Cardiac manifestations and outcomes of COVID-19 vaccine-associated myocarditis in the young in the USA: longitudinal results from the Myocarditis After COVID Vaccination (MACiV) multicenter study.

Background: We aimed to study the clinical characteristics, myocardial injury, and longitudinal outcomes of COVID-19 vaccine-associated myocarditis (C-VAM). Methods: In this longitudinal retrospective observational cohort multicenter study across 38 hospitals in the United States, 333 patients with C-VAM were compared with 100 patients with multisystem inflammatory syndrome in children (MIS-C). We included patients ≤30 years of age with a clinical diagnosis of acute myocarditis after COVID-19 vaccination based on clinical presentation, abnormal biomarkers and/or cardiovascular imaging findings. Demographics, past medical history, hospital course, biochemistry results, cardiovascular imaging, and follow-up information from April 2021 to November 2022 were collected. The primary outcome was presence of myocardial injury as evidenced by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging. Findings: Patients with C-VAM were predominantly white (67%) adolescent males (91%, 15.7 ± 2.8 years). Their initial clinical course was more likely to be mild (80% vs. 23%, p < 0.001) and cardiac dysfunction was less common (17% vs. 68%, p < 0.0001), compared to MIS-C. In contrast, LGE on CMR was more prevalent in C-VAM (82% vs. 16%, p < 0.001). The probability of LGE was higher in males (OR 3.28 [95% CI: 0.99, 10.6, p = 0.052]), in older patients (>15 years, OR 2.74 [95% CI: 1.28, 5.83, p = 0.009]) and when C-VAM occurred after the first or second dose as compared to the third dose of mRNA vaccine. Mid-term clinical outcomes of C-VAM at a median follow-up of 178 days (IQR 114-285 days) were reassuring. No cardiac deaths or heart transplantations were reported until the time of submission of this report. LGE persisted in 60% of the patients at follow up. Interpretation: Myocardial injury at initial presentation and its persistence at follow up, despite a mild initial course and favorable mid-term clinical outcome, warrants continued clinical surveillance and long-term studies in affected patients with C-VAM. Funding: The U.S. Food and Drug Administration.

Antimicrobial and Computational Studies of Newly Synthesized Benzotriazoles.

Antimicrobial Resistance (AMR) due to non-responding viruses, fungi, bacteria and parasites leads to discovery of new antimicrobial medicines which can control the risk of disease spread, severe illness, disability and death. Heterocyclic chemistry has always been a continuous supplier of novel antimicrobial agents which are in great demand in pharma sector. Therefore, compounds such as 1-(Chloromethyl)-1H-Benzotriazole, 1; 1-((1-H-benzo[d][1,2,3]triazol-1-yl)methyl)phenyl hydrazine, 2; 1-((1-H-benzo[d][1,2,3]triazol-1-yl)methyl)hydrazine, 3; and N-(benzo[e][1,2,4]triazin-4(3-H)-ylmethylbenzenamine, 4 were designed, and synthesized through conventional and microwave-assisted methods. All of these novel benzotriazoles were explored through in-vitro antimicrobial studies and in silico studies. Antimicrobial activity was carried out against bacterial strains Escherichia coli, Bacillus subtilis, and fungal strains Aspergillus niger and Candida albicans at concentrations 5, 10 and 15 mg/ml. In silico studies was carried out with 4CAW: Aspergillus fumigatus N-myristoyl transferase in complex with myristoyl CoA and a pyrazole sulphonamide ligand. Our antimicrobial and molecular docking studies revealed that all of the derivatives showed promising activity, moreover molecular docking gave significant values of ligand posed energy and docking run elapsed time which further endorsed the astonishing characteristic of benzotriazole derivatives esp. N-(benzo[e]a[1,2,4] triazin-4(3-H)-ylmethylbenzenamine for biological and therapeutic leads.

Rejuvenating bone marrow hematopoietic reserve prevents regeneration failure and hepatic decompensation in animal model of cirrhosis.

Background and aim: Bone marrow stem cells (BM-SCs) and their progeny play a central role in tissue repair and regeneration. In patients with chronic liver failure, bone marrow (BM) reserve is severally compromised and they showed marked defects in the resolution of injury and infection, leading to liver failure and the onset of decompensation. Whether BM failure is the cause or consequence of liver failure during cirrhosis is not known. In this study, we aimed to determine the underlying relationship between BM failure and regeneration failure in cirrhosis. Methodology: C57Bl/6(J) mice were used to develop chronic liver injury through intra-peritoneal administration of carbon tetrachloride (CCl4) for 15 weeks (0.1-0.5 ml/kg). Animals were sacrificed to study the transition of cirrhosis and BM defects. To restore the BM-SC reserve; healthy BM cells were infused via intra-BM infusion and assessed for changes in liver injury, regeneration, and BM-SC reserve. Results: Using a CCl4-induced animal - model of cirrhosis, we showed the loss of BM-SCs reserve occurred before regeneration failure and the onset of non-acute decompensation. Intra-BM infusion of healthy BM cells induced the repopulation of native hematopoietic stem cells (HSCs) in cirrhotic BM. Restoring BM-HSCs reserve augments liver macrophage-mediated clearance of infection and inflammation dampens neutrophil-mediated inflammation, accelerates fibrosis regression, enhances hepatocyte proliferation, and delays the onset of non-acute decompensation. Conclusion: These findings suggest that loss of BM-HSCs reserve underlies the compromised innate immune function of the liver, drives regeneration failure, and the onset of non-acute decompensation. We further provide the proof-of-concept that rejuvenating BM-HSC reserve can serve as a potential therapeutic approach for preventing regeneration failure and transition to decompensated cirrhosis.

Diverse role, structural trends, and applications of fluorinated sulphonamide compounds in agrochemical and pharmaceutical fields.

Our knowledge of fluorine's unique and complex properties has significantly increased over the past 20 years. Consequently, more sophisticated and innovative techniques have emerged to incorporate this feature into the design of potential drug candidates. In recent years, researchers have become interested in synthesizing fluoro-sulphonamide compounds to discover new chemical entities with distinct and unexpected physical, chemical, and biological characteristics. The fluorinated sulphonamide molecules have shown significant biomedical importance. Their potential is not limited to biomedical applications but also includes crop protection. The discovery of novel fluorine and Sulfur compounds has highlighted their importance in the chemical sector, particularly in the agrochemical and medicinal fields. Recently, several fluorinated sulphonamide derivatives have been developed and frequently used by agriculturalists to produce food for the growing global population. These molecules have also exhibited their potential in health by inhibiting various human diseases. In today's world, it is crucial to have a steady supply of innovative pharmaceutical and agrochemical molecules that are highly effective, less harmful to the environment, and affordable. This review summarizes the available information on the activity of Fluorine and Sulphonamide compounds, which have proven active in pharmaceuticals and agrochemicals with excellent environmental and human health approaches. Moreover, it focuses on the current literature on the chemical structures, the application of fluorinated sulphonamide compounds against various pathological conditions, and their effectiveness in crop protection.

The role of comprehensive stress cardiac MRI in autoimmune rheumatic disease: A review.

Cardiovascular disease is the leading cause of morbidity and mortality in patients with autoimmune rheumatic diseases. Much of this may be attributed to systemic inflammation resulting in coronary atherosclerosis and myocarditis. Cardiac magnetic resonance imaging is the gold standard for the evaluation of cardiac structure and function, including tissue characterization, which allows for detection of myocardial edema, inflammation, and fibrosis. Advances in parametric mapping and coronary flow reserve measurement techniques have the potential to change the diagnosis, risk stratification, and management of patients with autoimmune rheumatic diseases. We provide an overview of the current evidence and suggest potential future roles for the use of comprehensive cardiac magnetic resonance in patients with autoimmune rheumatic diseases in the field of cardio-rheumatology.

Risk Factors, Incidence, and Outcomes Associated With Clinically Significant Airway Ischemia.

Airway complications following lung transplantation remain an important cause of morbidity and mortality. We aimed to identify the incidence, risk factors and outcomes associated with clinically significant airway ischemia (CSAI) in our center. We reviewed 217 lung transplants (386 airway anastomoses) performed at our institution between February 2016 and December 2020. Airway images were graded using the 2018 ISHLT grading guidelines modified slightly for retrospective analysis. Airways were considered to have CSAI if they developed ischemia severity >B2, stenosis >50%, and/or any degree of dehiscence within 6-months of transplant. Regression analyses were used to evaluate outcomes and risk factors for CSAI. Eighty-two patients (37.8%) met criteria for CSAI. Of these, twenty-six (32%) developed stenosis and/or dehiscence, and 17 (21%) required interventions. Patients with CSAI had lower one-year (80.5% vs. 91.9%, p = 0.05) and three-year (67.1% vs. 77.8%, p = 0.08) survival than patients without CSAI. Factors associated with CSAI included younger recipient age, recipient diabetes, single running suture technique, performance of the left anastomosis first, lower venous oxygen saturation within 48-h, and takeback for major bleeding. Our single-center analysis suggests that airway ischemia remains a major obstacle in contemporary lung transplantation. Improving the local healing milieu of the airway anastomosis could potentially mitigate this risk.

Investigating the potential of delignified rice husk as a carbon-rich resource for extracting glucose and its utilization in biocement production through fungal isolates.

Burning rice straw is now a significant issue faced by different regions in India, as its burning releases harmful gases, mainly carbon dioxide. Various techniques are now in trend to utilize the rice straw, e.g., producing compressed natural gas using rice straw, bioethanol, etc., as a substrate for various microorganisms. A high quantity of non-utilized rice husk generates more ideas for its proper utilization. The cellulose, hemicellulose, and lignin found in rice straws can be a fungi growth medium. In this research, the delignification of rice husk is done by acid (2% and 4% H2SO4) and alkali (2% and 4% NaOH) at 121 °C at 103 kPa for 1 h to obtain crude carbon source which is further utilized for biomineralization. The glucose is subjected to qualitative and quantitative analysis using Molisch's and Dinitro salicylic tests. The delignification process showed a positive outcome when 2% H2SO4 is utilized maximum yield of 5.9 ug/ml free sugar concentration. Representing the highest glucose yield compared to the experiment's other acid and base substances used. Various techniques such as field emission-scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), and Fourier transformed infra-red (FTIR) spectroscopy are employed to examine surface and chemical alterations. The 2% H2SO4 pretreated rice husk is utilized for microbial-induced calcite precipitation using fungal isolates S1 (3), S1 (18), and S4 (1). The calcite and vaterite produced by biomineralization are confirmed using XRD for fungal isolates namely, S1 (3), S1 (18), and S4 (1) having percentage crystallinity of 59%, 46.428%, and 62.69% percentage crystallinity respectively.

Comparative life cycle assessment of environmental impacts and economic feasibility of tomato cultivation systems in northern plains of India.

To meet the growing demand for vegetable production and promote sustainable agriculture, it is imperative to implement effective input management and adopt eco-friendly farming practices. This study aims to compare the environmental impacts of conventional and organic tomato cultivation in the northern plains of India. This study utilizes SimaPro 9.1.1 software for a comprehensive cradle-to-farm gate Life Cycle Assessment (LCA), assessing production stages, identifying key environmental factors, and incorporating ReCiPe Midpoint and Endpoint methods with one-hectare as a functional unit. Findings reveal that conventional cultivation is more affected by fertilizer application and transplanting, while organic cultivation emphasizes transplanting and irrigation. Organic cultivation contributes 904.708 kg CO2, while conventional cultivation contributes 1307.917 kg CO2 to Global Warming potential. Switching to organic cultivation leads to a significant 35.04% decrease in all impact categories. Using the endpoint method, organic cultivation achieves a notable 27.16% reduction, scoring 58.30 compared to conventional cultivation's 80.04. The LCA analysis of tomato cultivation highlights Fertilizer application as the predominant environmental concern, emphasizing the need for sustainable techniques to minimize waste and mitigate environmental impacts. This study recommends imposing restrictions on fertilizer and pesticide use and formulating effective policies to promote the adoption of sustainable practices.

Vulnerability to functional decline is associated with noncardiovascular cause of 90-day readmission in hospitalized patients with heart failure.

BACKGROUND: Hospital readmission is common among patients with heart failure. Vulnerability to decline in physical function may increase the risk of noncardiovascular readmission for these patients, but the association between vulnerability and the cause of unplanned readmission is poorly understood, inhibiting the development of effective interventions. OBJECTIVES: We examined the association of vulnerability with the cause of readmission (cardiovascular vs. noncardiovascular) among hospitalized patients with acute decompensated heart failure. DESIGNS, SETTINGS, AND PARTICIPANTS: This prospective longitudinal study is part of the Vanderbilt Inpatient Cohort Study. MAIN OUTCOME AND MEASURES: The primary outcome was the cause of unplanned readmission (cardiovascular vs. noncardiovascular). The primary independent variable was vulnerability, measured using the Vulnerable Elders Survey (VES-13). RESULTS: Among 804 hospitalized patients with acute decompensated heart failure, 315 (39.2%) experienced an unplanned readmission within 90 days of discharge. In a multinomial logistic model with no readmission as the reference category, higher vulnerability was associated with readmission for noncardiovascular causes (relative risk ratio [RRR] = 1.36, 95% confidence interval [CI]: 1.06-1.75) in the first 90 days after discharge. The VES-13 score was not associated with readmission for cardiovascular causes (RRR = 0.94, 95% CI: 0.75-1.17). CONCLUSIONS: Vulnerability to functional decline predicted noncardiovascular readmission risk among hospitalized patients with heart failure. The VES-13 is a brief, validated, and freely available tool that should be considered in planning care transitions. Additional work is needed to examine the efficacy of interventions to monitor and mitigate noncardiovascular concerns among vulnerable patients with heart failure being discharged from the hospital.

Hyaluronic Acid-Conjugated Thermoresponsive Polymer-Based Bioformulation Enhanced Wound Healing and Gut Barrier Repair of a TNBS-Induced Colitis Injury Ex Vivo Model in a Dynamic Perfusion Device.

Impairment of intestinal epithelium is a typical feature of inflammatory bowel disease (IBD) that causes leakage of bacteria and antigens from the intestinal lumen and thus results in persistent immune activation. Hence, healing and regeneration of the damaged gut mucosa is a promising therapeutic approach to achieve deep remission in IBD. Currently, available systemic therapies have moderate effects and are often associated with numerous side effects and malignancies. In this study, we aimed to develop a topical therapy by chemically conjugating a temperature-responsive polymer, i.e., poly(N-isopropylacrylamide), along with hyaluronic acid to obtain a sprayable therapeutic formulation that upon colon instillation adheres to the damaged gut mucosa due to its temperature-induced phase transition and mucoadhesive properties. An ex vivo adhesion experiment demonstrates that this therapeutic formulation forms a thin physical coating on the mucosal lining at a physiological temperature within 5 min. Physicochemical characterization of (P(NIPAM-co-NTBAM)-HA) established this formulation to be biocompatible, hemo-compatible, and non-immunogenic. Prednisolone was encapsulated within the polymer formulation to achieve maximum therapeutic efficacy in the case of IBD-like conditions as assessed in a custom-fabricated perfusion-based ex vivo model system. Histological analysis suggests that the prednisolone-encapsulated polymer formulation nearly restored the mucosal architecture after 2,4,6-trinitrobenzenesulfonic acid-induced damage. Furthermore, a significant (p ≤ 0.001) increase in mRNA levels of Muc-2 and ZO-1 in treated groups further confirmed the mucosal epithelial barrier restoration.

Unknown presentation of a rare genetic disorder: Monogenic diabetes in young type 4 presenting with hepatic cysts and procoagulant state.

Maturity onset diabetes in young (MODY) is the most common form of monogenic diabetes, which characteristically presents in adolescents and young adults. Till date, pathogenic variations involving 14 different genes have been causally implicated with the development of MODY. Maturity onset diabetes in young type 4 (MODY-4) is a very rare form of MODY. We present here case of 28-year-old nonobese male patient with distinct family history of diabetes spanning two generations, incidentally, detected to have a rare form of diabetes on genetic analysis when he presented with recurrent thromboembolic manifestations: deep vein thrombosis and pulmonary thromboembolism. Our case highlights a previously unknown disease association of a rare genetic disorder. Increasing awareness about this genetic disorder and early identification of such cases will enhance our understanding of hitherto unknown disease associations and the pathophysiological role of genetic mutations. This may contribute to the improved treatment and prevention of debilitating diseases such as diabetes.

Pyrethroids toxicity in vertebrates and invertebrates and amelioration by bioactive compounds: A review.

Generations of different synthetic pesticides have been launched over time to maintain balance between production and consumption of the agricultural yield, control various disease programmes, store grains, etc. Pyrethroids, which are supposed to be non-toxic, have been excessively implemented and have contaminated soil and water bodies. Thus, pyrethroids cause severe and dreadful pernicious effects on various life forms residing in soil, air, and water. Various obnoxious effects of pyrethroids have been analyzed in the vertebrate and invertebrate systems of the animal kingdom. Pyrethroids, namely, Cypermethrin, Deltamethrin, Beta-cyfluthrin, Esfenvalerate, Fenvalerate, and Bifenthrin, have set out various types of degenerative and toxic impacts that include oxidative stress, hepatotoxicity, immunotoxicity involving thymic and splenic toxicity, neurotoxicity, nephrotoxicity, foetal toxicity, alterations in serum calcium and phosphate levels, cerebral and bone marrow degeneration, degeneration of the reproductive system, histological alteration, and DNA damage. Bioactive compounds like Diosmin, Curcumin, Rutin, Spirulina platensis, sesame oil, Naringin, Allicin, Piperine, alpha-lipoic acid, alpha-tocopherol, Cyperus rotundus L. tuber extract, herbal syrup from chicory and artichoke leaves, green tea extract, Quercetin, Trans-ferulic acid, Ascorbic acid, Propolis, ethanolic extract of grape pomace, and Melatonin have been reported to sublime the toxic effects of these pesticides. The expanding harmfulness of pesticides is a real and demanding issue that needs to be overcome, and bioactive compounds have been shown to reduce the toxicity in vivo as well as in vitro.

In silico analysis of Diosmetin as an effective chemopreventive agent against prostate cancer: molecular docking, validation, dynamic simulation and pharmacokinetic prediction-based studies.

Prostate cancer is the second most dangerous cancer type worldwide. While various treatment options are present i.e. agonists and antagonists, their utilization leads to adverse effects and due to this resistance developing, ultimately the outcome is remission. So, to overcome this issue, we have undertaken an in-silico investigation to identify promising and unique flavonoid candidates for combating prostate cancer. Using GOLD software, the study assessed the effectiveness of 560 natural secondary polyphenols against CDKN2. Protein Data Bank was used to retrieve the 3D crystal structure of CDKN2 (PDB Id: 4EK3) and we retrieved the structure of selected secondary polyphenols from the PubChem database. The compound Diosmetin shows the highest GOLD score with the selected Protein i.e. CDKN2 which is 58.72. To better understand the 2-dimensional and 3-dimensional interactions, the interacting amino acid residues were visualised using Discovery Studio 3.5 and Maestro 13.5. Using Schrodinger-Glide, the Diosmetin and CDKN2 were re-docked, and decoy ligands were docked to CDKN2, which was used to further ascertain the study. The ligands with the highest Gold score were forecasted for pharmacokinetics characteristics, and the results were tabulated and analysed. Utilising the Gromacs software and Desmond packages, 100 ns of Diosmetin molecular dynamics simulations were run to evaluate the structural persistence and variations of protein-ligand complexes. Additionally, our investigation revealed that Diosmetin had a better binding affinity with CDKN2 measuring 58.72, and it also showed remarkable stability across a 100-ns simulation. Thus, following in-vitro and in-vivo clinical studies, diosmetin might lead to the Prostate regimen.Communicated by Ramaswamy H. Sarma.

Non-resolution of acute kidney injury in the first week portends the development of chronic kidney disease in critically ill patients with cirrhosis.

BACKGROUND: Renal tubular epithelial cells (RTECs) cause maladaptive repair and perpetuate renal fibrosis. AIM: To evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL) and RTEC as risk factors for non-resolution of acute kidney injury (AKI-NR) at day seven and chronic kidney disease (CKD) in critically ill patients with cirrhosis. METHODS: We performed urinary NGAL and microscopy at enrolment and day 7 in all patients. We assessed 17 renal injury, endothelial injury and repair markers, genes for mitochondrial biogenesis by qRT-PCR in RTEC, and post-mortem renal biopsies for understanding mechanisms of AKI non-resolution (n = 30). RESULTS: We enrolled 310 patients, aged 48.1 ± 11.6 years, 87% male, 90% alcoholic. Of these, 36% had RTEC at enrolment, and 53% had AKI-NR on day 7. On mean follow-up of 136 days (range 43-365), 150 (48.3%) developed CKD. The presence of RTEC or granular casts, NGAL and AKI-NR were independent predictors of CKD development on competing risk analysis. Higher MCP-1, renal endothelial injury, decrease in tubular repair markers and failure of mitochondrial biogenesis in RTEC were seen in patients with AKI-NR compared with AKI-R (p < 0.05). Renal biopsies showed infiltration with monocyte-macrophage, increased α-SMA, and tubulointerstitial fibrosis. CONCLUSION: Almost two-thirds of critically ill patients with cirrhosis have AKI, which resolves in only one-half at day seven and predicts the development of CKD. Higher NGAL, RTEC, or granular casts were independent predictors of AKI-NR and CKD development. Enhanced tubular and endothelial injury, decreased repair, monocyte-macrophage infiltration and mitochondrial dysfunction in RTEC are associated with AKI non-resolution and risk of renal fibrosis.

Synthesis and characterization of peanut hull modified chitosan beads.

The incorporation of plant materials is an effective method to improve the stability of chitosan beads, as it further increases the adsorption of toxic dyes and metals from aqueous systems. In the present study, chitosan gels were impregnated with a novel type of powder as the groundnut hull powder in order to form composite beads by using a simple droplet-based microfluidic system. The beads were then characterised through various techniques such as SEM, TGA, FTIR, and XRD. Microscopic imaging revealed a change in the surface morphology of the composite beads, which became rough and wrinkled with more valley-like features and irregular cracks. FTIR data suggest that the impregnation of groundnut hull powder led to an increase in functional groups. The thermal analysis allowed for the assessment of composite bead hydration contents and indicated the presence of groundnut hull entrapped in the loaded beads, which was corroborated by vibrational spectroscopy. XRD analysis allows us to conclude that there is an involvement of groundnut hull in the chitosan gels, and the consequence of that is the formation of amorphous beads, which would make them suitable for the adsorption of toxic dyes and metals from water systems.

Acute exacerbation of interstitial lung disease in the intensive care unit: Principles of diagnostic evaluation and management.

Interstitial lung disease (ILD) is typically managed on an outpatient basis. Critical care physicians manage patients with ILD in the setting of an acute exacerbation (ILD flare) causing severe hypoxia. The principles of management of acute exacerbation of ILD are different from those used to manage patients with acute respiratory distress syndrome from sepsis, etc. Selected patients may be candidates for aggressive measures like extracorporeal membrane oxygenation and lung transplantation, while almost all patients will benefit from early palliative care. This review focused on the types of ILD, diagnosis, and management pathways for this challenging condition.

Safety and utility of indwelling pleural catheters in lung transplant recipients.

INTRODUCTION: The safety and efficacy of indwelling pleural catheters (IPCs) in lung allograft recipients is under-reported. METHODS: We performed a multicenter, retrospective analysis between 1/1/2010 and 6/1/2022 of consecutive IPCs placed in lung transplant recipients. Outcomes included incidence of infectious and non-infectious complications and rate of auto-pleurodesis. RESULTS: Seventy-one IPCs placed in 61 lung transplant patients at eight centers were included. The most common indication for IPC placement was recurrent post-operative effusion. IPCs were placed at a median of 59 days (IQR 40-203) post-transplant and remained for 43 days (IQR 25-88). There was a total of eight (11%) complications. Infection occurred in five patients (7%); four had empyema and one had a catheter tract infection. IPCs did not cause death or critical illness in our cohort. Auto-pleurodesis leading to the removal of the IPC occurred in 63 (89%) instances. None of the patients in this cohort required subsequent surgical decortication. CONCLUSIONS: The use of IPCs in lung transplant patients was associated with an infectious complication rate comparable to other populations previously studied. A high rate of auto-pleurodesis was observed. This work suggests that IPCs may be considered for the management of recurrent pleural effusions in lung allograft recipients.

A randomised-controlled trial (TARGET-C) of high vs. low target mean arterial pressure in patients with cirrhosis and septic shock.

BACKGROUND & AIMS: A high mean arterial pressure (MAP) target has been associated with improved renal outcomes in patients with cirrhosis, though it has not been studied in critically ill patients with cirrhosis and septic shock (CICs). We compared the efficacy of a high (80-85 mmHg; H-MAP) vs. low (60-65; L-MAP) target MAP strategy in improving 28-day mortality in CICs. METHODS: We performed open-label 1:1 randomisation of 150 CICs (H-MAP 75; L-MAP 75). The primary endpoint was 28-day mortality and secondary endpoints included reversal of shock, acute kidney injury (AKI) at day 5, the incidence of intradialytic hypotension (IDH), and adverse events. Endothelial markers were analysed in a subset of patients. RESULTS: The baseline characteristics were comparable. On intention-to-treat analysis, 28-day mortality (65% vs. 56%; p = 0.54), reversal of shock (47% vs. 53%; p = 0.41) and AKI development (45% vs. 31%;p = 0.06) were not different between the H-MAP and L-MAP groups, respectively. A lower incidence of IDH (12% vs. 48%; p <0.001) and higher adverse events necessitating protocol discontinuation (24% vs. 11%; p = 0.031) were noted in the H-MAP group. On per-protocol analysis (L-MAP 67; H-MAP 57), a significantly higher reversal of AKI (53% vs. 31%; p = 0.02) and a lower incidence of IDH (4% vs. 53%; p <0.001) were observed in the H-MAP group. Endothelial repair markers such as ADAMTS (2.11 ± 1.13 vs. 1.15 ± 0.48; p = 0.002) and angiopoietin-2 (74.08 ± 53.00 vs. 41.80 ± 15.95; p = 0.016) were higher in the H-MAP group. CONCLUSIONS: A higher MAP strategy does not confer a survival benefit in CICs, but improves tolerance to dialysis, lactate clearance and renal recovery. Higher adverse events indicate the need for better tools to evaluate target microcirculation pressures in CICs. IMPACT AND IMPLICATIONS: Maintaining an appropriate organ perfusion pressure during sepsis is the ultimate goal of haemodynamic management. A higher mean arterial pressure (MAP) improves renal outcomes in patients with hepatorenal syndrome. Patients with cirrhosis and septic shock have severe circulatory disturbances, low MAP, and poor tissue perfusion. In these patients, targeting higher MAP vs. lower MAP does not confer any survival benefit but is associated with more adverse events. A higher target strategy was associated with better tolerance and lesser episodes of hypotension on dialysis. Patients who could achieve the higher target MAP, without the development of adverse events, had improved renal outcomes and better lactate clearance. Higher MAP was also associated with improvements in markers of endothelial function. A higher target MAP strategy, with close monitoring of adverse events, may be recommended for patients with cirrhosis and septic shock. CLINICAL TRIAL NUMBER: NCT03145168.

Microbial Biosurfactant as an Alternate to Chemical Surfactants for Application in Cosmetics Industries in Personal and Skin Care Products: A Critical Review.

Cosmetics and personal care items are used worldwide and administered straight to the skin. The hazardous nature of the chemical surfactant utilized in the production of cosmetics has caused alarm on a global scale. Therefore, bacterial biosurfactants (BS) are becoming increasingly popular in industrial product production as a biocompatible, low-toxic alternative surfactant. Chemical surfactants can induce allergic responses and skin irritations; thus, they should be replaced with less harmful substances for skin health. The cosmetic industry seeks novel biological alternatives to replace chemical compounds and improve product qualities. Most of these chemicals have a biological origin and can be obtained from plant, bacterial, fungal, and algal sources. Various biological molecules have intriguing capabilities, such as biosurfactants, vitamins, antioxidants, pigments, enzymes, and peptides. These are safe, biodegradable, and environmentally friendly than chemical options. Plant-based biosurfactants, such as saponins, offer numerous advantages over synthetic surfactants, i.e., biodegradable, nontoxic, and environmentally friendly nature. Saponins are a promising source of natural biosurfactants for various industrial and academic applications. However, microbial glycolipids and lipopeptides have been used in biotechnology and cosmetics due to their multifunctional character, including detergency, emulsifying, foaming, and skin moisturizing capabilities. In addition, some of them have the potential to be used as antibacterial agents. In this review, we like to enlighten the application of microbial biosurfactants for replacing chemical surfactants in existing cosmetic and personal skincare pharmaceutical formulations due to their antibacterial, skin surface moisturizing, and low toxicity characteristics.

Insights into ovarian cancer: chemo-diversity, dose depended toxicities and survival responses.

Ovarian cancer has been one of the serious concerns for female health and medicinal practitioner all over the world. The wellness of over cancer patient is associated with survival responses which depends on many factors including chemotherapeutic diversity; treatment protocol; dose-dependent toxicity such as hematological toxicity and non-hematological toxicity. We found that the studied treatment regimens (TRs) (1-9) showed varying degree of hematological toxicities like moderate neutropenia (< 20%) critical neutropenia (> 20%), negligible leucopenia, critical leucopenia (> 20%), moderate thrombocytopenia (< 20%), critical thrombocytopenia (> 20%), moderate anemia (< 20%) and critical anemia (> 20%). The studied TRs showed varying degree of non-hematological toxicities like moderate nausea-vomiting (< 20%), critical nausea-vomiting (> 20%), moderate alopecia (< 20%), critical alopecia (> 20%), moderate fatigue (< 20%), critical fatigue (> 20%), moderate neurotoxicity (< 20%), critical neurotoxicity (> 20%), moderate diarrheas (< 20%). The studied TRs showed varying degree of survival responses like critical partial response (> 35%), remarkable overall responses (> 60%), critical overall responses (< 60%), remarkable stable disease (> 20%), critical stable disease (< 20%) and moderate progressive disease (< 20%). Out of the studied TRs 1-9, in case of TR 6, moderate non-hematological toxicity (NHT) and effective survival response (SR) is being diluted by critical hematological toxicity (HT). On the other hand, TR 8, 9 is showing critical HT, NHT and SR. Our analysis revealed that the toxicity of the existing therapeutic agents can be controlled through judicious decision of drug administration cycles and combination therapies.