Optimising Patient Outcomes in Tongue Cancer: A Multidisciplinary Approach.

A multidisciplinary approach to the management of tongue cancer is vital for achieving optimal patient outcomes. Nursing and allied health professionals play essential roles within the team. We developed symposia comprising a series of online lectures offering a detailed perspective on the role each discipline and consumer perspective has in the management of patients with tongue cancer. The topics, including epidemiology and prevention, diagnosis, treatment planning, surgery, adjuvant care, and the management of recurrent or metastatic disease, were thoroughly examined. The symposia highlighted the significance of fostering collaboration and continuous learning through a multidisciplinary approach. This initiative should be relevant to healthcare professionals, researchers, and policymakers striving to enhance patient outcomes in tongue cancer care through innovative collaboration.

Statistical modelling, optimization, and mechanistic exploration of novel ureolytic Enterobacter hormaechei IITISM-SA3 in cadmium immobilization under microbial inclusive and cell-free conditions through microbially induced calcite precipitation.

The study aimed to evaluate the potential of a novel isolated ureolytic Enterobacter hormaechei IITISM-SA3 in cadmium bioremoval through MICP. The optimization and modelling of the biotic and abiotic factors affecting the process of mineralization were also performed. In addition, the underlying mechanism of MICP-driven Cd mineralization under microbial-inclusive and cell-free conditions was revealed and supported through the characterization of the bio-precipitates obtained using various characterization techniques. The results indicated that the isolate could remove 97.18% Cd2+ of 11.4 ppm under optimized conditions of 36.86 h, pH 7.63, and biomass dose of 1.75 ml. Besides, the presence and absence of bacterial cells were found to influence both the morphologies and crystalline structures of precipitates. The precipitates obtained under microbial-inclusive conditions showed typical rhombohedral crystalline structures of the composition comprising CaCO3, CdCO3, and 0.67Ca0.33CdCO3. However, the crystalline nature of the precipitate reduced to a nano-sized granular structure in cell-free media. Unlike the cadmium mineralization process under microbial-inclusive media, where bacterial cells serve as nucleation sites for crystallization, the carbonate precipitation effectively captures Cd2+ through co-precipitation, chemisorption, or alternative mechanisms involving interactions between metal ions and CaCO3 under cell-free conditions. The findings presented suggest that using cell-free culture supernatant enriched with carbonate ions provides an avenue that could be harnessed for sustainable metal remediation.

Trends in age of tobacco use initiation over time in Bangladesh, India and Pakistan: analysis of cross-sectional nationally representative surveys.

OBJECTIVE: Tobacco use begins at an early age and typically leads to a long-term addiction. The age of initiation for tobacco use is not well studied in South Asia, where 22% of tobacco smokers and 81% of smokeless tobacco (SLT) users reside. METHODS: Data from the nationally representative Global Adult Tobacco Surveys in India, Bangladesh and Pakistan were analysed to examine patterns of initiation among smokers and smokeless tobacco users. RESULTS: Data on 94 651 individuals were analysed, of which 13 396 reported were ever daily smokers and 17 684 were ever SLT users. The proportion of individuals initiating tobacco use before the age of 15 years has increased over time. The rates of SLT initiation among those aged 15-24 years increased markedly in Bangladesh (by 7.8%) and Pakistan (by 37.7%) between 1983 and 1999-2000. Among males, the increase in SLT initiation was higher in individuals aged below 15 years compared with other age groups in India and Bangladesh. Smoking initiation among females aged below 15 years has also significantly increased in India over time. Compared with the initiation of tobacco smoking before the age of 15 years, a greater increase in the proportion of SLT users was observed in urban areas. CONCLUSION: Our findings indicate that the proportion of youth initiating tobacco (both smoking and smokeless) before the age of 15 years has increased over time in all three countries. Moreover, variations in age at initiation for different types of tobacco products across countries, and by rurality, were noticeable. Younger youths (aged up to 15 years) should therefore be a priority population for tobacco control interventions. Strategies such as raising the legal age of tobacco sale and use to 21 years, and, other measures under WHO Framework Convention on Tobacco Control (FCTC), may prevent underage use and avert lifelong addiction to tobacco products.

Cerebrospinal fluid tumor necrosis factor-alpha (TNF-α) levels in children with cerebral malaria.

This prospective cross-sectional study evaluated the diagnostic and prognostic role of cerebrospinal fluid (CSF) tumor necrosis factor-alpha (TNF-α) in children with cerebral malaria (CM) and its role in the differentiation of CM from non-cerebral severe malaria. CSF TNF-α was measured using a human TNF-α enzyme-linked immunosorbent assay kit of 39 cases of CM and 19 cases of non-cerebral severe malaria. CSF TNF-α levels were significantly higher in CM (p < 0.001). Based on the receiver operating characteristics curve, a cutoff value of CSF TNF-α was 5.7 pg/ml for diagnosis of CM with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 87.2%, 94.7%, 97.1% and 78.3% respectively. The cutoff value of CSF TNF-α was 13.7 pg/ml for predicting adverse outcomes in CM with sensitivity, specificity, PPV and NPV of 100%, 96.8%, 88.9% and 100%, respectively. However, the cutoff value of CSF TNF-α was 4.96 pg/ml for predicting adverse outcomes in non-cerebral severe malaria with a sensitivity, specificity, PPV and NPV of 100%, 94.1%, 88.9% and 100% respectively. So, CSF TNF-α is an excellent biomarker and can be used as a diagnostic and prognostic tool. More studies are needed to establish CSF TNF-α as a predictor of neurological sequelae.

Role of Neurokinin B in gametogenesis and steroidogenesis of freshwater catfish, Clarias batrachus.

Neurokinin B (NKB), a recently discovered neuropeptide, plays a crucial role in regulating the kiss-GnRH neurons in vertebrate's brain. NKB is also characterized in gonadal tissues; however, its role in gonads is poorly understood. Therefore, in the present study, the effects of NKB on gonadal steroidogenesis and gametogenesis through in vivo and in vitro approaches using NKB antagonist MRK-08 were evaluated. The results suggest that the NKB antagonist decreases the development of advanced ovarian follicles and germ cells in the testis. In addition, MRK-08 further reduces the production of 17ß-estradiol in the ovary and testosterone in the testis under both in vivo and in vitro conditions in a dose-dependent manner. Furthermore, the in vitro MRK-08 treatment of gonadal explants attenuated the expression of steroidogenic marker proteins, i.e., StAR, 3ß-HSD, and 17ß-HSD dose-dependently. Moreover, the MAP kinase proteins, pERK1/2 & ERK1/2 and pAkt & Akt were also downregulated by MRK-08. Thus, the study suggests that NKB downregulates steroidogenesis by modulating the expressions of steroidogenic marker proteins involving ERK1/2 & pERK1/2 and Akt/pAkt signalling pathways. NKB also appears to regulate gametogenesis by regulating gonadal steroidogenesis in the catfish.

Outcomes of children with idiopathic steroid resistant nephrotic syndrome: a single centre observational study / Desfechos de crianças com síndrome nefrótica idiopática córtico-resistente: um estudo observacional de centro único

ABSTRACT Introduction: Idiopathic steroid resistant nephrotic syndrome (SRNS) has variable outcomes in children. The primary objective of the present study was to assess the cumulative remission rate and the secondary objectives were to assess factors affecting the remission status, kidney function survival, and adverse effects of medications. Methods: One hundred fourteen patients with SRNS were included. Calcineurin inhibitor-based treatment protocol along with prednisolone and angiotensin-converting enzyme inhibitor were used, and patients were followed over 5 years. Results: Median age was 4.5 years; 53.5% of cases were between 1 to 5 years of age. Sixty-two patients (54.4%) were at initial stage and 52 (45.6%) were at a late SRNS stage. Median eGFRcr was 83.5 mL/min/1.73m2 at presentation. Of the 110 patients, 63 (57.3%) achieved remission [complete remission 30 (27.3%), partial remission 33 (30%)], and 47 (42.7%) had no remission. Kidney function survival was 87.3% and 14 cases (12.7%) had progression to CKD (G3-8, G4-3, G5-1, and G5D-2). Median duration of follow up was 36 months (IQR 24, 60). Age of onset, cyclosporine/tacrolimus, eGFRcr, and histopathology (MCD/FSGS) did not affect remission. Similarly, remission status in addition to age of onset, drug protocol, and histopathology did not significantly affect kidney function during a period of 5 years. Hypertension, cushingoid facies, short stature, cataract, and obesity were observed in 37.7, 29.8, 25.5, 17.5, and 0.7% of cases, respectively. Conclusion: About half of the cases achieved remission. Age of onset of disease, cyclosporine/tacrolimus use, and histopathological lesion neither affected remission status nor short-term kidney function survival in SRNS.

RESUMO Introdução: A síndrome nefrótica idiopática córtico-resistente (SNICR) apresenta desfechos variáveis em crianças. O objetivo principal deste estudo foi avaliar a taxa de remissão cumulativa. Os objetivos secundários foram avaliar fatores que afetam status de remissão, sobrevida da função renal e efeitos adversos de medicamentos. Métodos: Foram incluídos 114 pacientes com SNCR. Utilizou-se protocolo de tratamento baseado em inibidores de calcineurina juntamente com prednisolona e inibidor da enzima conversora de angiotensina. Os pacientes foram acompanhados durante 5 anos. Resultados: A idade mediana foi 4,5 anos; 53,5% dos casos tinham entre 1 e 5 anos. 62 pacientes (54,4%) estavam em estágio inicial; 52 (45,6%) em estágio tardio da SNCR. A TFGecr mediana foi 83,5 mL/min/1,73 m2 na apresentação. Dos 110 pacientes, 63 (57,3%) alcançaram remissão [remissão completa 30 (27,3%), remissão parcial 33 (30%)], e 47 (42,7%) não apresentaram remissão. A sobrevida da função renal foi 87,3%; 14 casos (12,7%) progrediram para DRC (G3-8, G4-3, G5-1, G5D-2). A duração mediana do acompanhamento foi 36 meses (IIQ 24, 60). Idade no início, ciclosporina/tacrolimus, TFGecr e histopatologia (DLM/GESF) não afetaram a remissão. Igualmente, status de remissão, além da idade no início, protocolo de medicamentos e histopatologia não afetaram significativamente a função renal por 5 anos. Observou-se hipertensão, fácies cushingoide, baixa estatura, catarata e obesidade em 37,7; 29,8; 25,5; 17,5; e 0,7% dos casos, respectivamente. Conclusão: Aproximadamente metade dos casos alcançou remissão. Idade no início, uso de ciclosporina/tacrolimus e lesão histopatológica não afetaram o status de remissão nem a sobrevida da função renal a curto prazo na SNICR.

Important Considerations in the Diagnosis and Management of Post-transplant Lymphoproliferative Disorder.

PURPOSE OF REVIEW: A relative lack of molecular and clinical studies compared to other lymphoid cancers has historically made it difficult to determine optimal management approaches in post-transplant lymphoproliferative disorder (PTLD). We sought to better define the "state of the science" in PTLD by examining recent advances in risk assessment, genomic profiling, and trials of PTLD-directed therapy. RECENT FINDINGS: Several major clinical trials highlight risk-stratified sequential therapy incorporating rituximab with or without chemotherapy as a rational treatment strategy in patients with CD20+ PTLD who do not respond to reduction of immunosuppression alone. Epstein Barr virus (EBV)-targeted cytotoxic lymphocytes are a promising approach in patients with relapsed/refractory EBV+ PTLD, but dedicated clinical trials should determine how autologous chimeric antigen receptor T cell therapy (CAR-T) may be safely administered to PTLD patients. Sequencing studies underscore the important effect of EBV infection on PTLD pathogenesis, but comprehensive genomic and tumor microenvironment profiling are needed to identify biomarkers that predict response to treatment in this clinically heterogeneous disease.

Combinatorial treatment rescues tumour-microenvironment-mediated attenuation of MALT1 inhibitors in B-cell lymphomas.

Activated B-cell-like diffuse large B-cell lymphomas (ABC-DLBCLs) are characterized by constitutive activation of nuclear factor κB driven by the B-cell receptor (BCR) and Toll-like receptor (TLR) pathways. However, BCR-pathway-targeted therapies have limited impact on DLBCLs. Here we used >1,100 DLBCL patient samples to determine immune and extracellular matrix cues in the lymphoid tumour microenvironment (Ly-TME) and built representative synthetic-hydrogel-based B-cell-lymphoma organoids accordingly. We demonstrate that Ly-TME cellular and biophysical factors amplify the BCR-MYD88-TLR9 multiprotein supercomplex and induce cooperative signalling pathways in ABC-DLBCL cells, which reduce the efficacy of compounds targeting the BCR pathway members Bruton tyrosine kinase and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1). Combinatorial inhibition of multiple aberrant signalling pathways induced higher antitumour efficacy in lymphoid organoids and implanted ABC-DLBCL patient tumours in vivo. Our studies define the complex crosstalk between malignant ABC-DLBCL cells and Ly-TME, and provide rational combinatorial therapies that rescue Ly-TME-mediated attenuation of treatment response to MALT1 inhibitors.

Recent advancements in cadmium-microbe interactive relations and their application for environmental remediation: a mechanistic overview.

The toxic and persistent nature of cadmium (Cd) in the environment has become a matter of concern with its drastic increase in the concentrations over past few decades. Among the various techniques, the microbial remediation has been accepted as an effective decontamination tool for environmental applications, which is sustainable over a period of time. The Cd decontamination potential of the microbes depends on various internal and external factors that play a crucial role in selection of the microbes for application in a particular environment. Thus, it is important to understand the role of these factors for optimal application of the microbes. This study provides an insight into the mechanisms involved between the microbes and the environmental Cd. The study also briefly reviews the mathematical models that have been used to predict the remediation potential of the microbes and the kinetics involved during the process. A critical analysis of the recent advancements in the techniques for use of bacteria, fungi, and algal cells to remove Cd has been also presented in the manuscript.

Prevalence of smoking and smokeless tobacco use during breastfeeding: A cross-sectional secondary data analysis based on 0.32 million sample women in 78 low-income and middle-income countries.

Background: Smoking and smokeless tobacco use during the postpartum period is well studied in high-income countries, whereas low-income and middle-income countries (LMICs) lack evidence. Methods: In this cross-sectional study we used data from the Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) conducted in 78 LMICs between January 2010 and December 2019 to study tobacco use among 0.32 million sample lactating women. Age-standardized prevalence of smoking and smokeless tobacco use was estimated and presented with a 95% Confidence Interval (CI) for 78 LMICs. Pooled estimates overall and by WHO regions were obtained using random-effects meta-analyses. Country-level and community-level variance to understand contextual factors was also quantified using multilevel modelling. Findings: Pooled prevalence of any tobacco use among breastfeeding women in LMICs was 3.61% (95% CI 3.53-3.70); with the lowest prevalence in regions of the Americas (1.44%, 1.26-1.63) and the highest in the Southeast Asia region (6.13%, 6.0-6.27). The pooled prevalence of tobacco smoking was reported to be 1.16% (1.11-1.21), with the highest prevalence in the Eastern Mediterranean region (4.27%, 3.88-4.67) and the lowest in the African region (0.81%, 0.76-0.86). The pooled prevalence of smokeless tobacco use was reported to be 2.56% (2.49-2.63), with the highest prevalence in the Southeast Asia region (4.92%, 4.80-5.04). Illiterate and poor women in LMICs bore the enormous burden of tobacco use. Interpretation: The prevalence of smoking and smokeless tobacco use among lactating women in LMICs varied considerably across different WHO regions. Considering the cross-sectional design of the study, caution is required while interpreting the results. To improve mothers' and children's health and nutrition outcomes and reduce health inequalities in LMICs, reducing tobacco use through evidence-based interventions is critical. Funding: None.

Comparative Evaluation of Efficacy and Safety of the Diode Laser (980 nm) and Sclerotherapy for the Treatment of Oral Pyogenic Granuloma.

Background: Pyogenic granuloma (PG) is a tumor-like, non-neoplastic lesion of the soft tissue that commonly appears in the oral cavity. Various treatment modalities have been discussed, including surgical excision, cryosurgery, curettage, electrodessication, corticosteroid injection, sclerotherapy, and lasers. This observational retrospective study compared effectiveness between diode lasers and sclerotherapy for PG treatment. Materials and Methods: From July 2016 to January 2021, data of oral PG cases treated with sclerotherapy and diode lasers were gathered. Patients were evaluated and categorized according to their gender, sex, site of lesions, size of lesions, number of sessions, details of side effects, details of the VAS (Visual Analogue Scale) on third postoperative day, response of treatment to individual groups, time required for complete resolution, and details of recurrence. Inferential statistical analysis was performed. Results: We included 73 patients, of whom 43 and 30 received laser and sclerotherapy treatment, respectively. Compared with the sclerotherapy group, the laser group had less side effects including pain, edema, ulceration, ecchymosis, infections, and scarring. The difference in postoperative pain (VAS scale) between the groups was statistically significant (p-value 0.004). Complete remission was seen in the laser group, while 3 cases of the sclerotherapy group had no response (p-value -0.034). The laser group experienced greater recurrence than did the sclerotherapy group. Conclusions: Both sclerotherapy with laser and 3% sodium tetradecyl sulfate are effective for treating oral PG. Sclerotherapy is more effective in preventing recurrence. In terms of side effects, diode lasers are superior to sclerotherapy.

Military exposures and lung cancer in United States veterans.

Lung cancer screening begins at age 50, with yearly low dose computed tomography (LDCT) scans until age 80, for patients determined to be high risk due to tobacco smoking. Veterans serving from World War II to the Gulf War are now at the age where LDCT is recommended. This recommendation from the United States Preventative Service Task Force includes patients who have a 20-pack year tobacco history and currently smoke or quit within the last 15 years. This recommendation does not consider additional risk factors such as exposures to lung carcinogens. We discuss unique operational and occupational exposures encountered while serving in the armed forces, which may potentially increase the risk of lung cancers in the Veteran population. The additional risk of lung cancer due to military exposure history is unclear and more work is needed to identify and quantify risk at an individual level. Increasing awareness at the provider level regarding the carcinogenic exposures encountered may allow a larger population of Veterans, not meeting traditional LDCT criteria, to benefit from lung cancer screening.

Microbiome as an immune regulator in health, disease, and therapeutics.

New discoveries in drugs and drug delivery systems are focused on identifying and delivering a pharmacologically effective agent, potentially targeting a specific molecular component. However, current drug discovery and therapeutic delivery approaches do not necessarily exploit the complex regulatory network of an indispensable microbiota that has been engineered through evolutionary processes in humans or has been altered by environmental exposure or diseases. The human microbiome, in all its complexity, plays an integral role in the maintenance of host functions such as metabolism and immunity. However, dysregulation in this intricate ecosystem has been linked with a variety of diseases, ranging from inflammatory bowel disease to cancer. Therapeutics and bacteria have an undeniable effect on each other and understanding the interplay between microbes and drugs could lead to new therapies, or to changes in how existing drugs are delivered. In addition, targeting the human microbiome using engineered therapeutics has the potential to address global health challenges. Here, we present the challenges and cutting-edge developments in microbiome-immune cell interactions and outline novel targeting strategies to advance drug discovery and therapeutics, which are defining a new era of personalized and precision medicine.

Peptide functionalized DNA hydrogel enhances neuroblastoma cell growth and differentiation.

Designing programmable biomaterials that could act as extracellular matrices and permit functionalization is a current need for tissue engineering advancement. DNA based hydrogels are gaining significant attention owing to their self-assembling properties, biocompatibility, chemical robustness and low batch to batch variability. The real potential of DNA hydrogels in the biomedical domain remains to be explored. In this work, a DNA hydrogel was coated on a glass surface and coupled to a synthetic IKVAV peptide by a chemical crosslinker. We observe enhanced neuronal differentiation, prolonged neurite length, dynamic movement of microtubules and cytoskeleton, and altered endocytic mechanisms in neuroblastoma-based stem cells for the peptide modified DNA hydrogel compared to the unmodified DNA hydrogel and controls. We anticipate that a peptide-modified DNA hydrogel could emerge as a promising scaffold coating material to develop nerve tissue conduits in the future for application in neuroscience and neuroregeneration.

Persistence of behavioral abnormalities following corticosteroid therapy in children with initial episode of idiopathic nephrotic syndrome: a prospective longitudinal observation / Persistência de anormalidades comportamentais após corticoterapia em crianças com episódio inicial de síndrome nefrótica idiopática: uma observação longitudinal prospectiva

Abstract Introduction: Treatment of nephrotic syndrome with corticosteroid can cause several side- effects including behavioral abnormalities. The objectives of the study were to observe the proportion of non-relapsers having persistence of behavioral abnormalities after completion of treatment of initial episode and compare the abnormalities with relapsers, and to determine risk factors for persistence. Methods: Seventy-five children with a first episode of idiopathic nephrotic syndrome and 60 normal children were rated by parents for behavioral problems using the Child Behavior Checklist. The Parenting Stress Index was also evaluated. The children were rated before treatment and 12 and 36 weeks after. Results: Both relapsers and non-relapsers showed abnormalities in internalizing and externalizing domains at 12 weeks of steroid therapy. Non-relapsers had abnormal scores in the internalizing domain in 63.5 % and externalizing domain in 48.1% of cases at 36 weeks. Relapsers had abnormal scores in all the three behavior domains, but a significantly higher proportion of relapsers had abnormal scores regarding total behavior (65.2% vs 28.8%, p<0.01) and child domains (100% vs 57.7%, p<0.001) of Parenting Stress Index in comparison to non-relapsers at 36 weeks. Occurrence of relapse increased the risk (odds ratio 5.76, 95% CI 1.35-10.76, p< 0.001) for persistence of abnormal total behavior at 36 weeks follow-up. Conclusion: Persistence of abnormalities was observed not only in relapsers but also in non-relapsers. Relapse was found to be a significant risk factor for persistence of abnormal behaviors in these patients.

Resumo Introdução: O tratamento da síndrome nefrótica com corticosteroide pode causar vários efeitos colaterais, incluindo anormalidades comportamentais. Os objetivos do estudo foram observar a proporção de não-recidivos com persistência de anormalidades comportamentais após conclusão do tratamento do episódio inicial, comparar as anormalidades com os recidivos, e determinar fatores de risco para persistência. Métodos: 75 crianças com primeiro episódio de síndrome nefrótica idiopática e 60 crianças normais foram avaliadas pelos pais por problemas comportamentais usando o Checklist de Comportamento Infantil. O Índice de Estresse Parental também foi avaliado. As crianças foram avaliadas antes do tratamento, 12 e 36 semanas após. Resultados: Tanto recidivos quanto não recidivos mostraram anormalidades nos domínios de internalização e externalização às 12 semanas de terapia com esteroides. Não-recidivos apresentaram pontuações anormais no domínio de internalização em 63,5%, e no domínio de externalização, em 48,1% dos casos em 36 semanas. Recidivos tiveram pontuações anormais em todos os três domínios de comportamento, mas uma proporção significativamente maior de recidivos apresentou pontuações anormais em relação ao comportamento total (65,2% vs 28,8%, p<0,01) e domínios infantis (100% vs 57,7%, p<0,001) do Índice de Estresse Parental em comparação com não recidivos às 36 semanas. A ocorrência de recidiva aumentou o risco (odds ratio 5,76, 95% IC 1,35-10,76, p< 0,001) de persistência de comportamento total anormal em 36 semanas de acompanhamento. Conclusão: A persistência de anormalidades foi observada não apenas em recidivos, mas também em não recidivos. A recidiva foi um fator de risco significativo para a persistência de comportamentos anormais nesses pacientes.

Extracellular Matrix in Synthetic Hydrogel-Based Prostate Cancer Organoids Regulate Therapeutic Response to EZH2 and DRD2 Inhibitors.

Following treatment with androgen receptor (AR) pathway inhibitors, ≈20% of prostate cancer patients progress by shedding their AR-dependence. These tumors undergo epigenetic reprogramming turning castration-resistant prostate cancer adenocarcinoma (CRPC-Adeno) into neuroendocrine prostate cancer (CRPC-NEPC). No targeted therapies are available for CRPC-NEPCs, and there are minimal organoid models to discover new therapeutic targets against these aggressive tumors. Here, using a combination of patient tumor proteomics, RNA sequencing, spatial-omics, and a synthetic hydrogel-based organoid, putative extracellular matrix (ECM) cues that regulate the phenotypic, transcriptomic, and epigenetic underpinnings of CRPC-NEPCs are defined. Short-term culture in tumor-expressed ECM differentially regulated DNA methylation and mobilized genes in CRPC-NEPCs. The ECM type distinctly regulates the response to small-molecule inhibitors of epigenetic targets and Dopamine Receptor D2 (DRD2), the latter being an understudied target in neuroendocrine tumors. In vivo patient-derived xenograft in immunocompromised mice showed strong anti-tumor response when treated with a DRD2 inhibitor. Finally, we demonstrate that therapeutic response in CRPC-NEPCs under drug-resistant ECM conditions can be overcome by first cellular reprogramming with epigenetic inhibitors, followed by DRD2 treatment. The synthetic organoids suggest the regulatory role of ECM in therapeutic response to targeted therapies in CRPC-NEPCs and enable the discovery of therapies to overcome resistance.

Diode Laser in the Management of Leukoplakia - A Retrospective Study.

Introduction: Leukoplakia is among the most common potentially malignant disorders encountered in clinical dental practice. The treatment of leukoplakia includes nonsurgical and surgical management. The surgical treatment includes excision, electrocauterisation, laser surgery or cryosurgery. This retrospective study aimed to analyse the efficacy of diode lasers in the management of leukoplakia. Methods: The sample consists of 56 cases with 77 leukoplakia sites treated with diode laser between January 2018 and December 2020 with a minimum of six months follow-up. For each patient, personal data was collected along with site of lesions, leukoplakia phase, type of treatment performed (laser ablation or laser excision), side effects, recurrences and malignant transformation. Inferential statistical analysis was then conducted. Results: After applying exclusion criteria, 56 cases with 77 leukoplakia sites were included in this study. Males aged >45 years were predominantly affected. Homogeneous leukoplakia (48.1%) was the most common phase. Recurrences were noted in 19.48% of the cases. Compared to laser excision, laser ablation had more recurrences. Gingival lesions showed a higher recurrence rate than other sites in the oral cavity. None of the cases showed malignant transformation. Discussion: Laser offers many advantages over other conventional methods including lesser postoperative pain and swelling, bloodless dry operating field and increased patient comfort and requires minimal local anaesthesia. The study concluded that diode laser is an effective surgical treatment modality for treating leukoplakia. Furthermore, the laser excision technique was found to be superior to laser ablation due to lesser recurrence.

Seasonal expression and distribution of kisspeptin1 (kiss1) in the ovary and testis of freshwater catfish, Clarias batrachus: A putative role in steroidogenesis.

The central role of kisspeptin (kiss) in mammalian reproduction is well established; however, its intra-gonadal role is poorly addressed. Moreover, studies investigating intra-gonadal role of kiss in fish reproduction are scanty, contradictory and inconclusive. The expression of kiss1 mRNA has been detected in the fish brain, and functionally attributed to the regulation of reproduction, feeding and behavior. The kiss1 mRNA has also been demonstrated in tissues other than the brain in some studies, but its cellular distribution and role at the tissue level have not been adequately addressed in fish. Therefore, an attempt was made in the present study to localize kiss1 in gonadal cells of the freshwater catfish, Clarias batrachus. This study reports the presence of kiss1 in the theca cells and granulosa cells of the ovarian oocytes and interstitial cells in the testis of the catfish. The role of kiss1 in the ovary and testis of the catfish was also investigated using kiss1 receptor (kiss1r) antagonist (p234). The p234 treatment decreased the production of 17ß-estradiol in ovary and testosterone in the testis by lowering the activities of 3ß-hydroxysteroid dehydrogenase and 17ß-hydroxysteroid dehydrogenase under both, in vivo as well as in vitro conditions. The p234 treatment also arrested the progression of oogenesis, as evident from the low number of advancing/advanced oocytes in the treated ovary in comparison to the control ovary. It also reduced the area and perimeter of the seminiferous tubules in the treated catfish testis. Thus, our findings suggest that kiss is involved in the regulation of gonadal steroidogenesis, independent of known endocrine/ autocrine/ paracine regulators, and thereby it accelerates gametogenic processes in the freshwater catfish.