Rouviere's Sulcus Analysis: A Critical Safety Analysis and a Guide to Safe Laparoscopic Cholecystectomy.

INTRODUCTION: Laparoscopic cholecystectomy (LC) is the most frequent surgical operation in general surgery. The focus of recent research has been on improving the procedure's safety. Over 80% of healthy livers have Rouviere's sulcus (RVS), which is a natural notch in the right lobe that is present in proximity to the confluence of the bile duct. It is frequently considered an important component of safety during LC. RVS demarcates the area of the common bile duct (CBD) from the liver bed for the gall bladder. This research intends to evaluate the frequency, its relation to CBD, and the critical view of safety (CVS) during LC. MATERIALS AND METHODS: An observational study was performed in a cohort of 50 patients listed for LC between September 2021 and September 2022. The presence of RVS was confirmed after liver retraction and dissection commenced. After the creation of CVS, its relationship with CBD was documented. Additionally, the position of the cystic lymph node was also documented during the dissection. RESULTS: The findings of this study revealed that out of 50 patients, only 40 (80%) had RVS. However, cystic lymph nodes were present more frequently in 48 (96%) patients. CVS was achieved in all the patients, and it revealed the presence of RVS above the cystic duct-CBD junction in 37 (74%), at the level of the junction in 11 (22%), and in two (4%) where the junction could not be demarcated. CONCLUSION: RVS is a reliable marker to dissect laterally to CBD while doing LC, which does not require any dissection and can be appreciated early during the procedure. However, its presence along with the cystic lymph node gives a better anatomical understanding of the area of CBD, thereby assisting in conducting the procedure safely.

A Literature-Derived Knowledge Graph Augments the Interpretation of Single Cell RNA-seq Datasets.

Technology to generate single cell RNA-sequencing (scRNA-seq) datasets and tools to annotate them have advanced rapidly in the past several years. Such tools generally rely on existing transcriptomic datasets or curated databases of cell type defining genes, while the application of scalable natural language processing (NLP) methods to enhance analysis workflows has not been adequately explored. Here we deployed an NLP framework to objectively quantify associations between a comprehensive set of over 20,000 human protein-coding genes and over 500 cell type terms across over 26 million biomedical documents. The resultant gene-cell type associations (GCAs) are significantly stronger between a curated set of matched cell type-marker pairs than the complementary set of mismatched pairs (Mann Whitney p = 6.15 × 10-76, r = 0.24; cohen's D = 2.6). Building on this, we developed an augmented annotation algorithm (single cell Annotation via Literature Encoding, or scALE) that leverages GCAs to categorize cell clusters identified in scRNA-seq datasets, and we tested its ability to predict the cellular identity of 133 clusters from nine datasets of human breast, colon, heart, joint, ovary, prostate, skin, and small intestine tissues. With the optimized settings, the true cellular identity matched the top prediction in 59% of tested clusters and was present among the top five predictions for 91% of clusters. scALE slightly outperformed an existing method for reference data driven automated cluster annotation, and we demonstrate that integration of scALE can meaningfully improve the annotations derived from such methods. Further, contextualization of differential expression analyses with these GCAs highlights poorly characterized markers of well-studied cell types, such as CLIC6 and DNASE1L3 in retinal pigment epithelial cells and endothelial cells, respectively. Taken together, this study illustrates for the first time how the systematic application of a literature-derived knowledge graph can expedite and enhance the annotation and interpretation of scRNA-seq data.

Preparation and quality by design assisted (Qb-d) optimization of bioceramic loaded microspheres for periodontal delivery of doxycycline hyclate.

PLGA (Lactic- co-glycolic acid) coated chitosan microspheres loaded with hydroxyapatite and doxycycline hyclate complex were developed in the present study for periodontal delivery. A modified single emulsion method was adopted for the development of microspheres. Formulation was optimized on the basis of particle size, drug loading and encapsulation efficiency with the central composite design using 23 factorial design. Microspheres were optimized and electron microscopy revealed their spherical shape and porous nature. In-vitro study showed initial burst and then sustained release behavior of the formulation for 14 days. Further, in-vitro antibacterial study performed on E. coli (ATCC-25922) and S. aureus (ATCC-29213) revealed concentration dependent activity. Also, in-vitro cyto-toxicity assessment ensures biocompatibility of the formulation with the fibroblast's cells. Overall, the quality by design assisted PLGA microspheres, demonstrated the desired attributes and were found suitable for periodontal drug delivery.

An in vitro Comparative Evaluation of the Sealing Ability of Five Different Root-end Filling Materials under Confocal Laser Microscopy.

AIM: The purpose of this in-vitro study was to compare and evaluate the best sealing ability of five different root end filling materials i.e. Silver Amalgam, RMGIC, Cermet Cement, MTA Angelus and Biodentine using ConFocal Laser Scanning Microscope. METHODS AND MATERIAL: 90 extracted caries free, maxillary incisor teeth were collected and were root canal treated using standardized technique. Apical root resections followed by retrograde cavity preparation were done with ultrasonic retrotip. The teeth were divided into six groups depending upon different root end filling materials (Amalgam, RMGIC, Cermet cement, MTA, Biodentine) and one control group and apical leakage was observed under confocal laser scanning microscope. STATISTICAL ANALYSIS USED: The data was analyzed by ANOVA and Post Hoc test. RESULTS: The mean dye penetration of different groups were Group I (Control Group) 0.00±(0.00) mm, Group II (Silver amalgam) 3.00±(0.00) mm, Group III (RMGIC) 1.84±(0.26) mm, Group IV (Cermet cement) 1.83 (0.25) mm, Group V (MTA) 1.25±(0.12) mm, Group VI (Biodentine) 0.26±(0.21) mm. CONCLUSION: It was concluded that Biodentine exhibits best sealing ability followed by mineral trioxide aggregate, followed by Cermet Cement and RMGIC, whereas silver amalgam exhibited least sealing ability.

A Complex Case of Polymyositis Overlapping With Hypothyroid Myopathy Without Underlying Autoimmune Thyroid Disorder.

A 78-year-old woman with a past medical history of hypothyroidism and Sjogren's syndrome presented with a two-month history of gradually progressive bilateral lower extremity weakness. Significant elevation in thyroid-stimulating hormone (TSH) and muscle enzyme, such as creatine kinase, was noticed on presentation. Due to concerns of hypothyroid myopathy, the patient was started on thyroxine and triiodothyronine supplementation. The patient reported no significant improvement in her weakness in the one-month follow-up. Laboratory workup revealed improving TSH levels but worsening creatine kinase levels. Electromyography study showed primarily myopathic features, such as abnormal insertional activity concerning for mild inflammatory myopathy. Muscle biopsy showed mild inflammatory exudate and features of myopathy with ongoing denervation. The patient was diagnosed with polymyositis and started on prednisone 0.5 mg/kg daily with a taper course and methotrexate. The patient reported significant improvement in her weakness when seen in six weeks with normalizing creatine kinase levels. The hallmark difference between hypothyroid myopathy (including polymyositis-like syndrome) and conventional polymyositis is the complete clinical recovery and resolution of laboratory abnormalities after treatment with thyroid hormone replacement in hypothyroid myopathy. There was no evidence of underlying autoimmune thyroid disorder which makes this case unique. This case highlights the complex case of polymyositis overlapping with hypothyroid myopathy with no underlying autoimmune disorder.

Non-ischemic Cardiomyopathy: A Rare Adverse Effect of Clozapine.

Clozapine is a dibenzodiazepine antipsychotic used for treatment-resistant schizophrenia. Its association with several side effects such as agranulocytosis, seizure, and insulin resistance is well known. Cardiac side effects such as myocarditis and cardiomyopathy are less common and have been seldom reported. Here we report an unusual case of clozapine-induced nonischemic dilated cardiomyopathy. A 50-year-old female with treatment-resistant schizophrenia on clozapine presented with gradually worsening shortness of breath, productive cough, and pleuritic chest pain. She was found to have non-ischemic dilated cardiomyopathy due to clozapine use as no other causative factor was found. Clozapine was gradually tapered and then discontinued. Repeat echocardiogram in three months revealed improvement in ejection fraction. This case is unique as it outlines clozapine as a rare cause of nonischemic cardiomyopathy, as discontinuation of the drug showed improvement in symptoms and heart function.

Knowledge synthesis of 100 million biomedical documents augments the deep expression profiling of coronavirus receptors.

The COVID-19 pandemic demands assimilation of all biomedical knowledge to decode mechanisms of pathogenesis. Despite the recent renaissance in neural networks, a platform for the real-time synthesis of the exponentially growing biomedical literature and deep omics insights is unavailable. Here, we present the nferX platform for dynamic inference from over 45 quadrillion possible conceptual associations from unstructured text, and triangulation with insights from single-cell RNA-sequencing, bulk RNA-seq and proteomics from diverse tissue types. A hypothesis-free profiling of ACE2 suggests tongue keratinocytes, olfactory epithelial cells, airway club cells and respiratory ciliated cells as potential reservoirs of the SARS-CoV-2 receptor. We find the gut as the putative hotspot of COVID-19, where a maturation correlated transcriptional signature is shared in small intestine enterocytes among coronavirus receptors (ACE2, DPP4, ANPEP). A holistic data science platform triangulating insights from structured and unstructured data holds potential for accelerating the generation of impactful biological insights and hypotheses.

Pericardial Effusion: Rare Adverse Effect of Clozapine.

Clozapine is a dibenzodiazepine antipsychotic used for resistant schizophrenia, which is known to be associated with side effects such as agranulocytosis, seizures, weight gain, and less commonly myocarditis/ cardiomyopathy. We present a case of a 20-year-old female who presented with chest pain, shortness of breath, and cough. She was later found to have clozapine-induced pericardial effusion that resolved after discontinuation of clozapine therapy. Our case discloses the importance to consider clozapine in the differential diagnosis of pericardial effusion as discontinuation of the drug leads to resolution of effusion, with no need for further treatment.

A Study of Prevalence of Peripheral Arterial Disease in Type 2 Diabetes Mellitus Patients in a Teaching Hospital.

Introduction: Diabetes mellitus is a major health problem in India as also the world. Peripheral arterial disease (PAD) is a known complication of diabetes which is relatively less commonly studied in comparison to other complications. The present study was undertaken to study the prevalence of PAD in diabetic patients in a teaching hospital. Materials and Methods: 200 type 2 diabetic patients from indoor as well as outdoor of a teaching hospital were included in the study. Ankle brachial pressure index was used to assess PAD. ABPI values of 0.9 or less were taken as indicative of PAD. Results: Out of 200 patients 72(36%) had evidence of PAD. There was a significant association between PAD and duration of diabetes, waist circumference, hypertension and microvascular complications. Conclusion: The prevalence of PAD in Type 2 diabetics was found to be 36% in our study. Screening for PAD should be done in all diabetic patients to detect this complication early.

Utility of saliva and hair follicles in donor selection for hematopoietic stem cell transplantation and chimerism monitoring.

Selection of an HLA identical donor is a critical pre-requisite for successful hematopoietic stem cell transplantation (HSCT). Most transplant centers utilize blood as the most common source of DNA for HLA testing. However, obtaining blood through phlebotomy is often challenging in patients with conditions like severe leucopenia or hemophilia, pediatric and elderly patients. We have used a simple in-house protocol and shown that HLA genotypes obtained on DNA extracted from saliva or hair are concordant with blood and hence can be used for selection of donors for HSCT or organ transplantation. Similarly, for post-HSCT chimerism monitoring, non-availability of pre-transplant DNA samples poses a major limitation of reference STR fingerprints. This study shows that DNA obtained post-HSCT from hair follicles can be used to generate pre-transplant patient specific fingerprints while the STR profiles obtained in saliva samples cannot as these display a mixed state of chimerism.

A prospective randomized controlled blinded study of three bronchodilators in infants with respiratory syncytial virus bronchiolitis on mechanical ventilation.

OBJECTIVE: To study patients with respiratory syncytial virus bronchiolitis in respiratory failure to make specific measurements reflecting airway resistance before and after treatment with commonly used agents. We hypothesized that racemic epinephrine would decrease airways resistance more effectively than levalbuterol, and levalbuterol would decrease airways resistance more effectively than racemic albuterol. Normal saline was used as a control. DESIGN: Prospective, randomized, controlled, blinded study. SETTING: Tertiary Pediatric Intensive Care Unit in a University affiliated hospital in the northeastern United States. PATIENTS: Twenty-two patients with respiratory syncytial virus bronchiolitis and in respiratory failure were enrolled. All were intubated and ventilated in a volume control mode and sedated. INTERVENTIONS: In a randomized, blinded fashion patients were given four agents: norepinephrine, levalbuterol, racemic albuterol, and normal saline at 6 hr intervals. MEASUREMENTS: As indicators of bronchodilation, peak inspiratory pressure and inspiratory respiratory system resistance were measured before and 20 mins after each agent was given. Thus, each patient acted as his/her own control. MAIN RESULTS: There were small but statistically significant decreases in peak inspiratory pressure after racemic epinephrine treatment, levalbuterol, and racemic albuterol. There was no change in peak inspiratory pressure after inhaled normal saline. Inspiratory respiratory system resistance fell significantly after all treatments, including saline. Heart rate rose significantly after inhaled bronchodilator treatments (p < 0.05 for all treatments). CONCLUSIONS: Similar statistically significant bronchodilation occurred after all three bronchodilators as indicated by a decrease in peak inspiratory pressure and respiratory system resistance, but these changes were small and probably clinically insignificant. However, side effects of bronchodilators, such as tachycardia, also occurred, and these may be clinically significant. Thus the benefit of bronchodilator treatment in these patients is small, does not differ among the drugs we studied and of questionable value.