GhJUB1_3-At positively regulate drought and salt stress tolerance under control of GhHB7, GhRAP2-3 and GhRAV1 in Cotton.

Climate change severely affects crop production. Cotton is one of the primary fiber crops in the world and its production is susceptible to various environmental stresses, especially drought and salinity. Development of stress tolerant genotypes is the only way to escape from these environmental constraints. We identified sixteen homologs of the Arabidopsis JUB1 gene in cotton. Expression of GhJUB1_3-At was significantly induced in the temporal expression analysis of GhJUB1 genes in the roots of drought tolerant (H177) and susceptible (S9612) cotton genotypes under drought. The silencing of the GhJUB1_3-At gene alone and together with its paralogue GhJUB1_3-Dt reduced the drought tolerance in cotton plants. The transgenic lines exhibited tolerance to the drought and salt stress as compared to the wildtype (WT). The chlorophyll and relative water contents of wildtype decreased under drought as compared to the transgenic lines. The transgenic lines showed decreased H2O2 and increased proline levels under drought and salt stress, as compared to the WT, indicating that the transgenic lines have drought and salt stress tolerance. The expression analysis of the transgenic lines and WT revealed that GAI was upregulated in the transgenic lines in normal conditions as compared to the WT. Under drought and salt treatment, RAB18 and RD29A were strongly upregulated in the transgenic lines as compared to the WT. Conclusively, GhJUB1_3-At is not an auto activator and it is regulated by the crosstalk of GhHB7, GhRAP2-3 and GhRAV1. GhRAV1, a negative regulator of abiotic stress tolerance and positive regulator of leaf senescence, suppresses the expression of GhJUB1_3-At under severe circumstances leading to plant death.

Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Acute Myocardial Infarction: A Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular (CV) outcomes in patients with or without Type 2 diabetes and heart failure (HF). However, studies have shown conflicting evidence regarding their efficacy in patients following acute myocardial infarction (MI). We conducted a pilot systematic review and meta-analysis to synthesise the available evidence regarding the effectiveness of SGLT2 inhibitors in MI. METHODS: A systematic literature search was conducted using PubMed/MEDLINE, the Cochrane Library and Embase databases to identify randomised controlled trials (RCTs) that compared clinical outcomes of SGLT2 inhibitors with placebo following MI. We conducted the statistical analysis using RevMan, version 5.4 and pooled risk ratios (RRs) along the corresponding 95% confidence interval (CI) for all outcomes. RESULTS: Five RCTs reporting data for 11,211 patients were included in our study. The mean follow-up duration was 43.8 weeks. Our pooled analysis showed that SGLT2 inhibitors significantly reduced the risk of hospitalisations for heart failure (HHF) (RR = 0.76, 95% CI: 0.61-0.88, p = 0.001) in patients with MI. However, the risk of all-cause mortality (RR = 1.05, 95% CI: 0.78-1.41, p = 0.76), CV mortality (RR = 1.04, 95% CI = 0.84-1.29, p = 0.73) and all-cause hospitalisations (RR = 1.06, 95% CI: 0.96-1.17, p = 0.25) remained comparable across the two groups. CONCLUSION: SGLT2 inhibitors reduce HHF without affecting all-cause mortality, CV mortality and all-cause hospitalisations. However, further evidence is required to reach a definitive conclusion.

Inhibition of forward and reverse transport of Ca2+ via Na+/Ca2+ exchangers (NCX) prevents sperm capacitation.

BACKGROUND: While calcium is known to play a crucial role in mammalian sperm physiology, how it flows in and out of the male gamete is not completely understood. Herein, we investigated the involvement of Na+/Ca2+ exchangers (NCX) in mammalian sperm capacitation. Using the pig as an animal model, we first confirmed the presence of NCX1 and NCX2 isoforms in the sperm midpiece. Next, we partially or totally blocked Ca2+ outflux (forward transport) via NCX1/NCX2 with different concentrations of SEA0400 (2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline; 0, 0.5, 5 and 50 µM) and Ca2+ influx (reverse transport) with SN6 (ethyl 2-[[4-[(4-nitrophenyl)methoxy]phenyl]methyl]-1,3-thiazolidine-4-carboxylate; 0, 0.3, 3 or 30 µM). Sperm were incubated under capacitating conditions for 180 min; after 120 min, progesterone was added to induce the acrosome reaction. At 0, 60, 120, 130, and 180 min, sperm motility, membrane lipid disorder, acrosome integrity, mitochondrial membrane potential (MMP), tyrosine phosphorylation of sperm proteins, and intracellular levels of Ca2+, reactive oxygen species (ROS) and superoxides were evaluated. RESULTS: Partial and complete blockage of Ca2+ outflux and influx via NCX induced a significant reduction of sperm motility after progesterone addition. Early alterations on sperm kinematics were also observed, the effects being more obvious in totally blocked than in partially blocked samples. Decreased sperm motility and kinematics were related to both defective tyrosine phosphorylation and mitochondrial activity, the latter being associated to diminished MMP and ROS levels. As NCX blockage did not affect the lipid disorder of plasma membrane, the impaired acrosome integrity could result from reduced tyrosine phosphorylation. CONCLUSIONS: Inhibition of outflux and influx of Ca2+ triggered similar effects, thus indicating that both forward and reverse Ca2+ transport through NCX exchangers are essential for sperm capacitation.

Modeling the liquid-liquid chromatography separation of cannabinoids from hemp extracts.

The separation of cannabinoids from hemp materials is nowadays one of the most promising industrial applications of liquid-liquid chromatography (LLC). Despite various experimental research efforts to purify cannabinoids, there are currently few works on process modeling. Thus, this study aimed to explore a straightforward approach to model the LLC separation of cannabinoids from two hemp extracts with different compositions. The feed materials were simplified to mixtures of preselected key components (i.e., cannabidiol, tetrahydrocannabinol, cannabigerol, and cannabinol). The elution profiles of cannabinoids were simulated using the equilibrium-cell model with an empirical nonlinear correlation. The model parameters were derived from the elution profiles of single-solute pulse injections. For the validation of the proposed approach, LLC separations with the two hemp extracts were performed in descending mode with the solvent system composed of hexane/methanol/water 10/8/2 (v/v/v). The injected sample concentrations were gradually increased from 5 to 100 mg/mL. The results showed that the approach could describe reasonably well the elution behavior of the cannabinoids, with deviations of only 1-2 min between simulated and experimental elution times. However, to improve the prediction accuracy, the model parameters can be refitted to the elution profiles of 3-4 systematically selected pulse injections with specific hemp extracts.

Intravenous iron therapy for heart failure and iron deficiency: An updated meta-analysis of randomized clinical trials.

Heart failure (HF) patients frequently exhibit iron deficiency, which is associated with a poor prognosis. Although various trials have been conducted, it is uncertain if intravenous (IV) iron replenishment improves clinical outcomes in HF patients with iron deficiency. A comprehensive literature search was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library from inception till 15 September 2023 to retrieve randomized controlled trials (RCTs) that compared IV iron therapy with placebo or standard of care in patients with HF and iron deficiency. Clinical outcomes were assessed by generating forest plots using the random-effects model and pooling odds ratios (ORs) or weighted mean differences (WMDs). Fourteen RCTs with 6651 patients were included. IV iron therapy showed a significantly reduced incidence of the composite of first heart failure hospitalization (HHF) or cardiovascular (CV) mortality as compared with the control group (OR = 0.73, 95% CI: 0.58 to 0.92). The IV iron therapy resulted in a trend towards lower CV mortality (OR = 0.88, 95% CI: 0.76 to 1.01), 1-year all-cause mortality (OR = 0.85, 95% CI: 0.71 to 1.02), and first HHF (OR = 0.73, 95% CI: 0.51 to 1.05), and an improved left ventricular ejection fraction (LVEF) (MD = 4.54, 95% CI: -0.13 to 9.21). Meta-regression showed a significant inverse moderating effect of baseline LVEF on the first HHF or CV death. In patients with HF and iron deficiency, IV iron therapy reduced the incidence of composite of first HHF or CV mortality. There was a trend of lower overall CV and 1-year all-cause mortality, first HHF, and improved LVEF with IV iron therapy.

Optical coherence tomography-guided vs. intravascular ultrasound-guided percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials.

Background: Optical coherence tomography (OCT) and intravascular ultrasound (IVUS) are superior to coronary angiography for guiding percutaneous coronary intervention (PCI). However, whether one technique is superior to the other is inconclusive. Methods: We searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception to November 2023 for randomized controlled trials (RCTs) comparing OCT and IVUS in patients undergoing PCI. RevMan 5.4 was used to pool outcomes with risk ratio (RR) as the effect measure. Results: Six RCTs (4,402 patients) were included in this meta-analysis. There was no significant difference between the OCT- and IVUS-guided PCI groups in the risk of major adverse cardiovascular events (RR 0.87, 95% CI: 0.65, 1.16; I2 = 0%) and cardiac mortality (RR 0.73, 95% CI: 0.24, 2.21; I2 = 0%). The results were consistent across the subgroups of the presence or absence of left main disease (P interaction >0.1). There were no significant differences between OCT and IVUS in the risk of target lesion revascularization (RR 0.78, 95% CI: 0.47, 1.30; I2 = 0%), target vessel revascularization (RR 1.06, 95% CI: 0.69, 1.62; I2 = 0%), target-vessel myocardial infarction (RR 0.79, 95% CI: 0.40, 1.53; I2 = 0%), stent thrombosis (RR 0.59, 95% CI: 0.12, 2.97; I2 = 0%), and all-cause mortality (RR 1.01, 95% CI: 0.53, 1.90; I2 = 0%). Conclusions: Our meta-analysis demonstrated similar clinical outcomes in OCT- and IVUS-guided PCI. New large-scale multicenter RCTs with long-term follow-up are required to confirm or refute our findings and provide more reliable results. Systematic Review Registration: PROSPERO, identifier, CRD42023486933.

The effect of oral anticoagulants on the incidence of dementia in patients with atrial fibrillation: A systematic review and meta-analysis.

Background: Dementia is a recognized complication of atrial fibrillation (AF). Oral anticoagulant (OAC) therapy can potentially be protective against this complication. Methods: A comprehensive search of MEDLINE and Embase for comparative observational studies reporting the efficacy of OAC therapy for the incidence of dementia in patients with AF was conducted from its inception until March 2023. Studies that had patients with prior use of OAC or with a previous history of dementia were excluded. Results: A total of 22 studies were included in this review involving 617,204 participants. The pooled analysis revealed that OAC therapy, including direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs), was associated with a reduced incidence of dementia in AF patients. Specifically, compared to non-OAC treatment, OACs demonstrated a significant reduction in dementia incidence (HR 0.68, 95 % CI [0.58, 0.80], p < 0.00001), with similar findings observed for DOACs (HR 0.69, 95 % CI [0.51, 0.94], p = 0.02) and VKAs (HR 0.73, 95 % CI [0.56, 0.95], p = 0.02). The comparison of DOAC vs VKA revealed that DOACs are associated with reduced risk of dementia (HR 0.87, 95 % CI [0.79, 0.96], p = 0.004). Conclusion: Our SR and meta-analysis showed that the use of OAC therapy is associated with a reduced risk of dementia in individuals with AF. However, our results are limited by the potential influence of confounding bias and significant heterogeneity in the analyses.

Immediate Versus Staged Complete Revascularization in Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

A strategy of complete revascularization (CR) is recommended in patients with acute coronary syndrome (ACS) and multivessel disease (MVD). However, the optimal timing of CR remains equivocal. We searched MEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing immediate CR (ICR) with staged CR in patients with ACS and MVD. Our primary outcomes were all-cause and cardiovascular mortality. All outcomes were assessed at 3 time points: in-hospital or at 30 days, at 6 months to 1 year, and at >1 year. Data were pooled in RevMan 5.4 using risk ratios as the effect measure. A total of 9 RCTs (7,506 patients) were included in our review. A total of 7 trials enrolled patients with ST-segment elevation myocardial infarction (STEMI), 1 enrolled patients with non-STEMI only, and 1 enrolled patients with all types of ACS. There was no difference between ICR and staged CR regarding all-cause and cardiovascular mortality at any time window. ICR reduced the rate of myocardial infarction and decreased the rate of repeat revascularization at 6 months and beyond. The rates of cerebrovascular events and stent thrombosis were similar between the 2 groups. In conclusion, the present meta-analysis demonstrated a lower rate of myocardial infarction and a reduction in repeat revascularization at and after 6 months with ICR strategy in patients with mainly STEMI and MVD. The 2 groups had no difference in the risk of all-cause and cardiovascular mortality. Further RCTs are needed to provide more definitive conclusions and investigate CR strategies in other ACS.

Case Report: A challenging diagnosis of an apocrine sweat gland carcinoma.

The differential diagnosis for an axillary mass in a patient with a previously treated malignancy is broad and definitive tissue diagnosis is required to guide treatment and surveillance strategies. We present the case of a 76-year-old African American male with a history of prostate cancer who presented with a left axillary mass two years after achieving remission from his prostate malignancy. Due to the diagnostic challenge, this excisional biopsy was reviewed at four different academic centers. Although no universal consensus among these institutions' pathologists, but in the context of clinical presentation and anatomic location, the overall clinical findings are consistent with apocrine sweat gland carcinoma. The mass was treated with complete local surgical excision, though regional lymph node metastasis occurred 2 years later. Multimodal treatment with surgery and radiation was done with removal of regional metastasis and no distant disease was identified. Primary apocrine carcinoma is a rare cutaneous neoplasm with less than 100 reported cases in the literature. A combination of clinical history and presentation, histomorphology, anatomical location, and immunohistochemistry is used to support the diagnosis and ultimately drive management.

Comparison of Rifaximin Alone and With Quinolones in the Primary Prevention of Spontaneous Bacterial Peritonitis in Patients With Decompensated Chronic Liver Disease.

Background In cirrhotic patients with ascites, primary prevention of spontaneous bacterial peritonitis (SBP) is a key strategy to lower morbidity and death. Rifaximin and fluoroquinolone used alternately as main prophylaxis are as effective as reported. This study aimed to compare the frequency of occurrence of SBP in patients with decompensated chronic liver disease treated with rifaximin alone and in combination with fluoroquinolone. Methodology A total of 76 patients with hepatitis C virus-related decompensated chronic liver disease and ascites were divided into two groups based on matching age, sex, and Child-Pugh class. Group A (38 patients) received rifaximin 1,100 mg/day in two divided doses with daily fluoroquinolone 400 mg/day, whereas group B (38 patients) received rifaximin 1,100 mg/day alone as a two dosage. The patients were monitored for up to three months. The study's endpoints were SBP, hepatocellular carcinoma, compliance failure, death, or liver transplantation. Results In this comparative study involving 76 patients, the demographic and clinical characteristics were assessed across two treatment groups: rifaximin alone (n = 38) and rifaximin with fluoroquinolone (n = 38). The combination therapy demonstrated a statistically significant reduction in SBP compared to rifaximin alone. Additionally, the overall survival rate was higher in the combination group. These findings suggest potential benefits of the combined approach in managing hepatic encephalopathy-related complications. Conclusions When compared to rifaximin alone for primary SBP prophylaxis, the combination of rifaximin with fluoroquinolone exhibited greater effectiveness with the same safety profile.

Fully Screen-Printed and Gentle-to-Skin Wet ECG Electrodes with Compact Wireless Readout for Cardiac Diagnosis and Remote Monitoring.

Recent advances in electrocardiogram (ECG) diagnosis and monitoring have triggered a demand for smart and wearable ECG electrodes and readout systems. Here, we report the development of a fully screen-printed gentle-to-skin wet ECG electrode integrated with a scaled-down printed circuit board (PCB) packaged inside a 3D-printed antenna-on-package (AoP). All three components of the wet ECG electrode (i.e., silver nanowire-based conductive part, electrode gel, and adhesive gel) are screen-printed on a flexible plastic substrate and only require 265 times less metal for the conductive part and 176 times less ECG electrode gel than the standard commercial wet ECG electrodes. In addition, our electrically small AoP achieved a maximum read range of 142 m and offers a 4 times larger wireless communication range than the typical commercial chip antenna. The adult volunteers' study results indicated that our system recorded ECG data that correlated well with data from a commercial ECG system and electrodes. Furthermore, in the context of a 12-lead ECG diagnostic system, the fully printed wet ECG electrodes demonstrated a performance similar to that of commercially available wet ECG electrodes while being gentle on the skin. This was confirmed through a blind review method by two cardiology consultants and one family medicine consultant, validating the consistency of the diagnostic information obtained from both electrodes. In conclusion, these findings highlight the potential of fully screen-printed wet ECG electrodes for both monitoring and diagnostic purposes. These electrodes could serve as potential candidates for clinical practice, and the screen-printing method has the capability to facilitate industrial mass production.

Suspected Burn From a 9-Voltage Battery.

Advancements in technology allow for the utilization of low-voltage battery-powered devices for patients admitted to the hospital. There have been rare cases of burns due to leakage of the internal contents from low-voltage batteries, but to date, there have been no reports of electrical burns caused by low-voltage batteries. We present the case of an 89-year-old female who presented to the general surgery service with a suspected electrical burn from laying on a 9-volt battery. The patient underwent operative debridement with no evidence of a deeper injury. The patient continues to follow up with an outpatient wound clinic and is healing well. This case highlights the importance of teaching and raising awareness of all small devices that may become entangled or lost in patients' linens, such as 9-volt telemetry batteries, to prevent harm.

Skin Biopsy as a Diagnostic Tool for Synucleinopathies.

Studies published in the last decade identified skin biopsies as a promising source of material for detecting alpha-synuclein (αSN). Alpha-synuclein gets deposited in the skin of patients with synucleinopathies, and therefore, a skin biopsy can be used to diagnose and confirm these diseases histopathologically. A skin biopsy can also be helpful for studies focusing on the nature of αSN deposits. The most important aspects of a biomarker are sensitivity, specificity, and technical feasibility. The potential for a skin biopsy to become the clinical tool of choice as a reliable biomarker for diagnosing synucleinopathies appears to be high, with consistently high sensitivity (>80%) and specificity approaching 100%. The review aims to provide an overview of the factors impacting skin biopsy's sensitivity, specificity, and feasibility in detecting dermal αSN deposits.

An open-source, automated, and cost-effective platform for COVID-19 diagnosis and rapid portable genomic surveillance using nanopore sequencing.

The COVID-19 pandemic, caused by SARS-CoV-2, has emphasized the necessity for scalable diagnostic workflows using locally produced reagents and basic laboratory equipment with minimal dependence on global supply chains. We introduce an open-source automated platform for high-throughput RNA extraction and pathogen diagnosis, which uses reagents almost entirely produced in-house. This platform integrates our methods for self-manufacturing magnetic nanoparticles and qRT-PCR reagents-both of which have received regulatory approval for clinical use-with an in-house, open-source robotic extraction protocol. It also incorporates our "Nanopore Sequencing of Isothermal Rapid Viral Amplification for Near Real-time Analysis" (NIRVANA) technology, designed for tracking SARS-CoV-2 mutations and variants. The platform exhibits high reproducibility and consistency without cross-contamination, and its limit of detection, sensitivity, and specificity are comparable to commercial assays. Automated NIRVANA effectively identifies circulating SARS-CoV-2 variants. Our in-house, cost-effective reagents, automated diagnostic workflows, and portable genomic surveillance strategies provide a scalable and rapid solution for COVID-19 diagnosis and variant tracking, essential for current and future pandemic responses.

Antimicrobial drug resistant features of Mycobacterium tuberculosis associated with treatment failure.

Tuberculosis stands as a prominent cause of mortality in developing countries. The treatment of tuberculosis involves a complex procedure requiring the administration of a panel of at least four antimicrobial drugs for the duration of six months. The occurrence of treatment failure after the completion of a standard treatment course presents a serious medical problem. The purpose of this study was to evaluate antimicrobial drug resistant features of Mycobacterium tuberculosis associated with treatment failure. Additionally, it aimed to evaluate the effectiveness of second line drugs such as amikacin, linezolid, moxifloxacin, and the efflux pump inhibitor verapamil against M. tuberculosis isolates associated with treatment failure. We monitored 1200 tuberculosis patients who visited TB centres in Lahore and found that 64 of them were not cured after six months of treatment. Among the M. tuberculosis isolates recovered from the sputum of these 64 patients, 46 (71.9%) isolates were simultaneously resistant to rifampicin and isoniazid (MDR), and 30 (46.9%) isolates were resistant to pyrazinamide, Resistance to amikacin was detected in 17 (26,5%) isolates whereas resistance to moxifloxacin and linezolid was detected in 1 (1.5%) and 2 (3.1%) isolates respectively. Among MDR isolates, the additional resistance to pyrazinamide, amikacin, and linezolid was detected in 15(23.4%), 4(2.6%) and 1(1.56%) isolates respectively. One isolate simultaneously resistant to rifampicin, isoniazid, amikacin, pyrazinamide, and linezolid was also identified. In our investigations, the most frequently mutated amino acid in the treatment failure group was Serine 315 in katG. Three novel mutations were detected at codons 99, 149 and 154 in pncA which were associated with pyrazinamide resistance. The effect of verapamil on the minimum inhibitory concentration of isoniazid and rifampicin was observed in drug susceptible isolates but not in drug resistant isolates. Rifampicin and isoniazid enhanced the transcription of the efflux pump gene rv1258 in drug susceptible isolates collected from the treatment failure patients. Our findings emphasize a high prevalence of MDR isolates linked primarily to drug exposure. Moreover, the use of amikacin as a second line drug may not be the most suitable choice in such cases.

Recent genome resequencing paraded COBRA-Like gene family roles in abiotic stress and wood formation in Poplar.

A cell wall determines the mechanical properties of a cell, serves as a barrier against plant stresses, and allows cell division and growth processes. The COBRA-Like (COBL) gene family encodes a putative glycosylphosphatidylinositol (GPI)-anchored protein that controls cellulose deposition and cell progression in plants by contributing to the microfibril orientation of a cell wall. Despite being studied in different plant species, there is a dearth of the comprehensive global analysis of COBL genes in poplar. Poplar is employed as a model woody plant to study abiotic stresses and biomass production in tree research. Improved genome resequencing has enabled the comprehensive exploration of the evolution and functional capacities of PtrCOBLs (Poplar COBRA-Like genes) in poplar. Phylogeny analysis has discerned and classified PtrCOBLs into two groups resembling the Arabidopsis COBL family, and group I genes possess longer proteins but have fewer exons than group II. Analysis of gene structure and motifs revealed PtrCOBLs maintained a rather stable motif and exon-intron pattern across members of the same group. Synteny and collinearity analyses exhibited that the evolution of the COBL gene family was heavily influenced by gene duplication events. PtrCOBL genes have undergone both segmental duplication and tandem duplication, followed by purifying selection. Promotor analysis flaunted various phytohormone-, growth- and stress-related cis-elements (e.g., MYB, ABA, MeJA, SA, AuxR, and ATBP1). Likewise, 29 Ptr-miRNAs of 20 families were found targeting 11 PtrCOBL genes. PtrCOBLs were found localized at the plasma membrane and extracellular matrix, while gene ontology analysis showed their involvement in plant development, plant growth, stress response, cellulose biosynthesis, and cell wall biogenesis. RNA-seq datasets depicted the bulk of PtrCOBL genes expression being found in plant stem tissues and leaves, rendering mechanical strength and rejoinders to environmental cues. PtrCOBL2, 3, 10, and 11 manifested the highest expression in vasculature and abiotic stress, and resemblant expression trends were upheld by qRT-PCR. Co-expression network analysis identified PtrCOBL2 and PtrCOBL3 as hub genes across all abiotic stresses and wood developing tissues. The current study reports regulating roles of PtrCOBLs in xylem differentiating tissues, tension wood formation, and abiotic stress latency that lay the groundwork for future functional studies of the PtrCOBL genes in poplar breeding.

Efficacy and safety of sodium-glucose cotransporter-2 inhibitors for heart failure with mildly reduced or preserved ejection fraction: a systematic review and meta-analysis of randomized controlled trials.

Aims: We sought to conduct a meta-analysis to evaluate the efficacy and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and HF with mildly reduced ejection fraction (HFmrEF). Methods: We searched the Cochrane Library, MEDLINE (via PubMed), Embase, and ClinicalTrials.gov till March 2023 to retrieve all randomized controlled trials of SGLT2i in patients with HFpEF or HFmrEF. Risk ratios (RRs) and standardized mean differences (SMDs) with their 95% confidence intervals (95% CIs) were pooled using a random-effects model. Results: We included data from 14 RCTs. SGLT2i reduced the risk of the primary composite endpoint of first HF hospitalization or cardiovascular death (RR 0.81, 95% CI: 0.76, 0.87; I2 = 0%); these results were consistent across the cohorts of HFmrEF and HFpEF patients. There was no significant decrease in the risk of cardiovascular death (RR 0.96, 95% CI: 0.82, 1.13; I2 = 36%) and all-cause mortality (RR 0.97, 95% CI: 0.89, 1.05; I2 = 0%). There was a significant improvement in the quality of life in the SGLT2i group (SMD 0.13, 95% CI: 0.06, 0.20; I2 = 51%). Conclusion: The use of SGLT2i is associated with a lower risk of the primary composite outcome and a higher quality of life among HFpEF/HFmrEF patients. However, further research involving more extended follow-up periods is required to draw a comprehensive conclusion. Systematic Review Registration: PROSPERO (CRD42022364223).

A Missense Pathogenic Variant in a Conserved Region of CNTNAP2 Is Associated with Obesity, Seizures, and Language Impairment in a Pakistani Family.

Introduction: In a consanguineous family, seven siblings born in three sibships showed a syndromic disorder characterized by obesity, seizures, and language impairment phenotypes, which appeared at early age or developed during early childhood. Methods: By whole-exome sequencing and subsequent Sanger sequencing, a novel homozygous missense variant (c.3371 T>A [p.Ile1124Asn]) in exon 20 of the CNTNAP2 gene was identified. Results: The pathogenic variant in this family is located within one of the laminin G-like 4 domains of CASPR2 and may cause loss of hydrophobic interactions of CASPR2 with its partner proteins. Single nucleotide and copy number variants in this gene have previously been related to Gilles de la Tourette syndrome, cortical dysplasia-focal epilepsy syndrome, schizophrenia, Pitt-Hopkins syndrome, and autism spectrum, attention deficit hyperactivity, and obsessive compulsive disorders. Yet, few studies described patients with CNTNAP2 variants showing diet-induced obesity. Conclusion: This report expands the phenotypic spectrum of this rare syndrome and provides deeper insights by documenting the clinical features and genetic findings of the patients.

Extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A meta-analysis of randomized controlled trials.

INTRODUCTION: Extracorporeal cardiopulmonary resuscitation (ECPR) is a resuscitation method for patients with refractory out-of-hospital cardiac arrest (OHCA). However, evidence from randomized controlled trials (RCTs) is lacking. METHODS: We searched several electronic databases until March 2023 for RCTs comparing ECPR with conventional CPR in OHCA patients. RevMan 5.4 was used to pool risk ratios (RR) with 95% confidence intervals (CIs). RESULTS: A total of four RCTs were included. The results of our meta-analysis showed no statistically significant benefit of ECPR regarding mid-term survival (RR 1.21; 95% CI 0.64 to 2.28; I2 = 48%; p = .55). We found a significant improvement with ECPR in mid-term favorable neurological outcome (RR 1.59; 95% CI 1.09 to 2.33; I2 = 0%; p = .02). There was no significant difference between ECPR and conventional CPR in long-term survival (RR 1.32; 95% CI 0.18 to 9.50; I2 = 64%; p = .79), and long-term favorable neurological outcome (RR 1.47; 95% CI 0.89 to 2.43; I2 = 25%; p = .13). There was an increased incidence of adverse events in the ECPR group (RR 3.22; 95% CI 1.18 to 8.80; I2 = 63%; p = .02). CONCLUSION: ECPR in OHCA patients was not associated with improved survival or long-term favorable neurological outcome but did improve favorable neurological outcome in the mid-term. However, these results are likely underpowered due to the small number of available RCTs. Large-scale confirmatory RCTs are needed to provide definitive conclusions.