Developmental events in the mandibular salivary gland of Indian sheep (Ovis aries): Morphological and histochemical studies.

At 22nd day of fetal development, the primordial anlage of mandibular gland was first noticed as a solid epithelial bud from oral epithelium. The terminal buds were arranged in the form of clusters with undifferentiated epithelial cells and terminated in a bulb like structure in 28-day-old fetus. The lumenization and branching of the main cord was noticed at 35th day. The primary septa, which divide the glandular mass into lobes was observed from 53rd day onwards which resulted in the formation of distinct lobulation at 58th day. At 61st day, the capsule formation was initiated by the aggregation of mesenchymal tissue. The terminal tubules differentiated to form the secretory end pieces and the tubular portion leads to the formation of intercalated and striated ducts at 98th day. Predominantly mucous types of acinar cells were seen from 108th day onwards. The number of lobules increased with steep increase in parenchyma from 128th day onwards. Micrometrical studies revealed that the mean diameter of acinar cells and all ducts was increased with the advancement of age and the significant differences were observed between groups. Localization of acidic and neutral mucopolysaccharides was observed in mucous cells and goblet cells. RESEARCH HIGHLIGHTS: The primordial anlage of mandibular salivary gland was seen at 22nd day. Lobulation of gland was appeared at 53rd day of development, however; it was completed at 58th day. At 98th day, the terminal tubules differentiated to form the secretory end pieces. The parenchyma of the gland showed predominantly mucous type of cells from 108th day onwards. Myoepithelial cells were first appeared as flattened basal cells initially around the developing acinar cells at 132nd day. Localization of acidic as well as neutral mucopolysaccharides was observed in mucous cells and goblet cells. Fine lipid droplets were observed in intralobular as well as interlobular connective tissue, however; phospholipids were observed in the cell membrane of secretory cells and ducts.

Comprehensive Analysis of Omicron Subvariants: EG.5 Rise, Vaccination Strategies, and Global Impact.

The emergence of new variants of the SARS-CoV-2 virus during the COVID-19 pandemic has prompted significant developments in the understanding, monitoring, and response to these strains. This comprehensive review focuses on two prominent variants of interest (VoI), XBB. 1.5 (Kraken) and XBB.1.16 ("Arcturus"), along with seven variants under observation (VuM), including EG.5. The World Health Organization (WHO) identified these variants in July 2023, highlighting EG.5's noteworthy rise in prevalence. EG.5, also known as "Eris," has exhibited an increased effective reproductive rate, prompting concerns about its contagiousness and immune evasion capabilities. With an altered spike protein in the Receptor-Binding Domain (RBD), EG.5 shares similarities with XBB.1.5 but surpasses it in prevalence, constituting 20% of COVID-19 cases in the United States by late August. EG.5's subvariant, EG.5.1, poses challenges with mutations like Q52H and F456L, contributing to its ability to bypass neutralizing antibodies. The global distribution of SARS-CoV-2 variants presents a dynamic landscape, with XBB.1.16 and other strains gaining prominence. The advent of the BA.2.86 variant further complicates the scenario, with its notable spread in regions lacking robust viral surveillance. A thorough analysis of mutations reveals the evolving nature of the Omicron variant, with distinct amino acid changes characterizing XBB.1.5, XBB.1.16, and EG.5. The WHO designates EG.5 as a "variant of interest" due to its increased contagiousness and potential immune evasion, emphasizing the need for vigilant monitoring. The risk assessment of EG.5 underscores its rapid development and growing prevalence globally. While booster vaccines targeting XBB.1.5 are in development, antiviral medications like nirmatrelvir/ritonavir (Paxlovid) continue to exhibit efficacy. In the context of the evolving variants, the FDA has granted emergency use authorization for updated COVID-19 vaccines targeting circulating strains, reflecting the adaptability of vaccination strategies to address emerging challenges. This comprehensive overview provides a nuanced understanding of the diverse Omicron subvariants, their global impact, and the ongoing efforts to combat their spread through vaccination and therapeutic interventions.

An imaging and diagnostic conundrum-the adrenal haemangioma.

The adrenal haemangioma, a rare benign vascular tumour, is increasingly detected through abdominal imaging. Just over 70 surgical cases have been reported since 1955. Their potential large size and overlapping imaging features with adrenocortical carcinoma poses a diagnostic challenge. Adrenalectomy is often needed for a definitive diagnosis due to inconclusive imaging. We report the case of a 61-year-old female presenting with an incidental finding of a right-sided 9.5-cm adrenal mass on imaging. Due to the risk of adrenocortical carcinoma with inconclusive imaging findings, an open right adrenalectomy was performed. The patient was discharged after 6 days with no complications. Post-surgical histopathology confirmed a diagnosis of adrenal haemangioma with a secondary adrenal pseudocyst. The presence of an adrenal incidentaloma with discordant radiological features proves to be a diagnostic conundrum. Therefore, in the setting of contradictory radiology and concerning mass size, we recommend adrenalectomy for definitive diagnosis of an adrenal haemangioma.

Evaluation of Tools to Assess Symptoms and Symptom Severity in Patients With Medically Unexplained Physical Symptoms: A Systematic Review and Narrative Synthesis.

A substantial portion of patients presenting to healthcare settings exhibit physical symptoms lacking clear, demonstrable organic causes. Accurate assessment of symptom severity is crucial for documenting outcomes and establishing treatment efficacy. This systematic review and narrative synthesis aims to provide researchers with insights into available and validated tools for assessing medically unexplained physical symptoms (MUPS). It involved comprehensive searches across electronic databases, including PubMed, Wiley, and Cochrane, adhering to PRISMA and COSMIN guidelines. The study comprised two phases: Phase 1 systematically reviewed tools for assessing MUPS symptoms and severity, while Phase 2 conducted a narrative synthesis of their measurement properties, focusing on validity and reliability. Out of 14,459 records, 191 articles were identified, leading to the recognition of 16 validated tools for assessing MUPS symptoms and severity. Most tools demonstrated excellent internal consistency and structural validity. However, the majority lacked cross-cultural validity. The choice of tools for the assessment of MUPS will assist clinicians and researchers in determining the severity of MUPS and developing a tailored treatment plan to improve the physical and psychological functioning of these patients.

The Pharmacologic Management of Cardiac Arrest.

The effectiveness of pharmacologic management of cardiac arrest patients is widely debated; however, several studies published in the past 5 years have begun to clarify some of these issues. This article covers the current state of evidence for the effectiveness of the vasopressor epinephrine and the combination of vasopressin-steroids-epinephrine and antiarrhythmic medications amiodarone and lidocaine and reviews the role of other medications such as calcium, sodium bicarbonate, magnesium, and atropine in cardiac arrest care. We additionally review the role of ß-blockers for refractory pulseless ventricular tachycardia/ventricular fibrillation and thrombolytics in undifferentiated cardiac arrest and suspected fatal pulmonary embolism.

Development and Validation of a Symptom Scale for Indian Patients With Medically Unexplained Physical Symptoms.

Introduction Patients with medically unexplained physical symptoms (MUPS) account for a substantial proportion of patients visiting the outpatient department. Diagnosis of MUPS is a challenge for most physicians. An accurate diagnosis relies on obtaining a detailed history from patients regarding the nature of their symptoms, their onset, and any associated aggravating or relieving factors. This study aims to develop a symptom scale for Indian patients with MUPS. Methods The study had a mixed-method study design. Phase 1 involved designing the questionnaire using qualitative techniques, such as literature reviews, focus-group discussions, expert evaluation, and pre-testing of a Hindi and English language Likert-rated interviewer-administered scale. In phase 2, the construct validity of the questionnaire was established using quantitative approaches among 116 patients diagnosed with MUPS. Results The final questionnaire consists of 38 items, with good internal consistency (Cronbach 𝛂 = 0.916). Confirmation sampling adequacy for factor analysis was done using the Kaiser-Meyer-Olkin test (KMO value = 0.792) and Bartlett's test of sphericity (p < 0.001). The newly developed scale showed a Pearson correlation coefficient of 0.568 (p < 0.001) with Patient Health Questionnaire (PHQ)-15 scores. Conclusion A reliable and valid tool has been developed to assess patients' symptoms with MUPS in English and Hindi languages. This questionnaire can be used for assessment, screening, and diagnostic purposes as well as to chart longitudinal changes in patients with MUPS.

Sessile serrated polyp detection rates after fecal immunochemical test or multitarget stool DNA test: Systematic review and meta-analysis.

Background and study aims Published studies report a higher adenoma detection rate (ADR) for FIT-DNA as compared with FIT. Data are less replete about the performance of stool-based tests for sessile serrated polyp (SSP) detection. We performed a meta-analysis to evaluate the performance of FIT and FIT-DNA testing for SSP detection rate (SSPDR) in patients undergoing colonoscopy for follow up of positive noninvasive tests. Methods A comprehensive literature search of multiple databases (until September 2022) was performed to identify studies reporting SSPDR in patients with positive FIT or FIT-DNA tests. The outcome was overall colonoscopy detection of any SSPs and advanced serrated polyps (ASP: SSP ≥ 10 mm and/or dysplasia). Results Included were 482,405 patients (52.4% females) with a mean age of 62.3 ± 4.4 years from 23 studies. The pooled SSPDR for all positive stool-based tests was 5.3% and higher for FIT-DNA (15.0%, 95% confidence interval [CI] 8.3-25.7) versus FIT (4.1%, 95% CI 3.0-5.6; P = 0.0002). The overall pooled ASP detection rate was 1.4% (95% CI 0.81-2.3) and higher for FIT-DNA (3.8 %, 95% CI 1.7-8.6) compared with FIT (0.71%, 95% CI 0.36-1.4; P <0.01). SSPDR with FIT-DNA was also significantly higher than FIT when the FIT cutoff was >10 ug/g and in FIT-positive patients in studies conducted in North America ( P <0.05). Conclusions FIT-DNA outperformed FIT in both SSP and ASP detection including FIT with a lower threshold cutoff of >10 ug/g. Further comparative studies are needed to assess the impact of our findings on colorectal cancer reduction.

The Risk of Crimean Congo Haemorrhagic Fever in India as a Growing Health Concern.

Every year witnesses an outbreak of some or the other zoonotic disease that causes the unparalled loss of human life. The year 2022 presented the outbreak of Crimean Congo haemorrhagic fever (CCHF), which brought unprecedented challenges to individuals as well as to the healthcare system all around the world, making it a serious health concern. Rising health concerns have highlighted the importance of managing and decreasing the further transmission of the CCHF virus. CCHF is one of tick-borne viral diseases, which spreads due to various reasons like changes in global warming, environmental influences, and other ecological factors. All these factors somehow impact the disease prevalence. This disease has a negative impact on both humans and livestock. The diverse climate and significant livestock population of India make it susceptible to the prevalence of CCHF. Therefore, it is the need of the hour to develop some strategies in order to tackle the challenges posed by CCHF. This article includes all the cases of CCHF that have occurred in India from the year 2011, along with the fatality rates associated with this disease. Also this study discusses the need to explore some specific drugs for the management and prevention of such diseases. In addition, the pathogenesis of the disease progression, along with some protective measures suggested by the government has been described for prevention of CCHF. Subsequently, this article attempted to draw attention towards the risk that may be posed by CCHF in the coming scenario, emphasizing the importance of taking proactive measures in anticipation of such risks.

Effectiveness of cognitive retraining intervention on weight loss and lifestyle-related behaviours among adults: A systematic review and meta-analysis.

INTRODUCTION: The review explores the potential benefits of cognitive retraining interventions in improving healthy lifestyle-related behaviours, and its possible use as an alternative or complementary approach to traditional weight loss interventions. METHOD: Studies were selected using different electronic databases (PubMed, Web of Science, Scopus, Embase), to identify RCTs published in the last 23 years on cognitive retraining interventions for weight loss. A total of 12 studies were finalized for systematic review and six for meta-analysis based on the inclusion criteria. The risk of bias was assessed by the two reviewers independently using the criteria outlined in the Joanna Briggs Institute Critical Appraisal Tool for RCTs. The R software was used to perform meta-analysis. RESULT: The overall effect estimates slightly favoured the intervention group, with a standardised mean difference (SMD) of -0.26 [95% CI (-0.58- 0.06) P < 0.05; I2 = 0.00%]. This suggests that although the effect was not statistically significant, cognitive retraining interventions may have a small effect on weight loss. The findings of the systematic review revealed that cognitive retraining interventions may be effective in modifying lifestyle behaviours and these changes may contribute in achieving and maintaining weight loss in the long run. CONCLUSION: Interventions exhibited a positive effect on weight loss. These interventions demonstrated promise in modifying lifestyle behaviours, suggesting a potential role in achieving and sustaining long-term weight loss. Further research is warranted to refine and validate these findings.

Molecular editing of NSC-666719 enabling discovery of benzodithiazinedioxide-guanidines as anticancer agents.

DNA polymerase ß (Polß) is crucial for the base excision repair (BER) pathway of DNA damage repair and is an attractive target for suppressing tumorigenesis as well as chemotherapeutic intervention of cancer. In this study, a unique strategy of scaffold-hopping-based molecular editing of a bioactive agent NSC-666719 was investigated, which led to the development of new molecular motifs with Polß inhibitory activity. NSC compound and its analogs (two series) were prepared, focusing on pharmacophore-based molecular diversity. Most compounds showed higher activities than the parent NSC-666719 and exhibited effects on apoptosis. The inhibitory activity of Polß was evaluated in both in vitro reconstituted and in vivo intact cell systems. Compound 10e demonstrated significant Polß interaction and inhibition characteristics, including direct, non-covalent, reversible, and comparable binding affinity. The investigated approach is useful, and the discovered novel analogs have a high potential for developing as anticancer therapeutics.

A comprehensive evaluation of predictors of obesity in women during the perimenopausal period: A systematic review and narrative synthesis.

INTRODUCTION: Obesity during perimenopausal transition can be attributed to various factors. Identifying these factors is crucial in preventing obesity and developing effective strategies to manage weight during this phase. This review aimed to systematically understand predictors of obesity during menopausal transition. METHODS: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched databases like PubMed, Wiley Online Library, and Cochrane Reviews. Cohort and cross-sectional studies in English language assessing obesity among menopausal women were included. The methodological quality was assessed using Joanna Briggs Checklist for critical appraisal. Risk of Bias (RoB) was generated using Review Manager 5.4.1 (RevMan). Identified predictors were assessed for overall quality of evidence using adopted Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: This review encompassed 42 studies, (21 cross-sectional and 21 cohort) with sample ranging from 164 to 107,243 across studies. Higher parity( ≥ 3 children) emerged as a strong predictor of obesity across seven studies, with good-quality evidence. Lower physical activity was another predictor, supported by eight studies with good-quality evidence. Sociodemographic factors like lower education(<8 years or < than college degree), socioeconomic background, menopausal transition, and older age at menarche showed associations with weight gain, with moderate-quality evidence. Lifestyle factors (high-fat consumption, sedentariness, active smoking status, and psychological difficulties) also showed moderate-quality evidence. CONCLUSION: This review underscores the multifaceted factors associated with obesity during the perimenopausal transition. Identifying these factors will be helpful in prevention and management of obesity among these women.

Effect of volume of instillate on the diagnostic utility of bronchoalveolar lavage galactomannan in patients with suspected chronic pulmonary aspergillosis-A pilot study.

BACKGROUND: Bronchoalveolar lavage (BAL) galactomannan (GM) is commonly used to diagnose Aspergillus-related lung diseases. However, unlike serum GM, which is measured in undiluted blood, BAL-GM is estimated using variable aliquots and cumulative volume of instillates during bronchoscopy. OBJECTIVE: Since different studies have reported varying diagnostic accuracy and cut-offs for BAL-GM in CPA, we hypothesized that the total volume of instillate and 'order/label' of aliquots significantly affects the BAL-GM values, which was evaluated as part of this study. PATIENTS & METHODS: We obtained 250 BAL samples from 50 patients (five from each) with suspected chronic pulmonary aspergillosis. BAL fluid was collected after instilling sequential volumes of 40 mL of normal saline each for the first four labels and a fifth label was prepared by mixing 1 mL from each of the previous labels. The GM level of each label was measured by PLATELIA™ ASPERGILLUS Ag enzyme immunoassay. This study measured the discordance, level of agreement, diagnostic characteristics (sensitivity, specificity and AUROC) and best cut-offs for BAL-GM in the different aliquots of lavage fluid. RESULTS: The study population, classified into CPA (28%) and non-CPA (72%) groups, based on ERS/ESCMID criteria (excluding BAL-GM) were not different with respect to clinico-radiological characteristics. The discordance of BAL-GM positivity (using a cut-off of >1) between the serial labels for the same patient ranged between 10% and 22%, while the discordance between classification using BAL-GM positivity (using a cut-off of ≥1) and clinic-radio-microbiological classification ranged between 18% and 30%. The level of agreement for serial labels was at best fair (<0.6 for all except one 'label'). The AUROC for the serial samples ranged between 0.595 and 0.702, with the '40 mL and the 'mix' samples performing the best. The best BAL-GM cut-off also showed significant variation between serial labels of varying dilutions (Range:1.01 - 4.26). INTERPRETATION: This study highlights the variation in BAL-GM measured and the 'positivity' between different 'labels' of aliquots of BAL, with the first aliquot and the mixed sample showing the best performances for diagnosis of CPA. Future studies should attempt to 'standardise' the instilled volume for BAL-GM estimation to standardise the diagnostic yield.

Insights into Translational and Biomedical Applications of Hydrogels as Versatile Drug Delivery Systems.

Hydrogels are a network of crosslinked polymers which can hold a huge amount of water in their matrix. These might be soft, flexible, and porous resembling living tissues. The incorporation of different biocompatible materials and nanostructures into the hydrogels has led to emergence of multifunctional hydrogels with advanced properties. There are broad applications of hydrogels such as tissue culture, drug delivery, tissue engineering, implantation, water purification, and dressings. Besides these, it can be utilized in the field of medical surgery, in biosensors, targeted drug delivery, and drug release. Similarly, hyaluronic acid hydrogels have vast applications in biomedicines such as cell delivery, drug delivery, molecule delivery, micropatterning in cellular biology for tissue engineering, diagnosis and screening of diseases, tissue repair and stem cell microencapsulation in case of inflammation, angiogenesis, and other biological developmental processes. The properties like swellability, de-swellability, biodegradability, biocompatibility, and inert nature of the hydrogels in contact with body fluids, blood, and tissues make its tremendous application in the field of modern biomedicines nowadays. Various modifications in hydrogel formulations have widened their therapeutic applicability. These include 3D printing, conjugation, thiolation, multiple anchoring, and reduction. Various hydrogel formulations are also capable of dual drug delivery, dental surgery, medicinal implants, bone diseases, and gene and stem cells delivery. The presented review summarizes the unique properties of hydrogels along with their methods of preparation and significant biomedical applications as well as different types of commercial products available in the market and the regulatory guidance.

Edge IoT Prototyping Using Model-Driven Representations: A Use Case for Smart Agriculture.

Industry 4.0 is positioned at the junction of different disciplines, aiming to re-engineer processes and improve effectiveness and efficiency. It is taking over many industries whose traditional practices are being disrupted by advances in technology and inter-connectivity. In this context, enhanced agriculture systems incorporate new components that are capable of generating better decision making (humidity/temperature/soil sensors, drones for plague detection, smart irrigation, etc.) and also include novel processes for crop control (reproducible environmental conditions, proven strategies for water stress, etc.). At the same time, advances in model-driven development (MDD) simplify software development by introducing domain-specific abstractions of the code that makes application development feasible for domain experts who cannot code. XMDD (eXtreme MDD) makes this way to assemble software even more user-friendly and enables application domain experts who are not programmers to create complex solutions in a more straightforward way. Key to this approach is the introduction of high-level representations of domain-specific functionalities (called SIBs, service-independent building blocks) that encapsulate the programming code and their organisation in reusable libraries, and they are made available in the application development environment. This way, new domain-specific abstractions of the code become easily comprehensible and composable by domain experts. In this paper, we apply these concepts to a smart agriculture solution, producing a proof of concept for the new methodology in this application domain to be used as a portable demonstrator for MDD in IoT and agriculture in the Confirm Research Centre for Smart Manufacturing. Together with model-driven development tools, we leverage here the capabilities of the Nordic Thingy:53 as a multi-protocol IoT prototyping platform. It is an advanced sensing device that handles the data collection and distribution for decision making in the context of the agricultural system and supports edge computing. We demonstrate the importance of high-level abstraction when adopting a complex software development cycle within a multilayered heterogeneous IT ecosystem.