Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications.

Vascular endothelial cells (ECs) play a central role in the pathophysiology of many diseases. The use of targeted nanoparticles (NPs) to deliver therapeutics to ECs could dramatically improve efficacy by providing elevated and sustained intracellular drug levels. However, achieving sufficient levels of NP targeting in human settings remains elusive. Here, we overcome this barrier by engineering a monobody adapter that presents antibodies on the NP surface in a manner that fully preserves their antigen-binding function. This system improves targeting efficacy in cultured ECs under flow by >1000-fold over conventional antibody immobilization using amine coupling and enables robust delivery of NPs to the ECs of human kidneys undergoing ex vivo perfusion, a clinical setting used for organ transplant. Our monobody adapter also enables a simple plug-and-play capacity that facilitates the evaluation of a diverse array of targeted NPs. This technology has the potential to simplify and possibly accelerate both the development and clinical translation of EC-targeted nanomedicines.

Oral health behaviours and oral health-related dietary behaviours: The interrelationship and determinants by latent class analysis.

OBJECTIVE: This study aimed to investigate the level of oral health behaviours (OHB) and oral health-related dietary behaviours (OHD-B) and to find out their relationship and their determinants among a relatively large sample of university students. Research design and participants: In a cross-sectional study, 535 Iranian university students were selected in order to investigate their OHB and OHD-B through a self-administrated questionnaire. MAIN OUTCOME MEASURES: Tooth brushing, flossing, use of fluoride toothpaste, and sugary snacking collected data on OHB. Consumption frequency of 16 common cariogenic and non-cariogenic foodstuffs was used for evaluation of OHD-B. Latent class analysis (LCA) and latent class regression (LCR) were applied to identify classes of OHB and OHD-B and their potential determinants, respectively. ANOVA, Chi-square and Spearman's correlation were used. RESULTS: In total, 49.7% and 53.2% of participants had good OHB and OHD-B, respectively. The results of LCR indicated that female gender (OR: 8.22, 95% CI: 3.42-19.72), higher age (OR: 1.39, 95% CI: 1.04-1.85), doctorate level (OR: 6.99, 95% CI: 2.22-21.98), and being single (OR: 3.54, 95% CI: 1.36-9.19) were related to good OHB. Furthermore, LCR analysis showed that students who lived with their families had greater chance for having good OHD-B (OR: 3.01, 95% CI: 2.00-4.53). Students with good OHD-B reported brushing and flossing their teeth more frequently than those with poor OHD-B (P⟨0.05). CONCLUSIONS: The shortage of favourable oral health behaviours among university students highlights the importance of planning oral health programs to improve their oral health, especially their dietary behaviours.

Higher dietary diversity score is associated with obesity: a case-control study.

OBJECTIVE: The present study was carried out to compare dietary diversity score (DDS) among overweight, obese, and normal-weight adults. STUDY DESIGN: This case-control study was conducted with a total of 200 cases (100 participants with obesity and 100 participants with overweight) and 300 controls (normal weight) matched by socio-economic status (SES), older than 18 years. METHODS: Dietary intakes were assessed using a self-administered Food Frequency Questionnaire. Data regarding physical activity and sociodemographic variables were gathered. DDS was computed based on the scoring of the five food groups emphasized in the United States Department of Agriculture Food Guide Pyramid. Anthropometric measurements were measured, and the body mass index and waist-to-hip ratio were calculated. RESULTS: The mean ± standard deviation of DDS was higher in participants with obesity (5.65 ± 1.32) than that in overweight participants (5.23 ± 1.23), while the lowest score was reported among normal-weight individuals (4.97 ± 1.42) (P < 0.001). The odds of obesity increased with each unit increase in DDS (odds ratio [OR]: 1.46; 95% confidence interval [CI]: 1.22, 1.74). However, the association became slightly weaker after adjusting for potential confounding factors (OR: 1.34; 95% CI: 1.07, 1.68). CONCLUSION: It was concluded that there was a significant positive association between DDS and obesity. However, additional investigations are warranted.

Dietary glycaemic index and glycaemic load and upper gastrointestinal disorders: results from the SEPAHAN study.

BACKGROUND: Little is known about the effects of carbohydrate, particularly any association between dietary glycaemic index or glycaemic load and uninvestigated heartburn or uninvestigated chronic dyspepsia in the community. The present study aimed to determine associations between dietary glycaemic index or glycaemic load and uninvestigated heartburn or uninvestigated chronic dyspepsia. METHODS: This cross-sectional study was conducted in 2987 adults. Dietary glycaemic index and glycaemic load were estimated using a validated food-frequency questionnaire. Uninvestigated heartburn and uninvestigated chronic dyspepsia were determined using a modified and validated version of the Rome III questionnaire. RESULTS: After controlling for various confounders, high glycaemic load was associated with an increased risk of uninvestigated heartburn [odds ration (OR) = 1.75; 95% confidence interval CI = 1.03, 2.97; P = 0.04] and uninvestigated chronic dyspepsia (OR = 2.14; 95% CI: 1.04, 4.37; P = 0.04) in men but not in women. In normal-weight individuals, high glycaemic index was related to an increased risk of uninvestigated heartburn (OR = 1.52; 95% CI: 1.07, 2.15; P = 0.02) and high glycaemic load to an increased risk of uninvestigated chronic dyspepsia (OR=1.78; 95% CI: 1.05, 3.01; P = 0.03). No significant associations were observed in subjects with excess body weight. CONCLUSIONS: Our data suggest that there are body mass index- and sex-specific associations between dietary carbohydrate quality with uninvestigated heartburn and uninvestigated chronic dyspepsia.

Defining the human copper proteome and analysis of its expression variation in cancers.

Copper (Cu) is essential for living organisms, and acts as a cofactor in many metabolic enzymes. To avoid the toxicity of free Cu, organisms have specific transport systems that 'chaperone' the metal to targets. Cancer progression is associated with increased cellular Cu concentrations, whereby proliferative immortality, angiogenesis and metastasis are cancer hallmarks with defined requirements for Cu. The aim of this study is to gather all known Cu-binding proteins and reveal their putative involvement in cancers using the available database resources of RNA transcript levels. Using the database along with manual curation, we identified a total of 54 Cu-binding proteins (named the human Cu proteome). Next, we retrieved RNA expression levels in cancer versus normal tissues from the TCGA database for the human Cu proteome in 18 cancer types, and noted an intricate pattern of up- and downregulation of the genes in different cancers. Hierarchical clustering in combination with bioinformatics and functional genomics analyses allowed for the prediction of cancer-related Cu-binding proteins; these were specifically inspected for the breast cancer data. Finally, for the Cu chaperone ATOX1, which is the only Cu-binding protein proposed to have transcription factor activities, we validated its predicted over-expression in patient breast cancer tissue at the protein level. This collection of Cu-binding proteins, with RNA expression patterns in different cancers, will serve as an excellent resource for mechanistic-molecular studies of Cu-dependent processes in cancer.

Evaluation of Self-Perceived Changes in Gastrointestinal Symptoms During Ramadan Fasting.

Little is known regarding the effects of Ramadan fasting on common gastrointestinal symptoms. The aim of this study was to assess the alterations of these symptoms in a healthy Iranian adult population during Ramadan. In a cross-sectional study, self-administered questionnaires were used to evaluate the alterations in seven groups of gastrointestinal symptoms (esophageal symptoms, dyspeptic symptoms, bloating and abdominal distension, constipation, diarrhea, abdominal pain, and nausea) after Ramadan. A total of 900 individuals participated in the study. Almost 87 % of participants reported to fast for at least 2 weeks during Ramadan. After adjusting for potential confounders, we found no relationship between alteration in frequency of gastrointestinal symptoms and Ramadan fasting, except for constipation which increased significantly after Ramadan fasting (odds ratio 1.99, 95 % confidence interval 1.05-3.80, P < 0.05). In addition, those who fasted for at least 2 weeks reported to experience severe or very severe constipation-related symptoms three times more in comparison with those who fasted for less than 2 weeks (P < 0.05). There was no relationship between severity of other gastrointestinal symptoms and Ramadan fasting. We found that Ramadan fasting does not increase frequency and severity of common gastrointestinal symptoms in the general population except for constipation that may be experienced more frequently and severely among those who fast for 2 weeks or more.

Efficacy and safety of oral insulin compared to subcutaneous insulin: a systematic review and meta-analysis.

INTRODUCTION: A systematic review and meta-analysis of interventional studies was conducted to compare the efficacy and safety of oral insulin versus subcutaneous (SC) insulin in diabetic patients. METHODS: Medline, Scopus, ISI Web of Knowledge and Cochrane Central Register of Controlled Trials were searched. Two independent reviewers evaluated studies for eligibility and quality and extracted the data. The primary outcomes were fasting blood glucose (FBG), 1h and 2h postprandial blood glucose, HbA1c, AUC of insulin, C max and T max of insulin, and T max of glucose infusion rate. Secondary outcomes were adverse events. RESULTS: Eleven studies (n = 373) met the inclusion criteria. Meta-analyses showed that there is no significant difference between oral and SC insulin in controlling HbA1c, FBG, 1 and 2 h postprandial blood glucose and producing C max of insulin (P > 0.05); however oral insulin had faster action as indicated by the shorter T max, compared to SC insulin (P < 0.05). The most included studies were varied in their methodological quality. CONCLUSION: This systematic review and meta-analysis showed that oral insulin is comparable to SC insulin with regard to glycemic efficacy and safety. However, is necessary to conduct additional studies in which oral insulin administered to large number of patients for long enough periods of time.

Total, dietary, and supplemental calcium intake and mortality from all-causes, cardiovascular disease, and cancer: A meta-analysis of observational studies.

AIMS: This systematic review and meta-analysis of observational studies was conducted to summarize the evidence on the association between calcium intake and mortality. METHODS AND RESULTS: PubMed, Institute for Scientific Information (ISI) (Web of Science), SCOPUS, SciRUS, Google Scholar, and Excerpta Medica dataBASE (EMBASE) were searched to identify related articles published through May 2014. We found 22 articles that assessed the association between total, dietary, and supplementary intake with mortality from all-causes, cardiovascular disease (CVD), and cancer. Findings from this meta-analysis revealed no significant association between total and dietary calcium intake and mortality from all-causes, CVD, and cancer. Subgroup analysis by the duration of follow-up revealed a significant positive association between total calcium intake and CVD mortality for cohort studies with a mean follow-up duration of >10 years (relative risk (RR): 1.35; 95% confidence interval (CI): 1.09-1.68). A significant inverse association was seen between dietary calcium intake and all-cause (RR: 0.84; 95% CI: 0.70-1.00) and CVD mortality (RR: 0.88; 95% CI: 0.78-0.99) for studies with a mean follow-up duration of ≤10 years. Although supplemental calcium intake was not associated with CVD (RR: 0.95; 95% CI: 0.82-1.10) and cancer mortality (RR: 1.22; 95% CI: 0.81-1.84), it was inversely associated with the risk of all-cause mortality (RR: 0.91; 95% CI: 0.88-0.94). CONCLUSIONS: We found a significant relationship between the total calcium intake and an increased risk of CVD mortality for studies with a long follow-up time and a significant protective association between dietary calcium intake and all-cause and CVD mortality for studies with a mean follow-up of ≤10 years. Supplemental calcium intake was associated with a decreased risk of all-cause mortality.

Frequency of bacteria causing urinary tract infections and their antimicrobial resistance patterns among pediatric patients in Western Iran from 2007-2009.

Urinary Tract infections ( UTIs) are among the most common infections in infants and neonates. The aim of the current study was to evaluate the frequency of bacteria causing UTI and their relevant drug resistance patterns among infants and neonates hospitalized in Ilam province, Western Iran during 2007-2009. A total of 220 cases of UTI were enrolled in this cross-sectional retrospective study. A standard checklist was used for demographic and clinical data to be collected from their health records. Data was then analyzed using SPSS version 16.0. More than two-thirds (64.8%) of the cases were female. E. coli (44.5%), Klebsiella spp., (18.6%), Enterobacter spp., (15%) and Staphylococcus spp. (12.7%) were the most common microorganisms isolated from UTIs, respectively. High rates of resistance to tetracycline, ampicillin, and nalidixic acid were observed among these isolates. Similar to other studies, E. coli was the most common bacteria causing UTI and showed a high rate of resistance against most of the antimicrobial agents. Determining the antimicrobial sensitivity can be helpful for physicians in choosing an appropriate treatment for patients suffering from UTI, and also to reduce the complications related to serious UTI.

The effect of antioxidant vitamins E and C on cognitive performance of the elderly with mild cognitive impairment in Isfahan, Iran: a double-blind, randomized, placebo-controlled trial.

PURPOSE: This study was carried out to investigate the effect of vitamins E and C on cognitive performance among the elderly in Iran. METHODS: About 256 elderly with mild cognitive impairment, aged 60-75 years, received 300 mg of vitamin E plus 400 mg of vitamin C or placebo daily just for 1 year. BACKGROUND: Demographic characteristics, anthropometric variables food consumption, cognitive function by Mini-Mental State Examination (MMSE), and some of the oxidative stress biomarkers were examined. RESULTS: Antioxidant supplementation reduced malondialdehyde level (P < 0.001) and raised total antioxidant capacity (P < 0.001) and glutathione (P < 0.01). The serum 8-hydroxydeoxyguanosine remained unchanged (P < 0.4). After adjusting for the covariates effects, MMSE scores following 6- (25.88 ± 0.17) and 12-month antioxidant supplementation (26.8 ± 0.17) did not differ from control group (25.86 ± 0.18 and 26.59 ± 0.18, respectively). CONCLUSION: Despite significant improvement in most of the oxidative stress biomarkers, antioxidants' supplementation was not observed to enhance cognitive performance. A large number of kinetic and/or dynamic factors could be suspected.

Patterns of diet-related practices and prevalence of gastro-esophageal reflux disease.

BACKGROUND: No studies have evaluated associations between patterns of diet-related practices as determined by latent class analysis (LCA) and gastro-esophageal reflux disease (GERD). We aimed to assess this relationship in a large sample of Iranian adults. METHODS: In a cross-sectional study in 4763 adults, diet-related practices were assessed in four domains, 'meal pattern', 'eating rate', 'intra-meal fluid intake', and 'meal-to-sleep interval', using a pretested questionnaire. LCA was applied to identify classes of diet-related practices. We defined GERD as the presence of heartburn sometimes, often or always. KEY RESULTS: The prevalence of GERD in the study population was 23.5% (n = 1120). We identified two distinct classes of meal patterns: 'regular' and 'irregular', three classes of eating rates: 'moderate', 'moderate-to-slow', and 'moderate-to-fast', two major classes of fluid ingestion with meals: 'moderate' and 'much intra-meal drinking', and two classes regarding the interval between meals and sleeping: 'short' and 'long meal-to-sleep' interval. After adjustment for potential confounders, subjects with 'irregular meal pattern' had higher odds of GERD compared with subjects with 'regular meal pattern' (OR: 1.21; 1.00-1.46). However, when taking into account BMI, the association disappeared. 'Long meal-to-sleep interval' was inversely associated with GERD compared with 'short meal-to-sleep interval' (OR: 0.73; 95% CI: 0.57-0.95). 'Eating rate' and 'intra-meal fluid intake' were not significantly associated with GERD. CONCLUSIONS & INFERENCES: Our data suggest certain associations between dietary patterns and GERD. These findings warrant evaluation in prospective studies to establish the potential value of modifications in dietary behaviors for the management of GERD.

The effect of cognitive behavioural psycho-education on premenstrual syndrome and related symptoms.

Premenstrual syndrome (PMS) is a distressing group of symptoms related to menstrual cycle during reproductive age. Its substantial burden on daily function and quality of life, particularly on mental aspects, was to the impetus for this study with the aim of determining the effectiveness of a psycho-educational package on premenstrual syndrome and related symptoms. In a randomized clinical trial, 123 (17-19-year-old) adolescent girls with PMS were randomized to psycho-educational intervention (including 62 subjects) and control (including 61) groups. The participants completed a demographic questionnaire, premenstrual syndrome symptom daily record scale and the Symptom Checklist-90-Revised (SCL-90-R). A paired and two independent samples t-test and chi-squared test were used for analysing data using SPSS statistical package. At the end of the study there was statistically significant decrease in severity of total PMS in intervention compared with control group (P < 0.001). Also, a significant difference in somatization, anxiety and hostility was observed between two groups (P < 0.05). However, depression marginally decreased (P < 0.1) in intervention group, and interpersonal sensitivity was not statistically different between intervention and control groups. Intervention alleviated the severity of PMS and related somatization, anxiety and hostility, yet it could not change the severity of depression and interpersonal sensitivity.

Reliability and validity of the Persian version of Foot and Ankle Ability Measure (FAAM) to measure functional limitations in patients with foot and ankle disorders.

OBJECTIVE: To translate the Foot and Ankle Ability Measure (FAAM) into Persian and to evaluate the psychometric properties of the Persian version of FAAM. METHODS: 93 patients with a range of foot and ankle disorders, completed the Persian version of the FAAM and Short-Form 36 Health Survey (SF-36) in the test session. With an interval of 2-6 days, 60 patients filled out the FAAM in the retest session. The FAAM is composed of two subscales including activities of daily living (ADL) and SPORTS. Internal consistency was assessed using Cronbach's alpha, test-retest reliability using intraclass correlation coefficient (ICC) and standard error of measurement (s.e.m.), item internal consistency and discriminant validity using Spearman's correlation coefficient and construct validity using Spearman's correlation coefficient and Independent t-test. RESULTS: Cronbach's alpha coefficient of 0.97 and 0.94 was obtained for ADL and SPORTS subscales, respectively. The ICC and s.e.m. were 0.98 and 3.13 for ADL and 0.98 and 3.53 for SPORTS subscale. Items were stronger measures of their hypothesized subscale than of other subscale. The ADL and SPORTS subscales had stronger correlation with SF-36 physical function (r=0.60, 0.53) and physical health summary measure (r=0.61, 0.48) than with SF-36 mental health (r=0.21, 0.10) and mental health summary measure (r=0.36, 0.27). A high correlation was found between FAAM scores and global scale of functional status for SPORTS (r=0.73) but not for ADL (r=0.42). FAAM scores were greater in individuals who rated their function as normal or nearly normal compared with those who rated as abnormal or severely abnormal for SPORTS (P=0.04) but not for ADL (P=0.15). CONCLUSION: The Persian version of FAAM is a reliable and valid measure to quantify physical functioning in patients with foot and ankle disorders.