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Background: Oral squamous cell carcinoma (OSCC) is a prevalent malignancy with significant morbidity and mortality. Identifying potential premalignant lesions is crucial for early detection and effective management. Lichen planus (LP), a chronic inflammatory disorder has been associated with an increased risk of developing OSCC. This study aimed to assess the diagnostic importance of p16 and p53 expression in identifying LP as a potential premalignant lesion for OSCC. Materials and Methods: A retrospective analysis was conducted on archived tissue samples from patients diagnosed with LP (n = 80) and OSCC (n = 60) between 2017 and 2022. Immunohistochemistry was performed to evaluate p16 and p53 protein expression levels in both LP and OSCC tissues. Clinical data, including patient demographics and lesion characteristics, were collected and correlated with the immunohistochemical findings. Results and Discussion: The results revealed a significantly higher prevalence of p16 and p53 expression in LP tissues compared to normal oral mucosa (P < 0.001). Notably, p16 expression was observed in 70% of LP cases, while p53 was detected in 55% of LP cases. Furthermore, a significant association was established between p53 expression and the presence of dysplasia within LP lesions (P = 0.003). This indicates the potential of p53 as a predictive biomarker for malignant transformation in LP. The correlation between p16 and p53 expression levels in LP and OSCC tissues suggests a potential mechanistic link between LP and OSCC development. Conclusion: This study underscores the diagnostic importance of p16 and p53 expression as potential markers for identifying LP as a premalignant lesion in the context of OSCC. The elevated prevalence of these markers in LP tissues suggests a potential role in predicting malignant transformation. The findings contribute to a deeper understanding of the molecular pathways underlying OSCC development from LP and emphasize the need for regular monitoring and early intervention in patients diagnosed with LP. Further prospective studies are warranted to validate these findings and to explore the clinical utility of p16 and p53 as biomarkers for predicting OSCC risk in LP patients.
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Non-financial reporting (NFR) has become crucial to corporate sustainability strategies as companies demonstrate their commitment to the environmental, social, and governance actions outlined in the United Nations Sustainable Development Goals (SDGs) Agenda 2030. Among the various mandatory NFR initiatives, Sustainability Reporting (SR) has emerged as a widely adopted practice by companies worldwide. A gap that the study addresses is the theoretical perspectives on SR in the context of SDG. Then we conduct a bibliometric and science mapping analysis of research trends on SR and precisely map SR research to SDGs which is also a gap in the current literature. We find an exponential increase in the number of publications and citations on SR, particularly after 2015, which coincides with increased public awareness and scrutiny of the SDGs. At the country level, Australia leads with a total of 13 SDGs, followed by the UK, Spain, and Italy, which each address 12 SDGs. Emerging economies such as Indonesia, Malaysia, and India have also increased their contributions since 2019. A keyword co-occurrence analysis identified three main clusters: stakeholder engagement, corporate governance, and accountability; sustainable development goals and climate change; and sustainability reporting and global reporting initiatives. All three clusters had highly cited publications related to SDG 8 (decent work), SDG 9 (industry innovation), and SDG 12 (responsible consumption). This highlights the interdisciplinary nature of SR and its relevance to multiple SDGs. The study is distinctive in that we utilized social network analysis to examine the SDG network based on SR publications, which also affirmed the centrality of SDG 9 and 12. We utilized the prominence percentile, which indicates the momentum of a particular topic, to identify future topics in SR that align with the SDGs. These include cause-related marketing, environmentally preferable purchasing decisions, environmental management systems, education for sustainability, and green computing.
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Mental health is a neglected health issue in developing countries. We test if mental health issues are particularly likely to occur among some of the most vulnerable children in developing countries: those that work. Despite falling in recent decades, child labor still engages 168 million children across the world. While the negative impacts of child labor on physical health are well documented, the effect of child labor on a child's psychosocial wellbeing has been neglected. We investigate this issue with a new dataset of 947 children aged 12-18 years from 750 households in 20 villages across five districts of Tamil Nadu, India. Our purpose-built survey allows for a holistic approach to the analysis of child wellbeing by accounting for levels of happiness, hope, emotional wellbeing, self-efficacy, fear and stress. We use a variety of econometric approaches, some of which utilize household-level fixed effects and account for differences between working and nonworking siblings. We document a robust, large and negative association between child labor and most measures of psychosocial wellbeing. The results are robust to a battery of exercises, including tests for selection on unobservables, randomization inference, instrumental variable techniques, and falsification exercises.
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Trabajo Infantil , Niño , Salud Infantil , Emociones , Humanos , India , Salud MentalRESUMEN
BACKGROUND: Radiation induced proctitis is frequently encountered during the radiation therapy of cervical and prostate cancers that causes pain and occasionally with bleeding and may affect the continuity of radiation therapy. AIMS AND OBJECTIVES: The purpose of the study is to look at the benefit of administration of an oral prebiotic amylase resistant starch in reducing the incidence of acute radiation proctitis, a distressing symptom in patients receiving radiation therapy for cancer of the cervix. MATERIAL AND METHODS: The study was conducted between 2011 and 2014 in 104 patients receiving radical chemo-radiotherapy for carcinoma cervix. Patients were randomized in to two arms, one receiving 30 gm of resistant starch and the other digestible starch on a daily basis throughout the course of the external radiotherapy. All patients received standard 4-field box radiation portals, 50 Gy in 25 fractions with 4 cycles of weekly concurrent Cisplatin. At completion of external beam radiotherapy, all patients underwent LDR/HDR brachytherapy. The study was double blinded and allocation was concealed from the investigators. The investigator recorded the radiotherapy related toxicity of the patients according to CTC V 3.0. The incidence and severity of grade 2-4 diarrhoea and proctitis were documented on a weekly basis and compared across the two groups and analyzed. Stool short chain fatty acid concentrations were measured at baseline at 2nd and 4th week and after 6 weeks of completion of radiotherapy in both study placebo arms and reported. The pattern of microbiota in the stool were also estimated in all patients at 4 time points. Two patients who progressed during therapy were not included in the analyses and two patients discontinued the intervention. A per protocol analyses was done. RESULTS: At analysis there were 50 patients in each arm. The severity of clinical proctitis was found to be similar in both groups of patients with 12.2 % of patients experiencing toxicity of grade 2 and above in digestible starch group versus 14.6% in the resistant starch group. Functional proctitis was similarly graded and it was found that 16.3 % patients in digestible starch group experienced toxicity against 10.2 % patients in the resistant starch group. This difference was seen at 4th week and continued in the subsequent weeks till the end of radiation. Both groups had similar reported toxicity at 6 weeks post intervention and similar incidence of grade 2 and above diarrhea. The resistant starch group was found to have 8% incidence as compared to 2% in the other group at the 5th and 6th week. The short chain fatty acid concentrations were not significantly different in the groups at any point. CONCLUSION: The study did not demonstrate a significant benefit in administering resistant starch over and above normal diet to patients receiving pelvic radiotherapy. The reasons may be attributed to concurrent use of chemotherapy and decrease in intestinal probiotics. The use of digestible starch in the control arm may have contributed to lower incidence of the toxicity endpoints as well.
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Suplementos Dietéticos , Proctitis/etiología , Proctitis/prevención & control , Traumatismos por Radiación/etiología , Traumatismos por Radiación/prevención & control , Almidón/administración & dosificación , Neoplasias del Cuello Uterino/complicaciones , Enfermedad Aguda , Administración Oral , Ácidos Grasos/análisis , Heces/química , Femenino , Humanos , Incidencia , Estadificación de Neoplasias , Radioterapia/efectos adversos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/radioterapiaRESUMEN
INTRODUCTION: Ectopic thymic tissue can arise as an asymptomatic neck mass, which may be detected on imaging studies. The aim of this study was to determine the incidence of ectopic thymic tissue in paediatric FNAs and to the correlate clinical, radiological and cytomorphological findings. METHODS: FNAs in children with neck and mediastinal lesions performed between January 2012 and July 2016 were reviewed for cases of ectopic thymus. These were then evaluated and correlated with the cytology findings. RESULTS: Of 739 FNAs, 13 (1.8%) cases from 11 patients showed ectopic thymic tissue. The targeted lesions were in the thyroid (n = 7), submandibular region (n = 1), superior mediastinum (n = 1) and paratracheal region (n = 1). The most common indication was for microcalcifications concerning for papillary thyroid carcinoma on ultrasound (n = 6). Imaging findings included fusiform lesions with linear and punctuate bright echoes. The cytology evaluation showed small lymphocytes with discohesive epithelioid cells in most cases, and proteinaceous fluid in the cystic case. There were rare macrophages and Hassall's corpuscles. Flow cytometry and/or immunostains were performed in all cases, supporting thymic origin. CONCLUSION: Ectopic thymic tissue is rarely present as a neck mass or thyroid nodule on FNA biopsy. The ultrasound imaging findings reveal a well-defined fusiform lesion with punctate bright echoes that could be misinterpreted as papillary thyroid carcinoma. The aspirates show a small lymphoid population, immunophenotypically compatible with thymic T-cells, in addition to scattered epithelial cells. Therefore, knowledge of the typical ultrasonographic and cytopathological features can help make a definitive diagnosis and avoid more invasive procedures in paediatric patients.
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Timo/patología , Glándula Tiroides/patología , Adolescente , Biopsia con Aguja Fina/métodos , Niño , Preescolar , Células Epiteliales/patología , Femenino , Humanos , Lactante , Masculino , Mediastino/patología , Cáncer Papilar Tiroideo/patología , Nódulo Tiroideo/patología , Ultrasonografía/métodosRESUMEN
Number sense, a spontaneous ability to process approximate numbers, has been documented in human adults, infants and newborns, and many other animals. Species as distant as monkeys and crows exhibit very similar neurons tuned to specific numerosities. How number sense can emerge in the absence of learning or fine tuning is currently unknown. We introduce a random-matrix theory of self-organized neural states where numbers are coded by vectors of activation across multiple units, and where the vector codes for successive integers are obtained through multiplication by a fixed but random matrix. This cortical implementation of the 'von Mises' algorithm explains many otherwise disconnected observations ranging from neural tuning curves in monkeys to looking times in neonates and cortical numerotopy in adults. The theory clarifies the origin of Weber-Fechner's Law and yields a novel and empirically validated prediction of multi-peak number neurons. Random matrices constitute a novel mechanism for the emergence of brain states coding for quantity.This article is part of a discussion meeting issue 'The origins of numerical abilities'.
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Cognición , Discriminación en Psicología , Haplorrinos/fisiología , Modelos Neurológicos , Adolescente , Animales , Niño , Preescolar , Haplorrinos/psicología , Humanos , Lactante , PsicofísicaRESUMEN
Lung cancer is the leading cause of cancer deaths in the U.S. with survival dramatically depending on stage at diagnosis. We had earlier reported that nanocytology of buccal cells can accurately risk-stratify smokers for the presence of early and late-stage lung cancer. To translate the technique into clinical practice, standardization of operating procedures is necessary to consistently yield precise and repeatable results. Here, we develop and validate simple, robust, and easily implementable procedures for specimen collection, processing, etc. in addition to a commercially-viable instrument prototype. Results of this work enable translation of the technology from academic lab to physicians' office.
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Vascular integrity is primarily determined by endothelial cell (EC) cytoskeletal structure that is differentially regulated by various stimuli. In this study, atomic force microscopy (AFM) was used to characterize structural and mechanical properties in the cytoskeleton of cultured human pulmonary artery EC (HPAEC) and human lung microvascular EC (HLMVEC) by determining elastic properties (Young's modulus) in response to endogenous barrier protective agents sphingosine 1-phosphate (S1P) and hepatocyte growth factor (HGF), or the barrier disruptive molecule thrombin. Initial studies in unstimulated cells indicate higher baseline peripheral elastic modulus values in HPAEC (mean 2.9 KPa) than in HLMVEC (1.8 KPa). After 30 min of stimulation, S1P induced the highest Young's modulus increase (6.1 KPa) compared to the other barrier enhancing stimuli, HGF (5.8 KPa) and the pharmaceutical agent and S1P analog FTY720 (4.1 KPa). In contrast, the barrier disruptive agent thrombin decreased values from 2.5 KPa to 0.7 KPa depending on the cell type and treatment time. AFM topographical imaging supports these quantitative biophysical data regarding differential peripheral elastic properties in EC. Overall, these AFM studies provide novel insights into the biomechanical properties of human lung EC that regulate vascular barrier function and have potential applicability to pathophysiologic vascular leak syndromes such as acute lung injury.
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Módulo de Elasticidad , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Pulmón/irrigación sanguínea , Fenómenos Biomecánicos , Línea Celular , Citoesqueleto/metabolismo , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Lisofosfolípidos/metabolismo , Microscopía de Fuerza Atómica , Arteria Pulmonar/citología , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Trombina/metabolismoRESUMEN
OBJECTIVE: To evaluate the obliteration rate and clinical outcome following linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) for intracranial arteriovenous malformation (AVM) in pediatric patients (age ≤18 years). METHODS: Factors associated with the obliteration rate and neurologic complications were studied retrospectively in pediatric patients who underwent LINAC-based SRS for AVM between June 1995 and May 2014. RESULTS: The study cohort comprised 36 males and 33 females, with a median age at the time of SRS of 14 years (range, 7-18 years). The mean AVM volume was 8.5 ± 8.7 cc (range, 0.6-41.8 cc). The median marginal dose of radiation delivered was 15 Gy (range, 9-20 Gy). Magnetic resonance imaging (MRI) demonstrated complete obliteration of the AVM in 44 of the 69 patients (63.8%), at a mean follow up of 27.5 months (range, 12-90 months). On subgroup analysis, 41 of the 53 AVMs of ≤14 cc in volume (77.3%) were obliterated. AVMs with a modified AVM radiosurgery score <1 had significantly shorter obliteration times from the time of SRS (P = .006). On multivariate analysis, the mean marginal dose of radiation delivered to the AVM was the sole significant predictor of obliteration (odds ratio, 1.6; 95% confidence interval, 1 to 2.4). CONCLUSIONS: A modest median marginal dose of 15 Gy (16 Gy in the obliterated AVM group vs. 12 Gy in the nonobliterated group) resulted in an obliteration rate of 66.7% after LINAC-based SRS for intracranial AVM, with low rate.
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Malformaciones Arteriovenosas Intracraneales/radioterapia , Radiocirugia/métodos , Dosificación Radioterapéutica , Adolescente , Angiografía de Substracción Digital , Angiografía Cerebral , Niño , Estudios de Cohortes , Femenino , Humanos , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Aceleradores de Partículas , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Due to their wide range of applications, porous polymers obtained from high internal phase emulsions have been widely studied using scanning electron microscopy. However, due to their lack of electrical conductivity, quantitative information of wall thicknesses and surface roughness, which are of particular interest to tissue engineering, has not been obtained. Here, Helium Ion Microscopy is used to examine uncoated polymer foams and some very strong but unexpected contrast is observed, the origin of which is established here. Based on this analysis, a method for the measurement of wall thickness variations and wall roughness measurements has been developed, based on the modeling of Helium ion transmission. The results presented here indicate that within the walls of the void structure there exist small features with height variations of ~30 nm and wall thickness variations from ~100 nm to larger 340 nm in regions surrounding interconnecting windows within the structure. The suggested imaging method is applicable to other porous carbon based structures with wall thicknesses in the range of 40-340 nm.
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Helio/química , Iones/química , Microscopía/métodos , Polímeros/química , Propiedades de SuperficieRESUMEN
An urinary tract infection (UTI) with Brevibacillus agri, an aerobic soil bacteria is discussed. The preliminary urine analysis tested negative for UTI, while the patient was diagnosed with focal pyelonephritis. The urine sample was analyzed for the presence of possible micro-organisms. The isolated micro-organism was phenotypically characterized and compared with a standard B. agri strain and an established uropathogen Eschericia coli, CFT073. Each experimental mouse was trans-urethrally infected using 2.5 × 10(8) c.f.u. for the generation of an UTI model. The kidney tissues were stored in buffered 10 % formaldehyde solution for histopathological analysis. The destruction of the glomerular and tubular morphology with prominent hemagglutination in the tubular region in the mouse kidneys were confirmed by light microscopic examination of the H&E stained sections. Hence, the identity of pathogen was confirmed using the 16S rRNA gene sequencing. The phylogenetic tree constructed using the 16S rRNA sequence obtained from the isolated microbial strain showed 99 % similarity with the strain, B. agri AB112716. Finally this study concludes based on the phenotypic characteristics, production of lipopolysaccharide, the ability to aggregate in the presence of ammonium sulphate, agglutinate erythrocytes in the presence of mannose, and the potential to resist the interactions of serum, the possibility that the soil microbe could have undergone genotypic modification to cause UTI. However, further detailed and in-depth genetic analysis are required to point out exactly how the soil bacterium has adapted itself to cause infection in a human subject.
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Brevibacillus/patogenicidad , Infecciones por Bacterias Grampositivas/microbiología , Infecciones Urinarias/microbiología , Animales , Brevibacillus/clasificación , Brevibacillus/genética , Brevibacillus/aislamiento & purificación , Eritrocitos/microbiología , Hemaglutinación , Humanos , Masculino , Ratones , Persona de Mediana Edad , Datos de Secuencia Molecular , Filogenia , Microbiología del Suelo , VirulenciaRESUMEN
Teleradiology allows transmission of medical images for clinical data interpretation to provide improved e-health care access, delivery, and standards. The remote transmission raises various ethical and legal issues like image retention, fraud, privacy, malpractice liability, etc. A joint FED watermarking system means a joint fingerprint/encryption/dual watermarking system is proposed for addressing these issues. The system combines a region based substitution dual watermarking algorithm using spatial fusion, stream cipher algorithm using symmetric key, and fingerprint verification algorithm using invariants. This paper aims to give access to the outcomes of medical images with confidentiality, availability, integrity, and its origin. The watermarking, encryption, and fingerprint enrollment are conducted jointly in protection stage such that the extraction, decryption, and verification can be applied independently. The dual watermarking system, introducing two different embedding schemes, one used for patient data and other for fingerprint features, reduces the difficulty in maintenance of multiple documents like authentication data, personnel and diagnosis data, and medical images. The spatial fusion algorithm, which determines the region of embedding using threshold from the image to embed the encrypted patient data, follows the exact rules of fusion resulting in better quality than other fusion techniques. The four step stream cipher algorithm using symmetric key for encrypting the patient data with fingerprint verification system using algebraic invariants improves the robustness of the medical information. The experiment result of proposed scheme is evaluated for security and quality analysis in DICOM medical images resulted well in terms of attacks, quality index, and imperceptibility.
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Algoritmos , Seguridad Computacional , Telerradiología/métodos , Confidencialidad , Humanos , Radiografía TorácicaRESUMEN
The present study was aimed to investigate the chemopreventive potential of troxerutin on 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis by evaluating the antioxidant and lipid peroxidation (LPO) status. Rats were randomly divided into six groups. Group I rats served as control. Group II rats received troxerutin (50 mg/kgb.w., p.o.) for 16 weeks. Groups III-VI rats received subcutaneous injections of DMH (20 mg/kgb.w., s.c.) once a week, for the first 4 weeks. In addition to DMH, groups IV-VI rats received troxerutin at the doses of 12.5, 25 and 50 mg/kgb.w., respectively. In DMH treated rats, our results showed decreased activities of antioxidants and increased levels of LPO in the liver. Moreover, LPO and antioxidants in the colon were found to be significantly diminished in DMH the treated rats. Furthermore, enhanced activity of colonic vitamin C and vitamin E levels were observed in DMH alone treated rats (group III), which was significantly reversed on troxerutin supplementation. Troxerutin at the dose of 25 mg/kgb.w. had shown profound beneficial effects by exhibiting near normal biochemical profile and well-preserved colon histology as compared to the other two tested doses (12.5 and 50 mg/kgb.w.). These findings suggest that troxerutin could serve as a novel agent for colon cancer chemoprevention.
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Antineoplásicos/farmacología , Neoplasias del Colon/metabolismo , Hidroxietilrutósido/análogos & derivados , 1,2-Dimetilhidrazina , Administración Oral , Animales , Ácido Ascórbico/metabolismo , Carcinógenos , Catalasa/metabolismo , Colon/efectos de los fármacos , Colon/metabolismo , Colon/patología , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/patología , Glutatión/metabolismo , Hidroxietilrutósido/farmacología , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Vitamina E/metabolismoRESUMEN
OBJECTIVES: The present study has aimed to evaluate chemopreventive potential of d-carvone on oxidative stress markers, biotransforming enzymes, incidence of colonic polyps and aberrant crypt foci (ACF) in 1,2-dimethylhydrazine (DMH)-induced experimental colon carcinogenesis. MATERIALS AND METHODS: Rats were randomly divided into six groups, with group I serving as control. Group II animals received d-carvone every day orally (20 mg/kg body weight) for 16 weeks; groups III-VI received subcutaneous injections of DMH (20 mg/kg body weight) once a week, for the first 4 weeks. In addition, groups IV-VI received different doses of d-carvone (5, 10 and 20 mg/kg body weight everyday orally) along with DMH injections. RESULTS: Our results revealed that supplementation with d-carvone significantly reduced incidence of polyps/ACF and ACF multiplicity in DMH-exposed rats compared to DMH-alone-exposed rats. Moreover, our results showed reduced activities of liver and circulatory antioxidants and increased levels of lipid peroxidation by products in DMH-exposed animals, which were significantly reversed on supplementation with d-carvone. In addition, colonic antioxidants and lipid peroxidation were significantly diminished in DMH-exposed rats, which were significantly elevated on supplementation with d-carvone. Furthermore, we also determined activities of biotransforming enzymes, which were found to be altered in DMH-exposed rats, but reversed on d-carvone supplementation. All these observations of changes were supported by histochemical findings. CONCLUSION: Overall, results obtained from this study suggest that d-carvone at 10 mg/kg body weight provided optimum protection and could be used as an effective chemopreventive agent against colon carcinogenesis induced by DMH.
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Carcinogénesis/efectos de los fármacos , Colon/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/enzimología , Monoterpenos/farmacología , Estrés Oxidativo/efectos de los fármacos , Lesiones Precancerosas/tratamiento farmacológico , 1,2-Dimetilhidrazina/efectos adversos , Focos de Criptas Aberrantes/tratamiento farmacológico , Focos de Criptas Aberrantes/enzimología , Focos de Criptas Aberrantes/metabolismo , Focos de Criptas Aberrantes/patología , Animales , Peso Corporal/efectos de los fármacos , Carcinogénesis/metabolismo , Carcinogénesis/patología , Quimioprevención/métodos , Colon/enzimología , Colon/metabolismo , Colon/patología , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Monoterpenos Ciclohexánicos , Glutatión/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Fase I de la Desintoxicación Metabólica/fisiología , Modelos Teóricos , Lesiones Precancerosas/enzimología , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/patología , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
ß-Sitosterol has been shown to have antidiabetic and antioxidant effects in animal models. The objective of the study is to investigate the effects of ß-sitosterol on insulin sensitivity, oxidative and nitrosative stress and lipid abnormalities in liver of high fat-fed rat model of insulin resistance (IR) and to assess whether nitric oxide (NO) is involved in its action. Adult male albino Wistar rats of body weight 150-180g were fed either control diet (CON) or high fat diet (HFD). Each dietary group was divided into two and treated or untreated with ß-sitosterol (10mg/kgb.w.(-1)day(-1)) for 4weeks. Inhibition of total nitric oxide synthase (NOS) by administration of nitro-l-arginine methyl ester (L-NAME) and inducible NOS (iNOS) by aminoguanidine (AG) in HFD and HFD+ ß-sitosterol groups were accomplished to identify the role of NO. After 28days, assays were performed in plasma and liver. HFD-fed rats showed hyperglycemia, hyperinsulinemia, IR, oxidative damage, nitrosative stress, lipid accumulation and elevated serum aminotransferases. Increased expression of iNOS and decreased expression of endothelial NOS (eNOS) were observed in them. Hepatic fat accumulation was further confirmed by histology. The biochemical and histological abnormalities associated with HFD feeding were significantly reduced by ß-sitosterol administration. Administration of L-NAME to HFD-fed rats caused decrease in insulin sensitivity and increase in oxidative stress. Co-administration of L-NAME for the last seven days to ß-sitosterol-treated HFD rats abolished the glucose lowering effect of ß-sitosterol, but the ability to decrease oxidative stress remained unaltered. On the other hand, administration of AG resulted in improved glucose homeostasis and antioxidant levels but decreased oxidative stress and enhanced antioxidant potential in both HFD and HFD+ ß-sitosterol treated groups. Thus, ß-sitosterol promotes insulin sensitivity in rats fed HFD possibly by improving NO levels. With additional studies, ß-sitosterol might be used as a functional drug or as an adjuvant in the management of IR and associated fatty liver disease.
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Dieta Alta en Grasa , Resistencia a la Insulina , Insulina/metabolismo , Óxido Nítrico/farmacología , Sitoesteroles/farmacología , Análisis de Varianza , Animales , Glucemia/efectos de los fármacos , Peso Corporal , Guanidinas/farmacología , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/química , Hígado/efectos de los fármacos , Hígado/patología , Masculino , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Nitritos/metabolismo , Tamaño de los Órganos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
BACKGROUND: The majority of women in rural India have poor or no access to cervical cancer screening services, although one-quarter of all cervical cancers in the world occur there. Several large trials have proven the efficacy of low-tech cervical cancer screening methods in the Indian context but none have documented the necessary components and processes of implementing this evidence in a low-resource setting. METHODS: This paper discusses a feasible model of implementation of cervical cancer screening programme in low-resource settings developed through a pilot research project carried out in rural Tamilnadu, India. The programme used visual inspection of cervix after acetic acid application (VIA) as a screening tool, nurses in the primary care centres as the primary screeners and peer educators within Self-Help Women groups to raise community awareness. RESULTS: The uptake of screening was initially low despite the access to a screening programme. However, the programme witnessed an incremental increase in the number of women accessing screening with increasing community awareness. CONCLUSIONS: The investigators recommend 4 key components to programme implementation in low-resource setting: 1) Evidence-based, cost-effective test and treatment available within the reach of the community; 2) Appropriate referral pathways; 3) Skilled health workers and necessary equipment; and 4) Optimisation of health literacy, beliefs, attitudes of the community.
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Detección Precoz del Cáncer , Práctica Clínica Basada en la Evidencia , Recursos en Salud , Pautas de la Práctica en Medicina , Investigación Biomédica Traslacional , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Femenino , Conductas Relacionadas con la Salud , Humanos , India/epidemiología , Persona de Mediana Edad , Proyectos Piloto , Pronóstico , Población Rural , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & controlRESUMEN
G-protein-coupled receptor 40 (GPR40), highly expressed in pancreatic ß-cells, mediates free fatty acid (FFA)-induced insulin secretion. This phase I, double-blind, randomized study investigated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of a novel, glucose-lowering GPR40 agonist, TAK-875 (q.d., orally × 14 days), in type 2 diabetics (placebo, n = 14; at 25, 50, 100, 200, or 400 mg, n = 45). Approximately dose-proportional increases in AUC(0-24) and C(max) occurred. TAK-875 showed good tolerability with no dose-limiting side effects. Two subjects (on TAK-875) had mild hypoglycemia, probably related to prolonged fasting after oral glucose tolerance tests (OGTTs). TAK-875 showed reductions from baseline in fasting (2 to -93 mg/dl) and post-OGTT glucose (26 to -172 mg/dl), with an apparent dose-dependent increase in post-OGTT C-peptide over 14 days. Consistent with preclinical data, TAK-875 apparently acts as a glucose-dependent insulinotropic agent with low hypoglycemic risk. Its PK is suitable for once-daily oral administration.
Asunto(s)
Benzofuranos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptores Acoplados a Proteínas G/metabolismo , Sulfonas , Administración Oral , Benzofuranos/administración & dosificación , Benzofuranos/farmacología , Disponibilidad Biológica , Glucemia/metabolismo , Péptido C/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Ácidos Grasos no Esterificados/metabolismo , Prueba de Tolerancia a la Glucosa/efectos adversos , Prueba de Tolerancia a la Glucosa/métodos , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacocinética , Insulina/metabolismo , Insulina/farmacocinética , Secreción de Insulina , Células Secretoras de Insulina/metabolismo , Sulfonas/administración & dosificación , Sulfonas/farmacología , Resultado del TratamientoRESUMEN
We assessed the effect of extending the range of cardiovascular (CV) end points to include hospitalization for unstable angina and hospitalization for coronary revascularization (Extended Major Adverse Cardiac Event criteria (MACE)) in addition to the standard ones, namely, CV-related death, nonfatal stroke, and nonfatal myocardial infarction (Core MACE). The trials selected for the analysis had a duration/follow-up period of ≥1 year and involved more than 1,000 subjects. Annual event rates (AERs) for Core MACE in patients with type 2 diabetes were estimated, and the duration of an event-driven CV outcome trial necessary to exclude ≥80% risk increase was modeled. All the studies revealed hazard ratios ≤1.0 for Core MACE end points whereas in 21% of the studies, the hazard ratio for hospitalization for unstable angina or coronary revascularization (Extended MACE) was >1 and was therefore discordant with Core MACE. The AERs for Core MACE ranged from 0.5% (recent clinical programs) to 6% (epidemiological studies); these low rates observed in recent programs would have the effect of increasing the duration required for a CV outcome trial. The addition of Extended MACE end points to the primary composite outcome in antidiabetic clinical trials is unlikely to obscure CV-related risk and may improve the feasibility of CV outcome trials.
Asunto(s)
Enfermedades Cardiovasculares/inducido químicamente , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Determinación de Punto Final/métodos , Hipoglucemiantes/efectos adversos , Biomarcadores/análisis , Ensayos Clínicos Fase III como Asunto/métodos , Método Doble Ciego , Estudios de Seguimiento , Hospitalización , Humanos , Hipoglucemiantes/uso terapéutico , Evaluación de Resultado en la Atención de Salud , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Factores de RiesgoRESUMEN
Metastatic squamous cell carcinoma in the pyloroduodenal region is uncommon. Cases have been reported where carcinoma of the lung has presented with metastasis to the duodenum. We present here the case of a 57-year-old lady who was found to have a metastasis in pyloroduodenal region while on treatment for carcinoma cervix. The patient developed features of intestinal obstruction and endoscopy showed a growth extending from pyloric antrum to first part of duodenum up to the junction of first and second part. A biopsy was taken from the duodenal area and it was reported as metastatic squamous cell carcinoma. This is one of the few reported cases of hematogenous visceral metastasis from carcinoma cervix. Since the disease was found to be advanced and her performance status was poor, she was provided best supportive care.