Human olfactory neurosphere-derived cells: A unified tool for neurological disease modelling and neurotherapeutic applications.

As one of the leading causes of global mortality and morbidity, various neurological diseases cause social and economic burdens. Despite significant advances in the treatment of neurological diseases, establishing a proper disease model, especially for degenerative and infectious diseases, remains a major challenging issue. For long, mice were the model of choice but suffered from serious drawbacks of differences in anatomical and functional aspects of the nervous system. Furthermore, the collection of post-mortem brain tissues limits their usage in cultured cell lines. Overcoming such limitations has prompted the usage of stem cells derived from the peripheral nervous system, such as the cells of the olfactory mucosa as a preferred choice. These cells can be easily cultured in vitro and retain the receptors of neuronal cells life-long. Such cells have various advantages over embryonic or induced stem cells, including homology, and ease of culture and can be conveniently obtained from diseased individuals through either biopsies or exfoliation. They have continuously helped in understanding the genetic and developmental mechanisms of degenerative diseases like Alzheimer's and Parkinson's disease. Moreover, the mode of infection of various viruses that can lead to post-viral olfactory dysfunction, such as the Zika virus can be monitored through these cells in vitro and their therapeutic development can be fastened.

Safety and efficacy of antithrombotics in outpatients with symptomatic COVID-19: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease (COVID-19) is a global health emergency, with well over six hundred million infections and over six million deaths to date. Besides other ramifications, it is also associated with inflammation and an augmented risk of thromboembolic complications. Despite this, the risks and benefits of antithrombotic drugs in patients with mild to moderate COVID-19 have not been well-established and remain controversial. OBJECTIVES: To evaluate the safety and efficacy of antithrombotic drugs on mild to moderate symptomatic COVID-19 patients by performing an updated systematic review and meta-analysis. METHODS: We queried electronic databases (PubMed, Cochrane Central, Scopus, and Embase) from their inception up to September 2022 for randomized controlled trials comparing antithrombotic drugs against placebo. The outcomes of interest were the need for hospital care, mortality, and thromboembolic events in the enrolled participants. Dichotomous outcomes were presented as risk ratio (RR) with 95 % confidence intervals (CIs) and were consolidated using random-effects model. MAIN RESULTS: Five eligible studies (Rivaroxaban/Apixaban, two; enoxaparin, two; Sulodexide, one), consisting of 2,005 participants with mild to moderate COVID-19, were included. Pooled results show that antithrombotics, when compared to placebo, do not significantly reduce all-cause mortality (RR 0.51, 95 % CI 0.15-1.68; P = 0.27; I2 = 0), thromboembolic events (RR 0.78, 95 % CI 0.17-3.51; P = 0.74; I2 = 0), need for hospitalization (RR 0.73, 95 % CI 0.51-1.03; P = 0.08; I2 = 0), nor significantly increase clinically relevant non-major bleeding events (RR 2.36, 95 % CI 0.56-9.89; P = 0.24; I2 = 0). However, when Sulodexide was compared independently to other antithrombotics, it significantly reduced the need for hospitalization (RR 0.60, 95 % CI 0.37-0.95; P = 0.03). CONCLUSIONS: Our pooled analysis was not able to establish statistically significant benefits or risks of using antithrombotic drugs in mild to moderate COVID-19 patients. To further improve our understanding of the efficacy, safety and risk profile of such a therapy, large sample randomized clinical trials are required on a wide scale.

Renally Dosed Cefepime Leading to Cefepime-Induced Neurotoxicity: A Case Report.

Cefepime is a broad-spectrum fourth-generation cephalosporin with activity against both gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. Cefepime is most commonly used for urinary tract infections, soft tissue infections, and febrile neutropenia. Up to 15% of ICU patients on cefepime may experience cefepime-induced neurotoxicity (CIN), with risk factors including renal dysfunction, excessive dosage, elevated serum cefepime concentrations, and history of prior brain injury. The adverse effects of CIN, including encephalopathy, seizures, and coma can be resolved with drug cessation, antiepileptics, or hemodialysis. Here, we present the case of CIN in a 59-year-old female patient with long-term cefepime antibiotic prescription for Pseudomonas bacteremia and endocarditis with multiple risk factors for reduced renal function. We discuss the relevant risk factors and preventive measures that may have prevented her from developing CIN, as well as the importance of early recognition and prevention of CIN in patient care.

Impact of Body Mass Index on outcomes in hospitalized heart failure patients with reduced versus preserved ejection fraction: a 1,699,494-individual analysis from the United States National Inpatient Sample.

BACKGROUND: Obesity's effect on outcomes in heart failure (HF) patients with reduced versus maintained ejection fraction (HFrEF and HFpEF) remains debatable. We evaluated hospital outcomes and healthcare expenditures in these patients based on their Body Mass Index (BMI). METHODS: Using the USA National Inpatient Sample (NIS) database, patients >18 years admitted with a primary diagnosis of HFrEF or HFpEF between January 1, 2004, and August 31, 2015, were studied. Patients were stratified into the following BMI categories: underweight, normal weight, overweight, obese, and morbidly obese. Adjusted multivariable analyses using Poisson regression models were used to study the association between BMI and hospital outcomes and healthcare costs. RESULTS: Overall, 1,699,494 patients were included. After full adjustment, obesity (OR=1.84; 95% CI: 1.22-2.76) and morbid obesity (OR=1.81; 95% CI: 1.22-2.70) increased the odds of in-hospital mortality compared with normal weight. When stratified per ejection fraction, underweight patients had higher odds of in-hospital mortality in HFrEF (OR=1.46; 95% CI: 1.06-2.01). Obese and morbidly obese patients had higher odds of in-hospital mortality in both HFrEF and HFpEF. Furthermore, obese and morbidly obese patients had a longer mean adjusted length of stay and higher health care expenses. CONCLUSIONS: Being underweight is associated with increased risk of in-hospital mortality in HFrEF patients. Obesity and morbid obesity increase the risk of in-hospital mortality and higher healthcare costs in both HFrEF and HFpEF. These findings have clinical significance for HF patients, and further research is needed to investigate the ideal weight for HF patients.

Efficacy of Allopurinol in Improving Endothelial Dysfunction: A Systematic Review and Meta-Analysis.

INTRODUCTION: Endothelial dysfunction has been implicated in various cardiovascular disorders as the initial pathology. Allopurinol has been shown to improve endothelial dysfunction in patients with gout, but its effect on cardiovascular patients is unclear. AIMS: We aim to assess allopurinol efficacy in improving endothelial dysfunction overall and in different disease states including but not limited to heart failure, chronic kidney disease, ischemic heart disease METHODS: We conducted a literature search of PubMed, Cochrane's Central Library, and Scopus until December 2022, including randomized controlled trials and double-arm observational studies. The primary outcome measure was endothelial function assessed by change in flow mediated dilation (FMD) RESULTS: Our meta-analysis included 22 studies with a total of 1472 patients. Our pooled analysis shows that allopurinol significantly improved FMD (WMD = 1.46%, 95% CI [0.70, 2.22], p < 0.01) compared to control. However, there was no significant difference between allopurinol and control for endothelial-independent vasodilation measured by forearm blood flow (WMD = 0.10%, 95% CI [- 0.89, 0.69], p = 0.80). Subgroup analysis indicated that the effect of allopurinol on FMD was more significant in diabetic and congestive heart failure patients. CONCLUSION: While allopurinol may improve endothelial function in various patient populations, further high-quality randomized controlled trials are needed to determine its efficacy in preventing cardiovascular disease exacerbation.

Guillain-Barré Syndrome Presenting as Symmetrical Proximal Muscle Weakness: An Atypical Presentation.

Guillain-Barré syndrome occurs via molecular mimicry when a trigger sets off an immune response on peripheral nerve epitopes. Patients typically report an antecedent infection, such as an upper respiratory infection or Campylobacter jejuni gastroenteritis. It is typically characterized by progressive, symmetric muscle weakness with absent/decreased deep tendon reflexes. Most cases in the literature report that the paralysis begins in the legs distally and ascends to the extremities. Patients may have sensory symptoms or dysautonomia as well. Notable variant forms include acute motor axonal neuropathy, acute motor/sensory neuropathy, Miller Fisher syndrome, and Bickerstaff brainstem encephalitis. Diagnosis is confirmed if a lumbar puncture shows albuminocytologic dissociation (typically 45 to 200 mg/dL). Nerve conduction studies may also be considered but are not necessary. Management is largely supportive, but intravenous immunoglobulin and/or plasmapheresis for more severe cases may be considered.

Folfirinox vs. Gemcitabine + Nab-Paclitaxel as the First-Line Treatment for Pancreatic Cancer: A Systematic Review and Meta-Analysis.

Background: The efficacy and safety of Folfirinox (FFX) or gemcitabine + nab-paclitaxel (GnP) to be used as the first-line drugs for pancreatic cancer (PC) is yet to be established. We conducted an analysis of retrospective studies to assess the efficacy and safety of these two regimens by comparing their survival and safety outcomes in patients with PC. Methods: We conducted an extensive review of two electronic databases from inception till February 2023 to include all the relevant studies that compared FFX with GnP published and unpublished work. Retrospective studies were only included. Overall survival (OS) and progression-free survival (PFS) were pooled using hazard ratios (HRs), while objective response rate (ORR) and safety outcomes were pooled using odds ratios (ORs) with 95% confidence interval (CI) using the random effects model. Results: A total of 7,030 patients were identified in a total of 21 articles that were shortlisted. Pooled results concluded that neither FFX nor GnP was associated to increase the OS time (HR: 0.93, 95% CI: 0.83 - 1.04; P = 0.0001); however, FFX was more likely associated with increased PFS when compared to GnP (HR: 0.88, 95% CI: 0.81 - 0.97; P < 0.0001). ORR proved to be non-significant between the two regimens (OR: 0.90, 95% CI: 0.64 - 1.27; P = 0.15). Safety outcomes included neutropenia, anemia, thrombocytopenia and diarrhea. GnP was more associated with diarrhea (OR: 1.96, 95% CI: 1.22 - 3.15; P = 0.001), while FFX was seen to cause anemia (OR: 0.70, 95% CI: 0.51 - 0.98; P = 0.10) in PC patients. Neutropenia and thrombocytopenia were in-significant in the two drug regimens (OR: 1.10, 95% CI: 0.92 - 1.31; P = 0.33 and OR: 0.83, 95% CI: 0.60 - 1.13; P = 0.23, respectively). Conclusion: FFX and GnP showed a significant difference in increasing the PFS, while no difference was observed while measuring OS. Safety outcomes showed that FFX and GnP shared similar safety profiles as FFX was associated with hematological outcomes, while GnP was more associated with non-hematological outcomes.

Effectiveness of Emergency versus Nonemergent Coronary Angiography After Out-of-Hospital Cardiac Arrest without ST-Segment Elevation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The optimal timing of coronary angiography (CAG) in patients after out-of-hospital cardiac arrest (OHCA) without ST-segment elevation remains controversial. Therefore, we conducted a meta-analysis of randomized control trials to investigate the effectiveness of emergency CAG versus delayed CAG in OHCA patients with a non-ST-segment elevated rhythm. PubMed, Scopus, CINAHL, Cochrane CENTRAL, and JBI databases were searched from inception to September 7, 2022. Our primary end point was survival with a good neurological outcome, whereas the secondary outcomes included short-term survival, mid-term survival, recurrent arrhythmias, myocardial infarction after hospitalization, major bleeding, acute kidney injury, and left ventricular ejection fraction. Nine randomized control trials involving 2,569 patients were included in this analysis. Our meta-analysis showed no significant difference in the improvement of neurological outcome (RR 0.96, 95% Confidence Interval [CI] [0.87, 1.06]), short-term survival (risk ratio [RR] 0.98, 95% CI [0.89, 1.08]), mid-term survival (RR 0.98, 95% CI [0.87, 1.10]), recurrent arrhythmias (RR 1.02, 95% CI [0.50, 2.06]), myocardial infarction (RR 0.66, 95% CI [0.13, 3.30]), major bleeding (RR 0.96, 95% CI [0.55, 1.69]), acute kidney injury (RR 1.20, 95% CI [0.32, 4.49]) and left ventricular ejection fraction (RR 0.89, 95% CI [0.69, 1.15]) in patients who underwent emergency CAG compared with delayed CAG patients. In conclusion, our analysis revealed that emergency CAG had no prognostic superiority over delayed CAG in patients with OHCA without ST-segment elevation.

Duet of Death: Biventricular Thrombus in a Methamphetamine User.

We present the case of a 60-year-old male who developed an ischemic stroke due to left ventricular (LV) thrombus emboli as a complication of methamphetamine-induced cardiomyopathy. The patient had a history of methamphetamine abuse, hypertension, and ischemic stroke with no residual deficits presented with new onset slurred speech, left-sided weakness, and numbness for two hours. Computed tomography (CT) of the head showed no acute changes, and a tissue plasminogen activator was given in the emergency department within 30 minutes of arrival. Urine drug screen (UDS) was positive for methamphetamine, and magnetic resonance imaging (MRI) of the brain showed acute cortical infarcts in the right frontal lobe and parietal lobe and chronic infarct in the left occipital lobe. Transthoracic echocardiography showed bilateral ventricular thrombus and severely reduced ejection fraction of 20-25%. The patient had no evidence of thrombophilia and was started on a heparin drip for thrombus and goal-directed medical therapy for heart failure with reduced ejection fraction (HFrEF). Upon discharge, the patient was prescribed the oral anticoagulant rivaroxaban. The LV thrombus emboli were attributed to causing ischemic stroke. This case highlights the potential risk of ischemic stroke due to LV thrombus emboli in patients with methamphetamine-induced cardiomyopathy.

Fat Pulmonary Embolism With Crazy-Paving Pattern Opacities and Pneumothorax: A Rare Complication of Liposuction.

Fat embolism syndrome (FES) is a rare multiorgan disease caused by microvascular obstruction by fat globules and free fatty acid-mediated endothelial injury leading to pro-inflammatory cytokine release. We present a rare case of a 54-year-old woman who underwent elective aesthetic liposuction and developed FES and pneumothorax within 12 hours of the procedure.

An Individual Patient-Level Meta-Analysis of Ischemic Versus Nonischemic Cardiomyopathy and Trajectory of Decongestion in Patients With Acute Decompensated Heart Failure.

Data are limited regarding the impact of ischemic cardiomyopathy (ICM) or non-ICM (NICM) on the trajectory of in-hospital decongestion among patients with acute decompensated heart failure (ADHF). Therefore, we aimed to assess the course of decongestion among patients admitted for ADHF by history of ICM and NICM. Patients included in the DOSE (Diuretic strategies in patients with acute decompensated heart failure), ROSE (ROSE acute heart failure randomized trial), and Ultrafiltration in decompensated heart failure with cardiorenal syndrome (CARRESS-HF) trials of patients with ADHF were categorized into ICM and NICM based on history. Among 762 patients included in our meta-analysis, 433 (56.8%) had a history of ICM. Patients with ICM were older (70.8 vs 63.9 years; p ≤0.001) and had higher rates of co-morbidities. After covariate adjustment, there was no significant differences between NICM and ICM regarding net fluid loss (4,952 vs 4,384 ml, p = 0.81) or mean change in serum N-terminal pro-brain natriuretic peptide (-2,162 vs -1,809 pg/ml, p = 0.092). Mean change in weight showed modest improvement in favor of patients with NICM, but this did not meet statistical significance (-8.24 vs -7.70 pounds, p = 0.068). After adjustment, there was no significant difference in the risk of 60-day composite all-cause mortality or hospitalization for HF among those with ICM versus NICM. Among patients with left ventricular ejection fraction <40%, NICM was associated with higher scoring on global sense of well-being (global visual analog scale; +25.5 vs +19.1, p = 0.023) and improvement in serum creatinine (-0.031 mg/100 ml vs +0.042 mg/100 ml, p = 0.009) at 72 hours. Among patients with left ventricular ejection fraction >40%, NICM was associated with decreased scoring on global visual analog scale at 72 hours (+15.7 vs +21.2, p = 0.049). In conclusion, more than half of the patients admitted for ADHF had ICM. History of ICM was not independently associated with a difference in course of decongestion, self-assessment of well-being and dyspnea, or short-term clinical outcomes.

A Systematic Review and Meta-Analysis on Effectiveness of Mineralocorticoid Receptor Antagonists in Reducing the Risk of Atrial Fibrillation.

Mineralocorticoid receptor antagonists (MRAs) are known to improve clinical outcomes in heart failure, particularly heart failure with reduced ejection fraction. However, the effect of MRAs on the incidence of and recurrence of atrial fibrillation (AF) is not well established. Therefore, databases, such as PubMed, EMBASE, and Cochrane Central, were searched from inception to September 2021 for randomized controlled trials of MRAs with AF as an outcome. Risk ratios (RRs) with 95% confidence interval (CIs) were combined using the random-effects model. A total of 10 randomized controlled trials (n = 11,356) were included. Our pooled analysis demonstrates that MRAs reduce the risk of AF occurrence by 23% compared with the control therapy (RR 0.77, 95% CI 0.65 to 0.91, p = 0.003, I2 = 40%). Subgroup analysis demonstrated that MRAs reduced the risk of both new-onset AF (RR 0.84, 95% CI 0.61 to 1.16, p = 0.28, I2 = 43%) and recurrent AF (RR 0.73, 95% CI 0.59 to 0.90, p = 0.004, I2 = 26%) similarly; p interaction = 0.48. Our meta-analysis concludes that MRAs reduce the risk of development of AF overall, with consistent effects in new-onset and recurrent AF.

Quantifying Yeast Microtubules and Spindles Using the Toolkit for Automated Microtubule Tracking (TAMiT).

Fluorescently labeled proteins absorb and emit light, appearing as Gaussian spots in fluorescence imaging. When fluorescent tags are added to cytoskeletal polymers such as microtubules, a line of fluorescence and even non-linear structures results. While much progress has been made in techniques for imaging and microscopy, image analysis is less well-developed. Current analysis of fluorescent microtubules uses either manual tools, such as kymographs, or automated software. As a result, our ability to quantify microtubule dynamics and organization from light microscopy remains limited. Despite the development of automated microtubule analysis tools for in vitro studies, analysis of images from cells often depends heavily on manual analysis. One of the main reasons for this disparity is the low signal-to-noise ratio in cells, where background fluorescence is typically higher than in reconstituted systems. Here, we present the Toolkit for Automated Microtubule Tracking (TAMiT), which automatically detects, optimizes, and tracks fluorescent microtubules in living yeast cells with sub-pixel accuracy. Using basic information about microtubule organization, TAMiT detects linear and curved polymers using a geometrical scanning technique. Images are fit via an optimization problem for the microtubule image parameters that are solved using non-linear least squares in Matlab. We benchmark our software using simulated images and show that it reliably detects microtubules, even at low signal-to-noise ratios. Then, we use TAMiT to measure monopolar spindle microtubule bundle number, length, and lifetime in a large dataset that includes several S. pombe mutants that affect microtubule dynamics and bundling. The results from the automated analysis are consistent with previous work and suggest a direct role for CLASP/Cls1 in bundling spindle microtubules. We also illustrate automated tracking of single curved astral microtubules in S. cerevisiae, with measurement of dynamic instability parameters. The results obtained with our fully-automated software are similar to results using hand-tracked measurements. Therefore, TAMiT can facilitate automated analysis of spindle and microtubule dynamics in yeast cells.

The Role of Vitamin D Supplementation Before Coronary Artery Bypass Grafting in Preventing Postoperative Atrial Fibrillation in Patients With Vitamin D Deficiency or Insufficiency: A Systematic Review and Meta-Analysis.

This study aims to evaluate the role of preoperative vitamin D supplementation before coronary artery bypass grafting (CABG) surgery in preventing postoperative atrial fibrillation (POAF) in vitamin D deficient or insufficient patients. Three randomized controlled trials (RCTs) comprising 448 subjects were selected after a detailed search was conducted on PubMed, Cochrane CENTRAL, Scopus, and Embase in December 2022. Analysis was run using RevMan (version 5.4.1; Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). The analysis collected risk ratio (RR) and 95% confidence interval (CI) data from the relevant studies, which were then pooled using a random effects model. A significance level of less than 0.05 (p<0.05) was considered significant. Our analysis showed that compared with the standard of care, preoperative vitamin D supplementation in vitamin D deficient and insufficient patients effectively reduced POAF after CABG surgery (RR=0.6, 95% CI=0.4-0.9, P=0.01). There was no significant difference in the duration of hospitalization between the vitamin D supplementation group compared with the control following CABG (mean difference -0.85, 95% CI -2.13 to 0.43, P = 0.19). This meta-analysis shows that preoperative vitamin D supplementation in vitamin D deficient and insufficient patients undergoing CABG can reduce the rate of POAF. As POAF is associated with many complications, providing vitamin D supplementation to individuals with a vitamin D deficiency undergoing CABG can improve long-term cardiovascular outcomes following surgery.

Remote Monitoring in Heart Failure patients: A Systemic Review and Meta-analysis.

Heart failure (HF) approximately affects about 1%-2% of the adult population in developed countries and is a leading cause of morbidity and mortality worldwide. Inadequate HF management occurs because of poor adherence to prescribed medications. This meta-analysis compares and contrasts standard care with remote medication monitoring in HF patients. Six randomized control trials were selected using the PubMed database from inception until October 25, 2022, incorporating a total of 2390 patients with HF, out of which 1260 were subjected to remote monitoring while the remaining were in the control group. An odds ratio (OR) with a confidence interval (CI) of 95% was calculated. Remote monitoring in HF patients did not significantly reduce the risks of Cardiovascular (CV) hospitalization <6 months (RR = 0.32, P = 0.27), emergency department (ED) visits (RR = 0.95, P = 0.56) and all-cause mortality (RR = 1.08, P = 0.36). However, a significant reduction in CV hospitalization >6 months was associated with remote monitoring (RR = 0.83, P = 0.002). The meta-analysis revealed that remote monitoring does not significantly reduce the risks of CV hospitalizations, ED visits, or mortality in patients with HF. Therefore, standard care methods must continue to be utilized in HF management.

Quantifying yeast microtubules and spindles using the Toolkit for Automated Microtubule Tracking (TAMiT).

Fluorescently labeled proteins absorb and emit light, appearing as Gaussian spots in fluorescence imaging. When fluorescent tags are added to cytoskeletal polymers such as microtubules, a line of fluorescence and even non-linear structures results. While much progress has been made in techniques for imaging and microscopy, image analysis is less well developed. Current analysis of fluorescent microtubules uses either manual tools, such as kymographs, or automated software. As a result, our ability to quantify microtubule dynamics and organization from light microscopy remains limited. Despite development of automated microtubule analysis tools for in vitro studies, analysis of images from cells often depends heavily on manual analysis. One of the main reasons for this disparity is the low signal-to-noise ratio in cells, where background fluorescence is typically higher than in reconstituted systems. Here, we present the Toolkit for Automated Microtubule Tracking (TAMiT), which automatically detects, optimizes and tracks fluorescent microtubules in living yeast cells with sub-pixel accuracy. Using basic information about microtubule organization, TAMiT detects linear and curved polymers using a geometrical scanning technique. Images are fit via an optimization problem for the microtubule image parameters that is solved using non-linear least squares in Matlab. We benchmark our software using simulated images and show that it reliably detects microtubules, even at low signal-to-noise ratios. Then, we use TAMiT to measure monopolar spindle microtubule bundle number, length, and lifetime in a large dataset that includes several S. pombe mutants that affect microtubule dynamics and bundling. The results from the automated analysis are consistent with previous work, and suggest a direct role for CLASP/Cls1 in bundling spindle microtubules. We also illustrate automated tracking of single curved astral microtubules in S. cerevisiae , with measurement of dynamic instability parameters. The results obtained with our fully-automated software are similar to results using hand-tracked measurements. Therefore, TAMiT can facilitate automated analysis of spindle and microtubule dynamics in yeast cells.

The kinesin-5 protein Cut7 moves bidirectionally on fission yeast spindles with activity that increases in anaphase.

Kinesin-5 motors are essential to separate mitotic spindle poles and assemble a bipolar spindle in many organisms. These motors crosslink and slide apart antiparallel microtubules via microtubule plus-end-directed motility. However, kinesin-5 localization is enhanced away from antiparallel overlaps. Increasing evidence suggests this localization occurs due to bidirectional motility or trafficking. The purified fission-yeast kinesin-5 protein Cut7 moves bidirectionally, but bidirectionality has not been shown in cells, and the function of the minus-end-directed movement is unknown. Here, we characterized the motility of Cut7 on bipolar and monopolar spindles and observed movement toward both plus- and minus-ends of microtubules. Notably, the activity of the motor increased at anaphase B onset. Perturbations to microtubule dynamics only modestly changed Cut7 movement, whereas Cut7 mutation reduced movement. These results suggest that the directed motility of Cut7 contributes to the movement of the motor. Comparison of the Cut7 mutant and human Eg5 (also known as KIF11) localization suggest a new hypothesis for the function of minus-end-directed motility and spindle-pole localization of kinesin-5s.

The Safety and Efficacy of GLP-1 Receptor Agonists in Heart Failure Patients: A Systematic Review and Meta-Analysis.

Evaluation of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) usage in heart failure (HF) patients with or without type 2 diabetes mellitus (T2DM) could be proven to be a critical breakthrough in treatment options available for these patients. Our study focuses on understanding the safety and efficacy of GLP-1 RAs in this patient population by pooling the data from 9 randomized controlled trials (RCTs) comprising 871 subjects. As compared with the placebo, GLP-1 RAs did not improve major adverse cardiovascular events (MACE) which include cardiovascular (CV) mortality and heart failure (HF) hospitalizations, our primary outcome. CV mortality (RR = 1.03, 95% CI = 0.56-1.88, P = 0.92) and HF hospitalizations (RR = 1.18, 95%CI = 0.93-1.51, P = 0.18). Similarly, GLP-1 RAs did not improve our secondary findings of left ventricular ejection fraction (LVEF) and 6-minute walk test (6MWT). LVEF (RR = 1.96, 95%CI = -0.16-4.07, P = 0.07) or 6 MWT (RR = 8.43, 95% CI = -2.69-19.56, P = 0.14). This meta-analysis shows that GLP-1 RAs do not improve cardiovascular outcomes in HF patients with or without T2DM.

A Rare Case of Postpartum Panhypopituitarism Without Imaging Evidence of Sheehan's Syndrome.

We present a case of a 35-year-old female with type 2 diabetes mellitus who delivered a female neonate via normal vaginal delivery without any peripartum complication and minimal blood loss. The patient developed features of panhypopituitarism in the post-partum period with imaging with CT and MRI showing unremarkable pituitary gland. This is a rare presentation of post-partum panhypopituitarism with normal imaging studies.