Lipogenic stearoyl-CoA desaturase-1 (SCD1) targeted virtual screening for chemical inhibitors: molecular docking / dynamics simulation and in vitro assessment of anti-NAFLD efficacy.

Amidst rising global prevalence of metabolic syndrome, the associated risk of non-alcoholic fatty liver disease (NAFLD) is also rapidly increasing. The pathogenesis of NAFLD starts with fat accumulation and progresses through inflammation and fibrotic sequel, often involving complex molecular mechanisms involving de novo lipogenesis. Stearoyl-CoA desaturase 1 (SCD1) enzyme, expressed in liver and adipose tissue, converts saturated fatty acids to monounsaturated fatty acids (MUFAs), contributing to triglyceride and cholesterol ester formation. In this study, potential SCD1 inhibitors were screened using the ZINC database of curated medically-approved drugs by virtual screening, molecular docking, and molecular dynamics simulations. The top-scoring five ligands with strong binding affinity against SCD1 were ZINC000003831151 > ZINC000001540998 > ZINC000003830713 > ZINC000000897251 > ZINC000002005305, which showed stable protein-ligand complexation and favorable pharmacokinetic attributes. The top ligand, Montelukast, was experimentally validated for its pharmacological efficacy in an in vitro cell culture model of steatosis (NAFLD). Montelukast showed a dose-dependent decrease in hepatic fat accumulation, reduced levels of free radicals, and lowered oxidative stress (P < 0.05). These outcomes suggest Montelukast to be a potential SCD1 inhibitor, with anti-NAFLD efficacy. These findings open new avenues for therapeutic development of the top 5 ligands in metabolic disorders involving SCD1.

A Study of Functional Outcome and Assessment of Role of Proximal Humerus Internal Locking System (Philos) Plating in Elderly Population with Proximal Humerus Fracture: A Case Series.

Introduction: The purpose of the study was to assess the functional outcome of proximal humerus fractures (2 part, 3 part, and 4 part) managed with a proximal humerus internal locking system (PHILOS). Materials and Methods: This retrospective study included 27 cases of proximal humerus fractures managed surgically between February 2021 and February 2022 with a proximal humerus internal locking system (PHILOS) plate. NEER classification was used to categorize the fractures. Functional assessment was done using Constant Murley's shoulder score and disabilities of the arm, shoulder, and hand. Subjects having metastatic and pathological fractures; associated fractures in the ipsilateral limb; having major nerve injury and cases of open fracture were excluded from this study. Results: The mean age was 55.63 ± 10.37 years. Of the total 27 cases of proximal humerus fractures, functional outcome was excellent (score 85-100) in 3.70% (n = 1) cases, good (score 71-85) in 81.49% (n = 22) cases, moderate (score 56-70) in 14.81% (n = 4), and poor (score 0-55) in none of the (n = 0) cases. In 92.60% of cases, follow-up showed no complications. Varus collapse and subacromial impingement, both occurring in 3.70% (n = 1) of the subjects, were noted in this study. Conclusion: Based on the findings of this retrospective study, it can be opined that PHILOS plating appears to be a secure option for proximal humerus fracture cases. It offers solid fixation, prompt mobilization, and excellent functional outcomes as observed in this study. In addition, very few post-operative complication rates again support our conclusion.

IS Intra-masseteric Dexamethasone Better than Intra-deltoid Injection in Reducing Post-operative Sequelae Following Impacted Third Molar Surgery?: A Randomized Clinical Study.

Aim: The post-operative sequelae of third molar surgical extractions need to be controlled in order to reduce patient morbidity. Dexamethasone is a well-researched drug which has established its merit as an anti-inflammatory agent. The aim of this randomized clinical study was to compare the patient-centric outcomes after pre-emptive intramuscular injection of dexamethasone into the masseter and deltoid, respectively. Materials and Methods: The outcomes measured were pain, facial swelling and mouth-opening postoperatively on Day 1, 3 and 7. The subjects were randomly divided into two groups. Group 1 received an intra-oral injection of 8 mg of dexamethasone into the masseter muscle and a placebo injection of distilled-water into the deltoid muscle 2 h before surgical removal of impacted mandibular third molar. Group 2 received an intra-oral placebo injection of distilled-water into masseter muscle and an 8 mg injection of dexamethasone into deltoid muscle. Results: On comparison, Group 1 patients experienced statistically significant less pain (VAS score on day 1, 3, and 7), facial swelling (day 1, 3), and restricted mouth-opening (day 1, 3). Conclusion: The study concluded that pre-emptive dexamethasone injection, at masseter or deltoid, is helpful in reducing post-operative sequelae of mandibular third molar extraction. However, the immediate post-operative outcomes were found to be better mitigated when the injection was administered locally into masseter muscle.

Assessment of cancer predisposition syndromes in children with leukemia and solid tumors: germline-genomic profiling and clinical features in a series of cases.

Cancer predisposition syndromes (CPS) are a group of genetic disorders that increase the risk of various cancers. Identifying CPS has a significant impact on the treatment plan, screening and follow-up strategy, and genetic counseling of the family. However, in children, it goes underdiagnosed in most clinical setups, especially in low- and middle-income (LMIC) countries. In the present study, we screened 60 pediatric oncology patients for a possible CPS based on pre-defined selection criteria. Six patients met the criteria, three of whom had hematological malignancy, while the remaining three had sarcoma. Whole exome sequencing was performed in the selected patients to confirm the diagnosis. Germline mutation in CPS-related genes was discovered in five of six cases, including novel mutations discovered in two. An adverse outcome was observed in all five patients with underlying cancer predisposition syndrome, with three having relapsed and two having progressive disease. Our study reflects a prevalence of 10% underlying CPS in a limited cohort of patient based on the phenotype-genotype approach in our cohort. Using pre-defined clinical selection criteria, screening can be directed to a high-risk patient cohort with high-pick up rate for CPS. The selection criteria could be utilized in any LMIC-based clinical setup for pediatric cancer patients who may benefit from modification of treatment as well as genetic counseling.

Posterolateral Versus Posteromedial Approach for Posterior Malleolus Fixation in Trimalleolar Fractures of the Ankle.

Background Ankle fractures, particularly those involving the posterior malleolus, are prevalent injuries that can lead to significant functional impairment if not managed appropriately. The choice of surgical approach for posterior malleolus fixation - posteromedial (PM) or posterolateral (PL) - remains a debate among orthopedic surgeons. The PM approach is a traditional technique involving extensive soft tissue dissection, while the PL approach offers improved visualization and precision with potentially less soft tissue disruption. Materials and methods  This prospective comparative study was conducted at the Department of Orthopedics, Dr. D. Y. Patil Hospital and Research Centre, Pune, between February 2022 and August 2024.A total of 42 patients with trimalleolar fractures involving the posterior malleolus were randomly assigned to either the PL or PM surgical groups, with 21 patients in each group. Surgical outcomes were assessed using the American Orthopedic Foot and Ankle Society (AOFAS) scores, articular surface step-off, range of motion (ROM), and complications such as osteoarthritis, infection, neurovascular injury, nonunion, and deep vein thrombosis at six months, 12 months, and final follow-up. Results Patients in the PL group demonstrated superior clinical outcomes with higher mean AOFAS scores at six-month (87.52 ± 2.92) and 12-month (90.28 ± 1.72) follow-ups compared to the PM group (84.95 ± 3.25 at six months; 88.86 ± 2.41 at 12 months), with statistically significant differences favoring the PL approach. However, as per the final follow-up, the difference in AOFAS scores between the two groups was not statistically significant. The PL group also had more patients with excellent ROM and fewer complications, such as arthritis, than the PM group. Conclusion  The PL approach for posterior malleolus fixation in trimalleolar fractures offers superior early functional outcomes and fewer complications than the PM approach. However, the long-term outcomes between the two approaches show no significant difference, indicating that both techniques can be effective depending on the specific fracture pattern and patient characteristics.

Posterior Ring Apophyseal Fracture (PRAF) in a 13-Year-Old Adolescent Girl Treated With Unilateral Biportal Endoscopy: A Case Report.

Posterior ring apophyseal fracture (PRAF) is a rare but significant cause of lower back pain and radiculopathy in adolescents, commonly occurring due to trauma or intense physical activity. This is a case report of a 13-year-old girl with PRAF associated with lumbar disc herniation (LDH) following a sports injury, emphasizing diagnostic challenges and surgical management. The patient underwent unilateral laminectomy for bilateral decompression through unilateral biportal endoscopy (UBE-ULBD) at the L4-L5 level. Postoperatively, the patient had significant clinical improvement in the visual analog scale (VAS) score for leg and back pain at one-month follow-up. Although rare, PRAF associated with LDH is an important differential diagnosis for post-traumatic lower back pain in adolescents. Accurate preoperative imaging and minimally invasive surgical techniques such as UBE-ULBD provide effective decompression and improved clinical outcomes, allowing for a quicker return to daily activities.

Real-Time Location Systems: Revolutionizing Porter Services for Improving Patient Care Efficiency.

BACKGROUND: Transport porters (TPTs) are essentially involved in supporting hospital operations and maintaining high-quality patient care. The traditional porter management lacks transmission of temporal and spatial information of the porters thus affecting porter operations. In this work, we investigate the barriers in traditional porter management and the impact of a real-time location system (RTLS) in improving time and cost efficiency for porter operations. METHODOLOGY: A six-month study was conducted at Medanta - The Medicity, Gurugram investigating the limitations of traditional management and efficiency of indoor porter tracking system (IPTS) on TPTs operational activities by assessing the waiting time and total turnaround time (TAT). The cost-effectiveness of IPTS was determined based on capital expenditure and return on investment (ROI) post-technology implementation. RESULTS: This study highlights that improvements are required in porter management as 175 out of 285 (62%) calls were unanswered by TPTs. Post deployment of IPTS, the TAT for A-wing was reduced from 28 minutes to 20 minutes, and for B-wing, it was reduced from 26 minutes to 18 minutes. Staff optimization of three and four porters was done for A-wing and B-wing, respectively. The capital expenditure was recovered by reduced wait time and optimization of staff, thereby anticipating a monthly saving of ₹0.18 million (US$ 2150). The effective outcome of IPTS porter management envisaged its expansion to inpatient medicine delivery with a substantial cost reduction of ₹8.0 million (US$ 96,000) over three years. CONCLUSION: The implementation of IPTS improved the operational activities of porters and improved staff utilization. Cost savings from staff optimization lays the groundwork for new technology integrations for long-term operational advancements.

Anomalous reverse mechanical polarization switching in negative piezoelectric CuInP2S6.

van der Waals ferroelectric CuInP2S6 (CIPS) has drawn significant attention not only because of its unique properties but also owing to its technological potential for nanoelectronics. Mechanical polarization switching provides a new approach to modulating polarization states through flexoelectricity. This approach is particularly favourable for CIPS to avoid surface damage under an electric field due to the coupling between polarization switching and ionic motion. Here, we report anomalous downward-to-upward polarization switching under tip force in CIPS nanoflakes, which is believed to stem from the competition between piezoelectric and flexoelectric fields induced by tip pressure, together with the unique quadruple-well state present in CIPS. This work provides novel insights into the polarization switching mechanism of CIPS, elucidating the interplay between competing piezoelectric and flexoelectric fields, and it may pave the way for the design of electromechanical devices based on flexoelectric engineering.

Exploration of the Sclerotinia sclerotiorum-Brassica pathosystem: advances and perspectives in omics studies.

The polyphagous phytopathogen Sclerotinia sclerotiorum causing Stem rot disease is a major biotic stress in Brassica, and affects the yield and quality in various crops of agricultural significance. It affects the crop at pre-maturity which causes a reduction in the seed yield and deteriorates the oil quality in rapeseeds and Indian mustard globally. The hemibiotrophic nature and long persistence in the soil as sclerotia have made this pathogen difficult to manage through conventional agronomical practices. Hence, for alternative strategies, it is important to understand the basic aspects of the pathogen and the pathogenesis processes in the host. The current developments in technologies for omics studies including whole-genomes, transcriptomes, proteomes, and metabolomes have deciphered various genes, transcription factors, effectors and their target molecules involved in interaction, disease establishment and pathogen progress in the host tissues. The current review encompasses the studies that were conducted to decipher the Brassica-S. sclerotiorum pathosystem and the molecular factors identified through multi-omics studies for their application in building resistance to Sclerotinia stem rot disease in the susceptible cultivars of oilseed Brassica.

A Pilot Real-World Study of Ultrasonography Findings of Hidradenitis Suppurativa in Indian Patients and Its Diagnostic and Therapeutic Implications.

Introduction Hidradenitis suppurativa (HS) is a multifactorial chronic inflammatory follicular disorder affecting apocrine gland-bearing areas of the body. We conducted an observational study to assess the ultrasonography (USG) findings in suspected HS patients at a tertiary care center in North India over 6 months. Aim The aim of this article was to study the USG findings in HS and correlate clinical and USG findings and scoring systems in HS with stage wise treatments. Materials and Methods All patients with a clinical suspicion of HS underwent an USG examination after clinical examination with a probe of 18 Hz frequency. Hurley's staging of patients was used to stage clinically, and the HS-SOS scoring and Doppler changes were assessed on USG. The treatment was revised in case of a change in the USG grading of severity. Results A total of 23 patients suspected of HS underwent USG evaluation, of which 12 (52%) were male and 9 (48%) were females, with the mean age being 25.3 years (range: 14-40 years). Based on the HS clinical grading, eleven patients (47.8%) were Hurley's stage I, six patients (26%) were stage II, and six patients (26%) were stage III. USG demonstrated that three patients had been misdiagnosed and had folliculitis (8.6%) and Crohn's disease (4.3%). Out of the remaining twenty patients with USG features of HS, based on HS SOS grading, three patients (15%) were grade I, seven (35%) were grade II, and ten (50%) were grade III. Of these, nineteen patients (95%) had axillary involvement, which was bilateral in 84% of cases. The other region affected was the groin in five patients (26.3%), while two had inframammary involvement (10.5%). On further characterization of the type of lesion, nodules (41; 40.6%) were the most common type of lesion by sinuses and thickened hair follicles in 31 (30.6%) patients. Based on USG findings, the management of 26% of patients was changed from medical to surgical intervention. Conclusion USG and Doppler are noninvasive bedside tools for the examination of HS, which helps to rule out differentials and delineate the extent and depth of the disease better by picking up subclinical lesions and help in determining disease activity by Doppler, which in turn helps in planning appropriate medical and surgical management of patients. It also identifies radiological parameters that help identify patients who could fail medical management.

Tunneling Nanotubes: The Cables for Viral Spread and Beyond.

Multicellular organisms require cell-to-cell communication to maintain homeostasis and thrive. For cells to communicate, a network of filamentous, actin-rich tunneling nanotubes (TNTs) plays a pivotal role in facilitating efficient cell-to-cell communication by connecting the cytoplasm of adjacent or distant cells. Substantial documentation indicates that diverse cell types employ TNTs in a sophisticated and intricately organized fashion for both long and short-distance communication. Paradoxically, several pathogens, including viruses, exploit the structural integrity of TNTs to facilitate viral entry and rapid cell-to-cell spread. These pathogens utilize a "surfing" mechanism or intracellular transport along TNTs to bypass high-traffic cellular regions and evade immune surveillance and neutralization. Although TNTs are present across various cell types in healthy tissue, their magnitude is increased in the presence of viruses. This heightened induction significantly amplifies the role of TNTs in exacerbating disease manifestations, severity, and subsequent complications. Despite significant advancements in TNT research within the realm of infectious diseases, further studies are imperative to gain a precise understanding of TNTs' roles in diverse pathological conditions. Such investigations are essential for the development of novel therapeutic strategies aimed at leveraging TNT-associated mechanisms for clinical applications. In this chapter, we emphasize the significance of TNTs in the life cycle of viruses, showcasing the potential for a targeted approach to impede virus-host cell interactions during the initial stages of viral infections. This approach holds promise for intervention and prevention strategies.

N-substituted-4-(pyridin-4-ylalkyl)piperazine-1-carboxamides and related compounds as Leishmania CYP51 and CYP5122A1 inhibitors.

CYP5122A1, an enzyme involved in sterol biosynthesis in Leishmania, was recently characterized as a sterol C4-methyl oxidase. Screening of a library of compounds against CYP5122A1 and CYP51 from Leishmania resulted in the identification of two structurally related classes of inhibitors of these enzymes. Analogs of screening hit N-(3,5-dimethylphenyl)-4-(pyridin-4-ylmethyl)piperazine-1-carboxamide (4a) were generally strong inhibitors of CYP51 but were less potent against CYP5122A1 and typically displayed weak inhibition of L. donovani promastigote growth. Analogs of screening hit N-(4-(benzyloxy)phenyl)-4-(2-(pyridin-4-yl)ethyl)piperazine-1-carboxamide (18a) were stronger inhibitors of both CYP5122A1 and L. donovani promastigote proliferation but also remained selective for inhibition of CYP51. Two compounds in this series, N-(4-((3,5-bis(trifluoromethyl)benzyl)oxy)phenyl)-4-(2-(pyridin-4-yl)ethyl)piperazine-1-carboxamide (18e) and N-(4-((3,5-di-tert-butylbenzyl)oxy)phenyl)-4-(2-(pyridin-4-yl)ethyl)piperazine-1-carboxamide (18i) showed modest selectivity for inhibiting L. donovani promastigote proliferation compared to J774 macrophages and were effective against intracellular L. donovani with EC50 values in the low micromolar range. Replacement of the 4-pyridyl ring present in 18e with imidazole resulted in a compound (4-(2-(1H-imidazol-1-yl)ethyl)-N-(4-((3,5-bis(trifluoromethyl)benzyl)oxy)phenyl)piperazine-1-carboxamide, 18p) with approximately fourfold selectivity for CYP5122A1 over CYP51 that inhibited both enzymes with IC50 values ≤ 1 µM, although selective potency against L. donovani promastigotes was lost. Compound 18p also inhibited the proliferation of L. major promastigotes and caused the accumulation of 4-methylated sterols in L. major membranes, indicating that this compound blocks sterol demethylation at the 4-position in Leishmania parasites. The molecules described here may therefore be useful for the future identification of dual inhibitors of CYP51 and CYP5122A1 as potential antileishmanial drug candidates and as probes to shed further light on sterol biosynthesis in Leishmania and related parasites.

Unicystic ameloblastoma: Clinico-radiological and histopathological correlation with management.

Unicystic ameloblastoma is a distinct entity of ameloblastoma characterized by slow growth and locally aggressive behavior. This retrospective study aimed to assess the efficacy of different treatment modalities of unicystic ameloblastoma, focusing on clinico-radiological and histopathological features. Data from patients diagnosed with unicystic ameloblastoma were retrospectively analyzed. Patients were categorized into luminal and intraluminal (Group A) and mural (Group B) variants based on the Ackermann classification, which has a significant influence on their biological behavior, treatment approaches, and prognosis. Patients in Group A underwent enucleation with chemical cauterization, peripheral ostectomy, and iodoform packing, whereas those in Group B were treated with resection and reconstruction. Post-operatively, the patients were subjected to radiographic assessments via digital orthopantomogram at regular intervals. Because of the rarity of unicystic ameloblastoma, only 17 patients were included in the study (Group A: 9 patients; Group B: 8 patients), with a mean follow-up of 4.9 years (range: 1.4-11.8 years). The primary outcome measure was the absence of recurrence, which indicated treatment success. No patient in either group experienced recurrence within the follow-up period. This study provides evidence supporting the successful treatment of luminal and intraluminal variants of unicystic ameloblastoma in young individuals using a conservative approach. However, the more aggressive mural variant demonstrated favorable outcomes with radical treatment. These findings emphasize the importance of the Ackermann classification in guiding treatment decisions for unicystic ameloblastoma and contribute valuable insights into optimizing therapeutic strategies based on clinico-radiological and histopathological findings.

Assessment of safety culture in radiotherapy facilities using safety performance indicators.

This paper describes the development of the Safety Performance Indicators (SPIs), the methodology for assessment of the safety culture of radiotherapy institutions using SPIs and common strengths and common areas for improvement. SPIs were categorized into eight sections which all together contain 23 attributes and each attribute has scoring criteria from 0 to 2 (in steps of 0.5). The maximum absolute cumulative score of SPIs was 46. A relative cumulative SPIs score of >80% indicates an institution strong commitment towards safety while score <50% indicates need for additional guidance to enhance safety culture. The assessment using SPIs was conducted for 17 radiotherapy institutions. The methodology of assessment includes interactive discussion, direct observations and document analysis. The relative cumulative SPIs score of seven institutions was found to be >80% while it was found in the range of 67.0% to 80% for the remaining ten institutions. Institutions were communicated about the cumulative SPIs score, areas of strengths, and areas for improvement. SPIs were found to be a good tool for safety culture assessment and can be utilized by the radiotherapy institutes for self-assessment to identify the areas of improvement. Based on SPIs score, regulatory body can grade the institutions from a radiation safety compliance point of view.

Role of Intraoperative Documentation: Avoidable Ulnar Nerve Injury During Implant Removal.

Injuries to the ulnar nerve during open reduction and internal fixation of distal humerus fractures are a well-known phenomenon. However, ulnar nerve injury during implant removal has not been well documented. We performed implant removal in a united distal humerus fracture with the aim of improving the elbow's range of motion. Even with proper surgical precautions in place, the ulnar nerve was damaged during dissection. This report aims to provide insight into this rare phenomenon, and the reasons for this injury are examined retrospectively. The importance of operation notes, the surgical approach, anterior transposition of the nerve, and how this and other factors could have helped the surgeons avoid this complication have also been highlighted.

Taking the Road Less Travelled: A Case Report of Distal Splenic Artery Embolisation via the Pancreaticoduodenal Arcade in Splenic Trauma With Celiac Artery Stenosis.

Celiac axis stenosis (CAS) is one of the most prevalent splanchnic arterial pathologies. It seldom results in clinically severe ischemic bowel disease because of the rich collateral circulation from the superior mesenteric artery. Knowledge about the collaterals in celiac artery stenosis guides various interventional procedures. Here, we describe a case of a 19-year-old female with American Association for the Surgery of Trauma (AAST) grade IV splenic injury found to have CAS. Distal splenic artery embolisation was performed via the collateral pathway through the pancreaticoduodenal arcade.

The Distribution Patterns of Rhesus (Rh) Antigens.

INTRODUCTION: The determination of one's blood group is dictated by the inheritance-based diversity in the presence or absence of RBC antigens on the surface. Extended Rhesus (Rh) antigens are the most clinically relevant antigens of blood group systems after the ABO blood group system in transfusion medicine. The aim of this study was to serologically assess the prevalence of extended Rh antigens across diverse blood group systems. METHODS: A total of 2043 samples were tested for the ABO blood group and Rh typing with monoclonal antisera. The Rh phenotyping (C, c, E, e ) was performed on all the samples. RESULTS: The most frequently observed ABO blood group was O (36.5%), while AB (13.6%) was identified as the least prevalent. Positive Rh D antigen was found in 91.6% of tested samples, while 8.4% were Rh D-negative. The most frequently encountered antigen was e, followed by D, while the least prevalent was E. DISCUSSION: Establishing a Rh phenotype repository for blood donors and conducting Rh phenotype assessments as part of pretransfusion testing before initiating the initial blood transfusion for each patient could significantly lower the patients' incidence of alloimmunization.