Menopausal symptom management: Fezolinetant's varied doses provide effective relief for vasomotor symptoms in women - A meta-analysis of 3291 participants.

Menopause represents the physiological transition when a woman's reproductive period ends associated with a variety of symptoms, including vasomotor symptoms, such as night sweats and hot flashes. This systematic review and meta-analysis aimed to assess the effectiveness and safety of oral Fezolinetant for treating vasomotor symptoms associated with menopause. Five electronic databases were searched from their inception until May 2023. Via the Cochrane risk of bias tool, two reviewers assessed the studies' quality. The primary outcomes were a decrease in VMSs frequency and severity and safety outcomes at 4 and 12 weeks. Data were extracted and then analyzed using RevMan software. This meta-analysis included six trials with a total of 3291 women that compared Fezolinetant to a placebo in the treatment of menopausal VMSs. After 4 and 12 weeks of therapy, fezolinetant at 30 mg QD or 45 mg QD substantially decreased the frequency and severity of VMSs per 24 hours compared to placebo. Fezolinetant at 90 mg BID, 30 mg QD, or 45 mg QD did not show a significant difference in the rate of treatment-emergent adverse events (TEAEs), headache, and TEAEs leading to permanent discontinuation compared to placebo. Fezolinetant proves to be a successful and well-tolerated remedy for menopausal women suffering from VMSs. Notably, the 45 mg daily dosage over 12 weeks exhibited significant efficacy. Nonetheless, extensive future trials are necessary to ascertain its long-term safety, effectiveness, and relative potency compared to alternative VMS treatments like hormone therapy.

La ménopause représente la transition physiologique lorsque la période de reproduction d'une femme se termine, associée à divers symptômes, notamment des symptômes vasomoteurs, tels que des sueurs nocturnes et des bouffées de chaleur. Cette revue systématique et méta-analyse visaient à évaluer l'efficacité et l'innocuité du Fezolinetant oral pour traiter les symptômes vasomoteurs associés à la ménopause. Cinq bases de données électroniques ont été consultées depuis leur création jusqu'en mai 2023. Via l'outil Cochrane sur le risque de biais, deux examinateurs ont évalué la qualité des études. Les principaux critères de jugement étaient une diminution de la fréquence et de la gravité des SVM ainsi que des critères de sécurité à 4 et 12 semaines. Les données ont été extraites puis analysées à l'aide du logiciel RevMan. Cette méta-analyse comprenait six essais portant sur un total de 3 291 femmes comparant Fezolinetant à un placebo dans le traitement des SVM ménopausiques. Après 4 et 12 semaines de traitement, le fézolinetant à la dose de 30 mg une fois par jour ou de 45 mg une fois par jour a considérablement réduit la fréquence et la gravité des SMV toutes les 24 heures par rapport au placebo. Le fézolinetant à la dose de 90 mg deux fois par jour, de 30 mg une fois par jour ou de 45 mg une fois par jour n'a pas montré de différence significative dans le taux d'événements indésirables survenus pendant le traitement (TEAE), de maux de tête et de TEAE conduisant à un arrêt définitif par rapport au placebo. Le fézolinetant s'avère être un remède efficace et bien toléré pour les femmes ménopausées souffrant de VMS. Notamment, la dose quotidienne de 45 mg sur 12 semaines a montré une efficacité significative. Néanmoins, de futurs essais approfondis sont nécessaires pour vérifier son innocuité, son efficacité et sa puissance relative à long terme par rapport aux traitements alternatifs du VMS comme l'hormonothérapie.

Stationary shapes of axisymmetric vesicles beyond lowest-energy configurations.

We conduct a systematic exploration of the energy landscape of vesicle morphologies within the framework of the Helfrich model. Vesicle shapes are determined by minimizing the elastic energy subject to constraints of constant area and volume. The results show that pressurized vesicles can adopt higher-energy spindle-like configurations that require the action of point forces at the poles. If the internal pressure is lower than the external one, multilobed shapes are predicted. We utilize our results to rationalize experimentally observed spindle shapes of giant vesicles in a uniform AC electric field.

Comparing the safety and effectiveness of various umbilical cord milking techniques and delayed cord clamping in full-term and preterm infants: A systematic review and meta-analysis.

We compare the hematocrit, hemoglobin, need for transfusion, recurrent phototherapy, serum bilirubin level, and serum ferritin at different time frames for the umbilical cord milking (UCM) and delayed cord clamping (DCC) in both full-term and preterm infants. A comprehensive search through various databases aimed to compare UCM and DCC studies until May 2nd, 2023. Cochrane and NIH tools assessed RCTs and cohorts, respectively. Meta-analysis employed Review Manager 5.4 software, calculating MD and RR with 95% CIs for continuous and dichotomous data. We included 20 studies with a total of 5189 infants. Regarding preterm infants, hematocrit level showed no significant difference between intact Umbilical Cord Milking (iUCM) compared to DCC (MD = -0.24, 95% CI [-1.11, 0.64]). Moreover, Neonatal death incidence was significantly higher with the UCM technique in comparison to DCC (RR = 1.28, 95% CI [1.01 to 1.62]). Regarding term and late preterm infants, Hematocrit level showed no significant difference between the iUCM or cUCM techniques compared to DCC (MD = 0.21, 95% CI [-1.28 to 1.69]), (MD = 0.96, 95% CI [-1.02 to 2.95]), respectively. UCM led to a higher risk of neonatal death in preterm infants compared to DCC. However, the incidence of polycythemia was lower in the UCM group. Additionally, UCM was associated with higher rates of severe IVH events. Based on these findings, DCC may be preferred due to its lower incidence of severe IVH and neonatal death.

Nous comparons l'hématocrite, l'hémoglobine, le besoin de transfusion, la photothérapie récurrente, le taux de bilirubine sérique et la ferritine sérique à différentes périodes pour la traite du cordon ombilical (UCM) et le clampage retardé du cordon (DCC) chez les nourrissons nés à terme et prématurés. Une recherche complète dans diverses bases de données visait à comparer les études UCM et DCC jusqu'au 2 mai 2023. Les outils Cochrane et NIH ont évalué les ECR et les cohortes, respectivement. La méta-analyse a utilisé le logiciel Review Manager 5.4, calculant le MD et le RR avec des IC à 95 % pour les données continues et dichotomiques. Nous avons inclus 20 études portant sur un total de 5 189 nourrissons. Concernant les nourrissons prématurés, le niveau d'hématocrite n'a montré aucune différence significative entre la traite du cordon ombilical intact (iUCM) et la DCC (DM = -0,24, IC à 95 % [-1,11, 0,64]). De plus, l'incidence des décès néonatals était significativement plus élevée avec la technique UCM qu'avec la technique DCC (RR = 1,28, IC à 95 % [1,01 à 1,62]). Concernant les nourrissons à terme et peu prématurés, le niveau = 0,21, IC à 95 % [-1,28 à 1,69]), (DM = 0,96, IC à 95 % [-1,02 à 2,95]), respectivement. L'UCM a entraîné un risque plus élevé de décès néonatal chez les nourrissons prématurés par rapport au DCC. Cependant, l'incidence de la polyglobulie était plus faible dans le groupe UCM. De plus, l'UCM était associée à des taux plus élevés d'événements IVH graves. Sur la base de ces résultats, le DCC peut être préféré en raison de sa plus faible incidence d'IVH grave et de décès néonatals. d'hématocrite n'a montré aucune différence significative entre les techniques iUCM ou cUCM par rapport à la technique DCC (DM.

Stationary shapes of axisymmetric vesicles beyond lowest-energy configurations.

We conduct a systematic exploration of the energy landscape of vesicle morphologies within the framework of the Helfrich model. Vesicle shapes are determined by minimizing the elastic energy subject to constraints of constant area and volume. The results show that pressurized vesicles can adopt higher-energy spindle-like configurations that require the action of point forces at the poles. If the internal pressure is lower than the external one, multilobed shapes are predicted. We utilize our results to rationalize the experimentally observed spindle shapes of giant vesicles in a uniform AC field.

Development and implementation of an Enhanced Recovery After Cranial Surgery pathway following supratentorial tumor resection at a tertiary care center.

OBJECTIVE: Controlling length of stay (LOS) reduces rates of nosocomial infections and falls, facilitates earlier return to daily activities, and decreases strain on the healthcare system. Complications following supratentorial tumor resection present early in the postoperative period, thereby enhancing the prospect of safe, early discharge. Here, the authors describe their initial experience with the development and implementation of an Enhanced Recovery After Cranial Surgery (ERACS) pathway following resection of supratentorial tumors in select patients. METHODS: This was a nonrandomized, ambispective quality improvement study of patients undergoing elective craniotomy for supratentorial tumor resection at New York University Langone Health between November 17, 2020, and May 19, 2022. Eligible patients were prospectively enrolled in either the ERACS pathway or the standard pathway. These prospective cohorts were compared to a retrospective cohort of patients who met eligibility criteria for the pathway. Patients in the ERACS pathway cohort were targeted for discharge on postoperative day 2. The primary outcome metric was hospital LOS. Secondary outcome metrics included duration of intensive care unit (ICU) care and rates of 30-day emergency department visits, readmissions, and complications. RESULTS: Over the study period, 188 of 317 patients (59.3%) who underwent supratentorial tumor resection met inclusion criteria for ERACS pathway enrollment. Sixty-three patients were enrolled in the ERACS pathway, and 125 patients completed the standard pathway. The historical cohort consisted of 332 patients who would have been eligible for ERACS enrollment. Patients in the ERACS pathway cohort had a median LOS of 1.93 days compared with 2.92 and 2.88 days for patients in the standard pathway and historical cohort, respectively (p < 0.001). There was a significant reduction in ICU utilization in ERACS pathway patients (16.0 ± 6.53 vs 29.5 ± 53.0 vs 21.8 ± 18.2 hours, p = 0.005). There were no differences in the rates of 30-day emergency department visits (12.7% vs 9.6% vs 10.9%, p = 0.809) and readmissions (4.8% vs 4.0% vs 7.8%, p = 0.279) between groups. CONCLUSIONS: Patients in the ERACS pathway cohort experienced reduced LOS and ICU utilization, with similar rates of adverse outcomes compared to standard pathway patients. The authors' initial experience suggests that an accelerated recovery pathway can be safely implemented following supratentorial tumor resection in select patients.

Efficacy of Massage on Pain Intensity in Post-Cesarean Women: a Systematic Review and Meta-Analysis.

Background: Cesarean section is a common surgical procedure that may be considered a safe alternative to natural birth and helps to resolve numerous obstetric conditions. Still, the Cesarean section is painful; relieving pain after a Cesarean section is crucial, therefore analgesia is necessary for the postoperative period. However, analgesia is not free of complications and contraindications, so massage may be a cost-effective method for decreasing pain post-Cesarean. Our study aims to determine the massage role in pain intensity after Cesarean sections. Methods: We searched five electronic databases for relevant studies. Data were extracted from the included studies after screening procedures. We calculated the pooled mean difference (MD) and standardized mean difference (SMD) for our continuous outcomes, using random or fixed-effect meta-analysis according to heterogenicity status. Interventional studies were assessed for methodological quality using the Cochrane risk-of-bias assessment tool, while observational studies were assessed using the National Institutes of Health's tools. Results: Our study included 10 RCTs and five observational studies conducted with over 1,595 post-Cesarean women. The pooled MDs for pain intensity considering baseline values either immediately or post 60-90 minutes were favoring the massagegroup over the control group as follows:(stand. MD = -2.64, 95% CI [-3.80, -1.48], p >.00001; MD = -2.64, 95% CI [-3.80, -1.48], p >.00001, respectively). While pooled MDsregarding post-intervention only eitherimmediately or post 60-90 minutes were:(stand. MD = -2.04, 95% CI [-3.26, -0.82], p =.001; stand. MD = -2.62, 95% CI [-3.52, -1.72],p > .00001, respectively). Conclusion: Our study found that using massage was superior to the control groups in decreasing pain intensity either when the pain was assessed immediately after or 60-90 minutes post-massage application.

The effects of Yakson touch and gentle human touch on preterm infants: A systematic review and meta-analysis.

We aim to collect the evidence of efficacy of Gentle Guman Touch (GHT) and Yakson Touch in preterm neonates as pain relief, heart rate, oxygen saturation, and urine cortisol level. We made our search through PubMed, Web of Science, Scopus, and Cochrane by the mid of March 2023. Randomized control trials (RCTs) were included, and the Cochrane risk of bias tool was utilized to assess their quality. Using Review Manager software, a meta-analysis was conducted. We computed the mean difference (MD) with a 95% confidence interval (CI) for the continuous data. During the examination, the Neonatal Infant Pain Scale (NIPS) was significantly reduced in the touch group compared to the control group (MD = -3.40, 95% CI [-4.15 to -2.64], P-value= 0.00001). After the examination, the NIPS score was also reduced by both Yakson touch and GHT compared to the control (MD = -2.14, 95% CI [-3.42 to -0.85], P-value <0.00001). Yakson touch and GHT are non-pharmacological, easy, and safe methods that can be used for painful interventions to reduce the pain experience of preterm infants from variable interventions. Both methods improved infant sleep and behavior. Preterm infants' heart rates and oxygen saturation were unaffected by Yakson touch or GHT.

Double-balloon catheter vs dinoprostone (PGE-2) insert for labour induction: A meta-analysis of 2493 pregnancies.

Induction of labor (IOL) is the stimulation of the uterus during pregnancy to begin the onset of labour. Nearly two of five pregnancies require IOL. We compared the effectiveness of double-balloon catheter (DBC) with dinoprostone (PGE-2) insert for labour induction from previous studies. We included randomized controlled trials (RCTs) that compared the safety and efficacy of DBC to PGE-2. To evaluate the studies, we utilized the Cochrane tool for risk of bias assessment. The rates of vaginal birth and cesarean section were the primary outcomes. We included ten RCTs in this meta-analysis with a total sample of 2493 singleton pregnancies. After 24 hours, there was no significant difference in the delivery rates between DBC and PGE-2 s [R.R=1.08, 95% CI, (0.77, 1.52), P.value=0.65], and the rate of cesarean delivery [R.R=1.03, 95% CI, (0.90; 1.18), P.value=0.65]. The DBC showed a significantly higher oxytocin use rate compared to the PGE-2 group [R.R=1.77, 95% CI, (1.41; 2.32), P.value<0.0001]. In the PGE-2 group, there was a significantly higher risk of uterine hyperstimulation, tachysystole, and umbilical artery PH levels below 7. There was no significant difference in the efficacy between the PGE-2 and DBC in terms of delivery rate in 24 hours and the rate of cesarean delivery except for a slight BISHOP score improvement with DBC. However, DBC showed a higher rate of oxytocin use compared to the PGE-2, the DBC seems to be safer with a lower risk of umbilical artery PH < 7, uterine hyperstimulation, and tachysystole incidence than PGE-2.

Safety and efficacy of combined ropivacaine and sufentanil compared with ropivacaine for cesarean sections: A systematic review and meta-analysis.

Cesarean sections are the most common operations in the United States and one of the most common worldwide. Using the lowest possible dose of anesthetic that provides painless delivery with the lowest adverse events is a major concern. We investigated the efficacy and safety of combined ropivacaine and sufentanil by pooling data from relevant studies. We searched PubMed, Web of sciences, Scopus, and Cochrane Library until the end of December 2021 and included all records with data about combined ropivacaine and sufentanil. We used Review Manager to pool data as a mean difference for continuous outcomes or risk ratio for dichotomous outcomes with a 95% confidence interval. Methodological quality was appraised using version one of the Cochrane risks of bias tool. Seven Randomized clinical trials with a total sample size of 730 women were included; the mean age of enrolled parturients ranged from 28 to 35 years. We found that combined sufentanil and ropivacaine were significantly associated with decreased risk of being aware and nervous during CS (presented by Sedation level 1) (RR: 0.05, 95%CI [0.01,0.33], P=0.002), decreased risk of shivering (RR=0.29, 95%CI [0.19,0.44], P<0.00001), nausea (RR=0.62, 95%CI [0.41, 0.92], P=0.02), and vomiting (RR=0.27, 95% CI [0.12, 0.61], P=0.002). However, combined sufentanil and ropivacaine slightly were associated with late-onset of sensory blockade (MD=0.41, 95%CI [0.13, 0.68], P=0.004) and less motor blockade of leg flexion at hip joint presented by Bromage Scale 0 (RR=7.15 95%CI [2.71, 18.86], P<0.0001). Combined ropivacaine and sufentanil were associated with a reduction in visceral pain and lower risks of hypotension, shivering, nausea, and vomiting, compared to isolated ropivacaine, with no difference regarding the incidence of bradycardia. Although Combined ropivacaine and sufentanil were associated with a higher risk of pruritus, the incidence of pruritus was reportedly proportionate with the used dose of sufentanil. However, combined ropivacaine and sufentanil may slightly delay the onset of the sensory blockade to pinprick at T10 with less motor blockade but with a smaller probability for women to be aware and nervous during CS.

Carbon fiber-reinforced PEEK spinal implants for primary and metastatic spine tumors: a systematic review on implant complications and radiotherapy benefits.

OBJECTIVE: By minimizing imaging artifact and particle scatter, carbon fiber-reinforced polyetheretherketone (CF-PEEK) spinal implants are hypothesized to enhance radiotherapy (RT) planning/dosing and improve oncological outcomes. However, robust clinical studies comparing tumor surgery outcomes between CF-PEEK and traditional metallic implants are lacking. In this paper, the authors performed a systematic review of the literature with the aim to describe clinical outcomes in patients with spine tumors who received CF-PEEK implants, focusing on implant-related complications and oncological outcomes. METHODS: A systematic review of the literature published between database inception and May 2022 was performed in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The PubMed database was queried using the terms "carbon fiber" and "spine" or "spinal." The inclusion criteria were articles that described patients with CF-PEEK pedicle screw fixation and had a minimum of 5 patients. Case reports and phantom studies were excluded. RESULTS: This review included 11 articles with 326 patients (237 with CF-PEEK-based implants and 89 with titanium-based implants). The mean follow-up period was 13.5 months, and most tumors were metastatic (67.1%). The rates of implant-related complications in the CF-PEEK and titanium groups were 7.8% and 4.7%, respectively. The rate of pedicle screw fracture was 1.7% in the CF-PEEK group and 2.4% in the titanium group. The rates of reoperation were 5.7% (with 60.0% because of implant failure or junctional kyphosis) and 4.8% (all because of implant failure or junctional kyphosis) in the CF-PEEK and titanium groups, respectively. When reported, 72.5% of patients received postoperative RT (41.0% stereotactic body RT, 30.8% fractionated RT, 25.6% proton, 2.6% carbon ion). Four articles suggested that implant artifact was reduced in the CF-PEEK group. Local recurrence occurred in 14.4% of CF-PEEK and 10.7% of titanium-implanted patients. CONCLUSIONS: While CF-PEEK harbors similar implant failure rates to traditional metallic implants with reduced imaging artifact, it remains unclear whether CF-PEEK implants improve oncological outcomes. This study highlights the need for prospective, direct comparative clinical studies.

Gender Disparities after Transcatheter Aortic Valve Replacement with Newer Generation Transcatheter Heart Valves: A Systematic Review and Meta-Analysis.

Previous studies have demonstrated gender disparities in mortality and vascular complications after transcatheter aortic valve replacement (TAVR) with early generation transcatheter heart valves (THVs). It is unclear, however, whether gender-related differences persist with the newer generation THVs. We aim to assess gender disparities after TAVR with newer generation THVs. The MEDLINE and Embase databases were thoroughly searched from inception to April 2023 to identify studies that reported gender-specific outcomes after TAVR with newer generation THVs (Sapien 3, Corevalve Evolut R, and Evolut Pro). The outcomes of interest included 30-day mortality, 1-year mortality, and vascular complications. In total, 5 studies (4 databases) with a total of 47,933 patients (21,073 females and 26,860 males) were included. Ninety-six percent received TAVR via the transfemoral approach. The females had higher 30-day mortality rates (odds ratio (OR) = 1.53, 95% confidence interval (CI) 1.31-1.79, p-value (p) < 0.001) and vascular complications (OR = 1.43, 95% CI 1.23-1.65, p < 0.001). However, one-year mortality was similar between the two groups (OR = 0.78, 95% CI 0.61-1.00, p = 0.28). The female gender continues to be associated with higher 30-day mortality rates and vascular complications after TAVR with newer generation transcatheter heart valves, while there was no difference in 1-year mortality between the genders. More data is needed to explore the causes and whether we can improve TAVR outcomes in females.

Complications during mechanical ventilation-A pediatric intensive care perspective.

Mechanical ventilation is a common procedure performed in pediatric intensive care units, with over 20% of patients requiring invasive ventilator support. The most common indication for endotracheal intubation and ventilation in the pediatric population is respiratory failure either due to respiratory embarrassment or neurologic pathology. Despite the use of ventilation modes that are lung protective in the pediatric population, complications of mechanical ventilation occur frequently. These include atelectasis, post-extubation stridor, perioral tissue damage, ventilator associated pneumonia, mucus plugging, pneumothorax, pneumomediastinum, and ICU neuromyopathy. The purpose of this review is to discuss the risk factors, presentation and management of complications associated with mechanical ventilation in the pediatric population.

Effects of the In Ovo Administration of L-ascorbic Acid on the Performance and Incidence of Corneal Erosion in Ross 708 Broilers Subjected to Elevated Levels of Atmospheric Ammonia.

Effects of the in ovo injection of various levels of L-ascorbic acid (L-AA) on the performance and corneal erosion incidence in Ross 708 broilers exposed to 50 parts per million (ppm) of atmospheric ammonia (NH3) after hatch were determined. A total of 1440 Ross 708 broiler embryos were randomly assigned to 4 treatments: non-injected (control), 0.85% sterile saline-injected (control), or saline containing 12 or 25 mg of L-AA. At hatch, 12 male chicks were randomly assigned to each of 48 battery cages with 12 replicate cages randomly assigned to each treatment group. All birds were exposed to 50 ppm of NH3 for 35 d and the concentration of NH3 in the battery cage house was recorded every 20 s. Mortality was determined daily, and mean body weight (BW), BW gain (BWG), average daily BW gain (ADG), and feed intake, as well as feed conversion ratio (FCR), were determined weekly. From 0 to 35 d of post-hatch age (doa), six birds from each cage were selected and sampled for eye erosion scoring. Incidences of corneal erosion were significantly higher at 21 and 28 doa in comparison to those at 14 and 35 doa, and at 21 doa, birds in the saline-injected group exhibited a higher incidence of corneal erosion compared to all other treatment groups. The in ovo injection of 12 mg of L-AA increased BWG (p = 0.043) and ADG (p = 0.041), and decreased FCR (p = 0.043) from 0 to 28 doa in comparison to saline-injected controls. In conclusion the in ovo administration of 12 mg of L-AA may have the potential to improve the live performance of broilers chronically exposed to high aerial NH3 concentrations, but further study is needed to determine the physiological and immunological factors that may contribute to this improvement.

Metastatic Breast Cancer to the Spine: Incidence of Somatic Gene Alterations and Association of Targeted Therapies With Overall Survival.

BACKGROUND: The increase in use of targeted systemic therapies in cancer treatments has catalyzed the importance of identifying patient- and tumor-specific somatic mutations, especially regarding metastatic disease. Mutations found to be most prevalent in patients with metastatic breast cancer include TP53, PI3K, and CDH1. OBJECTIVE: To determine the incidence of somatic mutations in patients with metastatic breast cancer to the spine (MBCS). To determine if a difference exists in overall survival (OS), progression-free survival, and progression of motor symptoms between patients who do or do not undergo targeted systemic therapy after treatment for MBCS. METHODS: This is a retrospective study of patients with MBCS. Review of gene sequencing reports was conducted to calculate the prevalence of various somatic gene mutations within this population. Those patients who then underwent treatment (surgery/radiation) for their diagnosis of MBCS between 2010 and 2020 were subcategorized. The use of targeted systemic therapy in the post-treatment period was identified, and post-treatment OS, progression-free survival, and progression of motor deficits were calculated for this subpopulation. RESULTS: A total of 131 patients were included in the final analysis with 56% of patients found to have a PI3K mutation. Patients who received targeted systemic therapies were found to have a significantly longer OS compared with those who did not receive targeted systemic therapies. CONCLUSION: The results of this study demonstrate that there is an increased prevalence of PI3K mutations in patients with MBCS and there are a significant survival benefit and delay in progression of motor symptoms associated with using targeted systemic therapies for adjuvant treatment.

Assessing membrane material properties from the response of giant unilamellar vesicles to electric fields.

Knowledge of the material properties of membranes is crucial to understanding cell viability and physiology. A number of methods have been developed to probe membranes in vitro, utilizing the response of minimal biomimetic membrane models to an external perturbation. In this review, we focus on techniques employing giant unilamellar vesicles (GUVs), model membrane systems, often referred to as minimal artificial cells because of the potential they offer to mimick certain cellular features. When exposed to electric fields, GUV deformation, dynamic response and poration can be used to deduce properties such as bending rigidity, pore edge tension, membrane capacitance, surface shear viscosity, excess area and membrane stability. We present a succinct overview of these techniques, which require only simple instrumentation, available in many labs, as well as reasonably facile experimental implementation and analysis.

Nizatidine interacts with ct-DNA causing genotoxicity and cytotoxicity: an assessment by in vitro, in vivo, and in silico studies.

H2 receptor antagonists are the medication given for treating stomach ulcers, but lately, reports have shown their role in healing several malignant ulcers. The present work entails the interaction of H2 blocker nizatidine with calf thymus (ct)-DNA for determining the binding mode and energetics of the interaction. Multi-spectroscopic, calorimetric, viscometric and bioinformatic analysis revealed that nizatidine interacted with ct-DNA via groove-binding mode and is characterised by exothermic reaction. Moreover, assessment of genotoxic potential of nizatidine in vitro was carried out in peripheral human lymphocytes by alkaline comet assay. DNA damage occurred at high concentrations of nizatidine. Genotoxicity of nizatidine was also evaluated in vivo by assessing cytogenetic biomarkers viz. micronuclei formation and chromosomal aberration test. Nizatidine was able to induce micronuclei formation and chromosomal damage at high dose. Additionally, cytotoxic activity of nizatidine was determined in cancer cell lines, namely HeLa and HCT-116 and compared with the normal human cell line HEK-293 employing MTT assay. It was observed that nizatidine was more toxic towards HeLa and HCT-116 than HEK-293. Cell morphology analysis by compound inverted microscopy further strengthens the finding obtained through MTT assay.

Predictors of In-Hospital Mortality and Home Discharge in Patients with Aneurysmal Subarachnoid Hemorrhage: A 4-Year Retrospective Analysis.

BACKGROUND: Factors associated with discharge disposition and mortality following aneurysmal subarachnoid hemorrhage (aSAH) are not well-characterized. We used a national all-payer database to identify factors associated with home discharge and in-hospital mortality. METHODS: The National Inpatient Sample was queried for patients with aSAH within a 4-year range. Weighted multivariable logistic regression models were constructed and adjusted for age, sex, race, household income, insurance status, comorbidity burden, National Inpatient Sample SAH Severity Score, disease severity, treatment modality, in-hospital complications, and hospital characteristics (size, teaching status, and region). RESULTS: Our sample included 37,965 patients: 33,605 were discharged alive and 14,350 were discharged home. Black patients had lower odds of in-hospital mortality compared with White patients (adjusted odds ratio [aOR] = 0.67, 95% confidence interval [CI] 0.52-0.86, p = 0.002). Compared with patients with private insurance, those with Medicare were less likely to have a home discharge (aOR = 0.58, 95% CI 0.46-0.74, p < 0.001), whereas those with self-pay (aOR = 2.97, 95% CI 2.29-3.86, p < 0.001) and no charge (aOR = 3.21, 95% CI 1.57-6.55, p = 0.001) were more likely to have a home discharge. Household income percentile was not associated with discharge disposition or in-hospital mortality. Paradoxically, increased number of Elixhauser comorbidities was associated with significantly lower odds of in-hospital mortality. CONCLUSIONS: We demonstrate independent associations with hospital characteristics, patient characteristics, and treatment characteristics as related to discharge disposition and in-hospital mortality following aSAH, adjusted for disease severity.

Bending Rigidity, Capacitance, and Shear Viscosity of Giant Vesicle Membranes Prepared by Spontaneous Swelling, Electroformation, Gel-Assisted, and Phase Transfer Methods: A Comparative Study.

Closed lipid bilayers in the form of giant unilamellar vesicles (GUVs) are commonly used membrane models. Various methods have been developed to prepare GUVs, however it is unknown if all approaches yield membranes with the same elastic, electric, and rheological properties. Here, we combine flickering spectroscopy and electrodefomation of GUVs to measure, at identical conditions, membrane capacitance, bending rigidity and shear surface viscosity of palmitoyloleoylphosphatidylcholine (POPC) membranes formed by several commonly used preparation methods: thin film hydration (spontaneous swelling), electroformation, gel-assisted swelling using poly(vinyl alcohol) (PVA) or agarose, and phase-transfer. We find relatively similar bending rigidity value across all the methods except for the agarose hydration method. In addition, the capacitance values are similar except for vesicles prepared via PVA gel hydration. Intriguingly, membranes prepared by the gel-assisted and phase-transfer methods exhibit much higher shear viscosity compared to electroformation and spontaneous swelling, likely due to remnants of polymers (PVA and agarose) and oils (hexadecane and mineral) in the lipid bilayer structure.

COVID-19 in a mosaic trisomy 13 patient with polycystic kidney disease.

Presentation, management, and outcomes of COVID-19 infections among younger patients is an area of medicine with deficits in research, likely due to the lower incidence of severe COVID-19 disease among the younger population. Management can be challenging, and clinicians often guide their decision-making based on the ever-changing protocols that are tailored mostly to the elderly population. Even more underrepresented in COVID-19 research are patients with chromosomal abnormalities and trisomy syndromes, as they appear less frequently, but have risk of increased morbidity and mortality due to underlying medical conditions. We describe a case of severe COVID-19 infection in a young patient with mosaic trisomy 13 and pre-existing polycystic kidney disease, who developed severe acute hypoxic respiratory failure and acute chronic kidney injury. The patient was provided maximal pharmacological support and her clinical course helps to shape the understanding of COVID-19 infections in the setting of chromosomal abnormalities and complex medical history.

Knowledge, attitudes, and practice with respect to antibiotic use among pharmacy students: a cross-sectional study.

OBJECTIVE: Antibiotic resistance is a major health threat and efforts should be intensified to reduce its burden. Healthcare providers, especially pharmacists, can be actively involved in the reduction of antibiotic resistance. However, negative practices among pharmacists have been observed. This study evaluated knowledge, attitudes, and practices (KAP) among Jordanian pharmacy students. PATIENTS AND METHODS: A cross-sectional study used an online questionnaire that was developed and distributed to Jordanian pharmacy students from five different universities. KAP scores were calculated, with students categorized into low and high levels based on each score mean. RESULTS: A total of 890 pharmacy students completed the questionnaire. High positive response rate (PR%) for the majority of the knowledge items was observed, exceeding 60% in all knowledge items, and similar PR% was observed in attitude items. The variables significantly associated with attitude were age [OR=0.92 (95% CI 0.87: 0.98), p=0.01] and knowledge [OR=1.35 (95% CI 1.01:1.82), p=0.04], while knowledge was significantly associated with practice [OR=0.23 (95% CI 0.16:0.31), p<0.001]. CONCLUSIONS: Jordanian pharmacy students showed adequate KAP toward the use of antibiotics although several aspects of malpractice were identified. Hence, adequate knowledge about antibiotics among pharmacy students should be ensured as knowledge is associated with attitudes and practices.