RESUMEN
With the evolution of multicellularity, communication among cells in different tissues and organs became pivotal to life. Molecular basis of such communication has long been studied, but genome-wide screens for genes and other biomolecules mediating tissue-tissue signaling are lacking. To systematically identify inter-tissue mediators, we present a novel computational approach MultiCens (Multilayer/Multi-tissue network Centrality measures). Unlike single-layer network methods, MultiCens can distinguish within- vs. across-layer connectivity to quantify the "influence" of any gene in a tissue on a query set of genes of interest in another tissue. MultiCens enjoys theoretical guarantees on convergence and decomposability, and performs well on synthetic benchmarks. On human multi-tissue datasets, MultiCens predicts known and novel genes linked to hormones. MultiCens further reveals shifts in gene network architecture among four brain regions in Alzheimer's disease. MultiCens-prioritized hypotheses from these two diverse applications, and potential future ones like "Multi-tissue-expanded Gene Ontology" analysis, can enable whole-body yet molecular-level systems investigations in humans.
Asunto(s)
Enfermedad de Alzheimer , Encéfalo , Humanos , Redes Reguladoras de Genes/genética , Enfermedad de Alzheimer/genéticaRESUMEN
BACKGROUND: Bovine tuberculosis (bTB) is a chronic disease that results from infection with any member of the Mycobacterium tuberculosis complex. Infected animals are typically diagnosed with tuberculin-based intradermal skin tests according to World Organization of Animal Health which are presently in use. However, tuberculin is not suitable for use in BCG-vaccinated animals due to a high rate of false-positive reactions. Peptide-based defined skin test (DST) antigens have been identified using antigens (ESAT-6, CFP-10 and Rv3615c) which are absent from BCG, but their performance in buffaloes remains unknown. To assess the comparative performance of DST with the tuberculin-based single intradermal test (SIT) and the single intradermal comparative cervical test (SICCT), we screened 543 female buffaloes from 49 organized dairy farms in two districts of Haryana state in India. RESULTS: We found that 37 (7%), 4 (1%) and 18 (3%) buffaloes were reactors with the SIT, SICCT and DST tests, respectively. Of the 37 SIT reactors, four were positive with SICCT and 12 were positive with the DST. The results show that none of the animals tested positive with all three tests, and 6 DST positive animals were SIT negative. Together, a total of 43 animals were reactors with SIT, DST, or both, and the two assays showed moderate agreement (Cohen's Kappa 0.41; 95% Confidence Interval (CI): 0.23, 0.59). In contrast, only slight agreement (Cohen's Kappa 0.18; 95% CI: 0.02, 0.34) was observed between SIT and SICCT. Using a Bayesian latent class model, we estimated test specificities of 96.5% (95% CI, 92-99%), 99.7% (95% CI: 98-100%) and 99.0% (95% CI: 97-100%) for SIT, SICCT and DST, respectively, but considerably lower sensitivities of 58% (95% CI: 35-87%), 9% (95% CI: 3-21%), and 34% (95% CI: 18-55%) albeit with broad and overlapping credible intervals. CONCLUSION: Taken together, our investigation suggests that DST has a test specificity comparable with SICCT, and sensitivity intermediate between SIT and SICCT for the identification of buffaloes suspected of tuberculosis. Our study highlights an urgent need for future well-powered trials with detailed necropsy, with immunological and microbiological profiling of reactor and non-reactor animals to better define the underlying factors for the large observed discrepancies in assay performance, particularly between SIT and SICCT.
Asunto(s)
Bison , Enfermedades de los Bovinos , Mycobacterium bovis , Tuberculosis Bovina , Femenino , Animales , Bovinos , Tuberculosis Bovina/diagnóstico , Búfalos , Tuberculina , Teorema de Bayes , Vacuna BCG , Prueba de Tuberculina/veterinaria , Sensibilidad y EspecificidadRESUMEN
Ibuprofen (IBP), the 29th most prescribed drug in the United States in 2019, is a widely used nonsteroidal anti-inflammatory drug (NSAID) comprising two enantiomers, (R)-IBP and (S)-IBP, collectively known as (RS)-IBP. This critical review examines analytical techniques for the enantioselective separation and determination of IBP enantiomers, crucial for pharmaceutical and clinical applications. The review focuses on state-of-the-art methods, including chromatographic techniques including high-performance liquid chromatography, gas chromatography, liquid chromatography-tandem mass spectrometry, and some other techniques. This review addresses pharmacokinetics, pharmacology, and side effects of each enantiomer, ensuring safe drug usage. By consolidating diverse analytical methods and their applicability in different matrices, this review serves as a valuable resource for researchers, analysts, and practitioners in pharmaceutical analysis, pharmacology, and clinical studies.
Asunto(s)
Ibuprofeno , Espectrometría de Masas en Tándem , Ibuprofeno/química , Estereoisomerismo , Espectrometría de Masas en Tándem/métodos , Cromatografía de Gases y Espectrometría de Masas , Cromatografía Líquida de Alta Presión/métodos , Preparaciones FarmacéuticasRESUMEN
BACKGROUND: Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by hamartomatous gastrointestinal polyps along with the characteristic mucocutaneous freckling. Multiple surgeries for recurrent intussusception in these children may lead to short bowel syndrome. Here we present our experience of management in such patients. METHODS: From January 2015 to December 2023, we reviewed children of PJS, presented with recurrent intussusceptions. Data were collected regarding presentation, management, and follow-up with attention on management dilemma. Diagnosis of PJS was based on criteria laid by World Health Organization (WHO). RESULTS: A total of nine patients were presented with age ranging from 4 to 17 years (median 9 years). A total of eighteen laparotomies were performed (7 outside, 11 at our centre). Among 11 laparotomies done at our centre, resection and anastomosis of bowel was done 3 times while 8 times enterotomy and polypectomy was done after reduction of intussusception. Upper and lower gastrointestinal endoscopy (UGIE & LGIE) was done in all cases while intraoperative enteroscopy (IOE) performed when required. Follow-up ranged from 2 months to 7 years. CONCLUSION: Children with PJS have a high risk of multiple laparotomies due to polyps' complications. Considering the diffuse involvement of the gut, early decision of surgery and extensive bowel resection should not be done. Conservative treatment must be tried under close observation whenever there is surgical dilemma. The treatment should be directed in the form of limited resection or polypectomy after reduction of intussusception.
Asunto(s)
Intususcepción , Síndrome de Peutz-Jeghers , Recurrencia , Humanos , Síndrome de Peutz-Jeghers/complicaciones , Síndrome de Peutz-Jeghers/cirugía , Intususcepción/cirugía , Intususcepción/terapia , Niño , Preescolar , Adolescente , Femenino , Masculino , Estudios Retrospectivos , Laparotomía/métodos , Estudios de SeguimientoRESUMEN
In North Bihar (NB), the conventional rice-wheat cropping system has led to soil, water, and environmental degradation, alongside low profitability, threatening sustainability. To address these concerns, a thorough field research was conducted over the course of three years to assess different methods of tillage and crop establishment in a rice, wheat, and greengram cycle. The experiment involved five scenarios with different combinations of crop rotation, tillage techniques, seeding procedures, fertilizer use, and irrigation strategies. Uncertainty analysis showed no significant change in mean and variance estimation among seven scenario replications at 5% significance level. Compared to traditional farming (SN-1), managing DSR-rice (SN-5) increased profitability by 17.56%, improved energy use efficiency (EUE) by 32.16%, and reduced irrigation by 24.76% and global warming potential (GWP) by 23.46%. Similarly, substituting zero tillage wheat (ZTW) SN-5 resulted in comparable profitability gains (18.25%) and significant improvements in irrigation (10 %), EUE (+48.65%), and GWP (-20 %) compared to SN-1. Green gram ZT also showed increased profitability (17.35%), with notable improvements in EUE (+38.31%) and GWP (-12.92%) compared to SN-1. Principal component and correlation analyses revealed relationships between total energy inputs, yields, economic returns, and sustainability indices, highlighting the benefits of crop rotation and tillage practices in optimizing resource use. The study suggests that compared to conventional systems, significant improvements in productivity, profitability, energy-use efficiency, and environmental mitigation can be achieved with Crop Rotation and Tillage Operations techniques.
Asunto(s)
Agricultura , Productos Agrícolas , Gases de Efecto Invernadero/análisis , Gases de Efecto Invernadero/metabolismo , India , Productos Agrícolas/crecimiento & desarrollo , Productos Agrícolas/metabolismo , Agricultura/economía , Agricultura/métodos , Oryza/crecimiento & desarrollo , Oryza/metabolismo , Triticum/crecimiento & desarrollo , Triticum/metabolismo , Verduras/crecimiento & desarrollo , Verduras/metabolismo , Incertidumbre , Energía Renovable/economía , Riego Agrícola/economía , Riego Agrícola/métodosRESUMEN
Castleman disease is an unusual, benign disorder of unknown etiology, characterized by the proliferation of the lymphoid tissue. It can have a unicentric or multicentric presentation, depending on the number of lymph nodes involved. On clinical examination and imaging, it can imitate a malignancy and the diagnosis can only be confirmed on histopathological examination. Retroperitoneal location and presentation in the pediatric age group are extremely rare. We report a case of an adolescent girl with a unicentric lymph nodal mass in the portocaval space which was completely excised.
RESUMEN
Introduction: Enhanced recovery after surgery (ERAS) is a multidisciplinary approach to optimize patient care. The goal of this approach is to reduce the body's reaction to surgical stress by optimizing the perioperative nutritional status, promoting analgesia without opioids, and early postoperative feeding. In pediatric patients, very limited literature is available for the application of ERAS protocol. This study was done to evaluate the application of ERAS protocol in pediatric hepatobiliary and pancreatic patients. Materials and Methods: This is a randomized prospective study conducted over a period of 2 years at a tertiary center in North India. A total of 40 hepatobiliary and pancreatic patients who were willing to participate in the study were included in the study. Patients were randomized by computer-generated method and data were collected regarding demography, clinical diagnosis, preoperative and postoperative workup, and peri-operative care including analgesia, pain scores, postoperative recovery, hospital stay, and complications. These patients were followed for 6 months postoperatively and the results were evaluated using SPSS software. Results: The study included 20 patients each in both the conventional and ERAS group with median ages of 11.5 years and 7.1 years, respectively. The data analysis showed that the ERAS group of patients had better outcomes in terms of hospital stay and drain removal time with significant statistical differences. Pain scores and complications are almost the same in both groups. Conclusion: Principles of ERAS can be safely applied in pediatric patients undergoing major surgery in the present era of emerging infections and also increasing patient burden without morbidity.
RESUMEN
MOTIVATION: Inter-organ/inter-tissue communication is central to multi-cellular organisms including humans, and mapping inter-tissue interactions can advance system-level whole-body modeling efforts. Large volumes of biomedical literature have fostered studies that map within-tissue or tissue-agnostic interactions, but literature-mining studies that infer inter-tissue relations, such as between hormones and genes are solely missing. RESULTS: We present a first study to predict from biomedical literature the hormone-gene associations mediating inter-tissue signaling in the human body. Our BioEmbedS* models use neural network-based Biomedical word Embeddings with a Support Vector Machine classifier to predict if a hormone-gene pair is associated or not, and whether an associated gene is involved in the hormone's production or response. Model training relies on our unified dataset Hormone-Gene version 1 of ground-truth associations between genes and endocrine hormones, which we compiled and carefully balanced in the embedded space to handle data disparities, such as between poorly- versus well-studied hormones. Our BioEmbedS model recapitulates known gene mediators of tissue-tissue signaling with 70.4% accuracy; predicts novel inter-tissue communication genes in humans, which are enriched for hormone-related disorders; and generalizes well to mouse, thereby holding promise for its extension to other multi-cellular organisms as well. AVAILABILITY AND IMPLEMENTATION: Freely available at https://cross-tissue-signaling.herokuapp.com are our model predictions & datasets; https://github.com/BIRDSgroup/BioEmbedS has all relevant code. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Asunto(s)
Redes Neurales de la Computación , Publicaciones , Animales , Hormonas , Humanos , RatonesRESUMEN
The emergence of antibiotic resistance prompts exploration of viable antimicrobial peptides (AMPs) designs. The present study explores the antimicrobial prospects of Apoptin nuclear localization sequence (NLS2)-derived peptide ANLP (PRPRTAKRRIRL). Further, we examined the utility of the NLS dimerization strategy for improvement in antimicrobial activity and sustained bio-stability of AMPs. Initially, the antimicrobial potential of ANLP using antimicrobial peptide databases was analyzed. Then, ANLP along with its two homodimer variants namely ANLP-K1 and ANLP-K2 were synthesized and evaluated for antimicrobial activity against Escherichia coli and Salmonella. Among three AMPs, ANLP-K2 showed efficient antibacterial activity with 12 µM minimum inhibitory concentration (MIC). Slow degradation of ANLP-K1 (26.48%) and ANLP-K2 (13.21%) compared with linear ANLP (52.33%) at 480 min in serum stability assay indicates improved bio-stability of dimeric peptides. The AMPs presented no cytotoxicity in Vero cells. Dye penetration assays confirmed the membrane interacting nature of AMPs. The zeta potential analysis reveals effective charge neutralization of both lipopolysaccharide (LPS) and bacterial cells by dimeric AMPs. The dimeric AMPs on scanning electron microscopy studies showed multiple pore formations on the bacterial surface. Collectively, proposed Lysine scaffold dimerization of Apoptin NLS2 strategy resulted in enhancing antibacterial activity, bio-stability, and could be effective in neutralizing the off-target effect of LPS. In conclusion, these results suggest that nuclear localization sequence with a modified dimeric approach could represent a rich source of template for designing future antimicrobial peptides.
Asunto(s)
Antiinfecciosos , Lipopolisacáridos , Animales , Chlorocebus aethiops , Lipopolisacáridos/metabolismo , Péptidos Catiónicos Antimicrobianos/farmacología , Dimerización , Células Vero , Antibacterianos/farmacología , Antibacterianos/química , Péptidos Antimicrobianos , Pruebas de Sensibilidad MicrobianaRESUMEN
Biochanin-A (BCA), is an isoflavonoid, exhibits protective effects against various diseases. This study was conducted to observe the effect of BCA on isoprenaline (ISP)-induced cardiac fibrosis and explore the underlying mechanism. The curative effect of BCA was investigated with oral administration for 14 days in ISP-induced cardiac fibrosis in mice. The fibrotic biomarkers, like collagen I and III, were estimated by ELISA. Commercial kits were used to estimate cholesterol, triglycerides, and creatine kinase-myocardial band (CK-MB) levels. The messenger ribonucleic acid (mRNA) expression studies were performed by quantitative real-time polymerase chain reaction. Gelatin zymography was used to study the expression of matrix metalloproteinases-2 (MMP-2). BCA co-administration significantly improved the morphometric parameters; including heart weight, heart weight to body weight, heart weight to tibial length, and lipid profile. BCA treatment showed a reduction in inflammatory cells and collagen deposition as depicted in the histopathology of heart tissues. The enhanced levels of collagen-I, III, and hydroxyproline were significantly decreased by BCA co-treatment, whereas CK-MB level was reduced slightly. BCA co-administration increased the activity of reduced glutathione enzyme, showing the antioxidative effects of BCA. BCA treatment significantly reduced interleukin-6 (Il6) inflammatory cytokine along with partially decreased mRNA expression of fibrotic signaling markers such as natriuretic peptide type B (Nppb), α-smooth muscle actin (Acta2), connective tissue growth factor (Ctgf), transforming growth factor ß (Tgfb), small mothers against decapentaplegic homolog-3 (Smad-3). However, BCA did not modify Mmp-2 expression, which was significantly increased by ISP. In conclusion, BCA exerts an antifibrotic effect by modulating lipid profile, enhancing antioxidant enzyme, and reducing collagen content and inflammation.
Asunto(s)
Lesiones Cardíacas , Metaloproteinasa 2 de la Matriz , Ratones , Animales , Fibrosis , Inflamación/tratamiento farmacológico , Colágeno/metabolismo , Colágeno Tipo I , Isoproterenol/toxicidad , ARN Mensajero/genética , LípidosRESUMEN
D-amino acids, the important components of the bacterial cell walls, are valuable molecular and genetic markers of bacterial-derived organic material in the environment. D-serine, a racemization product of L-serine is one such amino acid present in various prokaryotes and eukaryotes. It is a well-recognized regulator of various activities in the human nervous system. In plants, it has a role in the nitrogen cycle regulation and pollen tube growth. Serine enantiomers are present in different concentrations and few bacterial strains are reported to contribute to D-serine in the environment. During the present study, soil samples from different places in North India were collected and processed to isolate and screen the bacteria on M9 minimal media (Himedia) for D-serine synthesis. Thin-layer chromatography (TLC Silica gel 60 F 254 (20 × 20 cm, Merck, Darmstadt, Germany) and Mass spectroscopic analysis (Bruker MICROTOF II spectrometer) studies, etc were performed. D-serine-producing isolates were characterized as per standard procedures. Bacterial isolate A1C1 with maximum D-serine (0.919 ± 0.02 nM) synthesis under optimal growth conditions (37°C ± 0.5, 150 ± 0.5 RPM, and 7 ± 0.5 pH) was identified as Bacillus tequilensis based on 16sRNA sequencing. The isolate could be a valuable serine racemization tool for various industrial and environmental applications.
Asunto(s)
Bacillus , Serina , Humanos , Serina/análisis , Serina/química , Serina/metabolismo , Aminoácidos/metabolismo , Bacillus/metabolismo , Cromatografía en Capa DelgadaRESUMEN
BACKGROUND: PARP inhibitors (PARPi) have a well-established role in platinum-sensitive ovarian cancer (PSOC), in BRCA mutant (BRCAm), and homologous recombination deficiency (HRD) population. However, their role in wild type and homologous recombination proficient population is still not clear. METHODS: A meta-analysis of hazard ratios (HR) of randomized control trials (RCTs) was conducted to study the role of PARPi. The published RCTs comparing the efficacy of PARP inhibitors alone or in combination with chemotherapy and/or target therapies versus placebo/chemotherapy alone/target therapy alone in primary or recurrent ovarian cancer settings were selected. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. RESULTS: A total of 14 primary studies and 5 updated studies are considered, consisting of 5363 patients. Overall, HR for PFS was 0.50 [95% CI 0.40-0.62]. HR of PFS was 0.94 [95% CI 0.76-1.15] in the PROC group, 0.41 [95% CI 0.29-0.60] was in HRD with BRCA unknown (BRCAuk), 0.38 [95% CI 0.26-0.57] in HRD with BRCAm, and 0.52 [95% CI 0.38-0.71] in HRD with BRCAwt. In the HRP group, overall HR for PFS was 0.67 [95% CI 0.56-0.80], 0.61 [95% CI 0.38-0.99] in HRD unknown with BRCA wt, and 0.40 [95% CI 0.29-0.55] in BRCAm HR for PFS. Overall, HR for OS was 0.86 [95% CI 0.73-1.031]. CONCLUSIONS: The results suggest that PARPi have a meaningful clinical benefit in PSOC, HRD, BRACm, and also in HRP and PROC; however, the evidence is not sufficient to recommend their routine use and further studies are needed to expand their role in the HRP and PROC groups.
Asunto(s)
Neoplasias Ováricas , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Humanos , Femenino , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/genética , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Ensayos Clínicos Controlados Aleatorios como Asunto , MutaciónRESUMEN
Strongyloides stercoralis is responsible for a significant human parasitic infection known as strongyloidiasis. In addition, pulmonary strongyloidiasis is one of the most critical signs of disseminated strongyloidiasis. In this instance, S. stercoralis was unexpectedly discovered in bronchoalveolar lavage fluid.
Asunto(s)
Strongyloides stercoralis , Estrongiloidiasis , Animales , Humanos , Estrongiloidiasis/diagnóstico , Estrongiloidiasis/parasitología , Líquido del Lavado Bronquioalveolar/parasitología , PulmónRESUMEN
INTRODUCTION: Salivary gland neoplasms account for approximately 5% of head and neck tumours. The cytomorphology of fine needle aspiration material helps determine the preoperative assessment and risk stratification. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was developed to improve communication between the laboratory and treatment provider. AIMS AND OBJECTIVE: In the present study, we stratified all salivary gland lesions according to the MSRSGC and evaluated each category's concordance and risk of malignancy (ROM). MATERIALS AND METHODS: This was a 5 year retrospective study. First, all cases were assigned to one of the six MSRSGC categories. Then, following cytohistological correlation, the concordance rates and ROM were calculated based on the final histopathology report. RESULTS: A total of 354 cases were identified, with ages ranging from 2 to 88 years and the commonest age group was the 3rd to 4th decades. Categories I, II, III, IVA, IVB, V, and VI comprised 5.37% (19/354), 26.84% (95/354), 1.13% (04/354), 51.41% (182/354), 1.98% (07/354), 1.13% (04/354), and 12.15% (43/354) of the cases, respectively. The overall concordance rate between the cytological and histopathological diagnoses was 81.25% (65 out of 80 cases), with the sensitivity, specificity, positive predictive value, and negative predictive value at 43.48%, 96.49%, 83.33%, and 80.88%, respectively. CONCLUSION: The MSRSGC provides a better objective and structured way to communicate with the health care provider. In our study, the overall concordance rate was observed in 62/80 cases, with maximum concordance seen in categories III, IVB, and V of the MSRSGC.
Asunto(s)
Neoplasias de las Glándulas Salivales , Glándulas Salivales , Humanos , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estudios Retrospectivos , Centros de Atención Terciaria , Glándulas Salivales/patología , Neoplasias de las Glándulas Salivales/diagnóstico , Neoplasias de las Glándulas Salivales/patología , Medición de RiesgoRESUMEN
Non-dispersive infra-red (NDIR) detectors have become the dominant method for measuring atmospheric CO2, which is thought to be an important gas for honeybee colony health. In this work we describe a microcontroller-based system used to collect data from Senserion SCD41 NDIR sensors placed in the crown boards and queen excluders of honeybee colonies. The same sensors also provide relative humidity and temperature data. Several months of data have been recorded from four different hives. The mass change measurements, from hive scales, when foragers leave the hive were compared with the data from the gas sensors. Our data suggest that it is possible to estimate the colony size from the change in measured CO2, however no such link with the humidity is observed. Data are presented showing the CO2 decreasing over many weeks as a colony dies.
Asunto(s)
Dióxido de Carbono , Registros , Abejas , Animales , Humedad , TemperaturaRESUMEN
BACKGROUND: Pathological effects of dysglycemia and insulin resistance on atherosclerosis and cardiac remodeling starts as early as in the prediabetic state before the onset of overt diabetes. Activin A is a molecule with multiple functions, including an important part in glucose homeostatic mechanisms as well as inflammatory processes and is therefore being researched as a useful novel biomarker for prompt recognition of the risk of cardiovascular disease (CVD) in prediabetic individuals, thereby helping in disease prognostication and early institution of therapeutic measuresObjective: The study aimed to measure serum levels of activin A in prediabetic patients and evaluate them in comparison to normoglycemic controls. The association of activin A with carotid intima media thickness (CIMT), left ventricular diastolic dysfunction (LVDD), and homeostatic assessment of insulin resistance (HOMA-IR) was also studiedMaterials and methods: A total of 60 prediabetic cases and 60 normoglycemic control subjects [matched as per age, gender, and body mass index (BMI)] were recruited. Measurement of serum glucose levels (fasting and postprandial) and fasting insulin levels and glycated hemoglobin (HbA1c) levels were done in all the subjects. The values of HOMA-IR were computed using established formulae. Enzyme-linked immunosorbent assay (ELISA) kits were used for the evaluation of serum levels of activin A in both groups. Parameters for the two groups were compared. In the cases, CIMT (using B-mode ultrasound) and LVDD (using two-dimensional (2D) echocardiography) were measured and correlated with activin A levelsResults: Serum fasting insulin (mIU/L) was considerably higher in cases than in the controls (p < 0.001). HOMA-IR median [interquartile range (IQR)] was 4 (3.25-4.93) in some cases, and that in the control group was 1.2 (0.88-1.5) (p < 0.001). Serum activin A levels in the cases group had a median (IQR) of 263.55 (227.1-279.5) ng/mL, which was substantially greater as compared to the control group 159.9 (150.7-178.7) ng/mL (p < 0.001). A significant positive association of serum activin A levels with HOMA-IR (ρ = 0.75, p < 0.001) and CIMT (ρ = 0.50, p < 0.001) was found. In LVDD grade I and II groups, the serum levels of activin A were 257.86 (219.3-271.2) ng/mL and 269 (244.19-291.5) ng/mL, respectively (p = 0.12)Conclusion: A substantial proportion of morbidity and mortality related to dysglycemic states can be attributed to cardiovascular complications. Elevated levels of activin A in prediabetes can act as an indicator of subclinical CVD leading to early diagnosis and intervention.
Asunto(s)
Aterosclerosis , Enfermedades Cardiovasculares , Resistencia a la Insulina , Insulinas , Estado Prediabético , Humanos , Grosor Intima-Media Carotídeo , Enfermedades Cardiovasculares/complicaciones , Glucosa , Factores de Riesgo , Glucemia/análisis , InsulinaRESUMEN
Tuberculosis (TB) is among the top 10 infectious diseases worldwide. It is categorized among the leading killer diseases that are the reason for the death of millions of people globally. Although a standardized treatment regimen is available, non-adherence to treatment has increased multi-drug resistance (MDR) and extensive drug-resistant (XDR) TB development. Another challenge is targeting the death of TB reservoirs in the alveoli via conventional treatment. TB Drug resistance may emerge as a futuristic restraint of TB with the scarcity of effective Anti-tubercular drugs. The paradigm change towards nano-targeted drug delivery systems is mostly due to the absence of effective therapy and increased TB infection recurrent episodes with MDR. The emerging field of nanotechnology gave an admirable opportunity to combat MDR and XDR via accurate diagnosis with effective treatment. The new strategies targeting the lung via the pulmonary route may overcome the new incidence of MDR and enhance patient compliance. Therefore, this review highlights the importance and recent research on pulmonary drug delivery with nanotechnology along with prevalence, the need for the development of nanotechnology, beneficial aspects of nanomedicine, safety concerns of nanocarriers, and clinical studies.
Asunto(s)
Tuberculosis Extensivamente Resistente a Drogas , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Antituberculosos/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Sistemas de Liberación de Medicamentos , PulmónRESUMEN
BACKGROUND: Perivascular epitheloid cell tumor (PEComas) are characterized by expression of both muscles, most often smooth muscle actin (in ~80% of cases) and melanocytic markers (mainly HMB-45 and Melan A). TFE 3-associated PEComas are new variant which are poorly defined due to their limited reports in literature. These tumors lack response to targeted mTOR inhibitor therapy due to lack of mutation in TSC gene. Hereby, we are reporting a case of TFE3 associated pelvic PEComa showing excellent response to Everolimus. CASE PRESENTATION: A 45-year-old female presented with complaint of abdominal mass and bleeding per vaginum for 4 months. She had a history of total abdominal hysterectomy 3 years back in view of abnormal uterine bleeding and exploratory laprotomy 7 months back to remove some pelvic mass. Imaging suggested of ill-defined heterogenous mass of 9.3 x 9.2 x 16 cm involving the uterus, cervix, and upper 1/3 vagina. Multiple omental and peritoneal deposits were also seen, making probable diagnosis of carcinoma endometrium. USG guided biopsy showed cores of fibrous tissue with the presence of cells in sheets with granular eosinophillic cytoplasm; IHC showed positivity for TFE-3, H Caldesmon, GATA-3, and Melan A- and HMB-45; and Ki 67 index was 35%. The basis of above diagnosis of PEComa was made and she was started on Everolimus; repeat imaging after 3 months of therapy showed complete response. CONCLUSION: We are reporting first case of malignant pelvic TFE 3 PEComa showing response to mTOR therapy. Identification of TFE 3 PEComa is important because they showed different biologic behavior then their conventional PEComa.
Asunto(s)
Biomarcadores de Tumor , Neoplasias de Células Epitelioides Perivasculares , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Biomarcadores de Tumor/genética , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Neoplasias de Células Epitelioides Perivasculares/diagnóstico por imagen , Neoplasias de Células Epitelioides Perivasculares/tratamiento farmacológico , Neoplasias de Células Epitelioides Perivasculares/cirugía , Serina-Treonina Quinasas TORRESUMEN
BACKGROUND: India encountered two waves of COVID-19 pandemic with variability in its characteristics and severity. Concerns were raised over the safety of treatment, and higher morbidity was predicted for oncological surgery. The present study was conducted to evaluate and compare the rate of morbidity and mortality in patients undergoing curative surgery for cancer before and during the COVID-19 pandemic. METHOD: The prospectively obtained clinical data of 1576 patients treated between April 2019 and May 2021 was reviewed; of these, 959 patients were operated before COVID-19 and 617 during the pandemic. The data on complications, deaths, confirmed or suspected COVID-19 cases, and COVID-19 infection among health workers (HCW) was extracted. RESULTS: A 35% fall in number of surgeries was seen during the COVID period; significant fall was seen in genital and esophageal cancer. There was no difference in postoperative complication; however, the postoperative mortality was significantly higher. A total of 71 patients had COVID-19, of which 62 were preoperative and 9 postoperative, while 30/38 healthcare workers contracted COVID-19, of which 7 had the infection twice and 3 were infected after two doses of vaccination; there was no mortality in healthcare workers. CONCLUSION: The present study demonstrates higher mortality rates after surgery in cancer patients, with no significant change in morbidity rates. A substantial proportion of HCWs were also infected though there was no mortality among this group. The results suggest higher mortality in cancer patients despite following the guidelines and protocols.
Asunto(s)
COVID-19 , Gripe Humana , Neoplasias , COVID-19/epidemiología , Personal de Salud , Humanos , Gripe Humana/epidemiología , Neoplasias/epidemiología , Neoplasias/cirugía , Pandemias , Estudios RetrospectivosRESUMEN
BACKGROUND: The debate surrounding systematic lymphadenectomy in the epithelial cancers of the ovary (EOC) was temporarily put to rest by the LION trial. However, there was a glaring disparity between the number of patients registered and the number of patients randomized suggesting inadvertent selection. A subsequent meta-analysis after this trial included all types of studies in the literature (randomized, non-randomized, case series, and, retrospective cohort), thus diluting the results. METHODS: We conducted a meta-analysis of hazard ratios of randomized controlled trials, to study the role of systematic para-aortic and pelvic lymph node dissection in the EOC. A detailed search of MEDLINE, Cochrane, and Embase databases was done to look for the published randomized controlled trials (RCT) comparing lymphadenectomy versus no lymphadenectomy in EOC. A meta-analysis of hazard ratios (HR) was performed for overall survival (OS) and progression-free survival (PFS) using fixed and random effect models. The quality of the RCTs was evaluated on Jadad's score, and the risk of bias was estimated by the Cochrane tool. RESULTS: A total of 1342 patients with EOC were included for quantitative analysis. On meta-analysis, HR for PFS was 0.9 (95% CI 0.79-1.04) favoring lymphadenectomy. HR for OS was 1 (95% CI 0.84-1.18) signifying no benefit of systematic lymphadenectomy. CONCLUSION: The results show a trend towards increased PFS which did not reach statistical significance nor translate into any meaningful benefit in OS. There is still a need for a greater number of well-conducted, suitably powered trials to convincingly answer this question.