A Single Centre Experience of Effective Desensitization Strategy for Children with High Anti-HLA Donor-Specific Antibodies Undergoing Haploidentical Hematopoietic Stem Cell Transplantation.

To assess the incidence of anti-HLA donor-specific antibodies and the effectiveness of desensitization strategy in children who underwent haploidentical HSCT at our hospital. A retrospective review, management and outcomes of children with positive anti-HLA DSA who underwent haploidentical HSCT at our hospital from 2020 to 2022. Three patients with Thalassemia major were treated with 2 cycles of pretransplant immune suppression (PTIS) comprising Fludarabine and Dexamethasone in addition to desensitization. Five out of the 26 children who underwent haploidentical HSCT had positive anti-HLA DSA. Post desensitization, three out of the 5 children engrafted with sustained full donor chimerism, 1 patient developed primary graft rejection, while 1 patient died. It is feasible to desensitize children with high anti-HLA donor specific antibodies undergoing haploidentical HSCT to improve outcomes.

Comparison of porcine versus bovine surfactant in preterm respiratory distress syndrome: Evidence from real-world data. A multicentre collaboration from Karnataka.

BACKGROUND & OBJECTIVES: Porcine surfactant (200 mg/kg initial dose) seems to be superior to bovine surfactants (100 mg/kg) in respiratory distress syndrome (RDS). There is limited data on the choice of surfactant from the developing world. Logically, using higher doses of porcine surfactant comes with an additional cost burden. We decided to evaluate the clinical effects of different types of surfactants. METHODS: A retrospective analysis was conducted from August 2019 to December 2022 in six tertiary centers. Neonates 24-34 weeks of gestation with RDS requiring either porcine (200 mg/kg) or bovine surfactant (100 mg/kg) were enrolled. The proportion of BPD, redosing, and other morbidities in either group were analyzed. The outcomes in preterm ≥28 and <28 weeks subgroups were analyzed. RESULTS: Of 1149 eligible babies, 302 (26%) received surfactant after stabilization with CPAP. One hundred fifty-eight received porcine, and 144 received bovine surfactant. There was a higher BPD in porcine compared to the bovine group on univariate analysis [24 (15%) vs. 6 (4%); OR: 4; 95% CI: 1.6-10; p = 0.002]. On logistic regression, the gestational age and PDA requiring treatment were independent predictors of BPD, and the type of surfactant and centres did not influence BPD. Redosing [27 (17%) vs. 18 (12%), OR: 1.4; 95% CI: 0.7-2.7; p = 0.2] was not different between both surfactant types. Other morbidities like mortality, air leaks, invasive ventilation, and CPAP duration were also not different between the groups. CONCLUSION: We could not find a difference in the outcomes of BPD and redosing using porcine surfactant at 200 mg/kg compared to bovine surfactant. Considering the cost burden in the developing world, efficacy needs to be evaluated in randomized clinical trials.

Epidemiological and Histopathological Analysis of Head and Neck Cancers in Northern India- A Retrospective Review.

INTRODUCTION: Head and neck malignancies are responsible for 30% of all cancers in India with a dramatic increase in numbers due to widespread tobacco consumption. This study aims to assess the epidemiological and histopathological spectrum of these tumors. MATERIALS AND METHODS: A large retrospective review of 5469 biopsy-proven patients presenting between 2018 and 2022 with head and neck cancers was done. Tumors were analysed for distribution according to sites of presentations, gender, age and histopathological profiles. RESULTS: With a male-to-female ratio of 4.2:1, men constituted 80.80% of the study population. Mean age of presentation in women was 53.5 years, whereas men presented at an earlier age of 47.2 years. Oral cavity was the commonest site involved (59.7% cases) followed by the oropharynx (23.8% cases). Buccal mucosa was the commonest subsite involved with 1112 cases followed by tongue lesions with 1088 cases. Larynx was responsible for 17.04% of cases. All subsites were more commonly affected in men with the highest Male: Female ratio of 8.29:1 seen in larynx. The lowest ratio of 1.02:1 was seen in lesions of the face and scalp. Squamous cell carcinoma (SCC) was the most common histopathological diagnosis encountered in 88.97% of cases followed by basal cell carcinoma which was seen in 2.10% lesions. CONCLUSION: Oral cavity lesions constitute the bulk of head and neck cancer presentations in India. The disease is more prevalent in men overall and men present at a younger age in comparison to women. SCC is the most prominent histopathology encountered in our study.

Therapeutic proteins: developments, progress, challenges, and future perspectives.

Proteins are considered magic molecules due to their enormous applications in the health sector. Over the past few decades, therapeutic proteins have emerged as a promising treatment option for various diseases, particularly cancer, cardiovascular disease, diabetes, and others. The formulation of protein-based therapies is a major area of research, however, a few factors still hinder the large-scale production of these therapeutic products, such as stability, heterogenicity, immunogenicity, high cost of production, etc. This review provides comprehensive information on various sources and production of therapeutic proteins. The review also summarizes the challenges currently faced by scientists while developing protein-based therapeutics, along with possible solutions. It can be concluded that these proteins can be used in combination with small molecular drugs to give synergistic benefits in the future.

Advancements in enhancing cyber-physical system security: Practical deep learning solutions for network traffic classification and integration with security technologies.

Traditional network analysis frequently relied on manual examination or predefined patterns for the detection of system intrusions. As soon as there was increase in the evolution of the internet and the sophistication of cyber threats, the ability for the identification of attacks promptly became more challenging. Network traffic classification is a multi-faceted process that involves preparation of datasets by handling missing and redundant values. Machine learning (ML) models have been employed to classify network traffic effectively. In this article, we introduce a hybrid Deep learning (DL) model which is designed for enhancing the accuracy of network traffic classification (NTC) within the domain of cyber-physical systems (CPS). Our novel model capitalizes on the synergies among CPS, network traffic classification (NTC), and DL techniques. The model is implemented and evaluated in Python, focusing on its performance in CPS-driven network security. We assessed the model's effectiveness using key metrics such as accuracy, precision, recall, and F1-score, highlighting its robustness in CPS-driven security. By integrating sophisticated hybrid DL algorithms, this research contributes to the resilience of network traffic classification in the dynamic CPS environment.

Mapping the family incivility, dissatisfaction and organizational support after the COVID-19 outbreak.

BACKGROUND: Stress is a pivotal aspect of organizational psychology. Although an individual's attitude and behaviour at work have received greater investigation, scant attention has been given to family-related dynamics and their impact on work. OBJECTIVE: This study contributes to understanding work-family dynamics by investigating the connection between family incivility and job dissatisfaction during the pandemic. Based on the conservation of resources theory, the research explores the potential moderating role of perceived organizational support. METHODS: The investigation uses structural equation modelling (SEM) for data analysis while controlling for age, gender, and experience. Data has been collected with an adapted scale and time-lag technique in which the first wave encompassed independent variables and demographics. The second wave gathered moderator and dependent variables through a non-probability sampling of IT employees. RESULTS: Findings reveal a significant positive link between family incivility and job dissatisfaction, implying higher family incivility is linked to increased job dissatisfaction. Moreover, the study indicates that organizational support can mitigate the negative impact of family incivility on job dissatisfaction. CONCLUSION: This research underscores the pivotal role of organizational support in enhancing employee job outcomes. Hence, organizations should prioritize employee well-being, recognizing it as an integral aspect of their functioning.

Role of health literacy and primary health-care access in self-care management of hypertension.

Background: Globally, hypertension is the leading risk factor for men and women and the largest contributor to premature deaths and diseases in India. Health literacy (HL) and health-care access are important determinants for self-care management of hypertension. Objectives: The purpose of this study was to estimate the prevalence of HL, health-care access, and their importance in the self-care management of hypertension. Methods: A community-based cross-sectional study was conducted among 104 known hypertensive patients for 2 months from May to June 2022. Data were collected by face-to-face interviews using a pretested, preformed, and validated questionnaire, and tabulated and analyzed using Microsoft Excel and SPSS version 20 software. Results: Most of the participants (80, 76.9%) have low levels of HL. However, more than half of the (62, 59.6%) participants were satisfied with their access to primary health care. The age of the participants ranged from 38 to 80 years, and half of them (54, 51.9%) were middle-aged adults. The majority (66, 63.5%) of the patients belonged to lower-middle socioeconomic status, and 15.4% (16) were living alone. We found poor HL, and primary health-care access is statistically significantly associated with poor self-care management. Conclusion: Our findings confirm that HL and access to primary health care are crucial factors in the self-care management of hypertension in hypertensive patients.

Development of sustainable biomass residues for biofuels applications.

A comprehensive understanding of physiochemical properties, thermal degradation behavior and chemical composition is significant for biomass residues before their thermochemical conversion for energy production. In this investigation, teff straw (TS), coffee husk (CH), corn cob (CC), and sweet sorghum stalk (SSS) residues were characterized to assess their potential applications as value-added bioenergy and chemical products. The thermal degradation behavior of CC, CH, TS and SSS samples is calculated using four different heating rates. The activation energy values ranged from 81.919 to 262.238 and 85.737-212.349 kJ mol-1 and were generated by the KAS and FWO models and aided in understanding the biomass conversion process into bio-products. The cellulose, hemicellulose, and lignin contents of CC, CH, TS, and SSS were found to be in the ranges of 31.56-41.15%, 23.9-32.02%, and 19.85-25.07%, respectively. The calorific values of the residues ranged from 17.3 to 19.7 MJ/kg, comparable to crude biomass. Scanning electron micrographs revealed agglomerated, irregular, and rough textures, with parallel lines providing nutrient and water transport pathways in all biomass samples. Energy Dispersive X-ray spectra and X-ray diffraction analysis indicated the presence of high carbonaceous material and crystalline nature. FTIR analysis identified prominent band peaks at specific wave numbers. Based on these findings, it can be concluded that these residues hold potential as energy sources for various applications, such as the textile, plastics, paints, automobile, and food additive industries.

Restorative Rehabilitation of a Patient With Tooth Wear: A One-Year Clinical Follow-Up Report.

Tooth wear is a multifactorial process of complex aetiology. It may be considered a physiological or pathological process depending upon the rate and degree of occurrence. The patients may present with symptoms of sensitivity, pain, headaches or recurrent loss of restorations and prostheses, leading to loss of function. This case report describes the rehabilitation of a 65-year-old male patient with intrinsic dental erosion combined with generalised attrition. The restorative treatment aimed at restoring anterior guidance, establishing a stable occlusion for the patient with minimal intervention.

Immunogenicity and protective efficacy of an inactivated Newcastle disease virus vaccine encapsulated in poly-(lactic-co-glycolic acid) nanoparticles.

An immunization experiment was conducted in specific pathogen-free chickens with the inactivated Newcastle disease virus (NDV) vaccine encapsulated in the poly-(lactic-co-glycolic) acid (PLGA) nanoparticles (NP) to evaluate its immunogenicity and protective efficacy. The NDV vaccine was prepared by inactivating one virulent Indian strain of NDV belonging to Genotype VII by using beta-propiolactone. PLGA nanoparticles encapsulating inactivated NDV were prepared by the solvent evaporation method. Scanning electron microscopy and zeta sizer analysis revealed that the (PLGA+NDV) NP were spherical, with an average size of 300 nm, having a zeta potential of -6 mV. The encapsulation efficiency and loading efficiency were 72% and 2.4%, respectively. On immunization trial in chicken, the (PLGA+NDV) NP induced significantly (P < 0.0001) higher levels of HI and IgY antibodies with the peak HI titer of 28 and higher expression of IL-4 mRNA. The consistency of higher antibody levels suggests slow and pulsatile release of the antigens from the (PLGA+NDV) NP. The nano-NDV vaccine also induced cell mediated immunity with higher expression of IFN-γ indicating strong Th1 mediated immune responses in contrast to the commercial oil adjuvanted inactivated NDV vaccine. Further, the (PLGA+NDV) NP afforded 100% protection against the virulent NDV challenge. Our results suggested that PLGA NP have adjuvant potential on induction of humoral as well as Th1 biased cell mediated immune responses and also enhanced protective efficacy of the inactivated NDV vaccine. This study provides an insight for development of PLGA NP based inactivated NDV vaccine using the same genotype circulating in the field as well as for other avian diseases at exigencies.

The performance improvement analysis using Six Sigma DMAIC methodology: A case study on Indian manufacturing company.

The six-sigma methodology has been adopted by the industry as a business management tool to improve operational capabilities and reduce defects in any process. This study aims to present a case study on the implementation of the Six-Sigma DMAIC methodology with the purpose to reduce the rejection rate of rubber weather strips manufactured by XYZ Ltd. (name changed) situated in Gurugram, India. Weather strips are used in all four doors of cars for noise reduction, waterproofing, dust proofing, soundproofing, windproofing, and for improving air conditioning cooling, and heating effects. The overall rejection rate of both front and rear door rubber weather strips was 5.5% which was causing a huge loss to the company. The average rejection rate of rubber weather strips per day reduced from 5.5% to 3.08%. After implementing the Six-Sigma project findings the rejection was reduced from 153 pieces to 68 pieces helped the industry in saving the cost of a compound by Rs. 15,249 per month. The sigma level improved from 3.9 to 4.45 within three months with the implementation of one Six-Sigma project solution. The company was highly concerned about reducing the high rejection rate of rubber weather strips and decided to deploy Six Sigma DMAIC as a quality improvement tool. The industry was keen to reduce this high rejection rate to 2% and this target was materialized with the application of the Six-Sigma DMAIC methodology. The novelty of this study is to analyze performance improvement considering the Six Sigma DMAIC methodology to reduce the rejection rate of rubber weather strip manufacturing companies.

Outcomes of liver transplantation in children with Langerhans cell histiocytosis: Experience from a quaternary care center.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare but important cause of end-stage liver disease in children. Conventional chemotherapeutic agents that are otherwise the standard-of-care in LCH may be counterproductive in patients with hepatic decompensation. Furthermore, the precise role of liver transplantation (LT) in the management of LCH remains unclear. METHODS: Review of a prospectively collected database (January 2014 to December 2020) of children with liver disease was performed. All clinical details of patients with LCH managed at our center were collected and data analyzed. Based on the outcomes, a management algorithm was proposed. RESULTS: Of the eight (five male) patients referred to our unit, six (75%) underwent LT (four and two for compensated and decompensated cirrhosis, respectively). Median age at diagnosis of LCH was 25 (range: 9-48) months. Two patients, who had previously completed LCH-specific chemotherapy, underwent upfront LT for compensated cirrhosis. Other two patients with compensated cirrhosis showed evidence of active disease. They underwent LT following completion of chemotherapy. Two children with decompensated cirrhosis also had evidence of active disease and were started on modified chemotherapy Both of them had progression of liver disease while on chemotherapy. Hence, an urgent LT was performed which was followed by completion of chemotherapy in these patients. On a median follow-up of 30.5 (10.5-50) months, all post-LT patients were alive with stable graft function and showed no disease recurrence. CONCLUSION: We demonstrate that an algorithmic approach, along with newer chemotherapeutic agents, results in excellent outcomes in LCH patients with liver involvement. Larger multicentric studies on this rare disease are, however, needed to validate our findings.

An evidence and reasoning based differential diagnosis of a case of leprosy reinfection from reaction and relapse.

Leprosy is caused by Mycobacterium leprae (M. leprae) and is unique in terms of the chronicity of the disease and its prolonged treatment protocol. Even after the introduction of multidrug therapy (MDT) by World health organization (WHO), large numbers of new cases (nearly 200,000) of leprosy are reported yearly, indicating active transmission, especially in developing countries. Recurrent clinical manifestations after MDT can occur due to leprosy reactions, relapse or reinfection. It is very difficult to differentiate reaction, relapse and reinfection. Here we categorized a recent case of reoccurrence of leprosy as reinfection by differentiating it from reaction and relapse based on evidence and by analysing the clinical data of the patient.

Stimulated expression of ELR+ chemokines, VEGFA and TNF-AIP3 promote mycobacterial dissemination in extrapulmonary tuberculosis patients and Cavia porcellus model of tuberculosis.

Pathogenic mycobacteria induce and accelerate blood vessel formation driven by extensive inflammation during granuloma formation, which is a central feature of mycobacterial pathogenesis. Tumor necrosis factor-alpha (TNF-α) enhances the expression of vascular endothelial growth factor (VEGF) and glutamic acid-leucine-arginine (ELR+) chemokines, which are potent inducers of vascularization. Most of the reported research work contends that VEGF growth factor induces neovascularization in human tuberculosis (TB) patients, but the evidence is inconclusive. Considerable ambiguity exists concerning the factors responsible for miliary tuberculosis. To identify such factors, we proposed an alternative explanation that could be found in miliary tuberculosis (MTB) cases. We performed a comparative analysis of angiogenic factors TNF-α, VEGF, and angiogenic ELR+ CXC and CC chemokine ligands in extrapulmonary tuberculosis (EPTB) and pulmonary tuberculosis (PTB) patients. To observe the relationship of these factors with the severity of bacterial burden, guinea pigs were infected with Mycobacterium tuberculosis (M.tb) and levels of the angiogenic factors were examined at different time intervals. Expression of these factors also exhibited a significant positive correlation with bacterial burden in other organs like the spleen, liver, and lymph nodes. We demonstrated statistical data on bacterial burden at different time points following the dissemination of infection in guinea pigs. In this study, we observed that there was a stimulated increase in the expression of ELR+ chemokines and VEGF in EPTB patients as compared to PTB patients. Following increased dissemination, the host immune response clears bacteria from the lungs during disease progression in guinea pigs.

Wound Infiltration and Instillation Technique for Postoperative Analgesia Using Bupivacaine in Patients Undergoing Lumbar Spine Surgeries.

BACKGROUND: Pain relief after surgery continues to be a major medical challenge in clinical practice. Lumbar spine surgery is associated with significant postoperative pain. Providing optimal analgesia locally in the area of surgical wound, with little systemic side-effects, is a favourable option and has become an intrinsic part of multimodal analgesia. We aimed to assess and compare the effectiveness of local infiltration and instillation of bupivacaine for postoperative analgesia in patients undergoing lumbar spine surgery. MATERIALS AND METHODS: Forty-four adult patients of the American Society of Anesthesiologists (ASA) class I and II were randomly assigned into two groups, incorporating 22 patients per group. After the completion of lumbar spine surgery and after hemostasis was achieved, patients in group A received instillation of 20 ml of 0.25% bupivacaine at the surgical wound site and patients in group B received 20 ml of 0.25% bupivacaine infiltration into the paravertebral muscles on either side. Postoperative numerical rating scale (NRS) pain scores at 1, 2, 3, 4, 5, 6, 7, 8, 14, 20, and 24 hours; the time to first analgesic required, total rescue analgesic consumption, and adverse effects were recorded. Statistical analysis was done using IBM SPSS Statistics for Windows, Version 20.0 (Released 2011; IBM Corp, Armonk, New York, United States). RESULTS: Time to the first analgesic requirement was significantly longer in group A (12.39±1.56 hours) compared to the B group (2.48±0.58 hours) (P < 0.001). The amount of rescue analgesia (diclofenac sodium) required was significantly higher in group B (135.00±46.17 milligrams) compared to A (93.75±33.32 milligrams) (P = 0.001). The number of analgesic demands was higher in the infiltration group compared to the instillation group and was observed to be statistically significant. Hemodynamic parameters remained comparable between the groups. CONCLUSION: Local instillation of surgical wound site provided better pain control than infiltration technique and is effective and safe postoperative analgesia in patients undergoing laminectomy surgeries.

CARMIL2 Immunodeficiency with Epstein Barr Virus Associated Smooth Muscle Tumor (EBV-SMT). Report of a Case with Comprehensive Review of Literature.

Background: Primary immunodeficiency (PID) having defects related to lymphocyte cytotoxic pathway or T-cell dysfunction are well known for developing opportunistic infections and Epstein-Barr virus (EBV)-associated diseases. CARMIL2 deficiency is a recently described combined immunodeficiency (CID) disorder characterized by defective CD28-mediated T cell co-stimulation, altered cytoskeletal dynamics, susceptibility to various infections and Epstein Barr Virus smooth muscle tumor (EBV-SMT). Case report: We report a homozygous CARMIL2 pathogenic variant presenting with recurrent infections and EBV associated smooth muscle tumor (SMT) in a child. Conclusion: The present study reports that EBV SMT may occur in a child with CARMIL2 deficiency.

Pyrrolo[2,1-f][1,2,4]triazine: a promising fused heterocycle to target kinases in cancer therapy.

Cancer is the second leading cause of death worldwide responsible for about 10 million deaths per year. To date several approaches have been developed to treat this deadly disease including surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy, and synthetic lethality. The targeted therapy refers to targeting only specific proteins or enzymes that are dysregulated in cancer rather than killing all rapidly dividing cells, has gained much attention in the recent past. Kinase inhibition is one of the most successful approaches in targeted therapy. As of 30 March 2021, FDA has approved 65 small molecule protein kinase inhibitors and most of them are for cancer therapy. Interestingly, several kinase inhibitors contain one or more fused heterocycles as part of their structures. Pyrrolo[2,1-f][1,2,4]triazine is one the most interesting fused heterocycle that is an integral part of several kinase inhibitors and nucleoside drugs viz. avapritinib and remdesivir. This review articles focus on the recent advances made in the development of kinase inhibitors containing pyrrolo[2,1-f][1,2,4]triazine scaffold.

Role of ACE and ACE-2 in abrogated cardioprotective effect of ischemic preconditioning in ovariectomized rat heart

Abstract Ischemic heart disease is the leading cause of death in postmenopausal women. The activity of heart ACE increases whereas the activity of ACE-2 decreases after menopause. The present study was designed to investigate the role of ACE and ACE-2 in the abrogated cardioprotective effect of IPC in OVX rat heart. The heart was isolated from OVX rat and mounted on Langendorff's apparatus for giving intermittent cycles of IPC. The infarct size was estimated using TTC stain, and coronary effluent was analyzed for LDH, CK-MB, and nitrite release. IPC induced cardioprotection was significantly attenuated in the ovariectomized rat heart as compared to the normal rat heart. However, this attenuated cardioprotection was significantly restored by perfusion of DIZE, an ACE-2 activator, and captopril, an ACE inhibitor, alone or in combination noted in terms of decrease in myocardial infarct size, the release of LDH and CK-MB, and also increase in the release of NO as compared to untreated OVX rat heart. Thus, it is suggested that DIZE and captopril, alone or in combination restore the attenuated cardioprotective effect of IPC in OVX rat heart which is due to an increase in ACE-2 activity and decrease in ACE activity after treatment.