Synthesis and acid ionization constants of cyclic cystine peptides

Cyclic peptide disulfides of the general formula were synthesized from the corresponding peptide derivatives [Boc-Cys(Trt)(Gly)-_n-Cys(Trt)-OBu^t] by oxidation with iodine in methanol and by subsequent removal of the terminal groups with trifluoroacetic acid. Acid ionization constants of the obtained peptides were determined by potentiometric titration in aqueous KCl (0.1 mol/L) medium. All compounds have two dissociable hydrogens, corresponding to carboxyl (pK¹= 2.35–2.84) and to terminal amino group (pK₂= 5.61–6.93); pK₁, values show first an upward and then a downward trend with the increase in ring size; the opposite is true for pK₂, values. These trends could be tentatively attributed to the intramolecular salt bridge (-COO——-NH⁺₃-) formation.     

Initial validation of the SLEEP-50 questionnaire

Initial psychometric properties of the SLEEP-50 questionnaire, designed to detect sleep disorders as listed in the Diagnostic and Statistical Manual of Mental Disorders (4th ed., Text Revision), were examined. The sample consisted of 377 college students, 246 sleep patients, 32 nightmare sufferers, and 44 healthy volunteers. The internal consistency was high (Cronbach's alpha = .85); test-retest correlations fell between .65 and .89. Principal component analysis with a direct oblimin rotation revealed a factor structure that closely matched the designed structure. Sensitivity and specificity scores were promising for all sleep disorders; the agreement between all clinical diagnoses and SLEEP-50-classifications was substantial (kappa = .77). These initial findings indicate that the SLEEP-50 seems able to detect a variety of sleep disorders. The SLEEP-50 can aid in screening for common sleep disorders in the general population.     

Regional specificity of manganese accumulation and clearance in the mouse brain: implications for manganese‐enhanced MRI

Manganese‐enhanced MRI has recently become a valuable tool for the assessment of in vivo functional cerebral activity in animal models. As a result of the toxicity of manganese at higher dosages, fractionated application schemes have been proposed to reduce the toxic side effects by using lower concentrations per injection. Here, we present data on regional‐specific manganese accumulation during a fractionated application scheme over 8 days of 30 mg/kg MnCl₂, as well as on the clearance of manganese chloride over the course of several weeks after the termination of the whole application protocol supplying an accumulative dose of 240 mg/kg MnCl₂. Our data show most rapid accumulation in the superior and inferior colliculi, amygdala, bed nucleus of the stria terminalis, cornu ammonis of the hippocampus and globus pallidus. The data suggest that no ceiling effects occur in any region using the proposed application protocol. Therefore, a comparison of basal neuronal activity differences in different animal groups based on locally specific manganese accumulation is possible using fractionated application. Half‐life times of manganese clearance varied between 5 and 7 days, and were longest in the periaqueductal gray, amygdala and entorhinal cortex. As the hippocampal formation shows one of the highest T₁‐weighted signal intensities after manganese application, and manganese‐induced memory impairment has been suggested, we assessed hippocampus‐dependent learning as well as possible manganese‐induced atrophy of the hippocampal volume. No interference of manganese application on learning was detected after 4 days of Mn²⁺ application or 2 weeks after the application protocol. In addition, no volumetric changes induced by manganese application were found for the hippocampus at any of the measured time points. For longitudinal measurements (i.e. repeated manganese applications), a minimum of at least 8 weeks should be considered using the proposed protocol to allow for sufficient clearance of the paramagnetic ion from cerebral tissue. Copyright © 2012 John Wiley & Sons, Ltd.     

Counseling Fathers (2010) by C.Z. Oren and D.C. Oren

No abstract available for this article.     

A GCH1 haplotype confers sex‐specific susceptibility to pain crises and altered endothelial function in adults with sickle cell anemia

GTP cyclohydrolase (GCH1) is rate limiting for tetrahydrobiopterin (BH4) synthesis, where BH4 is a cofactor for nitric oxide (NO) synthases and aromatic hydroxylases. GCH1 polymorphisms are implicated in the pathophysiology of pain, but have not been investigated in African populations. We examined GCH1 and pain in sickle cell anemia where GCH1 rs8007267 was a risk factor for pain crises in discovery (n = 228; odds ratio [OR] 2.26; P = 0.009) and replication (n = 513; OR 2.23; P = 0.004) cohorts. In vitro, cells from sickle cell anemia subjects homozygous for the risk allele produced higher BH4. In vivo physiological studies of traits likely to be modulated by GCH1 showed rs8007267 is associated with altered endothelial dependent blood flow in females with SCA (8.42% of variation; P = 0.002). The GCH1 pain association is attributable to an African haplotype with where its sickle cell anemia pain association is limited to females (OR 2.69; 95% CI 1.21–5.94; P = 0.01) and has the opposite directional association described in Europeans independent of global admixture. The presence of a GCH1 haplotype with high BH4 in populations of African ancestry could explain the association of rs8007267 with sickle cell anemia pain crises. The vascular effects of GCH1 and BH4 may also have broader implications for cardiovascular disease in populations of African ancestry. Am. J. Hematol. 89:187–193, 2014. © 2013 Wiley Periodicals, Inc.     

Pupillometry tracks cognitive load and salience network activity in a working memory functional magnetic resonance imaging task

The diameter of the human pupil tracks working memory processing and is associated with activity in the frontoparietal network. At the same time, recent neuroimaging research has linked human pupil fluctuations to activity in the salience network. In this combined functional magnetic resonance imaging (fMRI)/pupillometry study, we recorded the pupil size of healthy human participants while they performed a blockwise organized working memory task (N‐back) inside an MRI scanner in order to monitor the pupil fluctuations associated neural activity during working memory processing. We first confirmed that mean pupil size closely followed working memory load. Combining this with fMRI data, we focused on blood oxygen level dependent (BOLD) correlates of mean pupil size modeled onto the task blocks as a parametric modulation. Interrogating this modulated task regressor, we were able to retrieve the frontoparietal network. Next, to fully exploit the within‐block dynamics, we divided the blocks into 1 s time bins and filled these with corresponding pupil change values (first‐order derivative of pupil size). We found that pupil change within N‐back blocks was positively correlated with BOLD amplitudes in the areas of the salience network (namely bilateral insula, and anterior cingulate cortex). Taken together, fMRI with simultaneous measurement of pupil parameters constitutes a valuable tool to dissect working memory subprocesses related to both working memory load and salience of the presented stimuli.     

提高孕产期保健质量是降低贫困地区壮族妇女孕产妇死亡的有力措施

目的 :提高贫困地区壮族农村住院分娩率 ,加强产时保健 ,提高贫困地区壮族农村产科质量 ,降低产后出血死亡率。在广西 30个老少边山穷地区 ,以项目和“母亲安全工程”为载体 ,在经济条件困难 ,基础设施落后 ,围产保健服务管理滞后的情况下 ,积极贯彻落实《母婴保健法》,依法规范围产保健服务管理 ,多方筹措资金 ,加强产科软、硬件建设 ,以项目工作为龙头 ,以科研为先导 ,积极推广适宜技术。以健康促进为目的 ,大力开展健康教育和生殖保健活动 ,使围产保健工作取得了较好成绩。30个贫困地区壮族农村近半数以上乡卫生院产科建设已达自治区标准 ,基本能满足贫困地区农民住院分娩的需求 ,并带动广西妇幼卫生工作的发展