A hepatocyte-specific transcriptional program driven by Rela and Stat3 exacerbates experimental colitis in mice by modulating bile synthesis.

Hepatic factors secreted by the liver promote homeostasis and are pivotal for maintaining the liver-gut axis. Bile acid metabolism is one such example wherein, bile acid synthesis occurs in the liver and its biotransformation happens in the intestine. Dysfunctional interactions between the liver and the intestine stimulate varied pathological outcomes through its bidirectional portal communication. Indeed, aberrant bile acid metabolism has been reported in inflammatory bowel disease (IBD). However, the molecular mechanisms underlying these crosstalks that perpetuate intestinal permeability and inflammation remain obscure. Here, we identify a novel hepatic gene program regulated by Rela and Stat3 that accentuates the inflammation in an acute experimental colitis model. Hepatocyte-specific ablation of Rela and Stat3 reduces the levels of primary bile acids in both the liver and the gut and shows a restricted colitogenic phenotype. On supplementation of chenodeoxycholic acid (CDCA), knock-out mice exhibit enhanced colitis-induced alterations. This study provides persuasive evidence for the development of multi-organ strategies for treating IBD and identifies a hepatocyte-specific Rela-Stat3 network as a promising therapeutic target.

Distinct melanocyte subpopulations defined by stochastic expression of proliferation or maturation programs enable a rapid and sustainable pigmentation response.

The ultraviolet (UV) radiation triggers a pigmentation response in human skin, wherein, melanocytes rapidly activate divergent maturation and proliferation programs. Using single-cell sequencing, we demonstrate that these 2 programs are segregated in distinct subpopulations in melanocytes of human and zebrafish skin. The coexistence of these 2 cell states in cultured melanocytes suggests possible cell autonomy. Luria-Delbrück fluctuation test reveals that the initial establishment of these states is stochastic. Tracking of pigmenting cells ascertains that the stochastically acquired state is faithfully propagated in the progeny. A systemic approach combining single-cell multi-omics (RNA+ATAC) coupled to enhancer mapping with H3K27 acetylation successfully identified state-specific transcriptional networks. This comprehensive analysis led to the construction of a gene regulatory network (GRN) that under the influence of noise, establishes a bistable system of pigmentation and proliferation at the population level. This GRN recapitulates melanocyte behaviour in response to external cues that reinforce either of the states. Our work highlights that inherent stochasticity within melanocytes establishes dedicated states, and the mature state is sustained by selective enhancers mark through histone acetylation. While the initial cue triggers a proliferation response, the continued signal activates and maintains the pigmenting subpopulation via epigenetic imprinting. Thereby our study provides the basis of coexistence of distinct populations which ensures effective pigmentation response while preserving the self-renewal capacity.

A multi-centric, single-blinded, randomized, parallel-group study to evaluate the effectiveness of nasoalveolar moulding treatment in non-syndromic patients with complete unilateral cleft lip, alveolus and palate (NAMUC study): a study protocol for a randomized controlled trial.

BACKGROUND: Cleft lip and palate (CLP) are among the most common congenital anomaly that affects up to 33,000 newborns in India every year. Nasoalveolar moulding (NAM) is a non-surgical treatment performed between 0 and 6 months of age to reduce the cleft and improve nasal aesthetics prior to lip surgery. The NAM treatment has been a controversial treatment option with 51% of the cleft teams in Europe, 37% of teams in the USA and 25 of cleft teams in India adopting this methodology. This treatment adds to the already existing high burden of care for these patients. Furthermore, the supporting evidence for this technique is limited with no high-quality long-term clinical trials available on the effectiveness of this treatment. METHOD: The NAMUC study is an investigator-initiated, multi-centre, single-blinded randomized controlled trial with a parallel group design. The study will compare the effectiveness of NAM treatment provided prior to lip surgery against the no-treatment control group in 274 patients with non-syndromic unilateral complete cleft lip and palate. The primary endpoint of the trial is the nasolabial aesthetics measured using the Asher McDade index at 5 years of age. The secondary outcomes include dentofacial development, speech, hearing, cost-effectiveness, quality of life, patient perception, feeding and intangible benefits. Randomization will be carried out via central online system and stratified based on cleft width, birth weight and clinical trial site. DISCUSSION: We expect the results from this study on the effectiveness of treatment with NAM appliance in the long term along with the cost-effectiveness evaluation can eliminate the dilemma and differences in clinical care across the globe. TRIAL REGISTRATION: ClinicalTrials.gov CTRI/2022/11/047426 (Clinical Trials Registry India). Registered on 18 November 2022. The first patient was recruited on 11 December 2022. CTR India does not pick up on Google search with just the trial number. The following steps have to be carried out to pick up. How to search: ( https://ctri.nic.in/Clinicaltrials/advsearch.php -use the search boxes by entering the following details: Interventional trial > November 2022 > NAMUC).

Assessment of naturally occurring radionuclides in surface soil and drinking water from western part of Yadgir district Karnataka, India.

Radionuclide activity of the selected radionuclides 238U, 232Th and 40K was measured in surface soil samples collected from 40 villages of the western part of Yadgir district of Karnataka. A 4″ × 4″ NaI (Tl) detector based on a gamma spectrometer is used for the estimation of radionuclides. The major type of soil in this region is sandy and red. The 222Rn activity concentrations in drinking water were determined by the Emanometry method. The 222Rn activity in ground water is found to vary from 1.73 to 155.6 Bql-1. The total annual effective doses because of 222Rn inhalation and ingestion range from 4.72 to 424.84 µSv y-1 with an average value of 108.8 µSv y-1, respectively. Among the sampling stations, Shahapur and Shorapur soil samples show higher activity values than the Kembhavi and Hunasagi sampling stations soil samples.

The Accuracy of Casts Obtained Using Different Impression Techniques and Impression Materials in Combined Parallel and Angulated Implants: An In Vitro Study.

Aim The aim of this in vitro study was to evaluate and compare the accuracy of casts made from two elastomeric impression materials (polyvinyl siloxane (PVS) and vinylsiloxanether (VSE)) using different impression techniques on parallel and angulated implants. Materials and methods The reference model was fabricated using auto-polymerizing acrylic resin on which three implant analogs were placed of which two were parallel to each other and the third at 20-degree mesial angulation. A total of 60 impressions were made of which 30 were by using PVS and 30 by VSE. For each material, 10 impressions were made by closed tray technique, 10 by open tray technique and 10 by open tray with sandblasting and adhesive coating of the impression copings technique. The inter-analog distances of the casts obtained were evaluated and compared with the reference model by a vision measuring machine. Data were analyzed using analysis of variance (ANOVA), Tukey's Honest Significant Difference (HSD) post hoc and independent samples t-test. Results When the inter-analog distances of the duplicate casts were compared with the reference model, the mean error rates for parallel implants decreased in the order of closed tray technique, open tray technique and open tray with sandblasting and adhesive coating of the impression copings technique for both PVS and VSE impression materials. Similarly, the same order was observed for angulated implants for both impression materials. Using the closed tray technique, there was no statistically significant difference in the accuracy of the cast between the two materials for parallel implants (P = 0.525) and also no significant difference between the two materials for angulated implants (P = 0.307). Similarly, there was no statistically significant difference in the accuracy of the cast between the two materials for parallel implants (P = 0.455) and also no significant difference between the two materials for angulated implants (P = 0.519) using the open tray technique. Whereas for the open tray with sandblasting and adhesive coating of the impression copings technique, VSE produced a more accurate cast than PVS for parallel implants and was statistically significant (P = 0.033); however, there was no significant difference between the two materials for angulated implants (P = 0.375). Conclusion For parallel implants, VSE by an open tray with sandblasting and adhesive coating of the impression copings technique produced a more accurate cast than PVS. For angulated implants, there was no significant difference between the two materials and it was only the technique that significantly affected the accuracy of the cast.

Heterotopic Pancreas: Unusual Cause of Usual Diarrhoea.

Heterotopic pancreas (HP) also known as ectopic pancreas, pancreatic crest or accessory pancreas is the normal pancreatic tissue, found in a remote area other than its natural location, with no anatomic or vascular connection to main pancreatic tissue. It is a rare congenital anomaly and has been reported at many locations such as stomach (antrum) and small intestine. HP is usually an incidental finding and asymptomatic, however there are reports of pancreatitis, obstruction, perforation and malignant transformation as uncommon manifestations. Diagnosis of HP is primarily based on histological examination either by biopsy or surgical excision. Surgery is the standard treatment for symptomatic HP patients. Herein, we present a case of a 58-year-old female, who presented to us with intractable diarrhoea due to HP in the jejunum and underwent minimally invasive surgery for definitive diagnosis and treatment.

Gastric Schwannoma-Two Unusual Cases with Usual Presentation and Review of Literature.

Schwannomas, also known as neurilemmomas, are characteristically benign, slow growing neoplasms originating from Schwann cell sheath. Gastrointestinal schwannomas are very rare with stomach being the most affected organ representing approximately 0.2% of all gastric tumours. Malignant transformation is rarely reported in these tumors and complete surgical resection with negative margins is the recommended treatment. Herein, we report our experience of 2 cases of gastric submucosal spindle cell tumour (SMT), which were preoperatively assumed to be as gastrointestinal stromal tumor (GIST), however postoperatively confirmed as schwannoma on immunohistochemical examination.

Comparison of efficacy of ultrasound-guided platelet rich plasma injection versus dry needling in lateral epicondylitis-a randomised controlled trial.

PURPOSE: To assess whether Ultrasound guided dry needling is adequate for both common extensor tendon tears and tendinosis or whether ultrasound guided platelet rich plasma (PRP) has a superior outcome when compared to dry needling when there are tears of the common extensor tendon. MATERIALS AND METHODS: This is a single-centre, single-blinded, randomised controlled trial conducted between November 2018 and April 2020. 40 patients diagnosed with lateral epicondylitis based on clinical and sonographic features and having comparable baseline characteristics were randomly assigned to the two study groups (dry needling and PRP). Inclusion criteria were patients aged 20 years or more who were symptomatic for at least 3 months with sonographic evidence of lateral epicondylitis. Exclusion criteria were complete tear of common extensor tendon confirmed on ultrasound and presence of other associated diseases like osteoarthritis of shoulder and elbow. RESULTS: There was significant improvement in the visual analogue scale pain score in PRP group compared to the dry needling group at 9 months. However, this difference was not evident at 3 and 6 months follow-up. Mean improvement in common extensor tendon thickness in PRP group (5.1 mm at 3 months and 4.3 mm at 6 months) was slightly better than dry needling (4.4 mm at 3 months and 4.0 mm at 6 months). There was no difference in tear (if present) healing between both groups at 3 months. However at 6 months follow up, PRP demonstrated significant (mean-2.5) healing in tear compared to dry needling (mean-3.1). CONCLUSION: Two injections of Ultrasound guided PRP are more beneficial non operative treatment compared to ultrasound guided dry needling, in lateral epicondylitis.

In vitro comparative evaluation of apical leakage using a bioceramic sealer with three different obturating techniques: A glucose leakage model.

Context: Bioceramic sealers have improved sealing ability by forming an interfacial apatite layer that chemically bonds the sealer and radicular dentin thus decrease apical leakage. Aim: This study aims to evaluate and compare the apical leakage of Cerafill RCS bioceramic sealer and gutta percha when used with three different obturating techniques. Materials and Methods: Thirty-four extracted single-rooted premolars were decoronated and prepared up to size F3. Then, the specimens were randomly divided into 3 experimental groups (n = 10) cold lateral obturation technique, warm vertical obturation technique, single-cone obturation technique, positive and negative control groups (n = 2), according to the obturation technique used along with a bioceramic sealer. To evaluate apical leakage, all specimens were mounted in a glucose leakage model and assessed at 7 and 14 days using an ultraviolet-visible spectrophotometer. Statistical Analysis: The results were subjected to ANOVA/Kruskal-Wallis ANOVA; followed by post hoc analysis using Bonferroni correction. Results: Significant differences were found in the cumulative leakage of all the three experimental groups. Significantly higher leakage was found in groups obturated using single-cone obturation technique as compared to warm vertical compaction technique at both 7 and 14 days. Conclusions: Warm vertical compaction showed a better sealing result than single-cone obturation techniques at all observation periods.

SWOT analysis of ortho-K practice in India.

PURPOSE: Orthokeratology (ortho-K) has been well established as a methodology for myopia correction and control its progression. A SWOT analysis serves as a strategic planning tool for intervention hence the purpose of this study to establish and implement ortho-K practice in India. METHOD: The study was conducted between December 2020 and June 2021. A prospective questionnaire-based study was conducted to elicit the responses in the SWOT study. Based on focus group discussion a set of five statements under strengths, weaknesses, opportunities and threats were identified. These were closed ended questions were based on a 5-point likert scale. The Content Validation Index (CVI) was computed for each item taking those answers relevant with a score of three and four on the Likert scale and omitting those with a score of one and two on the Likert scale as non-relevant. RESULTS: Strengths: 'Ortho-K is an excellent option for myopia control' was agreed by more than 50% of respondents. 67% of respondents agreed that advanced topographers has made ortho-K lens fitting easier. Weakness: More than 60% agreed that Ortho-K practice involves investment in instrumentation like topographers and trial lenses. 50% agreed that due to multiple follow up patients may be lost to follow up. OPPORTUNITY: 'Pandemic has necessitated the need for optometrists to explore myopia control options such as ortho-K' was agreed by more than 50%. Threats: 'Reluctance from adults and parents to try overnight contact lenses for myopia correction/control' was agreed by more than 50% of respondents. 62% agreed that atropine is perceived as an effective myopia control option by majority of the Indian ophthalmologists. CONCLUSION: Ortho-K as an emerging modality for Myopia management in India through SWOT analysis, allows practitioners as well as CL industry to approach Ortho-K appropriately with novel designs and practice patterns that suits the market needs.

Pankey Mann Schuyler Philosophy-Based Prosthetic Rehabilitation for an Amelogenesis Imperfecta Patient: A Case Report.

This clinical case report presents the prosthetic rehabilitation of a 23-year-old male patient with generalized discolored and worn-out teeth, which were of aesthetic and functional concern. In collaboration with the Department of Oral Medicine and Radiology and Oral Pathology, this clinical condition was diagnosed as amelogenesis imperfecta (AGI). AGI is a genetic odontological disorder that is an epithelial derivative of the developed tooth bud with enamel malformation. AGI typically affects both deciduous and permanent teeth. Patients generally have aesthetic complaints and compromised chewing efficiency with loss of vertical dimension. Prosthetically rehabilitating an AGI patient is a multidisciplinary approach to regain aesthetics, phonetics, and mastication. This article describes the full mouth rehabilitation, following the Pankey Mann Schuyler philosophy, of the patient with AGI involving all teeth. Full mouth rehabilitation was planned to restore aesthetics, phonetics, and mastication in four phases. First was prosthetic rehabilitation of the mandibular anterior teeth, followed by the maxillary anterior, mandibular posterior, and, finally, maxillary posterior teeth.

Radon activity and their radiological doses in drinking water of Chitradurga district, Karnataka, India.

In this investigation, radon activity concentration, inhalation and ingestion doses due to intake of radon in drinking water have been estimated in the Chitradurga district drinking water by using radon Emanometry technique. The average radon concentrations vary from 1.81 ± 0.11 to 300.33 ± 4.56 Bql-1 with a mean value of 56.01 ± 2.44 Bql-1. Most of the radon concentration levels are within the World Health Organization (WHO) and European Union (EU) commission recommended level of 100 Bql-1. About 70% of the drinking water had radon concentration level higher than the United States Environmental Protection Agency (USEPA) recommended Maximum Contamination Limit (MCL) of 11.1 Bql-1. The annual ingestion dose varies from 0.38 to 63.03 µSvy-1 with an average value of 11.75 µSvy-1. The estimated annual ingestion dose is well within the WHO recommended reference level of 100 µSvy-1.

Pigmented skin exhibits accelerated wound healing compared to the nonpigmented skin in Guinea pig model.

This study investigated and compared the wound healing kinetics of pigmented (PG) and non-pigmented (NP) skin in guinea pigs, focusing on histological and transcriptional changes. Full-thickness wounds created on PG and NP skin were evaluated at various time points post-injury. Fontana-Masson staining and ultrastructural analysis suggested the presence of melanin and melanosomes in PG skin, which coincided with an upregulation of melanogenic genes cKIT, TYR, and DCT. On day 9 post-wound, PG skin exhibited a rapid transition from the inflammatory to proliferative phase, which correlated with the reappearance of epidermal pigmentation whereas the NP skin exhibited a delayed neo-epidermis formation. Furthermore, the study revealed that melanocyte-derived growth factors (conditioned media) positively regulated keratinocyte migration while inhibiting fibroblast differentiation. These effects were more prominent in tyrosine-treated (hyperpigmented) melanocyte-CM as was TGF- ß expression. These findings provide valuable insights into the mechanisms underlying skin repair and pigmentation.

Suppression of perioperative stress response in elective abdominal surgery: A randomized comparison between dexmedetomidine and epidural block.

Background and Aims: Stress response after surgery induces local and systemic inflammation which may be detrimental if it goes unchecked. Blockade of afferent neurons or inhibition of hypothalamic function may mitigate the stress response. Material and Methods: A total of 50 consenting adult ASA I/II patients undergoing elective abdominal surgery were randomized to receive either dexmedetomidine (Group D) or epidural bupivacaine (Group E) in addition to balanced general anesthesia. Laparoscopic surgery, contraindications to epidural administration, history of psychiatric disorders, obesity (BMI >30 kg/m2), on beta blockers or continuous steroid therapy for >5 days over last 1 year, and known case of endocrine abnormalities or malignancy were excluded. Serum cortisol, blood glucose, and blood urea were estimated. Hemodynamic parameters, total dose of dexmedetomidine, bupivacaine, emergence characteristics, and analgesic consumption over 24 h postoperatively were recorded. Statistical comparisons were done using Student's t-test, repeated measure analysis of variance followed by Dunnett's test, generalized linear model and Chi-square/Fisher's exact test. A P value <0.05 was considered significant. Results: Serum cortisol levels were significantly lower in group E than group D 24 h after surgery (P = 0.029). Intraoperative and postoperative glucose level was lower in group E compared with group D. Time to request of first rescue analgesic was longer in group E than group D (P = 0.040). There was no significant difference between the number of doses of paracetamol required in the postoperative period (P = 0.198). Conclusion: Epidural bupivacaine was more effective than intravenous dexmedetomidine for suppression of neuroendocrine and metabolic response to surgery. Dexmedetomidine provided better hemodynamic stability at the time of noxious stimuli and postoperatively.

Comparative assessment of dexmedetomidine and butorphanol for attenuation of etomidate-induced myoclonus: A double-blind, randomised controlled study.

Background and Aims: Etomidate is a popular induction agent, but its use is associated with myoclonus in 50%-80% of non-premedicated patients. This study aims to compare dexmedetomidine and butorphanol for their relative efficacy in preventing etomidate-induced myoclonus. Methods: This randomised study was conducted after obtaining institutional ethical committee clearance and written informed consent from sixty American Society of Anesthesiologists (ASA) I or II consenting patients between 18 and 60 years of age of either sex who had been scheduled for elective surgeries under general anaesthesia. Patients were randomly allocated to dexmedetomidine 0.5 µg/kg (Group D) or butorphanol 0.015 mg/kg (Group B). Both the drugs were given as an infusion over a period of 10 min before induction of anaesthesia. The primary outcome was the incidence of myoclonic movements after etomidate, and the secondary outcomes were the severity of myoclonus, changes in the haemodynamic parameters and incidence of airway complications. Normally distributed variables were compared using Student's t-test, and non-normally distributed variables were compared using Mann-Whitney U test. Qualitative data were analysed using Chi-square/Fisher's exact test. A P-value <0.05 was considered significant. Results: The incidence of etomidate-induced myoclonus was significantly higher in group B compared to group D (P = 0.035). The median (interquartile range [IQR]) of myoclonus grade in patients of group D was 0.00 (0.00-3.00), and group B was 2.50 (0.00-3.00) (P = 0.035). Haemodynamics and airway-related complications were comparable between the groups. Conclusion: Dexmedetomidine was more effective than butorphanol in preventing etomidate-induced myoclonus.

Applying AI and Guidelines to Assist Medical Students in Recognizing Patients With Heart Failure: Protocol for a Randomized Trial.

BACKGROUND: The integration of artificial intelligence (AI) into clinical practice is transforming both clinical practice and medical education. AI-based systems aim to improve the efficacy of clinical tasks, enhancing diagnostic accuracy and tailoring treatment delivery. As it becomes increasingly prevalent in health care for high-quality patient care, it is critical for health care providers to use the systems responsibly to mitigate bias, ensure effective outcomes, and provide safe clinical practices. In this study, the clinical task is the identification of heart failure (HF) prior to surgery with the intention of enhancing clinical decision-making skills. HF is a common and severe disease, but detection remains challenging due to its subtle manifestation, often concurrent with other medical conditions, and the absence of a simple and effective diagnostic test. While advanced HF algorithms have been developed, the use of these AI-based systems to enhance clinical decision-making in medical education remains understudied. OBJECTIVE: This research protocol is to demonstrate our study design, systematic procedures for selecting surgical cases from electronic health records, and interventions. The primary objective of this study is to measure the effectiveness of interventions aimed at improving HF recognition before surgery, the second objective is to evaluate the impact of inaccurate AI recommendations, and the third objective is to explore the relationship between the inclination to accept AI recommendations and their accuracy. METHODS: Our study used a 3 × 2 factorial design (intervention type × order of prepost sets) for this randomized trial with medical students. The student participants are asked to complete a 30-minute e-learning module that includes key information about the intervention and a 5-question quiz, and a 60-minute review of 20 surgical cases to determine the presence of HF. To mitigate selection bias in the pre- and posttests, we adopted a feature-based systematic sampling procedure. From a pool of 703 expert-reviewed surgical cases, 20 were selected based on features such as case complexity, model performance, and positive and negative labels. This study comprises three interventions: (1) a direct AI-based recommendation with a predicted HF score, (2) an indirect AI-based recommendation gauged through the area under the curve metric, and (3) an HF guideline-based intervention. RESULTS: As of July 2023, 62 of the enrolled medical students have fulfilled this study's participation, including the completion of a short quiz and the review of 20 surgical cases. The subject enrollment commenced in August 2022 and will end in December 2023, with the goal of recruiting 75 medical students in years 3 and 4 with clinical experience. CONCLUSIONS: We demonstrated a study protocol for the randomized trial, measuring the effectiveness of interventions using AI and HF guidelines among medical students to enhance HF recognition in preoperative care with electronic health record data. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49842.

Retrieval of Chronically Implanted Dual-chamber Leadless Pacemakers in an Ovine Model.

BACKGROUND: The clinical utilization of leadless pacemakers (LPs) as an alternative to traditional transvenous pacemakers is likely to increase with the advent of dual-chamber LP systems. Since device retrieval to allow LP upgrade or replacement will become an important capability, the first such dual-chamber, helix-fixation LP system (Aveir DR; Abbott, Abbott Park, IL) was specifically designed to allow catheter-based retrieval. In this study, the preclinical performance and safety of retrieving chronically implanted dual-chamber LPs was evaluated. METHODS: Atrial and ventricular LPs were implanted in the right atrial appendage and right ventricular apex of 9 healthy ovine subjects. After ≈2 years, the LPs were retrieved using a dedicated transvenous retrieval catheter (Aveir Retrieval Catheter; Abbott) by snaring, docking, and unscrewing from the myocardium. Comprehensive necropsy/histopathology studies were conducted to evaluate device- and procedure-related outcomes. RESULTS: At a median of 1.9 years postimplant (range, 1.8-2.6), all 18 of 18 (100%) LPs were retrieved from 9 ovine subjects without complications. The median retrieval procedure duration for both LPs, from first-catheter-in to last-catheter-out, was 13.3 minutes (range, 2.5-36.4). Postretrieval, all right atrial, and right ventricular implant sites demonstrated minimal tissue disruption, with intact fibrous tissue limited to the distal device body. No significant device-related trauma, perforation, pericardial effusion, right heart or tricuspid valve injury, or chronic pulmonary thromboembolism were observed at necropsy. CONCLUSIONS: This preclinical study demonstrated the safe and effective retrieval of chronically implanted, helix-fixation, dual-chamber LP systems, paving the way for clinical studies of LP retrieval.