选择性头部降温对胎羊缺血性脑损伤纹状体神经元凋亡和星形胶质细胞增殖的影响

目的研究选择性头部降温对缺血性脑损伤胎羊纹状体神经元凋亡和星形胶质细胞增殖的影响。方法胎羊于妊娠117~124d时通过双侧颈动脉阻塞30min造成双侧脑缺血损伤,损伤后将胎羊随机分为:损伤组(n=10)、2h低温组(损伤后2h开始亚低温治疗,n=7)和6h低温组(损伤后6h开始亚低温治疗,n=8),另设正常对照组(n=5)。通过冷循环水进行选择性头部降温,取脑组织用免疫组化法检测胎羊纹状体caspase-3(半胱天冬氨酸酶-3),GFAP(胶质纤维酸性蛋白)和PCNA(增殖细胞核抗原)的表达。结果①纹状体神经元凋亡:正常对照组中,caspase-3表达极少(11.00±13.77),损伤组caspase-3免疫阳性细胞为177.70±48.69,明显增加(P=0.000),损伤后2h治疗组(54.14±39.44,P=0.000)和损伤后6h治疗组(122.43±52.36,P=0.017)均能减少caspase-3免疫阳性细胞。②纹状体星形胶质细胞增殖:与正常对照组(163.40±21.98)相比,缺血性脑损伤组的GFAP免疫阳性细胞明显增多(433.25±66.69,P=0.000),损伤后2h开始亚低温治疗(219.50±35.31,P=0.000)和损伤后6h开始亚低温治疗(272.50±86.20,P=0.000)均能减少GFAP免疫阳性细胞。③纹状体PCNA阳性细胞的表达:在正常对照组中,PCNA免疫阳性细胞较少,为153.40±12.46,缺血性脑损伤组的PCNA免疫阳性细胞明显增多(353.70±45.60,P=0.000),损伤后2h开始亚低温治疗(187.14±26.26,P=0.000)和损伤后6h开始亚低温治疗(230.25±67.46,P=0.000)均能减少PCNA免疫阳性细胞。结论亚低温可以抑制纹状体神经元的凋亡和星形胶质细胞的增殖,该作用可能为选择性头部降温的脑保护作用机制之一。     

The influence of children's self-report trait anxiety and depression on visual search for emotional faces

BACKGROUND: This study presents two experiments that investigated the relationship between 7- and 10-year-olds' levels of self-report trait anxiety and depression and their visual search for threatening (angry faces) and non-threatening (happy and neutral faces) stimuli. METHOD: In both experiments a visual search paradigm was used to measure participants' reaction times to detect the presence or absence of angry, happy or neutral schematic faces (Experiment 1) or cartoon drawings (Experiment 2). On target present trials, a target face was displayed alongside three, five or seven distractor items. On target absent trials all items were distractors. RESULTS: Both experiments demonstrated that on target absent (but not present) trials, increased levels of anxiety produced significantly faster search times in the angry face condition, but not in the neutral condition. In Experiment 2 there was some trend towards significance between anxiety and searches for happy faces in absent trials. There were no effects of depression on search times in any condition. CONCLUSION: The results support previous work highlighting a specific link between anxiety and attention to threat in childhood.     

High incidence of chromosomal abnormalities in oocyte donors

Oocyte donors are chosen among phenotypically normal and fertile women who are not expected to carry any chromosomal abnormality. A high incidence of balanced structural chromosomal rearrangements has been found within oocyte donors. This result raises the question of a possible bias in their recruitment with respect to their familial background and/or personal reproductive history.     

Effect of the Affordable Care Act on healthcare utilization for Veterans with spinal cord injuries and disorders

Context/Objective: Provisions of the Affordable Care Act (ACA) potentially increase insurance options for Veterans with disabilities. We examined Veterans with spinal cord injuries and disorders (SCI/D) to assess whether the ACA was associated with changes in healthcare utilization from Department of Veterans Affairs (VA) healthcare facilities.Design: Using national VA data, we investigated impacts on VA healthcare utilization pre- (2012/13) and post-ACA (2014/15) implementation with negative binomial regression models.Setting: VA healthcare facilities.Participants: 8,591 VA users with SCI/D. Veterans with acute myelitis, Guillain-Barré syndrome, multiple sclerosis, or amyotrophic lateral sclerosis were excluded as were patients who died during the study period.Interventions: We assessed VA healthcare utilization before and after ACA implementation.Outcome Measures: Total numbers of VA visits for SCI/D care, diagnostic care, primary care, specialty care, and mental health care, and VA admissions.Results: The number of VA admissions was 7% higher in the post than pre-ACA implementation period (P < 0.01). The number of VA visits post-implementation increased for SCI/D care (8%; P < 0.01) and specialty care (12%; P < 0.001). Conversely, the number of mental health visits was 17% lower in the post-ACA period (P < 0.001). Veterans with SCI/D who live <5 miles from their nearest VA facility received VA care more frequently than those ≥40 miles from VA (P < 0.001).Conclusion: Counter to expectations, results suggest that Veterans with SCI/D sought more frequent VA care after ACA implementation, indicating Veterans with SCI/D continue to utilize the lifelong, comprehensive care provided at VA.     

Functional significance of evolving protein sequence in dihydrofolate reductase from bacteria to humans

With the rapidly growing wealth of genomic data, experimental inquiries on the functional significance of important divergence sites in protein evolution are becoming more accessible. Here we trace the evolution of dihydrofolate reductase (DHFR) and identify multiple key divergence sites among 233 species between humans and bacteria. We connect these sites, experimentally and computationally, to changes in the enzyme’s binding properties and catalytic efficiency. One of the identified evolutionarily important sites is the N23PP modification (∼mid-Devonian, 415–385 Mya), which alters the conformational states of the active site loop in Escherichia coli dihydrofolate reductase and negatively impacts catalysis. This enzyme activity was restored with the inclusion of an evolutionarily significant lid domain (G51PEKN in E. coli enzyme; ∼2.4 Gya). Guided by this evolutionary genomic analysis, we generated a human-like E. coli dihydrofolate reductase variant through three simple mutations despite only 26% sequence identity between native human and E. coli DHFRs. Molecular dynamics simulations indicate that the overall conformational motions of the protein within a common scaffold are retained throughout evolution, although subtle changes to the equilibrium conformational sampling altered the free energy barrier of the enzymatic reaction in some cases. The data presented here provide a glimpse into the evolutionary trajectory of functional DHFR through its protein sequence space that lead to the diverged binding and catalytic properties of the E. coli and human enzymes.     

Increasing Preload Volume with Water Reduces Rated Appetite But Not Food Intake in Healthy Men Even with Minimum Delay Between Preload and Test Meal

Abstract

The role of gastric volume in the short-term control of eating in humans remains unclear, with some studies reporting that food volume alone can reduce appetite but others finding no such effect. A recent study in our laboratory, found effects of preload volume on subjective appetite (hunger, fullness) but not intake, and found effects of preload energy on intake but not appetite. That study used an interval of 30 min between serving preloads and the test meal, and the present study attempted to maximise the effects of the volume manipulation by removing the delay between the preload and test meal. We administered four soup-based preloads varying in volume (150 and 450 ml) using water, and energy density (1.4 and 4.2 kJ/ml) using maltodextrin, producing three energy levels (209, 629, 629 and 1886 kJ; repeated measures). These were followed immediately by an unlimited hot pasta lunch, during which food weight was monitored continuously by computer. Increasing soup volume at constant energy (629 kJ) reduced appetite ratings, but not intake. In contrast, increasing soup energy at constant volume (450 ml) reduced intake, without affecting appetite. The discrepancies between our results and other reported studies suggest that volume is more influential when intakes are large, or that there may be a threshold concentration for nutrients in the GI tract before volume alone is tangibly expressed in subsequent eating.