Comparison of Double Endobutton and Clavicular Hook Plate in Acromioclavicular Joint Disruption: A Systematic Review and Meta-analysis.

BACKGROUND: Acromioclavicular joint (ACJ) disruptions are corrected by surgery either with an endobutton or a hook plate. The results in the long term were found to be similar in many randomized controlled trials. This study aims to conduct a meta-analysis to evaluate the functional outcome and complications of double endo button versus clavicular hook plate (CHP) for ACJ disruption (Rockwood types III-VI). MATERIALS AND METHODS: Two authors independently searched related articles from electronic databases (PubMed, Google Scholar, MEDLINE, SCOPUS, and Web of Science) till January 26, 2022. The data were extracted from the related articles and analyzed by Stata software. For bias calculation of each study, the Newcastle-Ottawa scale and the RevMan 5.4 software were used. RESULTS: 14 cohort studies, 2 randomized control trial studies, and 1 case-control study including patients were selected in this meta-analysis. The results of our study showed a significantly higher Constant-Murley Score (WMD 5.79, 95% confidence interval [CI] 2.23-9.36), Visual Analog Scale (WMD- 0.63, 95% CI [-0.79, -0.46]) and University of California at Los Angeles shoulder score (UCLA) scale (WMD 3.32, 95% CI [2.87, 3.77]) for double endobutton group. At the same time, some complications like implant failure were more common in the double endobutton group. CONCLUSION: This meta-analysis shows better functional and clinical outcomes of shoulder joint for the treatment of acromioclavicular joint (ACJ) disruption cases (Rockwood types III-VI) with no need for secondary operation, unlike the CHP. Complications like subacromial erosion, ACJ arthrodesis, and infection rate are higher in the CHP group, whereas the chance of implant failure is higher in the double endobutton group.

RésuméLes perturbations de l'articulation acromio-claviculaire (ACJ) sont corrigées par chirurgie soit avec un endobouton, soit avec une plaque à crochets. Les résultats à long terme se sont révélés similaires dans de nombreux essais contrôlés randomisés. Cette étude vise à mener une méta-analyse pour évaluer les résultats fonctionnels et les complications du double endobouton par rapport à la plaque à crochet claviculaire (CHP) pour la perturbation de l'ACJ (Rockwood types III ­ VI).Matériels et méthodes:Deux auteurs ont recherché indépendamment des articles connexes dans des bases de données électroniques (PubMed, Google Scholar, MEDLINE, SCOPUS et Web of Science) jusqu'au 26 janvier 2022. Les données ont été extraites des articles connexes et analysées par le logiciel Stata. Pour le calcul du biais de chaque étude, l'échelle de Newcastle-Ottawa et le logiciel RevMan 5.4 ont été utilisés.Résultats:14 études de cohorte, 2 études d'essais contrôlés randomisés et 1 étude cas-témoins incluant des patients ont été sélectionnées dans cette méta-analyse. Les résultats de notre étude ont montré un score de Constant-Murley significativement plus élevé (WMD 5,79, intervalle de confiance [IC] à 95 % 2,23­9,36), une échelle visuelle analogique (WMD− 0,63, IC à 95 % [−0,79, −0,46]) et un score universitaire. de Californie sur l'échelle de score d'épaule de Los Angeles (UCLA) (WMD 3,32, IC à 95 % [2,87, 3,77]) pour le groupe à double endobouton. Dans le même temps, certaines complications comme l'échec de l'implant étaient plus fréquentes dans le groupe à double endobouton.Conclusion:Cette méta-analyse montre de meilleurs résultats fonctionnels et cliniques de l'articulation de l'épaule pour le traitement des cas de rupture de l'articulation acromio-claviculaire (ACJ) (types Rockwood III à VI) sans nécessité d'opération secondaire, contrairement à la CHP. Les complications telles que l'érosion sous-acromiale, l'arthrodèse de l'ACJ et le taux d'infection sont plus élevées dans le groupe CHP, alors que le risque d'échec de l'implant est plus élevé dans le groupe à double endobouton.

Correlation of Pseudocholinesterase Level with Clinical, Biochemical Parameters Including Cardiac Profile and the Outcome in Organophosphorus Poisoning.

BACKGROUND: Poisoning is a significant health hazard and a leading cause of morbidity and mortality worldwide. India, being a predominantly agrarian country, routinely employs organophosphate (OP) pesticides in farming, and they are readily available "over the counter." OPs exert their toxicity by interfering with the normal function of acetylcholine, an essential neurotransmitter throughout the autonomic and central nervous systems. Due to the limited availability of facilities and resources in health-care systems, and economically restraining patients, it is necessary to rely more on clinical features to assess the severity of poisoning and manage the condition properly. METHODOLOGY: It was a hospital-based prospective observational study that included patients aged >13 years in a tertiary care hospital. All patients were clinically evaluated based on their history and examination. The diagnosis was made based on characteristic clinical manifestations or evidence of exposure to organophosphorus compounds (corroborative evidence such as empty containers and the odor of gastric aspirates). Clinical severity was assessed and categorized according to the Peradeniya Organophosphorus Poisoning Scale (POP scale). A score of 0-3 is considered mild poisoning, 4-7 as moderate poisoning, and 8-11 as severe poisoning. RESULTS: Out of the 50 patients enrolled in the study, 17 (34.00%) were aged <20 years, 19 (38%) were in the 20-30 years age group, and 14 (28%) were aged >30 years. Ingestion is the only mode of exposure to poisoning. None of the patients had history of contact or inhalational exposure. Of the 50 cases, 12 (24.0%) were in the mild category, 26 (52.0%) in the moderate category, and 12 (24%) in the severe category on the POP grading. A comparison of the mean serum pseudocholinesterase, troponin-T, and pro-BNP levels with severity was performed. In mild OP poisoning, the mean serum PChE level was 2766.58 ± 1120.44; in moderate, it was 1969.35 ± 1330.07, and in severe, it was 701.83 ± 961.17. Pseudocholinesterase levels decreased progressively with increasing clinical severity from mild-to-severe cases, and this association was statistically significant (P < 0.001). Two-dimensional echocardiography screening done in all patients did not show any significant abnormalities. CONCLUSION: This study shows that serum PCE is reduced in OP poisoning and correlates with the clinical severity grading done by the POP scale and is also associated with an increase in the duration of intensive care unit stay. No significant evidence of direct cardiac injury was observed in this study. A low Glasgow Coma Scale score and an increased respiratory rate at presentation are associated with poor outcomes.

Résumé Contexte:L'empoisonnement est un risque important pour la santé et une cause principale de morbidité et de mortalité dans le monde. L'Inde, étant principalement pays agraire, utilise régulièrement des pesticides organophosphotés (OP) dans l'agriculture, et ils sont facilement disponibles «en vente libre¼. OPS exerce leur toxicité en interférant avec la fonction normale de l'acétylcholine, un neurotransmetteur essentiel à travers l'autonomie et le centre systèmes nerveux. En raison de la disponibilité limitée des installations et des ressources dans les systèmes de soins de santé, et de la contention économique des patients, il est nécessaire pour s'appuyer davantage sur les caractéristiques cliniques pour évaluer la gravité de l'empoisonnement et gérer correctement la condition.Méthodologie:c'était un Étude d'observation prospective basée à l'hôpital qui comprenait des patients âgés de> 13 ans dans un hôpital de soins tertiaires. Tous les patients étaient cliniquement évalué en fonction de leur histoire et de leur examen. Le diagnostic a été posé sur la base de manifestations cliniques caractéristiques ou de preuves de Exposition aux composés organophosphores (preuves corroborantes telles que les conteneurs vides et l'odeur des aspirations gastriques). Gravité clinique a été évalué et classé selon l'échelle d'empoisonnement de Peradeniya organophosphorus (échelle pop). Un score de 0 à 3 est considéré comme doux Empoisonnement, 4­7 comme empoisonnement modéré et 8-11 comme empoisonnement sévère.Résultats:Sur les 50 patients inscrits à l'étude, 17 (34,00%) étaient âgés de <20 ans, 19 ans (38%) dans le groupe d'âge de 20 à 30 ans et 14 (28%) étaient âgés de> 30 ans. L'ingestion est le seul mode d'exposition à empoisonnement. Aucun des patients n'avait des antécédents de contact ou d'inhalation. Sur les 50 cas, 12 (24,0%) étaient dans la catégorie légère, 26 (52,0%) Dans la catégorie modérée, et 12 (24%) dans la catégorie sévère sur le classement POP. Une comparaison de la pseudocholinestérase sérique moyenne, Les niveaux de troponine - T et pro-BNP avec gravité ont été réalisés. Dans l'empoisonnement à l'op léger, le taux de PCHE sérique moyen était de 2766,58 ± 1120,44; dans Modéré, c'était 1969.35 ± 1330,07, et en sévère, il était de 701,83 ± 961,17. Les niveaux de pseudocholinestérase ont diminué progressivement avec l'augmentation Gravité clinique des cas légers à sévère, et cette association était statistiquement significative ( P <0,001). Échocardiographie bidimensionnelle Le dépistage effectué chez tous les patients n'a montré aucune anomalie significative.Conclusion:cette étude montre que le PCE sérique est réduit en op empoisonnement et corréler avec le classement de gravité clinique effectué par l'échelle POP et est également associé à une augmentation de la durée de séjour de l'unité de soins intensifs. Aucune preuve significative de lésion cardiaque directe n'a été observée dans cette étude. Un score d'échelle de coma à faible Glasgow et un Une fréquence respiratoire accrue à la présentation est associée à de mauvais résultats.

Recent progress and new insights on semiconductor heterojunctions powered photocatalytic desulphurization: A review.

Desulphurization of fossil fuels is a critical process in reducing the sulphur content from environment, which is a major contributor to atmospheric pollution. Traditional desulphurization techniques, while effective, often involve high energy consumption and the use of harsh chemicals. Recently, photocatalytic desulphurization has emerged as a promising, eco-friendly alternative, leveraging the potential of photocatalysts especially semiconductor heterojunctions to enhance photocatalytic efficiency. This review comprehensively discusses the significance and mechanism of photocatalytic desulphurization reactions, designing of various heterojunctions such as conventional, p-n, Z-scheme and S-scheme, their charge transfer mechanism and properties and their contribution to the photocatalytic desulphurization activity. Heterojunctions, formed by combining different semiconductor materials, facilitate efficient charge separation and broaden the light absorption range, thereby improving the photocatalytic performance under visible light. Furthermore, the recent advancements in the heterojunction systems in the field of photocatalytic desulphurization activity have been discussed in detail and summarized. The current limitations and challenges in this particular field are also explored. The paper concludes with an outlook on future research directions and the potential industrial applications of heterojunction-powered photocatalytic desulphurization, emphasizing its role in achieving cleaner energy production and environmental sustainability.

Unveiling the potential of molecular imprinting polymer-based composites in the discovery of advanced drug delivery carriers.

Molecularly imprinted polymers (MIPs) are polymeric matrices that can mimic natural recognition entities, such as antibodies and biological receptors. Molecular imprinting of therapeutics is very appealing in the design of drug delivery systems since the specific and selective binding sites created within the polymeric matrix turn these complex structures into value-added carriers with tunable features, notably high drug-loading capacity and good control of payload release. MIPs possess considerable promise as synthetic recognition elements in 'theranostics'. Moreover, the high affinity and specificity of MIPs make them more advantageous than other polymer-based nanocomposites. This review summarizes the present state-of-the-art of MIP-based delivery systems for the targeted delivery of bioactives, with current challenges and future perspectives.

Achieving negative superficial resection margins with NBI and white light in carcinoma oral cavity: Could it be a norm?

INTRODUCTION: In India, oral cavity cancer rates are the highest, largely due to tobacco and areca nut use. The primary goal of oncologic surgery is complete tumor resection with adequate margins, yet no accepted guidelines exist margin identification. NBI enhances mucosal lesion detection and may improve margin assessment in OSCC. AIMS: This study aims to evaluate the proportion of negative superficial resection margins using NBI and to compare these results with margins assessed using white light (WL) examination. MATERIALS AND METHODS: The study at AIIMS, Rishikesh, included 38 patients with T1-T3 biopsy-proven OSCC. Surgical margins were marked using WL and NBI. Histopathology classified margins as clear (>5mm), close (1-5 mm), or involved. Sensitivity, specificity, and predictive values of NBI were calculated. RESULTS: The average NBI examination duration was 227 s. Negative margins were achieved in 68.42 % (>5mm) and 78.94 % (>3mm) of NBI cases, compared to 71.05 % and 84.21 % for WL. NBI had a sensitivity of 12.50 %, specificity of 96.67 %, and overall accuracy of 78.95 %. DISCUSSION: NBI showed high specificity but low sensitivity. This could be due to the smaller number of patients in NBI positive group. In the present study, the single positive margin identified with NBI could also have been detected with the combined approach of white light and palpation, ensuring that no positive margins were missed. CONCLUSION: NBI can complement WL for margin assessment in oral SCC but requires a long learning curve and a dedicated team. Integrating NBI into standard protocols could improve surgical outcomes and reduce recurrence.

IFNλ signaling in neutrophils enhances the pathogenesis of Bordetella pertussis infection.

Interferon lambda (IFN-λ) plays diverse roles in bacterial infections. Previously we showed that IFN-λ is induced in the lungs of B. pertussis-infected adult mice and exacerbates inflammation. Here, we report that mice lacking the IFN-λ receptor (IFNLR1) specifically on neutrophils (MRP8creIFNLR1fl/fl mice) exhibit reduced lung bacterial load and inflammation compared to WT mice during B. pertussis infection. In B. pertussis-infected wild type (WT) mice, lung type I and III IFN responses were higher than in MRP8creIFNLR1fl/fl mice, correlating with increased lung inflammatory pathology. There was an increased proportion of IFN-γ-producing neutrophils in the lungs of MRP8creIFNLR1fl/fl mice compared to WT mice. IFNLR1-/- neutrophils incubated with B. pertussis exhibited higher killing compared to WT neutrophils. Treatment of WT neutrophils with IFN-λ further decreased their bacterial killing capacity and treatment of WT mice with IFN-λ increased lung bacterial loads. Contributing to the differential killing, we found that IFNLR1-/- neutrophils exhibit higher levels of reactive oxygen species, myeloperoxidase [1], matrix metalloproteinase-9 (MMP9) activity, neutrophil extracellular traps (NETs), and IFN-γ secretion than WT neutrophils, and inhibiting NADPH oxidase inhibited bacterial killing in IFNLR1-/- neutrophils. B. pertussis induced IFN-λ secretion and IFNLR1 gene expression in mouse and human neutrophils and this was dependent on the bacterial virulence protein pertussis toxin (PTX). PTX enhanced bacterial loads in WT but not in MRP8creIFNLR1fl/fl or IFNLR1-/- mice. Thus, PTX disrupts neutrophil function by enhancing type III IFN signaling, which prevents neutrophils from effectively clearing B. pertussis during infection, leading to higher bacterial loads and exacerbation of lung inflammation.

Exploiting decarbonylation and dehydrogenation of formamides for the synthesis of ureas, polyureas, and poly(urea-urethanes).

Urea derivatives, polyureas, and poly(urea-urethanes) are materials of great interest. However, their current methods of synthesis involve toxic feedstocks - isocyanate and phosgene gas. There is significant interest in developing alternative methodologies for their synthesis from safer feedstocks. We report here new methods for the synthesis of urea derivatives, polyureas, and poly(urea-urethane) using a ruthenium pincer catalyst. In this approach, urea derivatives and polyureas are synthesized from the self-coupling of formamides and diformamides, respectively, whereas poly(urea-urethanes) are synthesized from the coupling of diformamides and diols. CO and H2 gases are eliminated in all these processes. Decarbonylation of formamides using such organometallic catalysts has not been reported before and therefore mechanistic insights have been provided using experiments and DFT computation to shed light on pathways of these processes.

Repurposing Duloxetine as a Potent Butyrylcholinesterase Inhibitor: Potential Cholinergic Enhancing Benefits for Elderly Individuals with Depression and Cognitive Impairment.

Despite the advent of new treatment strategies, cholinesterase inhibitors (ChEIs) are still the go-to treatment for dementia disorders. ChEIs act by inhibiting the main acetylcholine-degrading enzyme, acetylcholinesterase (AChE). Nonetheless, accumulating evidence indicates that the impact of inhibition of the sister enzyme, butyrylcholinesterase (BChE), could be even broader in older adults due to the multifaceted role of BChE in several biological functional pathways. Therefore, we employed an in silico modeling-based drug repurposing strategy to identify novel potent BChE inhibitors from the FDA drug database. This was followed by in vitro screening and ex vivo enzyme kinetic validation using human plasma samples as the source of BChE. The analysis revealed that the antidepressant drug, duloxetine, inhibited BChE with high selectivity in comparison to AChE. In contrast, two other antidepressants, namely, citalopram and escitalopram exhibited a weak to moderate activity. Ex vivo enzyme inhibition kinetic analyses indicated that duloxetine acted as a competitive inhibitor of BChE with an inhibition constant (K i) of 210 nM. This K i value is comparable with 100-400 nM concentration of duloxetine following normal dosages in humans, thereby indicating that duloxetine should be able to induce a pharmacologically and biologically relevant in vivo inhibition of BChE. Additionally, we performed the enzyme inhibition kinetic assessment in parallel for ethopropazine, a known potent selective BChE inhibitor, and physostigmine, a dual inhibitor of AChE and BChE. These analyses indicated that duloxetine should be considered a potent BChE inhibitor since its K i was comparable with ethopropazine (K i = 150 nM) but was 4 times smaller than that of physostigmine (K i = 840 nM). In conclusion, this study reports the discovery of duloxetine being a highly potent selective competitive BChE inhibitor. This, in turn, indicates that duloxetine could be the choice of antidepressive treatment in older adults with both depressive and dementia symptoms since it may offer additional clinically beneficial effects via this secondary mode of cholinergic enhancing action.

Evaluation of MicroRNA 145 and MicroRNA 155 as Markers of Cardiovascular Risk in Chronic Kidney Disease.

Background Chronic kidney disease (CKD) leads to a progressive decline in renal function, primarily due to deteriorating kidney structures. Vascular calcification is a key effect of CKD. MicroRNAs (miRNAs) play a significant role in the onset and progression of both cardiovascular illness and CKD. Aim The aim of this study was to compare biomarkers of endothelial dysfunction, 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (iPTH), miRNA 155, and miRNA 145, in patients with CKD versus controls. Methods We recruited 60 patients with CKD and 60 controls. All participants underwent brachial artery flow-mediated dilatation (FMD). Asymmetric dimethylarginine (ADMA) levels were measured using ELISA. Levels of miRNA 145 and miRNA 155 were quantified using real-time polymerase chain reaction (PCR). Results Serum levels of miRNA 145, miRNA 155, 25(OH)D, and FMD were significantly lower in CKD patients compared to controls. Conversely, serum ADMA and iPTH levels were significantly higher in CKD patients. There was a significant negative association between miRNA 145, miRNA 155, FMD, and 25(OH)D with ADMA and iPTH. Additionally, miRNA 145, miRNA 155, FMD, and 25(OH)D showed a significant positive correlation with estimated glomerular filtration rate (eGFR) and with each other. Conclusion Lower levels of miRNA 145 and miRNA 155 and increased endothelial dysfunction correlate with CKD severity, suggesting an accelerated risk for cardiovascular disease (CVD).

Rational design and computational evaluation of a multi-epitope vaccine for monkeypox virus: Insights into binding stability and immunological memory.

Multi-epitope vaccines strategically tackle rapidly mutating viruses by targeting diverse epitopes from different proteins, providing a comprehensive and adaptable immune protection approach for enhanced coverage against various viral variants. This research employs a comprehensive approach that includes the mapping of immune cells activating epitopes derived from the six structural glycoproteins (A29L, A30L, A35R, L1R, M1R, and E8L) of Monkeypox virus (Mpox). A total of 7 T-cells-specific epitopes, 13 B-cells-specific epitopes, and 5 IFN-γ activating epitopes were forecasted within these glycoproteins. The selection process focused on epitopes indicating high immunogenicity and favorable binding affinity with multiple MHC alleles. Following this, a vaccine has been formulated by incorporating the chosen epitopes, alongside adjuvants (PADRE peptide) and various linkers (EAAAK, GPGPG, and AAY). The physicochemical properties and 3D structure of the multi-epitope hybrid vaccine were analysed for characterization. MD simulations were employed to predict the binding stability between the vaccine and various pathogen recognition receptors such as TLRs (TLR1, TLR2, TLR4, and TLR6), as well as both class I and II MHC, achieved through hydrogen bonding and hydrophobic interactions. Through in silico cloning and immune simulation, it was observed that the multi-epitopes vaccine induced a robust memory immune response upon booster doses, forecasting protective immunity upon viral challenge. This protective immunity was characterized by the production of IgM + IgG antibodies, along with release of inflammatory cytokines like IFN-γ, and IL12, and the activation of various immune cells. This study offers valuable insights into the potential of a multi-epitope vaccine targeting the Mpox virus.

Primary tumor lymphangiogenesis in oral squamous cell carcinoma with N0 neck is the key determinant of its therapeutics.

BACKGROUND: Vascular Endothelial Growth Factor-C (VEGF-C) plays a critical role in tumor growth and invasion through lymphangiogenesis and helps to identify the variability of lymphatic potential of oral squamous cell carcinoma (OSCC) cases with or without lymph node metastasis. MATERIALS AND METHODS: A total of 65 cases of OSCC were included. The clinical details were obtained from patient records. The cases were grouped as N0 versus any N categories. All the cases were immunohistochemically evaluated for VEGF-C within the primary tumor using a standard protocol. An average of 5 lymph nodes were dissected from all neck dissection specimens and were evaluated histopathologically. The data obtained were statistically evaluated at 95% confidence interval and P ≤ 0.05. RESULTS: 100% cases in our study showed VEGF-C immunopositivity. The immunoreactivity increased linearly with advancing grades. A total of 31 out of 40 N0 OSCC revealed score 2 (26%-50%) of VEGF-C immunoreactivity. Eighteen cases were false negative clinically. CONCLUSION: Recognition of locoregional spread may empower clinicians for correct therapeutic decisions in N0 versus any N case.

Biochar and biosorbents derived from biomass for arsenic remediation.

Global groundwater contamination by Arsenic (As) presents a grave danger to the health of living beings and wildlife, demanding comprehensive remediation strategies. This review delves into the complex landscape of arsenic remediation, encompassing its chemical forms, occurrences, sources, and associated health risks. Advanced techniques, notably biomass-derived adsorbents, emerge as promising and cost-effective solutions. The exploration spans preparing and modifying biomass-derived adsorbents, unraveling their adsorption capacity, influencing factors, isotherms, kinetics, and thermodynamics. Noteworthy attention is given to plant-agricultural waste, algal-fungal-bacterial, and iron-modified biomass-derived adsorbents. The comprehensive discussion of the adsorption mechanism highlights the efficacy of low-cost biomass, particularly from plant, animal, and agricultural residues, offering a sustainable remedy for arsenic removal. This insightful review contributes to the understanding of evolving technologies essential for addressing arsenic contamination in wastewater, emphasizing the potential of renewable biomaterials in advancing efficient remediation practices.

Sublingual Atropine Administration for Clozapine-Induced Sialorrhea in Bipolar Disorder: A Case Report Highlighting its Efficacy, Safety Concerns and Challenges.

We discuss a case with off-label sublingual administration of atropine for clozapine-induced sialorrhea (CIS) after failure of two commonly used agents to manage CIS. Atropine had a demonstrable efficacy, as measured by means of sialometry conducted before and after its administration. The salivary rate, initially measured at 0.60 g/min one hour before atropine administration, reduced to 0.23 g/min two hours after administration. Sublingual administration of atropine was found to be an efficacious option for this patient, but safety issues particularly tachycardia and pragmatics such as risk of inadvertent overdose led to its discontinuation after the initial dose. Developing micro-dosing devices for sublingual atropine could enhance administration precision, reduce side effects, and provide a cost-effective solution. The case report also underscores the need to employ sialometry for the objective assessment of treatment outcomes in future research trials for hypersalivation.

Emerging Nanotechnology Involved in Skin Cancer: Pathogenesis, Biomarkers, Ethosomal Formulation and Future Perspective.

Skin cancer, which comprises both melanoma and non-melanoma forms, is frequently diagnosed as the predominant malignancy among today's population. Existing treatments are often prolonged and complex, have a low rate of success, and have side effects. This complexity leads to poor patient adherence and increases the risk of disease recurrence. Ethosomes, extensively studied for their applications in topical and transdermal therapies, are distinguished by their high ethanol content, which facilitates enhanced skin penetration and efficient drug delivery. Compared to traditional liposomes, ethosomes offer notable advantages due to their unique composition, demonstrating potential efficacy in treating various skin conditions, including basal cell carcinoma, squamous cell carcinoma, and melanoma. The present review provides a brief introduction to skin melanoma and its pathogenesis, signalling pathways, biomarkers, the need for ethogel-based drug delivery, applications of ethosomes against skin cancer, and clinical trials.

The BCOR-rearranged sarcoma involving the lung: Diagnosis with clinical outcome and literature review.

ABSTRACT: BCOR-rearranged sarcomas (BRS) constitute relatively newly described sarcomas, which, within the musculoskeletal sites, usually occur in the bones, followed by soft tissues. Primary BRS involving the visceral organs is very rare, and only a single case is reported in the lung. These tumors share overlapping morphological and immunohistochemical (IHC) features with other neoplasms, such as synovial sarcoma, Ewing sarcoma, as well as carcinosarcoma, the latter especially when occurring in the visceral organs. BCOR immunostaining is useful in triaging a tumor for molecular diagnosis, which constitutes the "essential" diagnostic criterion for these tumors. To report an extremely rare case of a BRS, confirmed by BCOR-rearrangement by fluorescence in situ hybridization (FISH), primarily occurring in the lung, emphasizing the diagnostic approach and management, along with review of literature. An18-year-old boy presented with complaints of left-sided chest pain, along with cough, fever, loss of appetite, and weight. On radio imaging, there was a complete collapse of the left lower lobe of lung with moderate pleural effusion. The biopsy showed a biphasic tumor comprising primitive round cells admixed with spindle cells. Immunohistochemically, the tumor cells were positive for BCOR, TLE1, and p53. FISH showed BCOR gene rearrangement. A diagnosis of primary BRS of lung was offered. The patient had a favorable response to the chemotherapy regime. BRS is an ultra-rare tumor, which rarely involves visceral organs. The lung is an exceptionally rare site, with only single reported case previously. An exact confirmation by molecular testing has treatment-associated implications. A review of similar reported cases is presented herewith.

Synovial Chondromatosis with Genu Valgum in a Patient of Wilson's Disease.

Introduction: Wilson's disease is an autosomal recessive condition where excessive amount of copper accumulates in the body, especially in the liver, brain, and eyes. It is caused by a mutation in the ATP7B gene on chromosome 13. In 25-30% of patients, joint involvement occurs at the later course of disease; osteoarthritis being the commonest manifestation. Synovial chondromatosis (SC) is a benign metaplasia which occurs in the synovial membrane and it results in the formation of intra-articular loose bodies (LB), but its occurrence in a patient of Wilson's disease has not yet been reported in medical literature. Case Report: A young male in his 30s, a diagnosed case of Wilson's disease on maintenance therapy of d-penicillamine, zinc, trientine, and lithium presented to the hospital with restriction of movement at the knee joints and a valgus deformity. Examination showed firm to hard globular swellings which were partly mobile around the knee joint. The Magnetic Resonance Imaging (MRI) findings were suggestive of a SC after which the patient underwent corrective surgery and debridement and removal of the LB and a histopathology report confirmed the diagnosis. The patient was followed up at 12 weeks and was found to have pain-free movements with minimal support. His 24-h urinary copper excretion was found to be within normal limits and his maintenance therapy was optimized. The patient was initiated on speech therapy for his persistent slurring of speech and psychiatric counseling for rehabilitation in social and personal life. The patient was advised for 6 monthly follow-up. Conclusion: This case summarizes the unique presentation of SC with genu valgum in a patient of Wilson's disease and hence warrants a keen eye for the physician and orthopedician alongside osteoarthritis; which has been widely reported in Wilson's disease, thus providing an opportunity for early correction of valgus deformity of the subject.

Recent advances and progress in immunotherapy of solid cancers.

Adoptive cell therapy using chimeric antigen receptor (CAR) technology has become mainstream by employing advanced engineering platforms to promote cancer immunotherapy. CAR T cells have shown remarkable efficacy in the treatment of hematological malignancies; however, the value of this therapy remains inconclusive in the context of solid tumors. Immunotherapy of solid tumors is restrained by several obstacles including the presence of an immunosuppressive tumor microenvironment (TME), limited tumor trafficking, inhibited immune cell infiltration, absence of tumor-specific antigens, and off-target toxicity and adverse events associated with these therapies. Despite recent advances in CAR T cell construction, including the integration of co-stimulatory domains and the creation of armed CAR T cells, with promising outcomes in the treatment of some solid tumors, there are still many unresolved obstacles that need to be overcome. To surmount these impediments to effective CAR T cell therapies, other immune cells, such as natural killer cells and macrophages, have been engineered to serve as appealing alternatives for successful cancer immunotherapy of solid tumors. CAR NK cells demonstrate significant clinical advantages due to their ready availability and minimal toxicity. CAR macrophage (M) cells provide considerable therapeutic potential due to their ability to penetrate the TME of solid tumors. In this review, we comprehensively examine the latest developments and prospects of engineered immune cell-based cancer immunotherapies specifically designed for treating solid tumors. In addition, we provide a concise overview of current clinical trials that are examining the safety and effectiveness of modified immune cells, such as CAR T, CAR NK, and CAR M, in their ability to specifically target solid tumors and promote improved therapeutic outcomes in patients with diverse solid cancers.

Precision medicine focus on the central nervous system: Non-invasive therapeutic agent delivery with focused ultrasound and microbubbles.

Focused ultrasound (FUS) combined with microbubble (MB) treatment is a promising strategy capable of accurately delivering molecular medicines and gene therapy to treat various disease states. The rapid progression and use of FUS technology, from its inception to applications in contemporary medicine, exemplifies the significance and expanding potential of this technology. FUS for drug delivery in the brain can overcome challenging obstacles posed by the blood-brain barrier (BBB) in treating central nervous system (CNS) disorders. Both FUS and magnetic resonance imaging-guided FUS are non-invasive techniques for effectively opening the BBB and enhancing the transportation of molecular medicines and imaging agents into the brain. By integrating MBs into this process, it is possible to disrupt the BBB, facilitating delivery of therapeutic compounds including neuropeptides, proteins, antibodies, chemotherapeutic drugs and recently viruses accurately into the CNS. The safety and versatility of ultrasound makes it an attractive approach for administering molecular medicines, with potential applications extending beyond neurological disorders to include cancer treatment and other medical fields. Preclinical and clinical studies confirm that FUS is safe and efficient in enhancing drug administration, particularly where delivery to a precise location in the CNS is required. Combination therapies that utilize FUS and MBs also provide synergistic responses in cancer therapy. Further refining FUS and MB approaches both from a mechanical and reagent perspective will be forthcoming in the future and prove valuable in precisely defining targets and broadening therapeutic applications. Continued development and applications of FUS and MB technologies will improve therapeutic outcomes and advance patient care in multiple diseases states. This will elevate FUS and MBs from infrequently used medical options to mainstream medical applications.

An electronic energy compensation method for flattening the energy response of SiPM-GGAG:Ce,B based gamma detector.

The energy response of gross gamma dose rate monitors needs to be flat in order to prevent overestimation of dose at low gamma energies. In this paper, a discriminator threshold modulation based electronic energy compensation algorithm has been proposed for SiPM-scintillator based gamma detectors. Theoretical simulation studies were carried out in order to optimize the parameters of the periodic ramp voltage used for modulation of the discriminator threshold of a SiPM-GGAG:Ce,B based gamma dose rate monitor. A customized threshold modulation circuit and signal processing electronics were developed for this gamma detector. For experimentally optimizing the parameters, the energy response studies of the detector, with and without the discriminator threshold modulation, were carried out. With the optimized parameters for a periodic ramp threshold, the count rates for 241Am (60 keV) and 60Co (1173 and 1332 keV) were observed to be within ±30% of the count rate obtained for 137Cs (662 keV). Using the electronic energy compensation techniques presented in this paper, a flat energy response of the SiPM-scintillator gamma detector for the energy range of 60 keV to 1.5 MeV could be achieved.

Experimental and theoretical validation for transmutation of palladium at electrochemical interfaces.

Electrolysis of D2O may be used as a portable neutron source with numerous applications without the complexity of huge reactor operations. Herein, we report reproducible fast neutron generation by electrolysis of D2O using palladium cathode and platinum anode, which was detected with diamond detector, gas filled 3He detectors after thermalisation with high density polythene, as well as novel epoxy resin and CR-39 detectors. Notably, a highly reproducible neutron generation at electrochemical surfaces of palladium electrode was observed and signature transmutation via Pd (d, n) Ag was corroborated. This was further explained using a theoretical model based on second order quantum perturbation theory.