Effect of gamma aminobutyric acid (GABA) or GABA with glutamic acid decarboxylase (GAD) on the progression of type 1 diabetes mellitus in children: Trial design and methodology

BackgroundEvidence suggests that GABA may reduce pancreatic inflammation, protect β-cells from autoimmune destruction, and potentiate the regeneration of new β-cells in the setting of type 1 diabetes mellitus (T1DM). The enzyme GAD, also expressed in human pancreatic β-cells, is an antigenic target of reactive T cells. We hypothesized that treatment of children with recent onset T1DM with GABA or combination GABA with GAD will preserve β-cell function and ameliorate autoimmune dysregulation.MethodsThis is a one-year, prospective, randomized, double-blind, placebo-controlled trial. Ninety-nine patients aged 4–18 years with newly diagnosed T1DM are randomized into three treatment groups: 1) oral GABA twice daily in addition to two injections of recombinant GAD enzyme, 2) oral GABA plus placebo GAD injections, or 3) placebo GABA and placebo GAD. Patients are evaluated at baseline and months 1, 5, 8 and 12. Mixed meal tolerance testing is performed at all but the 8-month visit. Laboratory studies will assess indices of beta and alpha cell function, glycemic control, immunophenotyping, and diabetes-related autoantibodies.ResultsThe primary outcome is the effect on pancreatic β-cell function as measured by meal-stimulated c-peptide secretion compared between the treatment groups before and after one year of treatment. Secondary outcomes include: 1) fasting and meal stimulated glucagon and proinsulin levels, 2) response in insulin usage by participants, 3) indices of immune cell function, and 4) effect on autoantibodies GAD65, ICA512, and ZnT8.Conclusions: This trial will determine the safety and efficacy of GABA and combination GABA/GAD therapy to delay T1DM progression in children.     

弥散张量成像在癫痫中的研究进展

癫痫作为多种病因引起的神经系统慢性、发作性疾病,严重影响着患者的生活质量,因此对其及时诊断和早期治疗极为重要。目前已有多种神经影像技术用于癫痫的定位、定侧和病理生理研究。弥散张量成像是利用水分子在组织中弥散的各向异性成像的磁共振技术,是目前唯一能在活体中无创性地显示脑白质纤维束的方法,它能敏感地显示脑部细微结构,并能揭示各个结构间的功能联系,有助于癫痫的研究。本文主要从癫痫的病因诊断、癫痫手术的辅助指导、癫痫的结构网络及其与癫病功能障碍的相关性研究等方面对DTI应用于癫痫的最新研究进展进行综述。     

Increased IL-10/IL-17 ratio is aggravated along with the prognosis of patients with chronic lymphocytic leukemia

ObjectiveThis study is to investigate the association between the Treg/Th17 cells and prognosis of chronic lymphocytic leukemia (CLL).MethodsTotally 50 CLL patients and 20 Health controls were included in this study. Regulatory T (Treg) cells and the cell subset secreting IL-17 (Th17) in peripheral blood were detected with flow cytometry. Serum levels of IL-10 and IL-17 were determined with ELISA, and expression of Foxp3 and RORγt was assessed with quantitative real-time PCR.ResultsTreg and Th17 cell proportions in peripheral blood in the CLL patients were significantly higher than control. Serum levels of IL-10 and IL-17, and expression of Foxp3 and RORγt, were significantly increased in the CLL patients. Ratios of Treg/Th17 and IL-10/IL-17 were significantly elevated in the CLL patients. Compared with those before treatment, Treg/Th17 and IL-10/IL-17 ratios were declined in the CLL patients in remission. Compared with the non-remission group, Treg cells were significantly decreased, while Th17 cells were significantly increased, resulting in decreased Treg/Th17 ratio, in the remission group. Moreover, the serum IL-10 level was significantly decreased, while the serum IL-17 level was significantly increased, resulting in declined IL-10/IL-17 ratio, in the remission group. Correlation analysis showed that, Treg and Th17 cell counts were significantly associated with CD38 and ZAP-70 expression in the CLL patients. Moreover, the IL-10/IL-17 ratio was also significantly associated with CLL prognostic factors.ConclusionAltered Treg/Th17 and IL-10/IL-17 ratios in CLL would be aggravated along with the disease progression, which might be used as indicators for the disease prognosis.     

Brain impedance variation of directional leads implanted in subthalamic nuclei of Parkinsonian patients

ObjectiveConventional deep brain stimulation (DBS) systems with ring-shaped leads generate spherical electrical fields. In contrast, novel directional leads use segmented electrodes. Aim of this study was to quantify the impedance variations over time in subjects with the directional Cartesia-Boston® system.MethodsImpedance records, programming settings, and clinical data of 11 consecutive Parkinsonian patients implanted with DBS directional leads in two Italian centers (Udine and Vicenza) were retrospectively evaluated. Data were collected before starting stimulation (in the operating room and at days 5 and 40) and after switching stimulation on at the successive follow-up visits (1, 6 and 12 months).ResultsDirectional leads have significantly higher impedance than ring leads. Stimulated contacts had always lower impedance compared to non-stimulated contacts. Before DBS-on, all contacts had higher impedance in the operating room, with an initial decrease five days post-surgery and a subsequent increase at day 40, more evident for directional contacts. The impedance of directional leads increased post-implantation at 1 and 6 months with a plateau at 12 months.ConclusionsThere was a significant difference between the directional and ring leads at baseline (before activation of DBS) and during follow-up (chronic DBS).SignificanceOur study reveals new information about the impedance of segmented electrodes that is useful for patient management during the initial test period, as well as during long-term DBS follow-up.     

Efficacy of lianhuaqingwen granules in the management of chronic rhinosinusitis without nasal polyps

ObjectivesChronic rhinosinusitis (CRS) is a complicated disease with clinical symptoms that are impacted by the absence or presence of nasal polyps (CRSsNP or CRSwNP). Understanding of the different treatments of CRS is very significant in selecting appropriate therapies and preventing exacerbation relevant to this chronic inflammation. This study was aimed to evaluate the effect of Chinese traditional medicine lianhuaqingwen granules on CRSsNP.Materials and methodsCRSsNP patients were enrolled and randomized into placebo or lianhuaqingwen (LHQW) granules treatment group (placebo or LHQW group). Their clinical symptoms were scored using Visual Analog Scale (VAS) and Sino-Nasal Outcome Test (SNOT)-22. Nitric oxide (NO) from nasal cavity and sinus and nasal resistance were also examined. Then, nasal biopsy samples and nasal lavage fluid (NLF) were obtained from these patients, and histologic characteristics of nasal mucosa and T cell subpopulations patterns in the NLF were evaluated. Finally, inflammatory mediators in the NLF were assessed in both groups.ResultsOne hundred and forty patients with CRSsNP finished this one-month study. VAS and SNOT-22 scores and nasal resistance were all decreased distinctly after the treatment of LHQW, but not after placebo. However, the nasal NO concentration was increased in LHQW administration group in comparison with placebo group. There were significant differences in above parameters between these two treatments. Histologic changes in nasal mucosa were improved only in LHQW group. CD4⁺ and CD8⁺ T cells were all downregulated in the LHQW treatment group, but not in placebo group. Inflammatory mediators from the NLF were decreased in LHQW treatment group compared to placebo group. Furthermore, there were significant changes between these two groups in CD4⁺ and CD8⁺ T cell subpopulations and concentrations of inflammatory substances.ConclusionThese findings demonstrate that LHQW granules treatment may control the inflammation in nasal mucosa and result in the improvement of CRSsNP. This Chinese medicine might become a promising therapy in the management of this disease.     

Prevalence and correlates of mild cognitive impairment among diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging results

IntroductionWe estimated the prevalence and correlates of mild cognitive impairment (MCI) among middle-aged and older diverse Hispanics/Latinos.MethodsMiddle-aged and older diverse Hispanics/Latinos enrolled (n = 6377; 50–86 years) in this multisite prospective cohort study were evaluated for MCI using the National Institute on Aging–Alzheimer's Association diagnostic criteria.ResultsThe overall MCI prevalence was 9.8%, which varied between Hispanic/Latino groups. Older age, high cardiovascular disease (CVD) risk, and elevated depressive symptoms were significant correlates of MCI prevalence. Apolipoprotein E4 (APOE) and APOE2 were not significantly associated with MCI.DiscussionMCI prevalence varied among Hispanic/Latino backgrounds, but not as widely as reported in the previous studies. CVD risk and depressive symptoms were associated with increased MCI, whereas APOE4 was not, suggesting alternative etiologies for MCI among diverse Hispanics/Latinos. Our findings suggest that mitigating CVD risk factors may offer important pathways to understanding and reducing MCI and possibly dementia among diverse Hispanics/Latinos.     

Predictors of postoperative acute kidney injury in patients undergoing hip fracture surgery: A systematic review and meta-analysis

BackgroundThe present study aimed to summarize the predictors of acute kidney injury (AKI) in patients after hip surgery.MethodsA literature search was performed using PubMed, EMBASE, Cochrane Library, and Web of Science for studies assessing the predictors of AKI after hip fracture surgery. Pooled odds ratio (OR) and mean difference (MD) of those who experienced AKI compared to those who did not were calculated for each variable. Evidence was assessed using the Newcastle–Ottawa Scale.ResultsTen studies with 34 potential factors were included in the meta-analysis. In the primary analysis, 12 factors were associated with AKI, comprising males (OR 1.25; 95% confidence interval (CI) 1.14–1.36), advanced age (MD 2.28; 95% CI 0.80–3.75), myocardial infarction (OR 1.39; 95% CI 1.18–1.63), hypertension (OR 1.46; 95% CI 1.13–1.89), diabetes (OR 1.84; 95% CI 1.40–2.42), chronic kidney disease (OR 3.66; 95% CI 2.21–6.07), hip arthroplasty (OR 1.35; 95% CI 1.22–1.50), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers use (OR 2.28; 95% CI 1.68–3.08), more intraoperative blood loss (MD 44.06; 95% CI 2.88–85.24), higher preoperative blood urea nitrogen levels (MD 5.29; 95% CI 3.38–7.20), higher preoperative serum creatinine levels (MD 0.4; 95% CI 0.26–0.53), and lower preoperative estimated glomerular filtration rate (MD −19.59; 95% CI −26.92–−12.26). Another 13 factors related to AKI in individual studies were identified in the systematic review.ConclusionRelated prophylaxis strategies should be implemented in patients involved with the above-mentioned characteristics to prevent AKI after hip surgery.