Prevalence and association between alcohol, tobacco, and COVID-19: a study from a tribal predominant district in eastern India.

Introduction: Alcohol and tobacco use has been proposed to significantly affect COVID-19 outcomes. The study aimed to estimate the prevalence of alcohol and tobacco use among COVID-19-positive patients and compare it with the general population prevalence rates. It also aimed to assess and determine the association between the severity of COVID-19 illness and the complications with alcohol and tobacco use. Method: For this, a cross-sectional, retrospective, telephone-based study was conducted using a structured questionnaire among COVID-19 diagnosed patients in the district of Deoghar of the Indian state of Jharkhand. A multinomial logistic regression is done to determine the association. Results: Among 1,425 patients interviewed, tobacco and alcohol were used by 22.31 and 9.96%, significantly more than the prevalence of tobacco (Z = 4.9485, p < 0.00001) and alcohol use (Z = 7.118, p < 0.00001), respectively, in the district (tobacco-11.7% and alcohol-4.8%).In a regression model, patients with co-morbidity had higher odds of severe [3.34 (1.99-5.62)] and moderate [2.95 (1.97-4.41)] COVID-19. Young [0.12 (0.04-0.38)] and middle-aged individuals [0.23 (0.13-0.4)], people below the poverty line 0.28 (0.11-0.69) are at lower odds of severe COVID-19. Tobacco users [1.58 (1.16-2.14)], alcohol users [1.53 (1.03-2.28)], incomplete vaccination [3.24 (1.49-7.01)], and patients with comorbidity [3.6 (2.79-4.68)] were found to have higher odds of post-COVID-19 complications. Discussion: People with COVID-19 in our study population had significantly higher tobacco and alcohol use compared to the general population. Tobacco and alcohol use significantly increases the risk of post-COVID-19 complications. The study highlights the need for addiction treatment services to prevent complications during future pandemics.

Tailoring Indocyanine Green J-Aggregates for Imaging, Cancer Phototherapy, and Drug Delivery: A Review.

Indocyanine green J-aggregates (ICG-Jagg) have emerged as a significant subject of interest in biomedical applications due to their unique optical properties, tunable size, and excellent biocompatibility. This comprehensive review aims to provide an in-depth exploration of ICG-Jagg, with a focus on elucidating the diverse facets of their preparation and the factors that influence the preparation process. Additionally, the review discusses their applications in biomedical diagnostics, such as imaging and contrast agents, as well as their utilization in drug delivery and various phototherapeutic interventions.

Epidemiology and Clinical Features of Burkholderia Bacteremia at a Hospital in India.

Burkholderia spp. are opportunistic pathogens that cause infection in patients with disrupted immunity. The study intended to demonstrate the epidemiology and clinical features associated with Burkholderia spp. bacteremia. This retrospective study was performed to assess the clinical and laboratory characteristics of patients whose blood cultures were growing Burkholderia spp. and, based on their underlying comorbidities, were subjected to survival analysis from January 2022 to December 2022 at a university hospital in northern India. Three hundred patients with Burkholderia spp. bacteremia were included in this study conducted over 1 year. The mean age of the patients was 33.86 years with a male predominance of 56.67% (170/300, 56.67%). Underlying malignancies (207/300, 69.0%) were the most common clinical diagnosis, and catheter in situ (300/300, 100.0%) was the most common risk factor. Burkholderia cenocepacia (244/300, 81.33%) was the most common Burkholderia spp. isolated. All isolates were highly susceptible to minocycline. Kidney disease (P = 0.029), hypertension (P = 0.005), type 2 diabetes mellitus (P = 0.039), and respiratory disease (P <0.001) in patients were significantly associated with death owing to Burkholderia spp. bacteremia, whereas patients with malignancies (P <0.001) and undergoing treatment were significantly associated with a better outcome when the microorganism was susceptible to empirical antibiotics. The presence of indwelling devices, mechanical ventilation (P <0.001), and a hemodialysis catheter (P = 0.026) were statistically significant risk factors associated with poor outcomes.

Cetuximab decorated redox sensitive D-alpha-tocopheryl- polyethyleneglycol-1000-succinate based nanoparticles for cabazitaxel delivery: Formulation, lung targeting and enhanced anti-cancer effects.

This research work aims to fabricate cetuximab (CTX) decorated cabazitaxel (CBZ) loaded redox-sensitive D-alpha-tocopheryl-polyethyleneglycol-1000-succinate (TPGS-SS) nanoparticles (NPs) for epidermal growth factor receptor (EGFR)-targeted lung tumor therapy.The NPs were prepared using a dialysis bag diffusion method to produce, non-redox sensitive non targeted (TPGS-CBZ-NPs), redox-sensitive nontargeted (TPGS-SS-CBZ-NPs), and targeted redox-sensitive NPs (CTX-TPGS-SS-CBZ-NPs). Developed NPs were characterized for particle sizes, polydispersity, surface charge, surface morphologies, and entrapment efficiency. Moreover, additional in vitro studies have been conducted, including in vitro drug release, cytotoxicity, and cellular uptake studies.The particle size and charge over the surface were found to be in the range of 145.6 to 308.06 nm and -15 to -23 mV respectively. The IC50 values of CBZ clinical injection (Jevtana®), TPGS-CBZ-NPs, TPGS-SS-CBZ-NPs, and CTX-TPGS-SS-NPs were found to be 17.54 ± 3.58, 12.8 ± 2.45, 9.28 ± 1.13 and 4.013 ± 1.05 µg/ml, suggesting the 1.37, 1.89 and 4.37-folds respectively, enhancement of cytotoxicity as compared to CBZ clinical injection, demonstrating a significant augmentation in cytotoxicity. In addition, the in-vitro cellular uptake investigation showed that CTX-TPGS-SS-CMN6-NPs accumulated significantly compared to pure CMN6, TPGS-CMN6-NPs, and TPGS-SS-CMN6-NPs in the A549 cells. Furthermore, the targeting efficiency of developed NPs were analysed by ultrasound/photoacoustic and IVIS imaging.

EGFR Targeted Redox Sensitive Chitosan Nanoparticles of Cabazitaxel: Dual-Targeted Cancer Therapy, Lung Distribution, and Targeting Studies by Photoacoustic and Optical Imaging.

In this research, we have modified tocopheryl polyethylene glycol succinate (TPGS) to a redox-sensitive material, denoted as TPGS-SH, and employed the same to develop dual-receptor-targeted nanoparticles of chitosan loaded with cabazitaxel (CZT). The physicochemical properties and morphological characteristics of all nanoparticle formulations were assessed. Dual-receptor targeting redox-sensitive nanoparticles of CZT (F-CTX-CZT-CS-SH-NPs) were developed by a combination of pre- and postconjugation techniques by incorporating synthesized chitosan-folate (F) and TPGS-SH during nanoparticle synthesis and further postconjugated with cetuximab (CTX) for epidermal growth factor receptor (EGFR) targeting. The in vitro release of the drug was seemingly higher in the redox-sensitive buffer media (GSH, 20 mM) compared to that in physiological buffer. However, the extent of cellular uptake of dual-targeted nanoparticles was significantly higher in A549 cells than other control nanoparticles. The IC50 values of F-CTX-CZT-CS-SH-NPs against A549 cells was 0.26 ± 0.12 µg/mL, indicating a 6.3-fold and 60-fold enhancement in cytotoxicity relative to that of dual-receptor targeted, nonredox sensitive nanoparticles and CZT clinical injection, respectively. Furthermore, F-CTX-CZT-CS-SH-NPs demonstrated improved anticancer activity in the benzo(a)pyrene lung cancer model with a higher survival rate. Due to the synergistic combination of enhanced permeability and retention (EPR) effect of small-sized nanoparticles, the innovative and redox sensitive TPGS-SH moiety and the dual folate and EGFR mediated augmented endocytosis have all together significantly enhanced their biodistribution and targeting exclusively to the lung which is evident from their ultrasound/photoacoustic and in vivo imaging system (IVIS) studies.

EGFR targeted albumin nanoparticles of oleanolic acid: In silico screening of nanocarrier, cytotoxicity and pharmacokinetics for lung cancer therapy.

This study aimed to develop cetuximab (CTX) functionalized albumin nanoparticles (ALB-NPs) of oleanolic acid for EGFR targeted lung cancer therapy. The molecular docking methodology has been applied for a selection of suitable nanocarrier. Various physicochemical parameters like particle size, polydispersity, zeta potential, morphology, entrapment efficiency, and in-vitro drug release of all the ALB-NPs were analyzed. Furthermore, the in-vitro qualitative and quantitative cellular uptake study revealed that higher uptake of CTX conjugated ALB-NPs than nontargeted ALB-NPs in A549 cells. The in-vitro MTT assay revealed that the IC50 value of CTX-OLA-ALB-NPs (4.34 ± 1.90 µg/mL) was significantly reduced (p < 0.001) than OLA-ALB-NPs (13.87 ± 1.28 µg/mL) in A-549 cells. CTX-OLA-ALB-NPs caused apoptosis in A-549 cells at concentrations equivalent to its IC50 value and blocked the cell cycle in the G0/G1 phases. The hemocompatibility, histopathology and lung safety study confirmed the biocompatibility of the developed NPs. In vivo ultrasound and photoacoustic imaging confirmed the targeted delivery of the NPs to lung cancer. The findings demonstrated that CTX-OLA-ALB-NPs have potential for site-specific delivery of OLA for effective and targeted therapy of lung carcinoma.

Recent Updates on Oncogenic Signaling of Aurora Kinases in Chemosensitive, Chemoresistant Cancers: Novel Medicinal Chemistry Approaches for Targeting Aurora Kinases.

The Aurora Kinase family (AKI) is composed of serine-threonine protein kinases involved in the modulation of the cell cycle and mitosis. These kinases are required for regulating the adherence of hereditary-related data. Members of this family can be categorized into aurora kinase A (Ark-A), aurora kinase B (Ark-B), and aurora kinase C (Ark-C), consisting of highly conserved threonine protein kinases. These kinases can modulate cell processes such as spindle assembly, checkpoint pathway, and cytokinesis during cell division. The main aim of this review is to explore recent updates on the oncogenic signaling of aurora kinases in chemosensitive/chemoresistant cancers and to explore the various medicinal chemistry approaches to target these kinases. We searched Pubmed, Scopus, NLM, Pubchem, and Relemed to obtain information pertinent to the updated signaling role of aurora kinases and medicinal chemistry approaches and discussed the recently updated roles of each aurora kinases and their downstream signaling cascades in the progression of several chemosensitive/chemoresistant cancers; subsequently, we discussed the natural products (scoulerine, Corynoline, Hesperidin Jadomycin-B, fisetin), and synthetic, medicinal chemistry molecules as aurora kinase inhibitors (AKIs). Several natural products' efficacy was explained as AKIs in chemosensitization and chemoresistant cancers. For instance, novel triazole molecules have been used against gastric cancer, whereas cyanopyridines are used against colorectal cancer and trifluoroacetate derivatives could be used for esophageal cancer. Furthermore, quinolone hydrazine derivatives can be used to target breast cancer and cervical cancer. In contrast, the indole derivatives can be preferred to target oral cancer whereas thiosemicarbazone-indole could be used against prostate cancer, as reported in an earlier investigation against cancerous cells. Moreover, these chemical derivatives can be examined as AKIs through preclinical studies. In addition, the synthesis of novel AKIs through these medicinal chemistry substrates in the laboratory using in silico and synthetic routes could be beneficial to develop prospective novel AKIs to target chemoresistant cancers. This study is beneficial to oncologists, chemists, and medicinal chemists to explore novel chemical moiety synthesis to target specifically the peptide sequences of aurora kinases in several chemoresistant cancer cell types.

A Prospective Study Comparing Stapler and Open Surgical Technique of Hemorrhoidectomy.

Introduction Hemorrhoids are basically anal cushions which turn out to be pathological giving rise to bleeding, pain and protrusion outside the anal canal. The chief complaint of patients with hemorrhoids is bleeding from the rectum which is usually painless and associated with episodes of defecation. The study was done to assess postoperative pain, time duration of the procedure, complications in the postoperative period, return to normal work, and recurrence between the stapler and open hemorrhoidectomy for grade III and IV hemorrhoids. Material and methods The present prospective study was conducted among 60 patients in the General Surgery department at Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar over the duration of two years presenting with grade III and IV degree hemorrhoids. Thirty patients each were divided into open hemorrhoidectomy and stapled hemorrhoidectomy groups. The study evaluated variables like operative time, stay at the hospital and postoperative complications and compared them between the two techniques. Follow-up of patients was done at regular intervals. Evaluation of postoperative pain was done using visual analogue scale (VAS) with ranges from 0 to 10. We evaluated the data using the chi-square test with a p-value <0.05 as significant. Results Of 60 patients, 47 (78.3%) were males and 13 (21.7%) were females with a male: female ratio being 3.6:1. The operating time and hospital stay were much less in the stapler hemorrhoidectomy group as compared to the open procedure group. Also, postoperative pain (visual analogue scale) was less in the stapler hemorrhoidectomy group with 36.7% of patients presenting with pain at one week, 23.3% at one month and 3.3% at three months in the open hemorrhoidectomy group whereas 13.3% presenting as pain in one week, 10% presenting at one month and none presenting at three months in the stapler hemorrhoidectomy group. There was recurrence seen in 10% of cases at three months in the open hemorrhoidectomy group as compared to the stapler hemorrhoidectomy group where no recurrence was found at three months follow-up. Conclusion Hemorrhoid offers a variety of surgical modalities of treatment. We have come to the conclusion that stapled hemorrhoidectomy has less complications and good patient compliance. It can be an effective option in the treatment of third and fourth-grade hemorrhoids. With proper training and expertise, stapler hemorrhoidectomy is a better and reliable technique for hemorrhoid surgery.

Assessment of various forms of cellulose-based Luffa cylindrica (mat, flakes and powder) reinforced polydimethylsiloxane composites for oil sorption and organic solvents absorption.

Oil spillage has damaged public health noticeably and contributed to significant environmental deterioration. As a result, a significant amount of effort has been spent on investigating and developing the sorbent materials capable of separating oil from water. Thus, the sorbent materials that could be effective particularly in oil spill disposal and resolve such environmental issue remain to be explored. We have proposed luffa cylindrica (LC)-polydimethylsiloxane (PDMS) composite forms to remove the oil and organic components that might be hazardous to aquatic organisms. The scaffolds were fabricated using hand lay-up method with various forms of luffa cylindrica i.e., LC mat, flakes and powder. Various characterizations such as scanning electron microscopy (SEM), atomic force microscopy (AFM), thermogravimetric analysis (TGA), effective porosity, surface wettability, mechanical stability, cytotoxicity and sorption behavior with respect to oil, phosphate buffer saline (PBS) and few organic solvents were performed. The results showed that the scaffold in combination with P-L flakes was highly effective in eradicating oil spills and removing harmful components of crude oil. Scaffolds composed of P-L mat, P-L flakes, P-L powder, and PDMS (P) exhibited oil absorption efficacy around 16.09 ± 4.62 %, 24.49 ± 3.55 %, 15.52 ± 2.67 % and 5.52 ± 1.44 %, respectively. We anticipate that the proposed scaffolds have the tremendous potential to provide a solution to this significant environmental remediation issue and to serve as a cost-effective method for removing oil spills and hazardous crude oil components.

Regenerative Potential of Human Breast Milk: A Natural Reservoir of Nutrients, Bioactive Components and Stem cells.

Human milk is a complex fluid that contains carbohydrates, lipids, proteins, and other bioactive molecules (immunoglobulins, lactoferrin, human milk oligosaccharides, lysozyme, leukocytes, cytokines, hormones, and microbiome) which provide nutritional, immunological, and developmental benefits to the infant. In addition to their involvement in the development, these bioactive compounds have a key role in anti-oncogenicity, neuro-cognitive development, cellular communication, and differentiation. As a result of technological advancements, it has been discovered that human breast milk contains cells that display many of the characteristics of stem cells with multilineage differentiation potentials. Do these cells have any specific properties or roles? Research efforts on breast milk cells have been mainly focused on leukocytes based on their immunological perspective in the early postpartum period. This review summarizes the nutritional components in human milk, i.e., the macro and micronutrients required for the growth and development of infants. Further, it discusses the research work reported concerning the purification, propagation, and differentiation of breast milk progenitor cells and highlights the advancements made in this newly emerging field of stem cell biology and regenerative medicine.

Chitosan-alginate nanoparticles of cabazitaxel: Design, dual-receptor targeting and efficacy in lung cancer model.

Cabazitaxel (CZT) loaded chitosan-alginate based (CSA) nanoparticles were developed with dual targeting functions of both folate receptor and epidermal growth factor receptor (EGFR) using ionic gelation technique. The chitosan-folate conjugate was synthesized, and characterized by using FTIR, NMR and Mass spectroscopy. The physicochemical parameters and morphology of all CSA nanoparticles were examined. The degree of conjugation of folic acid and cetuximab (CTXmab) was determined by UV-Visible spectroscopy and Bradford assay, respectively. Moreover, XPS analysis also supported the presence of the ligands on nanoparticles. The cellular-uptake study performed on A-549 cells demonstrated a significant enhancement in the uptake of dual-receptor targeted CSA nanoparticles than non-targeted and single-receptor targeted CSA nanoparticles. Further, CZT-loaded dual receptors targeted CSA nanoparticles also showed significantly lower IC50 values (~38 folds) than the CZT control against A-549 cells. Further, in-vivo histopathological evaluations of dual receptor-targeted CSA nanoparticles have demonstrated better safety in Wistar rats. Moreover, its treatment on the Benzo(a)pyrene (B(a)P) induced lung cancer mice model has showed the enhanced anticancer efficacy of CZT with a prolonged survival rate.

The silencing of ets-4 mRNA relies on the functional cooperation between REGE-1/Regnase-1 and RLE-1/Roquin-1.

Regnase-1 is an evolutionarily conserved endoribonuclease. It degrades diverse mRNAs important for many biological processes including immune homeostasis, development and cancer. There are two competing models of Regnase-1-mediated mRNA silencing. One model postulates that Regnase-1 works together with another RNA-binding protein, Roquin-1, which recruits Regnase-1 to specific mRNAs. The other model proposes that the two proteins function separately. Studying REGE-1, the Caenorhabditis elegans ortholog of Regnase-1, we have uncovered its functional relationship with RLE-1, the nematode counterpart of Roquin-1. While both proteins are essential for mRNA silencing, REGE-1 and RLE-1 appear to associate with target mRNA independently of each other. Thus, although the functional interdependence between REGE-1/Regnase-1 and RLE-1/Roquin-1 is conserved, the underlying mechanisms may display species-specific variation, providing a rare perspective on the evolution of this important post-transcriptional regulatory mechanism.

Temporal analysis of melanogenesis identifies fatty acid metabolism as key skin pigment regulator.

Therapeutic methods to modulate skin pigmentation has important implications for skin cancer prevention and for treating cutaneous hyperpigmentary conditions. Towards defining new potential targets, we followed temporal dynamics of melanogenesis using a cell-autonomous pigmentation model. Our study elucidates 3 dominant phases of synchronized metabolic and transcriptional reprogramming. The melanogenic trigger is associated with high MITF levels along with rapid uptake of glucose. The transition to pigmented state is accompanied by increased glucose channelisation to anabolic pathways that support melanosome biogenesis. SREBF1-mediated up-regulation of fatty acid synthesis results in a transient accumulation of lipid droplets and enhancement of fatty acids oxidation through mitochondrial respiration. While this heightened bioenergetic activity is important to sustain melanogenesis, it impairs mitochondria lately, shifting the metabolism towards glycolysis. This recovery phase is accompanied by activation of the NRF2 detoxication pathway. Finally, we show that inhibitors of lipid metabolism can resolve hyperpigmentary conditions in a guinea pig UV-tanning model. Our study reveals rewiring of the metabolic circuit during melanogenesis, and fatty acid metabolism as a potential therapeutic target in a variety of cutaneous diseases manifesting hyperpigmentary phenotype.

In silico analysis of kiss2, expression studies and protein-protein interaction with gonadotropin-releasing hormone 2 (GnRH2) and luteinizing hormone beta (LHß) in Heteropneustes fossilis.

Kisspeptins, encoded by the kiss genes, are neuropeptides that regulate the onset of puberty, maturation of gonads, and fertility in higher vertebrates including fishes. The gene ontology suggests that kisspeptin plays an important role not only in reproduction but also in cell signaling, immune response and metabolic processes, and to decipher protein-protein interactions, computational approach has been favored. The present investigation focuses on the detailed structural analysis and molecular docking of kiss2 gene using in silico tools. A putative kiss2 protein of 113 amino acids was encoded by an open reading frame of 342 bp kiss2 gene. The protein is of 13.12 kDa with isoelectric point of 9.45. The secondary structure of the protein indicates more than 50% random coils, followed by 34% of alpha helix and 13% extended strand. The protein was found to be extracellular and secretory in nature. Since, protein-protein interactions play a very crucial role in every cellular process and due to unavailability of crystal structure of our protein of interest in fishes computational approach has been employed. The 3D PDB modeling and the molecular docking of kiss2, Gonadotropin-releasing hormone 2 (GnRH2) and luteinizing hormone beta (LHß) proteins in fishes have been demonstrated applying protein-docking approach. Molecular interactions of kiss2 protein were the highest with kisspeptin receptor 2 and lowest for the neuropeptide FF-amide peptide precursor protein. Expression of kiss2 transcripts, mainly in the brain and ovary of H. fossilis, supports its hypothalamic-pituitary-gonadal axis signaling and reproductive function. Further, changes in expression patterns of kiss2 mRNA during different developmental stages, indicate its potential role in embryonic development also. The present study conclusively reveals interaction of kiss2 with other neuropeptides. Prediction of binding structures and identification of key residues in protein-protein interaction illustrate direct interaction among these proteins, playing a cardinal role in neuroendocrine regulation of reproduction in catfish. Communicated by Ramaswamy H. Sarma.

Expedition of sulfur-containing heterocyclic derivatives as cytotoxic agents in medicinal chemistry: A decade update.

This review article proposes a comprehensive report of the design strategies engaged in the development of various sulfur-bearing cytotoxic agents. The outcomes of various studies depict that the sulfur heterocyclic framework is a fundamental structure in diverse synthetic analogs representing a myriad scope of therapeutic activities. A number of five-, six- and seven-membered sulfur-containing heterocyclic scaffolds, such as thiazoles, thiadiazoles, thiazolidinediones, thiophenes, thiopyrans, benzothiazoles, benzothiophenes, thienopyrimidines, simple and modified phenothiazines, and thiazepines have been discussed. The subsequent studies of the derivatives unveiled their cytotoxic effects through multiple mechanisms (viz. inhibition of tyrosine kinases, topoisomerase I and II, tubulin, COX, DNA synthesis, and PI3K/Akt and Raf/MEK/ERK signaling pathways), and several others. Thus, our concise illustration explains the design strategy and anticancer potential of these five- and six-membered sulfur-containing heterocyclic molecules along with a brief outline on seven-membered sulfur heterocycles. The thorough assessment of antiproliferative activities with the reference drug allows a proficient assessment of the structure-activity relationships (SARs) of the diversely synthesized molecules of the series.

Eosinophilic Granulomatosis Polyangiitis (EGPA) Masquerading as a Mycotic Aneurysm of the Abdominal Aorta: Case Report and Review of Literature.

INTRODUCTION: Aortic involvement leading to aortitis in eosinophilic granulomatosis polyangiitis (EGPA) is infrequent, and only 2 cases have been reported so far in the literature. Even more so, aortic aneurysm, secondary to EGPA, has never been reported and remains a diagnostic and therapeutic challenge. Case Presentation. We present a 63-year-old Caucasian male patient with a prior diagnosis of EGPA presenting with abdominal pain, nausea, and loose stools to the emergency department. Physical examination showed periumbilical tenderness. He had no peripheral eosinophilia but had high C-reactive protein and procalcitonin levels. CT abdomen revealed a mycotic aneurysm involving the infrarenal abdominal aorta. The patient declined surgical repair initially and was treated with IV antibiotics only. Unfortunately, 24 hours later, the aneurysm ruptured, leading to emergent axillofemoral bypass surgery. Surgical biopsy showed aortitis, periaortitis, and active necrotizing vasculitis. CONCLUSION: Abdominal aneurysms should be considered a complication of EGPA, and earlier immunosuppressive therapy should be considered to prevent further complications.

Choroid plexus carcinoma in an adolescent male: a case report.

INTRODUCTION/BACKGROUND: Although central nervous system tumors are the most common etiology of malignancies in the pediatric age group, choroid plexus carcinomas are rare, with an annual incidence rate of 0.10 per 100,000 children. CASE PRESENTATION: We report the case of an adolescent male belonging to central India who had presented with a history of persistent headache, projectile vomiting, neck stiffness, and an episode of generalized tonic-clonic seizure. Neurological examination was suggestive of a space-occupying lesion. Further neuroimaging was suggestive of a large left-sided choroid plexus carcinoma, later confirmed on pathological examination. Gross total resection was achieved and followed by radiation therapy. His recovery was satisfactory without any major events despite suffering from such a malignancy with a poor prognosis. CONCLUSION: In the absence of a global consensus on choroid plexus carcinoma management, our patient underwent a successful gross total resection and received postoperative radiotherapy. He made a satisfactory recovery with a further plan to review with gadolinium-enhanced neuroimaging at a later date. We conclude that, when possible, achieving gross total resection is of utmost importance.

Human DND1-RRM2 forms a non-canonical domain swapped dimer.

RNA recognition motif (RRM) being the most abundant RNA binding domain in eukaryotes, is a major player in cellular regulation. Several variations in the canonical ßαßßαß topology have been observed. We have determined the 2.3 Å crystal structure of the human DND1-RRM2 domain. The structure revealed an interesting non-canonical RRM fold, which is maintained by the formation of a 3D domain swapped dimer between ß1 and ß4 strands across protomers. We have delineated the structural basis of the stable domain swapped dimer formation using the residue level dynamics of protein explored by NMR spectroscopy and MD simulations. Our structural and dynamics studies substantiate major determinants and molecular basis for domain swapped dimerization observed in the RRM domain.

Epidemiology and clinical outcome of ventilator-associated events at a tertiary care hospital from North India.

The aim of our study was to determine the incidence, microbiological profile, risk factors and outcomes of patients diagnosed with ventilator-associated events in our tertiary care hospital. In this prospective study, intensive care patients put on mechanical ventilation for >48 h were enrolled and monitored daily for ventilator-associated event according to Disease Centre Control guidelines. A ventilator-associated event developed in 33/250 (13.2%); its incidence was 3.5/100 mechanical ventilation days. The device utilisation rate was 0.86, 36.4% of patients had early and 63.6% late-onset ventilator-associated pneumonia whose most common causative pathogen was Acinetobacter sp. (63.6%). Various factors were significantly associated with a ventilator-associated event: male gender, COPD, smoking, >2 underlying diseases, chronic kidney disease and elevated acute physiological and chronic health evaluation II scores. Therefore, stringent implementation of infection control measures is necessary to control ventilator-associated pneumonia in critical care units.

Pharmacological preconditioning with phosphodiestrase inhibitor: an answer to stem cell survival against ischemic injury through JAK/STAT signaling.

Stem cell transplantation in regenerative medicine has been widely used in various disorders including cardiovascular diseases (CVD) and emerging next-generation therapy. However, transplanted stem cell encountered ischemia/reperfusion (IR) injury which is a major challenge for stem cell survival. During the acute phase after myocardial infarction (MI) cytokine-rich hostile microenvironment, extensive immune cell infiltration and lack of oxygen have been a bottleneck in cell-based therapy. During prolonged ischemia, intracellular pH and ATP level decrease results in anaerobic metabolism and lactate accumulation. Consequentially, ATPase-dependent ion transport becomes dysfunctional, contributing to calcium overload and cell death by apoptosis and necrosis. Although O2 level revitalizes upon reperfusion, a surge in the generation of reactive oxygen species (ROS) occurs with neutrophil infiltration in ischemic tissues further aggravating the injury. Ischemic preconditioning (IPC) of stem cells with a repeated short cycle of IR results in the release of chemical signals such as NO, ROS, and adenosine which triggers a cascade of signaling events that activates protein kinase C (PKC), Src protein tyrosine kinases, and nuclear factor κB (NF-κB) and subsequently increased synthesis of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), Heme oxygenase-1 [HO-1], aldose reductase, Mn superoxide dismutase, and anti-apoptotic genes (Mcl-1, BCl-xL, c-FLIPL, c-FLIPS). Pharmacological preconditioning uses a phosphodiestrase inhibitor, another mode of protecting stem cell or heart per se from impending ischemic injury in two phases. During the early phase of cardioprotection (2 h), PC leads to increased expression of survival factors like BCl2/Bax ratio while late phase (24 h) showed activation of the JAK/STAT survival pathway. Phosphorylation of STAT3 at two crucial residues, Tyr-705 and Ser-727, allows its entry inside the nucleus and upregulates the expression of protein kinase G-1 (PKG1) which evokes cardioprotective signaling. To confirm, heart-specific conditional STAT3 knockout mice undergone IR surgery, abolishing late-phase cardioprotective effects.