Effects of oral butyrate and inulin supplementation on inflammation-induced pyroptosis pathway in type 2 diabetes: A randomized, double-blind, placebo-controlled trial.

PURPOSE: Pyroptosis, a form of inflammatory programmed cell death, is activated in diabetic patients. This study was conducted to investigate the effects of daily consumption of sodium butyrate (NaBut) and high-performance (HP) inulin supplementation, individually or in combination, on the expression of pyroptosis-related genes, microRNA (miR) 146a-5p, miR-9-5p and biomarkers of oxidative stress in patients with type 2 diabetes (T2DM). METHODS: In this study, we conducted a randomized, double-blinded, placebo-controlled clinical involving sixty patients with type 2 diabetes. Participants received 600 mg/d of NaBut (group A), 10 g/d of HP inulin (group B), 600 mg/d of NaBut + 10 g/d of HP inulin (group C) or placebo (group D) for 45 consecutive days. We assessed the pyroptosis-related genes mRNA expression in peripheral blood mononuclear cells (PBMCs), as well as the plasmatic levels of miR-146a and miR-9 before and after the intervention. Moreover, blood samples of the patients at baseline and following the intervention were tested for total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase levels using enzyme-linked immunosorbent assay (ELISA). This study was registered on the Iranian Registry of Clinical Trials website (identifier: IRCT201605262017N29; https://www.irct.ir/). RESULTS: Following butyrate supplementation, the relative expression levels of TLR2/4, NF-κB1, Caspase-1, NLRP3, IL-1ß & IL-18 were significantly downregulated (p < 0.05). Furthermore, butyrate and concomitant use of butyrate and inulin caused a significant increase in the fold change of miR-146a and miR-9 compared with the placebo group (p < 0.05). Interestingly, the changes in total antioxidant capacity (p = 0.047) and superoxide dismutase (p = 0.006) were significantly increased after butyrate and concomitant use of butyrate and inulin supplement, respectively. CONCLUSION: In summary, the change in expression level of miR-146a-5p and miR-9-5p due to butyrate supplementation may have a pivotal role in alleviating of diabetes via inhibiting pyroptosis by targeting TLR2 and NF-κB1. These microRNAs might be considered as potential therapeutic targets in the treatment of type 2 diabetes but further researches is required to prove the link.

Effect of high-dose vitamin D supplementation in combination with weight loss diet on glucose homeostasis, insulin resistance, and matrix metalloproteinases in obese subjects with vitamin D deficiency: a double-blind, placebo-controlled, randomized clinical trial.

As there is limited and inconsistent evidence in potential role of vitamin D on insulin resistance and matrix metalloproteinases, this study aimed to examine the effect of vitamin D supplementation on glucose homeostasis, insulin resistance, and matrix metalloproteinases in obese subjects with vitamin D deficiency. A total of 44 participants with serum 25-hydroxyvitamin D (25(OH)D) level ≤ 50 nmol/L and body mass index (BMI) 30-40 kg/m2 were randomly allocated into receiving weight reduction diet with either 50 000 IU vitamin D3 pearl (n = 22) or placebo (n = 22) once weekly for 12 weeks. Primary outcomes were changes in fasting serum glucose (FSG), homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and matrix metalloproteinases (MMPs). Secondary outcomes were changes in weight, BMI, 25(OH)D, calcium, phosphorous and parathyroid hormone (PTH). Sun exposure and dietary intakes were also assessed. Serum levels of 25(OH)D3 increased significantly with a simultaneous decrease in serum concentration of PTH in the vitamin D group. Weight, BMI, FSG, and MMP-9 decreased significantly in both groups, and there were significant differences in changes in weight, serum 25(OH)D3, PTH, and MMP-9 levels between the groups. Within- and between-groups analysis revealed no significant differences in serum calcium, phosphorous, serum insulin, HOMA-IR, QUICKI, and MMP-2 after intervention. Our results indicated that improvement in vitamin D status resulted in greater reductions in weight and MMP-9 during weight loss. These preliminary results are sufficient to warrant a bigger study group.

Chronic neck pain and muscle activation characteristics of the shoulder complex.

INTRODUCTION: Neck pain is a very common musculoskeletal complaint in industrialized countries. Theoretically, chronic neck pain is thought to possibly change biomechanics and muscle activation patterns of the shoulder complex, causing its pain and dysfunction in the long term. PURPOSE: The present cross-sectional study was conducted to compare shoulder complex muscle activation characteristics in patients with chronic non-specific neck pain, compared to healthy participants. METHOD: Twenty patients with chronic neck pain and twenty healthy participants were recruited for the present study. Surface Electromyographic (sEMG) activity was recorded from four selected muscles (anterior and middle deltoid, upper and lower trapezius) during shoulder elevation with a predetermined load (25-30% of an individual's maximum voluntary exertion). RESULT: Results revealed only two significant increased onset delays in the anterior and middle deltoid,and a peak delay in the upper trapezius in chronic neck pain patients. Furthermore, increased onset delay for other muscles and decreased peak normalized amplitude (MVE%) for all muscles were found in chronic neck pain patients; however, these findings were not statistically significant. CONCLUSION: There were relationships between chronic non-specific neck pain and the shoulder muscle activation characteristic; hence, the alteration may be considered a predisposing factor for the shoulder dysfunction in future studies.

Pelvic floor rehabilitation in the treatment of women with dyspareunia: a randomized controlled clinical trial.

INTRODUCTION AND HYPOTHESIS: Dyspareunia, the symptom of painful sexual intercourse, is a common sexual dysfunction in reproductive-aged women. Because of its multifactorial etiology, a multidisciplinary approach may be required to treat it. Musculoskeletal factors play an important role; thus, rehabilitating the pelvic floor and modifying the tone of the pelvic floor muscles (PFMs) may be an effective way to treat this dysfunction. The aim of this randomized controlled clinical study was to evaluate the effects of pelvic floor rehabilitation techniques on dyspareunia. METHODS: Of 84 women, assessed for eligibility, 64 women with dyspareunia were randomized into two groups: the experimental group (n = 32) received electrotherapy, manual therapy, and PFM exercises and the control group (n = 32) had no treatment while on the waiting list. Evaluations of PFM strength and endurance, sexual function, and pain were made directly before and after 3 months of treatment and at the 3-month follow-up. RESULTS: Between-group changes showed significant improvement in the experimental group in comparison with control group. Mean difference in the PFM strength (according to the 0-5 Oxford scale) between groups was 2.01 and the mean difference of endurance was 6.26 s. Also, the mean difference in the Female Sexual Function Index score (the score ranges from 2 to 95) was 51.05, and the mean difference in the VAS score was 7.32. All of the changes were statistically significant (p < 0.05). CONCLUSIONS: According to the results, pelvic floor rehabilitation is an important part of a multidisciplinary treatment approach to dyspareunia.

Vitamin D supplementation has no effect on matrix metalloproteinases-2, -9, and tissue inhibitor matrix metalloproteinase-1 in subjects with metabolic syndrome: A pilot study.

The present randomized, double-blind, placebo controlled study aimed to evaluate the effect of vitamin D supplementation on matrix metalloproteinases-2, -9 (MMP-2 and MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in subjects with metabolic syndrome. Forty-six eligible subjects were randomly assigned to either vitamin D or placebo groups for 16 weeks. The participants were asked to take 50,000 IU vitamin D or matching placebo every week. Metabolic and anthropometric indices, serum MMP-2, MMP-9, TIMP-1 and high-sensitivity C-reactive protein (hsCRP) were assessed before and after intervention. Moreover, dietary intake, sun exposure and physical activity were also determined. The trial was registered at http://www.irct.ir (No. IRCT201409033140N14). Participants were 40.20 ± 4.60 y and 45.50% males. Compared to the baseline values, MMP-9 and TIMP-1 concentrations were decreased after 16 weeks in the intervention group (p = 0.03 and p = 0.04, respectively). However, the changes of MMP-2, MMP-9, TIMP-1 and hsCRP in the intervention group were not significant compared to the placebo group (p > 0.05). Furthermore, the metabolic or anthropometric indices between two study groups remained unchanged (p > 0.05). The findings of the present study demonstrated no effect of vitamin D supplementation on MMP-2, MMP-9 and TIMP-1 concentrations in subjects with metabolic syndrome. However, there is a need for more longitudinal trials to investigate the role of vitamin D on atherosclerosis and cardiovascular diseases in subjects with metabolic syndrome.

Volume of Anesthetic Agents and IANB Success: A Systematic Review.

The aim of this study was to provide an evidence-based answer to the question: "Is 3.6-mL volume of an anesthetic agent more effective than 1.8-mL volume in providing anesthesia for mandibular molars?" Following formulation of research question and keyword selection, a comprehensive search of the following databases was conducted: Cochrane library, PubMed, Scopus, Google Scholar, ProQuest, and Clinicaltrials.gov. Three-phase eligibility appraisal and quality assessment of the studies were carried out by 2 independent reviewers. To reduce clinical heterogeneity, the included studies were divided into 2 groups: studies on healthy teeth and studies on teeth with pulpitis. The data of included studies were statistically combined through meta-analysis using a fixed-effects model. A total of 20,778 records were initially retrieved from the search. Following screening and eligibility assessment, 8 studies met the eligibility criteria and were included for qualitative synthesis. Of those, 5 studies were qualified for meta-analysis. In the irreversible pulpitis group, increasing the volume of anesthetic agent from 1.8 to 3.6 mL significantly increased the success rate of inferior alveolar nerve block (risk ratio = 2.45, 95% CI: 1.67-3.59, p < .001). However, there was insufficient evidence to draw a conclusion regarding healthy teeth.

l-Carnosine supplementation attenuated fasting glucose, triglycerides, advanced glycation end products, and tumor necrosis factor-α levels in patients with type 2 diabetes: a double-blind placebo-controlled randomized clinical trial.

Considering the pathologic importance of metabolic disturbances, advanced glycation end products (AGEs), and chronic inflammation in diabetes mellitus and ameliorating potentials of l-carnosine in hampering these detritions and because these effects have not been investigated in patients with type 2 diabetes (T2D) so far, we conducted the current study. We hypothesized that l-carnosine would improve glycemic control, lipid profile, AGE, soluble receptor of AGEs (sRAGE), and inflammatory markers. In a randomized, double-blind, placebo-controlled clinical trial, 54 patients with T2D were recruited and assigned into either intervention group (n=27, receiving 2 capsules of l-carnosine 500 mg each) or control group (n=27). Blood samples and dietary intakes information were collected at baseline and after 12 weeks of intervention. l-Carnosine supplementation resulted in significant decrease in fat mass and an increase in fat-free mass in the intervention group compared with the placebo group (1.5% and 1.7%, respectively) (P<.05). A significant reduction in fasting blood glucose (13.1 mg/dL); glycated hemoglobin (.6%); and serum levels of triglycerides (29.8 mg/dL), carboxymethyl lysine (91.8 ng/mL), and tumor necrosis factor-α was detected in the l-carnosine group compared with the placebo group (P<.05). In the l-carnosine group, a significant reduction in serum pentosidine levels (2.8 ng/mL) was observed compared with those at baseline (P<.05). No significant differences were observed in dietary intake, body mass index, systolic and diastolic blood pressure, fasting insulin levels, homeostasis model assessment of insulin resistance and secretion, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, sRAGE, interleukin (IL)-6, and IL-1ß levels between the groups after adjusting for baseline values and covariates (P>.05). Collectively, l-carnosine lowered fasting glucose, serum levels of triglycerides, AGEs, and tumor necrosis factor-α without changing sRAGE, IL-6, and IL-1ß levels in T2D patients.

Vitamin K1 Supplementation Did Not Alter Inflammatory Markers and Clinical Status in Patients with Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is an inflammatory disorder in which the disease severity might be decreased by anti-inflammatory agents. There are several lines of evidence which support anti-inflammatory effects of vitamin K. The aim of this study was to examine whether vitamin K is a useful strategy for reducing inflammation in RA subjects. Materials and methods: In this double-blind placebo controlled trial, 58 patients with definitive RA were randomly allocated into two groups to receive vitamin K1 as phylloquinone [10 mg/day] or placebo pills for 8 weeks. Clinical status using disease activity score-28 (DAS-28) and serum concentrations of some inflammatory markers (IL-6, hs-CRP, TNFα) were assessed at baseline and at the end of intervention. Results: There were no significant differences between the two groups regarding any of the baseline characteristics. In the vitamin K1 group, a 27 % decrease in serum levels of IL-6 (P = 0.006) and a 13 % decrease in DAS-28 (P = 0.041) were observed. However, after adjusting for relevant confounders, i. e.; duration of RA, intake of folic acid supplements, energy intake, weight and baseline values of each variable, by comparing the two groups, we found no significant reduction in these markers. Conclusion: Vitamin K1 supplementation at 10 mg/day for 8 weeks had no significant effects on blood biomarkers of inflammation and disease severity of patients with rheumatoid arthritis compared with the placebo group.

Effect of Butyrate and Inulin Supplementation on Glycemic Status, Lipid Profile and Glucagon-Like Peptide 1 Level in Patients with Type 2 Diabetes: A Randomized Double-Blind, Placebo-Controlled Trial.

Studies on humans with diabetes mellitus showed that the crosstalk between the intestinal microbiota and the host has a key role in controlling the disease. The aim of this study was to evaluate the effects of sodium butyrate and high performance inulin supplementation simultaneously or singly on glycemic status, lipid profile, and glucagon-like peptide 1 level in adults with type 2 diabetes mellitus. Sixty patients were recruited for the study. The participants were randomly allocated, using randomized block procedure, to one of the four treatment groups (A, B, C, or D). Group A received sodium butyrate capsules, group B received inulin supplement powder, group C was exposed to the concomitant use of inulin and sodium butyrate, and group D consumed placebo for 45 consecutive days. Markers of glycemia, lipid profile, and glucagon-like peptide 1 were measured pre- and post-intervention. Dietary supplementation in groups A, B, and C significantly reduced diastolic blood pressure in comparison with the placebo group (p<0.05). Also, intra-group statistical analysis showed that only treatment with sodium butyrate + inulin (group C) significantly reduced fasting blood sugar (p=0.049) and waist to hip ratio (p=0.020). Waist circumference in groups B and C reduced significantly after the intervention (p=0.007 and p=0.011; respectively). The post hoc Tukey tests showed significant increase in glucagon-like peptide 1 concentration in groups A and C in comparison with group D (p<0.05). The results suggest that inulin supplementation may be useful to diabetic patients and these effects could be increased with butyrate supplement.

The effects of vitamin D supplementation on proatherogenic inflammatory markers and carotid intima media thickness in subjects with metabolic syndrome: a randomized double-blind placebo-controlled clinical trial.

PURPOSE: Metabolic syndrome may predispose to cardiovascular diseases. Since, in recent studies, vitamin D is advocated for cardioprotective roles, this study was designed to investigate the effects of vitamin D supplementation on proatherogenic inflammatory markers and common carotid intima media thickness in subjects with metabolic syndrome. METHODS: This randomized double blind clinical trial was conducted in Tabriz, Iran. Eligible subjects (n = 80) with metabolic syndrome were recruited thorough advertisement and randomized to receive either vitamin D (50,000 IU/week) or matching placebo for 16 weeks. Interlukin-6, high sensitivity C-reactive protein, vascular cell adhesion molecule-1, E-selectin, and common carotid intima media thickness were measured at the beginning and end of the study. The study was registered at http://www.irct.ir (code: IRCT201409033140N14). RESULTS: Sixteen weeks supplementation with vitamin D increased median of serum 25-hydroxy vitamin D [25(OH)D] and mean calcium levels (p < 0.001) in the intervention group. There was also a significant difference in parathyroid hormone level at the end of the study (p < 0.001). Vitamin D treatment reduced IL-6 level after 16 weeks (p = 0.027). Compared to baseline, vascular cell adhesion molecule-1 and E-selectin levels decreased significantly in vitamin D treated subjects; however, there were no significant differences between two groups. No effect of vitamin D supplementation was observed in either common carotid intima media thickness or high sensitivity C-reactive protein concentrations at the end of the study (p > 0.05). CONCLUSIONS: Vitamin D supplementation improved some proatherogenic inflammatory markers in subjects with metabolic syndrome. No changes of high sensitivity C-reactive protein and carotid intima media thickness were shown after 16 weeks.

The effect of n-3 polyunsaturated fatty acids on incidence and severity of oxaliplatin induced peripheral neuropathy: a randomized controlled trial.

BACKGROUND: Oxaliplatin induced peripheral neurotoxicity (OXIPN) is the major dose-limiting and long-lasting side effect of oxaliplatin. N-3 PUFAs have neuroprotective property via their effects on voltage-gated ion channels and by reducing the production of proinflammatory cytokines that causes neuropathy. This study was a randomized double blind placebo controlled trial to find the possible advantages of n-3 PUFAs for preventing and reducing the severity of OXIPN in patients with colon cancer. METHODS: Eligible patients with colon cancer randomly allocated to take n-3 PUFAs pearls, 640 mg t.i.d during chemotherapy with oxaliplatin and one month after the cessation of the treatment or placebo. All patients were evaluated for incidence and severity of OXIPN based on "reduced Total Neuropathy Score" in which clinical and electrophysiological assessments were included. RESULTS: Seventeen patients (47 %) of the n-3 PUFA supplemented group (n = 36) did not develop PN while it was 11 %(4 patients) in the placebo group (n = 35). There was a significant difference in PN incidence (OR = 0.14, .95 % CI = (0.04 to 0.49), p = 0.002). The difference of OXIPN severity was significant between the two study groups (B = -1.61, 0.95 % CI = (-2.59 to -0.62), p = 0.001). CONCLUSIONS: N-3 PUFAs may have neuroprotective effect for reducing the incidence and severity of OXIPN. Finding an effective prophylactic or symptomatic therapy for OXIPN would significantly improve the patients' quality of life. TRIAL REGISTRATION: IRCT201112158397N2.

Effects of Vitamin K on Matrix Metalloproteinase-3 and Rheumatoid Factor in Women with Rheumatoid Arthritis: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease characterized by an increase in some autoantibodies and proteolytic enzymes, leading to joint destruction. Although recent investigations have considered vitamin K as an anti-inflammatory nutrient with an important role in bone metabolism, there is currently limited information on its efficacy in RA. We aimed to examine the effects of vitamin K1 (phylloquinone) on the biomarker of joint destruction and autoantibody in patients with RA. MATERIALS AND METHODS: This was a randomized clinical trial in which 64 women with RA who fulfilled the eligibility criteria were randomly allocated to an intervention or a control group. Vitamin K1 or placebo was administered to the participants for 8 weeks. Baseline characteristics and anthropometric measures were obtained. Clinical status using disease activity score in 28 joints (DAS-28), serum levels of matrix metalloproteinase-3 (MMP-3), and rheumatoid factor (RF) were assessed before and after the intervention. RESULTS: The serum level of MMP-3 compared with the baseline values did not change significantly in the groups. However, the serum concentration of RF decreased significantly in the vitamin K1 group (p = 0.041). Intergroup comparison showed no significant change in RF serum level after adjusting for relevant confounders (p > 0.05). CONCLUSIONS: Vitamin K1 supplementation at 10 mg/day for 8 weeks did not alter joint destruction and immune status in the patients with RA compared with the controls.

Is there any place for resistant starch, as alimentary prebiotic, for patients with type 2 diabetes?

OBJECTIVE: The aim of the present study was to determine effects of Resistant Starch (RS2) on metabolic parameters and inflammation in women with type 2 diabetes (T2DM). METHODS: In this randomized controlled clinical trial, 60 females with T2DM were divided into intervention (n = 28) and placebo groups (n = 32). They received 10 g/d RS2 or placebo for 8 weeks, respectively. Fasting blood sugar (FBS), glycated hemoglobin (HbA1c), lipid profile, high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured at baseline and at the end of the trial. Paired t test, unpaired t-test and ANCOVA were used to compare the quantitative variables. The data were analyzed using SPSS software version 13.0. RESULTS: RS2 decreased HbA1c (-0.3%, -3.6%), TNF-α (-3.4 pg/mL, -18.9%), triglyceride (-33.4 mg/dL, -15.4%), and it increased HDL-c (+9.4 mg/dL, +24.6%) significantly compared with the placebo group (p < 0.05). Changes in FBS, total cholesterol, low-density lipoprotein, hs-CRP and IL-6 were not significant in the RS2 group compared with the control group. RS2 can improve glycemic status, inflammatory markers and lipid profile in women with T2DM. CONCLUSIONS: Although findings of the present study indicated positive effects of RS2 on inflammation and metabolic parameters, more studies are needed to confirm efficacy of RS2 as an adjunct therapy in diabetes.

Effect of beta glucan on white blood cell counts and serum levels of IL-4 and IL-12 in women with breast cancer undergoing chemotherapy: a randomized double-blind placebo-controlled clinical trial.

BACKGROUND: Breast cancer is the most common female malignancy in the world. Beta glucan can be a hematopoietic and an immune modulator agent in cancer patients. The aim of this trial was to determine the effect of beta glucan on white blood cell counts and serum levels of IL-4 and IL-12 in women with breast cancer undergoing chemotherapy. MATERIALS AND METHODS: This randomized double-blind placebo-controlled clinical trial was conducted on 30 women with breast carcinoma aged 28-65 years. The eligible participants were randomly assigned to intervention (n=15) or placebo (n=15) groups using a block randomization procedure with matching based on age, course of chemotherapy and menopause status. Patients in the intervention group received two 10-mg capsules of soluble 1-3, 1-6, D-beta glucan daily and the control group receiving placebo during 21 days, the interval between two courses of chemotherapy. White blood cells, neuthrophil, lymphocyte and monocyte counts as well as serum levels of IL-4 and IL-12 were measured at baseline and at the end of the study as primary outcomes of the study. RESULTS: In both groups white blood cell counts decreased after 21 days of the intervention, however in the beta glucan group, WBC was less decreased non significantly than the placebo group. At the end of the study, the change in the serum level of IL-4 in the beta glucan group in comparison with the placebo group was statistically significant (p=0.001). The serum level of IL-12 in the beta glucan group statistically increased (p=0.03) and comparison between two groups at the end of the study was significant after adjusting for baseline values and covariates (p=0.007). CONCLUSIONS: The findings suggest that beta glucan can be useful as a complementary or adjuvant therapy and immunomodulary agent in breast cancer patients in combination with cancer therapies, but further studies are needed for confirmation.

Objective and subjective assessments of lighting in a hospital setting: implications for health, safety and performance.

A field study was conducted to evaluate the illumination levels, to examine the effect of lighting conditions (including lighting characteristics and disturbances) on employee satisfaction, job performance, safety and health, and to compare the employees' perception of lighting level with actual illuminance levels in a hospital setting using both questionnaire and physical illuminance measurements. The illumination levels varied across different locations within the hospital and were lower than standards for 52.2% of the workplaces surveyed. Most respondents indicated that at least one of the four lighting characteristics (i.e. light level, type of light sources, light colour and use of daylight) was inappropriate, and that at least one of the three lighting disturbances (i.e. flickering lights, glare and unwanted shadows) was a major disturbance to them. The employees' perceptions of illuminance generally reflected the actual illuminance levels. The more appropriate maintenance or installation of lighting fixtures was rated as the most appropriate for improving lighting. The findings suggest that environmental ergonomics should be given a more prominent role in hospital building and workplace design to support safer healthcare facilities (for staff and potentially for patients). PRACTITIONER SUMMARY: Good lighting is essential to improve employee performance, health and safety. The findings suggest that quantitative physical measurements should be supplemented by qualitative subjective assessments to provide a more holistic approach where specific details about the lighting condition in each working environment are incorporated from the workers' perspective.