Measurement of Natriuretic Peptides in Patients with Suspected Heart Failure to Prevent Overuse of Echocardiography - a Pilot Study.

BACKGROUND: European Society of Cardiology (ESC) guidelines recommend measuring natriuretic peptides (BNP or NT-proBNP) in patients with suspected heart failure (HF) as a first-line tool. HF should be ruled-out if concen-trations of NT-proBNP are below 300 ng/L and 125 ng/L for acute HF and chronic HF, respectively. METHODS: Patients with suspected HF referred for transthoracic echocardiography (TTE) were enrolled; NT-pro-BNP concentrations were obtained from medical charts (measurement < 48 hours) or prospectively measured on the day of TTE. RESULTS: Out of 109 patients, NT-proBNP was measured by the referring department before TTE in 40 patients (36.7%), and 37.5% of these patients had NT-proBNP concentration below the rule-out threshold. NT-proBNP was measured in additional 38 patients on the day of TTE. Overall, 38.5% of the patients had a NT-proBNP concentration below the threshold value. CONCLUSIONS: Natriuretic peptides are not routinely measured in patients with suspected HF; systematic measurement would reduce unnecessary TTE by at least 38.5%.

Genetic Correlation of HBB, HFE and HAMP Genes to Endocrinal Complications in Egyptian Beta Thalassemia Major Patients.

Iron loading is regarded as the primary cause of endocrine abnormalities in thalassemia major patients. Thus, the purpose of the current research was to explore the impact of thalassemia genotypes, hepcidin antimicrobial peptide (HAMP) and hereditary hemochromatosis (HFE) gene variants, and hepcidin expression on serum ferritin and endocrinal complications in thalassemia patients. The study comprised fifty beta-thalassemia cases and fifty age- and sex-matched controls. Genotyping of the Beta-globin gene (HBB), HAMP, and exon 2 of the HFE gene was performed using Sanger sequencing. C282Y (c.845G > A) variant of the HFE gene was determined by PCR-RFLP. Hepcidin mRNA expression was assessed by qRT-PCR. Biochemical and hormonal studies were done for all patients. Hypogonadism and short stature were found in 56% and 20% of the investigated cases, respectively. Molecular studies reported a statistically higher frequency of the HAMP variant c.-582A > G in thalassemic patients than controls. Significant downregulation of hepcidin expression was found in cases compared to healthy subjects that was significantly associated with short stature. Considering the thalassemia alleles, the IVSI.1G > A (ß0) allele was statistically related to hypogonadism. Our results proposed that thalassemia genotypes and downregulated hepcidin expression were the potential risk factors for endocrinopathies in our cases. We also demonstrated an increased incidence of the HAMP promoter variant c.- 582A > G that might have a role in the pathogenesis of iron overload in thalassemic cases. Significant downregulation of hepcidin expression, that contributes to increased iron burden, could be used as a future therapeutic target in these patients.

Acute Appendicitis Incidence, Diagnostic Markers, and Sequelae; Dallah Hospital-Based Study in Riyadh, Saudi Arabia.

Background: Acute appendicitis is currently considered one of the most common acute surgical diseases of the abdomen and requires emergency surgery. It is also one of the most common abdominal emergencies in both developed and developing countries. The current study is aimed at assessing the specificity and sensitivity of Ultrasound and Computed Tomography in the diagnosis of appendicitis as well as the prevalence of its complications. The association of appendicitis with several laboratory findings will also be evaluated. Methodology: A retrospective study was conducted at Dallah-Namar Hospital, Riyadh City, Saudi Arabia. Results: 720 patients were differentially diagnosed with appendicitis in the study area. Of these, 618 patients had US abdomen/pelvis, with 15 (2.4%) showing positive findings. Amongst the 203 patients noted to have undergone abdominal CT,8 (4.0%) was found to have positive findings. Conclusion: The sensitivity of the US was determined to be relatively low. Also, serum creatinine was found to be elevated among all patients diagnosed with appendicitis. Further research with a larger sample size is needed to be conducted to further support the current findings.

Invisible and undervalued: A qualitative study of laboratory workers' experiences and perceptions of laboratory strengthening in Sierra Leone.

Background: The 2013-2016 West Africa Ebola outbreak highlighted the importance of laboratory capacity to outbreak response while also revealing its long-standing neglect. The outbreak prompted massive international investment into strengthening laboratory services across multiple healthcare settings. Objective: In this article, we explore hospital-based clinical laboratory workers' experiences and perceptions of their everyday working environment in Sierra Leone, and how recent investments in laboratory strengthening have shaped these. Methods: This qualitative study draws on in-depth interviews with eight laboratory workers and participant observation of laboratory practices at a tertiary referral hospital in Freetown between April 2019 and December 2019. Interview and observational data were coded and analysed using a reflexive thematic approach. Results: The Ebola outbreak prompted international investments in automated devices, biosafety training, and a new dedicated infectious diseases laboratory. However, little investment was made in the infrastructure and supply systems needed to sustain routine laboratory work or keep machines functioning. Laboratory workers perceived their work to be under-recognised and undervalued by the government, hospital managers and clinical staff, a perception compounded by under-use of the hospital's laboratory services by clinicians. Conclusion: Understanding laboratory technicians' views, experiences, and priorities is essential to any sustainable laboratory-strengthening effort. Investments in personnel should match investments in technologies and infrastructure for outbreak response. What this study adds: This study contributes to an understanding of how clinical laboratory personnel in Sierra Leone view and experience their work, and introduces the concept of social invisibility to explain these experiences.

Adipokine (adiponectin-rs1501299) Gene Variant and Patient Characteristics in Relation to Metabolic-associated Fatty Liver Disease.

Background: Several genetic and metabolic variables, most notably the variation in the adipokine gene rs1501298, have been linked to metabolic-associated fatty liver disease etiopathogenesis (MAFLD). Liver biopsy, the gold standard for diagnosing MAFLD, is an invasive procedure; therefore, alternative diagnostic methods are required. Consequently, the integration of these metabolic variables with some of the patients' characteristics may facilitate the development of noninvasive diagnostic methods that aid in the early detection of MAFLD, identification of at-risk individuals and planning of management strategies. Methods: This study included 224 Egyptians (107 healthy individuals and 117 MAFLD patients). Age, sex, BMI, clinical and laboratory characteristics, and rs1501299 adipokine gene polymorphisms were examined. The rs1501299 variant, insulin resistance, hypertension, obesity, blood pressure, lipid profile, hemoglobin A1C level, and hepatic fibrosis predictors were evaluated for MAFLD risk. The feasibility and effectiveness of developing non-invasive MAFLD diagnostic models will be investigated. Results: The +276G/T (rs1501299) polymorphism (GG vs GT/TT) was linked with MAFLD (OR: 0.43, CI: 0.26-0.69, P = 0.002). The GG variants had lower MAFLD rates than those of the GT and TT variants. In addition to altered lipid profiles, patients with MAFLD showed increased gamma-glutamyl transferase levels (GGT: 56 IU/L vs. 36 IU/L). Genetic diversity also affects the accuracy of hepatic fibrosis and steatosis prediction. Hepatic fibrosis and steatosis predictors had receiver operating characteristic (ROC) AUCs of 0.529%, 0.846%, and 0.700-0.825%, respectively. We examined a diagnostic model based on these variables and demonstrated its effectiveness. Conclusion: The Adipokine variant rs1501299 increased the risk of MAFLD. Identifying and genotyping this variation and other metabolic variables allow for a noninvasive diagnostic model for early MAFLD diagnosis and identification of those at risk. This study illuminates the prevention and management of MAFLD. Further research with more participants is needed to verify these models and to prove their MAFLD diagnostic efficacy.

Assessment of the impact of pregnancy and malaria infection on the variation of neutrophil levels in women from San, Mali.

BACKGROUND: In patients with severe neutropenia, infections can rapidly become serious and life-threatening. It is essential to understand whether pregnancy induces changes in neutrophil levels thereby posing an increased threat to the health of gravidae. METHODOLOGY: This cross-sectional study was conducted in San Health District (Mali) and involved pregnant women infected or not by malaria parasites and non-pregnant healthy volunteers. Subjects were categorized as having neutropenia, normal neutrophil levels, and neutrophilia regarding their neutrophil levels. A logistic regression analysis was performed to determine factors associated with neutrophil level variation in pregnant women. RESULTS: Whether or not the pregnant women were infected with malaria, 98 of the 202 cases (48.5%) showed neutrophilia. Surprisingly, 67 of the 71 cases of neutropenia (94.4%) observed in this study concerned healthy people who were not pregnant. The mean percentage of neutrophil levels was significantly (p < 0.001) lower (49.9%) in the first trimester compared to the second trimester of pregnancy (62.0%). A logistic regression model showed that compared to early pregnancy, the second (OR = 12.9, 95% CI 2.2-248.1, p = 0.018) and the third trimesters (OR = 13.7, 95% CI 2.3-257.5, p = 0.016) were strongly associated with the increase of neutrophil levels. CONCLUSIONS: Pregnancy can induce the production of mature neutrophils that are continually released into circulation. Neutrophil levels were lower during the first trimester of the pregnancy compared to the second and third trimesters, but not affected by the presence or absence of malaria infection.

Accuracy and consistency of online large language model-based artificial intelligence chat platforms in answering patients' questions about heart failure.

BACKGROUND: Heart failure (HF) is a prevalent condition associated with significant morbidity. Patients may have questions that they feel embarrassed to ask or will face delays awaiting responses from their healthcare providers which may impact their health behavior. We aimed to investigate the potential of large language model (LLM) based artificial intelligence (AI) chat platforms in complementing the delivery of patient-centered care. METHODS: Using online patient forums and physician experience, we created 30 questions related to diagnosis, management and prognosis of HF. The questions were posed to two LLM-based AI chat platforms (OpenAI's ChatGPT-3.5 and Google's Bard). Each set of answers was evaluated by two HF experts, independently and blinded to each other, for accuracy (adequacy of content) and consistency of content. RESULTS: ChatGPT provided mostly appropriate answers (27/30, 90%) and showed a high degree of consistency (93%). Bard provided a similar content in its answers and thus was evaluated only for adequacy (23/30, 77%). The two HF experts' grades were concordant in 83% and 67% of the questions for ChatGPT and Bard, respectively. CONCLUSION: LLM-based AI chat platforms demonstrate potential in improving HF education and empowering patients, however, these platforms currently suffer from issues related to factual errors and difficulty with more contemporary recommendations. This inaccurate information may pose serious and life-threatening implications for patients that should be considered and addressed in future research.

Reporting quality of heart failure randomized controlled trials 2000-2020: Temporal trends in adherence to CONSORT criteria.

AIM: Heart failure (HF) is a major cause of morbidity and mortality in older adults. Randomized controlled trials (RCTs) inform HF policy and practice, but the accurate interpretation of results is contingent on clear and transparent reporting. The CONsolidated Standards Of Reporting Trials (CONSORT) statement serves as a guide to RCT reporting. We evaluated the quality of reporting in HF RCTs in high-impact journals by assessing their adherence to CONSORT. METHODS AND RESULTS: We searched MEDLINE, EMBASE and CINAHL for HF RCTs published in high-impact journals 2000-2020. We assessed the proportion of CONSORT criteria that individual HF RCTs adhered to, and used the Jonckheere-Terpstra test to examine temporal trends in adherence. Multivariable linear regression explored the association between trial characteristics and adherence to CONSORT. Primary analysis assessed adherence to CONSORT 2010 update. A sensitivity analysis assessed adherence to the original (1996) CONSORT criteria. Among 221 RCTs analysed, the mean (standard deviation [SD]) adherence was suboptimal overall (mean [SD] adherence 69.7 [11.5]%) (5513/7913 criteria), with a temporal increase in adherence over the 20-year period (p < 0.001). Factors associated with adherence included publication after versus during/before 2010 (ß = 10.17, 95% confidence interval [CI] 7.64-12.70; p < 0.001); two-group parallel individual-level randomization versus other (including multi-group or cluster randomization) (ß = 5.81, 95% CI 2.88-8.73; p < 0.001); and multicentre versus single-centre trials (ß = 7.26, 95% CI 3.25-11.27; p < 0.001). There was no difference in trial adherence to the updated CONSORT (2010) versus the original (1996) CONSORT criteria, and temporal trends in adherence to both sets of criteria were similar, likely due to overlap between the two sets of criteria. Trials with greater adherence to CONSORT were published in higher impact factor journals, with a positive correlation (r = 0.312; p < 0.001). CONCLUSION: The quality of reporting in HF RCTs, as measured by CONSORT adherence, has improved over time but remains suboptimal.

Efficacy and Clinical Outcomes of mRNA COVID-19 Vaccine in Pregnancy: A Systematic Review and Meta-Analysis.

BACKGROUND: The world has witnessed one of the largest pandemics, dubbed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of December 2020, the USA alone reported 98,948 cases of coronavirus disease 2019 (COVID-19) infection during pregnancy, with 109 related maternal deaths. Current evidence suggests that unvaccinated pregnant women infected with SARS-CoV-2 are at a higher risk of experiencing complications related to COVID-19 compared to nonpregnant women. This review aimed to provide healthcare workers and non-healthcare workers with a comprehensive overview of the available information regarding the efficacy of vaccines in pregnant women. SUMMARY: We performed a systematic review and meta-analysis following PRISMA guidelines. The search through the database for articles published between December 2019 and October 2021 was performed. A comprehensive search was performed in PubMed, Scopus, and EMBASE databases for research publications published between December 2019 and October 2021. We focused on original research, case reports, case series, and vaccination side effect by authoritative health institutions. Phrases used for the Medical Subject Heading [MeSH] search included ("COVID-19" [MeSH]) or ("Vaccine" [MeSH]) and ("mRNA" [MeSH]) and ("Pregnant" [MeSH]). Eleven studies were selected and included, with a total of 46,264 pregnancies that were vaccinated with mRNA-containing lipid nanoparticle vaccine from Pfizer/BioNTech and Moderna during pregnancy. There were no randomized trials, and all studies were observational (prospective, retrospective, and cross-sectional). The mean maternal age was 32.2 years, and 98.7% of pregnant women received the Pfizer COVID-19 vaccination. The local and systemic adverse effects of the vaccination in pregnant women were analyzed and reported. The local adverse effects of the vaccination (at least 1 dose) such as local pain, swelling, and redness were reported in 32%, 5%, and 1%, respectively. The systemic adverse effects such as fatigue, headaches, new onset or worsening of muscle pain, chills, fever, and joint pains were also reported in 25%, 19%, 18%, 12%, 11%, and 8%, respectively. The average birthweight was 3,452 g. Among these pregnancies, 0.03% were stillbirth and 3.68% preterm (<37 weeks) births. KEY MESSAGES: The systemic side effect profile after administering the COVID-19 mRNA vaccine to pregnant women was similar to that in nonpregnant women. Maternal and fetal morbidity and mortality were lowered with the administration of either one or both the doses of the mRNA COVID-19 vaccination.

Molecular characterization of an outbreak-involved Bacillus anthracis strain confirms the spillover of anthrax from West Africa.

BACKGROUND: Anthrax, a zoonotic disease caused by the spore-forming bacterium Bacillus anthracis, remains a major global public health concern, especially in countries with limited resources. Sierra Leone, a West African country historically plagued by anthrax, has almost been out of report on this disease in recent decades. In this study, we described a large-scale anthrax outbreak affecting both animals and humans and attempted to characterize the pathogen using molecular techniques. METHODS: The causative agent of the animal outbreak in Port Loko District, Sierra Leone, between March and May 2022 was identified using the nanopore sequencing technique. A nationwide active surveillance was implemented from May 2022 to June 2023 to monitor the occurrence of anthrax-specific symptoms in humans. Suspected cases were subsequently verified using quantitative polymerase chain reaction. Full-genome sequencing was accomplished by combining long-read and short-read sequencing methods. Subsequent phylogenetic analysis was performed based on the full-chromosome single nucleotide polymorphisms. RESULTS: The outbreak in Port Loko District, Sierra Leone, led to the death of 233 animals between March 26th and May 16th, 2022. We ruled out the initial suspicion of Anaplasma species and successfully identified B. anthracis as the causative agent of the outbreak. As a result of the government's prompt response, out of the 49 suspected human cases identified during the one-year active surveillance, only 6 human cases tested positive, all within the first month after the official declaration of the outbreak. The phylogenetic analysis indicated that the BaSL2022 isolate responsible for the outbreak was positioned in the A.Br.153 clade within the TransEuroAsian group of B. anthracis. CONCLUSIONS: We successfully identified a large-scale anthrax outbreak in Sierra Leone. The causative isolate of B. anthracis, BaSL2022, phylogenetically bridged other lineages in A.Br.153 clade and neighboring genetic groups, A.Br.144 and A.Br.148, eventually confirming the spillover of anthrax from West Africa. Given the wide dissemination of B. anthracis spores, it is highly advisable to effectively monitor the potential reoccurrence of anthrax outbreaks and to launch campaigns to improve public awareness regarding anthrax in Sierra Leone.

Real-world evaluation of care for type 2 diabetes in Malaysia: A cross-sectional analysis of the treatment adherence to guideline evaluation in type 2 diabetes (TARGET-T2D) study.

AIM: Given a lack of data on diabetes care performance in Malaysia, we conducted a cross-sectional study to understand the clinical characteristics, control of cardiometabolic risk factors, and patterns of use of guideline-directed medical therapy (GDMT) among patients with type 2 diabetes (T2D), who were managed at publicly-funded hospitals between December 2021 and June 2022. METHODS: Patients aged ≥18 years with T2D from eight publicly-funded hospitals in the Greater Kuala Lumpur region, who had ≥2 outpatient visits within the preceding year and irrespective of treatment regimen, were eligible. The primary outcome was ≥2 treatment target attainment (defined as either HbA1c <7.0%, blood pressure [BP] <130/80 mmHg, or low-density lipoprotein cholesterol [LDL-C] <1.8 mmol/L). The secondary outcomes were the individual treatment target, a combination of all three treatment targets, and patterns of GDMT use. To assess for potential heterogeneity of study findings, all outcomes were stratified according to prespecified baseline characteristics namely 1) history of atherosclerotic cardiovascular disease (ASCVD; yes/no) and 2) clinic type (Diabetes specialist versus General medicine). RESULTS: Among 5094 patients (mean±SD age 59.0±13.2 years; T2D duration 14.8±9.2 years; HbA1c 8.2±1.9% (66±21 mmol/mol); BMI 29.6±6.2 kg/m2; 45.6% men), 99% were at high/very high cardiorenal risk. Attainment of ≥2 treatment targets was at 18%, being higher in General medicine than in Diabetes specialist clinics (20.8% versus 17.5%; p = 0.039). The overall statin coverage was 90%. More patients with prior ASCVD attained LDL-C <1.4 mmol/L than those without (13.5% versus 8.4%; p<0.001). Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors (13.2% versus 43.2%), glucagon-like peptide-1 receptor agonists (GLP1-RAs) (1.0% versus 6.2%), and insulin (27.7% versus 58.1%) were lower in General medicine than in Diabetes specialist clinics. CONCLUSIONS: Among high-risk patients with T2D, treatment target attainment and use of GDMT were suboptimal.

Surgical Written Consent in Aesthetic Plastic Surgery: A Plastic Center Audit of Surgical Consent Standards.

Background Informed consent is a fundamental aspect of modern medical practice that requires effective communication and an ample understanding of medical ethics, patient autonomy, and the legal obligations of healthcare professionals. Maintaining high-quality surgical informed consent is a crucial step in the healthcare process. Thus, we aimed to obtain surgical written consent on abdominoplasty, suction-assisted abdominal dermo lipectomy, and lower body lifting from our hospital database over three months (January to March, 2023) to assess our level across the American Society of Plastic Surgeons (ASPS) system. Results A total of 45 surgical written consents were obtained and 37 consents remained after exclusion. Bleeding, infection, and hematoma were mentioned in more than 80% of our consents. However, important complications such as ileus and umbilical malposition were never mentioned. Overall, the completion rate of written complications ranged from 14% to 56% in comparison to data from the ASPS. Conclusions Our results show a measurable inconsistency in surgical written consents at our center. Thus, establishing a comprehensive and accurate surgical written consent will aid in protecting our center against deficient surgical written consent accusations, improve the experience of patients, and enhance the quality of service provided by our center.

Single ChAdOx1 nCoV-19 dose elicits stronger immune response in previously infected individuals than in SARS-CoV2 naive persons.

BACKGROUND: Current vaccines against COVID-19 effectively reduce morbidity and mortality and are vitally important for controlling the pandemic. Between December 2020 and February 2021, adenoviral vector vaccines such as ChAdOx1 (AstraZeneca-Oxford) were put in use. Recent reports demonstrate robust serological responses to a single dose of messenger RNA vaccines in individuals previously infected with SARS-CoV-2. We aimed to study the association between previous COVID-19 infection and antibody levels after a single dose of ChAdOx1 nCoV-19. METHODS: This cross-sectional study was conducted on 657 individuals who were either convalescent or SARS-CoV-2 naive and had received one dose of ChAdOx1 (AstraZeneca). A questionnaire was used to collect data on age, sex, and self-reported history of COVID-19 infection. We then compared the average levels of immunoglobulin G (IgG) between the previously infected and COVID-19-naive participants. RESULTS: We compared the antibody responses of individuals with confirmed prior COVID-19 infection with those of individuals without prior evidence of infection. The mean antibody levels in those who reported no history of COVID-19 infection were substantially lower than in those who were previously infected, in both males and females. Sex-related differences were observed when we compared antibody levels between men and women. In males, anti-S IgG antibody levels were higher in those who had been previously infected (156.1 vs. 87.69 AU/mL, p = .009), compared with the same pattern was observed in females (113.5 vs. 90.69 AU/mL, p = .005). CONCLUSIONS: Previous COVID-19 infection is associated with higher levels of SARS-CoV-2 antibodies following ChAdOx1 (AstraZeneca) vaccination. Our finding supports the notion that a single dose of ChAdOx1 nCoV-19 administered post-SARS-CoV-2 infection serves as an effective immune booster. This provides a possible rationale for a single-dose vaccine regimen for previously infected individuals.

Development of an Anisotropic Hyperelastic Material Model for Porcine Colorectal Tissues.

Many colonic surgeries include colorectal anastomoses whose leaks may be life-threatening, affecting thousands of patients annually. Various studies propose that mechanical interaction between the staples and neighboring tissues may play an important role in anastomotic leakage. Therefore, understanding the mechanical behavior of colorectal tissue is essential to characterizing the reasons for this type of failure. So far, experimental data characterizing the mechanical properties of colorectal tissue have been few and inconsistent, which has significantly limited understanding their behavior. This research proposes an approach to developing an anisotropic hyperelastic material model for colorectal tissues based on uniaxial testing of freshly harvested porcine specimens, which were collected from several age- and weight-matched pigs. The specimens were extracted from the same colon tract of each pig along their circumferential and longitudinal orientations. We propose a constitutive model combining Yeoh isotropic hyperelastic material with fibers oriented in two directions to account for the hyperelastic and anisotropic nature of colorectal tissues. Experimental data were used to accurately determine the model's coefficients (circumferential, R2 = 0.9968; longitudinal, R2 = 0.9675). The results show that the proposed model can be incorporated into a finite element model that can simulate procedures such as colorectal anastomoses reliably.

Evaluation of Fasting and Probiotics in Reducing Postweaning Stress in Rabbits: Study of their Effects on Biochemical and Gene expression Patterns.

Postweaning stress in mammalian in vivo models leads to significant oxidative stress in the body as well as inducing hormonal disturbance. In this study, we assessed progressive alterations in reactive oxygen species (ROS), which at high levels can show oxidative stress, in addition to oxidative damage to the DNA structure of rabbits. Different groups of rabbits were fasted for 48 h per week for 3 weeks, fed a commercial diet with probiotics added (200 mg of Bacillus licheniformis and Bacillus subtilis), and fasted while being treated with probiotics. The results showed that weaning induced a significant elevation in oxidative stress markers, such as the ROS-related genes malate dehydrogenase 1 (MDH1) and flavin-containing monooxygenase 2 (FMO2), DNA damage, and hormonal disturbance. However, probiotic treatment resulted in significant decreases in the levels of malondialdehyde, cortisol, and triiodothyronine (T3); DNA damage; and apoptosis, as well as changes in the expression of ROS-related genes. On the other hand, supplementation with probiotics reduced these postweaning stress signs in fasted animal models by elevating the genes encoding catalase and superoxide dismutase as well as increasing glutathione peroxidase (GSH-Px), glutathione-s-transferase, alkaline phosphatase, glucose, and thyroxin (T4) levels. The results suggest that supplementation with probiotics accompanied by a fasting program could decrease oxidative stress, ROS genes, and genomic DNA damage and improve the hormonal status that is induced by postweaning stress in mammalian in vivo models.

Mitochondrial DNA variation in Aedes aegypti (Diptera: Culicidae) mosquitoes from Jeddah, Saudi Arabia.

Wolbachia (Hertig 1936) (Rickettsiales: Ehrlichiaceae) has emerged as a valuable biocontrol tool in the fight against dengue by suppressing the transmission of the virus through mosquitoes. Monitoring the dynamics of Wolbachia is crucial for evaluating the effectiveness of release programs. Mitochondrial (mtDNA) markers serve as important tools for molecular tracking of infected mitochondrial backgrounds over time but require an understanding of the variation in release sites. In this study, we investigated the mitochondrial lineages of Aedes aegypti (Linnaeus 1762) in Jeddah, Saudi Arabia, which is a prospective release site for the "wAlbBQ" Wolbachia-infected strain of this mosquito species. We employed a combination of comprehensive mitogenomic analysis (including all protein-coding genes) and mtDNA marker analysis (cox1 and nad5) using data collected from Jeddah. We combined our mitogenome and mtDNA marker data with those from previous studies to place mitochondrial variation in Saudi Arabia into a broader global context. Our findings revealed the presence of 4 subclades that can be broadly categorized into 2 major mitochondrial lineages. Ae. aegypti mosquitoes from Jeddah belonged to both major lineages. Whilst mitogenomic data offered a higher resolution for distinguishing Jeddah mosquitoes from the wAlbBQ strain, the combination of cox1 and nad5 mtDNA markers alone proved to be sufficient. This study provides the first important characterization of Ae. aegypti mitochondrial lineages in Saudi Arabia and offers essential baseline information for planning future molecular monitoring efforts during the release of Wolbachia-infected mosquitoes.

A novel automated peak frequency annotation algorithm for identifying deceleration zones and ventricular tachycardia ablation sites.

BACKGROUND: Current annotation of local fractionated signals during ventricular electroanatomic mapping (EAM) requires manual input subject to variability and error. OBJECTIVES: The purpose of this study was to evaluate a novel peak frequency (PF) annotation software for its ability to automatically detect late potentials (LPs) and local abnormal ventricular activity (LAVA), determine an optimal range for display, and assess its impact on isochronal late activation mapping (ILAM). METHODS: EAM data from 25 patients who underwent ventricular tachycardia (VT) ablation were retrospectively analyzed. Samplings of electrogram PFs from areas of normal bipolar voltage, areas of low voltage, and areas of low voltage with fractioned signals were performed. An optimal range of frequency display was identified from these patients and applied to a validation cohort of 10 prospective patients to assess high PF within scar as a predictor of VT ablation target sites, in particular deceleration zones (DZs) identified by ILAM, LP, and LAVA. RESULTS: Voltage and PF ranges of normal endocardial tissue varied widely. Using 220 Hz as a frequency cutoff value in areas of low bipolar voltage, areas of high fractionation were identified with sensitivity of 91% and specificity of 85% There was no significant reduction in targeted DZ surface areas, and colocalization with DZs was observed in all cases. Applied to the prospective cohort, PF predicted fractionated areas and DZ in 9 of 10 patients. CONCLUSION: A PF annotation algorithm with a cutoff of 220 Hz accurately identifies areas of fractioned signals and accurately predicts DZs during ILAM.

Multiple infusions of ex vivo-expanded regulatory T cells promote CD163+ myeloid cells and kidney allograft survival in non-lymphodepleted non-human primates.

Clinical verification of adoptively transferred regulatory T cell (Treg) efficacy in transplantation remains challenging. Here, we examined the influence of autologous ex vivo-expanded polyclonal Tregs on kidney graft survival in a clinically relevant non-human primate model. Peripheral blood Tregs were isolated and expanded using artificial antigen presenting cells. Immunosuppression was comprised of tapered tacrolimus and CTLA4 immunoglobulin, in five animals each without or with Treg infusions. Escalating Treg doses were administered 6, 10, 13, 16, 20, 23, 27 and 30 days after transplant. Infused Tregs were monitored for Treg signature, anti-apoptotic (Bcl-2) and proliferation (Ki67) marker expression. Treg infusions prolonged median graft survival time significantly from 35 to 70 days. Treg marker (Ki67 and Bcl-2) expression by infused Tregs diminished after their infusion but remained comparable to that of circulating native Tregs. No major changes in circulating donor-reactive T cell responses or total Treg percentages, or in graft-infiltrating T cell subsets were observed with Treg infusion. However, Treg infusion was associated with significant increases in CD163 expression by circulating HLA-DR+ myeloid cells and elevated levels of circulating soluble CD163. Further, graft-infiltrating CD163+ cells were increased with Treg infusion. Thus, multiple Treg infusions were associated with M2-like myeloid cell enhancement that may mediate immunomodulatory, anti-inflammatory and graft reparative effects.

A Systematic Review Exploring the Impact of Arteriovenous Fistula Ligature on High-Output Heart Failure in Renal Transplant Recipients.

BACKGROUND: Cardiovascular disease is the most common cause of death in renal transplant recipients (RTrs). High-output heart failure (HoHF) is a classic problem of RTrs with patent arteriovenous fistulae (AVF). Central to the entire discipline of transplant nephrology is the ligation of AVF in RTrs, with a patent AVF presenting with signs and symptoms of HoHF. AVF ligation has long been a topic of great interest in this population. To date, little attention has been paid to the effects of arteriovenous graft ligation on HoHF. This study systematically reviews the data for AVF ligation, aiming to provide its impact on HoHF in RTrs. METHODS: The present study adopts the Preferred Reporting Items for Systematic Reviews and Meta-analysis 2020 guidelines. Published studies were identified using a search strategy in PubMed, Scopus, PubMed Central, Science Direct, and Medline. The primary inclusion criterion for this review was RTrs with a patent AVF who exhibited clinical or imaging findings of HoHF. Articles dating back to the last decade that involved the human species were included in our review, and the search was restricted to the English language. Studies involving both male and female genders and those describing the adult population (aged > 19 years) were also a part of our inclusion criteria. RESULTS: After applying eligibility criteria, our electronic search yielded 1,461 articles. A total of 16 studies that involved 18,735 subjects were included in our review, which comprised 6 cohort studies, 4 case reports, 2 randomized control trials, 2 narrative reviews, 1 meta-analysis, and 1 case series. While the risk of bias of the narrative reviews was low, 1 of the randomized control trials had some overall concerns. The meta-analysis included in our review had moderate risk of bias, while 4 of the 6 cohort studies were of good quality. All of the case reports and series included in our review were of good quality. Of the 12 studies that reported genders, 10,949 were male and 6,416 were female. There was a notable reduction in left ventricular mass, left ventricular mass index, left ventricular end diastolic dimension, cardiac output, velocity index, and systemic vascular resistance index upon AVF ligation. CONCLUSIONS: A complete resolution of the clinical signs and symptoms of HoHF can be anticipated after AVF ligation in RTrs. Clinicians should always be on the lookout for signs and symptoms of cardiovascular decompensation in asymptomatic RTrs.