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1.
Asian J Psychiatr ; 99: 104121, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38986315

RESUMEN

BACKGROUND: The onset of psychosis brings unfamiliar experiences that can be disturbing for patients and their caregivers. Few studies from India (only one from North India) have examined these experiences from the perspective of the patient and caregiver. We explored experiences of first episode psychosis (FEP) patients and their caregivers within a North Indian context. METHOD: Semi-structured interviews were conducted in 2019 with ten FEP patients and their caregivers (total n=20) receiving out-patient care in a tertiary care centre. Topic guides focused on concerns/complaints, symptoms, help-seeking, and barriers and facilitators to treatment. Interviews were audio recorded, transcribed, and analysed using qualitative content analysis. RESULTS: Main categories of responses from patients and caregivers included: initial complaints for seeking help, initial emotional response, barriers to seeking treatment, perceived dysfunction and improvement, experienced stigma, understanding about illness, early follow-up, preventive measures and awareness programs. Caregivers undergo myriad of emotional reactions including anger, anxiety, guilt, and confusion. Symptoms other than psychotic symptoms were the primary complaint upon seeking help, and there was lack of understanding about the psychosocial model of care (role of medications acknowledged with little awareness regarding psychosocial interventions in recovery). Persisting occupational dysfunction despite perceived symptomatic improvement was described by both patients and caregivers. CONCLUSION: North Indian patients with FEP lack awareness of symptoms. Therefore, onus for seeking help often falls on their caregivers. Psychoeducation from first contact with services and increasing awareness about psychotic illness within the community might help address lack of awareness about symptoms, mental health services, early signs of relapse, and importance of psychosocial interventions in achieving functional recovery.

2.
Asian J Psychiatr ; 99: 104120, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38986314

RESUMEN

BACKGROUND: Home-based psychosocial care has the potential to improving outcomes in patients with schizophrenia and related disorders (SCZ). There is lack of India data for such care in early psychosis. We developed the "Saksham" programme, a bespoke self-managed home-based psychosocial care model, available in two formats: manual-based and mobile-application based. With the anticipated success of recruitment of early psychosis cases in our setting, we plan to test the such intervention in this population in future trials. AIM: To assess the feasibility of the Saksham programme intervention in people with SCZ and its clinical efficacy as an adjunct to treatment as usual. METHODS: Seventy-five patient-caregiver pairs (total n=150) were recruited. Patients received either: treatment-as-usual (TAU) (n=25), manual-based Saksham intervention+TAU (n=25), or app-based Saksham intervention+TAU (n=25). Feasibility (i.e. acceptability, practicality, demand, implementation and integration) was assessed at three-months. Participants were assessed for psychopathology, illness-severity, cognition, functioning, disability, and caregiver-coping at baseline, one-month, and three-month. The percentage changes over time were compared across three groups. RESULTS: More found the mobile application-based intervention acceptable and easy-to-use than the manual-based intervention (92 % vs 68 %, and 76 % vs 68 %, respectively). Psychopathology and caregiver-burden improved significantly in all three groups (p<0.05). Cognition, disability, functioning, and caregiver burden improved significantly in the two Saksham intervention groups, with greater improvement in the Saksham app group (p<0.05). CONCLUSION: Home-based intervention is feasible and acceptable in a low-resource setting, with preliminary evidence for effectiveness. These findings need corroboration with randomised controlled trials in early psychosis to ameliorate course of illness.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38996385

RESUMEN

Health care workers have faced a significant challenge because of the rise in cancer incidence around the world during the past 10 years. Among various forms of malignancy skin cancer is most common, so there is need for the creation of an efficient and safe skin cancer treatment that may offer targeted and site-specific tumor penetration, and reduce unintended systemic toxicity. Nanocarriers have thus been employed to get around the issues with traditional anti-cancer drug delivery methods. Invasomes are lipid-based nanovesicles having small amounts of terpenes and ethanol or a mixture of terpenes and penetrate the skin more effectively. Compared to other lipid nanocarriers, invasomes penetrate the skin at a substantially faster rate. Invasomes possess a number of advantages, including improved drug effectiveness, higher compliance, patient convenience, advanced design, multifunctionality, enhanced targeting capabilities, non-invasive delivery methods, potential for combination therapies, and ability to overcome biological barriers,. These attributes position invasomes as a promising and innovative platform for the future of cancer treatment. The current review provides insights into invasomes, with a fresh organizational scheme and incorporates the most recent cancer research, including their composition, historical development and methods of preparation, the penetration mechanism involving effect of various formulation variables and analysis of anticancer mechanism and the application of invasomes.

6.
Clin Genitourin Cancer ; 22(5): 102143, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-39032202

RESUMEN

INTRODUCTION: The renin-angiotensin system (RAS) has been demonstrated to modulate cell proliferation, desmoplasia, angiogenesis and immunosuppression. We examined the association of RAS inhibitors (RASi)-namely angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB)-with neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) preceding radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively investigated concurrent RASi use with NAC prior to RC in 302 patients with MIBC from 3 academic institutions. Outcomes included pathologic complete response (pCR) and overall survival (OS). Pathologic features, performance status (PS), clinical stage, type/number of cycles of NAC, and toxicities were collected. RESULTS: Overall pCR rate was 26.2% and 5-year OS was 62%. Concurrent ACEi intake with NAC approached significance for association with pCR (odds ratio [OR] = 1.71; 95% CI, 0.94-3.11; P = .077). Patients with cT3/4N0-N1 disease receiving ACEi had higher pCR rates (30.8% vs. 17.7%, P = .056) than those not on ACEi. Female sex had a statistically significant favorable interaction for pCR with ACEi intake (P = .044). ACEi intake was not associated with OS, while pCR, PS and lower clinical stage were significantly associated with improved OS. CONCLUSION: ACEi intake is potentially associated with increased pCR in patients with MIBC receiving NAC prior to RC, and this association is more pronounced in patients with higher clinical stage of disease at the initiation of therapy and female sex. Our data suggest the potential relevance of the RAS as a therapeutic target in aggressive MIBC.

7.
J Phys Chem B ; 128(28): 6657-6669, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38822803

RESUMEN

Leucine-rich repeat kinase 2 (LRRK2) remains a viable target for drug development since the discovery of the association of its mutations with Parkinson's disease (PD). G2019S (in the kinase domain) is the most common mutation for LRRK2-based PD. Though various types of inhibitors have been developed for the kinase domain to reduce the effect of the mutation, understanding the working of these inhibitors at the molecular level is still ongoing. This study focused on the exploration of the dissociation mechanism (pathways) of inhibitors from (WT and G2019S) LRRK2 kinase (using homology model CHK1 kinase), which is one of the crucial aspects in drug discovery. Here, two ATP-competitive type I inhibitors, PF-06447475 and MLi-2 (Comp1 and Comp2 ), and one non-ATP-competitive type II inhibitor, rebastinib (Comp3), were considered for this investigation. To study the unbinding process, random accelerated molecular dynamics simulations were performed. The binding free energies of the three inhibitors for different egression paths were determined using umbrella sampling. This work found four major egression pathways that were adopted by the inhibitors Comp1 (path1, path2, and path3), Comp2 (path1, path2 and path3), and Comp3 (path3 and path4). Also, the mechanism of unbinding for each path and key residues involved in unbinding were explored. Mutation was not observed to impact the preference of the particular egression pathways for both LRRK2-Comp1 and -Comp2 systems. However, the findings suggested that the size of the inhibitor molecules might have an effect on the preference of the egression pathways. The binding energy and residence time of the inhibitors followed a similar trend to experimental observations. The findings of this work might provide insight into designing more potent inhibitors for the G2019S LRRK2 kinase.


Asunto(s)
Diseño de Fármacos , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Simulación de Dinámica Molecular , Mutación , Enfermedad de Parkinson , Inhibidores de Proteínas Quinasas , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/antagonistas & inhibidores , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/metabolismo , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/genética , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/química , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/genética , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/metabolismo , Humanos , Indazoles , Pirimidinas
8.
Cureus ; 16(4): e59421, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38826597

RESUMEN

The traditional criteria for diagnosing preeclampsia include a new onset of hypertension and new-onset proteinuria at 20 weeks gestation. However recent studies suggest preeclampsia and even eclampsia may develop in the absence of either proteinuria or hypertension. This paper reports a dual tragedy of maternal and fetal loss after 36 weeks in the third trimester. Autopsy findings revealed an enlarged liver with multiple patchy hemorrhages, and histopathology confirmed submassive hepatic necrosis. Early diagnosis with timely referrals to higher centers is always helpful for the patients in such cases.

9.
bioRxiv ; 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38895411

RESUMEN

Populations can adapt to stressful environments through changes in gene expression. However, the role of gene regulation in mediating stress response and adaptation remains largely unexplored. Here, we use an integrative field dataset obtained from 780 plants of Oryza sativa ssp. indica (rice) grown in a field experiment under normal or moderate salt stress conditions to examine selection and evolution of gene expression variation under salinity stress conditions. We find that salinity stress induces increased selective pressure on gene expression. Further, we show that trans-eQTLs rather than cis-eQTLs are primarily associated with rice's gene expression under salinity stress, potentially via a few master-regulators. Importantly, and contrary to the expectations, we find that cis-trans reinforcement is more common than cis-trans compensation which may be reflective of rice diversification subsequent to domestication. We further identify genetic fixation as the likely mechanism underlying this compensation/reinforcement. Additionally, we show that cis- and trans-eQTLs are under different selection regimes, giving us insights into the evolutionary dynamics of gene expression variation. By examining genomic, transcriptomic, and phenotypic variation across a rice population, we gain insights into the molecular and genetic landscape underlying adaptive salinity stress responses, which is relevant for other crops and other stresses.

10.
Artículo en Inglés | MEDLINE | ID: mdl-38940214

RESUMEN

OBJECTIVES: The study provides a thorough examination of the rhizomes of Curcuma caesia Roxb., which is a medicinal substance sometimes referred to as black turmeric and has not been well studied. METHODS: The study examines the pharmacognostical characteristics, GC-MS profiling, and elemental analysis of the substance to determine its potential for use in medicine. The presence of heavy metal contamination in herbal products is a significant issue, which necessitates the use of Atomic Absorption Spectrophotometry to quantitatively analyze eight elements. RESULTS: The investigation validates the existence of crucial trace elements while guaranteeing that the levels of heavy metals are within the toxicity limits set by the World Health Organization. This indicates that the rhizome is safe for medicinal purposes. The selection of a solvent has a substantial impact on the efficiency of extraction. Acetone has the highest extraction yield, followed by ethanol and ethyl acetate. The GC-MS analysis uncovers a wide range of phytochemicals, such as alkaloids, flavonoids, phenols, tannins, steroids, and proteins. Additionally, particular solvents exclusively detect specific molecules. Epicurzerenone and zederone are chemicals that show promise for use in reducing inflammation and fighting cancer. CONCLUSIONS: On the basis of results it can be concluded that rhizome's quality based on acceptable physicochemical characteristics and provides a strong basis for future pharmacological research. The research has potential for the development of novel organic drugs, utilizing the abundant phytochemical composition of C. caesia Roxb. rhizomes.

11.
Indian J Psychiatry ; 66(5): 440-448, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38919577

RESUMEN

Background: Psychosocial interventions, crucial for recovery in patients with schizophrenia, have often been developed and tested in high income countries. We aimed at developing and validating home-based a booklet based psycho-social intervention with inputs from stakeholders: patients, families, and mental health professionals (MHP) for patients with schizophrenia and related disorders in low resource settings. Methods: We developed a preliminary version of psychosocial intervention booklets based on six themes derived from focus group discussions conducted with patients, families, and MHP. Initially, quantitative assessment of content validity was done by MHP on overall and Content Validity Index of individual items of the specific booklets, followed by in-depth interviews about their views. The booklets were modified based on their inputs. Further, pilot testing of manuals was done on the users - nine pairs of patients and caregivers followed by development of a final version of psycho-social intervention. Results: The percentage content validity of individual modules and overall booklets was ≥78.5% indicating good validity. Most MHP reported that the manuals were relevant and easy to use but were text-heavy, and lengthy. On pilot testing of modified manuals with patients and their family caregivers, majority (77.8%) of them found booklets useful and suggested that there should be separate booklets for both patients and caregivers for providing information and entering separate response for the activities, integrating helpful tips. Language should be simple. Finally, two sets of booklets ("info book" and "workbook") named 'Saksham' (meaning empowered) were created with specific modules (viz., 'Medicine adherence', 'Daily routine', 'Eating right', 'Physical activity', 'Physical health monitoring', 'Self-reliance', and 'Psychoeducation') for patients and caregivers each, in two languages (Hindi and English). Conclusion: Booklets with modules for psychosocial interventions for patients with schizophrenia and their caregivers were developed after establishing content validity and pilot testing.

12.
Photochem Photobiol ; 2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38922730

RESUMEN

Two novel cyclometalated ruthenium complexes, RC-4 and RC-5, featuring 1-phenylisoquinoline and phenyl quinazoline as ancillary ligands, respectively, were synthesized to investigate their viability with the environmentally friendly copper (Cu) redox mediator, [Cu(bpye)2]2+/+. The modification of the ligand environment resulted in variations in the energetics, photophysical properties, and photovoltaic performance of RC-4 and RC-5 sensitizers. Despite RC-5 sensitizer possessing a more positive ground state potential of 1.19 V versus the NHE, the RC-4 sensitizer, with a lower HOMO level of 0.72 V versus NHE, exhibited superior photovoltaic performance along with the Cu electrolyte, attributed to its enhanced light harvesting ability, improved lifetime and reduced back electron transfer, contributing to higher Jsc, Voc, and PCE.

13.
Anat Rec (Hoboken) ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38924700

RESUMEN

The existence of a previously unrecognized subarachnoid lymphatic-like membrane (SLYM) was reported in a recent study. SLYM is described as an intermediate leptomeningeal layer between the arachnoid and pia mater in mouse and human brains, which divides the subarachnoid space (SAS) into two functional compartments. Being a macroscopic structure, having missed detection in previous studies is surprising. We systematically reviewed the published reports in animals and humans to explore whether prior descriptions of this meningeal layer were reported in some way. A comprehensive search was conducted in PubMed/Medline, EMBASE, Google Scholar, Science Direct, and Web of Science databases using combinations of MeSH terms and keywords with Boolean operators from inception until 31 December 2023. We found at least eight studies that provided structural evidence of an intermediate leptomeningeal layer in the brain or spinal cord. However, unequivocal descriptions for this layer all along the central nervous system were scarce. Obscure names like the epipial, intermediate meningeal, outer pial layers, or intermediate lamella were used to describe it. Its microscopic/ultrastructural details closely resemble the recently reported SLYM. We further examined the counterarguments in current literature that are skeptical of the existence of this layer. The potential physiological and clinical implications of this new meningeal layer are significant, underscoring the urgent need for further exploration of its structural and functional details.

14.
J Insect Physiol ; 156: 104664, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38897288

RESUMEN

Like other lepidopteran insects, males of the tobacco cutworm moth, Spodoptera litura produce two kinds of spermatozoa, eupyrene (nucleate) and apyrene (anucleate) sperm. Formed in the testis, both kinds of sperm are released into the male reproductive tract in an immature form and are stored in the duplex region of the tract. Neither type of sperm is motile at this stage. When stored apyrene sperm from the duplex are treated in vitro with an extract of the prostatic region of the male tract, or with mammalian trypsin, they become motile; activation is greater and achieved more rapidly with increasing concentration of extract or enzyme. The activating effect of prostatic extract is blocked by soybean trypsin inhibitor (SBTI), also in a dose-dependent way. These results suggest that the normal sperm-activating process is due to an endogenous trypsin-like protease produced in the prostatic region. Proteomic analysis of S. litura prostatic extracts revealed a Trypsin-Like Serine Protease, TLSP, molecular weight 27 kDa, whose 199-residue amino acid sequence is identical to that of a predicted protein from the S. litura genome and is highly similar to predicted proteins encoded by genes in the genomes of several other noctuid moth species. Surprisingly, TLSP is only distantly related to Serine Protease 2 (initiatorin) of the silkmoth, Bombyx mori, the only identified lepidopteran protein so far shown to activate sperm. TLSP has features typical of secreted proteins, probably being synthesized as an inactive precursor zymogen, which is later activated by proteolytic cleavage. cDNA was synthesized from total RNA extracted from the prostatic region and was used to examine TLSP expression using qPCR. tlsp mRNA was expressed in both the prostatic region and the accessory glands of the male tract. Injection of TLSP-specific dsRNA into adult males caused a significant reduction after 24 h in tlsp mRNA levels in both locations. The number of eggs laid by females mated to adult males that were given TLSP dsRNA in 10 % honey solution, and the fertility (% hatched) of the eggs were reduced. Injecting pupae with TLSP dsRNA caused the later activation of apyrene sperm motility by adult male prostatic extracts to be significantly reduced compared to controls. Exposure of S. litura pupae to ionizing radiation significantly reduced expression of tlsp mRNA in the prostatic part and accessory gland of irradiated males in both the irradiated generation and also in their (unirradiated) F1 progeny. The implications of these findings for the use of the inherited sterility technique for the control of S. litura and other pest Lepidoptera are discussed.


Asunto(s)
Proteínas de Insectos , Espermatozoides , Spodoptera , Animales , Masculino , Spodoptera/genética , Spodoptera/enzimología , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Espermatozoides/efectos de la radiación , Interferencia de ARN , Secuencia de Aminoácidos , Genitales Masculinos/metabolismo , Genitales Masculinos/efectos de la radiación , Proteómica , Serina Proteasas/metabolismo , Serina Proteasas/genética , Radiación Ionizante , Serina Endopeptidasas/metabolismo , Serina Endopeptidasas/genética , Transcriptoma
15.
Theor Appl Genet ; 137(7): 169, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38913173

RESUMEN

The agricultural sector faces colossal challenges amid environmental changes and a burgeoning human population. In this context, crops must adapt to evolving climatic conditions while meeting increasing production demands. The dairy industry is anticipated to hold the highest value in the agriculture sector in future. The rise in the livestock population is expected to result in an increased demand for fodder feed. Consequently, it is crucial to seek alternative options, as crops demand fewer resources and are resilient to climate change. Pearl millet offers an apposite key to these bottlenecks, as it is a promising climate resilience crop with significantly low energy, water and carbon footprints compared to other crops. Numerous studies have explored its potential as a fodder crop, revealing promising performance. Despite its capabilities, pearl millet has often been overlooked. To date, few efforts have been made to document molecular aspects of fodder-related traits. However, several QTLs and candidate genes related to forage quality have been identified in other fodder crops, which can be harnessed to enhance the forage quality of pearl millet. Lately, excellent genomic resources have been developed in pearl millet allowing deployment of cutting-edge genomics-assisted breeding for achieving a higher rate of genetic gains. This review would facilitate a deeper understanding of various aspects of fodder pearl millet in retrospect along with the future challenges and their solution. This knowledge may pave the way for designing efficient breeding strategies in pearl millet thereby supporting sustainable agriculture and livestock production in a changing world.


Asunto(s)
Alimentación Animal , Cambio Climático , Productos Agrícolas , Pennisetum , Fitomejoramiento , Pennisetum/genética , Productos Agrícolas/genética , Productos Agrícolas/crecimiento & desarrollo , Sitios de Carácter Cuantitativo , Animales
16.
Cells ; 13(11)2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38891096

RESUMEN

Special AT-rich sequence binding protein-2 (SATB2) is a nuclear matrix protein that binds to nuclear attachment regions and is involved in chromatin remodeling and transcription regulation. In stem cells, it regulates the expression of genes required for maintaining pluripotency and self-renewal and epithelial-mesenchymal transition (EMT). In this study, we examined the oncogenic role of SATB2 in prostate cancer and assessed whether overexpression of SATB2 in human normal prostate epithelial cells (PrECs) induces properties of cancer stem cells (CSCs). The results demonstrate that SATB2 is highly expressed in prostate cancer cell lines and CSCs, but not in PrECs. Overexpression of SATB2 in PrECs induces cellular transformation which was evident by the formation of colonies in soft agar and spheroids in suspension. Overexpression of SATB2 in PrECs also resulted in induction of stem cell markers (CD44 and CD133), pluripotency-maintaining transcription factors (cMYC, OCT4, SOX2, KLF4, and NANOG), CADHERIN switch, and EMT-related transcription factors. Chromatin immunoprecipitation assay demonstrated that SATB2 can directly bind to promoters of BCL-2, BSP, NANOG, MYC, XIAP, KLF4, and HOXA2, suggesting SATB2 is capable of directly regulating pluripotency/self-renewal, cell survival, and proliferation. Since prostate CSCs play a crucial role in cancer initiation, progression, and metastasis, we also examined the effects of SATB2 knockdown on stemness. SATB2 knockdown in prostate CSCs inhibited spheroid formation, cell viability, colony formation, cell motility, migration, and invasion compared to their scrambled control groups. SATB2 knockdown in CSCs also upregulated the expression of E-CADHERIN and inhibited the expression of N-CADHERIN, SNAIL, SLUG, and ZEB1. The expression of SATB2 was significantly higher in prostate adenocarcinoma compared to normal tissues. Overall, our data suggest that SATB2 acts as an oncogenic factor where it is capable of inducing malignant changes in PrECs by inducing CSC characteristics.


Asunto(s)
Transición Epitelial-Mesenquimal , Factor 4 Similar a Kruppel , Proteínas de Unión a la Región de Fijación a la Matriz , Neoplasias de la Próstata , Factores de Transcripción , Humanos , Masculino , Transición Epitelial-Mesenquimal/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/genética , Factor 4 Similar a Kruppel/metabolismo , Proteínas de Unión a la Región de Fijación a la Matriz/metabolismo , Proteínas de Unión a la Región de Fijación a la Matriz/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Línea Celular Tumoral , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Regulación Neoplásica de la Expresión Génica , Autorrenovación de las Células , Proliferación Celular
17.
ACS Chem Neurosci ; 15(13): 2504-2519, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38902941

RESUMEN

Chronic hypoxic exposure triggers the onset and progression of cognitive dysfunction; however, the mechanisms underlying chronic hypoxia-induced neuroinflammation and its contribution to cognitive dysfunction remain poorly understood. Although inflammation and hypoxia are interdependent, numerous recent studies have linked the development of various human diseases to hypoxia-induced inflammation. In this study, we focused on the NLRP3 inflammasome with novel analogues of cytokine release inhibitory drug 3 (CRID3), a class of small molecule inhibitors for the NLRP3 inflammasome, to investigate their potential contribution to alleviating chronic hypoxia-induced neuroinflammation using the zebrafish model. The designed CRID3 analogues 6a-q were prepared from 2-methyl furan-3-carboxylate, following a four-step reaction sequence and fully characterized by NMR and mass spectral analysis. The administration of CRID3 analogues 6a-q led to a notable reduction in neuroinflammation and an increase in glial proliferation markers in both sexes. In addition, we investigated the potential effects of CRID3 analogues 6a-q through various behavioral tasks to assess their role in ameliorating post-hypoxic behavioral deficits and cognitive impairment. Notably, the study revealed that post-chronic hypoxia, male zebrafish exhibited significantly higher levels of inflammatory marker expression than females. Furthermore, we observed that the neurogenic response to treatment with CRID3 derivative 6o varied depending on the sex, with females showing a sex-specific differential increase in neurogenesis compared to males. This work emphasizes the significance of considering sex differences into account in developing therapeutic strategies for neurological disorders, as shown by the sex-specific molecular and behavioral changes in zebrafish cognitive impairment and neuroinflammation.


Asunto(s)
Antiinflamatorios , Hipoxia , Trastornos de la Memoria , Pez Cebra , Animales , Antiinflamatorios/farmacología , Trastornos de la Memoria/tratamiento farmacológico , Hipoxia/tratamiento farmacológico , Hipoxia/complicaciones , Hipoxia/metabolismo , Modelos Animales de Enfermedad , Masculino , Femenino , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología
18.
Artículo en Inglés | MEDLINE | ID: mdl-38853636

RESUMEN

KEY POINTS: Unilateral or destructive sinonasal disease should raise suspicion for tumor. Patients receiving biologic therapy for CRSwNP should be carefully selected. Tissue diagnosis should be considered prior to starting biologics for nasal polyposis.

19.
Asian J Psychiatr ; 98: 104103, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38905724

RESUMEN

BACKGROUND: Standard assessment and management protocols exist for first episode psychosis (FEP) in high income countries. Due to cultural and resource differences, these need to be modified for application in low-and middle-income countries. AIMS: To assess the applicability of standard assessment and management protocols across two cohorts of FEP patients in North and South India by examining trajectories of psychopathology, functioning, quality of life and family burden in both. METHOD: FEP patients at two sites (108 at AIIMS, North India, and 115 at SCARF, South India) were assessed using structured instruments at baseline, 3, 6 and 12 months. Standard management protocols consisted of treatment with antipsychotics and psychoeducation for patients and their families. Generalised estimating equation (GEE) modelling was carried out to test for changes in outcomes both across and between sites at follow-up. RESULTS: There was an overall significant improvement in both cohorts for psychopathology and other outcome measures. The trajectories of improvement differed between the two sites with steeper improvement in non-affective psychosis in the first three months at SCARF, and affective symptoms in the first three months at AIIMS. The reduction in family burden and improvement in quality of life were greater at AIIMS than at SCARF during the first three months. CONCLUSIONS: Despite variations in cultural contexts and norms, it is possible to implement FEP standard assessment and management protocols in North and South India. Preliminary findings indicate that FEP services lead to significant improvements in psychopathology, functioning, quality of life, and family burden within these contexts.

20.
Cureus ; 16(5): e60451, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38883069

RESUMEN

BACKGROUND: The key prognostic markers in acute lymphoblastic leukemia (ALL) include age, leukocyte count upon diagnosis, immunophenotype, and chromosomal abnormalities. Furthermore, there was a correlation between cytogenetic anomalies and specific immunologic phenotypes of ALL, which in turn had varied outcomes. The objective of this study was to examine the occurrence of cytogenetic abnormalities in individuals diagnosed with acute lymphoblastic leukemia. METHODS: The study employed a cross-sectional design to investigate genetic evaluation and clinical features in 147 ALL patients between March 2021 and August 2022. Demographic data (like age and sex), clinical manifestations, and hematological parameters were collected. Cytogenetic analysis (G-banding) was performed to identify chromosomal abnormalities. The mean±SD and analysis of variance (ANOVA) were used to assess associations and differences among variables using SPSS Version 24 (IBM Corp., Armonk, NY, USA). RESULTS: The study shows male n=85 and female n=62 in ALL patients, with prevalent clinical manifestations: fever n=100 (68.03%), pallor n=123 (83.67%), and lymphadenopathy n=65 (44.22%). The hematological parameters like hemoglobin (Hb) (6.14±2.5 g/dl), total leukocyte count (TLC) (1.7±1.05 cell/mm3), and platelet count (1.2±0.11 lac/mm3) show a significant variation (P<0.05) in patients aged 30-50 years. In addition, chromosomal abnormalities, particularly 46, XX, t(9;22), were prevalent, emphasizing the genetic heterogeneity of ALL. CONCLUSION: The study shows a male predominance with ALL, prevalent clinical manifestations, and significant hematological parameter variations in the 30-50 age group. Chromosomal abnormalities, notably 46, XX, t(9;22), underscore the genetic complexity of the disease, which necessitates tailored therapeutic interventions informed by genetic profiles.

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