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1.
NMR Biomed ; : e5144, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38556777

RESUMO

OBJECTIVES: To evaluate the role of combined intravoxel incoherent motion and diffusion kurtosis imaging (IVIM-DKI) and their machine-learning-based texture analysis for the detection and assessment of severity in prostate cancer (PCa). MATERIALS AND METHODS: Eighty-eight patients underwent MRI on a 3 T scanner after giving informed consent. IVIM-DKI data were acquired using 13 b values (0-2000 s/mm2) and analyzed using the IVIM-DKI model with the total variation (TV) method. PCa patients were categorized into two groups: clinically insignificant prostate cancer (CISPCa) (Gleason grade ≤ 6) and clinically significant prostate cancer (CSPCa) (Gleason grade ≥ 7). One-way analysis-of-variance, t test, and receiver operating characteristic analysis was performed to measure the discriminative ability to detect PCa using IVIM-DKI parameters. A chi-square test was used to select important texture features of apparent diffusion coefficient (ADC) and IVIM-DKI parameters. These selected texture features were used in an artificial neural network for PCa detection. RESULTS: ADC and diffusion coefficient (D) were significantly lower (p < 0.001), and kurtosis (k) was significantly higher (p < 0.001), in PCa as compared with benign prostatic hyperplasia (BPH) and normal peripheral zone (PZ). ADC, D, and k showed high areas under the curves (AUCs) of 0.92, 0.89, and 0.88, respectively, in PCa detection. ADC and D were significantly lower (p < 0.05) as compared with CISPCa versus CSPCa. D for detecting CSPCa was high, with an AUC of 0.63. A negative correlation of ADC and D with GS (ADC, ρ = -0.33; D, ρ = -0.35, p < 0.05) and a positive correlation of k with GS (ρ = 0.22, p < 0.05) were observed. Combined IVIM-DKI texture showed high AUC of 0.83 for classification of PCa, BPH, and normal PZ. CONCLUSION: D, f, and k computed using the IVIM-DKI model with the TV method were able to differentiate PCa from BPH and normal PZ. Texture features of combined IVIM-DKI parameters showed high accuracy and AUC in PCa detection.

2.
Eur Radiol ; 33(11): 8112-8121, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37209125

RESUMO

OBJECTIVES: To analyze the performance of deep learning in isodense/obscure masses in dense breasts. To build and validate a deep learning (DL) model using core radiology principles and analyze its performance in isodense/obscure masses. To show performance on screening mammography as well as diagnostic mammography distribution. METHODS: This was a retrospective, single-institution, multi-centre study with external validation. For model building, we took a 3-pronged approach. First, we explicitly taught the network to learn features other than density differences: such as spiculations and architectural distortion. Second, we used the opposite breast to enable the detection of asymmetries. Third, we systematically enhanced each image by piece-wise-linear transformation. We tested the network on a diagnostic mammography dataset (2569 images with 243 cancers, January to June 2018) and a screening mammography dataset (2146 images with 59 cancers, patient recruitment from January to April 2021) from a different centre (external validation). RESULTS: When trained with our proposed technique (and compared with baseline network), sensitivity for malignancy increased from 82.7 to 84.7% at 0.2 False positives per image (FPI) in the diagnostic mammography dataset, 67.9 to 73.8% in the subset of patients with dense breasts, 74.6 to 85.3 in the subset of patients with isodense/obscure cancers and 84.9 to 88.7 in an external validation test set with a screening mammography distribution. We showed that our sensitivity exceeded currently reported values (0.90 at 0.2 FPI) on a public benchmark dataset (INBreast). CONCLUSION: Modelling traditional mammographic teaching into a DL framework can help improve cancer detection accuracy in dense breasts. CLINICAL RELEVANCE STATEMENT: Incorporating medical knowledge into neural network design can help us overcome some limitations associated with specific modalities. In this paper, we show how one such deep neural network can help improve performance on mammographically dense breasts. KEY POINTS: • Although state-of-the-art deep learning networks achieve good results in cancer detection in mammography in general, isodense, obscure masses and mammographically dense breasts posed a challenge to deep learning networks. • Collaborative network design and incorporation of traditional radiology teaching into the deep learning approach helped mitigate the problem. • The accuracy of deep learning networks may be translatable to different patient distributions. We showed the results of our network on screening as well as diagnostic mammography datasets.


Assuntos
Neoplasias da Mama , Aprendizado Profundo , Humanos , Feminino , Mamografia/métodos , Densidade da Mama , Estudos Retrospectivos , Neoplasias da Mama/diagnóstico por imagem , Detecção Precoce de Câncer
3.
Int J Mol Sci ; 24(3)2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36769343

RESUMO

To explore changes in proteins and metabolites under stress circumstances, genomics, proteomics, and metabolomics methods are used. In-depth research over the previous ten years has gradually revealed the fundamental processes of plants' responses to environmental stress. Abiotic stresses, which include temperature extremes, water scarcity, and metal toxicity brought on by human activity and urbanization, are a major cause for concern, since they can result in unsustainable warming trends and drastically lower crop yields. Furthermore, there is an emerging reliance on agrochemicals. Stress is responsible for physiological transformations such as the formation of reactive oxygen, stomatal opening and closure, cytosolic calcium ion concentrations, metabolite profiles and their dynamic changes, expression of stress-responsive genes, activation of potassium channels, etc. Research regarding abiotic stresses is lacking because defense feedbacks to abiotic factors necessitate regulating the changes that activate multiple genes and pathways that are not properly explored. It is clear from the involvement of these genes that plant stress response and adaptation are complicated processes. Targeting the multigenicity of plant abiotic stress responses caused by genomic sequences, transcripts, protein organization and interactions, stress-specific and cellular transcriptome collections, and mutant screens can be the first step in an integrative approach. Therefore, in this review, we focused on the genomes, proteomics, and metabolomics of tomatoes under abiotic stress.


Assuntos
Proteômica , Solanum lycopersicum , Humanos , Solanum lycopersicum/genética , Genômica , Plantas/metabolismo , Metabolômica , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas
4.
J Indian Assoc Pediatr Surg ; 28(3): 233-241, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37389399

RESUMO

Objective: To evaluate the hepatic vasculature/tumor relations in hepatoblastoma patients with three-dimensional (3D) reformatted images after triple-phase multi-detector computed tomography (MDCT) and to compare these with the surgical findings to judge the accuracy of this investigation. Materials and Methods: The study was carried out in hepatoblastoma patients after appropriate neo-adjuvant chemotherapy, prior to resection. Images were postprocessed at a dedicated workstation for multi-planar reformations, maximum intensity projection, curved planar reformations, and volume-rendered technique reconstructions. The reporting was done as per a specific protocol by both the radiologist and surgeon (per-operative findings) and the accuracy of MDCT ascertained as per concordance between the surgical and imaging findings. Results: Fourteen children (13 boys, 1 girl) underwent surgery. Clinically, relevant information regarding vascular, tumor involvement, and interface with vessels was provided by the study in all cases. Although all tumors were deemed resectable on preoperative imaging, one procedure was abandoned due to an unanticipated portal cavernoma. While a few anatomical variations were unexpectedly encountered during surgery, there was good concordance overall between findings on imaging and surgical exploration. Conclusions: MDCT with 3D reformatting provides accurate virtual representations of the hepatic tumor. This allows simulation of surgical resection with decreased risk of vascular injury and postoperative liver failure.

5.
J Indian Assoc Pediatr Surg ; 28(2): 128-136, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37197242

RESUMO

Context: Gastrointestinal (GI) duplications are rare congenital malformations with diverse presentations. They usually present in the pediatric age, especially in the first 2 years of life. Aims: To present our experience with GI duplication (cysts) at a pediatric surgery tertiary care teaching institute. Settings and Design: It is a retrospective observational study undertaken in the department of pediatric surgery at our center between 2012 and 2022 for GI duplications. Materials and Methods: All children were analyzed for their age, sex, presentation, radiological evaluation, operative management, and outcomes. Results: Thirty-two patients were diagnosed with GI duplication. Slight male predominance was present in the series (M: F ≈ 4:3). Fifteen (46.88%) patients presented in the neonatal age group; 26 (81.25%) patients were under 2 years. In the majority of cases (n = 23, 71.88%), the presentation was acute onset. Double duplication cysts on opposite sides of the diaphragm were present in one case. The most common location was ileum (n = 17), followed by gallbladder (n = 6), appendix (n = 3), gastric (n = 1), jejunum (n = 1), esophagus (n = 1), ileocecal junction (n = 1), duodenum (n = 1), sigmoid (n = 1), and anal canal (n = 1). Multiple associations (malformations/surgical pathologies) were present. Intussusception (n = 6) was the most common, followed by intestinal atresia (n = 5), anorectal malformation (n = 3), abdominal wall defect (n = 3), hemorrhagic cyst (n = 1), Meckel's diverticulum (n = 1), and sacrococcygeal teratoma (n = 1). Four cases were associated with intestinal volvulus, three cases with intestinal adhesions, and two with intestinal perforation. Favorable outcomes were present in 75% of cases. Conclusion: GI duplications have varied presentations depending on site, size, type, local mass effect, mucosal pattern, and associated complications. The importance of clinical suspicion and radiology cannot be underrated. Early diagnosis is required to prevent postoperative complications. Management is individualized as per the type of duplication anomaly and its relation with the involved GI tract.

6.
Crit Rev Food Sci Nutr ; 62(19): 5245-5266, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33583257

RESUMO

Owing to their health-boosting properties and other appreciable properties, citrus fruit is widely consumed and commercialized worldwide. Destination markets around the world vary in their fruit quality requirements and are also highly influenced by climatic conditions, agronomical and postharvest practices. Hence, harvesting decisions are arduous. Maturity indices in citrus fruit are highly variable and dependent on the species and varieties, growing regions, and destination markets. For decades, determination of the maturity of citrus fruit and predicting the near time of harvesting was a challenge for producers, researchers, and food safety agencies. Thus, the current review provides a correlation between maturity and internal components and an overview of techniques of maturity determination for citrus fruits. Also, stress has been given to the destructive and nondestructive methods to determine the maturity level of different citrus species. The techniques presented in this review portray continuous productiveness as an excellent quality assessment, particularly as ripening and maturity analysis tools for citrus fruits. Traditional techniques are time-consuming, laborious, costly, destructive, and tedious. Thus, these nondestructive techniques hold great potential to replace conventional procedures.


Assuntos
Citrus , Frutas
7.
Neuroradiology ; 64(1): 77-93, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34128085

RESUMO

PURPOSE: To investigate ASL-MRI features of flow-diverted aneurysms, review their haemodynamic surrogates, and discuss their pertinent clinical implications. METHODS: Retrospective single institutional analysis was performed on the clinical and imaging data of patients who underwent digital subtraction angiography (DSA) and ASL-MRI after endovascular flow diversion for cerebral aneurysms. Pseudo-continuous ASL-MRI was performed with post-label delays of 1525-1800 ms. Intra-aneurysmal "trapped labelled spins" (TLS)-related hypersignal, as seen on cerebral blood flow (CBF)-weighted maps of ASL-MRI, was investigated. Intermodality equivalence with DSA [O'Kelly-Marotta (OKM) grading for occlusion], 3D-TOF-MRA, and 3D spin-echo T1-weighted ("black-blood") images was assessed. RESULTS: Ten cases were included. "TLS" signal was demonstrable in 7/8 (87.5%) of the DSA-visible flow-diverted aneurysms (OKM grade B3, n = 6; OKM grade A3, n = 2). No TLS was seen in both OKM-D (excluded) aneurysms. TLS was not visualised in an OKM-B3 aneurysm with < 3 mm opacifying remnant. 3D-TOF-MRA and ASL-MRI were discordant at 5 instances (45.4%; TOF-MRA false negative, n = 4; false positive, n = 1). Loss of flow void on black-blood images corresponded to the absence of TLS and vice versa in all cases but one. CONCLUSION: "Trapped labelled spins"-related signal on ASL-MRI occurs in patent large aneurysms that have undergone successful endovascular flow diversion. This phenomenon likely represents an interplay of a multitude of haemodynamic factors including decelerated intra-aneurysmal inflow and outflow restriction. Serial intra-saccular TLS signal changes may hold diagnostic value, including contexts where 3D-TOF-MRA interpretation becomes dubious. "Trapped labelled spins"-related signal as a non-invasive proxy marker of aneurysm patency can possibly obviate unnecessary DSA.


Assuntos
Aneurisma Intracraniano , Angiografia por Ressonância Magnética , Angiografia Digital , Angiografia Cerebral , Seguimentos , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Estudos Retrospectivos , Marcadores de Spin
8.
Indian J Med Res ; 155(3&4): 356-363, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-36124510

RESUMO

Background & objectives: Haemoptysis in children is potentially life-threatening. In most cases, the bleeding arises from the systemic circulation, and in 5-10 per cent of cases, it arises from the pulmonary circulation. The role of computed tomography angiography (CTA) in this setting is important. This study was undertaken (i) to study the role of single-phase split-bolus dual energy contrast-enhanced multidetector row CTA (DECTA) in the evaluation of haemoptysis in children; (ii) to analyze the patterns of abnormal vascular supply in the various aetiologies encountered. Methods: A retrospective study of 86 patients who underwent split bolus DECTA for the evaluation of haemoptysis was performed. Final diagnoses were categorized as normal computed tomography, active tuberculosis (TB), post-infectious sequelae, non-TB active infection, cystic fibrosis (CF), non-CF bronchiectasis, congenital heart disease (CHD), interstitial lung disease, vasculitis, pulmonary thromboembolism and idiopathic pulmonary haemosiderosis. Abnormal bronchial arteries (BAs) and non-bronchial systemic collateral arteries (NBSCs) were assessed for number and site and their correlation with underlying aetiologies. Results: A total of 86 patients (45 males, age from 0.3 to 18 yr, mean 13.88 yr) were included in the study; among these only two patients were less than five years of age. The most common cause of haemoptysis was active infection (n=30), followed by bronchiectasis (n=18), post-infectious sequelae (n=17) and CHD (n=7). One hundred and sixty five abnormal arteries were identified (108 BA and 57 NBSC), and were more marked in bronchiectasis group. Interpretation & conclusions: Active infections and bronchiectasis are the most common causes of haemoptysis in children. While post-infectious sequelae are less common, in patients with haemoptysis, the presence of any abnormal arteries correlates with a more frequent diagnosis of bronchiectasis. NBSCs are more common in post-infectious sequelae and CHD.


Assuntos
Artérias Brônquicas , Bronquiectasia , Hemoptise , Adolescente , Artérias Brônquicas/anormalidades , Artérias Brônquicas/diagnóstico por imagem , Bronquiectasia/complicações , Bronquiectasia/diagnóstico por imagem , Criança , Pré-Escolar , Angiografia por Tomografia Computadorizada/efeitos adversos , Hemoptise/etiologia , Humanos , Masculino , Estudos Retrospectivos
9.
J Neurovirol ; 27(4): 601-608, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34398444

RESUMO

The pathophysiology of the memory impairment following Herpes Simplex virus encephalitis is not yet established and understood. This study attempts to elucidate the role of white matter injury and its impact on neuropsychological outcome in patients with history of Herpes Simplex virus encephalitis. This is a single-institution prospective study assessing 9 patients and 15 matched controls utilizing a combination of MRI with diffusion tensor imaging and neuropsychological testing. Tract-based spatial statistics analysis was performed and correlated with neuropsychological outcomes. Significantly decreased fractional anisotropy (FA) values were noted in corpus callosum, corona radiata, left posterior thalamic radiation, cingulum, superior longitudinal fasciculus, fornix, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and uncinated fasciculus. Impaired facial recognition significantly correlated with reduction in FA of right uncinate fasciculus, right inferior longitudinal fasciculus, and splenium genu of corpus callosum. FA value of left cingulum significantly correlated with logical memory, auditory verbal learning. FA value of fornix correlated with visual recognition; FA value of left uncinate fasciculus with auditory verbal learning and delayed recall. In conclusion, this study demonstrates microstructural abnormalities involving several white matter tracts corresponding to neuropsychological deficits.


Assuntos
Encefalite por Herpes Simples/patologia , Transtornos da Memória/patologia , Substância Branca/patologia , Adolescente , Adulto , Idoso , Imagem de Tensor de Difusão/métodos , Encefalite por Herpes Simples/complicações , Encefalite por Herpes Simples/diagnóstico por imagem , Feminino , Humanos , Aprendizagem , Masculino , Transtornos da Memória/diagnóstico por imagem , Transtornos da Memória/virologia , Pessoa de Meia-Idade , Neuroimagem/métodos , Substância Branca/diagnóstico por imagem , Adulto Jovem
10.
Rapid Commun Mass Spectrom ; 35(19): e9161, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34240514

RESUMO

RATIONALE: Characterization of N,N'-substituted ureas was found to be challenging by nuclear magnetic resonance (NMR) spectroscopy, particularly N-di- and tri-alkylated ureas because of the absence of adjacent protons. In the present study, electrospray ionization tandem mass spectrometry has been used to differentiate positional isomeric pairs and to characterize a series of N,N'-substituted ureas, as these compounds have significant importance for drug discovery. Additionally, urea is an essential functionality in several bioactive compounds as well as a variety of clinically approved therapies. METHODS: High-resolution electrospray ionization tandem mass spectrometry (ESI-HR-MS/MS) has been used to characterize a series of N,N'-substituted urea derivatives and differentiate two pairs of positional isomers. The data was acquired by Xcaliber application in positive ionization mode. RESULTS: ESI-HR-MS/MS spectra of [M + H]+ ions of the positional isomeric urea derivatives 8a and 8b show distinct fragmentation patterns. For example, the MS/MS spectrum of the [M + H]+ ion of isomer 8a displays the abundant fragment ion at m/z 285.1595, which was totally absent in isomer 8b. This would be plausibly formed by the cleavage of the C-N bond of the urea group with the elimination of the isocyanate moiety. In contrast, the MS/MS spectrum of the [M + H]+ ion of isomer 8b shows an intense ion at m/z 311.1389 which is completely absent in isomer 8a which would be formed by the cleavage of the C-N bond attached to the ring nitrogen. Similarly, another pair of positional isomers, 8c and 8d, have been clearly distinguished by their fragmentation behaviour. In addition, a series of N,N'-substituted urea derivatives were studied to investigate the impact of different substitution on the fragmentation behaviour. CONCLUSIONS: The present study demonstrates that ESI-HR-MS/MS can be used to differentiate pairs of N,N'-substituted urea positional isomers and characterize a series of derivatives. It was observed that a characteristic fragment ion was formed by the C-N bond cleavage with the elimination of an isocyanate moiety. The proposed mechanism of fragmentation was supported by the change in the fragmentation pathway upon alkylation of the NH. In order to generalize this fragmentation pattern, a series of N-alkylated ureas was synthesized and studied by MS/MS.

11.
J Ultrasound Med ; 40(3): 621-635, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32798245

RESUMO

Renal cysts can be focal or diffuse and unilateral or bilateral. In childhood, most renal cysts are due to hereditary diseases rather than simple cysts or acquired cystic diseases, unlike adults. Inherited cystic diseases can be ciliopathies due to a primary ciliary defect (as in polycystic kidney diseases and nephronophthisis). Acquired causes include obstructive cystic dysplasia, dyselectrolytemia, and acquired cysts in renal replacement therapy. The final diagnosis requires a multispecialty approach, including radiology, pathology, and genetics. Imaging is a very important component in treating patients with cystic renal diseases. This article discusses the ultrasound findings of cystic renal diseases in children, along with a brief discussion of other imaging modalities and a suggested ultrasound reporting format.


Assuntos
Cistos , Doenças Renais Císticas , Neoplasias Renais , Rim Policístico Autossômico Recessivo , Adulto , Criança , Cistos/diagnóstico por imagem , Humanos , Doenças Renais Císticas/diagnóstico por imagem , Ultrassonografia
12.
J Food Sci Technol ; 58(11): 4442-4449, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34538928

RESUMO

The present study investigated the effect of different wine strains and inoculum size on the physicochemical, bioactive, and sensorial attributes of wine prepared from beetroot with varying TSS content (18 and 20°Brix) and inoculum sizes (5% (v/v) and 10% (v/v)). The beetroot wine produced by fermenting the must for 0-14 days and standard protocols adopted to analyze the wine properties. It was noticed that the acidity of wine increased and pH was found to be decreased as the fermentation days increased. In addition, alcohol content was significantly enhanced (> 10% by volume) in T5, which was higher than the other trials. In general, results of sensory and physicochemical analysis of different trials showed that T5 (TSS 18°Brix and inoculum size of 5% (v/v)) produced the wine of acceptable quality using Saccharomyces cerevisiae. The color properties revealed that the L* value increased as fermentation progressed. Wine prepared from T5 possessed TSS of 6.55°Brix, 3.96 pH, 0.35% titratable acidity, reducing sugar of 26.75 µg ml-1, 30.03% of DPPH free radical scavenging activity, phenol content (104.20 µg ml-1) and betalain content of 10.85 mg 100 g-1. There were significant differences in the taste, flavor, and overall acceptability of beetroot wines fermented for 14 days. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05136-y.

13.
Malays J Med Sci ; 28(1): 97-104, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33679225

RESUMO

BACKGROUND: Axillary dissection is one of the important components of modified radical mastectomy (MRM). The present study was conducted to compare surgical outcomes by using monopolar electrocautery and ultrasonic dissector for axillary dissection in MRM. METHODS: A parallel randomised controlled single blinded study was conducted with a sample size of 70 patients who were randomised into two groups. One group underwent MRM using ultrasonic dissector (Group A) and the other one using electrocautery (Group B). Intra- and post-operative outcomes were compared. RESULTS: Group A had an average operating time of 30.86 min, which was statistically less than that of Group B. The mean mop count and the daily drain output in Group A were less as compared to Group B and the differences were statistically significant. Drain was removed early in Group A as compared to Group B. However, post-operative pain scores and seroma formation were not statistically significant among the two groups. CONCLUSION: Ultrasonic dissector group had significantly lesser intra-operative bleeding, operating time and post-operative drain output when compared to electrocautery group. However, the two groups had no significant difference in post-operative pain scores and seroma formation.

14.
J Am Chem Soc ; 142(6): 3094-3103, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31927959

RESUMO

We describe the synthesis through visible-light photocatalysis of novel functionalized tetracyclic scaffolds that incorporate a fused azabicyclo[3.2.0]heptan-2-one motif, which are structurally interesting cores with potential in natural product synthesis and drug discovery. The synthetic approach involves an intramolecular [2 + 2] cycloaddition with concomitant dearomatization of the heterocycle via an energy transfer process promoted by an iridium-based photosensitizer, to build a complex molecular architecture with at least three stereogenic centers from relatively simple, achiral precursors. These fused azabicyclo[3.2.0]heptan-2-one-based tetracycles were obtained in high yield (generally >99%) and with excellent diastereoselectivity (>99:1). The late-stage derivatization of a bromine-substituted, tetracyclic indoline derivative with alkyl groups, employing a mild Negishi C-C bond forming protocol as a means of increasing structural diversity, provides additional modularity that will enable the delivery of valuable building blocks for medicinal chemistry. Density functional theory calculations were used to compute the T1-S0 free energy gap of the olefin-tethered precursors and also to predict their reactivities based on triplet state energy transfer and transition state energy feasibility.

15.
Bioorg Med Chem Lett ; 30(17): 127392, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738966

RESUMO

A novel series of cis-3,4-diphenylpyrrolidines were designed as RORγt inverse agonists based on the binding conformation of previously reported bicyclic sulfonamide 1. Preliminary synthesis and structure-activity relationship (SAR) study established (3S,4S)-3-methyl-3-(4-fluorophenyl)-4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxyprop-2-yl)phenyl)pyrrolidine as the most effective scaffold. Subsequent SAR optimization led to identification of a piperidinyl carboxamide 31, which was potent against RORγt (EC50 of 61 nM in an inverse agonist assay), selective relative to RORα, RORß, LXRα and LXRß, and stable in human and mouse liver microsomes. Furthermore, compound 31 exhibited considerably lower PXR Ymax (46%) and emerged as a promising lead. The binding mode of the diphenylpyrrolidine series was established with an X-ray co-crystal structure of 10A/RORγt.


Assuntos
Desenho de Fármacos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Pirrolidinas/química , Animais , Sítios de Ligação , Cristalografia por Raios X , Agonismo Inverso de Drogas , Humanos , Camundongos , Microssomos Hepáticos/metabolismo , Simulação de Dinâmica Molecular , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/agonistas , Receptor de Pregnano X/agonistas , Receptor de Pregnano X/metabolismo , Pirrolidinas/síntese química , Pirrolidinas/metabolismo , Relação Estrutura-Atividade
16.
J Indian Assoc Pediatr Surg ; 25(4): 248-250, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32939120

RESUMO

We, herein, present an extremely rare case of an esophageal atresia (EA) with distal tracheoesophageal fistula (TEF) with additional perforated membrane at the lower one-third of fistula. A neonate presented with difficulty in breathing and excessive frothing from the mouth. Radiograph with red rubber catheter in situ (obstruction at 10 cm from the gum margins) suggested EA with distal TEF. During thoracotomy, after ligation of fistula, a 6 Fr infant feeding tube was introduced into the distal esophagus which revealed obstruction at the lower one-third. An esophagotomy was performed; a membrane with opening at the center was identified. Following its excision, the esophageal end became dusky necessitating esophagostomy and feeding gastrostomy. A high index of suspicion for membranous obstruction at the lower one-third of fistula should be kept in mind while dealing with EA with distal TEF.

17.
J Indian Assoc Pediatr Surg ; 25(2): 76-79, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32139984

RESUMO

AIM AND OBJECTIVE: This study aimed to finding alternative ways for centers with nonavailability of ultrasonography or fluoroscopy for nonoperative pneumatic reduction of intussusceptions. MATERIALS AND METHODS: A total of 48 cases of intussusceptions were included in the study in-between October 2016 and March 2018. We tried stethoscope-guided pneumatic reduction using locally assembled equipment. The intraluminal pressure was monitored and maintained below 100 mmHg. A total of two attempts of 3 min each were allowed. We compared our results with the control group who have been performing laparotomy for every case of intussusception. RESULTS: There were 35 males and 13 females in our study. The average age of the patients was 7.5 months. Intussusceptions were reduced in 38 (80%) patients but could not be reduced in 10 (20%) patients. Majority of the intussusceptions had symptoms of at least 2 days. There were no complications such as perforation in our study. CONCLUSION: Stethoscope-guided pneumatic reduction seems to be a feasible and alternative effective method for the treatment of intussusceptions in children where availability of ultrasonography and skilled radiologist with overburden of work is a great issue.

18.
J Indian Assoc Pediatr Surg ; 25(5): 319-322, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33343116

RESUMO

Congenital pouch colon (CPC) is classified on the basis of anatomic morphology into five types. Congenital segmental intestinal dilatation associated with anorectal malformation (ARM) is very rare. We are adding two neonates of CPC type 2 associated with segmental dilatation of the ileum to single similar case described in the literature till date. Temporary stomas with excision of either of the pouches should be considered. "Defective mesenchyme formation during organogenesis" due to abnormal mesenchymal precursor cells is hypothesized as the cause for both ARM and different types of CPC.

19.
J Food Sci Technol ; 57(12): 4726-4732, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33087983

RESUMO

Bitterness and tartness are one of the crucial reasons for the poor commerciality of Pomelo fruits. The present study intends to optimize the process variables such as resin concentration (Amberlite IRA-400) (3-10 g), time exposure (10-60 s), and stirring speed (300-1000 rpm) for removal of naringin content and tartness using response surface methodology. All the independent variables have shown a significant effect on naringin content, titrable acidity, and vitamin C content of pomelo juice. The optimized process variables for debittering and deacidification were 3.27 g resin concentration, 60 s time and 1000 rpm stirring speed, and the naringin content and titrable acidity at these optimized conditions were 0.22 mg ml-1 and 0.64% citric acid equivalent respectively. The treated juice under optimum conditions was analyzed for physicochemical properties where pH, clarity, and L* value of juice increased. In contrast, total soluble solids, vitamin C content, and a* value decreased slightly. The finding of present investigation will be helpful to improve the commercial acceptability of the sour variety of citrus fruit juice.

20.
Homeopathy ; 108(1): 2-11, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30458554

RESUMO

BACKGROUND: During primary teething, children suffer from running nose, mild fever, diarrhoea and other mild irritations and inflammations. A public health programme, 'Homoeopathy for the Healthy Child', was undertaken on a pilot basis focusing on promotion of healthy teething by provision of home-based care through six pre-identified homeopathic medicines for complaints commonly observed during primary teething. This article assesses the feasibility of this programme and reports the impact of this initiative on teething profile in children and episodes of diarrhoea and upper respiratory tract infection (URTI). MATERIALS AND METHODS: Accredited Social Health Activists (ASHAs) were trained in child care and usage of a kit comprising six medicines, namely Calcarea phosphoricum 6X (CP), Ferrum phosphoricum 3X, Magnesium phosphoricum 6X, Belladonna 30C, Chamomilla 30C and Podophyllum 30C. Calcarea phosphoricum was given regularly to each participating child from 6 months to 1 year of age. Home-based care for diarrhoea, URTI and mild fever was provided by ASHAs using the other five medicines in the kit. Dentition pattern and diarrhoea/URTI episodes were recorded over a period of the next 12 months. RESULTS: Eleven thousand four-hundred and twenty-six children were followed up regularly. Amongst those who enrolled at 6-7 months, a larger proportion of children were approaching expected teething in successive months as compared with children enrolled at 12 months, thus indicating that teething delays, if any, were overcome during this period. Incidence of diarrhoea and URTI showed decrease in the months after enrolment. Children responded favourably to the medicines given by ASHAs at the time of diarrhoea/URTI episodes, and ASHAs expressed satisfaction with the programme. CONCLUSION: An approach with regular use of CP and home-based care with homeopathy through health workers for common problems in teething children is acceptable to the community and enhances outreach of services to the public at large. Observations in terms of the healthy teething period may be further validated through studies of homeopathy with suitable comparator group.


Assuntos
Saúde Pública/normas , Erupção Dentária , Diarreia/epidemiologia , Diarreia/etiologia , Homeopatia/métodos , Homeopatia/normas , Homeopatia/estatística & dados numéricos , Humanos , Índia/epidemiologia , Projetos Piloto , Saúde Pública/métodos , Saúde Pública/estatística & dados numéricos , Infecções Respiratórias/complicações , Infecções Respiratórias/epidemiologia
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