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BACKGROUND: Patients experiencing systemic patterns of disadvantage, such as racial/ethnic minorities and those with limited English proficiency, are underrepresented in research. This is particularly true for large pragmatic trials of potentially sensitive research topics, such as advance care planning (ACP). It is unclear how phone outreach may affect research participation by underrepresented individuals. OBJECTIVE: To assess the effect of phone outreach, in addition to standard mail survey recruitment, in a population-based ACP pragmatic trial at three academic health systems in California. DESIGN: Retrospective cohort study PATIENTS: Primary care patients with serious illness were mailed a survey in their preferred language. Patients who did not initially respond by mail received up to three reminder phone calls with the option of survey completion by phone. MAIN MEASURES: Effect of phone outreach on survey response rate associated with respondent demographic characteristics (e.g., Social Vulnerability Index [SVI], range 0 (low) to 1 (high)). RESULTS: Across the health systems, 5998 seriously ill patients were mailed surveys. We obtained completed surveys from 1215 patients (20% response rate); 787 (65%) responded after mail alone and 428 (35%) participated only after phone outreach. Patients recruited after phone outreach compared to mail alone were more socially vulnerable (SVI 0.41 v 0.35, P < 0.001), were more likely to report being a racial/ethnic minority (35% v 28%, P = 0.006), and non-English speaking (16% v 10%, P = 0.005). Age and gender did not differ significantly. The inclusion of phone outreach resulted in a sample that better represented the baseline population than mail alone in racial/ethnic minority (28% mail alone, 30% including phone outreach, 36% baseline population), non-English language preference (10%, 12%, 15%, respectively), and SVI (0.35, 0.37, 0.38, respectively). CONCLUSIONS: Phone outreach for a population-based survey in a pragmatic trial concerning a potentially sensitive topic significantly enhanced recruitment of underrepresented seriously ill patients.
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Planejamento Antecipado de Cuidados , Etnicidade , Humanos , Estudos Retrospectivos , Grupos Minoritários , Inquéritos e Questionários , TelefoneRESUMO
This study was designed to evaluate the effectiveness of recombinant polypeptide-p derived from Momordica charantia on diabetic rats. In this research, the optimized sequence of polypeptide-p gene fused to a secretion signal tag was cloned into the expression vector and transformed into probiotic Saccharomyces boulardii. The production of recombinant secretion protein was verified by western blotting, HPLC, and mass spectrometry. To assay recombinant yeast bioactivity in the gut, diabetic rats were orally fed wild-type and recombinant S. boulardii, in short SB and rSB, respectively, at two low and high doses as well as glibenclamide as a reference drug. In untreated diabetic and treated diabetic + SB rats (low and high doses), the blood glucose increased from 461, 481, and 455 (mg/dl), respectively, to higher than 600 mg/dl on the 21st day. Whereas glibenclamide and rSB treatments showed a significant reduction in the blood glucose level. The result of this study promised a safe plant-source supplement for diabetes through probiotic orchestration.
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Diabetes Mellitus Experimental , Probióticos , Saccharomyces boulardii , Ratos , Animais , Saccharomyces boulardii/genética , Saccharomyces cerevisiae/genética , Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Glibureto/metabolismo , Glibureto/uso terapêutico , Peptídeos/metabolismo , Proteínas Recombinantes/metabolismo , Clonagem MolecularRESUMO
BACKGROUND: Predicting the success of vaginal delivery is an important issue in preventing adverse maternal and neonatal outcomes. Thus, this study aimed to compare the success rate of vaginal birth by using trans-labial ultrasound and vaginal examination, and vaginal examination only in pregnant women with labor induction. METHODS: This was a comparative study including 392 eligible pregnant women with labor induction attending to a teaching hospital affiliated with Iran University of Medical Sciences from April to October 2018 in Tehran, Iran. Women were randomly assigned to two groups; the trans-labial ultrasound plus vaginal examination (group A), and the vaginal examination only (group B). Women were included in the study if they satisfied the following criteria: singleton pregnancy, 37 to 42 weeks of gestational age, fetal head presentation, a living fetus with no abnormalities, uncomplicated pregnancy, and no previous cesarean section or any uterine surgery. We used a partograph for both groups to assess the fetal head position and the fetal head station. In group 1, the Angle of Progression (AoP) and Rotation Angle (RA) were also assessed. Finally, the success and progression of vaginal delivery in two groups were compared by predicting the duration of delivery and mode of delivery. RESULTS: The findings showed that 8.68% of women in the trans-labial plus vaginal examination group delivered by cesarean section, while 6.13% in the vaginal examination only group delivered by cesarean section (P = 0.55). In women with cesarean section in positive fetal head stations, Angle of Progression (AoP) was significantly decreased ranging from 90 to 135 degrees compared to women who delivered vaginally (135-180 degrees; P < 0.001). In addition, the Rotation Angle (RA) was significantly decreased in women with cesarean section ranging from 0 to 30 degrees compared to women who delivered vaginally (60-90degrees; P < 0.001). Further analysis indicated that a higher risk of cesarean section was associated with vaginal examination only as compared to trans-labial ultrasound plus vaginal examination (HR: 8.65, P < 0.001). CONCLUSION: Angle of Progression (AoP) and Rotation Angle (RA) indexes might be useful parameters to predict labor progression and successful vaginal delivery among women undergoing labor induction.
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Cesárea , Gestantes , Recém-Nascido , Gravidez , Feminino , Humanos , Feto , Exame Ginecológico , Apresentação no Trabalho de Parto , Irã (Geográfico) , Trabalho de Parto InduzidoRESUMO
Background: This study aimed to compare sublingual misoprostol alone or combined with vaginal Isoniazid (INH) for first-trimester abortion. Methods: In this randomized controlled trial, 80 pregnant women with missed abortion candidates for first-trimester abortion were randomly assigned to two groups. The first group received 800 µg sublingual misoprostol every three hours maximum for three doses and the second group received 1500 mg vaginal INH followed by the same dose of misoprostol. Vaginal sonography was performed after 24 hours on both groups to observe any retained product of conception. In case of no response or incomplete abortion, the second course of misoprostol (with the same dose) was administered. The abortion (complete or incomplete) rate was reported within 48 hours after the first dose of misoprostol. Results: The rate of successful intervention (either complete or incomplete) abortion within 48 hours of misoprostol administration was 75% in both groups and was not significantly different (P value = 1). Also, hospitalization duration, abortion time, total misoprostol dosage, and the rate of side effects were similar in the two groups. Five patients in the misoprostol group and three in the misoprostol plus isoniazid group underwent emergent D&C because of heavy bleeding. Conclusion: A combined regimen of sublingual Misoprostol plus vaginal Isoniazid with the prescribed dosage has similar efficacy to sublingual misoprostol alone in first-trimester abortion.
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The present study compared the effects of Portulaca oleracea (P. oleracea) seed hydro-alcoholic extract, valsartan, and vitamin E on hemodynamic changes, oxidative stress markers and cardiac hypertrophy in a model of thyrotoxicosis. The hyperthyroid state was induced by intraperitoneal injection of levothyroxine (100 µg/kg) for 4 weeks in male adult rats. After 2 weeks, vitamin E (20 mg/kg), valsartan (8 mg/kg), and P. oleracea seed extract (400 mg/kg) were administered in three groups of thyrotoxic rats. The control group was given a daily injection of normal saline. Systolic blood pressure and heart rate were measured on three occasions with tail cuff. At the end of the fourth week, the animals were scarified and serum samples and heart tissue were collected for biochemical and histological studies. The levothyroxine increased heart rate and systolic blood pressure. A lower heart rate and reduced systolic blood pressure were observed in groups receiving valsartan and P. oleracea extract. The heart weight/body weight ratio increased in groups treated with levothyroxine, but in a microscopic study, cardiomyocyte width was not different between the groups. Levothyroxine increased the level of malondyaldehide and NO metabolite but reduced the thiol concentration, superoxide dismutase, and catalase activities. However, treatment with vitamin E and P. oleracea extract increased the thiol concentration, superoxide dismutase and catalase activities while decreasing malondyaldehide level. In addition, treatment with P. oleracea extract and valsartan decreased NO metabolite level. Treatment with P. oleracea extract improved levothyroxine induced oxidative stress and hemodynamic changes. These effects may be for antioxidant components.
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Portulaca , Animais , Pressão Sanguínea , Cardiomegalia/induzido quimicamente , Masculino , Estresse Oxidativo , Extratos Vegetais , Ratos , Valsartana , Vitamina ERESUMO
OBJECTIVES: The accurate, rapid diagnosis of stress urinary incontinence (SUI) in women can profoundly improve their sexual and psychosocial life. In this study, the diagnostic power of SUI was assessed by transperineal ultrasound. METHODS: In this hospital-based case-control study, married women who were referred to the gynecologic and ultrasound wards with negative urinalysis and culture results were enrolled by random sampling. Patients with positive cough signs based on the urodynamic testing data were considered cases, whereas control women showed no cough symptoms and were recruited from the same ward. RESULTS: There was a significant difference (P < .001) in bladder neck descent (mean ± SD, 10.89 ± 5.51 versus 7.08 ± 2.60 mm, respectively; P = .0001) and the retrovesical (ß) angle with the Valsalva maneuver (144.22° ± 19.63° versus 111.81° ± 24.47°; P < .001) between the case and control groups. Also, the ß angle without the Valsalva maneuver was higher in the case group (112.35° ± 23.10°) than the control group (120.17° ± 25.16°; P = .001). There was no case of a urinary leak, urethral diverticulitis, a bladder stone or mass, and cystourethrocele in the patients of each group. The results of multivariate logistic regression with a backward method showed that bladder neck descent (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.09-1.40), the ß angles with and without the Valsalva maneuver (OR, 1.1; 95% CI, 1.06-1.13; and OR, 1.04; 95% CI, 1.01-1.06) were the predictors of SUI. A ß angle higher than 127° with the Valsalva maneuver, with an area under the curve of 0.89 (95% CI, 0.75-0.96), could very well predict the SUI response. This finding shows that it can be very well used to distinguish between normal and non-normal responses, with 89% sensitivity and 79% specificity. CONCLUSIONS: The ß angle with the Valsalva maneuver could very well predict the SUI response.
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Incontinência Urinária por Estresse , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Ultrassonografia , Uretra/diagnóstico por imagem , Incontinência Urinária por Estresse/diagnóstico por imagem , UrodinâmicaRESUMO
A double-blind randomised trial was conducted on women with gestational age of 40-42 weeks of pregnancy and Bishop score of more than 5. The first group received oxytocin infusion and the second group received a titrated oral solution of misoprostol. Then, the two groups were compared by the primary outcome (the number of deliveries in the first 24 hours of intervention). The two groups did not have any significant difference in maternal and gestational age at the time of intervention, primary Bishop score, parity and neonatal weight. The number of deliveries in the first 24 hours was greater in the misoprostol group. Duration of onset of intervention to proper contractions was longer in the misoprostol group. However, the number of deliveries between 6-12 hours, 12-18 hours and 18-24 hours after induction was greater in the misoprostol group. The incidence of tachysystole and meconium was greater in the misoprostol group.Impact statementWhat is already known on this subject? Labour induction is widely used where the continuation of pregnancy might be dangerous for the mother or the baby. Of the various methods used for induction, misoprostol which is a prostaglandin E1 analogue has been reviewed more in recent years. Misoprostol has various routes of administration but in most studies only vaginal administration has been evaluated, leaving us with limited data about oral administration.What do the results of this study add? Oral misoprostol is a suitable method for labour induction and can be used as an alternative to oxytocin.What are the implications of these findings for clinical practice and/or further research? Misoprostol is not expensive, has a long shelf life, accessible in underdeveloped countries and rural areas and has several routes of administrations such as oral, sublingual and vaginal. Despite the fact that the oral route of misoprostol has a fast absorption and easier administration, there are relatively few studies assessing the the use of the oral route of misoprostol. Misoprostol is a suitable method for Labour induction and it has the potentials of being used as an alternative for oxytocin, however, the optimum dosages, the preferred route of administration, the maximum dose, the maximum time for administration, and maternal and neonatal safety should be studied more.
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Trabalho de Parto Induzido/métodos , Misoprostol/administração & dosagem , Ocitócicos/administração & dosagem , Ocitocina/administração & dosagem , Administração Intravenosa , Administração Oral , Adulto , Método Duplo-Cego , Feminino , Humanos , Gravidez , Nascimento a Termo , Resultado do Tratamento , Adulto JovemRESUMO
In outbred Western populations, most individuals with intellectual disability (ID) are sporadic cases, dominant de novo mutations (DNM) are frequent, and autosomal recessive ID (ARID) is very rare. Because of the high rate of parental consanguinity, which raises the risk for ARID and other recessive disorders, the prevalence of ID is significantly higher in near- and middle-east countries. Indeed, homozygosity mapping and sequencing in consanguineous families have already identified a plethora of ARID genes, but because of the design of these studies, DNMs could not be systematically assessed, and the proportion of cases that are potentially preventable by avoiding consanguineous marriages or through carrier testing is hitherto unknown. This prompted us to perform whole-exome sequencing in 100 sporadic ID patients from Iran and their healthy consanguineous parents. In 61 patients, we identified apparently causative changes in known ID genes. Of these, 44 were homozygous recessive and 17 dominant DNMs. Assuming that the DNM rate is stable, these results suggest that parental consanguinity raises the ID risk about 3.6-fold, and about 4.1 to 4.25-fold for children of first-cousin unions. These results do not rhyme with recent opinions that consanguinity-related health risks are generally small and have been "overstated" in the past.
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Genes Recessivos , Endogamia , Deficiência Intelectual/genética , Consanguinidade , Exoma/genética , Família , Feminino , Homozigoto , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/patologia , Irã (Geográfico)/epidemiologia , Masculino , Oriente Médio/epidemiologia , Mutação , Linhagem , Sequenciamento do ExomaRESUMO
This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to summarize the effect of ginger intake on weight loss, glycemic control and lipid profiles among overweight and obese subjects. We searched the following databases through November 2017: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The relevant data were extracted and assessed for quality of the studies according to the Cochrane risk of bias tool. Data were pooled using the inverse variance method and expressed as Standardized Mean Difference (SMD) with 95% Confidence Intervals (95% CI). Heterogeneity between studies was assessed by the Cochran Q statistic and I-squared tests (I2). Overall, 14 studies were included in the meta-analyses. Fourteen RCTs with 473 subjects were included in our meta-analysis. The results indicated that the supplementation with ginger significantly decreased body weight (BW) (SMD -0.66; 95% CI, -1.31, -0.01; P = 0.04), waist-to-hip ratio (WHR) (SMD -0.49; 95% CI, -0.82, -0.17; P = 0.003), hip ratio (HR) (SMD -0.42; 95% CI, -0.77, -0.08; P = 0.01), fasting glucose (SMD -0.68; 95% CI, -1.23, -0.05; P = 0.03) and insulin resistance index (HOMA-IR) (SMD -1.67; 95% CI, -2.86, -0.48; P = 0.006), and significantly increased HDL-cholesterol levels (SMD 0.40; 95% CI, 0.10, 0.70; P = 0.009). We found no detrimental effect of ginger on body mass index (BMI) (SMD -0.65; 95% CI, -1.36, 0.06; P = 0.074), insulin (SMD -0.54; 95% CI, -1.43, 0.35; P = 0.23), triglycerides (SMD -0.27; 95% CI, -0.71, 0.18; P = 0.24), total- (SMD -0.20; 95% CI, -0.58, 0.18; P = 0.30) and LDL-cholesterol (SMD -0.13; 95% CI, -0.51, 0.24; P = 0.48). Overall, the current meta-analysis demonstrated that ginger intake reduced BW, WHR, HR, fasting glucose and HOMA-IR, and increased HDL-cholesterol, but did not affect insulin, BMI, triglycerides, total- and LDL-cholesterol levels.
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Suplementos Nutricionais , Metaboloma , Obesidade/dietoterapia , Sobrepeso/dietoterapia , Redução de Peso , Zingiber officinale , Glicemia , Peso Corporal , HDL-Colesterol , LDL-Colesterol , Bases de Dados Factuais , Jejum , Zingiber officinale/química , Glucose , Homeostase , Humanos , Insulina , Resistência à Insulina , Lipídeos , Ensaios Clínicos Controlados Aleatórios como Assunto , TriglicerídeosRESUMO
Besides other benefits, curcumin is getting more recognized for its antioxidant and anti-inflammatory properties, highlighting the importance of curcumin application for chronic disease prevention. This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to assess the influence of curcumin-containing supplements on biomarkers of inflammation and oxidative stress. MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched till January 2018 for eligible studies. The selected studies were evaluated for their quality using the Cochrane risk of bias tool and relevant data were extracted from included studies. Data were pooled using the inverse variance method and expressed as standardized mean difference (SMD) with 95% confidence intervals (95% CI). Fifteen RCTs were included in the final analysis. The meta-analysis indicated that curcumin supplementation significantly decreased interleukin 6 (IL-6) (SMD -2.08; 95% CI [-3.90, -0.25]; p = 0.02), high-sensitivity C-reactive protein (hs-CRP) (SMD -0.65; 95% CI [-1.20, -0.10], p = 0.02), and malondialdehyde (MDA) concentrations (SMD -3.14; 95% CI [-4.76, -1.53], p < 0.001). Though, curcumin supplementation had no significant effect on tumor necrosis factor-alpha (SMD -1.62; 95% CI [-3.60, 0.36]; p = 0.10) and superoxide dismutase levels (SMD 0.34; 95% CI [-1.06, 1.74], p = 0.63). Overall, this meta-analysis suggests that taking curcumin-containing supplements may exert anti-inflammatory and antioxidant properties through a significant reduction in IL-6, hs-CRP, and MDA levels.
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Biomarcadores/sangue , Curcumina/farmacologia , Suplementos Nutricionais , Inflamação/dietoterapia , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Curcumina/administração & dosagem , Humanos , Inflamação/sangue , Inflamação/metabolismo , Interleucina-6/metabolismo , Malondialdeído/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Superóxido Dismutase/metabolismoRESUMO
The straightforward capture of oxidized phenothiazines with phenols under aerobic conditions represents a unique cross-dehydrogenative C-N bond-forming reaction in terms of operational simplicity. The mechanism of this cross-dehydrogenative N-arylation of phenothiazines with phenols has been the object of debate, particularly regarding the order in which the substrates are oxidized and their potentially radical or cationic nature. Understanding the selective reactivity of phenols for oxidized phenothiazines is one of the key objectives of this study. The reaction mechanism is investigated in detail by utilizing electron paramagnetic resonance spectroscopy, cyclic voltammetry, radical trap experiments, kinetic isotope effects, and solvent effects. Finally, the key reaction steps are calculated by using density functional theory (DFT) and broken-symmetry open-shell singlet DFT methods to unravel a unique biradical mechanism for the oxidative phenothiazination of phenols.
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This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to clarify the effect of melatonin supplementation on glycemic control. Databases including PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched until July 30th, 2018. Two reviewers independently assessed study eligibility, extracted data, and evaluated the risk of bias for included trials. Heterogeneity among included studies was assessed using Cochran's Q test and I-square (I2) statistic. Data were pooled using random-effect models and standardized mean difference (MD) was considered as the overall effect size. Twelve trials out of 292 selected reports were identified eligible to be included in current meta-analysis. The pooled findings indicated that melatonin supplementation significantly reduced fasting glucose (SMD=-6.34; 95% CI, -12.28, -0.40; p=0.04; I2: 65.0) and increased the quantitative insulin sensitivity check index (QUICKI) (SMD=0.01; 95% CI, 0.00, 0.02; p=0.01; I2: 0.0). However, melatonin administration did not significantly influence insulin levels (SMD=-1.03; 95% CI, -3.82, 1.77; p=0.47; I2: 0.53), homeostasis model assessment of insulin resistance (HOMA-IR) (SMD=-0.34; 95% CI, -1.25, 0.58; p=0.37; I2: 0.37) or HbA1c levels (SMD=-0.22; 95% CI, -0.47, 0.03; p=0.08; I2: 0.0). In summary, the current meta-analysis showed a promising effect of melatonin supplementation on glycemic control through reducing fasting glucose and increasing QUICKI, yet additional prospective studies are recommended, using higher supplementation doses and longer intervention period, to confirm the impact of melatonin on insulin levels, HOMA-IR and HbA1c.
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Glicemia/metabolismo , Diabetes Mellitus/tratamento farmacológico , Melatonina/administração & dosagem , Diabetes Mellitus/metabolismo , Suplementos Nutricionais/análise , Humanos , Resistência à Insulina , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
In the article, the name of the co-author was given incorrectly. The correct name of the author is Mohammad Ali Mansournia. In the abstract section the correct abbreviation of "mean difference" is MD.
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The main purpose of this study was to find effectiveness of 3D silk fibroin scaffold in comparison with co-culturing in presence of native cardiomyocytes on cardiac differentiation propensity of menstural blood(MenSCs)-versus bone marrow-derived stem-cells (BMSCs). We showed that both 3D fibroin scaffold and co-culture system supported efficient cardiomyogenic differentiation of MenSCs and BMSCs, as judged by the expression of cardiac-specific genes and proteins, Connexin-43, Connexin-40, alpha Actinin (ACTN-2), Tropomyosin1 (TPM1) and Cardiac Troponin T (TNNT2). No significant difference (except for higher expression of ACTN-2 in co-cultured MenSCs) was found between differentiation potential of the cells cultured in 3D fibroin scaffold and co-culture system. Collectively, our results imply that inductive signals served by biological factors of native cardiomyocytes to trigger cardiogenic differentiation of stem-cells may be efficiently provided by natural and biocompatible 3D fibroin scaffold suggesting the usefulness of this construct for cardiac tissue engineering.
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Células da Medula Óssea/metabolismo , Diferenciação Celular , Fibroínas/química , Menstruação , Miócitos Cardíacos/metabolismo , Células-Tronco/metabolismo , Alicerces Teciduais/química , Adulto , Animais , Antígenos de Diferenciação/biossíntese , Bombyx , Células da Medula Óssea/citologia , Células Cultivadas , Feminino , Humanos , Miócitos Cardíacos/citologia , Células-Tronco/citologia , Engenharia TecidualRESUMO
PURPOSE OF THE STUDY: There was inconsistent evidence about the benefit of vitamin D plus evening primrose oil (EPO) supplement intake on lipid profiles and reduced oxidative stress among women with polycystic ovary syndrome (PCOS). The current study was performed to evaluate the effects of vitamin D plus EPO supplementation on lipid profiles and biomarkers of oxidative stress in vitamin D-deficient women with PCOS. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled trial was performed among 60 vitamin D-deficient women with PCOS. Participants were randomly assigned into two groups to receive either 1000 IU vitamin D3 plus 1000 mg EPO (n = 30) or placebo (n = 30) for 12 weeks. Metabolic profiles were quantified at baseline and after the 12-week intervention. RESULTS: Compared with the placebo group, women in vitamin D and EPO co-supplementation group had significant increases in serum 25-hydroxyvitamin D (25(OH)D) (+10.7 ± 8.4 vs. -0.5 ± 1.6 ng/mL, p < 0.001) and plasma total glutathione (GSH) (+62.7 ± 58.0 vs. -0.7 ± 122.7 µmol/L, p = 0.01), while there were significant decreases in triglycerides (-7.3 ± 23.8 vs. +6.9 ± 26.3 mg/dL, p = 0.03), very low-density lipoprotein (VLDL) cholesterol levels (-1.5 ± 4.7 vs. +1.4 ± 5.3 mg/dL, p = 0.03), total/high-density lipoprotein cholesterol ratio (-0.3 ± 0.4 vs. -0.02 ± 0.4, p = 0.02), and malondialdehyde (MDA) concentration (-0.4 ± 0.4 vs. +0.5 ± 1.8 µmol/L, p = 0.008). CONCLUSION: Overall, vitamin D and EPO co-supplementation for 12 weeks among vitamin D-deficient women with PCOS significantly improved triglycerides, VLDL cholesterol, GSH, and MDA levels.
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Colecalciferol/farmacologia , Suplementos Nutricionais , Hipolipemiantes/farmacologia , Ácidos Linoleicos/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Estresse Oxidativo/efeitos dos fármacos , Óleos de Plantas/farmacologia , Síndrome do Ovário Policístico , Deficiência de Vitamina D , Vitamina D/análogos & derivados , Ácido gama-Linolênico/farmacologia , Adulto , Biomarcadores/sangue , Colecalciferol/administração & dosagem , HDL-Colesterol/sangue , HDL-Colesterol/efeitos dos fármacos , VLDL-Colesterol/sangue , VLDL-Colesterol/efeitos dos fármacos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Glutationa/sangue , Glutationa/efeitos dos fármacos , Humanos , Hipolipemiantes/administração & dosagem , Ácidos Linoleicos/administração & dosagem , Malondialdeído/sangue , Oenothera biennis , Óleos de Plantas/administração & dosagem , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/tratamento farmacológico , Triglicerídeos/sangue , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológico , Adulto Jovem , Ácido gama-Linolênico/administração & dosagemRESUMO
The advent of high-throughput sequencing technologies has led to an exponential increase in the identification of novel disease-causing genes in highly heterogeneous diseases. A novel frameshift mutation in CNKSR1 gene was detected by Next-Generation Sequencing (NGS) in an Iranian family with syndromic autosomal recessive intellectual disability (ARID). CNKSR1 encodes a connector enhancer of kinase suppressor of Ras 1, which acts as a scaffold component for receptor tyrosine kinase in mitogen-activated protein kinase (MAPK) cascades. CNKSR1 interacts with proteins which have already been shown to be associated with intellectual disability (ID) in the MAPK signaling pathway and promotes cell migration through RhoA-mediated c-Jun N-terminal kinase (JNK) activation. Lack of CNKSR1 transcripts and protein was observed in lymphoblastoid cells derived from affected patients using qRT-PCR and western blot analysis, respectively. Furthermore, RNAi-mediated knockdown of cnk, the CNKSR1 orthologue in Drosophila melanogaster brain, led to defects in eye and mushroom body (MB) structures. In conclusion, our findings support the possible role of CNKSR1 in brain development which can lead to cognitive impairment.
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Deficiência Intelectual/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Adulto , Animais , Encéfalo/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Família , Feminino , Genes Recessivos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Deficiência Intelectual/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Irã (Geográfico) , Sistema de Sinalização das MAP Quinases/genética , Masculino , Mutação , Linhagem , Transdução de Sinais , SíndromeRESUMO
Background: PI3K/Akt/mTOR pathway is a crucial pathway in the angiogenesis, tumour growth and cell differentiation of several cancers. The PI3K and KIT genes are key genes of this pathway. Previous studies have reported the importance of these genes in the development of gastrointestinal carcinoma, leukaemia, and melanomas. The role of mutations and overexpression of PI3K and KIT genes in breast cancer has been previously proved. This study investigates the correlation between PI3K and KIT gene mutations in sporadic breast cancer. Methods: Multiplex Ligation-dependent Probe Amplification (MLPA) technique was used to determine the Copy Number Variation (CNV) of PI3K and KIT genes in 34 breast cancer tumours and PCR-sequencing was used to detect the mutation in PI3K exons 9 and 20. Results: Our results reported that 27% of patients had CNV of the KIT gene; whereas, 20% and 17.5% of patients, had mutation and CNV in the PI3K gene, respectively. We did not found a significant correlation between the mutations of PI3K and KIT genes. Conclusion: About two-tenth of the patients revealed CNV and lesser than two-tenth indicated mutation in the PI3K gene, whereas one-third of the patients demonstrated CNV in the KIT gene. Thus, administration of the PI3K and KIT gene inhibitor drugs might be proposed to suppress breast cancer in patients with mutation and CNV of each of these individual genes.
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Regarding to critical roles of oogenesis in formation of ova or unfertilized eggs from the oogonia by mitotic division and subsequent differentiation, the identification of oogenesis-related proteins is of great interest. However, the experimental determination of proteins involved in oogenesis is expensive, time consuming and labor-intensive. Therefore, a new powerful discriminating model is indispensable for classifying oogenesis/non-oogenesis-related proteins with high accuracy and precision. Hereby, for the first time we developed a support vector machine based oogenesis protein prediction method which differentiates oogenesis from non-oogenesis proteins. By means of informative protein physicochemical properties and in addition parameter optimization scheme, our method yields a robust and consistent performance. Our model achieved 87.68% and 84.82% prediction accuracy by five-fold cross validation test for datasets with 90% and 50% identity, respectively. The prediction model was also assessed using the independent dataset and yielded 91.62% and 85.38% prediction accuracy for datasets with 90% and 50% identity, respectively, which further demonstrates the effectiveness of our method. Moreover, by applying 10 different feature weighting methods, the more important protein features for oogenesis/non-oogenesis-related proteins discrimination, including serine and glycine frequency, quasi-sequence-order, pseudo-amino acid composition, distribution and conjoint triad, were determined. The success rates revealed that our model can be considered as a new encouraging and strong model for predicting proteins involved in oogenesis with appropriate performance. To enhance the value of the practical applications of the proposed method, we developed a standalone software for predicting oogenesis candidate proteins called OOgenesis_Pred. This software is the first predictor ever established for identifying oogenesis proteins. We also showed the capability of OOgenesis_Pred by making oogenesis-related proteins prediction for some of the oogenesis candidate proteins. It is anticipated that OOgenesis_Pred will become a powerful tool for future proteomic studies related to oogenesis.
Assuntos
Proteínas de Ciclo Celular , Proteínas do Ovo , Meiose/fisiologia , Oogênese/fisiologia , Oogônios/metabolismo , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas do Ovo/genética , Proteínas do Ovo/metabolismo , Feminino , Humanos , Valor Preditivo dos Testes , Análise de Sequência de ProteínaRESUMO
INTRODUCTION: Limited data are available assessing the effects of oral carnitine supplementation on mental health parameters and biomarkers of oxidative stress of women with polycystic ovary syndrome (PCOS).This study was designed to determine the effects of oral carnitine supplementation on mental health parameters and biomarkers of oxidative stress in women with PCOS. METHODS: In the current randomized, double-blind, placebo-controlled trial, 60 patients diagnosed with PCOS were randomized to take either 250 mg carnitine supplements (n = 30) or placebo (n = 30) for 12 weeks. RESULTS: After 12 weeks' intervention, compared with the placebo, carnitine supplementation resulted in a significant improvement in Beck Depression Inventory total score (-2.7 ± 2.3 versus -0.2 ± 0.7, p < 0.001), General Health Questionnaire scores (-6.9 ± 4.9 versus -0.9 ± 1.5, p < 0.001) and Depression Anxiety and Stress Scale scores (-8.7 ± 5.9 versus -1.2 ± 2.9, p = 0.001). In addition, changes in plasma total antioxidant capacity (TAC) (+84.1 ± 151.8 versus +4.6 ± 64.5 mmol/L, p = 0.01), malondialdehyde (MDA) (-0.4 ± 1.0 versus +0.5 ± 1.5 µmol/L, p = 0.01) and MDA/TAC ratio (-0.0005 ± 0.0010 versus +0.0006 ± 0.0019, p = 0.003) in the supplemented group were significantly different from the changes in these indicators in the placebo group. CONCLUSIONS: Overall, our study demonstrated that carnitine supplementation for 12 weeks among patients with PCOS had favorable effects on parameters of mental health and biomarkers of oxidative stress.
Assuntos
Carnitina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Carnitina/farmacologia , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Estresse Oxidativo/efeitos dos fármacos , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/psicologia , Adulto JovemRESUMO
OBJECTIVE: Limited data are available for evaluating the effects of oral carnitine supplementation on weight loss and metabolic profiles of women with polycystic ovary syndrome (PCOS). This study was designed to determine the effects of oral carnitine supplementation on weight loss, and glycaemic and lipid profiles in women with PCOS. DESIGN, PATIENTS AND MEASUREMENTS: In a prospective, randomized, double-blind, placebo-controlled trial, 60 overweight patients diagnosed with PCOS were randomized to receive either 250 mg carnitine supplements (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were obtained at the beginning and the end of the study to quantify parameters of glucose homoeostasis and lipid concentrations. RESULTS: At the end of the 12 weeks, taking carnitine supplements resulted in a significant reduction in weight (-2·7 ± 1·5 vs +0·1 ± 1·8 kg, P < 0·001), BMI (-1·1 ± 0·6 vs +0·1 ± 0·7 kg/m(2) , P < 0·001), waist circumference (WC) (-2·0 ± 1·3 vs -0·3 ± 2·0 cm, P < 0·001) and hip circumference (HC) (-2·5 ± 1·5 vs -0·3 ± 1·8 cm, P < 0·001) compared with placebo. In addition, compared with placebo, carnitine administration in women with PCOS led to a significant reduction in fasting plasma glucose (-0·38 ± 0·36 vs +0·11 ± 0·97 mmol/l, P = 0·01), serum insulin levels (-14·39 ± 25·80 vs +3·01 ± 37·25 pmol/l, P = 0·04), homoeostasis model of assessment-insulin resistance (-0·61 ± 1·03 vs +0·11 ± 1·43, P = 0·04) and dehydroepiandrosterone sulphate (-3·64 ± 7·00 vs -0·59 ± 3·20 µmol/l, P = 0·03). CONCLUSIONS: Overall, 12 weeks of carnitine administration in PCOS women resulted in reductions in weight, BMI, WC and HC, and beneficial effects on glycaemic control; however, it did not affect lipid profiles or free testosterone.