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Abstract Spatiotemporal analysis is a critical tool for understanding COVID-19 spread. This study examines the pattern of spatial distribution of COVID-19 cases across India, based on data provided by the Indian Council of Medical Research (ICMR). The research investigates temporal patterns during the first, second, and third waves in India for an informed policy response in case of any present or future pandemics. Given the colossal size of the dataset encompassing the entire nation’s data during the pandemic, a time-bound convenience sampling approach was employed. This approach was carefully designed to ensure a representative sample from advancing timeframes to observe time-based patterns in data. Data were captured from March 2020 to December 2022, with a 5-day interval considered for downloading the data. We employ robust spatial analysis techniques, including the Moran’s I index for spatial correlation assessment and the Getis Ord Gi* statistic for cluster identification. It was observed that positive COVID-19 cases in India showed a positive auto-correlation from May 2020 till December 2022. Moran’s I index values ranged from 0.11 to 0.39. It signifies a strong trend over the last 3 years with $$r^2$$ r 2 of 0.74 on order 3 polynomial regression. It is expected that high-risk zones can have a higher number of cases in future COVID-19 waves. Monthly clusters of positive cases were mapped through ArcGIS software. Through cluster maps, high-risk zones were identified namely Kerala, Maharashtra, New Delhi, Tamil Nadu, and Gujarat. The observation is: high-risk zones mostly fall near coastal areas and hotter climatic zones, contrary to the cold Himalayan region with Montanne climate zone. Our aggregate analysis of 3 years of COVID-19 cases suggests significant patterns of interconnectedness between the Indian Railway network, climatic zones, and geographical location with COVID-19 spread. This study thereby underscores the vital role of spatiotemporal analysis in predicting and managing future COVID-19 waves as well as future pandemics for an informed policy response.

Pyruvate Kinase M2 (PKM2) mediates metabolic reshuffling and is ubiquitously upregulated in several cancer types. The non-metabolic function of PKM2 as key nuclear kinase and modulator of gene expression is instrumental in cancer progression and tumorigenesis. Here, we attempt to discern the non-canonical function of PKM2 as an epigenetic modulator and the underlying implication of this activity. Using 5'-FAM labelled reconstituted mononucleosome we have shown that PKM2 interacts with the complex through Histone H3 and possibly obstruct the access to DNA binding factors. Subsequently, the interaction negatively impacts the ATP dependent remodeling activity of Chromodomain Helicase DNA binding protein-7 (Chd7). Chd7 remodeling activity is required to ameliorate DNA damage and is crucial to genome stability. Our study shows that PKM2 blocks the Chd7 mediated sliding of nucleosome. It can be conjectured that stalling Chd7 may lead to impaired DNA damage and increased genomic instability. We propose a mechanism in which PKM2 negatively regulate nucleosome repositioning in chromatin and may exacerbate cancer by altering the nucleosome architecture. This research is imperative to our understanding of how altered cancer metabolism can potentially modulate the gene expression and sustain incessant proliferation by tweaking the chromatin topography.

Introduction: Social and familial stigma and prejudices make treatment-seeking difficult in women substance abusers. An analysis of various social, familial, personal, and other correlates of the treatment seekers can help in an appropriate understanding of the problem and can help in a better assessment, management and prevention of this problem. Aim: To study the socio-demographic and clinical profile of women attending a de-addiction centre in north eastern Uttar Pradesh, India. Design and Methodology: Out of the entire charts registered in the de-addiction unit of the psychiatry department of Sir Sunderlal hospital, Institute of Medical Science, Banaras Hindu University, Varanasi. The chart review of women substance abusers was undertaken. Results: The results indicated that in a period of two years 42 females had sought treatment typically the subjects were more than 21 years of age (76%), urban (69%), married (88.3%), belonging to nuclear family (76%), working (67%), illiterate (50%), and belonging to MSES (82%). The common substances were tobacco 75%, opioids 14.3%, cannabis 7.1%, and alcohol 2.6%. The mean age at onset of substance use was 33.5 years. The common factors associated with initiating use were pain, iatrogenic and positive family history of substance use (60%). Conclusions: The results suggest that the development of substance dependence in women is a combination of medical, personal, and social vulnerability factors, including the illicit prescriptions.

Introduction: Dexmedetomidine, an a2 agonist, can be used as an adjuvant in general anaesthesia as it attenuates the stress response to various noxious stimuli and helps in maintaining the perioperative haemodynamic stability along with sedation and not causing any significant respiratory depression in the postoperative period. Aim: To study the difference in haemodynamic responses of dexmedetomidine and fentanyl in patients undergoing laparoscopic surgery. Materials and Methods: Sixty patients were divided into two groups of 30 each randomly. In Group F, fentanyl 0.5 μg/kg as loading dose over 10 minutes prior to induction followed by 0.2-0.7 μg/kg/hr as maintenance dose and in Group D, Dexmedetomidine 0.5 μg/kg as loading dose over 10 minutes prior to induction followed by 0.2 μg/kg/hr-0.7 μg/kg/hr as maintenance dose till surgery was over. Haemodynamic variables and Visual Analogue Scale (VAS) scores were recorded continuously. Postoperative sedation and recovery were assessed by modified Ramsay sedation score. Results: Systolic Blood Pressure (SBP) fell by 9% in Group-D as compared to no fall in Group F during intubation. After intubation, 9% increase is seen in Group D v/s 19% in Group F. During the period of pneumoperitoneum upto 5 minutes post extubation, the SBP in Group D was significantly lower as compared to Group F rest duration, the difference was not significant between both groups. Heart Rate (HR) remained stable throughout the study except at laryngoscopy when it rose. Heart rate was similar in both groups at intubation, decreased by 3.51% in Group D as compare to 11.11% rise in Group F. Post intubate on, heart rate fell by 2% in Group D vs 15% rise in Group F. Diastolic Blood Pressure (DBP) remained higher than baseline than throughout the study. After intubation, 3% higher in Group D where as 15% in Group F increase was seen. In intraoperative period the difference between both groups was not significant. There was significant difference between two groups at 10 minutes, 45 minutes of pneumoperitoneum. End Tidal CO2 (ETCO2 ) was similar in both groups. Conclusion: Dexmedetomidine is better drug as compared to fentanyl for maintaining the haemodynamic response during intubation and intraoperative period.

Background: Substance abuse and mental disorder often coexist and may cause several consequences in sociooccupational functioning and health care and management. Indian data are sparse in this area. Objectives: The aim of the study was to examine the sociodemographic profile, pattern, and prevalence of alcohol and substance use among person suffering with mental illness and to compare with those without mental illness. Methods: A total of 80 treatment-seeking patients with mental illness and 80 nontreatment seeking healthy accompanying persons were assessed for current substance use. Mental illness was screened using Structured Clinical Interview for DSM-IV Axis I Disorders and the diagnosis was made as per DSM IV, semi-structured sociodemographic pro forma was also applied. The data collected were analyzed using the Chi-square and Student's t-test. Results: Substance use was found 2.5 times higher among cases (56.2%) than controls (22.5%). Substance-using participants comprised mainly males belonging to rural residence. The substance using cases were more unmarried, less educated, poorer economically, and more nuclear family structures that substance-using controls. When compared with non-substance using cases, cases with substance use had more males than females and lower education. Although both groups were almost similar in term of marital status, family structure, residence, and socioeconomic status. Among both groups, most common substance use was tobacco, followed by alcohol and cannabis. Although all the substances were more prevalent among cases than controls. The prevalence of any substance use was highest among cases with psychotic disorder (77.3%), followed by unipolar depression (62.5%), bipolar affective disorder (41.7%), and anxiety disorders (21.4%). Tobacco and cannabis use was most prevalent among cases suffering with psychotic disorders, whereas alcohol use was most prevalent among cases suffering with unipolar depression. Conclusions: Mentally ill individuals are vulnerable to develop substance use, thus they are doubly jeopardized. The susceptibility of these individuals stem from lesser insight, need for stimulation, to decrease the anhedonia induced by psychoactive medicines and poor awareness hence this group of individuals has several health and social consequences; therefore, they require due attention. A better care, support, and education are needed for substance using patients with mental illness to improve their prognosis and also help in their appropriate rehabilitation.

The chromatin landscape and promoter architecture are dominated by the interplay of nucleosome and transcription factor (TF) binding to crucial DNA sequence elements. However, it remains unclear whether nucleosomes mobilized by chromatin remodelers can influence TFs that are already present on the DNA template. In this study, we investigated the interplay between nucleosome remodeling, by either yeast ISW1a or SWI/SNF, and a bound TF. We found that a TF serves as a major barrier to ISW1a remodeling, and acts as a boundary for nucleosome repositioning. In contrast, SWI/SNF was able to slide a nucleosome past a TF, with concurrent eviction of the TF from the DNA, and the TF did not significantly impact the nucleosome positioning. Our results provide direct evidence for a novel mechanism for both nucleosome positioning regulation by bound TFs and TF regulation via dynamic repositioning of nucleosomes.

Chromatin assembly involves the combined action of ATP-dependent motor proteins and histone chaperones. Because motor proteins in chromatin assembly also function as chromatin remodeling factors, we investigated the relationship between ATP-driven chromatin assembly and chromatin remodeling in the generation of periodic nucleosome arrays. We found that chromatin remodeling-defective Chd1 motor proteins are able to catalyze ATP-dependent chromatin assembly. The resulting nucleosomes are not, however, spaced in periodic arrays. Wild-type Chd1, but not chromatin remodeling-defective Chd1, can catalyze the conversion of randomly-distributed nucleosomes into periodic arrays. These results reveal a functional distinction between ATP-dependent nucleosome assembly and chromatin remodeling, and suggest a model for chromatin assembly in which randomly-distributed nucleosomes are formed by the nucleosome assembly function of Chd1, and then regularly-spaced nucleosome arrays are generated by the chromatin remodeling activity of Chd1. These findings uncover an unforeseen level of specificity in the role of motor proteins in chromatin assembly.

The advent of the Internet as a global communication medium has brought about a new focus on an area of research in designing intelligent tutoring systems (ITS), that has not been adequately considered so far mainly due to the localised nature of most academic environments. The area is brought into focus due to the need for adaptation to local contexts in the case of ITS used by students in different parts of the world. The issue, however, is not limited to the use of academic resources at vast distances only. There is bound to be a distinction between the roles of "ITS designer teacher" and "ITS implementer teacher", with those involved possessing different personality attributes, styles, and preferences. Researchers frequently come across teachers who distrust the ITS as embodying the beliefs of the ITS designer and not their own pedagogy. This paper argues for the need of a Human Teacher Model in the ITS which provides adequate consideration of the attributes and role of a human teacher - both as a designing collaborator and a teaching collaborator within a joint cognitive system consisting of the ITS, students and human teachers.

PURPOSE: The present study deals with evaluation of crosslinked poly vinyl alcohol (PVA) as a potential disintegrant. METHODS: Crosslinking of PVA was carried out using glutaraldehyde as a crosslinker, in presence of acidic conditions. The crosslinking reaction was optimized for a) polymer: crosslinker ratio; b) temperature requirement and c) reaction duration. Certain physical parameters of the disintegrant (including sedimentation volume, hydration capacity, specific surface area and bulk and tap density) were determined and compared to the known disintegrants. Characterization was carried out using FT-IR, DSC, XRD, SEM and Photo microscopy studies. The developed excipient was also studied for acute toxicity in rats and found to be safe for oral use. RESULTS: Disintegration property of formed product was compared to known disintegrant (Ac-Di-Sol) and it was found to give better results. The disintegration mechanism of developed disintegrant was postulated based on results obtained from various physical evaluations including: Study of effect of disintegrant concentration, fillers, and hardness, mode of incorporation and method of granulation on disintegration activity. CONCLUSIONS: By changing the condition parameters of well known crosslinking reaction of PVA, we obtained a crosslinked product which had excellent disintegration activity, good flow and optimal tableting properties.

α-Amylases are essential biocatalysts representing a billion-dollar market with significant long-term global demand. They have varied applications ranging from detergent, textile, and food sectors such as bakery to, more recently, biofuel industries. Microbial α-amylases have distinct advantages over their plant and animal counterparts owing to generally good activities and better stability at temperature and pH extremes. With the scope of applications expanding, the need for new and improved α-amylases is ever-growing. However, scaling up microbial α-amylase technology from the laboratory to industry for practical applications is impeded by several issues, ranging from mass transfer limitations, low enzyme yields, and energy-intensive product recovery that adds to high production costs. This review highlights the major challenges and prospects for the production of microbial α-amylases, considering the various avenues of industrial bioprocessing such as culture-independent approaches, nutrient optimization, bioreactor operations with design improvements, and product down-streaming approaches towards developing efficient α-amylases with high activity and recyclability. Since the sequence and structure of the enzyme play a crucial role in modulating its functional properties, we have also tried to analyze the structural composition of microbial α-amylase as a guide to its thermodynamic properties to identify the areas that can be targeted for enhancing the catalytic activity and thermostability of the enzyme through varied immobilization or selective enzyme engineering approaches. Also, the utilization of inexpensive and renewable substrates for enzyme production to isolate α-amylases with non-conventional applications has been briefly discussed. [ABSTRACT FROM AUTHOR]

Introduction: One of the disabilities perceived by elderly people which has the most profound effect on day-to-day living is knee osteoarthritis. The present study focused on elderly people with objectives of assessing the prevalence of functional disabilities due to chronic musculoskeletal knee pain with concerned determinants. Assessment of quality of life (QoL) and exploring various perceptions regarding debility were ancillary objectives. Methodology: A cross-sectional study with a mixed method approach was conducted among elderly people at urban field practice area of one of the tertiary health-care institutes of Ahmedabad city, Gujarat. The calculated sample size of 220 was collected by systematic random sampling. A pretested, validated, semistructured questionnaire including Western Ontario and McMaster Universities (WOMAC) Osteoarthritis index with information pertaining to pain, stiffness, and functional disability was used to collect quantitative part. For qualitative assessment, in-depth interviews were taken using interview guide. Results: The prevalence of chronic knee pain was 70%, of which 63% had functional disability. Various determinants such as gender, age, socioeconomic class, occupation, and body mass index were found to have a statistically significant association with severity of knee pain/functional disability. Qualitative research revealed that majority of participants were dissatisfied with their current QoL, primarily due to dependent attitude for quotidian chores, while some of them perceived socially isolated due to compromised physical capacity. Acceptance for ailment with belief of “condition is common unpreventable fate in old-age” and surgical intervention with adverse/futile outcome in a few peer age-group cohorts enrooted attitude of not visiting any health-care facility among study participants. Conclusion: More than three-fifth of the study participants had severe/extreme WOMAC score which was most probable reason for perceived dissatisfied life quality. More than three-fifth of the study participants had severe/extreme WOMAC score representing reason for perceived dissatisfied life quality. Adopted common ethnicity of demeanor in routine chores found statistically significant association with functional disability, while certain beliefs were decisive for initiating or sustained treatment.

Background: The high contagiousness of the COVID 19 disease, the uncertain course, and the high morbidity and mortality has led to unprecedented burden on the health care system, especially when the crisis has gone on for more than 5 months with no end in sight. The chronic high degree stress has made burnout in health care workers (HCWs) a reality that needs urgent attention which can otherwise lead to compromised patient care apart from their own suffering. Aims and Objectives: This study was planned to assess and compare the burnout in doctors and nurses of our dedicated COVID 19 hospital, to understand its correlates, and look for any implications on future policy decisions. Materials and Methods: Our study assessed and compared the burnout in 150 doctors and 150 nurses of our dedicated COVID 19 hospital using the Copenhagen Burnout Inventory (CBI). The CBI Scale is a 19 item scale including three domains of burnout in the form of personal (1–6), work related (7–13), and patient related burnout (14–19). More than 25% average score on these items is taken as the presence of burnout. Results: We found burnout in 58% of all HCWs with 78% in doctors (n = 150) and 38% in nurses (n = 150), the difference being statistically significant. Multiple linear regression analysis was performed to find common factors affecting burnout among both the groups, which were female gender, facing stigma due to COVID 19 duty, regular exercise/yoga, and dissatisfaction with administrative services. Our findings propose to emphasize the need to address the impact of working under pressure for sustained periods among HCWs.

Introduction: The global scale of COVID-19 has been enormous, with the disease affecting 20 million people worldwide and resulting in 751,154 deaths by August 14, 2020. An increase in mental health problems is expected with an event of such scale, given past experience with epidemics such as severe acute respiratory syndrome and Ebola, among various vulnerable populations. One such population may be the family members of patients affected with COVID-19. Methods: This was a cross-sectional study. Five hundred and forty-one relatives of patients admitted in the COVID-19 wing of a tertiary care hospital were studied. Sociodemographic details were recorded and a Gujarati version of General Health Questionnaire-28 (GHQ-28) was applied. A total score of ≥4 on GHQ-28 was considered indicative of “caseness” or psychiatric morbidity and the population was divided into two groups based on whether the score was

Prostate adenocarcinoma is a common urologic malignant neoplasm in man. Distant cutaneous metastases (CMs) of prostate carcinoma are extremely rare with a reported incidence of 0.36% and usually they occur late. Clinically, cutaneous metastasis of prostate carcinoma can mimic other skin conditions such as cellulitis, sebaceous cyst, zosteriform lesions, telangectasias, and more, resulting in a poor recognition. Few cases of true cutaneous metastatic prostate carcinoma exist in the literature. We present a case, where the first sign of carcinoma of the prostate was CM over the anterior abdominal wall. Radiological and histopathological confirmation pointed to a diagnosis of carcinoma of the prostate. The patient was treated with orchidectomy and was started on bicalutamide. After 1 month of bicalutamide therapy there was subjective decrease in the size of the metastasis. A high index of suspicion is required while evaluating the different differential diagnoses of this entity particularly in elderly patients.

Tamoxifen is a selective oestrogen receptor modulator used for the treatment of oestrogen/progesterone receptor positive breast cancer. It possess antagonistic or agonistic activity depending on the tissue location i.e., antagonistic action on breast but agonist action on endometrium and bones. The side effects of tamoxifen include hot flushes, gynaecologic symptoms (vaginal dryness, vaginal discharge), depression, forgetfulness, sleep alterations, weight gain, alteration of lipoprotein metabolism, thromboembolic disorder. Tamoxifen, like oestrogens, increases the plasma level of triglycerides and liver secretion of Very Low Density Lipoprotein (VLDL). Moreover, it inhibits the key enzymes of triglyceride metabolism. However, there are few cases of severe tamoxifen induced hypertriglyceridemia and pancreatitis. Hypertriglyceridemia is one of the risk factor for acute pancreatitis. Here we present a case of tamoxifen-induced hypertriglyceridemia and acute pancreatitis in a 50-year-old female without any comorbidity. She was treated with supportive antibiotics and supportive therapy. About one week after discharge, patient was started on letrozole 2.5 mg once a day. Clinicians must be aware of this rare side effect of tamoxifen, so baseline and periodic testing of triglyceride level must be done to avoid such complications.