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Background: The course of inflammatory bowel diseases (IBD) has mainly been studied using different methods in single patient cohorts. The aim of the present study was to assess clinical aspects of disease outcome in a population-based cohort of IBD patients over a 4-year period in multiple centres across Europe. Methods: A total of 796 patients with IBD diagnosed in 10 centres between October 1991 and October 1993, registered at the EC IBD study centre (98% of the original cohort), participated in the study. Investigators filled out a standard follow-up form containing questions on the method of follow-up, vital status of the patient, change in diagnosis, extraintestinal manifestations, medical and surgical treatment, and physician's global assessment of disease activity. Results: Complete relief of the complaints was reported in 255 (48%) patients with ulcerative colitis (UC), 9 (50%) with indeterminate colitis (IC), but only in 87 (35%) of patients with Crohn disease (CD). Improvement was reported in 195 (37%) patients with UC, 113 (45%) with CD and 6 (33%) with IC. During the 4-year follow-up period, 23 patients died (14 UC, 8 CD, and 1 IC). The mean age at death was 69.3 years (s, 14.9 years). The deaths of three patients were recorded as directly due to IBD. Conclusions: With the present approach to therapeutic management the short-term outcome of patients with IBD seems to be favourable in 10 medical centres in the north and south of Europe. However, more detailed studies including both objective and subjective measures are necessary. [ABSTRACT FROM AUTHOR]

Two hundred and ten patients with Crohn's disease (CD) were identified in an epidemiological survey of inflammatory bowel disease in the Leiden Health Care Region of the Netherlands. The survey included all patients with CD seen between 1979-1983. The duration of disease ranged from less than one year to 48 years. Of the 210 patients with CD, 118 (56%) underwent surgical resection. Sixty one had an ileocaecal resection, 14 a proctocolectomy, in seven cases as a two stage procedure; 12 a segmental colectomy with end-to-end anastomosis and eight a subtotal colectomy with ileostomy. Twenty-one of these 118 patients (18%) had recurrences requiring reoperation; in 11 because of recurrence at the anastomotic site. Life table analysis showed that after 10 years 17% of patients required further resection for recurrence and 8% for relapse. By 20 years the rate of recurrence had risen to 56%. Patients over the age of 30 at first resection were at 1.5 fold greater risk of requiring further surgery than younger patients. The initial site of disease played no role in recurrence and there was no evidence that preoperative disease duration, delay in diagnosis, or late surgery had any effect on recurrence rates. This is one of the few community based studies to measure recurrence and relapse. A balanced appraisal is that surgery is not permanently curative, but the need for further resection may be lower than previously suggested. [ABSTRACT FROM PUBLISHER]

OBJECTIVE To evaluate the impact and effectiveness of an experiential interprofessional education workshop on noninvasive ventilation (NIV) in the setting of a neonatal intensive care unit. METHODS In the present cross-sectional study, a full-day workshop, consisting of didactic and hands-on components, was developed to assess knowledge and perceptions, and to disseminate the latest evidence and practical aspects of NIV use. All health care professionals (HCPs) were asked to participate. Pre- and post-participation questionnaires and knowledge tests were used to assess the effectiveness of knowledge transfer, and to seek participants' reflections on the utility of the workshop. RESULTS Among 214 participants, 206 (96%) and 195 (91%) completed the pre- and post-participation questionnaires, respectively. The majority agreed (14%) or strongly agreed (75%) that NIV education was important for their role. Participants scored their perceived comfort with NIV following the workshop highly (median 5 \[interquartile range (IQR) 1\]) on a five-point Likert scale and 96% would recommend it to a colleague. Median knowledge scores on NIV, assessed as percent correct responses, increased from 74% (IQR 16) to 86% (IQR 11) (P\

Aim: To develop a model for predicting the biological activity of compounds targeting the HIV-1 protease and to establish factors influencing enzyme inhibition. Materials & methods: Machine learning models were built based on a combination of Richard Bader's theory of Atoms in Molecules and topological analysis of electron density using experimental x-ray 'protein-ligand' complexes and inhibition constants data. Results & conclusion: Among all the models tested, logistic regression achieved the highest accuracy of 0.76 on the test set. The model's ability to differentiate between less active and highly active classes was relatively good, as indicated by an AUC-ROC score of 0.77. The analysis identified several critical factors affecting the biological activity of HIV-1 protease inhibitors, including the electron density contribution of hydrogen atoms, bond-critical points and particular amino acid residues. These findings provide new insights into how these molecular factors influence HIV-1 protease inhibition, emphasizing the importance of hydrogen bonding, glycine's flexibility and hydrophobic interactions in ligand binding.

Donepezil and memantine are second-generation antipsychotics widely used in the management of mild to moderate Alzheimer's disease. These drugs are highly selective for the central nervous system, targeting different neural pathways to mitigate cognitive decline. Donepezil is a reversible and specific acetylcholinesterase inhibitor, while memantine is an NMDA receptor antagonist which modulates glutamatergic activity. Although these medications are safe, they are associated with adverse effects, and cardiovascular complications are rare. The reported cardiac adverse drug reactions include bradycardia, atrioventricular block, and prolonged QT interval. We are reporting a case of an 81-year-old male patient with schizophrenia, Alzheimer's disease and bilateral sensorineural deafness receiving oral donepezil and memantine presented with second-degree atrioventricular block. The patient's atrioventricular block recovered completely in 2 to 3 weeks after the discontinuation of donepezil-memantine and with a short course of sympathomimetic drugs., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objective:  Intercenter variation and trends in postnatal steroids (PNS) use among preterm infants for prevention or treatment of bronchopulmonary dysplasia (BPD) is known. Understanding intracenter PNS use patterns facilitate implementation of center-specific change interventions to optimize outcomes.This study aimed to (i) quantify the proportion of infants who received PNS, and describe the timing, type, trends over time, regimen used, and deviations, and (2) describe the clinical characteristics and unadjusted outcomes of infants who received PNS., Study Design:  This was a cohort study in a quaternary neonatal intensive care unit including infants born at less than 33 weeks, and who received PNS for prevention or treatment of BPD between 2011 and 2021. Following data were included: proportion of babies who received PNS; type of PNS; age at initiation and duration; trends over time; deviation from published regimen; morbidity, mortality, and cointerventions., Results:  One hundred and eighty four infants (8% of <33 week' infants) received PNS. The median (interquartile range [IQR]) gestational age and birth weight were 25 (24-26) weeks and 720 (625-841) grams, respectively. The median (IQR) day of initiation and duration of PNS use were 29 (19-38) and 10 (10-22) days, respectively. One hundred and fifty-seven (85%) infants received dexamethasone (DX) and 22 (12%) received hydrocortisone as the first PNS course, and 71 (39%) infants received multiple courses. The proportion of infants receiving PNS remained unchanged, but the cumulative median dose received for BPD per patient increased by 56%. Nearly one-third of cumulative PNS dose came from PNS used for non-BPD indications. Forty-six percent infants had a deviation from published regimen (±20% deviation in duration or ±10% deviation in dose). Survival, survival without major morbidity, moderate-to-severe BPD, and technology dependence at discharge were 87, 2, 91, and 67%, respectively., Conclusion:  Increased variation in PNS use, deviation from published regimen, and concurrent PNS exposure from non-BPD indication offer insights into implementing interventions to improve processes., Key Points: · In this quaternary NICU, 8% of infants born before 33 weeks were administered postnatal steroids (PNS).. · The percentage of infants given PNS remained stable; however, the cumulative dose per patient for BPD rose.. · The study identified targeted interventions to minimize clinical practice variations at the center.., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: Biliary hamartomas are rare congenital development anomaly of bile ducts, which are detected incidentally. They often present as multiple lesions on liver surface which resembles metastatic lesions. We report a case of acute calculous cholecystitis ultimately diagnosed to have asymptomatic multiple biliary hamartomas., Case Description: A 42-year-old male with no co-morbidities presented with pain in upper abdomen associated with fever and vomiting. Contrast enhanced computed tomography (CECT) of abdomen showed acute calculous cholecystitis, hepatomegaly with fatty changes in liver. On laparoscopy the liver was found to have grey-white nodular lesions of about 0.5 cm in diameter scattered on the surface of both the lobes. One of the lesion was biopsied along with cholecystectomy., Discussion: Biliary hamartoma commonly referred to as "von Meyenburg complexes" are uncommon lesions found in the liver which are usually asymptomatic. In this case the patient presented with symptoms of acute cholecystitis but the biopsy report from liver lesions proved to be benign biliary hamartoma which on initial impression looked like multiple liver secondaries., Conclusion: We have described a case of an adult with multiple biliary hamartoma which was an incidental finding. Biliary hamartoma is a rare entity which can sometime mimic metastasis in the liver. Thus, histopathological confirmation is essential before planning any further treatment., Competing Interests: Declaration of competing interest Dr. Deepika C.A declares no conflict of interest in this study. Dr. Poornachandra Thejeswi declares no conflict of interest in this study. Dr. Shivananda Prabhu declares no conflict of interest in this study. Dr. Jyothi Kini declares no conflict of interest in this study. No external funding was obtained for this study., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The purpose of the study was to assess the effects of a novel technique involving facial stretching of the unaffected side along with a structured exercise for the affected side on facial symmetry and facial functions as compared to conventional exercise. A hospital-based parallel-group randomized trial was completed among patients with acute Bell's palsy in Mangalore, India. Participants were randomized to receive facial stretching and a structured exercise program (experimental group) or the conventional exercise regimen (conventional group). Primary outcomes were facial symmetry and voluntary movement; assessed by the Sunnybrook Facial Grading System (SFGS). Both regimens were given for 3 weeks, with baseline, 10th day, and 20th day assessments. Out of 31 participants screened, 24 were eligible and 12 participants each were assigned to experimental and conventional groups. Change scores revealed greater improvement in the SFGS score (p = 0.002) for the experimental group participants. Facial stretching and structured exercise program exhibited promising results in enhancing facial symmetry and function in acute Bell's palsy when compared to conventional exercise regimen., (© 2024. The Author(s).)

Purpose: Dematiaceous fungi, the third most common causative organism of fungal keratitis, constitute 3.5% to 43.5% of fungal keratitis worldwide. Several studies on filamentous fungi (Aspergillus and Fusarium) are available as opposed to that on dematiaceous fungal keratitis. This study aims to describe the profile of dematiaceous fungal keratitis in South India., Methods: This institutional cohort study on culture-proven dematiaceous fungal keratitis was performed in a single ophthalmology referral center in South India for a 6-year period. Records were analyzed for demographic, clinical, microbiological, and treatment outcomes for 3 months from the date of presentation., Results: This study comprised 312 cases involving dematiaceous fungal keratitis (DFK). During the study period, DFK accounted for 10% of microbial keratitis and 24.6% of fungal keratitis cases. The mean (standard deviation) age was 54 (14) years. Males were commonly affected (73.4%). Keratitis was ≤1/3rd depth in 47.8% of cases. Fifty-four cases (17.3%) demonstrated surface pigmentation, and 69 cases (22.1%) had endothelial plaque. Curvularia spp. (99 eyes, 31.7%) was the most common fungal isolate among the speciated fungi. Topical medications resulted in the healing of 63.5% of cases. A total of 193 cases (79%) healed, and 49 cases had to undergo therapeutic penetrating keratoplasty (TPK). Early TPK was performed for 20 cases (40.8%). Seventeen eyes (34.6%) maintained clear grafts at the end of 3 months., Conclusion: In this extensive study on DFK, we report a high incidence of this group of fungal keratitis. We found an excellent healing rate in our cohort of patients., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Background: Working memory (WM) is one of the most influential cognitive functions in encoding, registering, and retrieving information. It influences the learning process in children. Its role becomes essential, especially in a child with a learning disability (LD). Researchers worldwide are giving much prominence to WM, especially in devising cognitive retraining strategies for better cognitive functioning and academic attainment in these children. This current study aims to explore globally used instruments to measure this construct and review effective WM training models in the cognitive rehabilitation of children with LD. This study used a systematic review, availing the elaborate "Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA)" guidelines., Summary: The databases of Google Scholar, PubMed, and Web of Science were searched thoroughly, and those studies, which met the inclusion criteria, were considered for this review. Out of 770 studies found with keywords, only six met the inclusion criteria and were selected for a detailed analysis. The outcome of the current review provides trustworthy evidence of poor performance, especially in tasks involving verbal and executive WM in children with all types of learning disabilities (LD) and difficulties. The studies reviewed support the hypothesis that WM can improve with training and significantly improve children's academic attainment., Key Message: Further this review recommends that research and efforts must go into devising these cognitive training techniques. Children have high cerebral plasticity; hence, using cognitive training (emphasizing WM training and other cognitive functions) with them would enhance their cognitive functioning and capacity, improving their academic performance., Competing Interests: The authors declared no conflict of interest in the context of the research, authorship, and publication of this article., (© The Author(s) 2023.)

A xanthoma is an extremely rare condition that affects the soft tissues and bones and is characterized by a predominance of lipid-rich foamy histiocytes. The onset of xanthomas is frequently accompanied by primary or secondary hyperlipidemia. Primary bone xanthomas are very uncommon benign bone lesions that are not linked to hyperlipidemia. Histopathologically, they are distinguished by histiocytes, an abundance of foam cells or xanthoma cells that contain lipids, and a paucity of multinucleated giant cells. There have only been four reports of primary maxillary xanthoma in the medical literature. We present a rare primary intrabony xanthoma of the anterior maxilla in a 23-year-old normolipidemic female patient with solitary radiolucency. Using CD68, S-100, and CD1a immunohistochemical staining, it is possible to distinguish between macrophage/non-Langerhans histiocytes and Langerhans histiocytes. Therefore, a diagnosis of a central xanthoma of the jaws must be made., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Oral and Maxillofacial Pathology.)

Despite significant improvement in perinatal care and research, hypoxic ischemic encephalopathy (HIE) remains a global healthcare challenge. From both published research and reports of QI initiatives, we have identified a number of distinct opportunities that can serve as targets of quality improvement (QI) initiatives focused on reducing HIE. Specifically, (i) implementation of perinatal interventions to anticipate and timely manage high-risk deliveries; (ii) enhancement of team training and communication; (iii) optimization of early HIE diagnosis and management in referring centers and during transport; (iv) standardization of the approach when managing neonates with HIE during therapeutic hypothermia; (v) and establishment of protocols for family integration and follow-up, have been identified as important in successful QI initiatives. We also provide a framework and examples of tools that can be used to support QI work and discuss some of the perceived challenges and future opportunities for QI targeting HIE., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to assess if 24-hour in-house neonatologist (NN) coverage is associated with delivery room (DR) resuscitation/stabilization and outcomes among inborn infants <29 weeks' gestational age (GA)., Study Design: Survey-linked cohort study of 2,476 inborn infants of 23 to 28 weeks' gestation, admitted between 2014 and 2015 to Canadian Neonatal Network Level-3 neonatal intensive care units (NICUs) with a maternity unit. Exposures were classified using survey responses based on the most senior provider offering 24-hour in-house coverage: NN, fellow, and no NN/fellow. Primary outcome was death and/or major morbidity (bronchopulmonary dysplasia, severe neurological injury, late-onset sepsis, necrotizing enterocolitis, and retinopathy of prematurity). Multivariable logistic regression analysis was used to assess the association between exposures and outcomes and adjust for confounders., Results: Among the 28 participating NICUs, most senior providers ensuring 24-hour in-house coverage were NN (32%, 9/28), fellows (39%, 11/28), and no NN/fellow (29%, 8/28). No NN/fellow coverage and 24-hour fellow coverage were associated with higher odds of infants receiving DR chest compressions/epinephrine compared with 24-hour NN coverage (adjusted odds ratio [aOR] = 4.72, 95% confidence interval [CI]: 2.12-10.6 and aOR = 3.33, 95% CI: 1.44-7.70, respectively). Rates of mortality/major morbidity did not differ significantly among the three groups: NN, 63% (249/395 infants); fellow, 64% (1092/1700 infants); no NN/fellow, 70% (266/381 infants)., Conclusion: 24-hour in-house NN coverage was associated with lower rates of DR chest compressions/epinephrine. There was no difference in neonatal outcomes based on type of coverage; however, further studies are needed as ecological fallacy cannot be ruled out., Key Points: · Lower rates of DR cardiopulmonary resuscitation with 24h in-house NN coverage. · The type of 24h in-house coverage was not associated with mortality and/or major morbidity.. · High-volume centers more often have 24h in-house neonatal fellow coverage., Competing Interests: None declared., (Thieme. All rights reserved.)

Aim: To determine the level of knowledge and skill of basic life support (BLS) among undergraduate, postgraduate students, and general practitioners with and without regular attendance of the BLS Healthcare Provider course., Methodology: The study was carried out at two intervals with two groups. A random sample involving undergraduate students, postgraduate students, and dental professionals was selected for both study groups. Group 1 with 440 participants had not attended BLS for Healthcare Providers Course in the last two years. Group 2 with 410 participants had attended the BLS for Healthcare Providers course regularly once a year. First, participants in Group 1 were evaluated using an MCQ test with 30 questions about their knowledge and skills in BLS. Then, a well-trained BLS instructor team from Dental College & Hospital offered BLS healthcare provider courses to students and dentists. Subsequently, Group 2 participants who had completed a BLS course for healthcare providers last year were also assessed for their knowledge and skills in BLS using another MCQ test., Results: The marks obtained in the tests were tabulated and analyzed. To determine the association between variables with respect to mean knowledge score, t-test was employed. Multiple group comparison was made using analysis of variance and P < 0.05 was considered statistically significant. The group 1 participants score a mean of 5.7 marks against the Group 2 with a mean score of 27.4 marks out of 30 marks. Knowledge and skill in BLS skills among those in Group 1 without prior BLS training was mainly low. Dental practitioners performed marginally better than students in both groups., Conclusions: Based on the results, we make the following observations. With the introduction of BLS training into the academic curriculum and routine BLS hands-on workshops, all healthcare providers will be familiar with the BLS skills to effectively manage the life-threatening emergencies., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 National Journal of Maxillofacial Surgery.)

Increasing usage of plastic has led to the deposition of plastic in the environment which later become microplastic, a pollutant of global concern. These polymeric particles affect the ecosystem by increasing ecotoxicity and impeding the biogeochemical cycles. Besides, microplastic particles have been known for their role in aggravating the effect of various other environmental pollutants including organic pollutants and heavy metals. These microplastic surfaces are often colonized by the microbial communities also known as "plastisphere microbes" forming biofilms. These microbes include cyanobacteria like Nostoc, Scytonema, etc., and diatoms like Navicula, Cyclotella, etc. which become the primary colonizer. In addition to the autotrophic microbes, Gammaproteobacteria and Alphaproteobacteria dominate the plastisphere microbial community. These biofilm-forming microbes can efficiently degrade the microplastic in the environment by secreting various catabolic enzymes such as lipase, esterase, hydroxylase, etc. Besides, these microbes have shown great potential for the bioconversion of microplastic to polyhydroxyalkanoates (PHA), an energy efficient and sustainable alternative to the petroleum based plastics. Thus, these microbes can be used for the creation of a circular economy using waste to wealth strategy. This review provides a deeper insight into the distribution, transportation, transformation, and biodegradation of microplastic in the ecosystem. The formation of plastisphere by the biofilm-forming microbes has been described in the article. In addition, the microbial metabolic pathways and genetic regulations involved in the biodegradation have been discussed in detail. The article suggests the microbial bioremediation and upcycling of microplastic along with various other strategies to effectively mitigate the microplastic pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Increasing industrialization and anthropogenic activities have resulted in the release of a wide variety of pollutants into the environment including pesticides, polycyclic aromatic hydrocarbons (PAHs), and heavy metals. These pollutants pose a serious threat to human health as well as to the ecosystem. Thus, the removal of these compounds from the environment is highly important. Mitigation of the environmental pollution caused by these pollutants via bioremediation has become a promising approach nowadays. Actinobacteria are a group of eubacteria mostly known for their ability to produce secondary metabolites. The morphological features such as spore formation, filamentous growth, higher surface area to volume ratio, and cellular mechanisms like EPS secretion, and siderophore production in Actinobacteria render higher resistance and biodegradation ability. In addition, these bacteria possess several oxidoreductase systems (oxyR, catR, furA, etc.) which help in bioremediation. Actinobacteria genera including Arthrobacter, Rhodococcus, Streptomyces, Nocardia, Microbacterium, etc. have shown great potential for the bioremediation of various pollutants. In this review, the bioremediation ability of these bacteria has been discussed in detail. The utilization of various genera of Actinobacteria for the biodegradation of organic pollutants, including pesticides and PAHs, and inorganic pollutants like heavy metals has been described. In addition, the cellular mechanisms in these microbes which help to withstand oxidative stress have been discussed. Finally, this review explores the Actinobacteria mediated strategies and recent technologies such as the utilization of mixed cultures, cell immobilization, plant-microbe interaction, utilization of biosurfactants and nanoparticles, etc., to enhance the bioremediation of various environmental pollutants., Competing Interests: Conflict of interest statement The authors declare no competing interests., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

The COVID-19 pandemic has caused increased anxiety among medical students due to the uncertainty of the long-term effects on the future of medical education. There are currently insufficient studies aimed at investigating the changes in the mental health and studying habits of medical students during public health emergencies such as this pandemic, as well as methods that can be incorporated to appropriately manage anxiety effectively. To investigate the psychological impact and associated factors on medical students during the pandemic. This retrospective, cross-sectional study consisted of 291 medical students of the faculty of medical sciences at the university of the West Indies, St. Augustine campus, Trinidad and Tobago. The mental health and study habits of said students were assessed with the use of questionnaires via an online survey platform. Data of our study showed that 56% of the students were experiencing increased stress and anxiety. Students of 82.8% experienced irregular sleeping habits and 76.3% of participants experienced a change in eating habits brought on by the pandemic. Participants of 67.4% studied less than 4 hrs. a day, 61.5% were less productive, 62.2% showed an inability to focus and avoid distractions in their study environment during the COVID-19 pandemic. There is a need for proper supportive strategies to assist students in effectively managing anxiety and depression during public health emergencies such as COVID-19. It is suggested that all universities, colleges and education bodies alike implement a pandemic preparedness course as well as an accessible online support forum.

Kyasanur Forest Disease virus (KFDV), a neglected human pathogenic virus, is a Flavivirus that causes severe hemorrhagic fever in humans. KFDV is transmitted to humans by the bite of the hard tick ( Haemaphysalis spinigera ), which acts as a reservoir of KFDV. The recent expansion of the endemic area of KFDV is of concern and requires the development of new preventive measures against KFDV. Currently, there is no antiviral therapy against KFDV, and the existing vaccine has limited efficacy. To develop a new antiviral therapy against KFDV, we focused on the nonstructural proteins NS2B and NS3 of KFDV, which are responsible for serine protease activity. Viral proteases have shown to be suitable therapeutic targets in the development of antiviral drugs against many diseases. However, success has been limited in flaviviruses, mainly because of the important features of the active site, which is flat and highly charged. In this context, the present study focuses on the dynamics of NS2B and NS3 to identify potential allosteric sites in the NS2B/NS3 protease of KDFV. To our knowledge, there are no reports on the dynamics of NS2B and NS3 in KFDV, and the crystal structure of the NS2B/NS3 protease of KFDV has not yet been solved. Overall, we created the structure of the NS2B/NS3 protease of KFDV using AlphaFold and performed molecular dynamics simulations with and without NS2B cofactor to investigate structural rearrangements due to cofactor binding and to identify alternative allosteric sites. The identified allosteric site is promising due to its geometric and physicochemical properties and druggability and can be used for new drug development. The applicability of the proposed allosteric binding sites was verified for the best-hit molecules from the virtual screening and MD simulations.

Janus kinase 2 (JAK2) is emerging as a potential therapeutic target for many inflammatory diseases such as myeloproliferative disorders (MPD), cancer and rheumatoid arthritis (RA). In this study, we have collected experimental data of JAK2 protein containing 6021 unique inhibitors. We then characterized them based on Morgan (ECFP6) fingerprints followed by clustering into training and test set based on their molecular scaffolds. These data were used to build the classification models with various supervised machine learning (ML) algorithms that could prioritize novel inhibitors for future drug development against JAK2 protein. The best model built by Random Forest (RF) and Morgan fingerprints achieved the G-mean value of 0.84 on the external test set. As an application of our classification model, virtual screening was performed against Drugbank molecules in order to identify the potential inhibitors based on the confidence score by RF model. Nine potential molecules were identified, which were further subject to molecular docking studies to evaluate the virtual screening results of the best RF model. This proposed method can prove useful for developing novel target-specific JAK2 inhibitors., (© 2023 Wiley Periodicals LLC.)

Background: It is unclear whether the benefits of administration of antenatal corticosteroids in late preterm gestation outweigh its harms. We sought to understand whether patients and physicians need increased support to decide whether to administer antenatal corticosteroids in late preterm gestation, and their informational needs and preferences for decision-making roles related to this intervention; we also wanted to know if creation of a decision-support tool would be useful., Methods: We conducted individual, semistructured interviews with pregnant people, obstetricians and pediatricians in Vancouver, Canada, in 2019. Using a qualitative framework analysis method, we coded, charted and interpreted interview transcripts into categories that formed an analytical framework., Results: We included 20 pregnant participants, 10 obstetricians and 10 pediatricians. We organized codes into the following categories: informational needs to decide whether to administer antenatal corticosteroids; preferences for decision-making roles regarding this treatment; the need for support to make this treatment decision; and the preferred format and content of a decision-support tool. Pregnant participants wanted to be involved in decision-making about antenatal corticosteroids in late preterm gestation. They wanted information on the medication, respiratory distress, hypoglycemia, parent-neonate bonding and long-term neurodevelopment. There was variation in physician counselling practices, and in how patients and physicians perceived the balance of treatment harms and benefits. Responses suggested a decision-support tool may be useful. Participants desired clear descriptions of risk magnitude and uncertainty., Interpretation: Pregnant people and physicians would likely benefit from increased support to consider the harms and benefits of antenatal corticosteroids in late preterm gestation. Creation of a decision-support tool may be useful., Competing Interests: Competing interests: Jason Burrows is a committee chair with the Society of Obstetricians and Gynaecologists of Canada; regional division head of Maternal–Fetal Medicine with Fraser Health; regional department head and program medical director of the Maternal, Infant, Child and Youth (MICY) program with Fraser Health; chair of the quality management committee of the MICY program with Fraser Health; board member with the Canadian Obstetrics and Gynecology Review Program; and member of the department executive of the University of British Columbia Department of Obstetrics and Gynecology. Amelie Boutin reports a research scholar award from Fonds de recherche du Québec – Santé. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Prolonged periods spent outside the target range of oxygen saturation (SpO 2 ) in preterm infants, along with frequent desaturation events, predispose them to retinopathy of prematurity (ROP) and long-term neurodevelopmental impairment. The primary aim of this study was to increase the mean time spent within the target SpO 2 range (WTR) by 10% and to reduce the frequency of desaturation events by 5 events per patient day, respectively, within 18 months of implementing a care bundle., Methods: This study was completed in a 46-bed neonatal intensive care unit (NICU), involving 246 staff members and led by a quality improvement team. The change interventions included implementing new practice guidelines, reviewing daily summaries of SpO 2 maintenance, daily infant wellness assessment, standardizing workflow, and responding to SpO 2 alarms. In addition, we collected staff satisfaction and compliance with change interventions, resource use, and morbidity and mortality data at discharge., Results: The mean time spent WTR increased from 65.3% to 75.3%, and the frequency of desaturation events decreased from 25.1 to 16.5 events per patient day, respectively, with a higher magnitude of benefit in infants on days with supplemental oxygen. Postimplementation, the duration of high-frequency ventilation and supplemental oxygen were lower, but morbidity and mortality rates were similar. Staff satisfaction with training workshops, coaching, use of the infant wellness assessment tool, and SpO 2 alarm management algorithms were 74%, 82%, 80%, and 74%, respectively., Conclusion: Implementing a care bundle to improve oxygen maintenance and reduce desaturation events increased the time spent WTR and reduced the frequency of desaturation events., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Molecular docking is the most popular and widely used method for identifying novel molecules against a target of interest. However, docking procedures and their validation are still under intense development. In the present investigation, we evaluate a quantum free-orbital AlteQ method for evaluating docking complexes generated by taking EGFR complexes as an example. The AlteQ method calculates the electron density using Slater's type atomic contributions in the interspace between the receptor and the ligand. Since the interactions are determined by the overlap of electron clouds, they follow the complementarity principle, and an equation can be obtained that describes these interactions. The AlteQ method evaluates the quality of the interaction between the receptor and the ligand, how complementary the interactions are, and due to this, it is used to reject less realistic structures obtained by docking methods. Here, three different equations were used to determine the quality of the interactions in experimental complexes and docked complexes obtained using AutoDock Vina and AutoDock 4.2.6.Communicated by Ramaswamy H. Sarma.

Curcumin (diferuloylmethane) is bioactive phenolic compound which exerts diverse antimetastatic effect. Several studies have reported the antimetastatic effect of curcumin by its ability to modulate the epithelial-to-mesenchymal transition (EMT) process in different cancers, but underlying molecular mechanism is poorly understood. EMT is a highly conserved biological process in which epithelial cells acquire mesenchymal-like characteristics by losing their cell-cell junctions and polarity. As a consequence, deviation in cellular mechanism leads to cancer metastasis and thereby death. In this perspective, we explored the antimetastatic potential and mechanism of curcumin on the EMT process by establishing in vitro EMT model in lungs cancer (A549) cells induced by TGF-β1. Our results showed that curcumin mitigates EMT by regulating the expression of crucial mesenchymal markers such as MMP2, vimentin and N-cadherin. Besides, the transcriptional analysis revealed that the curcumin treatment differentially regulated the expression of 75 genes in NanoString nCounter platform. Further protein-protein interaction network and clusters analysis of differentially expressed genes revealed their involvement in essential biological processes that plays a key role during EMT transition. Altogether, the study provides a comprehensive overview of the antimetastatic potential of curcumin in TGF-β1-induced EMT in lung cancer cells., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03360-7., Competing Interests: Conflict of interestNo conflict of interest., (© King Abdulaziz City for Science and Technology 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: To evaluate the level of disability and identify an association between sociodemographic and clinical variables and disability in patients with bipolar disorder (BD)., Methods: This cross-sectional study was conducted in a tertiary care general hospital psychiatric unit with 100 patients with BD in partial or full remission ( DSM-IV-TR criteria) from January 2017 to March 2018. Patients were assessed using a semistructured proforma, the Mini-International Neuropsychiatric Interview 5.0-Hindi version, the Hamilton Depression Rating Scale (HDRS) or the Young Mania Rating Scale (YMRS), and the Indian Disability Evaluation and Assessment Scale (IDEAS)., Results: All patients with BD had at least mild disability. The mean ± SD IDEAS global score was 5.1 ± 2.59. Of the sample, 66% and 34% had mild or moderate, disability, respectively. The global score of disability was associated with the number of episodes, number of manic episodes, frequency of episodes in the past year, YMRS and HDRS scores, partial remission, and hospitalization. Categories of disability were associated with the type of last episode, type of remission, and treatment setting., Conclusions: Patients with BD had at least a mild level of disability even during remission. Disability worsened with the increasing number, frequency, and severity of episodes; number of manic episodes; partial remission; and hospitalization., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Purpose: Pythium insidiosum causes a rare sight-threatening keratitis and is a devastating ocular pathology with a high morbidity. It is frequently mistaken as fungal keratitis. Here we highlight a rare case of pediatric Pythium insidiosum keratitis which was successfully managed using an antibiotic combination of linezolid and azithromycin with cyanoacrylate glue., Case Description: A 9-year-old young male child presented to our clinic with defective vision, pain, redness in the right eye for 5 days post stick injury. In the right eye, Snellen's best-corrected visual acuity (BCVA) was 6/12 which deteriorated to hand movements within 5 days of treatment. Ocular examination revealed 6 × 5 mm dry-looking mid stromal corneal infiltrate with feathery margin involving the visual axis. The clinical picture was suggestive of fungal keratitis. Corneal scraping and smear examination with 10% KOH and Gram stain revealed long slender hyaline hyphae with sparse septations. Before the culture result, the patient was started on 5% Natamycin and 1% Itraconazole hourly, but still, the infiltrate progressed. Further, P. Insidiosum keratitis was considered as the differential, which was confirmed on blood agar culture. After receiving culture results, the patient was managed with 0.2% Linezolid and 1% Azithromycin hourly. Due to the rapid progression of infiltrate, corneal melt, and younger age, cyanoacrylate glue, and bandage contact lens were used. On the last follow-up, the BCVA recovered to 6/12., Conclusion and Importance: Prompt diagnosis, clinical awareness, and a specific treatment regime is needed for managing this devastating corneal entity. Cyanoacrylate glue due to its antibacterial properties can be a potential rescuer and can be considered for managing these cases.

Objective: To characterize variations in practices and outcomes for neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH) across Canadian tertiary Neonatal Intensive Care Units (NICUs)., Study Design: Retrospective study of neonates admitted for HIE and treated with TH in 24 tertiary NICUs from the Canadian Neonatal Network, 2010-2020. The two primary outcomes of mortality before discharge and MRI-detected brain injury were compared across NICUs using adjusted standardized ratios (SR) with 95% CI., Results: Of the 3261 neonates that received TH, 367 (11%) died and 1033 (37%) of the 2822 with MRI results had brain injury. Overall, rates varied significantly across NICUs for mortality (range 5-17%) and brain injury (range 28-51%). Significant variations in use of inotropes, inhaled nitric oxide, blood products, and feeding during TH were identified (p values < 0.01)., Conclusion: Significant variations exist in practices and outcomes of HIE neonates treated with hypothermia across Canada., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Psychiatric comorbidity in patients with bipolar disorder (BD) has been associated with an earlier onset, rapid cycling, worsening severity and outcome, and increased suicidality. Patients with BD have been reported to have poor quality of life (QOL) even during remission., Aims and Objectives: Estimate the prevalence of psychiatric comorbidity and assess the QOL in patients with BD, and find the associated sociodemographic and clinical variables., Materials and Methods: This cross-sectional study was done in a general hospital psychiatric unit on 100 patients (both inpatients and outpatients) with DSM-IV-TR BD in partial or complete remission. Patients were assessed using a semi-structured pro forma, Mini International Neuropsychiatric Interview 6.0 - Hindi version, Hamilton Rating Scale for Depression or Young Mania Rating Scale and World Health Organization QOL instrument, short-form (WHOQOL-BREF), Hindi Version., Results: Sixty-one percent of the sample had at least one psychiatric comorbidity, and the commonest comorbid disorders were substance use disorders (SUD) (30%) and anxiety disorders (AD) (28%). Male gender was identified as a predictor for comorbidity in BD. The mean QOL-BREF score was 85.96 ± 14.35. Poor QOL was associated with older age at onset of comorbidity, multiple comorbidities, mixed episodes, rapid cycling, partial remission, and increased severity of depression while patients with current hypomanic symptoms were found to have better QOL. BD with comorbidity had worse QOL than those without comorbidity., Conclusion: The majority of patients with BD had at least one comorbidity. SUD were the most common comorbid disorders. QOL, already poor in BD patients, was poorer in cases with comorbidity., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Industrial Psychiatry Journal.)

Background: Tuberculosis (TB) is one of the major systemic conditions which is a preventable and curable infection but remains a significant cause of death. The WHO, in its global plan to stop TB reports, that poor treatment has resulted in the evolution of Mycobacterium tuberculosis strains that do not respond to treatment with the standard first-line combination of anti- tuberculosis medicines, resulting in the emergence of multidrug-resistant tuberculosis in almost every country of the world.The present study was aimed to assess the physical and chemical property of stimulated and unstimulated saliva and identify if any association exist with alterations in taste perception in patients with antituberculosis medications., Methods: A total of 30 patients on anti-tuberculosis drugs were considered as cases and 30 healthy volunteers were considered as controls and included in the study. All study subjects were assessed for their physical property like flow rate, viscosity, pH and chemical property like sodium, potassium, calcium, phosphorous of stimulated and unstimulated saliva. All the subjects on Anti-tuberculosis drugs were assessed for change in taste perceptions using the standard questionnaire., Results: There is a significant decrease in the flow rate (0.34 ± 0.06) and pH (5.89 ± 0.37) of unstimulated saliva of patients and the flow rate (0.38 ± 0.07) and viscosity (1.34 ± 0.28) of stimulated saliva among the case group compare to the control group. All the electrolytes' concentrations such as sodium, potassium, calcium, and phosphorous values were significantly altered in stimulated and unstimulated saliva of the case group compared to the control group in which p-value < 0.05 was considered., Conclusion: There are significant changes in physical and chemical properties of both stimulated and unstimulated saliva which has an effect on taste perception inpatient with anti-tuberculosis medications. Hence, salivary flow rate, pH, viscosity, and salivary electrolytes of tuberculosis patients should be considered as important parameters in guiding the diet, so that there will be an improvement in their taste perception and medication protocol, thus maintaining their nutritional status which leads to improving their health., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Ltd.)

The rising plastic pollution deteriorates the environment significantly as these petroleum-based plastics are not biodegradable, and their production requires natural fuels (energy source) and other resources. Polyhydroxyalkanoates (PHAs) are bioplastic and a sustainable and eco-friendly alternative to synthetic plastics. PHAs can be entirely synthesized using various microorganisms such as bacteria, algae, and fungi. These value-added biopolymers show promising properties such as enhanced biodegradability, biocompatibility, and other chemo-mechanical properties. Further, it has been established that the properties of PHA polymers depend on the substrates and chemical composition (monomer unit) of these polymers. PHAs hold great potential as an alternative to petroleum-based polymers, and further research for economic production and utilization of these biopolymers is required. The review describes the synthesis mechanism and different properties of microbially synthesized PHAs for various applications. The classification of PHAs and the multiple techniques necessary for their detection and evaluation have been discussed. In addition, the synthesis mechanism involving the genetic regulation of these biopolymers in various microbial groups has been described. This review provides information on various commercially available PHAs and their application in multiple sectors. The industrial production of these microbially synthesized polymers and the different extraction methods have been reviewed in detail. Furthermore, the review provides an insight into the potential applications of this biopolymer in environmental, industrial, and biomedical applications., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Tobacco is the most significant social burden and the leading cause of death. Tobacco is derived from "Nicotiana tabacum" which has nicotine as the main component. There are various disadvantages from tobacco on health which are reported in the medical literature. But the risk of caries among these tobacco users, such as chewers and smokers, is still debatable. Hence, the present study aims to determine the prevalence of dental caries among tobacco chewers and smokers., Materials and Methods: In this study, 389 individuals were included. Out of 389 individuals, 304 were men and 85 were women aged between 18 and 60 years. They were classified into two groups. Group A had 207 individuals with habitual tobacco chewing, and Group B had 182 individuals with habitual tobacco smoking and provided a 6 months history. The DMFT index (Decayed, Missing, and filled teeth index-WHO modification 1997) was used to assess caries., Results: The study revealed a higher prevalence of dental caries among tobacco chewers compared to tobacco smokers. The DMFT scores were higher among gutka chewers compared to other types of tobacco use. The lower posterior tooth region showed higher dental caries in tobacco chewers compared to smokers., Conclusion: The higher presence of caries in the tobacco chewing group is due to the presence of sweeteners, which act as cariogenic agents. Similarly, smokers have a thiocyanate component that acts as an anticariogenic agent; therefore, the prevalence of caries was lower in tobacco smokers., Competing Interests: All authors declare that they have no conflict of interest., (© 2022 Published by Elsevier B.V. on behalf of Craniofacial Research Foundation.)