Hydrogel microsphere stem cell encapsulation enhances cardiomyocyte differentiation and functionality in scalable suspension system.

A reliable suspension-based platform for scaling engineered cardiac tissue (ECT) production from human induced pluripotent stem cells (hiPSCs) is crucial for regenerative therapies. Here, we compared the production and functionality of ECTs formed using our scaffold-based, engineered tissue microsphere differentiation approach with those formed using the prevalent scaffold-free aggregate platform. We utilized a microfluidic system for the rapid (1 million cells/min), high density (30, 40, 60 million cells/ml) encapsulation of hiPSCs within PEG-fibrinogen hydrogel microspheres. HiPSC-laden microspheres and aggregates underwent suspension-based cardiac differentiation in chemically defined media. In comparison to aggregates, microspheres maintained consistent size and shape initially, over time, and within and between batches. Initial size and shape coefficients of variation for microspheres were eight and three times lower, respectively, compared to aggregates. On day 10, microsphere cardiomyocyte (CM) content was 27 % higher and the number of CMs per initial hiPSC was 250 % higher than in aggregates. Contraction and relaxation velocities of microspheres were four and nine times higher than those of aggregates, respectively. Microsphere contractile functionality also improved with culture time, whereas aggregate functionality remained unchanged. Additionally, microspheres displayed improved ß-adrenergic signaling responsiveness and uniform calcium transient propagation. Transcriptomic analysis revealed that while both microspheres and aggregates demonstrated similar gene regulation patterns associated with cardiomyocyte differentiation, heart development, cardiac muscle contraction, and sarcomere organization, the microspheres exhibited more pronounced transcriptional changes over time. Taken together, these results highlight the capability of the microsphere platform for scaling up biomanufacturing of ECTs in a suspension-based culture platform.

Prevalence of masked hypertension in children with chronic kidney disease: a cross-sectional study.

BACKGROUND: Hypertension poses a significant risk as a complication of chronic kidney disease (CKD), contributing to its hastened advancement. Implementing ambulatory blood pressure monitoring (ABPM), a straightforward and non-invasive method proves beneficial in identifying masked hypertension. METHODS: A cross-sectional study was carried out involving children aged 5-15 years diagnosed with CKD to estimate the difference in masked HTN prevalence between the 2014 and 2022 AHA ABPM guidelines. The study encompassed a comprehensive assessment, including 24-h blood pressure monitoring and was performed using ABPM. Left ventricular mass (LVM) was computed based on measurements obtained from M-mode echocardiography. PWV was determined by calculating the ratio of distance (D) to time (t). RESULTS: We examined a cohort of 138 children diagnosed with CKD. Our findings reveal that, in accordance with the 2022 American Heart Association (AHA) ABPM guidelines, prevalence of masked hypertension stands at 29.7% marking a notable increase of 17.4% compared to the 2014 ABPM guidelines signifying a substantial proportion of undetected hypertensive cases. Furthermore, the prevalence of hypertension is 48.5% as detected by ABPM, marking a notable increase of 22.5%. CONCLUSIONS: A substantial occurrence of masked hypertension was identified in pediatric CKD patients through the application of ABPM. ABPM proves to be an effective tool for uncovering masked hypertension in children with CKD.

The efficient classification of breast cancer on low-power IoT devices: A study on genetically evolved U-Net.

Breast cancer is the most common cancer among women, and in some cases, it also affects men. Since early detection allows for proper treatment, automated data classification is essential. Although such classifications provide timely results, the resource requirements for such models, i.e., computation and storage, are high. As a result, these models are not suitable for resource-constrained devices (for example, IOT). In this work, we highlight the U-Net model, and to deploy it to IOT devices, we compress the same model using a genetic algorithm. We assess the proposed method using a publicly accessible, bench-marked dataset. To verify the efficacy of the suggested methodology, we conducted experiments on two more datasets, specifically CamVid and Potato leaf disease. In addition, we used the suggested method to shrink the MiniSegNet and FCN 32 models, which shows that the compressed U-Net approach works for classifying breast cancer. The results of the study indicate a significant decrease in the storage capacity of UNet with 96.12% compression for the breast cancer dataset with 1.97x enhancement in inference time. However, after compression of the model, there is a drop in accuracy of only 1.33%.

Discovery of potential natural therapeutics targeting cell wall biosynthesis in multidrug-resistant Enterococcus faecalis: a computational perspective.

BACKGROUND: Identifying therapeutic inhibitors of crucial enzymes involved in the peptidoglycan biosynthesis pathway is pivotal for developing new treatments against multidrug-resistant Enterococcus faecalis V583. MurM, an essential enzyme in this pathway, plays a significant role in the bacterium's cell wall synthesis, making it an attractive druggable target for novel antimicrobial strategies. This study explored the potential of natural compounds as inhibitors of MurM, aiming to discover promising drug candidates that could serve as the foundation for future therapeutic development. METHODS: The three-dimensional structure of MurM was predicted, optimized, and its binding pocket was analyzed by comparing it with related structures. Over 4,70,000 natural compounds from the COCONUT database were subjected to virtual high-throughput screening (vHTS). The top lead candidates were selected based on their Lipinski's profile, ADME profile, toxicity profile, estimated binding free energy (ΔG) and estimated inhibition constant (Ki). Interaction pattern analysis was used to evaluate the non-covalent interactions between the inhibitors and key residues in MurM's binding pocket. Molecular dynamics simulations were performed over 300 ns to assess the structural stability and impact of these inhibitors on MurM's enzyme. RESULTS: Three lead compounds-CNP0056520, CNP0126952, and CNP0248480-were identified and prioritized with estimated ΔG ranging from - 9.35 to -7.9 kcal/mol. Molecular dynamics simulations revealed minimal impact on MurM's overall structure and dynamics, with the candidate inhibitors forming stable protein-ligand complexes. These interactions were supported by several non-covalent interactions between the candidate inhibitors and key residues within MurM's binding pocket. CONCLUSION: These findings suggest that the identified natural product candidates could serve as promising inhibitors of MurM, potentially leading to novel therapeutics targeting cell wall biosynthesis in multidrug-resistant E. faecalis.

Computational Exploration of Limonin as a Potential Inhibitor of DapB in Klebsiella pneumoniae.

Klebsiella pneumoniae has emerged as a significant multidrug-resistant pathogen, classified as a critical priority by the World Health Organization. The rising rates of antibiotic resistance have led to increased therapeutic failures, diminishing the effectiveness of existing antibiotics. Consequently, there is an urgent need for alternative treatments to effectively inhibit the growth of K. pneumoniae and mitigate associated diseases. Phytochemicals have demonstrated potential advantages over traditional antibiotics, prompting their exploration as innovative therapeutic agents. This study aimed to identify phytochemicals that can inhibit dapB, a vital enzyme in the lysine biosynthesis pathway of K. pneumoniae, which is essential for protein synthesis and the cross-linking of the bacterial peptidoglycan cell wall. We screened 17,934 phytochemicals based on Lipinski's Rule of Five, along with their Absorption, Distribution, Metabolism, Excretion properties and toxicological parameters. Next, we conducted triplicate docking studies against dapB to evaluate the library further. The most promising molecules then underwent 100 ns Molecular Dynamics simulations in triplicate, followed by binding free energy calculations to identify potential dapB inhibitors. This in silico analysis highlighted limonin as a promising inhibitor of dapB in K. pneumoniae. Further experimental validation is crucial to enhance limonin's potential as a novel therapeutic agent against K. pneumoniae-associated diseases.

Phosphorylation by JNK switches BRD4 functions.

Bromodomain 4 (BRD4), a key regulator with pleiotropic functions, plays crucial roles in cancers and cellular stress responses. It exhibits dual functionality: chromatin-bound BRD4 regulates remodeling through its histone acetyltransferase (HAT) activity, while promoter-associated BRD4 regulates transcription through its kinase activity. Notably, chromatin-bound BRD4 lacks kinase activity, and RNA polymerase II (RNA Pol II)-bound BRD4 exhibits no HAT activity. This study unveils one mechanism underlying BRD4's functional switch. In response to diverse stimuli, c-Jun N-terminal kinase (JNK)-mediated phosphorylation of human BRD4 at Thr1186 and Thr1212 triggers its transient release from chromatin, disrupting its HAT activity and potentiating its kinase activity. Released BRD4 directly interacts with and phosphorylates RNA Pol II, PTEFb, and c-Myc, thereby promoting transcription of target genes involved in immune and inflammatory responses. JNK-mediated BRD4 functional switching induces CD8 expression in thymocytes and epithelial-to-mesenchymal transition (EMT) in prostate cancer cells. These findings elucidate the mechanism by which BRD4 transitions from a chromatin regulator to a transcriptional activator.

Electron donor-acceptor complex enabled photocascade strategy for the synthesis of trans-dihydrofuro[3,2-c]chromen-4-one scaffolds via radical conjugate addition of pyridinium ylide.

A visible-light-induced photocascade strategy is disclosed for the synthesis of trans-dihydrofuro[3,2-c]chromen-4-one scaffolds. The photocascade consists of electron donor-acceptor (EDA) complex enabled formation of arylidene coumarinone, followed by 1,4-radical conjugate addition (1,4-RCA) of an in situ generated pyridinium ylide radical (PyYR) towards diastereoselective formation of the trans-dihydrofuro[3,2-c]chromen-4-one scaffold in good to excellent yield. Thorough mechanistic investigations comprising photophysical, spectroscopic, electrochemical and DFT studies provide further insights into the reaction mechanism.

Unveiling MurM inhibitors in Enterococcus faecalis V583: a promising approach to tackle antibiotic resistance.

Enterococcus faecalis is commonly found in the GI tract of humans and animals. It causes various infections, especially in hospital environments, and shows growing antibiotic resistance. This study utilized a subtractive proteomics approach to find out the potential drug targets in E. faecalis. Unique metabolic pathways were analysed and compared to the host to minimize adverse effects. Among twenty nine pathogenic specific and seventy three host-pathogen common pathways identified using the KEGG database, sixty seven essential proteins were found through the DEG BLAST search. PSORTB predicted that forty cytoplasmic proteins could be suitable as druggable targets. Further analysis identified fourteen proteins with virulence properties using the VFDB BLAST. Among these, seven proteins with more than ten antigenic sites were subjected to DrugBank BLAST, identifying three novel and four existing drug targets. One of the crucial drug targets, MurM, was selected due to its critical role in peptidoglycan biosynthesis. The reason for selecting MurM is crucial for addressing antibiotic resistance, disrupting bacterial cell wall synthesis, and attaining selective antimicrobial activity. MurM belongs to the mixed αß class with two functional domains. The possible binding site residues of MurM are Trp31, Lys35, Trp38, Arg215, and Tyr219. Virtual screening identified potential lead candidates for MurM, and four were selected based on their physiochemical, pharmacokinetic, and structural properties. This study provides valuable insights into identifying and analysing a potential drug target, the MurM protein, and its inhibitors in E. faecalis V583.

Transcriptome wide changes in long noncoding RNAs in diabetic ischemic heart disease.

More than 10% of adults in the United States have type 2 diabetes mellitus (DM) with a 2-4 times higher prevalence of ischemic heart disease than the non-diabetics. Despite extensive research approaches to limit this life-threatening condition have proven unsuccessful, highlighting the need for understanding underlying molecular mechanisms. Long noncoding RNAs (lncRNAs), which regulate gene expression by acting as signals, decoys, guides, or scaffolds have been implicated in diverse cardiovascular conditions. However, their role in ischemic heart disease in DM remains poorly understood. We provide new insights into the lncRNA expression profile after ischemic heart disease in DM mice. We performed unbiased RNA sequencing of well-characterized type 2 DM model db/db mice or its control db/+ subjected to sham or MI surgery. Computational analysis of the RNA sequencing of these LV tissues identified several differentially expressed lncRNAs between (db/db sham vs. db/db MI) including Gm19522 and Gm8075. lncRNA Gm-19522 may regulate DNA replication via DNA protein kinases, while lncRNA Gm-8075 is associated with cancer gene dysregulation and PI3K/Akt pathways. Thus, the downregulation of lncRNAs Gm19522 and Gm8075 post-MI may serve as potential biomarkers or novel therapeutic targets to improve cardiac repair/recovery in diabetic ischemic heart disease.

Comparative evaluation of autologous tissue-engineered ocular and oral mucosal tissue grafts- a prospective randomized controlled trial.

BACKGROUND: Bilateral ocular surface disease resulting from Stevens Johnson Syndrome (SJS) and chemical injuries are visually debilitating and difficult to treat. Ocular surface reconstruction by various means has been reported with variable results. This study addresses an unmet need for a prospective clinical trial comparing the outcomes of transplanting autologous oral and conjunctival epithelial cell constructs on human amniotic membrane by ex vivo tissue engineering. METHODS: A prospective, randomized controlled clinical trial was prospectively applied for registration, with the clinical trial registry of India (CTRI), with the approval of the Institute Ethics Committee number IEC/NP-99/11.04.2014 and CTRI No. REF/2018/10/021791, the study also registered with the WHO-recognized trial registry, International Standard Randomised Controlled Trial Number (ISRCTN) registration reference number 45780. The study was conducted to compare clinical outcomes of two different tissue-engineered cell grafts, Cultivated Oral Mucosal Epithelial Transplantation (COMET) and Conjunctival Cultivated Epithelial Transplantation (CCET) for ocular surface reconstruction in patients with bilateral ocular surface disease due to Stevens-Johnson Syndrome or chemical injuries. Fifty patients were enrolled and randomized to either the COMET or CCET group. A uniform pre-op and post-op protocol using standard medications was followed for all patients Parameters assessed at baseline, day 1, 1 week, 2 weeks, 1 month, 2 months, 3 months and 6 months postoperatively included patient comfort, best corrected visual acuity (BCVA), ocular surface status and corneal clarity. The efficacy was measured in terms of improvement of vision, reduction in vascularization, symblepharon and corneal clarity. RESULTS: In the study, 50 patients (50 eyes; mean ages of 29 ± 15.86 years and 26.36 ± 10.85 years, respectively; range, 12-65 years) were enrolled, with 25 patients each in the COMET and CCET groups. Out of them, 36% were female and 64% were male; the causes were Steven Johnson syndrome (48), and chemical injury (2). Mean pre-operative BCVA was log MAR 1.73 ± 0.57 for COMET and 1.99 ± 0.33 for the CCET group. Pre-operatively all 50 enrolled patients had opaque corneas pre-operatively, symblepharon that extended to the cornea categorised as grade 3 and corneal vascularization that went beyond the pupil's boundary into the central zone encluaching on the visual axis. The minimal follow-up time was six months. Following surgery postoperatively, the BCVA considerably improved in the COMET group by 1.51 ± 0.58 compared to the CCET group by 1.91 ± 0.33 at 3 months. BCVA at 6 months was 1.73 ± 0.56 in the COMET group and 1.99 ± 0.31 in the CCET group, which is not statistically significant and comparable to the BCVA before surgery. The corneal clarity was significantly improved in COMET group 25 eye (100%) at 2 month, 3month and 19 eye (76%), 6eye (24%) at 6 months when compared to CCET group 15 eye improved (60%), 9 eyes (36%) not improved and one eye with opaque cornea (4%) at 2 months. 22 eye (88%) had not improved, 2 eye (8%) opaque cornea and 1 eye (4%) improved at 3 months. At 6 months 21 eye (84%) were not improved, 4 eye (16%) eye became opaqued at 6 months. Compared to preoperative conditions, both groups had improved corneal clarity significantly (p > 0.005). Of the 50 patients with grade 3 symblepharon extended to the cornea, were completely resolved 19 (76%) in COMET group when compared to CCET group 22 eye (88%) not improved. Similarly, 19 eye (76%) had a improvement in corneal vascularization when compared to the CCET group not improved 25 eye (100%) at 6months. No adverse event was observed in any of either group during the follow up periods. CONCLUSION: Both cell types are effective to restore the ocular surface integrity in bilateral ocular surface disease. Whereas COMET is safe and efficacious in terms of improvement of clinical parameters including, BCVA, corneal clarity, reduction in vascularization and preventing the recurrence of symblepharon postoperatively 3months and 6 months. In addition, the CCET group maintained the stability of the ocular surface and had improvement in corneal clarity and a decrease in vascularization at 3 months compared to their pre-operative characteristics.

Fluconazole-loaded Hyaluronic Acid-modified Transfersomal Hydrogels Containing D-panthenol for Ocular Delivery in Fungal Keratitis Management.

BACKGROUND: Fungal keratitis (mycotic keratitis) is an eye infection in which the cornea is infected by fungi and such fungal keratitis management can be effectively possible by ocular administration of antifungal drugs. OBJECTIVE: The main objectives of the present research were to develop and evaluate fluconazoleloaded transfersomal hydrogels for ocular delivery in the effective management of fungal keratitis. METHODS: A 23 factorial design-based approach was used for statistical optimization, where (A) the ratio of lipid to edge activators, (B) the amount of hyaluronic acid (% HA), and (C) the ratio of edge activators (sodium deoxycholate to Span 80) were taken as three factors. The average vesicle diameter (Z, nm) of transfersomes was taken as a response. Further, fluconazole-loaded transfersomes (FTO) were incorporated into 1% Carbopol 940-based hydrogel (OF1) and 2% HMPC K4M-based hydrogel (OF2) containing D-panthenol (5% w/w). RESULTS: The optimal variable setting for the optimized formulations of FTO was (A) = 9.15, (B) = 0.30%, and (C) = 3.00. FTO exhibited 66.39 nm Z, 0.247 polydispersity index, - 33.10 mV zeta potential, and 65.38 ± 1.77 % DEE, and desirable elasticity. TEM image of FTO demonstrated a unilamellar vesicular structure. The ex vivo ocular permeation of fluconazole from transfersomal hydrogels was sustained over 24 h. All the transfersomal hydrogels showed good bioadhesion and excellent antifungal activity with respect to the zone of inhibition against Candida albicans than Aspergillus fumigates, in vitro. HET-CAM study results demonstrated that both the hydrogels were nonirritant and safe for ocular. Short-term physical stability study suggested the stability of the developed formulation. CONCLUSION: The current research demonstrated a new way to enhance the ocular penetration of fluconazole via transfersomal hydrogel formulations for ocular delivery in the effective management of fungal keratitis.

Nanostructured Lipid Carrier-based Topical Gels as Novel Drug Delivery System: A Comprehensive Overview.

Nanostructured lipid carriers (NLCs) are lipidic nanocarriers that recover the permanency and capacity of drug payloads. NLCs are well-known as second-generation lipid nanocarriers with an unstructured matrix, presenting potentially advantageous nanocarrier systems with marketable opportunities because of reproducible production methodologies and biocompatible lipidic excipients. These (NLCs) are now recognized as a very promising nanocarrier structure for the efficient delivery of drugs via different administration routes. In recent years, several NLC-based gels have been developed and evaluated for topical delivery of many drugs and other therapeutic agents. This review article presents an overview of NLC-based topical gels investigated to deliver drugs via ocular, dermal, and transdermal routes. In addition, the classification, manufacturing, characterizations, advantages, and disadvantages of NLCs are addressed in this article. We also discussed different evaluations of NLC-based topical gels.

The EXO1/Polη/Polι axis as a promising target for miR-3163-mediated attenuation of cancer stem-like cells in non-small cell lung carcinoma.

BACKGROUND: Cancer stem-like cells (CSLCs) drive tumour progression and chemoresistance. The concerted efforts of EXO1 and TLS polymerases safeguard DNA integrity against chemotherapeutic drugs. In absence of potential drug targets, non-small cell lung carcinoma (NSCLC) patients have few therapeutic options. In current scenario, microRNAs offer a potential avenue for eradicating CSLCs. METHODS: EXO1 downregulation impact on CSLCs expansion was assessed via flow cytometry. Co-localisation of EXO1, Polη and Polι was validated through co-immunoprecipitation and confocal-imaging. The effects of co-downregulation of Polη and Polι on CSLC survival, repair synthesis, and mutagenesis were evaluated using flow cytometry and immunohistochemistry in cell lines and xenografts. MicroRNA targeting EXO1 was studied for its role in CSLCs regulation. RESULTS: EXO1 downregulation in NSCLC CSLCs induces DNA lesions, triggering apoptosis and enhances cisplatin sensitivity. It collaborates with Polη and Polι in DNA repair, contributing to cisplatin resistance in CSLCs. Absence of Polη and Polι impairs repair and reduces cisplatin-induced mutagenesis. Co-downregulation of Polη and Polι in xenografts reduces tumour proliferation significantly. MiR-3163 overexpression sensitises CSLCs to cisplatin via targeting EXO1/Polη/Polι axis, as shown in mechanistic studies. CONCLUSION: This study unveils a novel regulatory pathway involving EXO1/Polη/Polι axis and miR-3163, providing insights into CSLCs regulation in NSCLC. EXO1/Polη/Polι axis targeted by miR-3163, resulting in the inhibition of cell growth and induction of apoptosis in NSCLC CSLCs.

The role of Helicobacter pylori in augmenting the severity of SARS-CoV-2 related gastrointestinal symptoms: An insight from molecular mechanism of co-infection.

Coinfection of pathogenic bacteria and viruses is associated with multiple diseases. During the COVID-19 pandemic, the co-infection of other pathogens with SARS-CoV-2 was one of the important determinants of the severity. Although primarily a respiratory virus gastric manifestation of the SARS-CoV-2 infection was widely reported. This study highlights the possible consequences of SARS-CoV-2 -Helicobacter pylori coinfection in the gastrointestinal cells. We utilized the transfection and infection model for SARS-CoV-2 spike Delta (δ) and H. pylori respectively in colon carcinoma cell line HT-29 to develop the coinfection model to study inflammation, mitochondrial function, and cell death. The results demonstrate increased transcript levels of inflammatory markers like TLR2 (p < 0.01), IL10 (p < 0.05), TNFα (p < 0.05) and CXCL1 (p < 0.05) in pre-H. pylori infected cells as compared to the control. The protein levels of the ß-Catenin (p < 0.01) and c-Myc (p < 0.01) were also significantly elevated in pre-H. pylori infected group in case of co-infection. Further investigation of apoptotic and necrotic markers (Caspase-3, Caspase-8, and RIP-1) reveals a necroptotic cell death in the coinfected cells. The infection and coinfection also damage the mitochondria in HT-29 cells, further implicating mitochondrial dysfunction in the necrotic cell death process. Our study also highlights the detrimental effect of pre-H. pylori exposure in the coinfection model compared to post-exposure and lone infection of H. pylori and SARS-CoV-2. This knowledge could aid in developing targeted interventions and therapeutic strategies to mitigate the severity of COVID-19 and improve patient outcomes.

Antioxidant, antibacterial and antibiofilm activities of Pittosporum napaulense (DC.) against drug-resistant Staphylococcus aureus and Shigella sp.

Gandhamardan has a rich heritage of floristic diversity with undocumented medicinal plants, called Anukta Dravya having immense pharmacological values. Among them, Pittosporum napaulense (DC.) Rehder & E. H. Wilson is an important medicinal plant with widespread pharmacological importance. The antioxidant potential, antibacterial and antibiofilm activities of P. napaulense (DC.) were evaluated. The ethanolic extract showed the highest share of phenolic and flavonoid contents responsible for DPPH and ABTS radical scavenging activity with an IC50 of 5.58 and 5.28 µg/ml, respectively. In addition, the extracts also showed antibacterial and antibiofilm properties against multidrug-resistant bacterial strains, Staphylococcus aureus and Shigella sp. The biological activities of P. napaulense (DC.) bark could be attributed to the presence of phytoconstituents such as Malabaricone C, Borapetoside B, Kanzonol R. as evident from UPLC-Q-TOF-MS analysis. Based on the bioactivities; this plant could be explored for the development of potential therapeutic drug candidates against severe bacterial diseases.

Predictors of quality of life (QOL) and treatment adherence among children with nephrotic syndrome.

Introduction: Any significant changes in the growth and development of any aspect of life will ultimately affect the health-related quality of life (HRQOL) of children with nephrotic syndrome. Various factors can influence treatment adherence, which can promote or decline the child's quality of life (QOL). Objective: To assess the quality of life and adherence to treatment regimen and to identify the predictors of QOL and adherence to treatment regimen among children with nephrotic syndrome. Method: A cross-sectional study was conducted among 59 children with nephrotic syndrome who attended the Paediatric Department of AIIMS, Bhubaneswar, using the PedsQL 4.0 generic core scale to assess the quality of life and adherence response scale. Both descriptive and inferential statistics were performed using the SPSS 20 version. Results: The overall QOL median score was 93.48, with an IQR of 18.48, which indicated good QOL. A median score of treatment adherence was 16 with IQR 5, which indicated that the overall treatment adherence was good. Type of nephrotic syndrome (P = 0.014), developmental stage (P = 0.018), education of mother (P = 0.026), and occupation of mother (P = 0.026) were the variables predicted QOL. Duration of disease (P = 0.006) and duration of therapy (P = 0.005) significantly predicted treatment adherence. Conclusion: Children need continuous reinforcement on treatment adherence strategies to attain and maintain good QOL so that it can help to reduce the disease severity. Controlling the predictors that influence the QOL and treatment adherence has to be counseled among the parents so that their adherence can be sustained throughout the disease process to maintain good QOL.

Dual Signature of Chirality Induced Spin Selectivity through Spontaneous Resolution of 2D Metal-Organic Frameworks.

The Chiral-Induced Spin Selectivity (CISS) effect has emerged as a fascinating phenomenon within the realm of electron's spin manipulation, showcasing a unique interplay between electron's spin and molecular chirality. Subsequent to its discovery, researchers have been actively involved in exploring the new chiral molecules as effective spin filters. In the realm of observing the CISS effect, the conventional approach has mandated the utilization of two distinct enantiomers of chiral molecules. However, this present study represents a significant advancement by demonstrating the ability to control both spin states of electrons in a single system. In this work, we have demonstrated the preparation of chiral metal-organic frameworks (MOFs) via a "spontaneous resolution" process, obviating the requirement for chiral sources. Remarkably, this work signifies the first instance of achieving dual signature of spin selectivity from a single and exclusively achiral system through a spontaneous resolution process. This holds immense potential as it facilitates the production of two distinct spin-filtering materials from a unified system. In overall, the significant findings achieved using these robust and easily synthesized MOF crystals without the requirement for chiral medium represent a crucial advancement in enhancing the effectiveness of spin filtering materials to produce spintronic devices.

Bacterial profile of wound site infections and evaluation of risk factors for sepsis among road traffic accident patients from Apex Trauma Centre, Northern India.

Background. Among the most significant yet often ignored health issues worldwide are trauma and accidental injuries. India accounts for 11% of global deaths in road accidents, the highest in the world, according to the World Bank report. There are limited data about the bacterial contamination of road traffic accident (RTA) wounds and their antibiotic susceptibility patterns. Materials and Methods. This prospective study was conducted in a tertiary care centre in northern India from January 2023 to January 2024. Wound deep swabs or aspirates were collected from RTA patients with traumatic injuries at different time intervals. Gram stain and culture were performed, and positive aerobic culture was subjected to antibiotic susceptibility testing. Organism identification was done using MALDI-TOF MS and routine biochemical tests. Blood samples were also collected to rule out bloodstream infections during follow-up if the patient became febrile or showed symptoms of systemic infection. Sepsis was defined in those patients who had two or more scores in the systemic inflammatory response syndrome criteria with a positive microbiological culture. Risk factors were evaluated for sepsis on the basis of the patient's vitals, injury characteristics, procalcitonin, Glasgow Coma Scale (GCS) score, need for mechanical ventilation and complete blood count, which were obtained from the patient's admission file. Results. A total of 189 wound samples were collected, of which 99 (52.38%) samples showed the growth of microorganisms. The aerobic isolates included 69 (69.69%) Gram-negative bacilli, of which the majority were Klebsiella pneumoniae, 28 (28.28%) Gram-positive cocci, of which the majority were Staphylococcus aureus and 2 (2.02%) anaerobic isolates. Among the Gram-negative isolates, none of the isolates were resistant to colistin. All S. aureus isolates were susceptible to vancomycin, teicoplanin and levonadifloxacin. Sepsis developed in 50 (26.45 %) patients. Significant risk factors evaluated for sepsis were a raised procalcitonin level, a low GCS score, a higher injury severity score, the need for mechanical ventilation and a raised quick sequential organ failure assessment score. Conclusion. It is essential to ascertain the profile of microorganisms isolated from RTA wounds in order to reduce antibiotic resistance and deliver efficient treatment.