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OBJECTIVE: This cross-sectional study aimed to investigate the emergence of adeno-enterovirus conjunctivitis, with a focus on its clinical manifestations, prevalence, and implications within the context of acute epidemic conjunctivitis. METHODS: Real-time PCR analysis was employed to precisely identify the viral strain in conjunctival swab samples. A total of 80 patients were tested, and specific clinical symptoms were assessed. RESULTS: The study revealed the first documented case in India and the second worldwide of adeno-enterovirus conjunctivitis. The prevalence among the tested patients was significant, with 15% testing positive. Those infected with adeno-enterovirus exhibited shorter illnesses (≤3 days). Notably, clinical symptoms such as subconjunctival hemorrhage, chemosis, swelling, photophobia, and epiphora were significantly linked to this viral variant. Multivariable logistic regression analysis highlighted swelling and photophobia as robust predictors for identifying adeno-enterovirus conjunctivitis cases. CONCLUSION: The findings underscore the urgent need to recognize adeno-enterovirus conjunctivitis as a potential threat, capable of causing significant ocular morbidity. Swelling and photophobia emerged as robust predictors for identifying cases, emphasizing the importance of vigilant monitoring and comprehension of this viral variant. Proactive measures are essential to address its clinical implications and mitigate its impact on affected populations. Ongoing research is crucial to unravel the complete spectrum of adeno-enterovirus conjunctivitis and guide effective management strategies.
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In the era of wearable electronic devices, which are quite popular nowadays, our research is focused on flexible as well as stretchable strain sensors, which are gaining humongous popularity because of recent advances in nanocomposites and their microstructures. Sensors that are stretchable and flexible based on graphene can be a prospective 'gateway' over the considerable biomedical speciality. The scientific community still faces a great problem in developing versatile and user-friendly graphene-based wearable strain sensors that satisfy the prerequisites of susceptible, ample range of sensing, and recoverable structural deformations. In this paper, we report the fabrication, development, detailed experimental analysis and electronic interfacing of a robust but simple PDMS/graphene/PDMS (PGP) multilayer strain sensor by drop casting conductive graphene ink as the sensing material onto a PDMS substrate. Electrochemical exfoliation of graphite leads to the production of abundant, fast and economical graphene. The PGP sensor selective to strain has a broad strain range of â60%, with a maximum gauge factor of 850, detection of human physiological motion and personalized health monitoring, and the versatility to detect stretching with great sensitivity, recovery and repeatability. Additionally, recoverable structural deformation is demonstrated by the PGP strain sensors, and the sensor response is quite rapid for various ranges of frequency disturbances. The structural designation of graphene's overlap and crack structure is responsible for the resistance variations that give rise to the remarkable strain detection properties of this sensor. The comprehensive detection of resistance change resulting from different human body joints and physiological movements demonstrates that the PGP strain sensor is an effective choice for advanced biomedical and therapeutic electronic device utility.
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Dimetilpolisiloxanos , Grafito , Dispositivos Electrónicos Vestibles , Grafito/química , Humanos , Dimetilpolisiloxanos/química , MovimientoRESUMEN
With the increasing number of options for the treatment of moderate-to-severe atopic dermatitis, clinicians need guidance on a practical approach to selecting a systemic agent for specific patient populations. We convened an expert panel consisting of 12 members to conduct a literature review and summarize relevant data related to six scenarios of clinical interest: comorbid asthma, ocular surface disease, history of cancer, past and ongoing infections of interest (including herpes simplex virus, herpes zoster, hepatitis B, and tuberculosis), pregnancy and lactation, and the elderly. We performed a literature search and examined each clinical scenario with respect to three major categories of available systemic agents: traditional systemics (azathioprine, cyclosporine A, methotrexate, and mycophenolate mofetil), Janus kinase inhibitors (abrocitinib, baricitinib, and upadacitinib), and biologics (dupilumab, lebrikizumab, and tralokinumab). The expert panel and steering committee met virtually to review the data and discuss the drafted consensus statements. A modified Delphi process was used to arrive at a set of final consensus statements related to the systemic treatment of AD in these specific patient populations. To provide practical guidance on the choice of systemic therapy for atopic dermatitis in these six topics of clinical interest, 25 expert consensus statements and a summary of the supporting data are presented herein.
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Asma , Dermatitis Atópica , Femenino , Humanos , Anciano , Dermatitis Atópica/tratamiento farmacológico , Ciclosporina/uso terapéutico , Metotrexato/uso terapéutico , Ácido Micofenólico/uso terapéutico , Asma/tratamiento farmacológicoRESUMEN
Herein, a novel N-(4-(tert-butyl)-phenyl)-2-chloroacetamide functionalized thiacalix[4]arene architecture, viz TCAN2PA has been synthesized and the sensing behaviour towards metal ions were explored. The probe, TCAN2PA displayed "turn-on" fluorescence response towards Hg(II) ions in acetonitrile over a series of competing common metal ions. A bathochromic shift in absorption band along with a significant "Turn-On" fluorescence behaviour of TCAN2PA was observed upon interaction with Hg(II) ions. The lower rim modification of thiacalixarene with N-(4-(tert-butyl)-phenyl)-2-chloroacetamide actively contributes toward the fluorescence property due to the presence of strong electron-donating aryl amido substituent. Fluorescence titration experiments were conducted to find out the limit of detection and to understand binding stoichiometry as well. The electron transfer interactions between the electron rich TCAN2PA host with Hg(II) ions have been postulated which is also supported by computational modelling insights.
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OBJECTIVE: To highlight causal relationship between stress fracture in the presence of tarsal coalition and hindfoot pain in adolescents on magnetic resonance imaging (MRI). MATERIAL AND METHODS: A retrospective review was performed of the clinical and MRI imaging findings of 6 adolescents referred for MRI to evaluate symptoms of hindfoot pain with possible tarsal coalition. MRI studies were systematically assessed for cause of hindfoot pain, types of tarsal coalition, patterns of stress fractures, bone marrow oedema and any other associated features. RESULTS: All the 6 patients (4 male: 2 female) aged between 12 and 19 years developed insidious onset of hindfoot or midfoot pain over a period of weeks to months. On MRI, all 6 cases had features of fibrous tarsal coalition predominantly in the calcaneonavicular articulation (5 out of 6 patients). Associated stress fractures/response were in the posterior facet/body of the calcaneus (3), talar head (2), cuboid (1) and third metatarsal bone in one patient. CONCLUSION: Stress fractures/response adjacent to tarsal coalition could be because of altered biomechanics and can be an unusual cause of hindfoot pain in adolescents. A high index of suspicion and complementary MRI findings is crucial to interpret this condition to direct appropriate patient management.
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Calcáneo , Huesos Tarsianos , Coalición Tarsiana , Adolescente , Femenino , Humanos , Recién Nacido , Imagen por Resonancia Magnética/métodos , Masculino , Dolor , Huesos Tarsianos/diagnóstico por imagen , Coalición Tarsiana/complicaciones , Coalición Tarsiana/diagnóstico por imagenRESUMEN
Discoid menisci represent a range of morphological meniscal variants, most commonly involving the lateral meniscus. Clinical presentation ranges from an asymptomatic incidental finding to snapping, pain, swelling and reduced range of knee movement. Symptomatic presentation of discoid menisci is usually due to meniscal tears and instability resulting from abnormal meniscal morphology and ultrastructure, with absent peri-meniscal ligamentous and meniscocapsular attachments characteristic of the Wrisberg sub-type. This article reviews the current classification systems of discoid menisci, gross morphological characteristics of each sub-type and ultrastructure. Clinical presentation, arthroscopic findings and indirect radiological diagnostic criteria are described, as are the MRI findings of normal and pathological discoid menisci. Current concepts of surgical management and outcomes of the discoid meniscus are also briefly discussed.
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Artropatías , Menisco , Artroscopía/métodos , Humanos , Artropatías/cirugía , Articulación de la Rodilla/patología , Imagen por Resonancia Magnética , Meniscos Tibiales/patologíaRESUMEN
AIM: The present work involves encapsulation of herbal drug nanocurcumin into the virosomes and compared with a liposome in terms of their in vitro anti-proliferative, anti-inflammatory, and anti-migratory efficacy. METHODS: The anti-proliferative, anti-inflammatory, and anti-migratory efficacy of virosome and liposome were compared in HepG2 and CaCo2 cells by using MTT, Nitric oxide scavenging, and Wound healing assay, respectively. RESULTS: Size of the optimised NC-Virosome and NC-Liposome was 70.06 ± 1.63 and 265.80 ± 1.64 nm, respectively. The prepared NC-Virosome can be stored at -4 °C up to six months. The drug encapsulation efficiency of NC-Virosome and NC-Liposome was found to be 84.66 ± 1.67 and 62.15 ± 1.75% (w/w). The evaluated minimum inhibitory concentration (IC50 value) for NC-Virosome was 102.7 µg/ml and 108.1 µg/ml, while NC-Liposome showed 129.2 µg/ml and 160.1 µg/ml for HepG2 and CaCo2 cells, respectively. Morphological examination depicts detachment of the cells from substratum after exposure to NC-Virosome for 48 h. CONCLUSION: The prepared NC-Virosome provides remarkable in vitro efficacy in both the cell lines with site-specific drug-targeting potential as compared to the liposome, results proved its potential as a drug delivery vehicle for future therapy with reduced toxicity.
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Antineoplásicos Fitogénicos/uso terapéutico , Liposomas/química , Virosomas/química , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Antineoplásicos Fitogénicos/administración & dosificación , Células CACO-2 , Movimiento Celular/efectos de los fármacos , Curcumina/administración & dosificación , Curcumina/uso terapéutico , Sistemas de Liberación de Medicamentos , Excipientes , Células Hep G2 , Humanos , Pruebas de Sensibilidad Microbiana , Neoplasias/tratamiento farmacológico , Óxido Nítrico/química , Sales de Tetrazolio , Tiazoles , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Pacemakers and implantable cardioverter defibrillators are commonly encountered in clinical practice, and entails special consideration when magnetic resonance imaging (MRI) is required. It is estimated that 50-75% of patients with cardiac implantable electronic devices (CIED) will have an indication for MRI during their lifetime. Radiologists may want to recommend MRI or may be consulted about the need to perform MRI in a patient with a CIED, at which point they may need to approve or at least provide guidance as to whether MRI may be performed safely. Even in situations where final clearance will not be provided by the radiologist, he or she can provide valuable information by reviewing radiographs and determining (a) whether a device is MRI-conditional and MRI may ultimately be permitted, (b) is not MRI-conditional and MRI using the standard workflow will therefore not be approved, or (c) when additional information will clearly be required. CIED identification and verification of leads can be accomplished through review of the medical record and/or evaluation of a chest radiograph. In patients with MRI-conditional CIEDs (as well as with legacy CIEDs in those institutions that perform MRI of these patients), specific imaging protocols must be adhered to in order to prevent death or injury to the patient or damage to the device. In this update, we provide details regarding the above topics and provide an algorithm for integrating this information into a clinical workflow to efficiently triage patients with CIEDs who are being considered for MRI.
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Desfibriladores Implantables , Imagen por Resonancia Magnética , Desfibriladores Implantables/efectos adversos , Humanos , Imagen por Resonancia Magnética/efectos adversos , Tórax/diagnóstico por imagenRESUMEN
BACKGROUND: Obesity leads to an impairment of physical function that limits the ability to perform basic physical activities affecting quality of life. Literature on the effect of bariatric surgery on physical function is confounding and generally of low quality. METHODS: A comprehensive search was undertaken using MEDLINE, Scopus (including Embase), CENTRAL, PubMed, SPORTDiscus, Scirus and OpenGrey for published research and non-published studies to 31 March 2017. Studies employing objective measurement and self-reporting of physical function before and after bariatric surgery were included. The magnitude of experimental effect was calculated in terms of the standardized mean difference (MD), and confidence intervals were set at 95 per cent to reflect a significance level of 0·05. RESULTS: Thirty studies including 1779 patients met the inclusion criteria. Physical function improved after bariatric surgery at 0-6 months (MD 0·90, 95 per cent c.i. 0·60 to 1·21; P < 0·001), more than 6 to 12 months (MD 1·06, 0·76 to 1·35; P < 0·001) and more than 12 to 36 months (MD 1·30, 1·07 to 1·52; P < 0·001). Objective assessment of physical function after bariatric surgery showed improvement at 0-6 months (MD 0·94, 0·57 to 1·32; P < 0·001), more than 6 to 12 months (MD 0·77, 0·15 to 1·40; P = 0·02) and more than 12 to 36 months (MD 1·04, 0·40 to 1·68; P = 0·001). Self-reported assessment of physical function showed similar improvements at 0-6 months (MD 0·80, 0·12 to 1·47; P = 0·02), more than 6 to 12 months (MD 1·42, 1·23 to 1·60; P < 0·001) and more than 12 to 36 months (MD 1·41, 1·20 to 1·61; P < 0·001) after a bariatric procedure. CONCLUSION: Bariatric surgery improves physical function significantly within 6 months of the procedure and this effect persists over time to 36 months after surgery, whether measured objectively or by self-reporting.
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Cirugía Bariátrica/métodos , Ejercicio Físico/fisiología , Obesidad Mórbida/cirugía , Calidad de Vida , Pérdida de Peso/fisiología , Humanos , Obesidad Mórbida/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND: Airway epithelial injury is a crucial component of acute and severe asthma pathogenesis and a promising target for treatment of refractory asthma. However, the underlying mechanism of epithelial injury remains poorly explored. Although high levels of polyamines, mainly spermine, have been found in asthma and comorbidity, their role in airway epithelial injury and the cause of their altered levels in asthma have not been explored. METHODS: We measured key polyamine metabolic enzymes in lung samples from normal and asthmatic subjects and in mice with OVA-induced allergic airway inflammation (AAI). Polyamine metabolism was modulated using pharmacologic/genetic modulators. Epithelial stress and apoptosis were measured by TSLP levels and TUNEL assay, respectively. RESULTS: We found loss of the polyamine catabolic enzymes spermidine/spermine-N (1)-acetyltransferase-1 (SAT1) and spermine oxidase (SMOX) predominantly in bronchial epithelial cells (BECs) of human asthmatic lung samples and mice with AAI. In naïve mice, SAT1 or SMOX knockdown led to airway hyper-responsiveness, remodeling, and BEC apoptosis. Conversely, in mice with AAI, overexpression of either SAT1 or SMOX alleviated asthmatic features and reduced TSLP levels and BEC apoptosis. Similarly, while pharmacological induction of SAT1 and SMOX using the polyamine analogue bis(ethyl)norspermine (BENSPM) alleviated asthmatic features with reduced TSLP levels and BEC apoptosis, pharmacological inhibition of these enzymes using BERENIL or MDL72527, respectively, worsened them. Spermine accumulation in lungs correlated with BEC apoptosis, and spermine treatment caused apoptosis of human BEAS-2B cells in vitro. CONCLUSIONS: Spermine induces BEC injury. Induction of polyamine catabolism may represent a novel therapeutic approach for asthma via reversing BEC stress.
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Asma/metabolismo , Epitelio/lesiones , Poliaminas/metabolismo , Sistema Respiratorio/patología , Espermina/metabolismo , Animales , Apoptosis , Asma/etiología , Células Epiteliales/química , Células Epiteliales/enzimología , Células Epiteliales/patología , Humanos , Pulmón/enzimología , Ratones , Espermina/efectos adversosRESUMEN
Diselenodipropionic acid (DSePA), a pharmacologically important derivative of selenocystine was evaluated for acute toxicity, mutagenic safety and metabolic stability. The estimated median oral lethal dose (LD50) cut-off of DSePA in mice and rat models was â¼200â¯mg/kg and â¼25â¯mg/kg respectively, which is considerably higher than the reported oral LD50 dose of its parent compound. Subsequently DSePA treatment in absence and presence of rat liver S9 fraction was found to be non-mutagenic at the tested doses up to 1â¯mM in rifampicin resistance assay and up to 6â¯mM in Ames test. In vitro degradation studies indicated that DSePA was more stable in S9 fraction of human compared to rat. The kinetic parameters Km and Vmax of DSePA degradation estimated using rat S9 fraction was 9.81⯵M and 1.06â¯nmol/ml/min respectively. Further, DSePA treatment (1-50⯵M) with or without rat S9 fraction did not induce any toxicity in human intestinal epithelial cells (Int 407) while showing comparable bioactivity of glutathione peroxidase (GPx) level. In conclusion, superior metabolic stability of DSePA in human S9 fraction with a concomitant lack of mutagenic effects suggests that it may be a suitable derivative of selenocytine for future biological studies.
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Cistina/análogos & derivados , Compuestos de Organoselenio/metabolismo , Propionatos/efectos adversos , Compuestos de Selenio/efectos adversos , Animales , Cistina/metabolismo , Células Epiteliales/efectos de los fármacos , Femenino , Glutatión Peroxidasa/metabolismo , Humanos , Ratones , Mutagénesis/efectos de los fármacos , Pruebas de Mutagenicidad/métodos , Mutágenos/toxicidad , Ratas , Ratas WistarRESUMEN
Background Ovarian cancer is the second most common type of female genital tract malignancy. Treatment planning differs for benign, borderline and malignant subtypes of surface epithelial tumours and depends on accurate histopathological diagnosis. A pre-operative diagnosis of the nature of ovarian tumors is not always reliable. Frozen section is a valuable diagnostic tool in rapid intraoperative categorization of ovarian masses and thereby helps in planning the surgical management. Adequate management and treatment of ovarian carcinoma requires a complete surgical staging supported by frozen-section examination. To achieve this goal it is necessary to have a high level of accuracy. Objective To assess the accuracy of intra-operative frozen section in the diagnosis of various categories of ovarian neoplasm conducted in Rajiv Gandhi Cancer Institute and Research Centre. Method Intra-operative frozen sections for suspected ovarian neoplasm that underwent surgery as primary line of therapy at this institution were analyzed retrospectively from Jan. 2014 - Dec. 2015. The results of frozen section were compared with the final histopathology diagnosis on paraffin sections and the overall accuracy, sensitivity, specificity, positive and negative predictive values were determined. Result The study included 159 cases and the mean age of patients was 44.72±14.28 years (Range 19-75 years). The mean size of tumor was 12.5±5.9 cm. Sensitivity of frozen section for benign, borderline and malignant tumors was 98.53%, 73.33% and 94.74% respectively and the related specificities were 95.60%, 96.53% and 100% respectively. There were 150 concordant cases and 9 discordant cases. Overall diagnostic accuracy of frozen section was 94.33%. Conclusion Intra-operative frozen section diagnosis appeared to be an accurate and comparable technique for the histopathology diagnosis of ovarian tumors.
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Secciones por Congelación/normas , Neoplasias Ováricas/diagnóstico , Adulto , Anciano , Femenino , Humanos , Cuidados Intraoperatorios/métodos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
NKG2D (KLRK1) is a C-type lectin receptor present on natural killer (NK) cells, γδ, CD8+ and CD4+ T cells. Upon ligand binding, NKG2D mediates activatory and co-stimulatory signals to NK cells and activated CD4+ T cells, respectively. Polymorphisms in NKG2D predispose to infectious diseases, cancer, transplantation and autoimmune disorders. We studied the influence of this NK receptor polymorphism on predisposition to and modification of the disease phenotype in patients with rheumatoid arthritis (RA). Eight different single nucleotide polymorphisms (SNP) in the NKG2 gene were genotyped in 236 patients with RA and 187 controls using Taqman 5' nuclease assays. NKG2D genotype/allele frequency did not differ between patients and controls. Subgroup analysis showed that the frequency of A allele of NKG2D9 and T allele of NKG2D10 was significantly higher in patients with deformities (a marker of severe disease) [11 versus 5%, Pc = 0·03, odds ratio (OR) = 2·44, 95% confidence interval (CI) = 1·09-5·98 and 10 versus 4%, Pc = 0·04, OR = 2·45, 95% CI = 1·05-6·39, respectively], while the frequency of alleles G of NKG2D9 and A of NKG2D10 was greater in patients without deformities (Pc = 0·03, OR = 0·41, 95% CI = 0·17-0·91 and Pc = 0·04, OR = 0·41, 95% CI = 0·16-0·96). Similar trends of association were observed with deforming phenotype of RA in female patients and deforming young onset RA subgroups. Haplotype analysis revealed that the frequency of haplotype G-C-A-G-A-T-C-C was higher in patients than in controls (12 versus 8%, P = 0·04, OR = 1·61, 95% CI = 1·01-2·55), suggesting that it may predispose to RA. Our study suggests that the NKG2D gene polymorphisms may modify the risk of development and severity of RA.
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Artritis Reumatoide/genética , Predisposición Genética a la Enfermedad/genética , Subfamilia K de Receptores Similares a Lectina de Células NK/genética , Polimorfismo de Nucleótido Simple/genética , Adolescente , Adulto , Anciano , Alelos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Haplotipos/genética , Humanos , Lectinas Tipo C , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Adulto JovenRESUMEN
OBJECTIVES: Several parameters, including branch pulmonary artery (PA) diameter and Doppler-derived PA acceleration-to-ejection time ratio (AT/ET), peak late-systolic/early-diastolic reversed flow (PEDRF) and pulsatility index (PI) response to maternal hyperoxia, have been used to investigate fetal pulmonary health. Lower AT/ET, increased PEDRF and lack of PI response to hyperoxia have been observed in fetuses with severe lung hypoplasia and are considered markers of pulmonary vascular resistance. We sought to further define the evolution of PA diameter and Doppler parameters and their response to maternal hyperoxia in healthy fetuses. METHODS: Fifty-four prospectively recruited women with healthy pregnancy underwent fetal echocardiography from 18-36 weeks of gestation. After baseline branch PA diameter and Doppler assessment, oxygen (8-10 L/min) was administered by non-reservoir facemask for 10 min and PA Doppler parameters were reassessed. RESULTS: Branch PA diameters and AT/ET increased linearly with gestational age, while PEDRF increased quadratically (P < 0.001 for all) and PA-PI did not change. In response to maternal hyperoxia, although most fetuses demonstrated a significant decrease in PI for both branch PAs (right PA, P = 0.025; left PA, P = 0.040) ≥ 30 weeks, significant variability was observed in PI response with 31% of cases demonstrating either no response or a slight decrease. No other parameter demonstrated a measurable change in response to maternal hyperoxia. CONCLUSIONS: From the mid-trimester, fetal branch PA diameters and AT/ET increase linearly and PEDRF increases quadratically, whereas PI remains unchanged. Although maternal hyperoxia triggers a significant decrease in PA-PI after 30 weeks, variability in this response may reduce its utility in clinical practice. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
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Hiperoxia/fisiopatología , Complicaciones Cardiovasculares del Embarazo/fisiopatología , Segundo Trimestre del Embarazo/fisiología , Tercer Trimestre del Embarazo/fisiología , Arteria Pulmonar/fisiopatología , Adulto , Ecocardiografía Doppler/métodos , Femenino , Feto/embriología , Feto/fisiopatología , Edad Gestacional , Voluntarios Sanos , Humanos , Hiperoxia/diagnóstico por imagen , Hiperoxia/embriología , Embarazo , Complicaciones Cardiovasculares del Embarazo/diagnóstico por imagen , Complicaciones Cardiovasculares del Embarazo/etiología , Estudios Prospectivos , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/embriología , Ultrasonografía Prenatal/métodos , Resistencia Vascular/fisiologíaRESUMEN
Retraction: 'Aetiology and clinical profile of children with 46, XY differences of sex development at an Indian referral centre' by Vasundhera Chauhan, Rima Dada, Vandana Jain The above article, published online on 8 August 2016 in Wiley Online Library (http://wileyonlinelibrary.com), has been retracted by agreement between the authors, the Journal Editors-in-Chief, Wolf-Bernhard Schill and Ralf Henkel, and Blackwell Verlag GmbH. The retraction has been agreed as the result of an unresolved dispute between the first author and a colleague research fellow due to the inclusion of data from patients who were simultaneously enrolled in two studies being conducted separately by the two parties. Reference Chauhan, V., Dada, R. and Jain, V. (2016), Aetiology and clinical profile of children with 46, XY differences of sex development at an Indian referral centre. Andrologia. doi:10.1111/and.12663.
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Growth hormone deficiency (GHD) results from variations affecting the production and release of growth hormone (GH) and is of 2 types: isolated growth hormone deficiency (IGHD) and combined pituitary hormone deficiency (CPHD). IGHD results from mutations in GH1 and GHRHR while CPHD is associated with defects in transcription factor genes PROP1, POU1F1, and HESX1. The present study reports on screening of POU1F1, PROP1, and HESX1 in CPHD patients and the novel variations identified. Fifty-one CPHD patients from 49 unrelated families clinically diagnosed on the basis of biochemical and imaging investigations along with 100 controls were enrolled. Detailed family history was noted from all participants and 5 ml blood samples drawn were processed for DNA isolation followed by direct sequencing of POU1F1, PROP1, and HESX1genes. Of the 51 patients, 8 were females and 43 were males. Mean height standard deviation score (SDS) and weight SDS were -5.50 and -2.76, respectively. Thirty-six of the 51 patients underwent MRI of which 9 (25%) had normal pituitary structure and morphology while 27 (75%) showed abnormalities. Molecular analysis revealed 10 (20%) patients to have POU1F1 and PROP1 mutations/variations of which 5 were novel and 2 previously reported. No mutations were identified in HESX1. The novel variations identified were absent in the 100 healthy individuals screened and the control database Exome Aggregation Consortium (ExAC). Reported POU1F1 and PROP1 mutation hotspots were absent in our patients. Instead, novel POU1F1 changes were identified suggesting existence of a distinct mutation spectrum in our population.
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Proteínas de Homeodominio/genética , Hipopituitarismo/genética , Mutación/genética , Factor de Transcripción Pit-1/genética , Secuencia de Bases , Niño , Codón/genética , Análisis Mutacional de ADN , Femenino , Mutación del Sistema de Lectura/genética , Homocigoto , Humanos , Masculino , Modelos Moleculares , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
A series of novel substituted oxacalix[4]arene has been synthesized and explored for their biological profile by evaluating anticancer, antifungal and antibacterial properties. The derivatives have been characterized by various spectroscopic techniques such as IR, (1)H NMR, (13)C NMR and Mass spectrometry. Many compounds showed strong inhibition (MIC) in the range of â¼0-50 µM with interesting cytotoxic activities against Hela cells in particular. The compounds were theoretically evaluated by docking studies as potential histone deacetylase inhibitors (HDACi). The study indicates that compounds bound adequately with HDAC, and hence complemented the experimental findings.
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Antineoplásicos/síntesis química , Calixarenos/química , Inhibidores de Histona Desacetilasas/síntesis química , Histona Desacetilasas/química , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Antifúngicos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Sitios de Unión , Calixarenos/síntesis química , Calixarenos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Hongos/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Células HeLa , Inhibidores de Histona Desacetilasas/química , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Humanos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Estructura Terciaria de ProteínaRESUMEN
A novel fluorescent thiacalix[4]arene-tetra-(quinoline-8-sulfonate) (TCTQ8S) was synthesized by condensation of thiacalix[4]arene (TCA) and 8-quinoline sulfonyl chloride(8QSC). TCTQ8S was characterized by ESI-MS, (1)H-NMR and (13)C-NMR spectroscopic methods. TCTQ8S was found to be an efficient "turn-off" fluorescent sensor for the selective and sensitive recognition of Co(II) ions. The Job's plot measurement reveals a 1:1 stoichiometric ratio. The designed chemosensor exhibited high selectivity toward Co(II) ions vs. other tested metal ions, with a detection limit of up to 1.038 × 10(-9) M. The binding constant and quantum yield for the complex were also determined. Molecular docking studies have been successfully performed to support 1:1 binding of TCTQ8S with the Co(II) metal ion. TCTQ8S was evaluated for real sample analysis on water sample for the detection of Co(II). Graphical Abstract Thiacalix derivatized fluorescent sensor for the selective detection of Co(II).
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AIM: To evaluate the clinical feasibility and accuracy of acoustic radiation force impulse (ARFI) elastography for the detection of liver fibrosis in patients with chronic viral hepatitis. MATERIALS AND METHODS: ARFI-based ultrasound elastography was performed in 69 patients with chronic liver disease (CLD) of viral aetiology and 36 healthy volunteers. Fifty-eight patients with CLD also underwent liver biopsy. RESULTS: ARFI was feasible in all 36 healthy volunteers and all 69 CLD patients, while valid measurements were obtained in 65 patients (95.6%) and all healthy volunteers. The mean shear-wave velocity (SWV) in healthy volunteers was 1.12±0.2 m/s. A gradual increase in mean SWV was noted from fibrosis of Grade F0 to F6 (Ishak's score) and a high positive correlation was found between the mean SWV on ARFI and fibrosis scores at liver biopsy (rho=0.789). The difference between the mild (F1 and F2) versus significant fibrosis (F3 and F4) was also statistically significant (p<0.001). The difference in the SWV measurements obtained from consecutive groups (i.e., F1 versus F2, F2 versus F3, and F3 versus F4) was not statistically significant. Using the area under the receiver operating characteristic curve (AUROC), the best calculated cut-off SWVs for the presence of fibrosis (≥F1), significant fibrosis (≥F3), severe fibrosis (≥F4), and cirrhosis (F6) were found to be 1.207, 1.347, 1.513, and 1.92 m/s, respectively. ARFI values were significantly higher in cirrhotic patients than in other patients (p<0.001). CONCLUSIONS: ARFI elastography allows valid non-invasive evaluation of liver stiffness and may help to distinguish between no/mild fibrosis and significant fibrosis and guide management decisions.