatment of H. pylori infection were included. Eradication rate, compliance of the patients and side effects were specified as the primary outcomes. RevMan 5.4 software was used to analyze the RCTs and provide pooled risk ratio (RR) with 95% confidence intervals (CI). Systematic searches, study selection, data extraction, risk of bias assessment and statistical analysis were performed by two independent researchers according to the predesigned criteria on the PROSPERO.

RESULTS AND DISCUSSION: A total of 8 RCTs with 2012 patients qualified for evaluation. The results showed that the eradication rate of VPZ-containing regimens was significantly superior to PPI-containing regimens for both intention-to-treat (RR, 1.14; 95% CI: 1.06-1.23; p = 0.0006) and per-protocol analyses (RR, 1.12; 95% CI: 1.04-1.20; p = 0.003). Subgroup analysis based on treatment regimens, eradication experience and clarithromycin resistance, as well as sensitivity analysis further confirmed this finding. In addition, there was no significant difference in compliance (RR, 1.02; 95% CI: 0.98-0.1.05; p = 0.35) and the frequency of adverse events (RR, 0.84; 95% CI: 0.70-1.00; p = 0.05) between the regimens.

WHAT IS NEW AND CONCLUSION: Compared with PPI-based regimens, the VPZ-containing regimens showed a comparable or even superior eradication rate of H. pylori in terms of overall comparison and comparison of different treatment regimens, eradication experience and clarithromycin resistance. In addition, VPZ-based regimens have better tolerability and fewer adverse events. More future studies are needed to evaluate the impact of some differences in patient characteristics.

TRIAL REGISTRATION: PROSPERO CRD42021229598.

PMID:35247003 | DOI:10.1111/jcpt.13637

J Cosmet Dermatol. 2022 Mar 5. doi: 10.1111/jocd.14897. Online ahead of print.

ABSTRACT

Aging is an inevitable process. Eyebrows, cheeks, mandible and neck are the areas that are the most vulnerable to the aging process. The most commonly thread lifted areas of the face are the jawline, midface, eyebrows and the neck. In this retrospective study, patients who were treated with thread-lifting between January 2018 and April 2020 were evaluated and the following were noted: the age and gender of the patient; the type of thread used; number of threads used; treatment area; patient satisfaction; and complications. The effects of age, type of thread used, number of threads used and treatment area on patient satisfaction were analysed statistically.The relationship between age and patient satisfaction is statistically insignificant, p=0.697. The relationship between patient satisfaction and the type of the thread used was insignificant, p=0.533. There is no relationship between the number of threads used and patient satisfaction, p=0.783. There is no difference in patient satisfaction between treatment areas, p=0.930. The most commonly observed complications were edema, pain and ecchymosis. We report that the patient satisfaction in thread-lifting is independent of the patient’s age, treatment area, type of thread used and the number of threads used. Our study is novel since it is the first study to report that the age of the patient and the thread type do not effect patient satisfaction.

PMID:35246938 | DOI:10.1111/jocd.14897

Int J Ment Health Nurs. 2022 Mar 4. doi: 10.1111/inm.12987. Online ahead of print.

ABSTRACT

Clinical learning experiences are known to exacerbate nursing student anxiety, causing them to present to clinical placement in distressed, meaning anxious, states. Students already living with anxiety are also more likely to suffer setbacks at this time. Supervising Registered Nurses (RNs), in the clinical settings, struggle to support this student cohort. A professional development activity was designed to introduce RNs to higher education and nursing students’ known mental health concerns (such as anxiety) and to arm them with strategies for working with distressed students. A research approach that enabled researchers to collaborate with participants was employed to design the intervention. A study evaluated the impact of the educational intervention with 45 Australian RN supervisors. Two tailed T-tests were chosen to explore the statistical difference between pre- and post-test mean results across the survey items. A 95% confidence interval was used. Statistical significance was set at <0.05. The evaluation indicated the activity could be useful for improving supervising RNs’ mental health literacy, thus enhancing their understanding of how to work with distressed students. Participants recommended the activity be offered to any staff supporting student clinical learning. Collaboration between nursing researchers and nursing clinical staff produced a meaningful professional development activity and motivated the participants to increase their mental health literacy and understanding of strategies to support distressed students. Future projects should adopt similar approaches that would support both RNs’ ability to support students’ during clinical learning and students in distress would also benefit.

PMID:35246903 | DOI:10.1111/inm.12987

J Nurs Manag. 2022 Mar 4. doi: 10.1111/jonm.13575. Online ahead of print.

ABSTRACT

AIMS: To analyse the prevalence and levels of burnout syndrome in nurse managers and to evaluate the relationship between burnout and related sociodemographic, occupational and psychological factors.

BACKGROUND: Burnout syndrome, defined as an emotional response to chronic stress, is a major problem among nurse managers.

METHODS: The study was conducted using a cross-sectional survey design and data collected by the Maslach Burnout Inventory, The revised NEO Five Factor Inventory and the Educational-Clinical Questionnaire for Anxiety and Depression. The sample population consisted of 86 nurse managers from different hospitals from the Public Health Service of Andalusia, Spain.

RESULTS: 22.4% of the participants presented high levels of emotional exhaustion, 21% experienced depersonalisation and 57.6% had little sense of personal accomplishment. Working long shifts was related to burnout. Emotional exhaustion and depersonalisation were predicted by depression, while personal accomplishment was predicted by conscientiousness, agreeableness and openness.

CONCLUSIONS: 34.1% of the participants presented high levels of burnout, manifested by feelings of low personal accomplishment. Psychological and occupational factors play an important role in the development of this syndrome.

IMPLICATIONS FOR NURSING MANAGEMENT: nurse managers should seek to detect burnout among staff and colleagues matching the risk profile for this condition and promote interventions to prevent it.

PMID:35246900 | DOI:10.1111/jonm.13575