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Background: Diastasis Recti Abdominis (DRA), a separation of the 2 bellies of the rectus abdominis at the linea alba, may occur in more than half of all pregnancies. Due to hormonal changes and a growing uterus, the abdominal muscles become over-stretched and weak, compromising posture, trunk stability, respiration, trunk motion, and vaginal delivery. Exercise to strengthen the abdominal musculature during pregnancy may affect the presence and size of DRA, however, no research has specifically examined this relationship. Purpose: The purpose of this project was to determine the effect of an abdominal strengthening exercise program on the presence and size of DRA in pregnant women. Study Design: A 2 group, between subjects, quasi-experimental post-test design. Methods: Subjects were comprised of 8 pregnant women participating in an abdominal exercise program and 10 non-exercising pregnant women. Diastis recti abdominis was measured using a digital caliper at 3 marked sites along the midline of each subject's abdomen: 4.5 cm above the umbilicus, at the umbilicus, and 4.5 cm below the umbilicus. Two measurements were taken at each site, and the average was used for statistical analyses. Descriptive statistics were generated, and independent t-tests were performed on each subject characteristic. An analysis of covariance was computed with the number of previous pregnancies as the covariate to control for the difference between the subject groups. Results: Ninety percent of non-exercising pregnant women exhibited DRA while only 12.5% of exercising women had the condition. The mean DRA located 4.5 cm above the umbilicus was 9.6 mm (+/- 6.6) for the exercise group and 38.9 mm (+/- 17.8) for the non-exercise group. The mean DRA located at the umbilicus was 11.4 mm (+/- 3.82) for the exercise group and 59.5 mm (+/- 23.6) for the non-exercise group. The mean DRA located 4.5 cm below the umbilicus was 8.2 mm (+/- 7.4) for the exercise group and 60.4 (+/- 29.0) for the non-exercise group. Conclusions: The occurrence and size of DRA is much greater in non-exercising pregnant women than in exercising pregnant women. Because of the integral role the abdominal muscles play in functional activities we recommend examining pregnant and postpartum women for the presence of DRA. [ABSTRACT FROM AUTHOR]

Purpose: Patients with multiple myeloma (MM) experience significant symptom burden. We used a symptom monitoring app to longitudinally characterize the MM treatment experience in detail based on line of therapy (LOT)., Methods: Adults with MM on active treatment completed weekly symptom monitoring surveys. Patients on their 4th LOT or greater were considered heavily pretreated. We characterized moderate to very severe (MOD-VS) symptom prevalence, weekly symptom burden, symptom bother (FACT-GP5), and health-related quality of life (HR-QoL) (EORTC QLQ-C30 Item 30) per LOT., Results: We considered 109 patients on LOT < 4 and 47 on LOT ≥ 4. The top MOD-VS symptoms were fatigue (71.6% of patients), muscle pain (59.8%), general pain (51.6%), numbness/tingling (48.4%), and insomnia (47.6%). More patients on LOT ≥ 4 experienced numbness/tingling (66.7% vs. 41.3%; OR 2.84, 95% CI 1.27-6.37; p = 0.0098) and fatigue (83.3% vs. 65.6%; OR 2.60, 95% CI 0.96-7.09; p = 0.0557). Some symptoms (fatigue, muscle pain, anxiety) persisted for months among patients on LOT ≥ 4, but patients on LOT < 4 also had unmet longitudinal needs (numbness/tingling, dyspnea). Patients on LOT ≥ 4 had more weeks with ≥ 3 MOD-VS symptoms (27.1% of weeks vs. 15.7%; OR 2.56, 95% CI 1.07-6.08; p = 0.0337) and experienced high symptom bother more often (39.1% of surveys vs. 30.0%; OR 4.23, 95% CI 1.37-13.10; p = 0.0123). HR-QoL was similar between groups., Conclusion: Heavily pretreated patients experienced greater symptom burden and bother, but patients at earlier LOTs also had unmet needs. Interventions are needed to improve symptom management in MM regardless of LOT, but most pressingly for heavily pretreated patients., Competing Interests: Declarations Ethics approval This study was performed in accordance with the Declaration of Helsinki. This study utilized a prospectively collected database of electronic patient-reported outcomes; we obtained approval from the Institutional Review Board at Duke University Medical Center for analysis of these data (Pro00108428). Consent to participate Informed consent was obtained from all individual participants included in the study. Competing interests Mihir N. Patel has received royalties from Prepped Health (Agreement #012617, HOPE). Suzanne Johnson and Julie Scott are employees of and hold stock or stock options in Carevive Systems, Inc. Thomas W. LeBlanc has received honoraria for consulting/advisory boards from AbbVie, Agilix, Agios/Servier, Apellis, Astellas, AstraZeneca, Beigene, BlueNote, BMS/Celgene, Genentech, GSK, Lilly, Meter Health, Novartis, and Pfizer; speaking related honoraria from AbbVie, Agios, Astellas, BMS/Celgene, GSK, Incyte, and Rigel; equity interest in Dosentrx and ThymeCare (stock options in a privately-held company); royalties from UpToDate; research funding from AbbVie, American Cancer Society, AstraZeneca, BMS, Deverra Therapeutics, Duke University, GSK, Jazz Pharmaceuticals, the Leukemia and Lymphoma Society, the National Institute of Nursing Research/ National Institutes of Health, and Seattle Genetics. All other authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Drug-resistant tuberculosis (DR-TB) represents a pressing global health issue, leading to heightened morbidity and mortality. Despite extensive research efforts, the escalation of DR-TB cases underscores the urgent need for enhanced prevention, diagnosis, and treatment strategies. This review delves deep into the molecular and genetic origins of different types of DR-TB, highlighting recent breakthroughs in detection and diagnosis, including Rapid Diagnostic Tests like Xpert Ultra, Whole Genome Sequencing, and AI-based tools along with latest viewpoints on diagnosis and treatment of DR-TB utilizing newer and repurposed drug molecules. Special emphasis is given to the pivotal role of novel drugs and discusses updated treatment regimens endorsed by governing bodies, alongside innovative personalized drug-delivery systems such as nano-carriers, along with an analysis of relevant patents in this area. All the compiled information highlights the inherent challenges of current DR-TB treatments, discussing their complexity, potential side effects, and the socioeconomic strain they impose, particularly in under-resourced regions, emphasizing the cost-effective and accessible solutions. By offering insights, this review aims to serve as a compass for researchers, healthcare practitioners, and policymakers, emphasizing the critical need for ongoing R&D to improve treatments and broaden access to crucial TB interventions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

For medical emergencies, such as acute ischemic stroke, rapid drug delivery to the target site is essential. For many small molecule drugs, this goal is unachievable due to poor solubility that prevents intravenous administration, and less obviously, by extensive partitioning to plasma proteins and red blood cells (RBCs), which greatly slows delivery to the target. Here we study these effects and how they can be solved by loading into nanoscale drug carriers. We focus on fingolimod, a small molecule drug that is FDA-approved for treatment of multiple sclerosis, which has also shown promise in the treatment of stroke. Unfortunately, fingolimod has poor solubility and very extensive partitioning to plasma proteins and RBCs (in whole blood, 86% partitions to RBCs, 13.96% to plasma proteins, and 0.04% is free). We develop a liposomal formulation that slows the partitioning of fingolimod to RBCs and plasma proteins, enables intravenous delivery, and additionally prevents fingolimod toxicity to RBCs. The liposomal formulation nearly completely prevented fingolimod adsorption to plasma proteins (association with plasma proteins was 98.4 ± 0.4% for the free drug vs. 5.6 ± 0.4% for liposome-loaded drug). When incubated with whole blood in vitro, the liposomal formulation greatly slowed partitioning of fingolimod to RBCs and also eliminated deleterious effects of fingolimod on RBC rigidity, morphology, and hemolysis. In vivo, the liposomal formulation delayed fingolimod partitioning to RBCs for over 30 min, a critical time window for stroke. Fingolimod-loaded liposomes showed improved efficacy in a mouse model of post-stroke neuroinflammation, completely sealing the leaky blood-brain barrier (114 ± 11.5% reduction in albumin leak into the brain for targeted liposomes vs. 38 ± 16.5% reduction for free drug). This effect was only seen for liposomes modified with antibodies to enable targeted delivery to the site of action, and not in unmodified, long-circulating liposomes. Thus, loading fingolimod into liposomes prevented partitioning to RBCs and associated toxicities and enabled targeted delivery. This paradigm can be used for tuning the blood distribution of small molecule drugs for the treatment of acute illnesses requiring rapid pharmacologic intervention., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background and objective Scalp dandruff, a prevalent dermatological condition marked by flaking and itching, affects a large segment of the population. Sun exposure, genetics, and dryness, along with winter conditions, indoor heating, and hard water, all contribute to moisture loss and scalp imbalance. This study aimed to evaluate the safety, efficacy, and tolerability of a novel regimen combining a scalp scrub with hydroxy acid derivatives for exfoliation and dandruff removal, and a serum containing copper tripeptide-1, witch hazel ( Hamamelis virginiana) , hesperidin, hyaluronic acid, and pea protein ( Pisum sativum ) for hydration and scalp health. Methods This prospective, interventional, open-label, single-center study assessed the safety, efficacy, and in-use tolerability of a scalp scrub and serum regimen for mild to moderate dandruff. Ethical approval was granted by ACEAS - Independent Ethics Committee and all participants provided written consent. The study evaluated changes in Adherent Scalp Flaking Score (ASFS), scalp hydration with the Corneometer ® CM 825, hair thickness, hair density, and scalp condition using CASLite Nova. Scalp appearance and treatment usage perception were evaluated on day 1, day 8, and day 15. Statistical analysis was conducted using SPSS Statistics v29.0.1.0 (IBM Corp., Armonk, NY) and Microsoft Excel 2019, with results reported as p-values and 95% confidence intervals (CI). Results As per the ASFS scale for adherent scalp flaking, a significant improvement of 61.24% (p<0.0001) was observed by day 15. Assessments with CASLite Nova showed significant increases in hair density and hair thickness by 12.48% (p<0.0001) and 25.36% (p<0.0001), respectively. Regarding scalp condition, the proportion of individuals with a dry scalp and significant keratin decreased from 65.52% at baseline to 6.9% by day 15. The incidence of dry scalp with fine dandruff also decreased from 6.9% at baseline to 0% by day 15. Conversely, the percentage of individuals with a dry scalp and some keratin increased from 27.59% at baseline to 48.28% by day 15. Also, the proportion of subjects with a normal scalp, characterized by good hair density and thickness, increased from 0% at baseline to 44.83% by day 15. Scalp skin hydration, measured by Corneometer® CM 825, showed a significant improvement of 76.24% (p<0.0001) from baseline to day 15. Overall, there were notable enhancements in scalp appearance, with reductions in itchiness, redness, roughness, and scaliness. All subjects reported satisfaction with the treatment. Conclusions The ThriveCo scalp regimen (scalp scrub + serum) has been demonstrated to be both effective and safe in treating and reducing scalp dandruff in healthy adults. The regimen significantly reduced ASFS by effectively removing visible scalp flakes from day 1 to day 15 with continuous use. Furthermore, the kit improved overall scalp condition, increased skin hydration, and enhanced the scalp's appearance. The components include scalp scrub with hydroxy acid derivatives for exfoliation and dandruff removal, and a serum containing copper tripeptide-1, Hamamelis virginiana , hesperidin, hyaluronic acid, and pea protein ( Pisum sativum ) for hydration and overall scalp health over the 15-day treatment period. The synergistic effects of this regimen work to clear visible dandruff flakes, reduce adherent scalp flaking, rejuvenate the scalp, and simultaneously strengthen the hair., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. ACEAS – Independent Ethics Committee issued approval NB230034-AL. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Maheshvari N. Patel, Nayan K. Patel declare(s) employment from NovoBliss Research Private Limited. Apeksha M. Merja declare(s) personal fees from NovoBliss Research Private Limited. Saurav Patnaik declare(s) employment from Anveya Living Private Limited. Anveya Living Private Limited is the Manufacturer of the test products ThriveCo Exfoliating Scrub and ThriveCo Vitalizing Serum. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Patel et al.)

Introduction Acne is a common inflammatory condition characterized by comedones, papules, and pustules, often resulting from increased sebum production influenced by hormones such as insulin-like growth factor-1 and androgens. Factors like Cutibacterium acnes , medications, sun exposure, cosmetics, and genetics exacerbate acne. This study aims to assess the safety and effectiveness of a novel acne treatment regimen, including a cleanser and serum containing Diacnemide™ (manufactured by Beaucience India Private Limited, Faridabad, India), in improving acne symptoms in adults. Methods This prospective, interventional, open-label, single-center, single-arm clinical study was designed to evaluate the safety, efficacy, and in-use tolerability of the test treatment regimen (serum + cleanser) for facial acne. Ethical approval was obtained from the Independent Ethics Committee, and all participants provided written consent. The study assessed changes in the severity of acne by dermatological assessment using the Investigator's Global Assessment (IGA) scale, changes in inflammatory and non-inflammatory lesions, skin hydration, sebum levels, and facial blemishes using various bioinstrumentations from Courage+Khazaka Electronic GmbH, Germany - Visiopor® PP34N, Corneometer® CM 825, Sebumeter® SM 815, and Mexameter® MX 18, respectively. Evaluations were conducted at baseline, T15 minutes, day 8, and day 15 post-usage. Statistical analyses were performed using SPSS (version 29.0.1.0) and Microsoft® Excel 2019 software, with results reported using p-values and confidence intervals at a 5% significance level. Results Porphyrin measurements showed significant reductions over time, with a 27.18% decrease in quantity and a 39.86% reduction by day 15 (p < 0.0001). Porphyrin values dropped by 2.61% after 15 minutes and 7.82% by day 15 (p < 0.05). Skin hydration increased significantly, with a 97.54% increment after 15 minutes and a 102.74% increment by day 15 (p < 0.0001). Sebum levels were restored to normal levels with the dry skin observed at baseline, showing a 34.45% improvement on day 8 and 75.75% by day 15 (p < 0.0001). Facial dark spots were reduced by 10.66% by day 8 and 14.64% by day 15 (p < 0.0001), and erythema levels decreased significantly. Acne severity showed notable improvement, with 50% of the subjects having moderate acne at baseline, reduced to 20.69% with mild acne, and 79.31% with almost clear skin by day 15. Subject responses indicated high satisfaction, with 100% agreeing on the test treatment's effectiveness in reducing acne, oiliness, and inflammation and improving hydration and skin texture. Conclusion The ThriveCo acne regimen (serum + cleanser) manufactured by Anveya Living Private Limited, India, is both effective and safe for treating facial acne in healthy adults with acne. It significantly reduces porphyrin size and quantity, indicating a strong inhibition of P. acnes , and visibly improves dark spots and skin hydration. The components - Diacnemide™ and zinc pyrrolidone carboxylic acid - in the cleanser regulate sebum production and provide anti-inflammatory benefits, while the serum, containing Diacnemide™ and niacinamide, enhances skin barrier function and balances lipids. The synergistic effects of the ThriveCo Goodbye Acne Cleanser and Serum in this regimen effectively target surface bacteria like C. acnes and deeper follicular issues, promoting healthier skin and reducing acne-related symptoms., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. ACEAS – Independent Ethics Committee issued approval NB230034-AL. All seven members of the committee, who reviewed the documents, gave a favorable opinion on the same, as the areas of concern on the safety of the investigational products have been found to be addressed in the protocol. The committee, therefore, expects to strictly adhere to the safety and precautionary measures incorporated in the protocol. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Maheshvari N. Patel, Nayan K. Patel declare(s) employment from NovoBliss Research Private Limited. Apeksha M. Merja declare(s) personal fees from NovoBliss Research Private Limited. Saurav Patnaik declare(s) employment from Anveya Living Private Limited. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Patel et al.)

This technical review provides a comprehensive overview of spinal tumor ablation and vertebral augmentation. These percutaneous minimally invasive procedures offer significant survival and palliative pain relief benefits for patients with pathological vertebral fractures. Vertebral augmentation, which includes vertebroplasty and kyphoplasty, involves injecting cement into fractured vertebral bodies to restore height. While vertebroplasty involves the direct injection of cement into a fractured vertebral body, kyphoplasty involves using a balloon to create a low-pressure cavity to allow for cement injection to restore the vertebral body height. Over the years, this technique has evolved into a straightforward process, though it presents certain technical challenges discussed in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Context: Prognostication challenges contribute to delays in advance care planning (ACP) for patients with cancer near the end of life (EOL)., Objectives: Examine a quality improvement mortality prediction algorithm intervention's impact on ACP documentation and EOL care., Methods: We implemented a validated mortality risk prediction machine learning model for solid malignancy patients admitted from the emergency department (ED) to a dedicated solid malignancy unit at Duke University Hospital. Clinicians received an email when a patient was identified as high-risk. We compared ACP documentation and EOL care outcomes before and after the notification intervention. We excluded patients with intensive care unit (ICU) admission in the first 24 hours. Comparisons involved chi-square/Fisher's exact tests and Wilcoxon rank sum tests; comparisons stratified by physician specialty employ Cochran-Mantel-Haenszel tests., Results: Preintervention and postintervention cohorts comprised 88 and 77 patients, respectively. Most were White, non-Hispanic/Latino, and married. ACP conversations were documented for 2.3% of hospitalizations preintervention vs. 80.5% postintervention (P<0.001), and if the attending physician notified was a palliative care specialist (4.1% vs. 84.6%) or oncologist (0% vs. 76.3%) (P<0.001). There were no differences between groups in length of stay (LOS), hospice referral, code status change, ICU admissions or LOS, 30-day readmissions, 30-day ED visits, and inpatient and 30-day deaths., Conclusion: Identifying patients with cancer and high mortality risk via machine learning elicited a substantial increase in documented ACP conversations but did not impact EOL care. Our intervention showed promise in changing clinician behavior. Further integration of this model in clinical practice is ongoing., (Published by Elsevier Inc.)

Nanomedicine has long pursued the goal of targeted delivery to specific organs and cell types but has yet to achieve this goal with the vast majority of targets. One rare example of success in this pursuit has been the 25+ years of studies targeting the lung endothelium using nanoparticles conjugated to antibodies against endothelial surface molecules. However, here we show that such "endothelial-targeted" nanocarriers also effectively target the lungs' numerous marginated neutrophils, which reside in the pulmonary capillaries and patrol for pathogens. We show that marginated neutrophils' uptake of many of these "endothelial-targeted" nanocarriers is on par with endothelial uptake. This generalizes across diverse nanomaterials and targeting moieties and was even found with physicochemical lung tropism (i.e., without targeting moieties). Further, we observed this in ex vivo human lungs and in vivo healthy mice, with an increase in marginated neutrophil uptake of nanoparticles caused by local or distant inflammation. These findings have implications for nanomedicine development for lung diseases. These data also suggest that marginated neutrophils, especially in the lungs, should be considered a major part of the reticuloendothelial system (RES), with a special role in clearing nanoparticles that adhere to the lumenal surfaces of blood vessels.

Image-guided ablation procedures have become a mainstay in cancer therapy. Typically performed from a percutaneous approach, thermal-based ablation procedures rely heavily on imaging guidance both prior to and during the procedure itself. Advances in imaging as they relate to ablation procedures are as important to successful treatments as advancements in the ablation technology itself. Imaging as it relates to procedural planning, targeting and monitoring, and assessment of procedural endpoint is the focus of this article., (Thieme. All rights reserved.)

Introduction Scalp dandruff is a common dermatological condition characterized by flaking and itching of the scalp, affecting a significant portion of the population. Effective assessment methods are crucial for evaluating treatment outcomes. This study aimed to establish the reliability and correlation of three assessment techniques: Adherent Scalp Flaking Score (ASFS), phototrichogram using CASLite Nova, and the 60-second hair combing test. Methods This open-label, single-arm, single-center, prospective clinical study enrolled 12 adult subjects with mild to moderate dandruff. Evaluations were conducted before and after a standardized hair-wash intervention using three methods: ASFS, phototrichogram using CASLite Nova, and the 60-second hair combing test. The primary objective was to establish correlations between these assessment techniques. Inter-evaluator and inter-operator reliability were assessed using Fleiss Multirater Kappa. Results Significant reductions in dandruff were observed across all methods post-hair wash. The ASFS decreased from 23.67±2.06 at baseline to 6.67±4.46, showing a mean reduction of 17.00±5.22 (71.40%, p<0.001). phototrichogram analysis revealed that 60.42% of the total (n=96) scalp zones assessed were in normal condition post-hair wash compared to none at baseline. The 60-second hair combing test showed a reduction in non-adherent flakes, with 58.33% of subjects displaying light flakes and 41.67% showing no flakes post-hair wash. The chi-squared test indicated a significant association (p<0.001) between ASFS and phototrichogram results. Inter-evaluator variability for ASFS and the hair combing test demonstrated substantial agreement (Kappa=0.692 and 0.637, respectively, p<0.0001). Inter-operator reliability for phototrichogram also showed substantial agreement (Kappa=0.746, p<0.0001). Conclusion The study confirms the reliability and consistency of ASFS, phototrichogram, and the 60-second hair combing test in assessing scalp dandruff. The significant correlations of ASFS and phototrichogram via CASLite Nova validate their use in clinical settings. Comprehensive training for evaluators and operators is essential to achieve reproducible and accurate results. These findings provide a robust framework for future studies and clinical assessments of scalp dandruff., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. ACEAS Independent Ethics Committee issued approval NB240024-NB-V. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Apeksha M. Merja declare(s) personal fees from NovoBliss Research Private Limited. The above-mentioned author is a consultant dermatologist to NovoBliss Research. There are no other potential conflicts of interest to disclose. Maheshvari N. Patel, Nayan K. Patel, Dhruvil U. Gajera, Arnav K. Purani, and Jemini H. Pandya declare(s) employment from NovoBliss Research Private Limited. The above-mentioned authors are employees of NovoBliss Research. There are no other potential conflicts of interest to disclose. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Patel et al.)

Lipid nanoparticles (LNPs) have transformed genetic medicine, recently shown by their use in COVID-19 mRNA vaccines. While loading LNPs with mRNA has many uses, loading DNA would provide additional advantages such as long-term expression and availability of promoter sequences. However, here we show that plasmid DNA (pDNA) delivery via LNPs (pDNA-LNPs) induces acute inflammation in naïve mice which we find is primarily driven by the cGAS-STING pathway. Inspired by DNA viruses that inhibit this pathway for replication, we co-loaded endogenous lipids that inhibit STING into pDNA-LNPs. Specifically, loading nitro-oleic acid (NOA) into pDNA-LNPs (NOA-pDNA-LNPs) ameliorates serious inflammatory responses in vivo enabling prolonged transgene expression (at least 1 month). Additionally, we demonstrate the ability to iteratively optimize NOA-pDNA-LNPs' expression by performing a small LNP formulation screen, driving up expression 50-fold in vitro . Thus, NOA-pDNA-LNPs, and pDNA-LNPs co-loaded with other bioactive molecules, will provide a major new tool in the genetic medicine toolbox, leveraging the power of DNA's long-term and promoter-controlled expression.

The Re(I) organometallic compounds [(Re(CO)3L1-6 )Cl], where Ligand(L) = Tryptanthrin derivatives were prepared and characterized by various spectroscopic techniques. To assess the binding capacities and binding manner, tests of Calf thymus DNA under the impact of organometallic complexes were conducted using absorption titration and viscosity measuring techniques. Data from the research mentioned above point to an intercalation type of binding, which was verified by the docking study. Swiss ADME tools carried out an ADME study. The work focuses on computing the molecular orbital energies for the synthesized compounds using the density functional theory (DFT). The compounds were tested against the MCF-7 cell line to determine their anticancer effects. It was observed that their IC50 values were equivalent to those of the standard medication, indicating that they had a similar antiproliferative impact.

Lipid nanoparticles (LNPs) have become the dominant drug delivery technology in industry, holding the promise to deliver RNA to up or down-regulate any protein of interest. LNPs have mostly been targeted to specific cell types or organs by physicochemical targeting in which LNP's lipid compositions are adjusted to find mixtures with the desired tropism. Here lung-tropic LNPs are examined, whose organ tropism derives from containing either a cationic or ionizable lipid conferring a positive zeta potential. Surprisingly, these LNPs are found to induce massive thrombosis. Such thrombosis is shown in the lungs and other organs, and it is shown that it is greatly exacerbated by pre-existing inflammation. This clotting is induced by a variety of formulations with cationic lipids, including LNPs and non-LNP nanoparticles, and even by lung-tropic ionizable lipids that do not have a permanent cationic charge. The mechanism depends on the LNPs binding to and then changing the conformation of fibrinogen, which then activates platelets and thrombin. Based on these mechanisms, multiple solutions are engineered that enable positively charged LNPs to target the lungs while ameliorating thrombosis. The findings illustrate how physicochemical targeting approaches must be investigated early for risks and re-engineered with a careful understanding of biological mechanisms., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Two camps have emerged for targeting nanoparticles to specific organs and cell types: affinity moiety targeting and physicochemical tropism. Here we directly compare and combine both using intravenous (IV) lipid nanoparticles (LNPs) designed to target the lungs. We utilized PECAM antibodies as affinity moieties and cationic lipids for physicochemical tropism. These methods yield nearly identical lung uptake, but aPECAM LNPs show higher endothelial specificity. LNPs combining these targeting methods had >2-fold higher lung uptake than either method alone and markedly enhanced epithelial uptake. To determine if lung uptake is because the lungs are the first organ downstream of IV injection, we compared IV vs intra-arterial (IA) injection into the carotid artery, finding that IA combined-targeting LNPs achieve 35% of the injected dose per gram (%ID/g) in the first-pass organ, the brain, among the highest reported. Thus, combining the affinity moiety and physicochemical strategies provides benefits that neither targeting method achieves alone.

Background: The healthcare managers need to develop the managerial skills and use it for better healthcare delivery. A manager requires leadership skill to empower employees and motivate them to work in an efficient manner to achieve organizational goal. Motivating employees/subordinates and developing positive attitude toward them is one of the crucial skills that the leader needs to develop. The way health team works as a unit affects the outcome and needs good leader. With this background, the current study tends to explore the managerial skills of middle-level managers., Objectives: 1. To assess the leadership and team management skills of middle-level managers and 2. To find out motivational factors used by managers., Materials and Methods: A cross-sectional study was conducted among district-level healthcare managers and medical officers. Data collection was performed via semistructured and scale-based questionnaire and analyzed using Microsoft office excel., Results: 60% of managers had participative leadership style. Team work skills were fair enough among the managers. 53% of medical officers were freshly appointed with experience of less than one year. The middle-level managers used appreciation of work (41.8%) as major motivator of the team., Conclusions: The middle-level healthcare managers have good leadership quality as well as teamwork skills. Appreciation of work is commonly used motivator., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

Background: Due to the rarity of pediatric diseases, collaborative research is the key to maximizing the impact of research studies. A research needs assessment survey was created to support initiatives to foster pediatric interventional radiology research., Objective: To assess the status of pediatric interventional radiology research, identify perceived barriers, obtain community input on areas of research/education/support, and create metrics for evaluating changes/responses to programmatic initiatives., Materials and Methods: A survey link was sent to approximately 275 members of the Society for Pediatric Interventional Radiology (SPIR) between May and October 2020. Data was collected using a web-based interface. Data collected included practice setting, clinical role, research experience, research barriers, and suggestions for future initiatives., Results: Fifty-nine surveys were analyzed with a staff physician survey response rate of 28% (56/198). A wide range of practice sizes from 15 countries were represented. Respondents were predominantly staff physicians (95%; 56/59) with an average of 11 years (range: 1-25 years) of clinical experience working at academic or freestanding children's hospitals. A total of 100% (59/59) had research experience, and 70% (41/58) had published research with a mean of 30 peer-reviewed publications (range: 1-200). For job security, 56% (33/59) of respondents were expected or required to publish, but only 19% (11/58) had research support staff, and 42% (25/59) had protected research time, but of those, 36% (9/25) got the time "sometimes or never." Lack of support staff, established collaborative processes, and education were identified as top barriers to performing research., Conclusions: The needs assessment survey demonstrated active research output despite several identified barriers. There is a widespread interest within the pediatric interventional radiology community for collaborative research., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Jatyadi taila (JT) is a well-known Ayurvedic wound-healing product, comprising 16 different medicinally important plants, including Curcuma longa, Terminalia chebula, and Jasminum officinale., Objective: The proposed work discusses the development and validation of the green and economical stability-indicating HPTLC method for quantification of the key marker phytoconstituents, curcumin (CUR), gallic acid (GA), and ursolic acid (UA), from JT., Method: Quality standard parameters for JT were determined following standard procedures. The marker constituents CUR, GA, and UA were resolved from JT using toluene-ethyl acetate-formic acid (6:2:1, v/v/v) as the mobile phase and subsequently derivatized to estimate UA. The developed plates were subjected to HPTLC-MS analysis. All constituents were subjected to forced degradation to determine the proposed technique's stability-indicating property and the accelerated stability studies of marketed formulation and marker constituents. Greenness evaluation of the method was aided by the AGREE methodology., Results: The Rf values of CUR, GA, and UA were found to be 0.60 and 0.60; 0.27 and 0.28; and 0.74 and 0.77 from reference standard and oil samples respectively, when analyzed at 366 nm, 290 nm, and 366 nm, respectively. HPTLC-MS was carried out to verify the active constituents present in JT. The constituents followed first-order degradation kinetics. The quantity of CUR, GA, and UA in JT was reduced at the end of accelerated stability studies. The developed approach was validated in compliance with the International Conference on Harmonization (ICH) Q2 (R2) guideline., Conclusions: Among the chosen key markers, GA was highly unstable during forced degradation. JT should be stored at a controlled temperature using more protective packaging material to ensure its quality and efficacy., Highlights: The developed method can be used as a quality control tool for JT as it can be used to determine the stability of the key marker compounds the herbal formulation., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Biosimilar drugs have broadened the treatment options in assisted reproductive technology (ART). Real-world data comparing clinical outcomes of originator follitropin alfa (Gonal-f ® ) with its biosimilars are required to enrich the body of evidence for clinical decision-making on choice of drug., Aims: To compare the ART outcomes in patients receiving originator follitropin (Gonal-f ® ) and its biosimilars in clinical setting., Settings and Design: Medical records of 364 infertile women who underwent ART between 2016 and 2020 at Akanksha Hospital and Research Institute, Gujrat, India, were retrospectively analysed., Materials and Methods: Participants were divided into two cohorts based on treatment (Gonal-f ® cohort; N = 174 and biosimilar cohort; N = 190), each cohort further subdivided into group A (age <35 years) and group B (age ≥35 years). Fresh or frozen embryo transfer was performed as per the standard procedures of the clinic. Pregnancy rates and live birth rate (LBR) were the primary main outcome measures in this study., Statistical Analysis Used: Descriptive statistics and Chi-square test were used for analysis., Results: The number of oocytes retrieved from Gonal-f ® and biosimilar cohorts were comparable (13.3 vs. 14.4). Compared to biosimilars, Gonal-f ® treatment resulted in higher yield of cleavage stage and blastocyst stage embryos, and the proportion of women with good quality embryos was higher in the Gonal-f ® cohort than the biosimilar cohort (83.3% vs. 69.5%). Patients receiving Gonal-f ® reported higher pregnancy rates (59.2% vs. 39.7%) and LBR (43% vs. 17.7%) compared to those receiving biosimilars., Conclusions: Gonal-f ® (originator follitropin) treatment could result in higher pregnancy rates and LBR in comparison to biosimilars in real-world setting., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Human Reproductive Sciences.)

Lymphocyte antigen 6K (LY6K) is a small GPI-linked protein that is normally expressed in testes. Increased expression of LY6K is significantly associated with poor survival outcomes in many solid cancers, including cancers of the breast, ovary, gastrointestinal tract, head and neck, brain, bladder, and lung. LY6K is required for ERK-AKT and TGF-β pathways in cancer cells and is required for in vivo tumor growth. In this report, we describe a novel role for LY6K in mitosis and cytokinesis through aurora B kinase and its substrate histone H3 signaling axis. Further, we describe the structural basis of the molecular interaction of small molecule NSC243928 with LY6K protein and the disruption of LY6K-aurora B signaling in cell cycle progression due to LY6K-NSC243928 interaction. Overall, disruption of LY6K function via NSC243928 led to failed cytokinesis, multinucleated cells, DNA damage, senescence, and apoptosis of cancer cells. LY6K is not required for vital organ function, thus inhibition of LY6K signaling is an ideal therapeutic approach for hard-to-treat cancers that lack targeted therapy such as triple-negative breast cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Sphagnum magellanicum is one of two Sphagnum species for which a reference-quality genome exists to facilitate research in ecological genomics. Phylogenetic and comparative genomic analyses were conducted based on resequencing data from 48 samples and RADseq analyses based on 187 samples. We report herein that there are four clades/species within the S. magellanicum complex in eastern North America and that the reference genome belongs to Sphagnum divinum. The species exhibit tens of thousands (RADseq) to millions (resequencing) of fixed nucleotide differences. Two species, however, referred to informally as S. diabolicum and S. magni because they have not been formally described, are differentiated by only 100 (RADseq) to 1000 (resequencing) of differences. Introgression among species in the complex is demonstrated using D-statistics and f 4 ratios. One ecologically important functional trait, tissue decomposability, which underlies peat (carbon) accumulation, does not differ between segregates in the S. magellanicum complex, although previous research showed that many closely related Sphagnum species have evolved differences in decomposability/carbon sequestration. Phylogenetic resolution and more accurate species delimitation in the S. magellanicum complex substantially increase the value of this group for studying the early evolutionary stages of climate adaptation and ecological evolution more broadly., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

Biren Parikh Introduction  Hormonal status and HER2 expression are valuable biomarkers and dictate the management of the patients diagnosed with invasive breast cancer (IBC). It is crucial to identify the patients who truly respond to anti-HER2 targeted therapy. Updated 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines has recommended certain modifications in HER2 interpretation by fluorescence in situ hybridization (FISH) with concomitant immunohistochemistry (IHC). Objectives  We aimed to evaluate HER2 FISH interpretation in IBC with equivocal IHC results as per 2018 ASCO/CAP recommendations and compare FISH results with hormonal receptor status. Materials and Methods  FISH results of 502 cases of IBC with equivocal IHC report between January 2016 to January 2022 were reviewed retrospectively. FISH results were categorized according to ASCO/CAP guidelines 2018 into five respective groups. Results  FISH testing in IHC equivocal cases showed 219 (43.6%) cases were classic amplified (positive) belonged to group 1, 217(43.2%) cases were classic nonamplified (negative) fell into group 5, 39 (7.8%) and 02 (0.4%) patients were in group 2 (negative) and group 3 (positive), and 25 (5.0%) cases were in group 4 (negative). About 52.1 and 49.3% of cases with estrogen receptor and progesterone receptor positivity were reported as HER2 positive. Among 502 cases, 25 equivocal cases according to the 2013 guidelines were redefined as HER2 negative and 02 (0.4%) cases reported positive were classified negative as per updated 2018 guidelines. Conclusion  Revised 2018 guidelines is helpful in accurate identification of HER2 status and in avoiding targeted therapy in unwarranted cases. Updated 2018 guidelines has removed equivocal HER2-FISH category that has eliminated management dilemma in these cases. Only long-term clinical follow-up will establish the validity of the updated guidelines., Competing Interests: Conflict of Interest None declared., (MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: In the ongoing COVID-19 pandemic, an increased incidence of ROCM was noted in India among those infected with COVID. We determined risk factors for rhino-orbito-cerebral mucormycosis (ROCM) post Coronavirus disease 2019 (COVID-19) among those never and ever hospitalized for COVID-19 separately through a multicentric, hospital-based, unmatched case-control study across India., Methods: We defined cases and controls as those with and without post-COVID ROCM, respectively. We compared their socio-demographics, co-morbidities, steroid use, glycaemic status, and practices. We calculated crude and adjusted odds ratio (AOR) with 95% confidence intervals (CI) through logistic regression. The covariates with a p-value for crude OR of less than 0·20 were considered for the regression model., Results: Among hospitalised, we recruited 267 cases and 256 controls and 116 cases and 231 controls among never hospitalised. Risk factors (AOR; 95% CI) for post-COVID ROCM among the hospitalised were age 45-59 years (2·1; 1·4 to 3·1), having diabetes mellitus (4·9; 3·4 to 7·1), elevated plasma glucose (6·4; 2·4 to 17·2), steroid use (3·2; 2 to 5·2) and frequent nasal washing (4·8; 1·4 to 17). Among those never hospitalised, age ≥ 60 years (6·6; 3·3 to 13·3), having diabetes mellitus (6·7; 3·8 to 11·6), elevated plasma glucose (13·7; 2·2 to 84), steroid use (9·8; 5·8 to 16·6), and cloth facemask use (2·6; 1·5 to 4·5) were associated with increased risk of post-COVID ROCM., Conclusions: Hyperglycemia, irrespective of having diabetes mellitus and steroid use, was associated with an increased risk of ROCM independent of COVID-19 hospitalisation. Rational steroid usage and glucose monitoring may reduce the risk of post-COVID., Competing Interests: The authors have declared that no competing interests exist.

Pyrazine-bipyrazole-based µ-oxo bridged dinuclear Au(III) complexes were synthesized and characterized by various spectrometric ( 1 H-NMR, 13 C (APT) NMR, FT-IR, Mass spectrometry) and analytical techniques (elemental analysis and conductance measurement). The evaluation of DNA binding activity by UV-Vis absorption spectra and viscosity measurement demonstrated that all the compounds intercalate in between the stacks of DNA base pair and the binding constant values were observed in the range of 5.4 × 10 4 -2.17 × 10 5  M -1 . The molecular docking study also supports the intercalation mode of binding. The anti-proliferation activity of complexes on A549 (Lung adenocarcinoma) cells by MTT assay demonstrated IC 50 values in the range of 47.46 -298.12 μg/mL. The genotoxicity of compounds was checked by smearing observed in the DNA of S. pombe cell under the influence of complexes. The in vivo cytotoxicity of compounds against brine shrimp demonstrated the LC 50 values in the range of 4.59-27.22 μg/mL. The promising results of the Au(III) complexes received significant attention and make them suitable for the new metallodrugs after the detailed mechanistic biological study., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: To evaluate the usefulness of a published clinical decision support tool to predict the likelihood of a retrievable inferior vena cava (IVC) filter being maintained as a permanent device., Methods: This multicenter retrospective cohort study included 1498 consecutive patients (852 men and 646 women; median age, 60 years; range, 18-98 years) who underwent retrievable IVC filter insertion between January 2012 and December 2019. The indications for IVC filtration, baseline neurologic disease, history of venous thromboembolism (VTE), and underlying malignancy were recorded. Accuracy, sensitivity, and specificity of a published clinical support tool were calculated to determine the usefulness of the tool., Results: The majority of filters (1271/1498 [85%]) were placed for VTE with a contraindication to anticoagulation. A history of VTE was present in 811 of 1498 patients (54%) patients; underlying malignancy in 531 of 1498 patients (35%), and neurological disease in 258 of 1498 patients (17%). Of the 1498 filters, 456 (30%) were retrieved, 276 (18%) were maintained as permanent devices on follow-up, and 766 (51%) filters were not retrieved. The accuracy of the clinical prediction model was 61%, sensitivity was 60%, and specificity was 62%., Conclusions: A previously published clinical decision support tool to predict permanence of IVC filters had modest usefulness in the examined population; this factor should be taken into account when using this clinical decision support tool outside of the original study population. Future studies are required to refine the predictive capability of IVC filter decision support tools for broader use across different patient populations., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Mitochondrial superoxide (O 2 - ) production is implicated in aging, neurodegenerative disease, and most recently epilepsy. Yet the specific contribution of neuronal O 2 - to these phenomena is unclear. Here, we selectively deleted superoxide dismutase-2 (SOD2) in neuronal basic helix-loop-helix transcription factor (NEX)-expressing cells restricting deletion to a subset of excitatory principle neurons primarily in the forebrain (cortex and hippocampus). This resulted in nSOD2 KO mice that lived into adulthood (2-3 months) with epilepsy, selective loss of neurons, metabolic rewiring and a marked mitohormetic gene response. Surprisingly, expression of an astrocytic gene, glial fibrillary acidic protein (GFAP) was significantly increased relative to WT. Further studies in rat primary neuron-glial cultures showed that increased mitochondrial O 2 - , specifically in neurons, was sufficient to upregulate GFAP. These results suggest that neuron-specific mitochondrial O 2 - is sufficient to drive a complex and catastrophic epileptic phenotype and highlights the ability of SOD2 to act in a cell-nonautonomous manner to influence an astrocytic response., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hereditary multiple exostoses (HME) are an autosomal dominant skeletal disorder characterized by the development of multiple benign osteochondromas (exostoses) that frequently involve long bones of the body. Less commonly, the ribs are a site of involvement, and long-term friction between an exostosis and pleura can produce a hemothorax or pneumothorax. The purpose of this study is to provide a comprehensive review of existing literature on pneumothorax or hemothorax secondary to costal exostosis in HME patients. We reviewed the databases of PubMed and Embase and included data as current as of February 15, 2021. All case reports included cases of hemothorax or pneumothorax in patients with a known personal or family history of HME. After evaluation for inclusion based on eligibility criteria, 18 cases were included. The average age at presentation was 11.7 years (range: 3-32), and most patients were male (83%). Hemothoraces occurred in 15 cases, while pneumothoraces occurred in three cases. All cases were evaluated using chest X-ray and CT scan, and the majority of the cases were treated with surgical resection of the exostosis, either with video-assisted thoracoscopic surgery (VATS; 61%) or thoracotomy (22%). Outcomes were successful with no cases of recurrence after surgical intervention. Although rare, costal exostosis should be considered as a differential in patients presenting with pneumothorax or hemothorax and past medical history or physical exam findings suggestive of HME. Immediate evaluation and surgical intervention to resect costal exostosis are essential to reduce the risk of recurrent life-threatening injury., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Sheaffer et al.)

N, S donor ligands (L 1 -L 5 ){L 1 -L 5  = 1,5-bis(4-chlorophenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole (L 1 ), 1-(4-bromophenyl)-5-(4-chlorophenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole (L 2 ), 5-(4-chlorophenyl)-3-(thiophen-2-yl)-1-(p-tolyl)-4,5-dihydro-1H-pyrazole (L 3 ), 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole (L 4 ), 5-(4-chlorophenyl)-1-(4-nitrophenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole (L 5 )} were synthesized by Claisen-Schmidt condensation and characterized by spectrometric methods. The complexes (I-V) were synthesized by ligand combination followed by metal chelation. The binding of the rhenium complexes to Herrin sperm DNA was monitored by UV spectroscopy and viscosity measurements. The groove binding was suggested as the most possible mode, and the K b values of the complexes were calculated. The mode of interaction was furthermore confirmed by molecular docking. Brine shrimp lethality and Saccharomyces cerevisiae cytotoxicity against the eukaryotic and prokaryotic cells showed the toxic nature of the synthesized compounds. All compounds were found active against S. cerevisiae, which was confirmed by increased ROS production, and DNA damage as compared to untreated yeast cell culture. The oxidative harm to cell structures was affirmed by lipid peroxidation. An antimicrobial study was carried out by estimating minimum inhibitory concentration against two Gram-positive and three Gram-negative bacteria. All complexes show good antiproliferative activity against the HCT 116 cell line. All synthesized complexes are biologically more active than the corresponding ligands.

Variable and low oral bioavailability (4-11%) of lumefantrine (LUF), an anti-malarial agent, is characterized by very low solubility in aqueous vehicle. Thus, the present study was intended to formulate lyophilized nanosuspensions of LUF to resolve its solubility issues for the improvement of oral bioavailability. A three level 3 2 factorial design was applied to analyze the influence of independent variables, concentration of polysorbate 80 (X 1 ) and sonication time (X 2 ) on the responses for dependent variables, particle size (Y 1 ) and time to 90% release of LUF (t 90 ) (Y 2 ). Optimized formulation (F3) has shown to possess lowest particle size (95.34 nm) with minimum t 90 value (⁓3 mins), which was lyophilized to obtain the dry powder form of the nanosuspension. The characterization parameters confirmed the amorphous form of LUF with good stability and no chemical interactions of the drug with the incorporated components. Further, saturation solubility study revealed increased solubility of the LUF nanosuspension (1670 µg/mL) when compared to the pure drug (212.33 µg/mL). Further, rate of dissolution of LUF from the nanosuspension formulations were found to be significantly ( p  < 0.05) higher when compared to the pure drug. Fabricated lyophilized nanosuspension was found to be stable at 25 ± 2 °C/60 ± 5% RH and 40 ± 2 °C/75 ± 5% RH for the duration of three months. In conclusion, lyophilized nanosuspension showed ∼8-folds increase in drug release, which indicated a better way to offer higher release of LUF in controlling malaria.

Biological applications of platinum group metal-based complexes have been widely explored in synthetic and inorganic chemistry. The compounds have been subjected to DNA binding, DNA cleavage, In-vivo and In-vitro photocytotoxicity (HCT-116 cell line) and bacteriostatic activities. Binding constant of complexes are 1.42-5.62 × 10 4 M -1 , whereas that of ligands are 1.12-4.72 × 10 4 M -1 . K sv of complexes are about 1.32-5.21 × 10 3 M -1 , whereas K f is about 1.24-6.83 × 10 3 M -1 . IC 50 of compounds screened using HCT-116 cell line in dark are found to be 121-342 μg/mL. Whereas photocytotoxicity is found in the range of 48-316 μg/mL. Docking energy of molecules have been evaluated to evaluate efficacy of binding. Molecular docking energy of complexes are in the range of -286.00 to -303.11 kJ/mol. Whereas that of ligands are -254.03 to -282.96 kJ/mol. MIC of complexes are 47 ± 2.5 to 77.50 ± 7.5 μM. LC 50 values of ligands fall in the range of 4.05-19.72 μg/mL and that of Os(IV) complexes fall in the range of 3.99-15.99 μg/mL. The Os(IV) complexes dominate in proving its potentiality compared to N, N-donor ligands in biological activities. [Formula: see text]Communicated by Ramaswamy H. Sarma.

Osmium(IV) pyrazole compounds and ligands were synthesized and well characterised. Ligands were characterized by heteronuclear NMR spectroscopy ( 1 H & 13 C), elemental analysis, IR spectroscopy and liquid crystal mass spectroscopy. Os(IV) complexes were characterized by ESI-MS, ICP-OES, IR spectroscopy, conductance measurements, magnetic measurements and electronic spectroscopy. Binding of compounds with HS-DNA were evaluated using viscosity measurements, absorption titration, fluorescence quenching, and molecular docking, which show effective intercalation mode exhibited by compounds. Binding constant of Os(IV) complexes are found to be 8.1 to 9.2 × 10 4  M -1 . Bacteriostatic and cytotoxic activities were carried out to evaluate MIC, LC 50 , and IC 50 . The compounds have been undergone bacteriostatic screening using three sets of Gram +ve and two sets of Gram -ve bacteria. MIC of complexes are found to be 72.5-100 μM, whereas that of ligands fall at about 122.5-150 μM.. LC 50 count of ligands fall in the range of 16.22-17.28 μg/mL whereas that of complexes of Os(IV) fall in the range of 4.87-5.87 μg/mL. IC 50 of osmium compounds were evaluated using HCT-116 cell line. All the Os(IV) compounds show moderate IC 50 .

Osmium (IV) complexes with pyrazole nucleus containing ligands were synthesized. Os(IV) compounds were characterized using ESI-MS, ICP-OES, IR spectroscopy, electronic spectroscopy, conductance, and magnetic measurements. Whereas, ligands were characterized by heteronuclear spectroscopy, ( 1 H and 13 C), IR spectroscopy, and elemental analysis. All the compounds were tested for their potential to interact with HS-DNA by absorption titration, fluorescence spectroscopy, viscosity measurement, and docking study. The quenching constant and Stern Volmer constant values were calculated using fluorescence study. The synthesized compounds were studied for in-vitro bacteriostatic and cytotoxic activities. The cancer cell line studies of all the synthesized complexes were carried out on human lung cancer cells (A549).Supplemental data for this article is available online at https://doi.org/10.1080/15257770.2021.1921795 .

Patients with advanced cancer and their families frequently encounter clinical and logistical challenges related to end-of-life care. Hospice provides interdisciplinary and holistic care to meet patients' biomedical, psychosocial, and spiritual needs in the last phases of life. Despite increasing general acceptance and use among patients with cancer, hospice remains underused. Underuse stems from ongoing misconceptions regarding hospice and its purpose, coupled with the rapid development of novel anticancer treatments, such as immunotherapies and targeted therapies, that have changed the landscape of possibilities. Furthermore, rapid evolutions in how end-of-life care is structured and reimbursed for will affect how oncology patients will intersect with hospice care. In this review, we explore the current and future challenges to greater integration of hospice care in the care of patients with advanced cancer and propose five recommendations as part of the path forward.

Hetero mononuclear rhenium(I) metal complexes (I-V) using different substituted indole-pyrazoline based ligands were synthesized and characterized by spectroscopic and analytical methods. The binding of the rhenium complexes to Herring sperm DNA was monitored by UV spectroscopy, viscosity measurements, and molecular docking studies; groove binding was suggested as the most possible mode and the DNA-binding constants of the complexes were evaluated. In vivo and in vitro cytotoxicity of compounds were evaluated against the brine shrimp and S. cerevisiae cells. An antimicrobial study was carried out by estimating MIC (Minimum Inhibitory Concentration) against two Gram-positive and three Gram-negative bacteria. All synthesized complexes are biologically more active than the corresponding ligands. The anti-proliferation activity of complexes was evaluated on MCF-7, HCT116, and A549 cancer cells by MTT assay. The toxicity profile of synthesized compounds was confirmed by H 2 O 2 production by reactive oxygen species. The increased concentration of lipid peroxidation end products increased free radicals, which enhancing the oxidative stress level in living organisms and results in cell death., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The neutral rhenium(I) complexes (I-VI) of type [ReCl(CO)3Ln-] where L1 = 7-phenyl-5-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidine, L2 = 7-(4-bromophenyl)-5-(pyridin-2-yl)pyrazolo[1,5-a]pyrimi- dine, L3 = 7-(4-chlorophenyl)-5-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidine, L4 = 7-(2-chlorophenyl) -5-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidine, L5 = 7-(4-methoxyphenyl)-5-(pyridin-2-yl)pyrazolo [1,5-a]pyrimidine, L6 = 5-(pyridin-2-yl)-7-(p-tolyl)pyrazolo[1,5-a]pyrimidine were synthesized and characterized by 13C-APT, 1H-NMR, IR, electronic spectra, magnetic moment and conductance measurement. The anti-proliferative activity on HCT116 cells by MTT assay suggests potent cytotoxic nature of complexes, even some complexes have better activity than standard drug cisplatin, oxaliplatin, and carboplatin. The complexes found to have better antimicrobial activity compare to pyrazolo pyrimidine ligands. The theoretical study of compounds-DNA interactions was examined by molecular docking as a supportive tool to the experimental data, which suggests the groove mode of binding. The values of docking energy for compounds-DNA interaction were found in the range of -230.31 to -288.34 kJ/mol. The intrinsic binding constant values of complexes (1.1-3.5×105 M-1) were found higher than the ligands (0.32-1.8×105 M-1).

The aim of this study was to investigate the alterations in the neuroendocrine-immune functions by using human peripheral blood mononuclear cells (hPBMCs) from three age groups (young, middle-aged, and old) of men and women for the analyses of lymphocyte proliferation and cytokine production, expression of cell signaling molecules, nitric oxide (NO) production, and expression of p-tyrosine hydroxylase (TH). Serum was examined for levels of testosterone in men, 17-β-estradiol in women, and cortisol in both sexes. Lymphoproliferation, expression of p-ERK, p-CREB, p-Akt, and p-TH, and levels of serum sex steroid hormones declined with age in men and women. However, TNF-α production and serum cortisol level increased with age in men and women. mTOR expression was higher in older men while it was lower in older women. IFN-γ and IL-6 production and expression of p-TH and p-mTOR were differentially regulated in men and women. These results suggest that intracellular signaling mediators may be involved in the age-related alterations in the neuroendocrine-immune interactions in men and women., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Sclerotherapy or surgical resection is options for symptomatic venous malformations (VM). Sclerotherapy may require repetitive intervention and resection is often avoided due to operative morbidity. The purpose of this study was to report use of single-stage n-butyl cyanoacrylate glue embolization and surgical resection of focal VM., Methods: A review of patients with focal VM who underwent glue embolization followed by resection at a single tertiary care vascular malformations center was performed. All embolizations were performed with ultrasound and fluoroscopy under the same anesthetic as resection. Patient characteristics and outcomes were evaluated., Results: Fifteen procedures were performed in 12 patients with a total of 20 VM addressed, as several patients had multiple VM. Mean age was 16 ± 9 years. Malformation locations included scalp, hip, gluteal, labial, toe, finger, face, lip, chest, and foot and size ranged from 1.0 to 10.5 cm. Median (range) of prior sclerotherapy treatments was 3 (0-5) and three patients previously underwent surgical resection. Median blood loss was zero (0-10) mL. Surgical complications occurred after five procedures (33%) including superficial wound dehiscence and cellulitis. No complications required readmission or reoperation. At a median follow up of 195 (103-266) days, no patients have required additional treatment., Conclusion: Glue embolization and resection of focal VM of variable size and location appears to have durable results and low surgical morbidity. This single-stage procedure, often performed as an outpatient, may be utilized as upfront treatment for symptomatic malformations or for VM refractory to other treatments., (© 2019 Wiley Periodicals, Inc.)

Ruthenium(III) complexes [Ru(bphtpy)(PPh3)Cl3] (bphfpy = diphenylfuranylpyridine derivatives) were synthesized and characterized by LCMS, IR spectroscopy, elemental analysis and magnetic measurements. All the complexes were screened for their antibacterial activity in terms of minimum inhibitory concentration against two Gram-positive and three Gram-negative bacterial species. DNA binding study by absorption titration and viscosity measurement shows that complexes bind in an intercalating mode, which is also confirmed by molecular docking. All the complexes were also screened for the DNA nuclease property of pUC19 plasmid DNA. The cytotoxicity study of the synthesized complexes was performed to elucidate the LC50 values to find out the toxicity profile of the complexes.

Vascular dysfunction associated with hypertension comprises hypercontractility and impaired vasodilation. We have previously demonstrated that triiodothyronine (T3), the active form of thyroid hormone, has vasodilatory effects acting through rapid onset mechanisms. In the present study, we examined whether T3 mitigates vascular dysfunction associated with hypertension. To test the direct effects of T3 in hypertensive vessels, aortas from female Dahl salt-sensitive (Dahl SS) rats fed a high-salt diet (8% NaCl, HS group) and their age-matched controls fed a standard low-salt diet (0.3% NaCl, LS group) for 16 weeks were isolated and used in ex vivo vascular reactivity studies. We confirmed that the HS group exhibited a higher systolic blood pressure in comparison with the control LS group and displayed aortic remodeling. Aortas from both groups were pretreated with T3 (0.1 μ M) for 30 minutes at 37°C in a 5% CO 2 incubator before functional vascular studies. T3 treatment significantly attenuated hypercontractility and improved impaired endothelium-dependent vasodilation in aortas from the HS group. These vascular improvements in response to T3 were accompanied by increased phosphorylation of vasodilator-stimulated phosphoprotein (VASP) at serine 239, a vasodilatory factor of the cGMP-dependent protein kinase (PKG)/VASP signaling pathway in vascular smooth muscle cells. Moreover, increased production of reactive oxygen species in aortas from the HS group were significantly reduced by T3, suggesting a potential antioxidant effect of T3 in the vasculature. These results demonstrate that T3 can mitigate hypertension-related vascular dysfunction through the VASP signaling pathway and by reducing vascular ROS production. SIGNIFICANCE STATEMENT: This study demonstrates that triiodothyronine (T3) directly acts on vascular tone and has a beneficial effect in hypertension-induced vascular dysfunction. T3 augmented vasodilation and diminished vasoconstriction in blood vessels from hypertensive rats in association with activation of the protein kinase G/vasodilator-stimulated phosphoprotein signaling pathway that activates vascular relaxation and exerted an antioxidant effect. Collectively, these results show that T3 is a potential vasoprotective agent with rapid action on hypertension-related vascular dysfunction., (Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: Data on the cost of snakebite injuries may inform key pillars of universal health coverage including proper planning, allocation, and utility of resources. This study evaluated the injuries, management, and costs resulting from snakebites at Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH) in Kenya.  Methods: In total, medical records of 127 snakebite victims attending JOOTRH between January 2011 and December 2016 were purposely selected and data on the age, gender, type of residence (urban or rural), part of the body bitten, time of bite, injuries, pre-hospital first aid, time to hospital, length of stay, treatment, and costs were collected. Regression analysis was used to predict the total indirect cost of snakebite injuries and p≤ 0.05 was considered significant. Mortality and loss of income of hospitalized victims were considered as direct costs. Results: It was found that 43 victims were 13-24 years of age, 64 were female, 94 were from rural areas, 92 were bitten on the lower limbs, 49 were bitten between 6.00 pm and midnight, 43 attempted pre-hospital first aid, and the median time to hospital was 4.5 hours. Antivenom, supportive therapy, antibiotics, antihistamines, corticosteroids, analgesics, and non-steroidal anti-inflammatory drugs were used. Cellulitis, compartment syndrome, gangrenous foot, psychiatric disorder, and death were the main complications. Most victims spent 1-5 days in hospital and the median cost of treating a snakebite was 2652 KES (~$26). Drugs, ward charges, and nursing procedures were the highest contributors to the total indirect cost. Victims hospitalized for 6-10 days and >10 days incurred 32% and 62% more costs, respectively, compared to those hospitalized for 1-5 days.  Conclusions: The longer snakebite victims are hospitalized, the higher the cost incurred. Continuous medical education on the correct management of snakebites should be encouraged to minimize complications that may increase hospital stays and costs incurred., Competing Interests: No competing interests were disclosed., (Copyright: © 2019 Okumu MO et al.)