Syndecans and diabetic complications: A narrative review.

Syndecan (SDC) is a member of the heparan sulfate proteoglycan (HSPG) family. It appears to play a role in the aetiology of diabetic complications, with decreased levels of SDCs being reported in the kidney, retina, and cardiac muscle in models of diabetes mellitus (DM). The reduced levels of SDCs may play an important role in the development of albuminuria in DM. Some studies have provided the evidence supporting the mechanisms underlying the role of SDCs in DM. However, SDCs and the molecular mechanisms involved are complex and need to be further elucidated. This review focuses on the underlying molecular mechanisms of SDCs that are involved in the development and progression of the complications of DM, which may help in developing new strategies to prevent and treat these complications.

Online exercise added to ergonomic advice for reducing habitual upper body postures: A randomized trial.

BACKGROUND: Online learning during the COVID-19 pandemic is associated with unfavorable habitual upper body postures. OBJECTIVE: This study explored whether adding a remedial exercise routine to an ergonomic advice intervention, delivered remotely, is helpful for reducing habitual postures of the neck, shoulders, and upper back. DESIGN: Pragmatic randomized controlled trial. METHODS: 42 male adolescent students, initially selected with a forward head posture, were randomized to one of two intervention groups: ergonomic advice alone or exercise + ergonomic advice. Outcome measures were specific postural angles of, measured by a photogrammetric profile technique using a bespoke app before and after the 8-week intervention period. RESULTS: During online learning, most students used mobile phones (76%), while 35% used a table-chair-computer arrangement. At 8-week follow-up, a statistically significant reduction of forward head, shoulder protraction, and thoracic kyphosis angles was found in both groups (P < 0.001). However, the effect was significantly greater in the exercise + ergonomic advice group (P < 0.001): forward head, shoulder protraction, and thoracic kyphosis angles reduced by some 9, 6, and 5° respectively, compared with 4° for head and 2° for shoulder and thoracic angles for the ergonomic advice alone group. CONCLUSION: The results show that, a remedial online exercise routine is a beneficial addition to an ergonomic advice program for improving unfavorable habitual upper body postures. The impact of this intervention may extend beyond postural issues related just to online learning at home.

The association of preoperative hematologic parameters with short-term clinical outcomes in rectal cancer: A feature importance analysis.

BACKGROUND: Various hematologic parameters have been proposed as prognostic factors in rectal cancer management, but data are conflicting and unclear. This study is designed to investigate the prognostic factor capability of preoperative hematologic parameters with postoperative morbidities and mortality in rectal cancer patients undergoing curative resection. METHODS: All 200 consecutive rectal cancer patients diagnosed at Ghaem University Hospital from 2017 to 2022 were retrospectively evaluated. The receiver operating characteristic (ROC) curves and machine learning (ML) algorithms of Random Forest, Recursive Feature Elimination, simulated annealing, Support Vector Machine, Decision Tree, and eXtreme Gradient Boosting were administered to investigate the role of preoperative hematologic parameters accompanied by baseline characteristics on three clinical outcomes including surgical infectious complications, recurrence, and death. RESULTS: The frequency of infectious complications was correlated with the surgical procedure, while tumor recurrence was significantly influenced by T stage and N stage. In terms of mortality, alongside T and N stage, the status of resection margin involvement was significantly correlated. Based on the ROC analysis, the NLR >2.69, MPV ≤9 fL, and PDW ≤10.5 fL were more classified patients to mortality status. Likewise, the PLT >220 109/L, MPV ≤9 fL, PDW ≤10.4 fL, and PLR >13.6 were correlated with recurrence. However, all factors examined in this study were not significant classifiers for the outcome of surgical infectious complications. The results of ML algorithms were also in line with ROC analysis. CONCLUSION: According to the results of both ROC analysis and ML models, preoperative hematologic parameters are considerable prognostic factors of postoperative outcomes in rectal cancer patients, and are recommended to be monitored by clinicians to prevent unfavorable outcomes.

Efficacy and safety of N-acetyl-L-leucine in patients with ataxia telangiectasia: A randomized, double-blind, placebo-controlled, crossover clinical trial.

BACKGROUND: Ataxia telangiectasia (AT) is an autosomal recessive multisystem disorder. Most patients have progressive cerebellar ataxia, oculocutaneous telangiectasia, frequent pulmonary infection, and an increased risk of malignancies. Although N-acetyl-dl-leucine (ADLL) has shown some efficacy in patients with AT, its more pharmacologically active enantiomer, N-acetyl-l-leucine (NALL), has just recently been investigated in ataxic individuals. The current study assessed the efficacy of NALL in patients with AT. METHODS: This 2 × 2 crossover, double-blind, randomized clinical trial was conducted on 20 patients with AT. After excluding four patients, 16 subjects (eight females, eight males; mean age 9.8 ± 3.5 years) with a definitive genetic diagnosis of AT were randomly assigned to one of two study groups, with one group receiving 1-4 g/day NALL or a placebo for six weeks. Subjects then had a 4-week washout before crossing over to the other treatment for an additional six weeks. The Spinocerebellar Ataxia Functional Index (SCAFI) and the Scale for Assessment and Rating of Ataxia (SARA) score assessed patients' motor function. Quality of life (QOL) was evaluated by a specialist using the PedsQL questionnaire. Fasting blood samples were taken from all subjects before and after each intervention to determine potential side effects. RESULTS: Although patients' nausea and constipation were improved, the results failed to reveal any significant benefits of NALL treatment on ataxia symptoms. NALL treatment had no significant effects on SARA, SCAFI-9HPT (9-hole peg test) nondominant, SCAFI-9HPT dominant, or SCAFI-8WMT (8 m walking time) (p > 0.05). Our patient's Physical Health score in Child self-report and Parent proxy-report did not significantly change in the treatment group compared to the placebo (p > 0.05). Furthermore, there were no significant changes in energy and macronutrient intake after NALL treatment. None of the volunteers reported serious or moderate side effects. CONCLUSIONS: To the best of our knowledge, this was the first placebo-controlled, randomized clinical trial exploring NALL's potential effects for treating AT. Despite improvements in some symptomss, NALL intervention failed to improve motor function significantly. However, patients' nausea and constipation were improved by NALL, which can be a relevant benefit clinically.

Predicting the 10-year incidence of dyslipidemia based on novel anthropometric indices, using data mining.

BACKGROUND: The aim was to establish a 10-year dyslipidemia incidence model, investigating novel anthropometric indices using exploratory regression and data mining. METHODS: This data mining study was conducted on people who were diagnosed with dyslipidemia in phase 2 (n = 1097) of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study, who were compared with healthy people in this phase (n = 679). The association of dyslipidemia with several novel anthropometric indices including Conicity Index (C-Index), Body Roundness Index (BRI), Visceral Adiposity Index (VAI), Lipid Accumulation Product (LAP), Abdominal Volume Index (AVI), Weight-Adjusted-Waist Index (WWI), A Body Shape Index (ABSI), Body Mass Index (BMI), Body Adiposity Index (BAI) and Body Surface Area (BSA) was evaluated. Logistic Regression (LR) and Decision Tree (DT) analysis were utilized to evaluate the association. The accuracy, sensitivity, and specificity of DT were assessed through the performance of a Receiver Operating Characteristic (ROC) curve using R software. RESULTS: A total of 1776 subjects without dyslipidemia during phase 1 were followed up in phase 2 and enrolled into the current study. The AUC of models A and B were 0.69 and 0.63 among subjects with dyslipidemia, respectively. VAI has been identified as a significant predictor of dyslipidemias (OR: 2.81, (95% CI: 2.07, 3.81)) in all models. Moreover, the DT showed that VAI followed by BMI and LAP were the most critical variables in predicting dyslipidemia incidence. CONCLUSIONS: Based on the results, model A had an acceptable performance for predicting 10 years of dyslipidemia incidence. Furthermore, the VAI, BMI, and LAP were the principal anthropometric factors for predicting dyslipidemia incidence by LR and DT models.

Female infertility and dietary antioxidant index (DAI); a case-control study.

BACKGROUND: Adequate intake of natural antioxidants may improve female fertility. The aim of this study was to examine the link between female infertility and dietary antioxidant index (DAI). METHODS: This case-control study was conducted on 125 women with recently diagnosis of reduced ovarian reserves (AMH < 1.1) as the case group and 125 women with normal ovarian reserve as the control group in Rasht, Iran. The amount of food intake was assessed using the food frequency questionnaire (FFQ) and the DAI was calculated to estimate the antioxidant capacity of the diet. RESULTS: Regarding dietary intake, the infertile women had a lower intake of potassium (2789.25 ± 777 vs. 2593.68 ± 443 mg/d, P = 0.02), magnesium (204.12 ± 66 vs. 189.73 ± 34 mg/d, P = 0.03), copper (0.93 ± 0.40 vs. 0.82 ± 0.20 mg/d, P < 0.01), vitamin C (133.99 ± 46 vs. 122.62 ± 24 mg/d, P = 0.02), and fiber (14.53 ± 3 vs. 13.44 ± 2 g/d, P < 0.05), and a higher intake of cholesterol (205.61 ± 58 vs. 227.02 ± 46 mg/d, P < 0.01) than the control group (All P < 0.05). The DAI was negatively associated with infertility (OR: 0.94, CI 95%: 0.88-0.97, P = 0.03). The association remained significant after adjustments for age, BMI, the underlying diseases, fertility frequency, IVF failure, and calorie intake. CONCLUSION: Following an antioxidant-rich diet may reduce the risk of infertility. More longitudinal studies are warranted to confirm these results and discover the underlying mechanisms.

Home schooling during the COVID-19 pandemic: A randomized controlled trial of online exercise and ergonomics advice protocols on upper body symptoms.

BACKGROUND: Understanding of students' musculoskeletal health under home-schooling during the COVID-19 pandemic is limited. OBJECTIVES: (1) To investigate the prevalence and severity of musculoskeletal symptoms in home-schooled adolescents during the COVID-19 pandemic. (2) To evaluate the effect of an online exercise + ergonomics advice protocol on symptoms, compared with ergonomics advice alone. DESIGN: Cross-sectional symptom survey identifying eligible participants, followed by a pragmatic randomized controlled trial. SETTING: Online classes. PARTICIPANTS: Survey: 354 students (mean 16.6 years). TRIAL: 188 students with upper body musculoskeletal symptoms. INTERVENTIONS: Randomization to three groups (physical therapy exercises + ergonomics postural advice, ergonomics postural advice alone, nonintervention control) stratified by the site of symptoms (neck, shoulder, upper back). Interventions were orally delivered online (via WhatsApp) supplemented with written/illustrative material. Follow-up occurred at 8 weeks. OUTCOME MEASURES: Survey: prevalence of symptoms (Nordic Questionnaire). TRIAL: primary outcome = change in intensity of upper body symptoms (visual analogue scale); secondary outcome = number of participants reporting improvement in upper body symptoms. RESULTS: The 12-month prevalence of musculoskeletal disorders in the survey was 38% neck, 28% shoulder, and 35% upper back, with mean pain intensity of 3.6, 3.9, and 3.8, respectively, on 0-10 visual analogue scale: Two-thirds reported symptoms in multiple anatomical regions. In the trial, there was no statistically significant difference between the exercise + ergonomics group and ergonomics alone group on the primary outcome, yet both groups showed reduced symptom intensity compared with control (p < .001). More participants in the exercise + ergonomics group reported improvement than in the ergonomics advice alone group (p < .02). CONCLUSIONS: The prevalence of musculoskeletal symptoms was relatively high in home-schooled adolescents. Symptoms can be reduced by ergonomics advice with or without exercises, but the effect is enhanced by the addition of physical therapy exercises. The latter approach may be considered for improving schoolchildren's musculoskeletal health in the usual classroom setting.

Curcumin's effect on serum zinc, copper and magnesium levels in obese individuals.

Objective: The obesity prevalence is growing worldwide. There is strong evidence indicating that a disturbance of zinc, copper and magnesium concentrations is associated with the development of obesity and its related diseases. Our aim was to determine the effect of curcumin supplementation on serum zinc, magnesium and copper in obese individuals. Materials and Methods: In this randomized crossover trial study, thirty obese patients with an age range of 18 to 65 years were randomized to treatment with curcumin 1 g/day or placebo for 30 days. There was then a two-week wash-out period, after which, subjects crossed to the alternate regimen. Serum levels of zinc, copper and magnesium were determined at baseline and at the end of the study. Results: The study groups were similar to each other in base line characteristics. We did not observe significant impacts (p>0.05) of curcumin on Cu, Zn, Mg serum concentrations. Conclusion: Curcumin administration at a dose of 1 g/day for 30 days did not affect serum Cu, Zn, Mg levels in obese subjects.

Association between dietary copper and cardiovascular disease: A narrative review.

Cardiovascular disease (CVD) is a major cause of mortality and morbidity. Several studies have investigated the relationship between trace element status, including copper status, and CVDs in population studies; however, there are controversies about the role of dietary copper and CVD. We aimed to review the association between dietary copper intake with CVD and this association's related factors by reviewing both animal models and human studies. Some animal model studies have reported a strong relationship between dietary copper intake and atherogenesis based on the possible molecular pathways, whilst other studies have not confirmed this relationship. Human studies have not revealed a relationship between CVDs and dietary copper intake, but there is uncertainty about the optimal amount of dietary copper intake in relation reducing the risk of CVDs. These associations may be influenced by ethnicity, gender, underlying co-morbidities and the methods used for its measurement.

Association between the rs2241883 polymorphism of the fatty acid-binding protein-1 (FABP1) gene and obesity in a population of MASHAD study cohort.

BACKGROUND AND AIMS: The fatty acid-binding proteins (FABPs) gene polymorphisms are related to several metabolic properties. We investigated the association of SNPs rs2241883 of FABP 1 gene with obesity to evaluate the role of FABP1 gene in the pathogenesis of obesity in the population of MASHAD study cohort. METHODS: In this cross-sectional study, 2731 individuals (1883 Obese and 848 nonobese) aged 35 to 65 years old, were enrolled from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study cohort. DNA Quantitation was determined using the NanoDrop®-1000 instrument (NanoDrop-Technologies). The rs2241883 polymorphisms were genotyped by double ARMs PCR (double amplification refractory mutation system) reactions. Data analysis was carried out using SPSS 22 and a p < 0.05 was set for statistical significance. RESULTS: The results showed that after adjusting for confounding factors, subjects having the CC genotype for rs2241883 polymorphism were at a higher risk of BMI ≥ 30 mg/kg2 with OR of 1.79 (CI = 1.05-3.07; p = 0.03) and 1.76 (CI = 1.04-2.99; p = 0.04) comparing with reference group using codominant and dominant models, respectively. CONCLUSION: The results showed that CC genotype for rs2241883 polymorphism is related to an increased risk of the obesity in dominant and codominant models in a population of MASHAD study cohort.

The national health program for vitamin D supplementation in a developing country.

BACKGROUND: Previous studies have reported a high frequency of vitamin D deficiency (VDD) among different age groups in Iran. AIMS: In this study, the current coverage, status of vitamin D supplement taking, and program efficacy have been evaluated by the Office of Nutrition Department Society in Iran since 2014. METHODS: This study was conducted in collaboration with the International UNESCO center for Health-Related Basic Sciences and Human Nutrition and the Office of Nutrition Department Society. Sixty three medical universities were included in the current study to calculate the availability, accessibility and acceptability coverages. Furthermore, 3 medical universities including Mashhad (MUMS), Qom (QUMS) and Zahedan (ZAUMS) University of Medical Sciences were selected based on the results of the National Integrated Micronutrient Survey 2012 (NIMS-II study), in order to assess the status of vitamin D supplement intake in all age ranges. RESULTS: Quantitative analysis showed that availability coverage was 74.96% and 77.56% and accessibility was 80.70% and 83.26% in elderly and middle-aged subjects, respectively in 2018. The acceptability was approximately 43.7% and 43.9% among elderly and middle-aged participants, respectively. The availability and acceptability coverage was 80.99% and 85.0% among students in high schools. The mean vitamin D supplement uptake frequency was 27.0% (n = 387); 20.7% and 29.2% in rural and urban area, respectively (P = 0.001). The results showed that there was no significant difference in serum vitamin D levels between urban (20.41 ± 6.43 ng/ml) and rural areas, (P = 0.887). There was no significant difference in the serum vitamin D concentrations between men and women (P = 0.461). CONCLUSIONS: The frequency of taking vitamin D supplements was 27.0% in Iran in 2018. The frequency of taking of vitamin D supplements among vitamin D deficient group (serum vitamin D levels <19.99 ng/ml) was 43.6%. Lack of knowledge was the most important reason for not taking vitamin D supplement. Moreover, the serum vitamin D levels have increased in subjects aged 18-30 years old after the implementation of the vitamin D supplementary program.

Data mining approaches for type 2 diabetes mellitus prediction using anthropometric measurements.

BACKGROUND: The aim of this study was to evaluate the anthropometric measurements most associated with type 2 diabetes mellitus (T2DM) using machine learning approaches. METHODS: A prospective study was designed for a total population of 9354 (43% men and 57% women) aged 35-65. Anthropometric measurements include weight, height, demispan, Hip Circumference (HC), Mid-arm Circumference (MAC), Waist Circumference (WC), Body Roundness Index (BRI), Body Adiposity Index (BAI), A Body Shape Index (ABSI), Body Mass Index (BMI), Waist-to-height Ratio (WHtR), and Waist-to-hip Ratio (WHR) were completed for all participants. The association was assessed using logistic regression (LR) and decision tree (DT) analysis. Receiver operating characteristic (ROC) curve was performed to evaluate the DT's accuracy, sensitivity, and specificity using R software. RESULTS: Traditionally, 1461 women and 875 men with T2DM (T2DM group). According to the LR, in males, WC and BIA (p-value < 0.001) and in females, demispan and WC (p-value < 0.001) had the highest correlation with T2DM development risk. The DT indicated that WC has the most crucial effect on T2DM development risk, followed by HC, and BAI. CONCLUSIONS: Our results showed that in both men and women, WC was the most important anthropometric factor to predict T2DM.

Investigating the inflammatory status in the patients candidate for second angiography after coronary stent implantation.

BACKGROUND: Inflammation has been shown to be an important feature of atherosclerosis. We aimed to assess a profile of inflammatory cytokines and growth factors in patients with established coronary artery disease (CAD), 12 months after stent implantation. METHODS: A total of 193 patients with CAD, who were candidates for angiography, 12 months after stent implantation (cases), were compared with 107 patients with CAD, who were candidates for their first angiography (controls). Fasting blood glucose (FBG), triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and high-sensitive C-reactive protein (hs-CRP) were measured using routine methods. The serum concentrations of IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, MCP-1, EGF and VEGF were determined using competitive chemiluminescence immunoassays. RESULTS: Serum levels of FBG (p = .002), TG (p = .029) and hs-CRP (p = .005) were significantly lower in cases than controls. The cytokines and growth factor profiles in cases were significantly different from controls. After multivariate analysis, serum levels of IL-2 (p < .001), IL-4 (p = .028) were significantly lower in cases compared with the controls while serum levels of IL-8, TNF-α, MCP-1, EGF and VEGF were significantly higher in the cases (p < .001). CONCLUSIONS: In patients with CAD and higher consumption of drug used (statins, aspirin and glucose lowering agents) to mitigate the risk of a secondary event, the level of hs-CRP one year after stent implantation decreased despite of significant higher serum levels of pro- and anti-inflammatory cytokines and growth factors.

The Effects of N-Acetyl-L-Leucine on the Improvement of Symptoms in a Patient with Multiple Sulfatase Deficiency.

Multiple Sulfatase Deficiency (MSD) is a rare autosomal recessive disease with specific clinical findings such as psychomotor retardation and neurological deterioration. No therapy is available for this genetic disorder. Previous studies have shown that N-acetyl-L-leucine (NALL) can improve the neurological inflammation in the cerebellum.In the current study, the effects of NALL on ataxia symptoms and quality of life were explored in a patient with MSD.This study was a crossover case study. The subject, a girl aged 12 years old, received NALL at a dose of 3 g/day (1 g in the morning, 1 g in the afternoon, and 1 g in the evening). A fasting blood sample was taken from the subject to evaluate side effects before the intervention and 4 weeks after taking supplement/placebo in every study stage. The ataxia moving symptoms were evaluated using the Scale for the Assessment and Rating of Ataxia (SARA) score in every study stage. Dietary intake was measured using 24-h dietary recall before and after the intervention. The diet compositions were assessed by Nutritionist IV software. Serum IL-6 level was measured using an ELISA kit.There was no significant change in complete blood count (CBC) and serum biochemical factors in the patient with MSD after receiving NALL (3 g/day) over 4 weeks. The SARA score was reduced by 25%. The gait whose maximum score accounts for approximately one-fifth of the maximum total SARA score (8/40) was decreased. The heel-to-shin slide, the only SARA item performed without visual control, was also improved after therapy. Furthermore, there was a downward trend in the 8MWT (8.71 to 7.93 s). Regarding quality of life assessments, the parent and child reported improved quality of life index, physical health, and emotional function after taking NALL. Moreover, total energy intake was increased with NALL treatment through the study period.Supplementation with NALL at a dose of 3 g/day over 4 weeks was well tolerated and improved ataxia symptoms, quality of life measure, and serum IL-6 levels in the patient with MSD. Further proof-of-concept trials are warranted to confirm the present findings.

The Effect of N-Acetyl-DL-Leucine on Neurological Symptoms in a Patient with Ataxia-Telangiectasia: a Case Study.

Ataxia-telangiectasia (AT) is a rare autosomal recessive disorder with no available curative treatment. Although the positive effects of N-acetyl-DL-leucine on cerebellar ataxia have been reported previously, there is little evidence of N-acetyl-DL-leucine's effects in patients with AT. This study assessed the effect of 16 weeks N-acetyl-DL-leucine supplementation on ataxia symptoms in a 9-year-old female with AT. The subject consumed 4 g/day N-acetyl-DL-leucine (2 g in the morning and 2 g in the evening) for 16 weeks. Safety was assessed via clinical blood chemistry prior to the intervention and after 6 and 16 weeks. Additionally, The Scale for the Assessment and Rating of Ataxia (SARA) score was used to assess the drug's effects on ataxia symptoms at baseline, 6, 12, and 16 weeks. Quality of life has also been evaluated by a specialist using the PedsQL questionnaire.Despite some initial (first week only) nausea and constipation, supplementation with N-acetyl-DL-leucine was well tolerated and safe according to blood chemistry measures. The SARA score progressively improved, and by week 16 had improved by 11.0 points (48.88%). Parent and self-reported quality of life assessments indicated physical, emotional, social, and school functions all improved by 16 weeks. Supplementation with N-acetyl-DL-leucine at a dose of 4 g/day for 16 weeks was well tolerated and significantly improved ataxia symptoms and quality of life measures in a young child with AT.

Associação do Genótipo e Fenótipo da Paraoxonase-1 com Angiografia Positiva para Doença Arterial Coronariana / Association of Paraoxonase-1 Genotype and Phenotype with Angiogram Positive Coronary Artery Disease

Resumo Fundamento Tem sido demonstrado que um aumento dos níveis séricos de PON1 é protetor contra vários distúrbios. Foi relatado que vários polimorfismos de nucleotídeo único (SNPs, single nucleotide polymorphisms ) do gene PON1 estão associados a níveis e atividade de proteínas enzimáticas séricas. Objetivos Investigar a associação de SNPs do PON1 e atividade da paraoxonase sérica com a doença arterial coronariana (DAC). Métodos Foram estudados 601 pacientes não relacionados submetidos à angiografia coronária, incluindo aqueles com estenose >50% (N=266) e aqueles com estenose <30% (N=335). Os SNPs rs662 e rs840560 do gene da paraoxonase foram determinados utilizando o método ARMS-PCR e o SNP rs705379 foi genotipado utilizando análise de PCR-RFLP. A atividade da paraoxonase sérica foi medida utilizando paraoxon como substrato. O valor de p<0,05 foi considerado significante. Resultados A atividade da paraoxonase sérica não foi significativamente diferente entre os grupos de estudo. Após ajuste para idade, sexo, hipertensão, diabetes mellitus e dislipidemia, o genótipo GG e o modelo codominante de rs662 foram positivamente associados a uma angiografia positiva (respectivamente, OR = 2,424, IC 95% [1,123-5,233], p <0,05, OR = 1,663, IC 95% [1,086-2,547]). A atividade da paraoxonase sérica foi significativamente maior no alelo G e variante GG do polimorfismo rs662, alelo A e variante AA de rs854560 e alelo C e variante CC de rs705379. A análise de haplótipos mostrou que o haplótipo ATC foi significativamente mais prevalente no grupo com angiografia negativa. A análise entre os grupos indicou que o alelo A de rs662 foi significativamente associado à menor atividade da paraoxonase no grupo com angiografia positiva (p=0,019). Conclusões A presença do alelo G do polimorfismo de nucleotídeo único rs662 está independentemente associada ao aumento do risco de DAC.

Abstract Background It has been shown that increased serum PON1 levels are protective against several disorders. Several single nucleotide polymorphisms (SNPs) of the PON1 gene have been reported to be associated with serum enzyme protein levels and activity. Objective To investigate the association of SNPs of PON1 and serum paraoxonase activity with coronary artery disease (CAD). Methods A total of 601 unrelated patients who underwent coronary angiography including those who had >50% stenosis (N=266) and those with <30% stenosis (N=335) were studied. The Paraoxonase gene rs662 and rs840560 SNPs were determined using the ARMS-PCR method and the rs705379 SNP was genotyped using PCR-RFLP analysis. Serum paraoxonase activity was measured using paraoxon as a substrate. A p value of p<0.05 was considered as significant. Results Serum paraoxonase activity was not significantly different between the study groups. After adjustment for age, sex, hypertension, diabetes mellitus and dyslipidemia, the GG genotype and co-dominant model of rs662 was positively associated with a positive angiogram (respectively, OR=2.424, 95%CI [1.123-5.233], p<0.05, OR=1.663, 95%CI [1.086-2.547]). Serum paraoxonase activity was significantly higher in the G allele and GG variant of rs662, A allele and AA variant of rs854560 and C allele and CC variant of rs705379. The haplotype analysis has shown that the ATC haplotype was significantly more prevalent among the angiogram negative group. The analysis between groups indicated that the A allele of rs662 was significantly associated with lower paraoxonase activity in the positive angiogram group (p=0.019). Conclusions The presence of the G allele of the rs662 single nucleotide polymorphism is independently associated to increased risk of CAD.

Association of Paraoxonase-1 Genotype and Phenotype with Angiogram Positive Coronary Artery Disease. / Associação do Genótipo e Fenótipo da Paraoxonase-1 com Angiografia Positiva para Doença Arterial Coronariana.

BACKGROUND: It has been shown that increased serum PON1 levels are protective against several disorders. Several single nucleotide polymorphisms (SNPs) of the PON1 gene have been reported to be associated with serum enzyme protein levels and activity. OBJECTIVE: To investigate the association of SNPs of PON1 and serum paraoxonase activity with coronary artery disease (CAD). METHODS: A total of 601 unrelated patients who underwent coronary angiography including those who had >50% stenosis (N=266) and those with <30% stenosis (N=335) were studied. The Paraoxonase gene rs662 and rs840560 SNPs were determined using the ARMS-PCR method and the rs705379 SNP was genotyped using PCR-RFLP analysis. Serum paraoxonase activity was measured using paraoxon as a substrate. A p value of p<0.05 was considered as significant. RESULTS: Serum paraoxonase activity was not significantly different between the study groups. After adjustment for age, sex, hypertension, diabetes mellitus and dyslipidemia, the GG genotype and co-dominant model of rs662 was positively associated with a positive angiogram (respectively, OR=2.424, 95%CI [1.123-5.233], p<0.05, OR=1.663, 95%CI [1.086-2.547]). Serum paraoxonase activity was significantly higher in the G allele and GG variant of rs662, A allele and AA variant of rs854560 and C allele and CC variant of rs705379. The haplotype analysis has shown that the ATC haplotype was significantly more prevalent among the angiogram negative group. The analysis between groups indicated that the A allele of rs662 was significantly associated with lower paraoxonase activity in the positive angiogram group (p=0.019). CONCLUSIONS: The presence of the G allele of the rs662 single nucleotide polymorphism is independently associated to increased risk of CAD.

FUNDAMENTO: Tem sido demonstrado que um aumento dos níveis séricos de PON1 é protetor contra vários distúrbios. Foi relatado que vários polimorfismos de nucleotídeo único (SNPs, single nucleotide polymorphisms ) do gene PON1 estão associados a níveis e atividade de proteínas enzimáticas séricas. OBJETIVOS: Investigar a associação de SNPs do PON1 e atividade da paraoxonase sérica com a doença arterial coronariana (DAC). MÉTODOS: Foram estudados 601 pacientes não relacionados submetidos à angiografia coronária, incluindo aqueles com estenose >50% (N=266) e aqueles com estenose <30% (N=335). Os SNPs rs662 e rs840560 do gene da paraoxonase foram determinados utilizando o método ARMS-PCR e o SNP rs705379 foi genotipado utilizando análise de PCR-RFLP. A atividade da paraoxonase sérica foi medida utilizando paraoxon como substrato. O valor de p<0,05 foi considerado significante. RESULTADOS: A atividade da paraoxonase sérica não foi significativamente diferente entre os grupos de estudo. Após ajuste para idade, sexo, hipertensão, diabetes mellitus e dislipidemia, o genótipo GG e o modelo codominante de rs662 foram positivamente associados a uma angiografia positiva (respectivamente, OR = 2,424, IC 95% [1,123-5,233], p <0,05, OR = 1,663, IC 95% [1,086-2,547]). A atividade da paraoxonase sérica foi significativamente maior no alelo G e variante GG do polimorfismo rs662, alelo A e variante AA de rs854560 e alelo C e variante CC de rs705379. A análise de haplótipos mostrou que o haplótipo ATC foi significativamente mais prevalente no grupo com angiografia negativa. A análise entre os grupos indicou que o alelo A de rs662 foi significativamente associado à menor atividade da paraoxonase no grupo com angiografia positiva (p=0,019). CONCLUSÕES: A presença do alelo G do polimorfismo de nucleotídeo único rs662 está independentemente associada ao aumento do risco de DAC.

Therapeutic effects of statins on osteoarthritis: A review.

Osteoarthritis (OA) is a progressive joint disease. The etiology of OA is considered to be multifactorial. Currently, there is no definitive treatment for OA, and the existing treatments are not very effective. Hypercholesterolemia is considered a novel risk factor for the development of OA. Statins act as a competitive inhibitor of the ß-hydroxy ß-methylglutaryl-CoA (HMG-CoA) reductase and are widely used to manage hypercholesterolemia. Inhibition of HMG-CoA reductase results in reduced synthesis of a metabolite named mevalonate, thereby reducing cholesterol biosynthesis in subsequent steps. By this mechanism, statins such as atorvastatin and simvastatin could potentially have a preventive impact on joint cartilage experiencing osteoarthritic deterioration by reducing serum cholesterol levels. Atorvastatin can protect cartilage degradation following interleukin-1ß-stimulation. Atorvastatin stimulates the STAT1-caspase-3 signaling pathway that was shown to be responsible for its anti-inflammatory effects on the knee joint. Simvastatin had chondroprotective effects on OA in vitro by reducing matrix metalloproteinases expression patterns. In this study, we tried to review the therapeutic effects of statins on OA.

The positive short-term effect of dexamethasone on ataxia symptoms in a patient with ataxia-telangiectasia: A case report.

Oral dexamethasone was administered at a dose of 0.075 mg/kg/day for a boy with ataxia-telangiectasia. The SARA score was improved by 7.0 points after dexamethasone treatment over a period of 28 days. The body weight was increased by 1.4 kg after 4 weeks leading to dose titration to 0.05 mg/kg/day.

Age and sex-specific reference intervals for prooxidant-antioxidant balance, anti-heat-shock protein 27 (anti-hsp27), and routine laboratory tests in the middle-aged adult population.

INTRODUCTION: We aimed to define specific reference intervals (RIs) for 11 biomarkers including inflammatory and oxidative stress biomarkers, liver, and renal function tests in a healthy Iranian adult population for the first time. METHODS: CLSI Ep28-A3 guidelines were then used to calculate accurate age- and sex- as well as body mass index (BMI)-specific RIs. RESULTS: RIs for studied biomarkers showed no significant age and sex-specific differences, except for uric acid, which had higher concentrations in men when compared to women. Additionally, after partitioning the participants based on the BMI with a cutoff point of 25 kg/m2 , only the levels of hs-CRP were positively associated with higher BMI (RI for BMI>25: 0.51-7.85 mg/L and for BMI<25: 0.40-4.46 mg/L). RI for PAB and anti-hsp-27 were reported 4.69-155.36 HK and 0.01-0.70 OD in men and women aged 35-65 years old. CONCLUSION: Partitioning by sex and BMI was only required for uric acid and hs-CRP, respectively, while other biomarkers required no partitioning. These results can be expected to valuably contribute to improve laboratory test result interpretation in adults for improved monitoring of various diseases in the Iranian population.