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Adverse drug reactions (ADRs) are a significant public health concern and a leading cause of hospitalization; they are estimated to be the fourth leading cause of death and increasing healthcare costs worldwide. Carrying a genetic variant could alter the efficacy and increase the risk of ADRs associated with a drug in a target population for commonly prescribed drugs. The use of pre-emptive pharmacogenetic/omic (PGx) testing can improve drug therapeutic efficacy, safety, and compliance by guiding the selection of drugs and/or dosages. In the present narrative review, we examined the current evidence of pre-emptive PGx testing-based treatment for the prevention of ADRs incidence and hospitalization or emergency department visits due to serious ADRs, thus improving patient safety. We then shared our perspective on the importance of preemptive PGx testing in clinical practice for the safe use of medicines and decreasing healthcare costs.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Testes Farmacogenômicos , Humanos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Hospitalização , Custos de Cuidados de Saúde , FarmacogenéticaRESUMO
AIM: To investigate whether the Vesical Imaging-Reporting and Data System (VI-RADS) could be used to develop a new non-invasive preoperative grade-prediction system to partially predict high-grade bladder cancer (HG-BC). MATERIALS AND METHODS: The present study enrolled 89 primary BC patients prospectively from March 2022 to June 2023. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of VI-RADS for predicting HG-BC and muscle-invasive bladder cancer (MIBC) in the entire group. In the low VI-RADS (≤2) group, the decision tree-based method was used to obtain significant predictors and construct the decision-tree model (DT model). The performance of the DT model and low VI-RADS scores for predicting HG-BC was determined using ROC, calibration, and decision curve analyses. RESULTS: At a cut-off of ≥3, the specificity and positive predictive value of VI-RADS for predicting HG-BC in the entire group was 100%, and the area under the ROC curve (AUC) was 0.697. Among 65 patients with low VI-RADS scores, the DT model showed an AUC of 0.884 in predicting HG-BC compared to 0.506 for low VI-RADS scores. Calibration and decision curve analyses showed that the DT model performed better than the low VI-RADS scores. CONCLUSION: Most VI-RADS scores ≥3 correspond to HG-BCs. VI-RADS could be used as a grouping imaging biomarker for a pathological grade-prediction procedure, which in combination with the DT model for low VI-RADS (≤2) populations, would provide a potential preoperative non-invasive method of predicting HG-BC.
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Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Biomarcadores , Árvores de Decisões , Imageamento por Ressonância Magnética/métodos , Estudos RetrospectivosRESUMO
In dietary risk assessment of plant protection products, residues of active ingredients and their metabolites need to be evaluated for their genotoxic potential. The European Food Safety Authority recommend a tiered approach focussing assessment and testing on classes of similar chemicals. To characterise similarity, in terms of metabolism, a metabolic similarity profiling scheme has been developed from an analysis of 69 α-chloroacetamide herbicides for which either Ames, chromosomal aberration or micronucleus test results are publicly available. A set of structural space alerts were defined, each linked to a key metabolic transformation present in the α-chloroacetamide metabolic space. The structural space alerts were combined with covalent chemistry profiling to develop categories suitable for chemical prioritisation via read-across. The method is a robust and reproducible approach to such read-across predictions, with the potential to reduce unnecessary testing. The key challenge in the approach was identified as being the need for metabolism data individual groups of plant protection products as the basis for the development of the structural space alerts.
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Acetamidas , Herbicidas , Testes de Mutagenicidade , Acetamidas/toxicidade , Acetamidas/química , Medição de Risco , Herbicidas/toxicidade , Herbicidas/química , Resíduos de Praguicidas/toxicidade , Humanos , Mutagênicos/toxicidade , Mutagênicos/química , AnimaisRESUMO
OBJECTIVES: The primary objective of the study was to assess the factors that influenced the increased failure rate among first-year Indian medical students who appeared for the Maharashtra University of Health Science (MUHS) summative university examination, having experienced the competency-based medical education (CBME) curriculum for the first time amid the coronavirus disease (COVID-19) pandemic. METHODS: A retrospective cross-sectional online questionnaire-based study was undertaken between July 2021 and November 2021, in which first-year Indian medical students who were enrolled in the Bachelor of Medicine, Bachelor of Surgery (MBBS) program in the year 2019 and appeared for the MUHS summative university examination in February 2021 were invited to participate. Analysis was done using JASP (v0.16.0.0), and the odds ratio for failure was calculated at a significance level of P < 0.05. RESULTS: Responses were obtained from 360 individuals, of whom 74.5% had passed and 25.5% had failed (n = 360). The odds of failure in first-year MBBS summative university examination was higher in students with irregular Internet access, irregular device access, an unsupportive peer environment in college, a National Entrance cum Eligibility Test score below 500, an unsupportive family environment during the lockdown, severe stress, severe depression, testing positive for COVID-19 before the exam, death in the family during the exam, and failing in terms and prelims and students of male gender ( P < 0.01). CONCLUSION: The total failure rate of 27% in the MUHS examination was mainly attributed to interplay between the student's mental health, lack of devices or Internet, and the changed assessment part of the CBME curriculum. Surprisingly, lecture frequencies, teaching patterns, and study resources did not influence the failure rate. These results can be used to formulate interventions that will help to improve academic performance and mental health students and thus help them adapt to the new curriculum.
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COVID-19 , Educação Baseada em Competências , Currículo , Educação de Graduação em Medicina , SARS-CoV-2 , Estudantes de Medicina , Humanos , COVID-19/epidemiologia , Estudantes de Medicina/psicologia , Estudos Transversais , Masculino , Índia/epidemiologia , Feminino , Estudos Retrospectivos , Educação de Graduação em Medicina/métodos , Educação Baseada em Competências/métodos , Fracasso Acadêmico , Pandemias , Adulto Jovem , Inquéritos e Questionários , Adulto , Avaliação Educacional/métodosRESUMO
1. A study was conducted to assess the possibility of totally replacing supplemental phosphorus sources in White Leghorn (WL) layer diets (aged 28 to 45 weeks of age) with microbial phytase supplementation. One thousand commercial layers (HyLine White) of 28 weeks of age were housed in California cages fitted in open-sided poultry shed at the rate of 20 layers in each replicate. Ten replicates were randomly allotted to each treatment, and the respective diet was fed from 28 to 45 weeks of age.2. A control diet (CD) containing the recommended levels of non-phytate phosphorus (3.6 g/kg NPP) and four other test diets (2-5) having sub-optimal levels of NPP (2.4, 2.0, 1.6 and 1.2 g/kg), but with supplemental microbial phytase (600 FTU/kg) were prepared and fed for the trial duration.3. The layers fed with lower levels of NPP with phytase had the same laying performance as the group fed the CD. Egg production, feed efficiency, egg mass, shell defects, egg density, shell weight, shell thickness, ash content and breaking strength of the tibia and sternum were not affected by feeding the lowest concentration of NPP (1.2 g/kg) plus microbial phytase.4. Phytase supplementation in diets with sub-optimal levels of NPP (2.4, 2 and 1.6 g/kg) significantly improved the Haugh unit score compared to those fed the CD.5. It was concluded that supplemental phosphorus can be completely replaced with microbial phytase (600 FTU/kg) in a diet without affecting egg production, shell quality or bone mineral variables in WL layers (28 to 45 weeks).
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6-Fitase , Ração Animal , Galinhas , Dieta , Suplementos Nutricionais , 6-Fitase/administração & dosagem , 6-Fitase/metabolismo , Animais , Galinhas/fisiologia , Galinhas/crescimento & desenvolvimento , Ração Animal/análise , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Fósforo na Dieta/metabolismo , Distribuição Aleatória , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Fósforo/metabolismo , Relação Dose-Resposta a Droga , BrancosRESUMO
This study reveals the possibility of distinct ablation mechanisms at different radial positions of the ablated track on GaAs when ablated with femtosecond pulses in distilled water. From the center to the edges of the ablated track, fascinating features such as micron-sized cones, nano-pores, and nano-ripple trenches (average size of 60-70â nm) were observed. The requirement for simulations incorporating the variations in a Gaussian beam fluence and dynamics of the melt flow/surrounding media is discussed. Deep-subwavelength structures, i.e., nano-ripple trenches with a ripple size of â¼λ/11 are achieved on the GaAs surface in this study. Further, these GaAs surface structures acted as excellent hybrid surface-enhanced Raman spectroscopy platforms upon gold coating.
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In order to guarantee the desired quality of machined products, a reliable surface roughness assessment is essential. Using a surface profile metre with a contact stylus, which can produce accurate measurements of surface profiles, is the most popular technique for determining the surface roughness of machined items. One of the limitations of this technique is the work piece surface degradation brought on by mechanical contact between the stylus and the surface. Hence, in this paper, a roughness assessment technique based on the suggested Taylor-Gorilla troops optimizer-based Deep Neuro-Fuzzy Network (Taylor-GTO based DNFN) is proposed for estimating the surface roughness. Pre-processing, data augmentation, feature extraction, feature fusion, and roughness estimation are the procedures that the suggested technique uses to complete the roughness estimate procedure. Roughness estimation is performed using DNFN that has been trained using Taylor-GTO, which was created by combining the Taylor series with the Gorilla troop's optimizer. The created Taylor-GTO based DNFN model has minimum Mean Absolute Error, Mean Square Error, and RMSE of 0.403, 0.416, and 1.149, respectively.
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Aprendizado Profundo , Gorilla gorilla , Animais , Propriedades de SuperfícieRESUMO
AIM: To explore the value of quantitative image features of gadoxetic acid-enhanced magnetic resonance imaging (MRI) for predicting Gglypican-3 (GPC3) expression of single hepatocellular carcinoma (HCC) ≤3 cm. MATERIALS AND METHODS: One hundred and forty-nine patients with histopathologically confirmed HCC were included retrospectively. Quantitative image features and clinicopathological parameters were analysed. The significant predictors for GPC3 expression were identified using multivariate logistic regression analyses. Nomograms were constructed from the prediction model and the progression-free survival (PFS) rate was evaluated by the Kaplan-Meier method. RESULTS: The tumour-to-liver signal intensity (SI) ratio on the hepatobiliary phase (HBP; odds ratio [OR] = 0.004; p=0.001), serum alpha-fetoprotein (AFP) > 20 ng/ml (OR=6.175; p<0.001), and non-smooth tumour margin (OR=4.866; p=0.002) were independent significant factors for GPC3 expression. When the three factors were combined, the diagnostic specificity was 97.7% (42/43). The nomogram based on the predictive model performed satisfactorily (C-index: 0.852). Kaplan-Meier curves showed that patients with GPC3-positive HCCs have lower PFS rates than patients with GPC3-negative HCCs (Log-rank test, p=0.006). CONCLUSION: The tumour-to-liver SI ratio on the HBP combined with serum AFP >20 ng/ml and non-smooth tumour margin are potential predictive factors for GPC3 expression of small HCC ≤3cm. GPC3 expression is correlated with a poor prognosis in HCC patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas/análise , Glipicanas , Estudos Retrospectivos , Gadolínio DTPA , Imageamento por Ressonância Magnética/métodos , Meios de ContrasteRESUMO
In dietary risk assessment of plant protection products, residues of active ingredients and their metabolites need to be evaluated for their genotoxic potential. The European Food Safety Authority recommend a tiered approach focussing assessment and testing on classes of similar chemicals. To characterise similarity, in terms of metabolism, a metabolic similarity profiling scheme has been developed from an analysis of 46 chemicals of strobilurin fungicides and their metabolites for which either Ames, chromosomal aberration or micronucleus test results are publicly available. This profiling scheme consists of a set of ten sub-structures, each linked to a key metabolic transformation present in the strobilurin metabolic space. This metabolic similarity profiling scheme was combined with covalent chemistry profiling and physico-chemistry properties to develop chemical categories suitable for chemical prioritisation via read-across. The method is a robust and reproducible approach to such read-across predictions, with the potential to reduce unnecessary testing. The key challenge in the approach was identified as being the need for metabolism data and individual groups of plant protection products as the basis for the development of such profiling schemes.
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AIM: We introduced routine probiotic supplementation (RPS) of preterm infants in June 2012. We previously reported that RPS reduced the incidence of necrotising enterocolitis (NEC) and mortality in such infants. In this study, we assessed if the benefits of RPS were sustained for infants in the current era. METHOD: We compared the outcomes of preterm infants in recent epoch 3 (RPS, 1st June 2014 to 31st December 2019) versus epoch 2 (RPS, 1st June 2012 to 31st May 2014) and epoch 1 (no RPS, 1st December 2008 to 30th November 2010). Multiple logistic and Cox regression models were used to compare the outcomes. RESULTS: There were 645 infants in epoch 1, 712 in epoch 2 and 1715 in epoch 3. Age at full feeds was significantly lower in epoch 3 vs. 2 and epoch 3 vs. 1 in infants <28 weeks of gestation. NEC and late-onset sepsis (LOS) were significantly lower in epoch 3 vs. 1 in infants <28 weeks. LOS and age at full feeds were significantly lower in epoch 3 vs. 2 and epoch 3 vs. 1 in infants with gestation 28 to 32 weeks. CONCLUSION: The benefits associated with RPS were sustained during epoch 3.
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Enterocolite Necrosante , Doenças do Prematuro , Probióticos , Sepse , Lactente , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Probióticos/uso terapêutico , Incidência , Doenças do Prematuro/epidemiologia , Enterocolite Necrosante/epidemiologia , Enterocolite Necrosante/prevenção & controle , Recém-Nascido de muito Baixo PesoRESUMO
Exposure to a prototypic air pollutant ozone (O3) has been associated with the activation of neuroendocrine stress response along with neural changes in oxidative stress (OS), inflammation, and Alzheimer's disease-like pathologies in susceptible animal models. We hypothesized that neural oxidative and transcriptional changes induced by O3 in stress responsive regions are sex-dependent. Male and female adult Long-Evans rats were exposed to filtered air or O3 for two consecutive days (0.8 ppm, 4 h/day) and brain regions were flash-frozen. Activities of cerebellar OS parameters and mitochondrial complex I, II, and IV enzymes were assessed to confirm prior findings. We assessed transcriptional changes in hypothalamus (HYP) and hippocampus (HIP) for markers of OS, microglial activity and glucocorticoid signaling using qPCR. Although there were no O3 or sex-related differences in the cerebellar activities of OS and mitochondrial enzymes, the levels of protein carbonyls and complex II activities were higher in females regardless of O3. There were no statistical differences in baseline expression of genes related to OS (Cat, Dhcr24, Foxm1, Gpx1, Gss, Nfe2l2, Sod1) except for lower HYP Sod1 expression in air-exposed females than males, and higher HIP Gss expression in O3-exposed females relative to matched males. Microglial marker Aif1 expression was higher in O3-exposed females relative to males; O3 inhibited Itgam only in males. The expression of Bdnf in HIP and HYP was inhibited by O3 in both sexes. Genes related to glucocorticoid signaling (Fkbp4, Fkbp5, Hsp90aa1, Hspa4, nr3c1, nr3c2) showed sex-specific effects due to O3 exposure. Baseline expression of HIP Fkbp4 was higher in females relative to males. O3 inhibited Nr3c1 in female HIP and male HYP, but Nr3c2 was inhibited in male HYP. Fkbp4 expression was higher in O3-exposed females when compared to matched males, whereas Fkbp5 was expressed at higher levels in both brain regions of males and females. These results indicate that sex-specific brain region responses to O3 might, in part, be caused by OS and regulation of glucocorticoid signaling.
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Ozônio , Ratos , Masculino , Feminino , Animais , Ozônio/toxicidade , Glucocorticoides/farmacologia , Superóxido Dismutase-1 , Ratos Long-Evans , Estresse Oxidativo , Hipocampo , HipotálamoRESUMO
1. An experiment was conducted with White Leghorn layers (Babcock BV 300) to optimise the feed withdrawal schedule for egg-laying hens (67 to 80 weeks) reared in open-sided poultry houses during the tropical summer season.2. Four feeding schedules (1. ad libitum access to the layer feed, 2. feed withdrawal from 9 AM-5 PM, 3. 11 AM-5 PM, and 4. 1 PM-5 PM followed by free access to the layer feed) were examined. Each feeding schedule was offered to 12 replicates consisting of 12 layers housed in four adjacent cages (45.7 × 35.6 × 43.2 cm).3. Fasting the layers from 1-5 pm reduced egg production compared to layers fasting from 9 or 11 am. The FI/egg or unit egg mass was highest in layers fasted from 1-5 pm. In the 9 am-5 pm fasted group, the cloacal temperature (CT) increased significantly at 11 am and gradually reduced at 3 pm. In the 1-5 pm fasted group, the CT remained higher at 3 pm and 5 pm.4. The cell-mediated immune response in layers fasted from 9 am or 11 am was higher than those fed ad libitum or 1-5 pm fasted group. Lipid peroxidation was higher in layers 1-5 pm fasted group, and significantly lower LP was found in groups that fasted from 9 am or 11 am. In general, the activities of serum antioxidant enzymes (glutathione peroxidase, glutathione reductase, superoxide dismutase) were higher in layers that fasted from 9 am or 11 am compared to those that had ad libitum feed or fasted from 1-5 pm.5. It was concluded that the feed withdrawal should be initiated during the forenoon (9 AM/11 am-5 pm) for optimum production and to reduce oxidative stress in egg-laying hens reared during summer in the tropical region.
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Antioxidantes , Galinhas , Animais , Feminino , Galinhas/fisiologia , Dieta/veterinária , Estações do Ano , Aves Domésticas , Ração Animal/análise , Oviposição , OvosRESUMO
1. The study was carried out to determine the effects of supplementing organic (OG) or inorganic (IOG) Se to record the performance, immune and anti-oxidant response in broiler chickens.2. One-day-old Vencobb-400 (50.1 ± 0.84 g; n = 280) male broiler chicks were allocated randomly into seven treatments to give eight replicates containing five chicks each and housed in deep littered floor pens (76 cm × 91 cm) for a period of 42 d.3. The control diet (CD) was formulated without any Se supplementation (diet I), CD plus 0.15, 0.30 or 0.45 mg/kg OG Se (diets II, III and IV, respectively) and CD plus 0.15, 0.30 or 0.45 mg/kg IOG Se (diets V, VI and VII, respectively).4. Feed intake (FI), body weight gain (BWG), immune variables and mRNA expression profile of hepatic selenoproteins (SepW, GSHPx1, TrxR and GSHPx3) genes were determined. The BWG, FI and feed conversion ratio did not differ among various dietary treatments.5. The lipid peroxidation and activity of RBC catalase were lower (P < 0.05) in groups fed diets supplemented OG Se compared to those fed IOG Se and CD. The activity of GSH Px was higher among the groups fed diet supplemented OG Se compared to those groups fed OG Se and CD. However, supplementing diets with OG or IOG Se did not affect humoral or cell mediated immune responses.6. The expression levels of SepW were higher (P < 0.01) among the groups supplemented with OG Se. Expression levels of GSH-Px1, TrxR and GSHPx3 were higher (P < 0.01) among the groups supplemented with OG Se compared to those groups fed IOG Se or CD.7. Supplementing OG Se improved the activities of anti-oxidant enzymes and hepatic expression of selenoproteins genes in the present study. However, supplementing OG or IOG Se did not affect growth performance and immune variables in broiler chickens.
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Antioxidantes , Galinhas , Masculino , Animais , Suplementos Nutricionais , Ingestão de AlimentosRESUMO
1. A study was conducted to assess the impact of supplementing-graded concentrations of emulsifier on the production performance, gut microbial count, and digestibility of nitrogen and energy in broiler chicken fed diets without AGP.2. Male broiler chicks (n = 1500; Vencobb-430), aged one-day-old, were randomly allocated into six dietary groups each with 10 replicates of 25 birds each. A maize-soybean and meat and bone meal-based basal diet without antibiotic (AGP) growth promoter served as negative control (NC). The basal diet was supplemented with BMD (AGP, bacitracin methylene disalicylate-BMD 100 g/T), which served as the positive control (PC). Emulsifier was added to the NC diets at either 250 g/ton in all phases (250-All), 250 g in starter and grower phases, and 500 g in the finisher phase (250:250:500), 250 g in starter and 500 g in both grower and finisher phases (250:500:500) and 500 g in all phases (500 g-All).3. Two broilers per replicate were slaughtered to record carcase traits and gut microbial count on day 43. There was significant improvement in body weight gain (BWG) and reduced FCR in broilers fed 250:250:500 and 250:500:500 g emulsifiers compared to other treatment groups. Carcase traits and faecal microbial count did not differ among treatments. The inclusion of BMD significantly improved nitrogen (N) digestibility compared to the NC group. The digestibility of emulsifier-supplemented groups was similar to those fed by the BMD group except for the 500-All group, which was an intermediary between NC and other emulsifier-fed groups.4. It was concluded that supplementation with emulsifier (250:250:500 or 250:500:500) without antibiotic growth promoter significantly improved FCR and body weight gain similar to broilers receiving antibiotic growth promoter, which was associated with increased ileal digestibility of N and energy.
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Antibacterianos , Galinhas , Animais , Masculino , Antibacterianos/farmacologia , Dieta/veterinária , Suplementos Nutricionais , Nutrientes , Nitrogênio/farmacologia , Peso Corporal , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , DigestãoRESUMO
Objectives: To analyze the influence of vitamin D supplementation on clinical efficacy and drug retention rate of vedolizumab (VDZ) in patients with ulcerative colitis (UC). Methods: Retrospective study. By retrieving the clinical database of the Second Affiliated Hospital of Wenzhou Medical University, the patients with moderately to severely active UC were collected, who underwent VDZ treatment from January 2020 to June 2022. The modified Mayo score and Mayo endoscopic score (MES) were employed to evaluate disease activity and intestinal inflammation in UC patients, respectively. According to whether vitamin D was supplemented during VDZ treatment, the patients were divided into supplementary group and non-supplementary group. According to baseline serum 25(OH) D level, UC patients were divided into vitamin D deficiency group and non-deficiency group. According to whether vitamin D was supplemented, the patients of each group were divided into supplementary subgroup and non-supplementary subgroup, respectively. The clinical response rate, clinical remission rate and mucosal healing rate at week 30 after receiving VDZ treatment and the retention rate of VDZ at the 72nd week were observed. The effect of baseline serum 25 (OH) D level on the efficacy of vitamin D supplementation was analyzed by chi-square test. The effects of vitamin D supplementation on the clinical efficacy and drug retention of VDZ in UC were analyzed by chi-square test and Kaplan-Meier curve, respectively. Results: A total of 80 patients with moderately to severely active UC, who were aged (39.4±13.0) years(18-75 years), 37 male and 43 female, were included. There were 43 cases in supplementary group and 37 cases in non-supplementary group. There were 59 cases in the deficiency group, including 32 cases in the supplementary subgroup and 27 cases in the non-supplementary subgroup. There were 21 cases in the non-deficiency group, including 11 cases in the supplementary subgroup and 10 cases in the non-supplementary subgroup. At week 30, the average level of serum 25(OH) D was shown to be higher in supplementary group than that at week 0 [(24.5±5.4) vs (17.7±6.7) µg/L, P<0.001]. At week 30, in contrast with non-supplementary group, erythrocyte sedimentation rate(ESR)[75.0% (24.3%, 86.7%) vs 32.7% (-2.6%, 59.3%), P=0.005] and modified Mayo score [(4.7±2.8) vs (2.3±2.7) points, P<0.001] and MES score [(1.2±1.1) vs (0.4±0.9) points, P=0.001] were significantly reduced, clinical response rate [79.1%(34/43) vs 56.8%(21/37), P=0.032], clinical remission rate [67.4%(29/43) vs 29.7%(11/37), P=0.001] and mucosal healing rate [72.1%(31/43) vs 37.8%(14/37), P=0.002] were higher. At week 72, drug retention rate of VDZ was shown to be higher in supplementary group than in non-supplementary group [55.8%(24/43) vs 27.0%(10/37), P=0.004]. The further analysis showed that vitamin D supplementation could only improve clinical response rate[71.9%(23/32) vs 44.4%(12/27), P=0.033], clinical remission rate[62.5%(20/32) vs 14.8%(4/27), P<0.001], mucosal healing rate[68.8%(22/32) vs 22.2%(6/27), P<0.001] and drug retention rate [53.1%(17/32) vs 13.8%(4/27), P=0.001] in the patients with vitamin D deficiency. Conclusion: Vitamin D supplementation contributes to improving clinical response rate, clinical remission rate, mucosal healing rate and drug retention rate of VDZ in UC patients.
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Colite Ulcerativa , Humanos , Feminino , Masculino , Colite Ulcerativa/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Vitaminas , Vitamina D/uso terapêutico , Suplementos NutricionaisRESUMO
The study focuses on identifying and screening natural products (NPs) based on their structural similarities with chemical drugs followed by their possible use in first-line treatment to COVID-19 infection. In the present study, the in-house natural product libraries, consisting of 26,311 structures, were screened against potential targets of SARS-CoV-2 based on their structural similarities with the prescribed chemical drugs. The comparison was based on molecular properties, 2 and 3-dimensional structural similarities, activity cliffs, and core fragments of NPs with chemical drugs. The screened NPs were evaluated for their therapeutic effects based on their predicted in-silico pharmacokinetic and pharmacodynamics properties, binding interactions with the appropriate targets, and structural stability of the bound complex using molecular dynamics simulations. The study yielded NPs with significant structural similarities to synthetic drugs currently used to treat COVID-19 infections. The study proposes the probable biological action of the selected NPs as Anti-retroviral protease inhibitors, RNA-dependent RNA polymerase inhibitors, and viral entry inhibitors.
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Produtos Biológicos , Tratamento Farmacológico da COVID-19 , Antivirais/farmacologia , Produtos Biológicos/farmacologia , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , SARS-CoV-2RESUMO
Psychosocially-stressed individuals might have exacerbated responses to air pollution exposure. Acute ozone exposure activates the neuroendocrine stress response leading to systemic metabolic and lung inflammatory changes. We hypothesized chronic mild stress (CS) and/or social isolation (SI) would cause neuroendocrine, inflammatory, and metabolic phenotypes that would be exacerbated by an acute ozone exposure. Male 5-week-old Wistar-Kyoto rats were randomly assigned into 3 groups: no stress (NS) (pair-housed, regular-handling); SI (single-housed, minimal-handling); CS (single-housed, subjected to mild unpredicted-randomized stressors [restraint-1 h, tilted cage-1 h, shaking-1 h, intermittent noise-6 h, and predator odor-1 h], 1-stressor/day*5-days/week*8-weeks. All animals then 13-week-old were subsequently exposed to filtered-air or ozone (0.8-ppm) for 4 h and immediately necropsied. CS, but not SI animals had increased adrenal weights. However, relative to NS, both CS and SI had lower circulating luteinizing hormone, prolactin, and follicle-stimulating hormone regardless of exposure (SI > CS), and only CS demonstrated lower thyroid-stimulating hormone levels. SI caused more severe systemic inflammation than CS, as evidenced by higher circulating cytokines and cholesterol. Ozone exposure increased urine corticosterone and catecholamine metabolites with no significant stressor effect. Ozone-induced lung injury, and increases in lavage-fluid neutrophils and IL-6, were exacerbated by SI. Ozone severely lowered circulating thyroid-stimulating hormone, prolactin, and luteinizing hormone in all groups and exacerbated systemic inflammation in SI. Ozone-induced increases in serum glucose, leptin, and triglycerides were consistent across stressors; however, increases in cholesterol were exacerbated by SI. Collectively, psychosocial stressors, especially SI, affected the neuroendocrine system and induced adverse metabolic and inflammatory effects that were exacerbated by ozone exposure.
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Absorbers for long-wavelength infrared (LWIR) are designed to have a reduced geometry fitted to a gold cross antenna and numerically studied. Compared to the square membrane geometry widely used in conventional microbolometers, the reduced geometry results in smaller thermal capacities of the vanadium dioxide (VO2) and silicon nitride (Si3N4) layers. However, near-field focusing by the cross antenna leads to a high LWIR absorption. Calculations show that the temperature change per incident energy increases with a decrease in the arm width, and the reduced absorber surpasses the square geometry for all incident angles and polarizations. The antenna-based reduced absorber studied here could serve as an alternative geometry for high-performance microbolometers.
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We herein present a case of live related kidney transplant recipient who initially developed severe coronavirus (COVID-19) disease associated with E.coli related pyelonephritis and graft dysfunction, who improved over one week only to deteriorate in the second week, with fever, oligoanuria and refractory shock. A postmortem allograft biopsy revealed angioinvasive mucormycosis. With the resurgence of mucormycosis during the COVID-19 pandemic, the transplant team should add allograft mucormycosis as a rare differential for severe graft dysfunction and oligoanuria in the COVID-19-infected kidney transplant recipient.
Assuntos
COVID-19 , Transplante de Rim , Mucormicose , Pielonefrite , Aloenxertos , COVID-19/complicações , Humanos , Transplante de Rim/efeitos adversos , Mucormicose/complicações , Mucormicose/tratamento farmacológico , Mucormicose/microbiologia , Pandemias , Pielonefrite/complicaçõesRESUMO
AIM: To determine whether the tumour volume measurement on preoperative contrast-enhanced computed tomography (CT) could be used to predict the overall survival patients with large hepatocellular carcinoma (>5 cm) after resection. MATERIALS AND METHODS: This study included 171 patients with surgically confirmed hepatocellular carcinoma who underwent preoperative CT. The largest diameter, the product of the axial dimension, tumour volume, and tumour-to-liver volume ratio (TTLVR) on CT images were measured and calculated. The univariate and multivariate Cox proportional hazard ratio regression models were used to identify the impact of the tumour burden-related risk factors on overall survival. RESULTS: In multivariate analysis, TTLVR (p=0.042) and major vascular invasion (p=0.006) were independently associated with overall survival of patients with hepatocellular carcinoma after the resection. The group in which the patients had a low TTLVR showed higher cumulative survival rates than patients with a TTLVR (p=0.004). Patients with a low TTLVR (≤26.23%) and absence of major vascular invasion had significantly higher cumulative survival rates compared to those patients with hepatocellular carcinoma with either or both the risk factors (p=0.001). CONCLUSION: A higher TTLVR in combination with the presence of major vascular invasion was associated with poorer overall survival in patients with large hepatocellular carcinoma after resection.