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2.
Front Hum Neurosci ; 15: 734179, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34744661

RESUMEN

One important aspect of human cognition involves the learning of structured information encountered in our environment, a phenomenon known as statistical learning. A growing body of research suggests that learning to read print is partially guided by learning the statistical contingencies existing between the letters within a word, and also between the letters and sounds to which the letters refer. Research also suggests that impairments to statistical learning ability may at least partially explain the difficulties experienced by individuals diagnosed with dyslexia. However, the findings regarding impaired learning are not consistent, perhaps partly due to the varied use of methodologies across studies - such as differences in the learning paradigms, stimuli used, and the way that learning is assessed - as well as differences in participant samples such as age and extent of the learning disorder. In this review, we attempt to examine the purported link between statistical learning and dyslexia by assessing a set of the most recent and relevant studies in both adults and children. Based on this review, we conclude that although there is some evidence for a statistical learning impairment in adults with dyslexia, the evidence for an impairment in children is much weaker. We discuss several suggestive trends that emerge from our examination of the research, such as issues related to task heterogeneity, possible age effects, the role of publication bias, and other suggestions for future research such as the use of neural measures and a need to better understand how statistical learning changes across typical development. We conclude that no current theoretical framework of dyslexia fully captures the extant research findings on statistical learning.

3.
Eur J Cancer ; 157: 198-213, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34536944

RESUMEN

The first (2017) and sixth (2021) multistakeholder Paediatric Strategy Forums focused on anaplastic lymphoma kinase (ALK) inhibition in paediatric malignancies. ALK is an important oncogene and target in several paediatric tumours (anaplastic large cell lymphoma [ALCL], inflammatory myofibroblastic tumour [IMT], neuroblastoma and hemispheric gliomas in infants and young children) with unmet therapeutic needs. ALK tyrosine kinase inhibitors have been demonstrated to be active both in ALK fusion-kinase positive ALCL and IMT. ALK alterations differ, with fusions occurring in ALCL, IMT and gliomas, and activating mutations and amplification in neuroblastoma. While there are many ALK inhibitors in development, the number of children diagnosed with ALK driven malignancies is very small. The objectives of this ALK Forum were to (i) Describe current knowledge of ALK biology in childhood cancers; (ii) Provide an overview of the development of ALK inhibitors for children; (iii) Identify the unmet needs taking into account planned or current ongoing trials; (iv) Conclude how second/third-generation inhibitors could be evaluated and prioritised; (v) Identify lessons learnt from the experience with ALK inhibitors to accelerate the paediatric development of other anti-cancer targeted agents in the new regulatory environments. There has been progress over the last four years, with more trials of ALK inhibitors opened in paediatrics and more regulatory submissions. In January 2021, the US Food and Drug Administration approved crizotinib for the treatment of paediatric and young adult patients with relapsed or refractory ALCL and there are paediatric investigation plans (PIPs) for brigatinib and for crizotinib in ALCL and IMT. In ALCL, the current goal is to investigate the inclusion of ALK inhibitors in front-line therapy with the aim of decreasing toxicity with higher/similar efficacy compared to present first-line therapies. For IMT, the focus is to develop a joint prospective trial with one product in children, adolescents and adults, taking advantage of the common biology across the age spectrum. As approximately 50% of IMTs are ALK-positive, molecular analysis is required to identify patients to be treated with an ALK inhibitor. For neuroblastoma, crizotinib has not shown robust anti-tumour activity. A focused and sequential development of ALK inhibitors with very good central nervous system (CNS) penetration in CNS tumours with ALK fusions should be undertaken. The Forum reinforced the strong need for global academic collaboration, very early involvement of regulators with studies seeking possible registration and early academia-multicompany engagement. Innovations in study design and conduct and the use of 'real-world data' supporting development in these rare sub-groups of patients for whom randomised clinical trials are not feasible are important initiatives. A focused and sequenced development strategy, where one product is evaluated first with other products being assessed sequentially, is applicable for ALK inhibitors and other medicinal products in children.

4.
Cureus ; 13(7): e16681, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34466318

RESUMEN

The Africanized honey bee commonly referred to as the "killer bee," is a hybrid of the East African lowland honey bee with various European honey bees. These bees tend to be more hostile as compared to other bee species. Their stings may have devastating clinical sequelae, including cardiovascular, cerebrovascular events, and fatalities. We report the first-in-Caribbean case of a middle-aged woman who experienced stress-related, Takotsubo cardiomyopathy (also known as stress-related cardiomyopathy [SRC]) after being afflicted with innumerable Africanized honey bee stings. Key clinical message: The clinician should be cognizant of Takotsubo's cardiomyopathy as a potential sequela of Hymenoptera envenomation and anaphylaxis.

5.
Artículo en Inglés | MEDLINE | ID: mdl-34523175

RESUMEN

AIM: Paediatric head injuries (PHI) are the most common cause of trauma-related emergency department (ED) presentations. This study sought to report the incidence of PHI in Australia, examine the temporal trends from 2014 to 2018 and estimate the patient and population-level acute care costs. METHODS: Taking a public-sector health-care perspective, we applied direct and indirect hospital costs for PHI-related ED visits and acute admissions. All costs were inflated to 2018 Australian dollars ($). The patient-level analysis was performed with data from 17 841 children <18 years old enrolled in the prospective Australasian Paediatric Head Injury Study. Mechanisms of injury were characterised by the total and average acute care costs. The population-level data of PHI-related ED presentations were obtained from the Independent Hospital Pricing Authority. Age-standardised incidence rates (IR) and incidence rate ratios (IRR) were calculated, and negative binomial regression examined the temporal trend. RESULTS: The age-standardised IR for PHI was 2734 per 100 000 population in 2018, with a significant increase over 5 years (IRR 1.13, 95% confidence interval (CI) 1.12-1.14; P < 0.001) and acute care costs of $154 million. Falls occurred in 70% of the study cohort, with average costs per episode of $666 (95% CI: $627-$706), accounting for 47% of acute care costs. Transportation-related injuries occurred in 4.1% of the study cohort, with average costs per episode of $8555 (95% CI: $6193-$10 917), accounting for 35% of acute care costs. CONCLUSION: PHI have increased significantly in Australia and are associated with substantial acute care costs. Population-based efforts are required for road safety and injury prevention.

6.
Acad Emerg Med ; 28(10): 1124-1133, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34236116

RESUMEN

BACKGROUND: The Pediatric Emergency Care Applied Research Network (PECARN) head trauma clinical decision rules informed the development of algorithms that risk stratify the management of children based on their risk of clinically important traumatic brain injury (ciTBI). We aimed to determine the rate of ciTBI for each PECARN algorithm risk group in an external cohort of patients and that of ciTBI associated with different combinations of high- or intermediate-risk predictors. METHODS: This study was a secondary analysis of a large multicenter prospective data set, including patients with Glasgow Coma Scale scores of 14 or 15 conducted in Australia and New Zealand. We calculated ciTBI rates with 95% confidence intervals (CIs) for each PECARN risk category and combinations of related predictor variables. RESULTS: Of the 15,163 included children, 4,011 (25.5%) were aged <2 years. The frequency of ciTBI was 8.5% (95% CI = 6.0%-11.6%), 0.2% (95% CI = 0.0%-0.6%), and 0.0% (95% CI = 0.0%-0.2%) in the high-, intermediate-, and very-low-risk groups, respectively, for children <2 years and 5.7% (95% CI = 4.4%-7.2%), 0.7% (95% CI = 0.5%-1.0%), and 0.0% (95% CI = 0.0%-0.1%) in older children. The isolated high-risk predictor with the highest risk of ciTBI was "signs of palpable skull fracture" for younger children (11.4%, 95% CI = 5.3%-20.5%) and "signs of basilar skull fracture" in children ≥2 years (11.1%, 95% CI = 3.7%-24.1%). For older children in the intermediate-risk category, the presence of all four predictors had the highest risk of ciTBI (25.0%, 95% CI = 0.6%-80.6%) followed by the combination of "severe mechanism of injury" and "severe headache" (7.7%, 95% CI = 0.2%-36.0%). The very few children <2 years at intermediate risk with ciTBI precluded further analysis. CONCLUSIONS: The risk estimates of ciTBI for each of the PECARN algorithms risk group were consistent with the original PECARN study. The risk estimates of ciTBI within the high- and intermediate-risk predictors will help further refine clinical judgment and decision making on neuroimaging.


Asunto(s)
Traumatismos Craneocerebrales , Servicios Médicos de Urgencia , Adolescente , Algoritmos , Niño , Estudios de Cohortes , Traumatismos Craneocerebrales/epidemiología , Técnicas de Apoyo para la Decisión , Servicio de Urgencia en Hospital , Humanos , Lactante , Estudios Prospectivos , Medición de Riesgo , Tomografía Computarizada por Rayos X
7.
Front Neurol ; 12: 639179, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34108926

RESUMEN

Introduction: Cognitive impairment after concussion has been widely reported, but there is no reliable imaging biomarker that predicts the severity of cognitive decline post-concussion. This study tests the hypothesis that patients with a history of concussion and persistent cognitive impairment have fractional anisotropy (FA) and mean diffusivity (MD) values from diffusion tensor imaging (DTI) that are specifically associated with poor performance on the Montreal Cognitive Assessment (MoCA). Methods: Fifty-three subjects (19 females) with concussions and persistent cognitive symptoms had MR imaging and the MoCA. Imaging was analyzed by atlas-based, whole-brain DTI segmentation and FLAIR lesion segmentation. Then, we conducted a random forest-based recursive feature elimination (RFE) with 10-fold cross-validation on the entire dataset, and with partial correlation adjustment for age and lesion load. Results: RFE showed that 11 DTI variables were found to be important predictors of MoCA scores. Partial correlation analyses, corrected for age and lesion load, showed significant correlations between MoCA scores and right fronto-temporal regions: inferior temporal gyrus MD (r = -0.62, p = 0.00001), middle temporal gyrus MD (r = -0.54, p = 0.0001), angular gyrus MD (r = -0.48, p = 0.0008), and inferior frontal gyrus FA (r = 0.44, p = 0.002). Discussion: This is the first study to demonstrate a correlation between MoCA scores and DTI variables in patients with a history of concussion and persistent cognitive impairment. This kind of research will significantly increase our understanding of why certain persons have persistent cognitive changes after concussion which, in turn, may allow us to predict persistent impairment after concussion and suggest new interventions.

8.
J Investig Med High Impact Case Rep ; 9: 23247096211024027, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34121486

RESUMEN

Ventricular noncompaction is a rare, heterogeneous cardiomyopathy characterized by marked trabeculations and deep intertrabecular spaces with clinical sequelae of heart failure, arrhythmias, and cardioembolic events. In this article, we describe a patient with isolated right ventricular noncompaction who presented with submassive pulmonary embolism, which was managed with long-term direct oral anticoagulation.


Asunto(s)
Cardiomiopatías , Insuficiencia Cardíaca , Embolia Pulmonar , Cardiomiopatías/complicaciones , Cardiomiopatías/diagnóstico por imagen , Insuficiencia Cardíaca/etiología , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Embolia Pulmonar/complicaciones , Embolia Pulmonar/diagnóstico por imagen
9.
Curr Opin Infect Dis ; 34(3): 228-237, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33741796

RESUMEN

PURPOSE OF REVIEW: Early diagnosis of central nervous system (CNS) infections is crucial given high morbidity and mortality. Neuroimaging in CNS infections is widely used to aid in the diagnosis, treatment and to assess the response to antibiotic and neurosurgical interventions. RECENT FINDINGS: The Infectious Diseases Society of America (IDSA) guidelines have clear recommendations for obtaining a computerized tomography of the head (CTH) prior to lumbar puncture (LP) in suspected meningitis. In the absence of indications for imaging or in aseptic meningitis, cranial imaging is of low utility. In contrast, cranial imaging is of utmost importance in the setting of encephalitis, bacterial meningitis, ventriculitis, bacterial brain abscess, subdural empyema, epidural abscess, neurobrucellosis, neurocysticercosis, and CNS tuberculosis that can aid clinicians with the differential diagnosis, source of infection (e.g., otitis, sinusitis), assessing complications of meningitis (e.g., hydrocephalus, venous sinus thrombosis, strokes), need for neurosurgical interventions and to monitor for the response of therapy. Novel imaging techniques such as fast imaging employing steady-state acquisition (FIESTA), susceptibility-weighted imaging (SWI), and chemical exchange saturation transfer (CEST) contrast are briefly discussed. SUMMARY: Though the radiological findings in CNS infections are vast, certain patterns along with clinical clues from history and examination often pave the way to early diagnosis. This review reiterates the importance of obtaining cranial imaging when necessary, and the various radiological presentations of commonly encountered CNS infections.


Asunto(s)
Infecciones del Sistema Nervioso Central/diagnóstico por imagen , Infecciones Bacterianas del Sistema Nervioso Central/diagnóstico por imagen , Infecciones Bacterianas del Sistema Nervioso Central/microbiología , Infecciones Bacterianas del Sistema Nervioso Central/patología , Infecciones Fúngicas del Sistema Nervioso Central/diagnóstico por imagen , Infecciones Fúngicas del Sistema Nervioso Central/microbiología , Infecciones Fúngicas del Sistema Nervioso Central/patología , Infecciones del Sistema Nervioso Central/microbiología , Infecciones del Sistema Nervioso Central/parasitología , Infecciones del Sistema Nervioso Central/patología , Humanos , Neurocisticercosis/diagnóstico por imagen , Neurocisticercosis/parasitología , Neurocisticercosis/patología
10.
Mini Rev Med Chem ; 21(14): 1965-1997, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33390134

RESUMEN

INTRODUCTION: Herb, Zanthoxylum armatum DC., commonly called Indian prickly ash, and Nepal pepper (family Rutaceae), is widely utilized in the traditional medicinal system. OBJECTIVE: The current review provides requisite data for collecting descriptive information on the organoleptic, microscopical, ethnobotanical use, and phytochemicals and pharmacological properties of Z. armatum; therefore, it may help in forming a bridge between research gaps and the upcoming future findings for most of the researches. MATERIALS AND METHODS: The systematic literature survey was conducted using the PRISMA methodology. The collective information was gathered from books, renowned journals, and electronic databases including Science Direct, Web of Science, Scopus and PubMed from 1966 to 2020. RESULTS: Most of the bioactive metabolites are isolated and characterized till date, such as monoterpenes in essential oil and lignan components are reported to be present in the herbs. Several in vitro and in vivo pharmacological bioassays revealed the potential of Z. armatum having as possessing antimicrobial, antifungal, antibacterial, and hepatoprotective effects and so on. CONCLUSION: Therefore, the current review summarizes the organoleptic, microscopy, phytochemistry and biological activities of Z. armatum, providing more emphasis on in vitro as well as in-vivo studies along with clinical research, helpful in exploring the potential efficacy of the plant.


Asunto(s)
Fitoquímicos/química , Zanthoxylum/química , Antiinfecciosos/química , Antiinfecciosos/aislamiento & purificación , Antiinfecciosos/farmacología , Hongos/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Medicina Tradicional , Aceites Volátiles/química , Aceites Volátiles/farmacología , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Componentes Aéreos de las Plantas/química , Componentes Aéreos de las Plantas/metabolismo , Extractos Vegetales/química , Zanthoxylum/metabolismo
11.
Curr Pharm Biotechnol ; 22(12): 1591-1601, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33504302

RESUMEN

Coronavirus-19 is a severe acute respiratory disorder in humans which has become a major health problem. It spreads out very rapidly throughout the world since it has been first identified in Wuhan, China (December 2019). The causative virus is known as severe acute respiratory syndrome coronavirus 2. And the World Health Organization has named this respiratory syndrome as a new epidemic disease called COVID-19. The incidence of COVID-19 continued to increase with three million confirmed infected cases and with 244,000 death cases worldwide. Until now there is no specific treatment or vaccine available against COVID- 19. The collective information about the different aspects of COVID-19 viral infection has been gathered from renowned journals, and electronic databases including Science Direct, Web of Science, Scopus and PubMed from 1990 to 2020. This manuscript has highlighted the transmission and symptoms of Covid-19. Therefore, these studies show how the SARS-CoV 2 can facilitate the debut of the virus into targeted host cells.


Asunto(s)
COVID-19 , China/epidemiología , Brotes de Enfermedades , Humanos , SARS-CoV-2
12.
Clin Cancer Res ; 27(9): 2378-2382, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33288660

RESUMEN

On June 15, 2020, the FDA granted accelerated approval to lurbinectedin for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Approval was granted on the basis of the clinically meaningful effects on overall response rate (ORR) and duration of response (DOR), and the safety profile observed in a multicenter, open-label, multicohort clinical trial (PM1183-B-005-14, NCT02454972), referred to as Study B-005, in patients with advanced solid tumors. The trial included a cohort of 105 patients with metastatic SCLC who had disease progression on or after platinum-based chemotherapy. The confirmed ORR determined by investigator assessment using RECIST 1.1 in the approved SCLC patient population was 35% [95% confidence interval (CI): 26-45], with a median DOR of 5.3 (95% CI: 4.1-6.4) months. The drug label includes warnings and precautions for myelosuppression, hepatotoxicity, and embryo-fetal toxicity. This is the first drug approved by the FDA in over 20 years in the second line for patients with metastatic SCLC. Importantly, this approval includes an indication for patients who have platinum-resistant disease, representing an area of particular unmet need.

13.
Autophagy ; 17(10): 3124-3139, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33249983

RESUMEN

The ubiquitin-proteasome system (UPS) and autophagy-lysosomal pathway (ALP) are two major protein degradation pathways in eukaryotic cells. Initially considered as two independent pathways, there is emerging evidence that they can work in concert. As alterations of UPS and ALP function can contribute to neurodegenerative disorders, cancer and cardiac disease, there is great interest in finding targets that modulate these catabolic processes. We undertook an unbiased, total genome high-throughput screen to identify novel effectors that regulate both the UPS and ALP. We generated a stable HEK293 cell line expressing a UPS reporter (UbG76V-mCherry) and an ALP reporter (GFP-LC3) and screened for genes for which knockdown increased both UbG76V-mCherry intensity and GFP-LC3 puncta. With stringent selection, we isolated 80 candidates, including the transcription factor ZNF418 (ZFP418 in rodents). After screen validation with Zfp418 overexpression in HEK293 cells, we evaluated Zfp418 knockdown and overexpression in neonatal rat ventricular myocytes (NRVMs). Endogenous and overexpressed ZFP418 were localized in the nucleus. Subsequent experiments showed that ZFP418 negatively regulates UPS and positively regulates ALP activity in NRVMs. RNA-seq from Zfp418 knockdown revealed altered gene expression of numerous ubiquitinating and deubiquitinating enzymes, decreased expression of autophagy activators and initiators and increased expression of autophagy inhibitors. We found that ZPF418 activated the promoters of Dapk2 and Fyco1, which are involved in autophagy. RNA-seq from Zfp418 knockdown revealed accumulation of several genes involved in cardiac development and/or hypertrophy. In conclusion, our study provides evidence that ZNF418 activates the ALP, inhibits the UPS and regulates genes associated with cardiomyocyte structure/function.Abbreviations: ACTN2, actinin alpha 2; ALP, autophagy-lysosomal pathway; COPB1, COPI coat complex subunit beta 1; DAPK2, death associated protein kinase 2; FYCO1, FYVE and coiled-coil domain autophagy adaptor 1; HEK293, human embryonic kidney cells 293; HTS, high-throughput screen; LC3, microtubule associated protein 1 light chain 3; NRVMs, neonatal rat ventricular myocytes; RNA-seq, RNA sequencing; RPS6, ribosomal protein S6; TNNI3, troponin I, cardiac 3; UPS, ubiquitin-proteasome system; shRNA, short hairpin RNA; SQSTM1/p62, sequestosome 1; VPS28, VPS28 subunit of ESCRT-I; ZNF418/ZFP418, zinc finger protein 418.

14.
J Diet Suppl ; 18(3): 278-292, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32449638

RESUMEN

Manilkara hexandra (Roxb; Family:sapotaceae) is reported to exert preventive effect in several experimental ulcer models. However, there is no report of M. hexandra on gastric ulcer healing property. Thus, the present study was designed to evaluate the gastric ulcer healing activity of methanolic stem bark extract of M. hexandra (MH) and to derive a plausible molecular level of mechanism of action. MH was subjected to several phytochemical screening tests and standardized to quercetin by HPTLC. In the first pharmacological experiment, the standardized MH (50, 100 and 200 mg/kg) was carried out for ulcer healing activity against acetic acid (AA)-induced gastric ulcer in male rats. MH (100 and 200 mg/kg) ameliorated AA-induced rat gastric lesions. Further, MH (100 and 200 mg/kg) attenuated AA-induced changes in the levels of lipid peroxidation (LPO), reduced glutathione (GSH), oxidized glutathione (GSSG) and ratio of GSH/GSSG and activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) enzymes, and level of hame oxygenase-1 (HO-1) in stomach tissue. In the subsequent set of experiment, trigonelline (30 mg/kg; p.o.), a potent Nrf2 antagonist, significantly abrogated the gastric ulcer healing activity of MH (100 mg/kg) in AA challenged animals. Further, trigonelline attenuated the effects of MH (100 mg/kg) on the levels of LPO, GSH, GSSG and ratio of GSH/GSSG and activity of SOD, CAT, GPx and GR enzymes, and level of HO-1 in AA challenged rodents. These observations implicate the fact that MH could be a better therapeutic alternative in the management of gastric ulcer.


Asunto(s)
Manilkara , Extractos Vegetales/uso terapéutico , Úlcera Gástrica , Ácido Acético , Animales , Catalasa , Mucosa Gástrica , Glutatión , Masculino , Manilkara/química , Corteza de la Planta/química , Ratas , Ratas Wistar , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Superóxido Dismutasa
15.
Artículo en Inglés | MEDLINE | ID: mdl-33172906

RESUMEN

Fanconi anemia (FA) is a clinically heterogenous and genetically diverse disease with 22 known complementation groups (FA-A to FA-W), resulting from the inability to repair DNA interstrand cross-links. This rare disorder is characterized by congenital defects, bone marrow failure, and cancer predisposition. FANCA is the most commonly mutated gene in FA and a variety of mostly private mutations have been documented, including small and large indels and point and splicing variants. Genotype-phenotype associations in FA are complex, and a relationship between particular FANCA variants and the observed cellular phenotype or illness severity remains unclear. In this study, we describe two siblings with compound heterozygous FANCA variants (c.3788_3790delTCT and c.4199G > A) who both presented with esophageal squamous cell carcinoma at the age of 51. The proband came to medical attention when he developed pancytopenia after a single cycle of low-dose chemotherapy including platinum-based therapy. Other than a minor thumb abnormality, neither patient had prior findings to suggest FA, including normal blood counts and intact fertility. Patient fibroblasts from both siblings display increased chromosomal breakage and hypersensitivity to interstrand cross-linking agents as seen in typical FA. Based on our functional data demonstrating that the c.4199G > A/p.R1400H variant represents a hypomorphic FANCA allele, we conclude that the residual activity of the Fanconi anemia repair pathway accounts for lack of spontaneous bone marrow failure or infertility with the late presentation of malignancy as the initial disease manifestation. This and similar cases of adult-onset esophageal cancer stress the need for chromosome breakage testing in patients with early onset of aerodigestive tract squamous cell carcinomas before platinum-based therapy is initiated.


Asunto(s)
Neoplasias Esofágicas/genética , Proteína del Grupo de Complementación A de la Anemia de Fanconi/genética , Anemia de Fanconi/genética , Sistemas CRISPR-Cas , Rotura Cromosómica , ADN , Reparación del ADN , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/diagnóstico , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/metabolismo , Anemia de Fanconi/diagnóstico , Anemia de Fanconi/terapia , Fibroblastos/metabolismo , Edición Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Mutación
16.
Crit Rev Ther Drug Carrier Syst ; 37(4): 305-329, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32865928

RESUMEN

The main objective of drug(s) formulation is to enhance the bioavailability of the drug within the body. Some of the challenging issues associated with poorly water-soluble drugs concern solubility and bioavailability factors. To overcome these problems, new technologies, such as lipid-based drug delivery systems including micro or nano emulsifying drug delivery system, have gained importance in recent years, due to their enhanced solubility and bioavailability in the gastrointestinal tract. Such systems are incorporated or solubilized within the lipid excipients or mixed with oils or surfactants/co-solvents to facilitate the solubility and absorption rate, which can enhance the bioavailability of the targeted drug. This review provides a comprehensive summary about the properties, factors affecting formulations, excipients, formulation techniques, and characterization of self-emulsifying drug delivery systems. It also focuses on the new approaches concerned with SEDDS.


Asunto(s)
Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/métodos , Emulsionantes/química , Animales , Disponibilidad Biológica , Excipientes/química , Humanos , Lípidos/química , Aceites , Tamaño de la Partícula , Solubilidad , Solventes , Tensoactivos , Agua
17.
J Pharm Pharmacol ; 72(12): 1694-1714, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32729204

RESUMEN

OBJECTIVES: Carissa carandas is an evergreen thorny shrub (Apocynaceae family), commonly, known as karonda. It has small berry-shaped fruits, used as additive in many pickles or as a spice in northern India. METHODS: The present review covers the literature survey from 1968 to 2020. The data have been collected from various journals, books, thesis and some of the electronic search via Internet-based information such as PubMed, Google Scholar, ScienceDirect, EBSCO, online electronic journals, SpringerLink, Wiley and Ayush. KEY FINDINGS: From literature survey, it has been found that the herbal drug contains wide variety of flavonoids, phenolic acids, steroids, volatile oils, lignans, alkaloids, polysaccharides and so on. These phytochemicals exhibit a range of pharmacological activities including antioxidant, anti-inflammatory, antidiabetic, antimicrobial and antifungal properties. CONCLUSIONS: This current review offers primary data for further research work. The in-vitro evaluations as well as in-vivo models/experiments have provided a biosynthetic observation for its various ethno-pharmacological uses and even pharmacological properties. This review would provide all valuable information which will be beneficiary to conduct some important pharmacokinetic and toxicological research works on human models with respect to ensure the effects of active ingredients in the body and even to validate its safety issues in clinical aspects.


Asunto(s)
Antiinfecciosos/farmacología , Antiinflamatorios/farmacología , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/farmacología , Apocynaceae , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Animales , Antiinfecciosos/aislamiento & purificación , Antiinfecciosos/toxicidad , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/toxicidad , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/toxicidad , Antioxidantes/aislamiento & purificación , Antioxidantes/toxicidad , Apocynaceae/química , Interacciones Alimento-Droga , Interacciones de Hierba-Droga , Humanos , Fitoquímicos/aislamiento & purificación , Fitoquímicos/toxicidad , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad
18.
Clin Infect Dis ; 71(15): 807-812, 2020 07 28.
Artículo en Inglés | MEDLINE | ID: mdl-32240285

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) causes a range of illness severity. Mild illness has been reported, but whether illness severity correlates with infectivity is unknown. We describe the public health investigation of a mildly ill, nonhospitalized COVID-19 case who traveled to China. METHODS: The case was a Maricopa County resident with multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive specimens collected on 22 January 2020. Contacts were persons exposed to the case on or after the day before case diagnostic specimen collection. Contacts were monitored for 14 days after last known exposure. High-risk contacts had close, prolonged case contact (≥ 10 minutes within 2 m). Medium-risk contacts wore all US Centers for Disease Control and Prevention-recommended personal protective equipment during interactions. Nasopharyngeal and oropharyngeal (NP/OP) specimens were collected from the case and high-risk contacts and tested for SARS-CoV-2. RESULTS: Paired case NP/OP specimens were collected for SARS-CoV-2 testing at 11 time points. In 8 pairs (73%), ≥ 1 specimen tested positive or indeterminate, and in 3 pairs (27%) both tested negative. Specimens collected 18 days after diagnosis tested positive. Sixteen contacts were identified; 11 (69%) had high-risk exposure, including 1 intimate contact, and 5 (31%) had medium-risk exposure. In total, 35 high-risk contact NP/OP specimens were collected for SARS-CoV-2 testing; all 35 pairs (100%) tested negative. CONCLUSIONS: This report demonstrates that SARS-CoV-2 infection can cause mild illness and result in positive tests for up to 18 days after diagnosis, without evidence of transmission to close contacts. These data might inform public health strategies to manage individuals with asymptomatic infection or mild illness.


Asunto(s)
Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/transmisión , Neumonía Viral/diagnóstico , Neumonía Viral/transmisión , Adulto , Arizona , Betacoronavirus/patogenicidad , COVID-19 , Prueba de COVID-19 , China , Técnicas de Laboratorio Clínico , Trazado de Contacto/métodos , Infecciones por Coronavirus/virología , Humanos , Masculino , Pandemias , Neumonía Viral/virología , SARS-CoV-2 , Síndrome Respiratorio Agudo Grave/diagnóstico , Síndrome Respiratorio Agudo Grave/virología , Manejo de Especímenes/métodos , Viaje
19.
Arch Clin Neuropsychol ; 35(5): 528-538, 2020 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-32188967

RESUMEN

OBJECTIVE: With the rising burden of dementia globally, there is a need to harmonize dementia research across diverse populations. The Addenbrooke's Cognitive Examination-III (ACE-III) is a well-established cognitive screening tool to diagnose dementia. But there have been few efforts to standardize the use of ACE-III across cohorts speaking different languages. The present study aimed to standardize and validate ACE-III across seven Indian languages and to assess the diagnostic accuracy of the test to detect dementia and mild cognitive impairment (MCI) in the context of language heterogeneity. METHODS: The original ACE-III was adapted to Indian languages: Hindi, Telugu, Kannada, Malayalam, Urdu, Tamil, and Indian English by a multidisciplinary expert group. The ACE-III was standardized for use across all seven languages. In total, 757 controls, 242 dementia, and 204 MCI patients were recruited across five cities in India for the validation study. Psychometric properties of adapted versions were examined and their sensitivity and specificity were established. RESULTS: The sensitivity and specificity of ACE-III in identifying dementia ranged from 0.90 to 1, sensitivity for MCI ranged from 0.86 to 1, and specificity from 0.83 to 0.93. Education but not language was found to have an independent effect on ACE-III scores. Optimum cut-off scores were established separately for low education (≤10 years of education) and high education (>10 years of education) groups. CONCLUSIONS: The adapted versions of ACE-III have been standardized and validated for use across seven Indian languages, with high diagnostic accuracy in identifying dementia and MCI in a linguistically diverse context.


Asunto(s)
Disfunción Cognitiva , Demencia , Lenguaje , Cognición , Disfunción Cognitiva/diagnóstico , Demencia/diagnóstico , Humanos , India , Pruebas Neuropsicológicas , Reproducibilidad de los Resultados
20.
J Educ Health Promot ; 9: 20, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32154315

RESUMEN

BACKGROUND: India is at the nascent stage of competency-based medical education. Faculties trained in medical education are the main driving force for change. The present study explores the perception of faculties about the current practices and problems in medical/dental/nursing undergraduate assessment, barriers to adoption of best practices, and solutions for addressing them. METHODOLOGY: A qualitative study was designed and data collected through an asynchronous online discussion forum. A group of 31 health professionals (FAIMER fellows selected on the basis of active participation in department of medical education of respective colleges) participated in the forum. An open-ended topic guide with prompts was designed. The forum was initiated by release of discussion topics (threads) at the start of the month and remained in forum throughout the month. Researchers moderated and recorded day-to-day events. All online forum data were coded line by line and analyzed using conventional content analysis. RESULTS: Four categories generated were: (1) Low utility of current skill assessment system due to low validity and reliability; (2) Barrier in adopting newer assessment tool due to the absence of felt need of faculties and students, mistaken beliefs, and limited resources; (3) Poor implementation of newer assessment tools such as formatives and objective structured clinical examination with no blueprinting; and (4) Solutions proposed were regular formative assessment, criterion-based examination, quality-assured faculty development programs, and administrative support. CONCLUSIONS: Barriers in adopting newer assessment tools are related to the faculty's perception and resource constraint. This can be addressed by quality-assured faculty development programs and effective implementation of competency-based education.

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