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Background The development of cytomegalovirus (CMV) infection after kidney transplant remains a significant cause of posttransplant morbidity, graft loss, and mortality. Despite appropriate antiviral therapy, recipients without previous CMV exposure can currently be allocated a kidney from a donor with previous CMV infection (D+R-) which carries the greatest risk of posttransplant CMV infection and associated complications. Preferential placement of CMV D- organs in negative recipients (R-) has been shown to reduce the risk of viral infection and associated complications. Methods To assess the long-term survival and economic benefits of allocation policy reforms, a decision analytic model was constructed to compare receipt of CMV D- with CMV D+ organ in CMV R- recipients using data from transplant registry, Medicare claims, and pharmaceutical costs. Results For CMV R- patients, receipt of a CMV D- organ was associated with greater average survival (14.3 vs 12.6 years), superior quality-adjusted life years (12.6 vs 9.8), and lower costs ($529 512 vs $542 963). One-way sensitivity analysis demonstrated a survival advantage for patients waiting as long as 30 months for a CMV D- kidney. Conclusions Altering national allocation policy to preferentially offer CMV D- organs to CMV R- recipients could improve survival and lower costs after transplant if appropriately implemented.

Both congestive heart failure (HF) and atrial fibrillation (AF) are important and increasingly common forms of cardiovascular disease in the 21st century. Heart failure is often complicated by AF, and AF can exacerbate and, in some cases, cause HF, also known as tachycardia-induced cardiomyopathy (TIC). Restoration and maintenance of sinus rhythm in the majority of AF patients with TIC can lead to an improvement in left ventricular function and dramatic symptomatic relief. This can be accomplished by surgical ablation; specifically, the Cox-Maze IV procedure (CMP IV), in those refractory to medical and catheter-based ablation, and those patients undergoing concomitant cardiac operation. However, many surgeons are reluctant to perform stand-alone or concomitant CMP IV in this high-risk cohort of patients. In this review, the over three decades of experience with surgical ablation will be reviewed along with the essential information that surgeons need to be aware of as they participate in the team-based care of patients with AF and HF.

Endovascular stenting of the ascending aorta has been described for various aortic pathologies, including type A dissection in patients who are prohibitive risk for open surgery. Endovascular treatment of ascending aortic pathology poses unique anatomic and technical challenges related to aortic morphology. Herein, we present a novel technique of endovascular ascending stent graft delivery from a transfemoral approach for treatment of an acute type A dissection, utilizing a snare-guided deployment technique to facilitate favorable device deployment.

Amaç: Yenidoğan sarılığı, yenidoğan bebeklerin cilt ve skleralarının sarımsı bir renk alması ve serum bilirubin düzeylerinin yükselmesi ile karakterizedir.Bu çalışmada Irak'ın Diyala ilindeki primigravidlerin yenidoğan sarılığı ile ilgili bilgi, uygulama ve tutumlarının değerlendirilmesi amaçlanmıştır.Gereç ve Yöntemler: 1 Ocak 2022-31 Mart 2022 tarihleri arasında hastane ve sağlık ocaklarında primigravid 165 kadına yenidoğan sarılığı ile ilgili bilgi, uygulama ve tutumlarını değerlendirmek için anket uygulandı.Bulgular: Kadınların %71.4'ü yenidoğan sarılığının iki belirtisini bilse de %78.8'i yenidoğan sarılığının tehlikeli belirtilerinden hiçbirini bilmiyordu. Kadınların %28.4'ü yenidoğan sarılığının tedavisi için iki etkili tedavi yöntemi olduğunu biliyordu. Kadınların %57.6'sı yenidoğan sarılığının ciddi komplikasyonlarından habersizdi.Sonuç: Bu çalışmadaki primigravidlerin çoğu, bebekleri sarılık olduğunda geleneksel tedaviyi kullanmadan doktorları ziyaret etmeye karar verdi., Objective: Neonatal jaundice is characterized by a yellowish coloration of the skin and sclera of newborn infants and elevated serum bilirubin levels.In this study, it was aimed to evaluate the knowledge, practices and attitudes of primigravidas in Diyala province of Iraq regarding neonatal jaundice.Material and Methods: A questionnaire was applied to 165 women who were primigravidas between January 1, 2022 and March 31, 2022 in hospitals and health centers to evaluate their knowledge, practices and attitudes about neonatal jaundice.Results: Although 71.4% of the women knew the two signs of neonatal jaundice, 78.8% of them did not know any of the dangerous signs of neonatal jaundice. 28.4% of women knew that there are two effective treatment methods for the treatment of neonatal jaundice. 57.6% of the women were not aware of any of the severe complications of neonatal jaundice.Conclusion: Most of the primigravida in this study decided to visit physicians when their babies have jaundice without using traditional treatment.

General life stress and HIV-related stress have been independently associated with negative mental health outcomes for people living with HIV (PLWH), including anxiety and depression. HIV-positive sexual minority men (SMM) may experience both forms of stress, resulting in concurrent effects that independently exacerbate functional impairment related to anxiety and depression. This study examined general life stress, HIV-related stress, and functional impairment due to depression and anxiety in a sample of 87 HIV-positive SMM. Data were collected in late 2015 and early 2016. The Perceived Stress Scale (PSS), HIV/AIDS Stress Scale (HASS), Overall Anxiety Severity and Impairment Scale, and Overall Depression Severity and Impairment Scale were used. Each variable was positively correlated with each other in bivariate analyses, but in multivariable models, PSS (β = .53, p

Aim Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disease that typically manifests with cardiac arrhythmias, progressive heart failure and sudden cardiac death (SCD). ACM is mainly caused by mutations in genes encoding desmosome proteins. Desmosomes are cell-cell adhesion structures and hubs for mechanosensing and mechanotransduction. The objective was to identify the dysregulated molecular and biological pathways in human ACM in the absence of overt heart failure. Methods and results Transcriptomes in the right ventricular endomyocardial biopsy samples from three independent individuals carrying truncating mutations in the DSP gene and 5 control samples were analyzed by RNA-Seq (discovery group). These cases presented with cardiac arrhythmias and had a normal right ventricular function. The RNA-Seq analysis identified ∼5,000 differentially expressed genes (DEGs), which predicted suppression of the Hippo and canonical WNT pathways, among others.Dysregulated genes and pathways, identified by RNA-Seq, were tested for validation in the right and left ventricular tissues from 5 independent autopsy-confirmed ACM cases with defined mutations (validation group), who were victims of SCD and had no history of heart failure. Protein levels and nuclear localization of the cWNT and Hippo pathway transcriptional regulators were reduced in the right and left ventricular validation samples. In contrast, levels of acetyltransferase EP300, known to suppress the Hippo and canonical WNT pathways, were increased and its bona fide target TP53 was acetylated. RNA-Seq data identified apical junction, reflective of cell-cell attachment, as the most disrupted biological pathway, which was corroborated by disrupted desmosomes and intermediate filament structures. Moreover, the DEGs also predicted dysregulation of over a dozen canonical signal transduction pathways, including the Tec kinase and integrin signaling pathways. The changes were associated with increased apoptosis and fibro-adipogenesis in the ACM hearts. Conclusion Altered apical junction structures is associated with activation of the EP300-TP53 and suppression of the Hippo/cWNT pathways in human ACM caused by defined mutations in the absence of an overt heart failure. The findings implicate altered mechanotransduction in the pathogenesis of ACM. Translational perspective The findings suggest that altered mechanosensing at the cell-cell junction instigates a cascade of molecular events through the activation of acetyltransferase EP300/TP53 and suppression of gene expression through the Hippo/canonical WNT pathways in human arrhythmogenic cardiomyopathy (ACM) caused by defined mutations. These molecular changes occur early and in the absence of overt heart failure. Consequently, one may envision cell type-specific interventions to target the dysregulated transcriptional, mechanosensing, and mechanotransduction pathways to prevent the evolving phenotype in human ACM.

Background: Arrhythmogenic cardiomyopathy (ACM) manifests with sudden death, arrhythmias, heart failure, apoptosis, and myocardial fibro-adipogenesis. The phenotype typically starts at the epicardium and advances transmurally. Mutations in genes encoding desmosome proteins, including DSP (desmoplakin), are major causes of ACM. Methods: To delineate contributions of the epicardium to the pathogenesis of ACM, the Dsp allele was conditionally deleted in the epicardial cells in mice upon expression of tamoxifen-inducible Cre from the Wt1 locus. Wild type (WT) and Wt1-Cre ERT2 :Dsp W/F were crossed to Rosa26 mT/mG (R26 mT/mG ) dual reporter mice to tag the epicardial-derived cells with the EGFP (enhanced green fluorescent protein) reporter protein. Tagged epicardial-derived cells from adult Wt1-Cre ERT2 :R26 mT/mG and Wt1-Cre ERT2 : R26 mT/mG :Dsp W/F mouse hearts were isolated by fluorescence-activated cell staining and sequenced by single-cell RNA sequencing. Results: WT1 (Wilms tumor 1) expression was progressively restricted postnatally and was exclusive to the epicardium by postnatal day 21. Expression of Dsp was reduced in the epicardial cells but not in cardiac myocytes in the Wt1-Cre ERT2 :Dsp W/F mice. The Wt1-Cre ERT2 :Dsp W/F mice exhibited premature death, cardiac dysfunction, arrhythmias, myocardial fibro-adipogenesis, and apoptosis. Single-cell RNA sequencing of ≈18 000 EGFP-tagged epicardial-derived cells identified genotype-independent clusters of endothelial cells, fibroblasts, epithelial cells, and a very small cluster of cardiac myocytes, which were confirmed on coimmunofluorescence staining of the myocardial sections. Differentially expressed genes between the paired clusters in the 2 genotypes predicted activation of the inflammatory and mitotic pathways—including the TGFβ1 (transforming growth factor β1) and fibroblast growth factors—in the epicardial-derived fibroblast and epithelial clusters, but predicted their suppression in the endothelial cell cluster. The findings were corroborated by analysis of gene expression in the pooled RNA-sequencing data, which identified predominant dysregulation of genes involved in epithelial–mesenchymal transition, and dysregulation of 146 genes encoding the secreted proteins (secretome), including genes in the TGFβ1 pathway. Activation of the TGFβ1 and its colocalization with fibrosis in the Wt1-Cre ERT2 :R26 mT/mG :Dsp W/F mouse heart was validated by complementary methods. Conclusions: Epicardial-derived cardiac fibroblasts and epithelial cells express paracrine factors, including TGFβ1 and fibroblast growth factors, which mediate epithelial–mesenchymal transition, and contribute to the pathogenesis of myocardial fibrosis, apoptosis, arrhythmias, and cardiac dysfunction in a mouse model of ACM. The findings uncover contributions of the epicardial-derived cells to the pathogenesis of ACM.

Hypertrophic cardiomyopathy (HCM) is a genetic disease of the myocardium characterized by a hypertrophic left ventricle with a preserved or increased ejection fraction. Cardiac hypertrophy is often asymmetrical, which is associated with left ventricular outflow tract obstruction. Myocyte hypertrophy, disarray, and myocardial fibrosis constitute the histological features of HCM. HCM is a relatively benign disease but an important cause of sudden cardiac death in the young and heart failure in the elderly. Pathogenic variants (PVs) in genes encoding protein constituents of the sarcomeres are the main causes of HCM. PVs exhibit a gradient of effect sizes, as reflected in their penetrance and variable phenotypic expression of HCM. MYH7 and MYBPC3 , encoding β-myosin heavy chain and myosin binding protein C, respectively, are the two most common causal genes and responsible for ≈40% of all HCM cases but a higher percentage of HCM in large families. PVs in genes encoding protein components of the thin filaments are responsible for ≈5% of the HCM cases. Whereas pathogenicity of the genetic variants in large families has been firmly established, ascertainment causality of the PVs in small families and sporadic cases is challenging. In the latter category, PVs are best considered as probabilistic determinants of HCM. Deciphering the genetic basis of HCM has enabled routine genetic testing and has partially elucidated the underpinning mechanism of HCM as increased number of the myosin molecules that are strongly bound to actin. The discoveries have led to the development of mavacamten that targets binding of the myosin molecule to actin filaments and imparts beneficial clinical effects. In the coming years, the yield of the genetic testing is expected to be improved and the so-called missing causal gene be identified. The advances are also expected to enable development of additional specific therapies and editing of the mutations in HCM.

Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery, and is associated with increased morbidity and mortality. Inflammation has been implicated as an etiology of POAF. Mitochondrial DNA (mtDNA) has been shown to initiate inflammation. This study analyzed inflammatory mechanisms of POAF by evaluating mtDNA, neutrophils, and cytokines/chemokines in the pericardial fluid and blood after cardiac surgery.Blood and pericardial fluid from patients who underwent coronary artery bypass or heart valve surgery, or both, were collected intraoperatively and at 4, 12, 24, and 48 hours postoperatively. Real-time polymerase chain reaction was used to quantify mtDNA in the pericardial fluid and blood. A Luminex (Luminex Corp, Austin, TX) assay was used to study cytokine and chemokine levels. Flow cytometry was used to analyze neutrophil infiltration and activation in the pericardial fluid.Samples from 100 patients were available for analysis. Postoperatively, mtDNA and multiple cytokine levels were higher in the pericardial fluid versus blood. Patients who had POAF had significantly higher levels of mtDNA in the pericardial fluid compared with patients who did not (P.001, area under the curve 0.74). There was no difference in the mtDNA concentration in the blood between the POAF group and non-POAF group (P = .897). Neutrophil concentration increased in the pericardial fluid over time from a baseline of 0.8% to 56% at 48 hours (P.01).The pericardial space has a high concentration of inflammatory mediators postoperatively. Mitochondrial DNA in the pericardial fluid was strongly associated with the development of POAF. This finding provides insight into a possible mechanism of inflammation that may contribute to POAF, and may offer novel therapeutic targets.

Recent advances in the field of interventional cardiology have allowed for more complex procedures to be performed percutaneously. Ability to obtain safe large bore vascular access is frequently the key factor to procedural success. Meticulous technique for successful vascular access incorporates the understanding of anatomic landmarks, ultrasound, fluoroscopy, and micropuncture. Adequate hemostasis at the end of the case can be achieved through careful use of commercially available vascular closure devices. Although access-related vascular complications are uncommon, early recognition is key to successful management. Arterial tortuosity and calcification can present a significant challenge to successful common femoral artery access.

Importance: Current evidence suggests that transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is possible among symptom-free individuals but limited data are available on this topic in healthcare workers (HCW). The quality and acceptability of self-collected nasopharyngeal swabs (NPS) is unknown. Objective: To estimate the prevalence of SARS-CoV-2 infection and to assess the acceptability of self-collected NPS among HCW. Design: Cross-sectional convenience sample enrolled between April 20th and June 24th, 2020. We had >95% power to detect at least one positive test if the true underlying prevalence of SARS-CoV2 was > 1%. Setting: The metropolitan area surrounding Minneapolis and St. Paul, Minnesota. Participants: HCW free of self-reported upper respiratory symptoms were recruited. Exposures: Participants completed questionnaires regarding demographics, household characteristics, personal protective equipment (PPE) utilization and comorbidities. Outcomes: A participant self-collected nasopharyngeal swab (NPS) was obtained. SARS-CoV-2 infection was assessed via polymerase chain reaction. NPS discomfort was assessed on a scale of 1 (no discomfort) - 10 (extreme discomfort). NPS duration and depth into the nasopharynx, and willingness to perform future self-collections were assessed. Results: Among n=489 participants 80% were female and mean age+/-SD was 41+/-11. Participants reported being physicians (14%), nurse practitioners (8%), physicians assistants (4%), nurses (51%), medics (3%), or other which predominantly included laboratory technicians and administrative roles (22%). Exposure to a known/suspected COVID-19 case in the 14 days prior to enrollment was reported in 40% of participants. SARS-CoV-2 was not detected in any participant. The mean+/-SD discomfort level of the NPS was 4.5+/-2.0. 95% of participants reported that their self-swab was longer than or equal to the duration of patient swabs they had previously performed, and 89% reported the depth to be deeper than or equal to the depth of previous patient swabs. Over 95% of participants reported a willingness to repeat a self-collected NP swab in the future. Conclusions and Relevance: The point prevalence of SARS-CoV-2 infection was likely very low in symptom-free Minnesota healthcare workers from April 20th and June 24th, 2020. Self-collected NP swabs are well-tolerated and a viable alternative to provider-collected swabs to preserve PPE.

COVID-19 is a multiorgan systemic inflammatory disease caused by SARS-CoV-2 virus. Patients with COVID-19 often exhibit cardiac dysfunction and myocardial injury, but imaging evidence is lacking. In the study we detected and evaluated the severity of myocardial dysfunction in COVID-19 patient population using two-dimensional speckle-tracking echocardiography (2-D STE). A total of 218 consecutive patients with confirmed diagnosis of COVID-19 who had no underlying cardiovascular diseases were enrolled and underwent transthoracic echocardiography. This study cohort included 52 (23.8%) critically ill and 166 noncritically ill patients. Global longitudinal strains (GLSs) and layer-specific longitudinal strains (LSLSs) were obtained using 2-D STE. Changes in GLS were correlated with the clinical parameters. We showed that GLS was reduced (P P P 2, RR = 0.42, P R = −0.20, P = 0.006) and inflammatory cytokines, particularly IL-6 (R = −0.21, P = 0.003). In conclusions, our results demonstrate that myocardial dysfunction is common in COVID-19 patients, particularly those who are critically sick. Changes in indices of myocardial strain were associated with indices of inflammatory markers and hypoxia, suggesting partly secondary nature of myocardial dysfunction.

Highlights • Performances of five commercial ELISA (EDI, AnshLabs, Dia.Pro, NovaTec, and Lionex) for detecting anti-SARS-CoV-2 IgG was evaluated. • Samples used in this study are from diverse national background and the negative group contains samples that are seropositive for all other HCoV. • All assays showed low sensitivity during the early stages (≤7 from symptom onset); however, it was greatly improved overtime. • Lionex showed the highest specificity (98.6%), followed by EDI and Dia.Pro (97.1%,), NovaTec (85.7%), and AnshLabs (75.7%). • Lionex, which measures antibodies to the S1 protein, demonstrated the best performance and doesn’t cross-react with any other HCoV., Objectives To evaluate and compare the performances of five commercial ELISA assays (EDI, AnshLabs, Dia.Pro, NovaTec, and Lionex) for detecting anti-SARS-CoV-2 IgG. Methods 70 negative control samples (collected before the COVID-19 pandemic) and samples from 101 RT-PCR-confirmed SARS-CoV-2 patients (collected at different time points from symptoms onset: ≤7, 8-14, and >14 days) were used to compare the sensitivity, specificity, agreement, positive and negative predictive values of each assay with RT-PCR. A concordance assessment between the five assays was also conducted. Cross-reactivity with other HCoV, non-HCoV respiratory viruses, non-respiratory viruses, and nuclear antigens was investigated. Results Lionex showed the highest specificity (98.6%, 95%CI: 92.3-99.8), followed by EDI and Dia.Pro (97.1%, 95%CI: 90.2-99.2), NovaTec (85.7%, 95%CI: 75.7-92.1), then AnshLabs (75.7%, 95%CI: 64.5-84.2). All ELISA kits cross-reacted with one anti-MERS IgG positive sample except Lionex. The sensitivity was low during the early stages of the disease but improved over time. After 14 days from symptoms onset, Lionex and NovaTec showed the highest sensitivity at 87.9% (95%CI: 72.7-95.2) and 86.4% (95%CI: 78.5-91.7), respectively. The agreement with RT-PCR results based on Cohen’s kappa was as follows: Lionex (0.89)> NovaTec (0.70)> Dia.Pro (0.69)> AnshLabs (0.63)> EDI (0.55). Conclusion The Lionex ELISA, which measures antibodies solely to the S1 protein, demonstrated the best performance.

The purpose is using the occlusive hydrocolloid dressing (OHD) and gauze dressing (GD) to compare incidence of infection of wound and cost-effectiveness of dressing after hernia operation in children. Eighty children was undergo hernia surgery, wounds were dressing by OHD or GD. Hydrocolloid dressing was remain till suture was removed, and GD changed every day after operation. Calculations of cost dressing mean dressing alterations frequency and cost for each dressing in every treatment cluster. There are no variances amongst the two clusters concerning the incidence of wound infection. OHD was less costly and complex than GD, and GD necessary to be altered each day (p = 0.001). In conclusion, OHD is less costly to use, and less complex than GD because GD wanted to be altered more times during the period of healing.

Background A case-control study was performed to examine age, gender, and ABO blood groups in 1014 Iraqi hospitalized cases with Coronavirus disease 2019 (COVID-19) and 901 blood donors (control group). The infection was molecularly diagnosed by detecting coronavirus RNA in nasal swabs of patients. Results Mean age was significantly elevated in cases compared to controls (48.2 ± 13.8 vs. 29.9 ± 9.0 year; probability [p] < 0.001). Receiver operating characteristic analysis demonstrated the predictive significance of age in COVID-19 evolution (Area under curve = 0.858; 95% CI: 0.841 – 0.875; p < 0.001). Males outnumbered females in cases (60.4 vs. 39.6%) and controls (56 vs. 44%). Stratification by age group (< 30, 30 – 39, 40 – 49 and ≥ 50 years) revealed that 48.3% of cases clustered in the age group ≥ 50 years. ABO blood group analysis showed that group A was the most common among cases, while group O was the most common among controls (35.5 and 36.7%, respectively). Blood groups A (35.5 vs. 32.7; corrected p [pc] = 0.021), A+AB (46.3 vs. 41.7%; pc = 0.021) and A+B+AB (68.0 vs. 63.3%; pc = 0.007) showed significantly elevated frequencies in cases compared to controls. Logistic regression analysis estimated odds ratios (ORs) of 1.53 (95% confidence interval [CI]: 1.16 - 2.02), 1.48 (95% CI: 1.14 - 1.93) and 1.50 (95% CI: 1.17 - 1.82) for blood groups A, A+AB and A+B+AB, respectively. Blood group frequencies showed no significant differences between age groups of cases or controls. Regarding gender, male cases were marked with increased frequency of group A (39.9 vs. 28.9%) and decreased frequency of group O (25.9 vs. 41.0%) compared to female cases. Independent re-analysis of ABO blood groups in male and female cases demonstrated that group A was increased in male cases compared to male controls (39.9 vs. 33.1%; OR = 1.65; 95% CI: 1.24 - 2.21; pc = 0.006). On the contrary, no significant differences were found between females of cases and controls. Conclusions The study results indicated that blood group A may be associated with an increased risk of developing COVID-19, particularly in males.

Background Carcinoid syndrome is a rare disease caused by malignant neuroendocrine neoplasms. When vasoactive substances enter the systemic circulation, the triad of cutaneous flushing, bronchospasm, and diarrhoea often characterize carcinoid syndrome. Rarely, carcinoid syndrome can progress to involve the cardiac system, a condition known as carcinoid heart disease, often affecting right-sided valvular structures. Case summary Here, we present a case of malignant carcinoid syndrome with associated carcinoid heart disease in a 63-year-old female. The diagnosis of her dual regurgitant and stenotic valvular disease is detailed, with accompanying two- and three-dimensional echocardiographic images demonstrating the patient’s complex tricuspid dysfunction. Discussion Carcinoid heart disease encompasses a rare but important subset of valvular dysfunction caused by circulating vasoactive substances. Diagnosis utilizing serum studies, computed tomography scans, and echocardiography can help expedite the diagnosis and treatment of such rare conditions, and assist in the avoidance of complications. Despite its relatively well-recognized clinical presentation, carcinoid syndrome and its associated heart disease still remains a challenging condition to manage and treat, often requiring the input of several subspecialties to treat the condition appropriately.

Lovastatin is one of the most important compounds that is produced from some filamentous fungi, being employed in the reduction of hypocholesterolemia. The results of screening, after the collection of seventy-three local fungal isolates from different areas, demonstrated that the local isolate Aspergillus terreus A50 was the best isolate for lovastatin production, with a concentration of 12.66 µg/ml, through the submerged fermentation. Lovastatin produced from A. terreus A50 showed antimicrobial activities against a Candida albicans isolate. Solid state fermentation (SSF) was the best system to produce the highest yield of lovastatin by A. terreus A50 as compared to the submerged fermentation (SmF) system, with and without agitation. The optimum conditions for lovastatin production by SSF were also determined. The parameters included carbon sources (wastes), carbon sources mixture, incubation temperature, and moisturizing solution, which are commonly used in classical procedures. The results showed that a higher lovastatin production of 102.321 µg/gm substrate was obtained in the culture containing wheat bran and oat bran (1:1 w:w), sodium acetate, moisture ratio of 1.2 v:w, pH 7, incubation temperature of 30 °C and incubation period of 6 days. Some of these parameters, including pH, incubation period, and moisture ratio were determined by utilizing the Response Surface Method (RSM) as a statistical approach.

Research suggests that the science of undetectable viral load (VL) status and HIV transmission—conveyed with the slogan “Undetectable = Untransmittable” or “U = U”—has gaps in acceptance despite ro...

Mutation in the LMNA gene, encoding lamin A/C, causes a diverse group of diseases called laminopathies. Cardiac involvement is the major cause of death and manifests as dilated cardiomyopathy, heart failure, arrhythmias, and sudden death. There is no specific therapy for LMNA-associated cardiomyopathy. We report that deletion of Lmna in cardiomyocytes in mice leads to severe cardiac dysfunction, conduction defect, ventricular arrhythmias, fibrosis, apoptosis, and premature death within 4 weeks. The phenotype is similar to LMNA-associated cardiomyopathy in humans. RNA sequencing, performed before the onset of cardiac dysfunction, led to identification of 2338 differentially expressed genes (DEGs) in Lmna-deleted cardiomyocytes. DEGs predicted activation of bromodomain-containing protein 4 (BRD4), a regulator of chromatin-associated proteins and transcription factors, which was confirmed by complementary approaches, including chromatin immunoprecipitation sequencing. Daily injection of JQ1, a specific BET bromodomain inhibitor, partially reversed the DEGs, including those encoding secretome; improved cardiac function; abrogated cardiac arrhythmias, fibrosis, and apoptosis; and prolonged the median survival time 2-fold in the myocyte-specific Lmna-deleted mice. The findings highlight the important role of LMNA in cardiomyocytes and identify BET bromodomain inhibition as a potential therapeutic target in LMNA-associated cardiomyopathy, for which there is no specific effective therapy.

ObjectivesTransgender men who have sex with men (TMSM) represent an understudied population in relation to screening for HIV and sexually transmitted infections (STIs). We examined HIV and STI testing prevalence among TMSM along with the factors associated with testing in a diverse US nationwide sample of TMSM.MethodsData from a cross-sectional online convenience sample of 192 TMSM were analysed using multivariable binary logistic regression models to examine the association between sociodemographic and behavioural factors and lifetime testing for HIV, bacterial STIs and viral STIs, as well as past year testing for HIV.ResultsMore than two-thirds of TMSM reported lifetime testing for HIV (71.4%), bacterial STIs (66.7%), and viral STIs (70.8%), and 60.9% had received HIV testing in the past year. Engaging in condomless anal sex with a casual partner whose HIV status is different or unknown and having fewer than two casual partners in the past 6 months were related to lower odds of lifetime HIV, bacterial STI, viral STI and past year HIV testing. Being younger in age was related to lower probability of testing for HIV, bacterial STIs and viral STIs. Furthermore, TMSM residing in the South were less likely to be tested for HIV and viral STIs in their lifetime, and for HIV in the past year. Finally, lower odds of lifetime testing for viral STIs was found among TMSM who reported no drug use in the past 6 months.ConclusionsThese findings indicate that a notable percentage of TMSM had never tested for HIV and bacterial and viral STIs, though at rates only somewhat lower than among cisgender MSM despite similar patterns of risk behaviour. Efforts to increase HIV/STI testing among TMSM, especially among those who engage in condomless anal sex, are needed.

Background Babies of women with heterozygous pathogenic glucokinase (GCK) variants causing mild fasting hyperglycemia are at risk of macrosomia if they do not inherit the variant. Conversely, babies who inherit a pathogenic hepatocyte nuclear factor 4α (HNF4A) diabetes variant are at increased risk of high birth weight. Noninvasive fetal genotyping for maternal pathogenic variants would inform pregnancy management. Methods Droplet digital PCR was used to quantify reference and variant alleles in cell-free DNA extracted from blood from 38 pregnant women heterozygous for a GCK or HNF4A variant and to determine fetal fraction by measurement of informative maternal and paternal variants. Droplet numbers positive for the reference/alternate allele together with the fetal fraction were used in a Bayesian analysis to derive probability for the fetal genotype. The babies’ genotypes were ascertained postnatally by Sanger sequencing. Results Droplet digital PCR assays for GCK or HNF4A variants were validated for testing in all 38 pregnancies. Fetal fraction of ≥2% was demonstrated in at least 1 cell-free DNA sample from 33 pregnancies. A threshold of ≥0.95 for calling homozygous reference genotypes and ≤0.05 for heterozygous fetal genotypes allowed correct genotype calls for all 33 pregnancies with no false-positive results. In 30 of 33 pregnancies, a result was obtained from a single blood sample. Conclusions This assay can be used to identify pregnancies at risk of macrosomia due to maternal monogenic diabetes variants.

Background Patients with nonobstructive hypertrophic cardiomyopathy (nHCM) often experience a high burden of symptoms; however, there are no proven pharmacological therapies. By altering t...

Chronic kidney disease (CKD) is a permanent loss of kidney function which is diagnosed when the glomerular filtration rate (GFR) is under 60 ml\min\1.73m2 for more than three months. The present study was conducted at Kidney Transplant and Dialysis Center in the Medical City in Baghdad from October 2018 to April 2019. Sixty CKD patients with an age ranged of 40 to 65 years and 25 healthy subjects were involved in this study. Blood samples were collected to evaluate the levels of kidney function parameters and thyroid hormones. The levels of urea, creatinine and uric acid showed highly significant (p ≤ 0.01) increases in CKD patient in comparison with the control group, while the values of GFR and creatinine clearance showed highly significant (p ≤ 0.01) decreases. The results of thyroid hormones showed highly significant (p < 0.01) decreases in the levels of T3 and T4 along with a highly significant (p < 0.01) increase in the level of TSH in the patients.

Several studies have demonstrated no linked HIV transmissions in serodifferent sexual encounters where the partner with HIV has an undetectable viral load. As a result, awareness and dissemination of treatment as prevention, and movements such as "Undetectable = Untransmittable" (U = U), has grown.We conducted an online cross-sectional survey from November 2017 through September 2018 to gather data from a total of 111,747 sexual minority men (SMM) in the United States.Participants provided sociodemographic data and answered questions regarding biomedical status, HIV and STI prevention behaviors, drug use, condomless anal sex, and perceived accuracy of the U = U message. We conducted analyses to understand factors associated with perceived accuracy of U = U stratified by HIV status.Overall, 53.2% of the sample perceived U = U as accurate, with the highest rates among HIV-positive SMM (83.9%), followed by HIV-negative (53.8%) and status-unknown (39.0%) SMM. Multivariable models showed accuracy beliefs were, on average, 1-2% higher for each consecutive month of recruitment. Consistent with previous work, there was greater heterogeneity among HIV-negative and unknown men, with several factors differentiating perceived accuracy, compared with SMM with HIV. Perceived transmission risk levels with undetectable partners were skewed well above accurate levels, and greater perceived transmission risk was associated with lower perceived accuracy of U = U.Public confidence in treatment as prevention and U = U is growing, but clear, unequivocal messaging about the effectiveness of U = U is critical. Owing to misunderstandings of risk, language that focuses on protective benefits rather than transmission risks may reach more people and allow for better comparisons with PrEP and condoms.

Objective This study examined psychological and sexual health indicators associated with positive feelings and discrimination at the intersection of race and gender among Black gay, bisexual, and other sexual minority men (SMM). Method Participants were a national sample of 1,064 Black SMM (Mdn age = 28) who responded to self-report measures of positive feelings and discrimination associated with being a Black man, psychological distress, self-efficacy, emotional awareness, and sexual HIV risk and protective behavior. Using structural equation modeling, we examined associations between the positive feelings and discrimination scales and the psychological and sexual health indicators. We also tested age as a moderator of these associations. Results Our results indicated that positive feelings about being a Black man were significantly positively associated with self-efficacy (b = 0.33), emotional awareness (b = 0.16), and sexual protective behavior (b = 0.93) and negatively associated with psychological distress (b = -0.26) and sexual risk behavior (b = -0.93). Except for emotional awareness and sexual protective behavior, discrimination as a Black man was also associated with these variables, though to a lesser magnitude for positive health indicators. Moderation results showed that, except for the association between positive feelings and emotional awareness, younger men generally had stronger associations between health indicators and the positive feelings and discrimination scales. Conclusions These results suggest that positive feelings, in addition to discrimination, at the intersection of race and gender play an important role in the psychological and sexual health of Black SMM, especially earlier in their lives. (PsycINFO Database Record (c) 2020 APA, all rights reserved).