Type 2 Diabetes with Comorbid Depression in Relation to Cognitive Impairment: an Opportunity for Prevention?

Studies show poor glycemic control is associated with increased risk of dementia among patients with Type 2 diabetes, indicating potential for prevention of dementia with improved glycemia. Emerging evidence suggests that a relationship between short-term glycemic control and cognitive function exists in Type 2 diabetes. However, detailed mechanisms relating diabetic dementia are lacking, as other concurrent conditions, such as depression, may also increase the risk of dementia in Type 2 diabetes. We examined the effects of glycemic control and depression on cognitive function in 88 patients (mean age, 67 ± 4 years) whose A1c (glycosylated hemoglobin) levels, comorbid depression, mini-mental state examination (MMSE) scores were recorded at baseline. Seventeen patients had depression; 14 agreed on anti-depressants. In 6 months, 69 patients reached A1c goal of < 7% (A1c from 9.7 ± 0.8 to 6.4 ± 0.3) while cognition improved significantly (MMSE scored from 20.2 ± 3.5 to 26.2 ± 2.1, p < 0.05). Cognitive increment in controlled diabetes was more consistently observed if their underlying depression was effectively treated (n ? 14). Nineteen patients did not reach A1c goal of < 7% (A1c from 9.6 ± 0.9 to 8.9 ± 0.9) while cognitive increment was minimal (MMSE scored from 20.6 ± 4.9 to 21.3 ± 5.1, p > 0.05). Cognitive decrements were observed among depressed diabetics who refused anti-depressants. Multivariate analysis adjusted for age, education, alcohol use, and other variables yielded similar results. We found controlled glycemia and depression prevent cognitive decline. Further research into mechanisms of cognitive impairment in diabetes may allow us to challenge the concept of dementia in those patients as an irremediable disease.     

Evaluación funcional y cognitiva en una población urbana de mayores de 89 años. Estudio NonaSantFeliu

Introductionthe increase in life expectancy should be characterized by an increase in disability-free life. We assessed functional and cognitive capacity in an urban population older than 89 years, as well as possible gender variations.Material and methodsthe NonaSantFeliu study is a longitudinal, observational, population-based study. We present the first crosssectional survey of 186 inhabitants older than 89 years in a city. Sociodemographic data were gathered. We assessed basic activities of daily living with the Barthel Index (BI), instrumental activities with the Lawton Index (LI), cognitive status with the Mini-Mental State Examination (MMSE) and comorbidity with the Charlson Index (CI).Resultsof 186 examined nonagenarians, 143 (76.5%) were women. The mean age SD was 93.1 ± 3.1 years. One-hundred forty nine (80.2%) were widowed and 26% were institutionalized. The mean BI was 60.8 ± 30; 56% were functionally independent or had slight dependence. The mean LI was 2.1 ± 2.8. The mean MMSE score was 21 ± 11; 56% had an MMSE score higher than 23. The mean CI was 1.4 ± 1.7. No significant differences were found by gender.Conclusionsdespite their advanced age, most of the nonagenarians showed mild functional and cognitive impairment with low comorbidity. No significant differences were observed by gender. Future studies should help to detect nonagenarians at high risk of rapid impairment to allow early initiation of interventions to delay the development of further incapacity.     

Bee Venom Ameliorates Cognitive Dysfunction Caused by Neuroinflammation in an Animal Model of Vascular Dementia

Vascular dementia (VaD) is caused by the reduction of blood supply by vessel occlusion and is characterized by progressive cognitive decline. VaD incidence has been growing due to the aging population, placing greater strain on social and economic resources. However, the pathological mechanisms underlying VaD remain unclear. Many studies have used the bilateral common carotid artery occlusion (BCCAO) animal model to investigate potential therapeutics for VaD. In this study, we investigated whether bee venom (BV) improves cognitive function and reduces neuroinflammation in the hippocampus of BCCAO animals. Animals were randomly divided into three groups: a sham group (n = 15), BCCAO control group (n = 15), and BV-treated BCCAO group (n = 15). BCCAO animals were treated with 0.1 μg/g BV at ST36 (“Joksamli” acupoint) four times every other day. In order to investigate the effect of BV treatment on cognitive function, we performed a Y-maze test. In order to uncover any potential relationship between these results and neuroinflammation, we also performed Western blotting in the BCCAO group. Animals that had been treated with BV showed an improved cognitive function and a reduced expression of neuroinflammatory proteins in the hippocampus, including Iba-1, TLR4, CD14, and TNF-α. Furthermore, we demonstrated that BV treatment increased pERK and BDNF in the hippocampus. The present study thus underlines the neuroprotective effect of BV treatment against BCCAO-induced cognitive impairment and neuroinflammation. Our findings suggest that BV may be an effective complementary treatment for VaD, as it may improve cognitive function and attenuate neuroinflammation associated with dementia.     

Effect of Probiotic Soy Milk on Serum Levels of Adiponectin,Inflammatory Mediators,Lipid Profile,and Fasting Blood Glucose Among Patients with Type II Diabetes Mellitus

Probiotic therapies are going to be an effective alternative therapeutic strategy in the treatment and management of diabetes. The mechanism behind the essential effects of probiotic therapies in diabetic patients was not fully understood. The objective of this study was to evaluate the effects of probiotic soy milk containing Lactobacillus planetarum A7 on inflammation, lipid profile, fasting blood glucose, and serum adiponectin among patients with type 2 diabetes mellitus. Forty patients with type 2 diabetes, at the age of 35–68 years old, were assigned to two groups in this randomized, double-blind, controlled clinical trial. The patients in the intervention group consumed 200 ml/day of probiotic soy milk containing L. planetarum A7 and those in control group consumed 200 ml/day of pure soy milk for 8 weeks. Serum TNF-α, C reactive protein, adiponectin, lipid profile, and fasting blood glucose were determined before and after intervention. In intervention group, serum adiponectin in pre- and post-treatment did not show any significant changes (2.52 ± 0.74 vs 2.84 ± 0.61, P = 0.658), as well as changes in serum TNF-α and C reactive protein (172.44 ± 5.7 vs 172.83 ± 7.6, P = 0.278, 4.2 ± 1.4 vs 4.5 ± 1.9, P = 0.765, respectively). Low-density cholesterol and high-density cholesterol changed significantly (P = 0.023, P = 0.017, respectively), but fasting blood glucose did not show any significant changes. The results of this study showed that consumption of probiotic soy milk and soy milk has no effect on serum adiponectin and inflammation, but it can change lipid profile among type 2 diabetic patients.     

A novel haplotype within C-reactive protein gene influences CRP levels and coronary heart disease risk in Northwest Indians

According to several epidemiological and clinical studies, the concentration of C-reactive protein (CRP) in blood is associated with the risk of coronary heart disease (CHD). However, these studies are limited in high incidence and prevalence area of North-West India. The present case control study investigated the contribution of three relevant CRP single nucleotide polymorphisms: ?717A>G located in the promoter region (rs2794521), +1059G>C on exon2 (rs1800947) and +1444C>T in the 3′ UTR (rs1130864) in 180 angiographically verified CHD cases and 175 control subjects. Minor allele frequencies (G, C and T) of rs2794521, rs1800947 and rs1130864 are observed to be 21.1, 11.7, 29.4 and 11.4, 10.0, 19.7 % in CHD cases and controls respectively. AA genotype of ?717A>G and TT genotype of +1444C>T were significantly associated (P = 0.02 & 0.03 respectively) with the risk of CHD whereas, +1059G and +1444T were found to be strongly related (P = 0.023 & P = 0.008 respectively) with multivariable adjusted CRP levels. AGT Haplotype was significantly associated with the adjusted CRP levels (P < 0.05). Disease association analysis revealed that haplotype AGT influences CHD risk (OR 2.4, 95 % CI 1.23–4.84, P = 0.006) which exacerbates after correcting the confounding effects of risk variables (OR 2.5, 95 % CI 1.27–4.99, P = 0.004). With the global index of Akaike information criterion, it has been observed that the carrying each single unit of this susceptibility haplotype increases CHD risk by a value of 2.41 ± 0.439 (β ± SE) in the recessive mode.     

The effects of depression,anxiety and sleep disturbances on cognitive impairment in patients with chronic obstructive pulmonary disease

The purpose of this study was to investigate the effects of depression, anxiety and sleep disturbances on cognitive functions in chronic obstructive pulmonary disease (COPD) patients. In this prospective case-control study, demographic data, smoking history, depression, anxiety, sleep quality and cognitive status of 48 COPD patients and 36 healthy volunteers aged 40–90 years were recorded. The Beck depression inventory (BDI), the Beck anxiety inventory (BAI), and Pittsburgh Sleep Quality Index (PSQI) were used to assess depression, anxiety and sleep quality, respectively in COPD patients. Cognitive performance was studied by the mini-mental state examination. The mean age of patients with COPD was 65.3 ± 9.4 years, and disease duration was 9.6 ± 7.8 years. Male sex ratio, smoking, BDI score, BAI score, total PSQI score, sleep latency, sleep duration, average use of sleep aids and sleep disturbances in patients with COPD were significantly higher than the control group (p < 0.05). When cognitive impairment was compared by age, FVC, FEV, FEV/FVC, PEF values and smoking, no statistically significant relationship was found (p > 0.05). A statistically significant relationship was established between cognitive impairment and severity of disease, presence of anxiety, presence of depression and sleep quality. In our study, we found that sleep disorders, depression and anxiety comorbid with COPD increased cognitive impairment as well as the severity of disease. We believe that this finding is important in terms of reducing the risk of cognitive impairment, preventing misdiagnosis and treatment of the aforementioned comorbid diseases.     

Genetic Polymorphism of <Emphasis Type="Italic">GABRR2</Emphasis> Modulates Individuals’ General Cognitive Ability in Healthy Chinese Han People

Previous studies have indicated that the cognitive impairment or deficit is associated with GABAergic signaling in central nervous system. Inspired by the finding that receptor GABRR2 modulates concentration of GABA and phasic inhibitory GABAergic transmission in brain. This study investigated to what extent a genetic variant (c.1423C>T, rs282129) of GABRR2 gene modulates individuals’ general cognitive ability in 987 Chinese Han people. Results showed a significant influence of GABRR2 gene polymorphism on individuals’ Raven’s Standard Progressive Matrices (RSPM) performance (F = 3.58, P = .028 by ANOVA and χ ² = 9.35, P = .009 by K–W test, respectively), even if non-genetic factors were partialed out (gender, major, types of birthplace, and socioeconomic index) (B = ?.67, SE = .26, t = 2.63, P = .009). The finding provided a strong evidence, to our knowledge, for the view that genetic variant of GABRR2 gene may contribute to the difference of individuals’ general cognitive ability, independently.     

Cross-talk between macrophages,smooth muscle cells,and endothelial cells in response to cigarette smoke: the effects on MMP2 and 9

The aim of the present study was to analyze the expression of sex-determining region Y-related high mobility group box 4 (SOX4) in non-small cell lung cancer (NSCLC) and its correlation with clinicopathologic characteristics, including the survival of NSCLC patients. To observe initially the expression status of SOX4 in lung squamous cell carcinoma and adenocarcinoma at gene expression omnibus. The expression of SOX4 mRNA and protein was examined in NSCLC tissues and normal lung tissues through real-time PCR and immunohistochemistry. Meanwhile, the relationship of SOX4 expression levels with clinical characteristics of 168 NSCLC patients was analyzed by immunohistochemistry. Univariate and multivariate analyses were performed to determine the association between SOX4 expression and prognosis of NSCLC patients. In our results, SOX4 expression was increased in NSCLC tissues compared with paired normal lung tissues in microarray data (GSE3268). SOX4 mRNA and protein expression were markedly higher in NSCLC tissues than in normal lung tissues (P = 0.001 and P = 0.001, respectively). Using immunohistochemistry, high levels of SOX4 protein were positively correlated with status of differentiated degree (high vs. middle, P = 0.004; high vs. low, P < 0.001), clinical stage (I–II vs. III–IV, P < 0.001), T classification (T1–T2 vs. T3–T4, P = 0.004), N classification (N0–N1 vs. N2–N3, P = 0.002), and M classification (M0 vs. M1, P = 0.011) in NSCLC. Moreover, the higher level of SOX4 expression was markedly correlated with poor overall survival in NSCLC patients (P < 0.001). Multivariate analysis suggested that increased SOX4 expression was a poor independent prognostic predictor for NSCLC patients (P = 0.002). In conclusion, SOX4 plays an important role on NSCLC progression and prognosis and may serve as a convictive prognostic biomarker for NSCLC patients.     

A comparative study on efficiency of adult fibroblasts and amniotic fluid-derived stem cells as donor cells for production of hand-made cloned buffalo (Bubalus bubalis) embryos

The efficiency of two cell types, namely adult fibroblasts, and amniotic fluid stem (AFS) cells as nuclear donor cells for somatic cell nuclear transfer by hand-made cloning in buffalo (Bubalus bubalis) was compared. The in vitro expanded buffalo adult fibroblast cells showed a typical “S” shape growth curve with a doubling time of 40.8 h and stained positive for vimentin. The in vitro cultured undifferentiated AFS cells showed a doubling time of 33.2 h and stained positive for alkaline phosphatase, these cells were also found positive for undifferentiated embryonic stem cell markers like OCT-4, NANOG and SOX-2, which accentuate their pluripotent property. Further, when AFS cells were exposed to corresponding induction conditions, these cells differentiated into osteogenic, adipogenic and chondrogenic lineages which was confirmed through alizaran, oil red O and alcian blue staining, respectively. Cultured adult fibroblasts and AFS cells of passages 10–15 and 8–12, respectively, were used as nuclear donors. A total of 94 embryos were reconstructed using adult fibroblast as donor cells with cleavage and blastocyst production rate of 62.8 ± 1.8 and 19.1 ± 1.5, respectively. An overall cleavage and blastocyst formation rate of 71.1 ± 1.2 and 29.9 ± 2.2 was obtained when 97 embryos were reconstructed using AFS cells as donor cells. There were no significant differences (P > 0.05) in reconstructed efficiency between the cloned embryos derived from two donor cells, whereas the results showed that there were significant differences (P < 0.05) in cleavage and blastocyst rates between the cloned embryos derived from two donor cell groups. Average total cell numbers for blastocyst generated using AFS cells (172.4 ± 5.8) was significantly (P < 0.05) higher than from adult fibroblasts (148.2 ± 6.1). This study suggests that the in vitro developmental potential of the cloned embryos derived from AFS cells were higher than that of the cloned embryos derived from adult fibroblasts in buffalo hand-made cloning.     

血清尿酸、白介素6、P-tau181与阿尔茨海默病患者认知功能、日常生活能力和预后的关系分析

摘要 目的：探讨血清尿酸（UA）、白细胞介素-6（IL-6）、磷酸化Tau181（P-tau181）与阿尔茨海默病（AD）患者认知功能、日常生活能力和预后的关系。方法：选择2018年5月至2021年1月上海交通大学医学院附属第九人民医院与上海交通大学医学院附属第九人民医院黄浦分院收治的98例AD患者（AD组）和71例门诊体检的健康志愿者（对照组）,检测血清UA、IL-6、P-tau181水平,使用简易智力状态检查量表（MMSE）、蒙特利尔认知评估量表（MoCA）评估患者认知功能,Barthel指数（BI）评估患者日常生活能力。所有患者出院后随访1年,统计随访期间不良预后发生情况。Pearson相关性分析UA、IL-6、P-tau181与MMSE、MoCA、BI的相关性,多因素Logistic回归分析AD患者预后不良的危险因素。结果：AD组血清UA水平和MMSE、MoCA评分、BI低于对照组（P＜0.05）,IL-6、P-tau181水平高于对照组（P＜0.05）。AD患者血清UA水平与MMSE、MoCA评分、BI呈正相关（P＜0.05）,IL-6、P-tau181水平与MMSE、MoCA评分、BI呈负相关（P＜0.05）。多因素Logistic回归分析结果显示：长期卧床、AD痴呆阶段、高水平IL-6、高水平P-tau181是AD患者预后不良的危险因素（P＜0.05）,高水平UA是保护因素（P＜0.05）。结论：AD患者血清UA水平降低,IL-6、P-tau181水平升高,且与认知功能障碍、日常生活能力降低以及预后不良有关,检测血清UA、IL-6、P-tau181可辅助评估AD病情和预后。     

The Effects of Synbiotic Supplementation on Pregnancy Outcomes in Gestational Diabetes

Synbiotics are known to exert multiple beneficial effects, including anti-inflammatory and antioxidative actions. This study was designed to evaluate the effects of synbiotic administration on biomarkers of inflammation, oxidative stress, and pregnancy outcomes among gestational diabetic (GDM) women. This randomized, double-blind, placebo-controlled clinical trial was carried out among 60 subjects with GDM who were not on oral hypoglycemic agents. Patients were randomly assigned to consume either one synbiotic capsule containing Lactobacillus acidophilus strain T16 (IBRC-M10785), L. casei strain T2 (IBRC-M10783), and Bifidobacterium bifidum strain T1 (IBRC-M10771) (2 × 10⁹ CFU/g each) plus 800 mg inulin (HPX) (n = 30) or placebo (n = 30) for 6 weeks. Compared with the placebo, synbiotic supplementation significantly decreased serum high-sensitivity C-reactive protein (hs-CRP) (? 1.9 ± 4.2 vs. +1.1 ± 3.5 mg/L, P = 0.004), plasma malondialdehyde (MDA) (? 0.1 ± 0.6 vs. + 0.3 ± 0.7 μmol/L, P = 0.02), and significantly increased total antioxidant capacity (TAC) (+ 70.1 ± 130.9 vs. ? 19.7 ± 124.6 mmol/L, P = 0.009) and total glutathione (GSH) levels (+ 28.7 ± 61.5 vs. ? 14.9 ± 85.3 μmol/L, P = 0.02). Supplementation with synbiotic had a significant decrease in cesarean section rate (16.7 vs. 40.0%, P = 0.04), lower incidence of hyperbilirubinemic newborns (3.3 vs. 30.0%, P = 0.006), and newborns’ hospitalization (3.3 vs. 30.0%, P = 0.006) compared with the placebo. Synbiotic supplementation did not affect plasma nitric oxide (NO) levels and other pregnancy outcomes. Overall, synbiotic supplementation among GDM women for 6 weeks had beneficial effects on serum hs-CRP, plasma TAC, GSH, and MDA; cesarean section; incidence of newborn’s hyperbilirubinemia; and newborns’ hospitalization but did not affect plasma NO levels and other pregnancy outcomes. http://www.irct.ir: www.irct.ir: IRCT201704205623N108     

蒙特利尔认知评估量表在血管性认知功能障碍中的应用分析

目的:研究蒙特利尔认知评估量表(MoCA)诊断临界值在宁夏回族自治区患有血管性认知功能障碍(VCI)中的应用价值。方法:对宁夏回族自治区人民医院神经内科住院治疗的126例脑血管功能性认知缺陷患者分为非痴呆性血管认知功能障碍(VCIND)组53例、认知功能正常(NCI)组47例和血管性痴呆(VaD)组26例,分别予以简易精神状态量表(MMSE)和MoCA进行认知能力检测,分析比较三组患者的诊断效果。结果:将认知功能障碍MoCA临界值26分定义认知功能障碍时,VCIND组MoCA评分结果显示敏感度86.8%、准确度94.3%;VaD组敏感度100.0%、准确度88.5%与MMSE比较均有统计学意义(P0.05)。结论:采用MoCA在VCI筛查评估中的诊断效果极佳,具有良好的敏感性、特异度和信度,临床推荐应用。     

Magnesium Supplementation and the Effects on Wound Healing and Metabolic Status in Patients with Diabetic Foot Ulcer: a Randomized,Double-Blind,Placebo-Controlled Trial

Hypomagnesemia is associated with the development of neuropathy and abnormal platelet activity, both of which are risk factors for diabetic foot ulcer (DFU). This study was carried out to evaluate the effects of magnesium administration on wound healing and metabolic status in subjects with DFU. This randomized, double-blind, placebo-controlled trial was performed among 70 subjects with grade 3 DFU. Subjects were randomly divided into two groups (35 subjects each group) to receive either 250 mg magnesium oxide supplements or placebo daily for 12 weeks. Pre- and post-intervention wound depth and appearance were scored in accordance with the “Wagner-Meggitt’s” wound assessment tool. Fasting blood samples were taken at baseline and after the 12-week intervention to assess related markers. After the 12-week treatment, compared with the placebo, magnesium supplementation resulted in a significant increase in serum magnesium (+0.3 ± 0.3 vs. ?0.1 ± 0.2 mg/dL, P < 0.001) and significant reductions in ulcer length (?1.8 ± 2.0 vs. ?0.9 ± 1.1 cm, P = 0.01), width (?1.6 ± 2.0 vs. ?0.8 ± 0.9 cm, P = 0.02), and depth (?0.8 ± 0.8 vs. ?0.3 ± 0.5 cm, P = 0.003). In addition, significant reductions in fasting plasma glucose (?45.4 ± 82.6 vs. ?10.6 ± 53.7 mg/dL, P = 0.04), serum insulin values (?2.4 ± 5.6 vs. +1.5 ± 9.6 μIU/mL, P = 0.04), and HbA1c (?0.7 ± 1.5 vs. ?0.1 ± 0.4%, P = 0.03) and a significant rise in the quantitative insulin sensitivity check index (+0.01 ± 0.01 vs. ?0.004 ± 0.02, P = 0.01) were seen following supplementation of magnesium compared with the placebo. Additionally, compared with the placebo, taking magnesium resulted in significant decrease in serum high-sensitivity C-reactive protein (hs-CRP) (?19.6 ± 32.5 vs. ?4.8 ± 11.2 mg/L, P = 0.01) and significant increase in plasma total antioxidant capacity (TAC) concentrations (+6.4 ± 65.2 vs. ?129.9 ± 208.3 mmol/L, P < 0.001). Overall, magnesium supplementation for 12 weeks among subjects with DFU had beneficial effects on parameters of ulcer size, glucose metabolism, serum hs-CRP, and plasma TAC levels. Clinical trial registration number: http://www.irct.ir: IRCT201612225623N96     

Effects of infliximab on sister chromatid exchanges and chromosomal aberration in patients with rheumatoid arthritis

The aim of this study was to evaluate in a 24-weeks the effect of anti-TNF-alpha, infliximab, on cytogenetic biomarkers in peripheral lymphocytes of patients with rheumatoid arthritis (RA). A total of 40 patients with RA met the criteria to be treated with methotrexate (15 mg/week) were evaluated. Twenty patients, randomly selected, were treated with infliximab in addition to methotrexate (group I), whereas the other 20 patients continued with only methotrexate treatment (group M). Twenty healthy volunteers matched for age, gender and smoking habits served as control group (group C). At baseline, sister chromatid exchange rate was 7.20 ± 2.21 in group I, 7.40 ± 1.60 in group M and 4.97 ± 1.32 in group C (P < 0.01 vs group I and M). After 24-weeks, sister chromatid exchange rate was 7.87 ± 2.54 in group I and 7.81 ± 1.95 in group M (P = ns). High frequency cells count was 4.9 % and 4.7 % in the groups I and M, respectively, at the end of the study (P = ns). The basal chromosomal aberration frequency was 4.90 % in group I and 5.20 % in groups M; after 24-weeks, this was 5.10 % in group I and 5.10 % in groups M (P = ns). Infliximab treatment, for 24 weeks, did not increase the cytogenetic biomarkers in patients with RA. Our data show that the use of infliximab has not a genotoxic effect in patients with RA.     

Serum and cerebrospinal fluid concentrations of homoarginine,arginine, asymmetric and symmetric dimethylarginine,nitrite and nitrate in patients with multiple sclerosis and neuromyelitis optica

The pathogenic hallmarks of multiple sclerosis (MS) and neuromyelitis optica (NMO) are cellular and humoral inflammatory infiltrates and subsequent demyelination, or astrocytic cell death in NMO, respectively. These processes are accompanied by disruption of the blood–brain barrier as regularly observed by gadolinium enhancement on magnetic resonance imaging. The role of the l-arginine/nitric oxide (NO) pathway in the pathophysiology of neuroinflammatory diseases, such as MS and NMO, remains unclear. In the present study, we measured the concentrations of the nitric oxide (NO) metabolites nitrate and nitrite, the endogenous substrates of NO synthase (NOS) l-arginine (Arg) and l-homoarginine (hArg), and asymmetric dimethylarginine (ADMA), the endogenous inhibitor of NOS activity, in the serum and cerebrospinal fluid (CSF) of patients with MS, NMO or other neurologic diseases (OND). MS (551 ± 23 nM, P = 0.004) and NMO (608 ± 51 nM, P = 0.006) patients have higher ADMA concentrations in serum than healthy controls (HC; 430 ± 24 nM). For MS, this finding was confirmed in CSF (685 ± 100 nM in relapsing–remitting multiple sclerosis, RRMS; 597 ± 51 nM in secondary progressive multiple sclerosis, SPMS) compared with OND (514 ± 37 nM; P = 0.003). Serum concentrations of Arg (61.1 ± 9.7 vs. 63.6 ± 4.9 µM, P = 0.760), hArg (2.62 ± 0.26 vs. 2.52 ± 0.23 µM, P = 0.891), nitrate (38.1 ± 2.2 vs. 38.1 ± 3.0 µM) and nitrite (1.37 ± 0.09 vs. 1.55 ± 0.03 µM) did not differ between MS and OND. Also, CSF concentrations of hArg (0.685 ± 0.100 µM in RRMS, 0.597 ± 0.051 µM in SPMS, 0.514 ± 0.037 µM in OND), nitrate (11.3 ± 0.6 vs. 10.5 ± 0.3 µM) and nitrite (2.84 ± 0.32 vs. 2.41 ± 0.11 µM) did not differ between the groups. In NMO patients, however, serum Arg (117 ± 11 vs. 64 ± 4.9 μM, P = 0.004), nitrate (29 ± 2.1 vs. 38 ± 3 μM, P = 0.03), and nitrite (1.09 ± 0.02 vs. 1.55 ± 0.033 µM, P < 0.0001) were significantly different as compared to OND. Symmetric dimethylarginine (SDMA) concentration did not differ in serum between MS and HC (779 ± 43 vs. 755 ± 58 nM, P = 0.681) or in CSF between MS and OND patients (237 ± 11 vs. 230 ± 17 nM, P = 0.217). Our study suggests a potential role for ADMA and Arg in neuroinflammatory diseases with diverse functions in MS and NMO. Higher ADMA synthesis may explain reduced NO availability in NMO. hArg and SDMA seem not to play an important role in MS and NMO.     

The Report of Sustained Low-Efficiency Dialysis (SLED) Treatment in Fifteen Patients of Severe Snakebite

To investigate the therapeutic efficacy of sustained low-efficiency dialysis (SLED) in severe snakebite patients. Fifteen patients of severe snakebite was treated with SLED from July 2005 to August 2009 were included in the study. Central venous access was established in all patients. SLED was administered using Dialog⁺ dialyzer (B. Braun, Germany). SLED sessions were 6–12 h in duration at a blood flow rate of 200 ml/min and a dialysate flow rate of 300 ml/min. Heparin or low molecular weight heparin was used as anticoagulant. Biochemical indicators, APACHE II scores before and after SLED, and clinical outcomes were evaluated. The levels of serum creatinine, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, creatine kinase isozyme MB, and creatine kinase were significantly lower than the level before SLED (P < 0.05); the level of cholinesterase was significantly higher after SLED (P < 0.01); the APACHE II score before SLED was 14.1 ± 3.8, but decreased significantly to 7.9 ± 1.4, 6.2 ± 1.1, and 4.2 ± 0.8 on days 1, 2, and 7 after SLED, respectively (P < 0.01). Three patients died on days 1, 3, and 4 after SLED, respectively. The remaining twelve patients were either cured or showed improvement at the time of discharge. The survival rate was 80 % where as mortality was 20 %. SLED may be an effective treatment option in severe snakebite patients. It can reduce mortality, thereby, resulting in increased survival rates.     

Use of yeast (<Emphasis Type="Italic">Pichia kudriavzevii</Emphasis>) as a novel feed additive to ameliorate the effects of aflatoxin B<Subscript>1</Subscript> on broiler chicken performance

The aim of this study was to evaluate the efficacy of autochthonous Pichia kudriavzevii as a novel bioadsorbent for aflatoxin B₁ (AFB₁). The selection of this yeast was based on the AFB₁ adsorption capacity previously demonstrated in vitro (Magnoli et al. 2016). One-day-old Cobb broilers (n = 160) were randomly assigned to four dietary treatments (T1: basal diet (B); T2: B + 0.1% yeast; T3: B + AFB₁, 100 μg/kg; T4: B + 0.1% yeast + AFB₁, 100 μg/kg). Performance parameters (average daily weight gain body, average daily consumption, feed conversion ratio, carcass weight, and dead weight), biochemical parameters (albumin, globulin, and albumin/globulin), liver pathological changes, and AFB₁ residual levels in the liver and excreta were evaluated. Significant differences (P < 0.05) in performance parameters were observed among treatments and controls: T3 group showed the lowest average daily body weight gain value while in T4 group, the value of this parameter increased significantly (P < 0.05). T3 and T4 groups showed the lowest and highest values for average daily feed consumption, respectively. The feed conversion ratio (FC) showed no significant differences among treatments. T3 group showed the lowest dead weight and carcass weight compared with T1 group. The biochemical parameters showed no significant differences among treatments. T3 group showed macroscopic and microscopic liver changes compared to the control. Aflatoxin B₁ levels (μg/g) were detected in broiler livers and showed significant differences among treatments (P < 0.05). In conclusion, native P. kudriavzevii incorporation (0.1%) in broiler diets containing AFB₁ was shown to be effective in ameliorating the adverse effects of AFB₁ on production.     

The Influences of Chromium Supplementation on Glycemic Control,Markers of Cardio-Metabolic Risk,and Oxidative Stress in Infertile Polycystic ovary Syndrome Women Candidate for In vitro Fertilization: a Randomized,Double-Blind,Placebo-Controlled Trial

This study was carried out to investigate the effects of chromium intake on glycemic control, markers of cardio-metabolic risk, and oxidative stress in infertile polycystic ovary syndrome (PCOS) women candidate for in vitro fertilization (IVF). This randomized double-blind, placebo-controlled trial was done among 40 subjects with infertile PCOS candidate for IVF, aged 18–40 years old. Individuals were randomly allocated into two groups to take either 200 μg/day of chromium (n?=?20) or placebo (n?=?20) for 8 weeks. Biochemical parameters were assessed at baseline and at end-of-trial. Compared with the placebo, taking chromium supplements led to significant reductions in fasting plasma glucose (??2.3?±?5.7 vs. +?0.9?±?3.1 mg/dL, P?=?0.03), insulin levels (??1.4?±?2.1 vs. +?0.4?±?1.7 μIU/mL, P?=?0.004), homeostatic model of assessment for insulin resistance (??0.3?±?0.5 vs. +?0.1?±?0.4, P?=?0.005), and a significant increase in quantitative insulin sensitivity check index (+?0.004?±?0.008 vs. ??0.001?±?0.008, P?=?0.03). In addition, chromium supplementation significantly decreased serum triglycerides (??19.2?±?33.8 vs. +?8.3?±?21.7 mg/dL, P?=?0.004), VLDL- (??3.8?±?6.8 vs. +?1.7?±?4.3 mg/dL, P?=?0.004) and total cholesterol concentrations (??15.3?±?26.2 vs. ??0.6?±?15.9 mg/dL, P?=?0.03) compared with the placebo. Additionally, taking chromium supplements was associated with a significant increase in plasma total antioxidant capacity (+?153.9?±?46.1 vs. ??7.8?±?43.9 mmol/L, P?<?0.001) and a significant reduction in malondialdehyde values (?0.3?±?0.3 vs. +?0.1?±?0.2 μmol/L, P?=?0.001) compared with the placebo. Overall, our study supported that chromium administration for 8 weeks to infertile PCOS women candidate for IVF had beneficial impacts on glycemic control, few variables of cardio-metabolic risk, and oxidative stress.     

Effects of yokukansan on behavioral and psychological symptoms of vascular dementia: an open-label trial

Previous clinical trials suggest that the traditional Japanese medicine yokukansan has beneficial effects on the behavioral and psychological symptoms of dementia (BPSD). The present study was conducted to elucidate the efficacy of yokukansan on BPSD in patients with vascular dementia. Thirteen Japanese patients (9 men and 4 women) who were diagnosed as having vascular dementia (VaD) according to the diagnostic criteria of NINDS-AIREN were subjected to the open-label clinical trial in which yokukansan (7.5g/day) has been given for 4 weeks. Their mean age was 71.2±6.5 years. The BPSD was evaluated using the Neuropsychiatric Inventory (NPI), cognitive function was evaluated by the Mini-Mental State Examination (MMSE), the activities of daily living was evaluated by Barthel index (BI) and Disability Assessment for Dementia (DAD), and the extrapyramidal signs were evaluated by United Parkinson's Disease Rating Scale (UPDRS). The mean NPI was 33.0±17.3 and 23.6±13.9 for the baseline and after treatment, respectively. It was significantly improved after treatment (p<0.05). In the NPI-subcategories, there was a significant improvement in agitation and disinhibition after the treatment. There was no significant change in MMSE, BI, DAD or UPDRS before and after the treatment. There was no adverse effect during the treatment period. The present results suggest that yokukansan is beneficial for the treatment of BPSD in VaD patients.     

Comparison of Acyclovir and Multistrain <Emphasis Type="Italic">Lactobacillus brevis</Emphasis> in Women with Recurrent Genital Herpes Infections: a Double-Blind,Randomized, Controlled Study

We performed a randomized double-blind controlled trial to compare the efficacy and safety of multistrain probiotic and acyclovir in women patients with recurrent genital herpes simplex virus type 2 (HSV-2) infections. Eighty-one patients enrolled in the study were being treated with multistrain Lactobacillus brevis one vaginal capsule every 12 h and oral acyclovir 400 mg twice daily for 6 months. Of 53 patients who completed both treatment courses, no important differences were identified between acyclovir and probiotic for the primary and secondary efficacy endpoint, resolution of episode (hazard ratio, 0.60; 95% CI, 0.3429 to 1.0663; P = 0.08), lesion healing time (hazard ratio, 0.57; 95% CI, 0.3034 to 1.0717, P = 0.08), viral shedding (hazard ratio, 0.54; 95% CI, 0.3027 to 0.9750, P = 0.04), and percentage of pain (hazard ratio, 0.48; 95% CI, 0.2708 to 0.8545, P = 0.01). The median time to first and second recurrence after treatment were 43 and 121 days in patients receiving acyclovir and 33 and 118 days in patients receiving probiotic (HR 2.61; 95% CI, 1.4427 to 4.7546, P = 0.001, and HR 0.62; 95% CI, 0.3500 to 1.1133, P = 0.1, respectively). No clinically important effects happened during the probiotic treatment but some of adverse events reported in patients taking acyclovir. Easy availability, low cost, and no side effect of L. brevis are valuable properties of probiotic therapy compared with acyclovir. Therefore, we concluded that multistrain L. brevis could play an important role in suppression of recurrent genital herpes simplex virus infection.