Dietary acid load and cirrhosis-related mortality: a prospective cohort study.

As a global health concern, cirrhosis contributes significantly to morbidity and mortality. This prospective cohort study aimed to investigate the association between dietary acid load (DAL) and cirrhosis-related mortality. Present study was conducted on 121 patients with newly diagnosed cirrhosis who were followed up for 48 months. Anthropometric measures, nutritional status and dietary intakes were assessed and DAL was estimated based on potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores. Crude and multivariable-adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazard analyses. Participants in the high PRAL and NEAP scores had significantly higher intakes of grains and lower intakes of fruits and vegetables. Also, the intake of dairy products and legumes, nuts and seeds decreased significantly with increasing NEAP score. After adjustment of all the confounders, the risk of mortality in the second and third tertiles of PRAL was 5.9 times and 10.97 higher than those in the first tertile, respectively (P trend: 0.006). Similarly, comparing the risk of mortality in the second and third tertiles with the first tertile of NEAP showed a 4.46-fold and 12.3-fold increased risk, respectively (P trend: 0.010). Our findings suggested that DAL was significantly associated with cirrhosis-related mortality and highlight the need for further research to understand the underlying mechanisms and establish optimal DAL levels in cirrhotic patients.

Escherichia coli cytosine deaminase: Structural and biotechnological aspects.

Suicide gene therapy involves introducing viral or bacterial genes into tumor cells, which enables the conversion of a nontoxic prodrug into a toxic-lethal drug. The application of the bacterial cytosine deaminase (bCD)/5-fluorocytosine (5-FC) approach has been beneficial and progressive within the current field of cancer therapy because of the enhanced bystander effect. The basis of this method is the preferential deamination of 5-FC to 5-fluorouracil by cancer cells expressing cytosine deaminase (CD), which strongly inhibits DNA synthesis and RNA function, effectively targeting tumor cells. However, the poor binding affinity of toward 5-FC compared to the natural substrate cytosine and/or inappropriate thermostability limits the clinical applications of this gene therapy approach. Nowadays, many genetic engineering studies have been carried out to solve and improve the activity of this enzyme. In the current review, we intend to discuss the biotechnological aspects of Escherichia coli CD, including its structure, functions, molecular cloning, and protein engineering. We will also explore its relevance in cancer clinical trials. By examining these aspects, we hope to provide a thorough understanding of E. coli CD and its potential applications in cancer therapy.

Relationship Between Dairy Intake and Hospitalization Risk and Disease Severity in Patients With COVID-19.

The aim of this study was to investigate whether dairy intake was associated with the severity of coronavirus disease 2019 (COVID-19) disease and the probability of hospitalization of patients. This cross-sectional study was conducted on 141 patients with COVID-19 with an average age of 46.23 ± 15.88 years. The number of men (52.5%) participating in this study was higher than that of women. The association between dairy intake and COVID-19 was evaluated by multivariable logistic regression analysis. The risk of hospitalization in the highest tertile of dairy intake was 31% lower than in the lowest tertile (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.37-1.25, p trend = 0.023). Higher milk and yogurt intake was associated with a reduced risk of hospitalization due to COVID-19. Patients in the third tertiles were about 65% (p for trend = 0.014) and 12% (p for trend = 0.050) less likely to be hospitalized than those in the first tertile, respectively. Dairy consumption, especially low-fat ones, was associated with a lower risk of hospitalization due to COVID-19 and lower severity of COVID-19.

Dietary protein intake and mortality among survivors of liver cirrhosis: a prospective cohort study.

BACKGROUND: Liver cirrhosis is a worldwide burden and is associated with poor clinical outcomes, including increased mortality. The beneficial effects of dietary modifications in reducing morbidity and mortality are inevitable. AIM: The current study aimed to evaluate the potential association of dietary protein intake with the cirrhosis-related mortality. METHODS: In this cohort study, 121 ambulatory cirrhotic patients with at least 6 months of cirrhosis diagnosis were followed-up for 48 months. A 168-item validated food frequency questionnaire was used for dietary intake assessment. Total dietary protein was classified as dairy, vegetable and animal protein. We estimated crude and multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), applying Cox proportional hazard analyses. RESULTS: After full adjustment for confounders, analyses showed that total (HR = 0.38, 95% CI = 0.2-1.1, p trend = 0.045) and dairy (HR = 0.38, 95% CI = 0.13-1.1, p trend = 0.046) protein intake was associated with a 62% lower risk of cirrhosis-related mortality. While a higher intake of animal protein was associated with a 3.8-fold increase in the risk of mortality in patients (HR = 3.8, 95% CI = 1.7-8.2, p trend = 0.035). Higher intake of vegetable protein was inversely but not significantly associated with mortality risk. CONCLUSION: A comprehensive evaluation of the associations of dietary protein intake with cirrhosis-related mortality indicated that a higher intakes of total and dairy protein and a lower intakes of animal protein are associated with a reduced risk of mortality in cirrhotic patients.

Dietary fiber intake and mortality among survivors of liver cirrhosis: A prospective cohort study.

Background: Liver cirrhosis is associated with significant nutritional risks and poor survival rates. Little is known about the impact of dietary factors on metabolic complications and mortality from cirrhosis. Aim: The present study investigated the potential associations between dietary fibers and the risk of cirrhosis-related mortality. Methods: In this prospective study, 121 ambulatory cirrhotic patients with more than six months of cirrhosis diagnosis were followed-up for 4 years. Dietary intakes were assessed using a 168-item semi-quantitative validated food frequency questionnaire. Crude and multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated through cox proportional hazards regression models. Results: Comparing the highest versus the lowest tertile, soluble and insoluble fiber intake was associated with 62% (HR = 0.38, 95% CI = 0.045-3.5, p trend = 0.047) and 73% (HR = 0.27, 95% CI = 0.06-1.2, p trend = 0.021) lower mortality risk, respectively, after full adjustment for potential confounders. Higher intakes of total fiber were inversely but non-significantly associated with mortality risk. Conclusion: Comprehensive assessment of dietary fiber intake associations with cirrhosis-related mortality showed that higher intakes of soluble and insoluble fiber were significantly associated with reduced mortality risk.

Investigation of the frequencies of various B cell populations in non-responder healthcare workers in comparison with responders to hepatitis B virus vaccination.

BACKGROUND: Hepatitis B is a major global health problem. More than 90% of hepatitis B-vaccinated immunocompetent adults become fully immune. The main purpose of vaccination is immunization. Whether non-responders have a lower percentage of total or antigen-specific memory B cells in comparison with responders is still controversial. We aimed to assess and compare the frequency of various B cell subpopulations in non-responders and responders. METHODS: Fourteen responders and 14 non-responders of hospital healthcare workers were enrolled in this study. We used flow cytometry to evaluate various CD19+ B cell subpopulations using fluorescent-labeled antibodies against CD19, CD10, CD21, CD27 and IgM and ELISA to evaluate total anti-HBs antibodies. RESULTS: We found no significant differences in the frequency of various B cell subpopulations between the non-responder and responder groups. Furthermore, the frequency of the isotype-switched memory B cell population was significantly higher in the atypical memory B cell subset compared with the classical memory B cell subset in the responder and total groups (p=0.010 and 0.003, respectively). CONCLUSIONS: Responders and non-responders to HBsAg vaccine had comparable memory B cell populations. Whether anti-HBs Ab production has a correlation with the level of class switching in B lymphocytes in healthy vaccinated individuals needs further investigation.

The association of dietary approach to stop hypertension (DASH) diet with hospitalization risk in patients with COVID-19.

Background and aim: Given the importance of dietary habits in the immune system, the current study aimed at investigating the association between Dietary Approach to Stop Hypertension (DASH) diet and risk of hospitalization due to COVID-19. Methods: Dietary data of 141 patients with COVID-19 were collected using 147-item food frequency questionnaire. DASH score in this cross-sectional study was calculated based on eight components, including fruits, vegetables, legumes and nuts and seeds, whole grains, low-fat dairy, red or processed meats, sweetened beverages, and sodium. Multivariable logistic regression models were applied to estimate the OR and 95% CI for hospitalization due to COVID-19 in each tertile of DASH score. Results: Mean ± SD of DASH score in inpatients (n=74) and outpatients (n= 87) was 22.5 ± 4.57 and 25.34 ± 4.23, respectively. The risk of hospitalization in the highest tertile of DASH score was 81% lower than the lowest tertile (OR=0.19, 95%CI: 0.07-0.55, P trend = 0.001 after adjustment for age, sex, BMI, energy intake). Also, more intake of fruits, vegetables and low-fat dairy products and less intake of sodium, red and processed meat were each significantly associated with reduced risk of hospitalization due to COVID-19. Conclusions: Our data provide evidence that adherence to DASH-style diet was associated with lower risk of hospitalization due to COVID-19.

Malnutrition and its association with the mortality in liver cirrhosis; a prospective nutritional assessment in two referral centers in Iran.

INTRODUCTION: Liver cirrhosis is a chronic condition caused by different conditions including viral infection, alcoholism, and autoimmune disorders. Malnutrition is one of the complications of liver cirrhosis that is associated with poor outcomes. This study aimed to determine the association of malnutrition with mortality in liver cirrhosis patients. METHODS: This prospective cross-sectional study was conducted on liver cirrhosis patients who were referred to two referral centers for liver disease in Tehran, Iran. Patients' information including demographics (age, gender, etiology of cirrhosis, alcohol and smoking history) in addition to triceps skinfold (TSF), mid-arm circumference (MAC), Child-Pugh score and Model for End-Stage Liver Disease (MELD) score were recorded in all patients. Patients were classified into A, B, and C categories based on the Subjective Global Assessment (SGA) questionnaire. RESULTS: Among 121 participants (68.6%) were males and the mean age was 54.78. Viral infections were the most common etiology and 65 patients (56.2%) were in the classification A of Child-Pugh Score. TSF (P = 0.001) and MAC (P = 0.003) were significantly lower in SGA class C. The survival rate in SGA class C was significantly lower than other groups (P < 0.001; log-rank test). The risk of mortality in patients with SGA class A and B was 85% (HR value: 0.15; 95% CI: 0.02-0.87; P = 0.03) and 76% (HR value: 0.24; 95% CI: 0.06-0.83; P = 0.02) lower than those with SGA class C. CONCLUSION: Anthropometric and SGA measure are two easy and accessible methods for assessing malnutrition and mortality in liver cirrhosis patients.

Factors related to hypermetabolism in individuals with type 2 diabetes mellitus and non-alcoholic fatty liver disease.

Considering the progressive prevalence and co-occurrence of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD), as well as the current evidence suggesting the elevated levels of basal metabolic rate (BMR) among these individuals, the present study aimed to identify factors determining hypermetabolism in such subjects. This cross sectional study was conducted in 30 to 53-year-old individuals with concurrent T2DM and NAFLD (controlled attenuation parameter score ≥ 260 dB/m). Resting energy expenditure (REE) was determined by an indirect calorimetry device. Hypermetabolism was defined as an elevated measured REE > 110% of the predicted REE. The multivariate logistic regression test was used for detecting factors associated with hypermetabolism. Between September, 2017, and March, 2018, a total of 95 eligible participants (64.40% male) with both T2DM and NAFLD were included, while 32.63% of them were classified as hypermetabolic. Overall, the mean recruitment age ± standard deviation and median (interquartile range) body mass index were 44.69 ± 5.47 years and 30.20 (27.80-33.30) kg/m2, respectively. Demographic, anthropometric and biochemical variables did not vary significantly across two groups except for total body water, low-density lipoprotein cholesterol and dipeptidyl peptidase 4 (DPP-4) inhibitors (p < 0.05). According to the results of multivariable logistic regression analyses, hypermetabolism had a positive association with adiponectin (odds ratio [OR] 1.167, 95% confidence interval [CI] 1.015-1.342, p = 0.030), physical activity (OR 1.134, 95% CI 1.002-1.284, p = 0.046), alanine transaminase (OR 1.062, 95% CI 1.006-1.122, p = 0.031) and diastolic blood pressure (OR 1.067, 95% CI 1.010-1.127, p = 0.021). However, fat free mass was inversely related to hypermetabolism (OR 0.935, 95% CI 0.883-0.991, p = 0.023). Adiponectin, alanine transaminase, physical activity, diastolic blood pressure and fat free mass were independently associated with hypermetabolism in subjects with NAFLD and T2DM.

Plant-based diet and COVID-19 severity: results from a cross-sectional study.

Although previous findings have shown the beneficial role of healthy eating pattern on the human immune system, the association between plant-based diet and COVID-19 severity has not yet been elucidated. This study aimed to determine the possible role of plant-based diet index (PDI) in COVID-19 severity. This cross-sectional, multicentral study was conducted on 141 patients with confirmed COVID-19. Dietary intakes of the patients were evaluated using a validated food frequency questionnaire. Then, PDI was compared between patients who needed to be hospitalised (considered severe cases), and those who got treatment at home (considered non-severe cases). After adjustment for confounders including age, sex, energy intake and body mass index, lower odds of hospitalisation were found for participants having a greater score of overall PDI (OR per 10 units increase: 0.42; 95% CI 0.22 to 0.80) and healthy PDI (OR per 10 unit increase: 0.45; 95% CI 0.26 to 0.78). In conclusion, our data presented that there is a relation between PDI and lower risk of hospitalisation in COVID-19 patients, possibly through boosting the immune function.

Differential Effects of the Lateral Hypothalamus Lesion as an Origin of Orexin and Blockade of Orexin-1 Receptor in the Orbitofrontal Cortex and Anterior Cingulate Cortex on Their Neuronal Activity.

Introduction: Introduction: Several studies have demonstrated that orexins may regulate different forms of affective and cognitive processes during wakefulness. The Orbitofrontal Cortex (OFC) and Anterior Cingulate Cortex (ACC), as an essential part of the Prefrontal Cortex (PFC), have a crucial role in cognitive processes such as reward and decision-making. They also have a high amount of orexin receptor type 1 (OX1Rs). Methods: In the present study, we inhibited OX1Rs in this area after a 10-min baseline recording to find out the role of OX1Rs in the OFC neuron's firing rate. Next, we inhibited the lateral hypothalamus (LH) as the primary source of orexinergic neurons. Afterward, using a single-unit recording technique in rats, we detected the effects of the lateral hypothalamus on the firing rate and activity pattern of the ACC or OFC neurons. Results: Data showed that the blockade of OX1Rs in the OFC could excite 8 and inhibit 1 neuron(s) out of 11. In addition, the blockade of OX1Rs in the ACC could excite 6 and inhibit 3 neurons out of 10. LH inactivation excited 5 out of 12 neurons and inhibited 6 in the ACC. It also excited 8 and inhibited 6 neurons out of 14 in the OFC. These data suggest that the blockade of OX1Rs excites 72% of the neurons, but LH inactivation had a stimulating effect on only 50% of neurons in two main subregions of the PFC. Conclusion: Accordingly, PFC neurons may receive the orexinergic inputs from the LH and indirectly from other sources. Highlights: Blockade of orexin receptors 1 in ACC alter neural activity in this region.Blockade of orexin receptors 1 in OFC alter neural activity in this region.Lateral hypothalamus inhibition increase neural activity of only 50% neurons in ACC and OFC. Plain Language Summary: The discovery of the neuropeptide orexin/hypocretin in 1998 and subsequent research during the past 20 years revealed an important role for the lateral hypothalamus (LH) in driving the reward pathway, sleep and awake circuits, decision making and psychotic disorders. But our knowledge towards the function of this neurotransmitter on neural activity in specific areas of the brain is limited. In this study we decided to clear the specific role of orexin receptors placed in the two crucial areas of medial prefrontal cortex (mPFC) and the orexin projections from LH on neural firing rates in those regions. In the present study, we investigated the following items by using an in vivo extracellular single-unit recording technique in rats and our data shown that the effect of blocking of orexin receptors1 in mPFC caused a different results than inhibition of the origin of orexin projection in LH as a source of it.

Evaluating macro- and micronutrients and food groups intake with the risk of developing inflammatory bowel disease: Is there any association?

Growing clinical evidence represented that certain dietary components are involved in inflammatory bowel disease (IBD) development and progression. This research, therefore, aimed to evaluate whether there exists any relationship between nutrients and IBD. This case-control study from 2017 to 2019 was performed on 145 newly diagnosed IBD patients and 145 BMI-, sex-, and age-matched healthy controls who were recruited from a hospital clinic. A validated 168-item food frequency questionnaire was completed by each participant. Anthropometric measurements and physical activity levels were measured for all participants. Stata software was used to analyze all data. Of the 234 study individuals who participated, 112 were IBD patients and 122 were healthy people. The higher amount of seafood and cholesterol was related to an increased risk of IBD and ulcerative colitis development; however, individuals who had a higher intake of calcium were less likely to have Crohn's compared to the healthy group. There was a positive relation between honey and jam, seafood, organ meats, salt, fruits on trees, fruit juice, olives, and nuts and the probability of IBD, but there was a negative association between refined grains, potatoes, salty snacks, legumes, dairy, and cruciferous and the probability of IBD. Higher consumption of seafood and cholesterol was positively connected with a higher risk of IBD development in the current case-control study. A substantial association was seen between honey and jam, seafood, organmeats, salt, fruit on trees, fruit juice, olives, and nut consumption and IBD developement.

Salt consumption and mortality risk in cirrhotic patients: results from a cohort study.

Since conducting a long-term randomised clinical trial is not logical and feasible to find the optimum dosage of salt intake in patients with cirrhosis, cohort studies are the best design to assess the long-term effects of dietary salt on the survival of cirrhotic patients. This cohort study aimed to evaluate the association between dietary intake of salt and mortality risk in cirrhotic patients. The present study was designed as a cohort in three referral hospitals in Iran in 2018. One hundred and twenty-one patients aged between 20 and 70 years with established cirrhosis were recruited. Dietary intakes, demographic data and disease severity were evaluated at the baseline. Participants were followed up annually. Crude survival was greater in patients with low-to-moderate salt consumption rather than in those with high consumption, and in non-consumers [34⋅26 (95 % CI 33⋅04, 35⋅49) v. 30⋅41 (95 % CI 27⋅13, 33⋅69) v. 32⋅72 (95 % CI 30⋅63, 34⋅80), P = 0⋅028; log-rank test]. Using the Cox proportional hazard model, it was shown that the risk of mortality in the high-salt consumption category was approximately 126 % higher than that of the reference category (non-consumers) [HR value 2⋅26, (95 % CI 0⋅91, 5⋅63)], while this risk for the low-to-moderate consumption group was about 28 % lower than the reference category [HR value 0⋅72, (95 % CI 0⋅26, 1⋅99), P-trend = 0⋅04]. In conclusion, a high daily dietary intake of salt might increase the rate of mortality and moderate salt restriction (instead of elimination of salt) decreases the risk of death.

The effect of low FODMAP diet with and without gluten on irritable bowel syndrome: A double blind, placebo controlled randomized clinical trial.

BACKGROUND & AIM: Although the effects of low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet on amelioration of irritable bowel syndrome (IBS) symptoms have been reported previously, it has not yet been elucidated whether the gluten of wheat and barley induces the symptoms or only their fructans lead to aggravation of the symptoms. The aim of this study was to assess the effect of low FODMAPs diet with vs. without gluten on clinical symptoms in IBS patients. METHODS: In this double-blind, placebo-controlled randomized trial, forty nine IBS patients were randomly assigned to placebo and/or intervention group. Patients in the intervention group received 5 gr/day of gluten powder with low FODMAP diet, while placebo group received 5 gr of rice flour as placebo, with low FODMAP diet. Quality of life (QoL) and IBS-SSS (symptom severity score) were measured before and after the intervention using a valid QoL questionnaire and a standard visual analog scale, respectively. RESULTS: Significant improvements were observed in total scores of IBS-SSS (-32% vs. - 49%), abdominal pain intensity (-45% vs. -52%), and frequency (-26 vs. -46%), abdominal distension (-29% vs. -63%), Interference with community function (-14% vs. -45%) and quality of life (+23 vs. +32%) in both gluten and placebo groups respectively (P < 0.05). Only 5 patients in the gluten-containing diet reported exacerbation of their symptoms. CONCLUSION: Exacerbation of IBS symptoms after wheat and barley consumption is due to their fructan, and not related to their gluten content in most of the patients. CLINICAL TRIAL REGISTRATION NO: IRCT20100524004010N29.

Confusion in Gonadal Dysgenesis Terminology Persisting beyond Chicago Consensus Statement on Disorders of Sexual Development.

The terminology of gonadal dysgenesis conditions is considerably abstruse and variable. Despite some efforts in the 2006 Chicago Consensus Statement on DSD , it is still difficult to assign a category and name for some distinct conditions in this document. The rest of the literature has used redundant and variable words, e.g. partial, pure, and complete gonadal dysgenesis suffering equivocality and redundancy, aggravating this inconclusiveness. We attempted to highlight this problem and propose an easier terminology blueprint.   Abstract: The terminology of gonadal dysgenesis conditions is considerably abstruse and variable. Despite some efforts in the 2006 Chicago Consensus Statement on DSD , it is still difficult to assign a category and name for some distinct conditions in this document. The rest of the literature has used redundant and variable words, e.g. partial, pure, and complete gonadal dysgenesis suffering equivocality and redundancy, aggravating this inconclusiveness. We attempted to highlight this problem and propose an easier terminology blueprint.

Blockade of the orexin 1 receptors in the nucleus accumbens' shell reversed the reduction effect of olanzapine on motivation for positive reinforcers.

Effort-based choice of high reward requires one to decide how much effort to expend for a certain amount of reward. Orexin is a crucial neuropeptide in the physiological aspect especially a variety of affective and cognitive processes. The nucleus accumbens (NAc) is a region of the neural system that serves effort-related high reward choices andthe Orexin 1 receptor (OX1R) is distributed extensively throughout the nucleus accumbens shell (AcbS). Olanzapine (OLZ), a typical antipsychotic drug, has a high affinity to D2 as an antagonist, and also partial agonistic-like action at D2 receptors has been reported. We examined the interaction of OLZ with the orexinergic receptor 1 in AcbS on effort- related high reward choice when two goal arms were different in the amount of accessible reward. The animals had to pass the barrier for receiving a high reward in one arm (HRA) or obtain a low reward in the other arm without any cost. Before surgery, all animals were selecting the HRA on almost every trial.During test days, the rats received local injections of either DMSO 20% /0.5 µl, as vehicle or SB334867 (30, 100, 300 nM/0.5 µl), as selective OX1R antagonist, within the AcbS. Other group received OLZ (32 µM/0.5 µl DMSO20%) / vehicle alone or 5 min after administration of SB334867 (300 nM/0.5 µl). The results showed that administration of OLZ in the AcbS alters rat's preference for high reward. On the other hand, blocked of the OX1R (300 nM/0.5 µl) in this region could reverse the effect of OLZ, however, administration of the OX1R antagonists alone in the AcbS led to decreasing rat's preference for high reward. This result indicates that the orexin-1 antagonist might affect some effects of antipsychotic drugs.

Intermittent Catheterization Frequency and Interval in Children: Are We Clear Enough?

Intermittent catheterization has been introduced as a lifesaving management strategy in cases of bladder neuromuscular dysfunction both in adults and children. Surprisingly there are scarce data or even clear professional opinions about interval and frequency of catheterization attempts in children. This may have a considerable impact specially in children with vastly variable bladder capacity and function. We tried to throw light on this problem, suggest a simple estimation and propose a more frequent catheterization schedule than commonly perceived, as an either temporizing or extenuating resort before cystoplasty in some cases.

An integration of environmental awareness into flexible supply chains: a trade-off between costs and environmental pollution.

Today, environmental awareness is highly interested in supply chains and logistics networks with regard to sustainable development goals. This proposes a bi-objective linear mathematical model comprising supply chain flexibility dimensions. The proposed model is to integrate environmental considerations into a flexible supply chain as an optimization framework. The first objective function is to minimize the costs, while the second one minimizes the environmental impacts of automotive industry. The goal of this paper is to find a trade-off between the total cost and the environmental pollution with regard to the supply chain flexibility dimensions. We suggest adding four different supply chain flexibility dimensions to the model which are budget for transportation, trained labor team to help the packaging process, number of active plants, and outsourcing the painting process flexibilities to curb harmful emissions from factories while reducing the costs. Six flexibility scenarios are proposed in this study to do the sensitivity analysis. The model is applicable with the use of a real data set derived from an automotive parts factory located in Iran. We use an improved augmented ε-constraint method to address the proposed bi-objective optimization framework. The results show that choosing the model with all flexibility dimensions is the best initiative to promote sustainable development, since it leads to a significant reduction in costs and environmental pollution.

Effect of resveratrol on menstrual cyclicity, hyperandrogenism and metabolic profile in women with PCOS.

AIM: The aim of this randomized trial was to find whether resveratrol could improve menstrual dysfunction, clinical signs (i.e., acne and hair loss), and the biochemical evidence of hyperandrogenism in the women with PCOS. METHODS: Women, in the age range of 18-40 years, diagnosed with PCOS, as defined by the Rotterdam criteria, and no other known cause of abnormal menstruation, were recruited. Participants were randomized based on a 1:1 ratio, to either 1000 mg resveratrol or 1000 mg placebo daily groups, for a period of 3 months. RESULTS: Seventy-eight patients were randomized: 39 to the resveratrol group and 39 to placebo. Results were analyzed according to the intention-to-treat principle. At the end of study, it was found that women who received resveratrol had a statistically higher regular menstruation rate, as compared to those who got placebo (76.47% vs. 51.61%; p = 0.03), and lower hair loss (32.10% vs. 68.00%; p = 0.009). We also found no significant differences between the two groups in terms of ovarian and adrenal androgens, sex hormone binding globulin (SHBG) levels, free androgen index (FAI), glycoinsulinemic metabolism and lipid profile. Moreover, the resveratrol treatment did not interfere with the thyroid, liver and kidney functions. The negative effect of resveratrol on the body composition was also observed, though not influencing changes in the weight, relative to the placebo group. CONCLUSION: Resveratrol improved menstrual cyclicity and hair loss, even though levels of androgens, insulin and lipids remained unchanged.

Glutamine Supplementation Enhances the Effects of a Low FODMAP Diet in Irritable Bowel Syndrome Management.

Background and Aims: Although irritable bowel syndrome is one of the most common gastrointestinal disorders presented to gastroenterologists, therapeutic strategies are not yet well-established. Accordingly, we conducted a randomized, double-blind, placebo-controlled, clinical trial to evaluate the possible superiority of adding glutamine supplement to low fermentable oligo- di- monosaccharides and polyols (FODMAP) diet in patients with irritable bowel syndrome (IBS). Methods: Eligible adults were randomized to receive a low FODMAP diet either with glutamine (15 g/day) or a placebo for 6 weeks. The primary endpoint was a significant reduction in IBS-symptom severity score (IBS-SSS). Secondary endpoints were changes in IBS symptoms, stool frequency, consistency, and quality of life. Results: The study group enrolled 50 patients, among which 22 participants from each group completed the study protocol. The glutamine group had significant changes in total IBS-severity score, dissatisfaction of bowel habit and interference with community function (58% reduction; P < 0.001, 57% reduction; P < 0.001, 51% reduction; P = 0.043, respectively). Improvement in IBS-severity score of more than 45% was observed in 22 of 25 participants (88%) in the glutamine group, while it was only 15 of 25 participants (60%) in the control group (p = 0.015). No serious adverse events were observed. Conclusions: Our findings indicated the superiority of adding glutamine supplementation to a low FODMAP diet in amelioration of IBS symptoms while confirming the beneficial effects of a low FODMAP diet in IBS management.