RESUMEN
Stromal-epithelial communication is an absolute necessity when it comes to the morphogenesis and pathogenesis of solid tissues, including the prostate and breast. So far, signalling pathways of several growth factors have been investigated. Besides such chemical factors, non-coding RNAs such as miRNAs have recently gained much interest because of their variety and complexity of action. Prostate and breast tissues being highly responsive to steroid hormones such as androgen and estrogen, respectively, it is not surprising that a huge set of available literature critically investigated the interplay between such hormones and miRNAs, especially in carcinogenesis. This review showcases our effort to highlight hormonally-related miRNAs that also somehow perturb the regular stromal-epithelial interactions during carcinogenesis in the prostate and breast. In future, we look forward to exploring how hormonal changes in the tissue microenvironment bring about miRNA-mediated changes in stromal-epithelial interactome in carcinogenesis and cancer progression.
Asunto(s)
Neoplasias de la Mama , MicroARNs , Neoplasias de la Próstata , Células del Estroma , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Masculino , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Células del Estroma/metabolismo , Células del Estroma/patología , Femenino , Células Epiteliales/metabolismo , Células Epiteliales/patología , Comunicación Celular/genética , Animales , Microambiente Tumoral/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
Virtual screening (VS) is an integral and ever-evolving domain of drug discovery framework. The VS is traditionally classified into ligand-based (LB) and structure-based (SB) approaches. Machine intelligence or artificial intelligence has wide applications in the drug discovery domain to reduce time and resource consumption. In combination with machine intelligence algorithms, VS has emerged into revolutionarily progressive technology that learns within robust decision orders for data curation and hit molecule screening from large VS libraries in minutes or hours. The exponential growth of chemical and biological data has evolved as "big-data" in the public domain demands modern and advanced machine intelligence-driven VS approaches to screen hit molecules from ultra-large VS libraries. VS has evolved from an individual approach (LB and SB) to integrated LB and SB techniques to explore various ligand and target protein aspects for the enhanced rate of appropriate hit molecule prediction. Current trends demand advanced and intelligent solutions to handle enormous data in drug discovery domain for screening and optimizing hits or lead with fewer or no false positive hits. Following the big-data drift and tremendous growth in computational architecture, we presented this review. Here, the article categorized and emphasized individual VS techniques, detailed literature presented for machine learning implementation, modern machine intelligence approaches, and limitations and deliberated the future prospects.
Asunto(s)
Inteligencia Artificial , Descubrimiento de Drogas , Humanos , Ligandos , Descubrimiento de Drogas/métodos , AlgoritmosRESUMEN
Data related to psychiatric manifestations in subacute sclerosing panencephalitis (SSPE) is currently available only in the form of isolated case reports. In this systematic review, we evaluated the spectrum of psychiatric manifestations and their impact on the course and outcome of SSPE. Data were obtained from 4 databases (PubMed, Embase, Scopus, and Google Scholar), with the most recent search conducted on March 27, 2023. The PRISMA guidelines were followed, and the PROSPERO registration number for the protocol is CRD42023408227. SSPE was diagnosed using Dyken's criteria. Extracted data were recorded in an Excel spreadsheet. To evaluate the quality of the data, the Joanna Briggs Institute Critical Appraisal tool was employed. Our search resulted in 30 published reports of 32 patients. The mean age was 17.9 years. Schizophrenia, catatonia, and poorly characterized psychotic illnesses were the 3 most common psychiatric presentations that were seen in 63% (20/32) of cases. Catatonia was seen in 4 patients. Affective disorders, mania, and depression were reported among 22% (7/32) cases. In approximately 81% (26/32) cases, the course of SSPE was acute fulminant. Treatment with antipsychotic drugs had poor or no response. Out of 17 patients, who received antipsychotic drugs, 6 patients noted severe extrapyramidal adverse effects. SSPE often masquerades as a psychiatric disorder. Unresponsive psychiatric symptoms, early extrapyramidal signs, and progressive encephalopathy indicate SSPE.
Asunto(s)
Panencefalitis Esclerosante Subaguda , Panencefalitis Esclerosante Subaguda/complicaciones , Humanos , Catatonia/etiología , Catatonia/diagnóstico , Adolescente , EsquizofreniaRESUMEN
Measles inclusion-body encephalitis (MIBE) is rare, with insights largely from case studies. We systematically analyzed subacute Sclerosing Panencephalitis (SSPE) cases in immunocompromised patients, identifying distinctive clinical and neuroimaging features. These findings could facilitate MIBE diagnosis without the need for brain biopsies. Our systematic review on MIBE and HIV-related SSPE adhered to PRISMA guidelines and was registered with PROSPERO. We searched multiple databases and followed a detailed inclusion process with independent reviews and quality assessment. Data on patient demographics, clinical features, and outcomes were compiled. A review of 39 studies on 49 MIBE patients and 8 reports on HIV-positive SSPE patients was conducted. Acute lymphoblastic leukemia, HIV, organ transplants, and malignancies were common precursors to MIBE. Perinatal HIV was prevalent among SSPE cases. Seizures were the primary symptom in MIBE, often drug-resistant and progressing to status epilepticus or epilepsia partialis continua, whereas periodic myoclonus was universal in SSPE. Neuroimaging showed distinct patterns for each group, and histopathology confirmed measles virus presence in 39% of MIBE cases. MIBE patients typically progressed to coma and death. In conclusion, MIBE and SSPE in HIV-infected patients present with distinct clinical pictures but identical brain pathological abnormalities.
Asunto(s)
Sarampión , Neuroimagen , Panencefalitis Esclerosante Subaguda , Humanos , Panencefalitis Esclerosante Subaguda/diagnóstico por imagen , Panencefalitis Esclerosante Subaguda/patología , Panencefalitis Esclerosante Subaguda/complicaciones , Neuroimagen/métodos , Sarampión/complicaciones , Sarampión/patología , Sarampión/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Encéfalo/patologíaRESUMEN
This letter provides a critical assessment of a previous study on the utility of whole tumor apparent diffusion coefficient (ADC) histogram characteristics in predicting meningioma progesterone receptor expression. While acknowledging the benefits of employing classical diffusion-weighted imaging (DWI) for non-invasive tumor evaluation, it also emphasizes significant drawbacks. Advanced imaging techniques such as diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) were not used in the study, which could have provided a more comprehensive understanding of tumor microstructure and heterogeneity. Furthermore, the inclusion of necrotic and cystic areas in ADC analysis may distort results due to their different diffusion properties. While focusing on first-order ADC histogram characteristics is useful, it ignores the potential insights gained from higher-order features and texture analysis. These limitations indicate that future research should combine improved imaging modalities with thorough analytical methodologies to increase the predictive value of imaging biomarkers for meningioma features and progesterone receptor expression.
Asunto(s)
Imagen de Difusión por Resonancia Magnética , Neoplasias Meníngeas , Meningioma , Receptores de Progesterona , Meningioma/diagnóstico por imagen , Meningioma/patología , Meningioma/metabolismo , Humanos , Receptores de Progesterona/metabolismo , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/metabolismo , Imagen de Difusión por Resonancia Magnética/métodos , FemeninoRESUMEN
BACKGROUND: Burns constitute a major global health challenge, causing over 11 million injuries and 300,000 deaths annually and surpassing the economic burden of cervical cancer and HIV combined. Despite this, patient-level financial consequences of burn injuries remain poorly quantified, with a significant gap in data from low- and middle-income countries. In this study, we evaluate financial toxicity in burn patients. METHODS: A prospective, multicenter cohort study was conducted across two tertiary care hospitals in India, assessing 123 adult surgical in-patients undergoing operative interventions for burn injuries. Patient sociodemographic, clinical, and financial data were collected through surveys and electronic records during hospitalization and at 1, 3, and 6 months postoperatively. Out-of-pocket costs (OOPCs) for surgical burn treatment were evaluated during hospitalization. Longitudinal changes in income, employment status, and affordability of basic subsistence needs were assessed at the 1-, 3-, and 6-month postoperative time point. Degree of financial toxicity was calculated using a combination of the metrics catastrophic health expenditure and financial hardship. Development of financial toxicity was compared by sociodemographic and clinical characteristics using logistic regression models. RESULTS: Of the cohort, 60% experienced financial toxicity. Median OOPCs was US$555.32 with the majority of OOPCs stemming from direct nonmedical costs (US$318.45). Cost of initial hospitalization exceeded monthly annual income by 80%. Following surgical burn care, income decreased by US$318.18 within 6 months, accompanied by a 53% increase in unemployment rates. At least 40% of the cohort consistently reported inability to afford basic subsistence needs within the 6-month perioperative period. Significant predictors of developing financial toxicity included male gender (odds ratio, 4.17; 95% confidence interval, 1.25-14.29; P = 0.02) and hospital stays exceeding 20 days (odds ratio, 11.17; 95% confidence interval, 2.11-59.22; P ≤ 0.01). CONCLUSIONS: Surgical treatment for burn injuries is associated with substantial financial toxicity. National and local policies must expand their scope beyond direct medical costs to address direct nonmedical and indirect costs. These include burn care insurance, teleconsultation follow-ups, hospital-affiliated subsidized lodging, and resources for occupational support and rehabilitation. These measures are crucial to alleviate the financial burden of burn care, particularly during the perioperative period.
Asunto(s)
Quemaduras , Estrés Financiero , Adulto , Humanos , Masculino , Quemaduras/epidemiología , Quemaduras/cirugía , Estudios de Cohortes , Costo de Enfermedad , Complicaciones Intraoperatorias , Estudios Prospectivos , FemeninoRESUMEN
BACKGROUND: During the COVID-19 pandemic-associated mucor epidemic, acute antifungal drug shortage necessitated the exploration of other antifungals based on culture sensitivity. Itraconazole is a cheap, safe, and effective antifungal in sensitive cases. METHODOLOGY: We enrolled itraconazole-sensitive COVID-19-associated mucormycosis during the mucormycosis pandemic. After the intensive phase course of liposomal amphotericin B, Itraconazole was offered in susceptible cases during the maintenance phase along with standard of care. These patients were clinically and radiologically followed for 6 months. RESULTS: We enrolled 14 patients (Male: Female-11:3) of Rhino-orbito-cerebral mucormycosis (ROCM) which included 12 diabetics. All patients had facial swelling, orbital swelling, visual impairment, and headache. MRI showed involvement of bilateral sinus (10/14), orbital extension (13/14), cavernous sinus (5/14), cerebral part of the internal carotid artery (3/14), and brain infarcts (4/14). All 14 patients showed sensitivity to Itraconazole with 12 having minimum inhibitory concentration (MIC) ≤ 1 µg/ml and 2 having MIC ≤ 2 µg/ml. Follow-up at 6 months showed clinical improvement in the majority (11/14) and radiological improvement in six out of seven scanned patients. CONCLUSION: Our study shows the potential therapeutic role of oral Itraconazole in ROCM.
Asunto(s)
Anfotericina B , Antifúngicos , Itraconazol , Mucormicosis , Rhizopus oryzae , Humanos , Masculino , Itraconazol/uso terapéutico , Itraconazol/administración & dosificación , Femenino , Mucormicosis/tratamiento farmacológico , Anfotericina B/uso terapéutico , Anfotericina B/administración & dosificación , Antifúngicos/uso terapéutico , Antifúngicos/administración & dosificación , Persona de Mediana Edad , Adulto , Rhizopus oryzae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , COVID-19/complicaciones , Anciano , Quimioterapia Combinada , Resultado del TratamientoRESUMEN
The outbreak of SARS-CoV-2, also known as the COVID-19 pandemic, is still a critical risk factor for both human life and the global economy. Although, several promising therapies have been introduced in the literature to inhibit SARS-CoV-2, most of them are synthetic drugs that may have some adverse effects on the human body. Therefore, the main objective of this study was to carry out an in-silico investigation into the medicinal properties of Petiveria alliacea L. (P. alliacea L.)-mediated phytocompounds for the treatment of SARS-CoV-2 infections since phytochemicals have fewer adverse effects compared to synthetic drugs. To explore potential phytocompounds from P. alliacea L. as candidate drug molecules, we selected the infection-causing main protease (Mpro) of SARS-CoV-2 as the receptor protein. The molecular docking analysis of these receptor proteins with the different phytocompounds of P. alliacea L. was performed using AutoDock Vina. Then, we selected the three top-ranked phytocompounds (myricitrin, engeletin, and astilbin) as the candidate drug molecules based on their highest binding affinity scores of -8.9, -8.7 and -8.3 (Kcal/mol), respectively. Then, a 100 ns molecular dynamics (MD) simulation study was performed for their complexes with Mpro using YASARA software, computed RMSD, RMSF, PCA, DCCM, MM/PBSA, and free energy landscape (FEL), and found their almost stable binding performance. In addition, biological activity, ADME/T, DFT, and drug-likeness analyses exhibited the suitable pharmacokinetics properties of the selected phytocompounds. Therefore, the results of this study might be a useful resource for formulating a safe treatment plan for SARS-CoV-2 infections after experimental validation in wet-lab and clinical trials.
Asunto(s)
Antivirales , Tratamiento Farmacológico de COVID-19 , Proteasas 3C de Coronavirus , Fitoquímicos , SARS-CoV-2 , Humanos , Antivirales/farmacología , Antivirales/química , Antivirales/uso terapéutico , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Proteasas 3C de Coronavirus/metabolismo , Proteasas 3C de Coronavirus/química , COVID-19/virología , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Fitoquímicos/farmacología , Fitoquímicos/química , Fitoquímicos/uso terapéutico , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/química , Inhibidores de Proteasas/uso terapéutico , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/enzimologíaRESUMEN
Grass carp intestinal waste-mediated biosynthesized nanosilver (AgNPs) was valorized using guaran and zeolite matrices, resulting in AgNPs-guaran, AgNPs-zeolite, and AgNPs-guaran -zeolite composites. The valorized products were examined using Environmental Scanning Electron Microscopy, Energy Dispersive X-ray analysis and X-ray Diffraction analysis to confirm uniform dispersion and entrapment of AgNPs within the matrixes. These valorized products were evaluated for their efficacy in detoxifying the ubiquitous and toxic hexavalent chromium (Cr6+) in aquatic environments, with Anabas testudineus exposed to 2 mg l-1 of Cr6+ for 60 days. Remarkable reduction of Cr6+ concentration to 0.86 ± 0.007 mg l-1 was achieved with AgNPs-guaran-zeolite composite, indicating successful reclamation of contaminated water and food safety assurance. Consistency in results was further corroborated by minimal stress-related alterations in fish physiological parameters and integrated biomarker response within the experimental group treated with the AgNPs-guaran-zeolite composite. Despite observed chromium accumulation in fish tissues, evidence of physiological stability was apparent, potentially attributable to trivalent chromium accumulation, serving as an essential nutrient for the fish. Additionally, the challenge study involving Anabas testudineus exposed to Aeromonas hydrophila exhibited the lowest cumulative mortality (11.11%) and highest survival rate (87.5%) within the same experimental group. The current study presents a novel approach encompassing the valorization of AgNPs for Cr6+ detoxification under neutral to alkaline pH conditions, offering a comprehensive framework for environmental remediation.
Asunto(s)
Biomarcadores , Cromo , Nanopartículas del Metal , Plata , Contaminantes Químicos del Agua , Zeolitas , Animales , Cromo/química , Zeolitas/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/toxicidad , Plata/química , Plata/toxicidad , Nanopartículas del Metal/química , Nanopartículas del Metal/toxicidad , Hidrogeles/química , Bioacumulación , Inactivación Metabólica , Galactanos , Mananos , Gomas de PlantasRESUMEN
BACKGROUND: Anomalous left brachiocephalic vein (ALBCV) is a rare venous anomaly. Double Left brachiocephalic vein is the rarest type of ALBCV anomaly. CASE REPORT: Here we report a case of gentleman with post myocardial infarction ventricular tachycardia who underwent ICD implantation, where we could not place the lead initially through left side. CT angiography revealed presence of a duplicated circumaortic left BCV. It's cranial limb coursing normally anterior to arch and compressed at its confluence with RBCV and the caudal limb with a subaortic course draining into the RSVC. We report this first case of double LBCV along with right sided aortic arch and aberrant origin of LSCA arising from Kommerel's diverticulum. CONCLUSION: This case highlights that interventional cardiologists should be aware of these venous anomalies for proper planning and implantation of CIED successfully via transvenous approach.
RESUMEN
Intratumoral multi-injection strategy enhances the efficacy of magnetic nanoparticle hyperthermia therapy (MNPH). In this study, criteria for the selection of injections and their location depending on the tumor shape/geometry are developed. The developed strategy is based on the thermal dosimetry results of different invasive 3D tumor models during MNPH simulation. MNPH simulations are conducted on physical tumor tissue models encased within healthy tissue. The tumor shapes are geometrically divided into a central tumor region containing maximum tumor volume and a peripheral tumor portion protruding in any random direction. The concepts of core and invasive radius are used to geometrically divide the tumor volume. Primary & secondary injections are used to inject MNP fluid into these respective tumor regions based on the invasiveness of the tumor. The optimization strategy is devised based on the zone of influence of primary & secondary injection. Results indicate that the zone of influence of secondary injection lies between 0.7 and 0.8 times the radial distance between the center of the tumor core and branch node point (extreme far endpoint on the invasive tumor surface). Additionally, the multi-injection strategy is more effective when the protrusion volume exceeds10%of the total volume. The proposed algorithm is used to devise multi-injection strategies for arbitrarily shaped tumors and will assist in pre-planning magnetic nanoparticle hyperthermia therapy.
Asunto(s)
Hipertermia Inducida , Neoplasias , Hipertermia Inducida/métodos , Humanos , Neoplasias/terapia , Neoplasias/patología , Nanopartículas de Magnetita/uso terapéutico , Simulación por Computador , Algoritmos , Modelos Biológicos , Carga TumoralRESUMEN
This critical review of Kaddoura et al.'s article on sacubitril/valsartan in heart failure patients underscores the importance of considering potential adverse effects, including renal failure, hyperkalemia, angioedema, and increased reports of sudden cardiac death. It highlights the need for rigorous monitoring and precise treatment regimens, especially in diabetic heart failure patients. Additionally, the review questions the generalizability of the study's results to diverse healthcare settings and emphasizes the importance of grounded patient follow-up data for accurate long-term assessment. These considerations are vital for informed decision-making regarding sacubitril/valsartan use in heart failure management.
Asunto(s)
Desfibriladores Implantables , Insuficiencia Cardíaca , Disfunción Ventricular Izquierda , Humanos , Volumen Sistólico , Análisis de Costo-Efectividad , Tetrazoles/uso terapéutico , Valsartán , Insuficiencia Cardíaca/terapia , Disfunción Ventricular Izquierda/inducido químicamenteRESUMEN
Steroid-induced acute pancreatitis is a rare form of pancreatitis that requires intensive care and has a high morbidity and mortality rate as there is no specific treatment. Management of steroid-induced pancreatitis is generally non-specific and supportive. Here, we are presenting a man in his 40s presented with epigastric pain, fever and vomiting. The patient was diagnosed case of rheumatoid arthritis, for which he was receiving regular 5 mg oral prednisolone therapy. Based on history, and clinical, biochemical and radiological imaging a diagnosis of steroid-induced pancreatitis was made, which was successfully managed with the help of ulinastatin and other supportive treatments. A serine protease inhibitor like ulinastatin may be used early in the clinical management of steroid-induced pancreatitis.
Asunto(s)
Glicoproteínas , Pancreatitis , Prednisolona , Inhibidores de Tripsina , Humanos , Masculino , Prednisolona/uso terapéutico , Pancreatitis/inducido químicamente , Pancreatitis/tratamiento farmacológico , Adulto , Inhibidores de Tripsina/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Glucocorticoides/efectos adversosRESUMEN
This perspective sheds light on the transformative impact of recent computational advancements in the field of protein therapeutics, with a particular focus on the design and development of antibodies. Cutting-edge computational methods have revolutionized our understanding of protein-protein interactions (PPIs), enhancing the efficacy of protein therapeutics in preclinical and clinical settings. Central to these advancements is the application of machine learning and deep learning, which offers unprecedented insights into the intricate mechanisms of PPIs and facilitates precise control over protein functions. Despite these advancements, the complex structural nuances of antibodies pose ongoing challenges in their design and optimization. Our review provides a comprehensive exploration of the latest deep learning approaches, including language models and diffusion techniques, and their role in surmounting these challenges. We also present a critical analysis of these methods, offering insights to drive further progress in this rapidly evolving field. The paper includes practical recommendations for the application of these computational techniques, supplemented with independent benchmark studies. These studies focus on key performance metrics such as accuracy and the ease of program execution, providing a valuable resource for researchers engaged in antibody design and development. Through this detailed perspective, we aim to contribute to the advancement of antibody design, equipping researchers with the tools and knowledge to navigate the complexities of this field.
RESUMEN
It is an urgent needs to address climate change and pollution in aquatic systems using suitable mitigation measures to avoid the aquatic animals' extinction. The vulnerability and extinction of the aquatic animals in the current scenario must be addressed to enhance safe fish food production. Taking into consideration of such issues in fisheries and aquaculture, an experiment was designed to mitigate high temperature (T) and low pH stress, as well as arsenic (As) pollution in fish using copper (Cu) containing diets. In the present investigation, the Cu-containing diets graded with 0, 4, 8, and 12 mg kg-1 were prepared and fed to Pangasianodon hypophthalmus reared under As, low pH, and high-temperature stress. The gene expression was highly affected in terms of the primary, secondary, and tertiary stress response, whereas supplementation of Cu-containing diet mitigates the stress response. Oxidative stress genes such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were significantly upregulated by stressors (As, As + T, and As + pH + T). Whereas, heat shock protein (HSP 70), inducible nitric oxide synthase (iNOS), metallothionine (MT), caspase 3a (Cas 3a), and cytochrome P450 (CYP 450) were highly upregulated by stressors, while dietary Cu at 8 mg kg-1 diet significantly downregulated these gene expressions. Indeed, the immunity-related genes viz. TNFα, Ig, TLR, and immune-related attributes viz. albumin, globulin, total protein, A:G ratio, blood glucose, NBT, and myeloperoxidase (MPO) were also improved with Cu-containing diets. Cu containing diets substantially improved neurotransmitter enzyme (AChE) and vitamin C (Vit C). DNA damage was also reduced with supplementation of Cu at 8 mg kg-1 diet. The growth index viz. final body weight gain (%), specific growth rate, protein efficiency ratio, food conversion ratio, relative feed intake, and daily growth index were noticeably enhanced by Cu diets (4 and 8 mg kg-1 diet). The growth-related genes expressions viz. growth hormone (GH), growth hormone regulator 1 (Ghr1), growth hormone regulator ß (Ghrß,) myostatin (MYST), and somatostatin (SMT) supported the growth enhancement with Cu at 8 mg kg-1 diet. The bioaccumulation of As was reduced with Cu-containing diets. The fish were infected with Aeromonas hydrophila at the end of the 105 days experimental trial. Cu at 8 mg kg-1 diet improved immunity, reduced the cumulative mortality, and enhanced the relative percentage survival of the fish. The results revealed that the innovative Cu diets could reduce the extinction of the fish against climate change and pollution era and produce the safest production that is safe to humans for consumption.
Asunto(s)
Bagres , Suplementos Dietéticos , Animales , Humanos , Antioxidantes/metabolismo , Cobre , Dieta , Bagres/fisiología , Hormona del Crecimiento , Alimentación Animal/análisisRESUMEN
The persistent challenges posed by pollution and climate change are significant factors disrupting ecosystems, particularly aquatic environments. Numerous contaminants found in aquatic systems, such as ammonia and metal toxicity, play a crucial role in adversely affecting aquaculture production. Against this backdrop, fish feed was developed using quinoa husk (the byproduct of quinoa) as a substitute for fish meal. Six isonitrogenous diets (30%) and isocaloric diets were formulated by replacing fish meal with quinoa husk at varying percentages: 0% quinoa (control), 15, 20, 25, 30 and 35%. An experiment was conducted to explore the potential of quinoa husk in replacing fish meal and assess its ability to mitigate ammonia and arsenic toxicity as well as high-temperature stress in Pangasianodon hypophthalmus. The formulated feed was also examined for gene regulation related to antioxidative status, immunity, stress proteins, growth regulation, and stress markers. The gene regulation of sod, cat, and gpx in the liver was notably upregulated under concurrent exposure to ammonia, arsenic, and high-temperature (NH3 + As + T) stress. However, quinoa husk at 25% downregulated sod, cat, and gpx expression compared to the control group. Furthermore, genes associated with stress proteins HSP70 and DNA damage-inducible protein (DDIP) were significantly upregulated in response to stressors (NH3 + As + T), but quinoa husk at 25% considerably downregulated HSP70 and DDIP to mitigate the impact of stressors. Growth-responsive genes such as myostatin (MYST) and somatostatin (SMT) were remarkably downregulated, whereas growth hormone receptor (GHR1 and GHRß), insulin-like growth factors (IGF1X, IGF2X), and growth hormone gene were significantly upregulated with quinoa husk at 25%. The gene expression of apoptosis (Caspase 3a and Caspase 3b) and nitric oxide synthase (iNOS) were also noticeably downregulated with quinoa husk (25%) reared under stressful conditions. Immune-related gene expression, including immunoglobulin (Ig), toll-like receptor (TLR), tumor necrosis factor (TNFα), and interleukin (IL), strengthened fish immunity with quinoa husk feed. The results revealed that replacing 25% of fish meal with quinoa husk could improve the gene regulation of P. hypophthalmus involved in mitigating ammonia, arsenic, and high-temperature stress in fish.
Asunto(s)
Arsénico , Bagres , Chenopodium quinoa , Animales , Suplementos Dietéticos/análisis , Chenopodium quinoa/genética , Arsénico/toxicidad , Amoníaco , Ecosistema , Dieta , Antioxidantes , Caspasas , Alimentación Animal/análisisRESUMEN
The current investigation explores the mechanisms of ammonia and arsenic toxicity, along with high-temperature stress, which other researchers rarely addressed. Pangasianodon hypophthalmus was exposed to low doses of ammonia and arsenic (1/10th of LC50, 2.0 and 2.68 mg L-1, respectively) and high temperature (34 °C) for 105 days. The following treatments were applied: control (unexposed), arsenic (As), ammonia (NH3), ammonia + arsenic (NH3 + As), ammonia + temperature (NH3 + T), and NH3 + As + T. Cortisol levels significantly increased with exposure to ammonia (NH3), arsenic (As), and high temperature (34 °C) compared to the unexposed group. Heat shock protein (HSP 70), inducible nitric oxide synthase (iNOS), and metallothionein (MT) gene expressions were notably upregulated by 122-210%, 98-122%, and 64-238%, respectively, compared to the control. Neurotransmitter enzymes (acetylcholine esterase, AChE) were significantly inhibited by NH3 + As + T, followed by other stressor groups. The apoptotic (caspase, Cas 3a and 3b) and detoxifying (cytochrome P450, CYP P450) pathways were substantially affected by the NH3 + As + T group. Immune (total immunoglobulin, Ig; tumor necrosis factor TNFα; and interleukin IL) and growth-related genes (growth hormone, GH; growth hormone regulator, GHR1 and GHRß; myostatin, MYST and somatostatin, SMT) were noticeably upregulated by NH3 + As + T, followed by other stress groups, compared to the control group. Weight gain %, protein efficiency ratio, feed efficiency ratio, specific growth rate, and other growth attributes were significantly affected by low doses of ammonia, arsenic, and high-temperature stress. Albumin, total protein, globulin, A:G ratio, and myeloperoxidase (MPO) were highly affected by the As + NH3 + T group. Blood profiling, including red blood cells (RBC), white blood count (WBC), and hemoglobin (Hb), were also impacted by stressor groups compared to the control group. Genotoxicity, as DNA damage, was significantly higher in groups exposed to NH3 + As + T (89%), NH3 + T (78%), NH3 (73), NH3 + As (71), and As (68%). The bioaccumulation of arsenic was substantially higher in liver and kidney tissues. The present study contributes to understanding the toxicity mechanisms of ammonia and arsenic, as well as high-temperature stress, through different gene expressions, biochemical attributes, genotoxicity, immunological status, and growth performance of P. hypophthalmus.
Asunto(s)
Arsénico , Arsénico/toxicidad , Amoníaco , Temperatura , Antioxidantes/metabolismo , Hormona del CrecimientoRESUMEN
Disseminated cysticercosis is defined by multiple brain lesions and involvement of other body sites. Cysticidal treatment in disseminated cysticercosis is considered life-threatening. We conducted a systematic review of all published cases and case series to assess the safety and efficacy of cysticidal treatment. We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42022331895) to assess the safety and efficacy of cysticidal treatment. Using the search term "disseminated neurocysticercosis OR disseminated cysticercosis," databases like PubMed, Scopus, Embase, and Google Scholar were searched. Outcomes included death and secondary measures like clinical improvement and lesion reduction. We calculated the predictors of primary outcome (death) using the binary logistic regression analysis. We reviewed 222 published cases from 101 publications. Approximately 87% cases were reported from India. Of 222 cases, 134 (60%) received cysticidal treatment. Follow-up information was available from 180 patients, 11 of them died, and 169 showed clinical improvement. The death rate was 4% (5 out of 114) in patients treated with cysticidal drugs plus corticosteroids, in comparison with 13% (5 out of 38) in patients who were treated with corticosteroids alone. All patients using only praziquantel faced fatality. Death predictors identified were altered sensorium and lack of treatment with albendazole. We noted that the risk of death after cysticidal treatment is not as we expected, and a multicentric randomized controlled trial is needed to resolve this issue.
Asunto(s)
Cisticercosis , Neurocisticercosis , Humanos , Resultado del Tratamiento , Neurocisticercosis/tratamiento farmacológico , Neurocisticercosis/mortalidad , Cisticercosis/tratamiento farmacológico , Cisticercosis/mortalidad , Antihelmínticos/uso terapéutico , Albendazol/uso terapéutico , Praziquantel/uso terapéutico , Masculino , Corticoesteroides/uso terapéutico , Femenino , AdultoRESUMEN
Pediatric burns pose a significant health burden in LMICs. Despite efforts to address burn prevention and management, morbidity and mortality rates remain high, particularly among children. Understanding pediatric burn epidemiology and predictors of clinical outcomes is crucial for developing effective prevention strategies and improving patient-care. This retrospective cohort study analyzed pediatric burn patients admitted to a tertiary burn-center in India, between March-2022 and December-2023. Demographic date, burn characteristics, treatments, complications and outcomes were collected. Statistical analysis, including logistic and linear regression, was conducted to identify predictors of mortality, sepsis, and hospital stay length. Among 332 pediatric burn patients, median age was 3 years, with a male predominance. Scald burns were the most common, followed by electrical and flame burns. Median total body surface area burned was 20%, with upper and lower extremities most affected. The incidence of electrical burns increased with age and was associated with a longer length of stay. Mortality rate was 14.2%, with age >10 years, male gender, and TBSA >30% predicting mortality. Complications like sepsis significantly increased mortality risk, while deep burns were associated with longer hospital stays. This study underscores importance of targeted prevention efforts and specialized care. Scald burns among young children highlight the need for safer cooking practices, while the high incidence of electrical burns in older children suggests age-specific education interventions are necessary. Predictors of mortality identified can guide risk assessment and resource allocation, emphasizing the importance of infection control and wound management strategies in improving outcomes.