Toxicological aspects of trans fat consumption over two sequential generations of rats: Oxidative damage and preference for amphetamine

Chronic consumption of processed food causes structural changes in membrane phospholipids, affecting brain neurotransmission. Here we evaluated noxious influences of dietary fats over two generations of rats on amphetamine (AMPH)-conditioned place preference (CPP). Female rats received soybean oil (SO, rich in n-6 fatty acids (FA)), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans fatty acids (TFA)) for two successive generations. Male pups from the 2nd generation were maintained on the same supplementation until 41 days of age, when they were conditioned with AMPH in CPP. While the FO group showed higher incorporation of n-3 polyunsaturated-FA (PUFA) in cortex/hippocampus, the HVF group showed TFA incorporation in these same brain areas. The SO and HVF groups showed AMPH-preference and anxiety-like symptoms during abstinence. Higher levels of protein carbonyl (PC) and lower levels of non-protein thiols (NPSH) were observed in cortex/hippocampus of the HVF group, indicating antioxidant defense system impairment. In contrast, the FO group showed no drug-preference and lower PC levels in cortex. Cortical PC was positively correlated with n-6/n-3 PUFA ratio, locomotion and anxiety-like behavior, and hippocampal PC was positively correlated with AMPH-preference, reinforcing connections between oxidative damage and AMPH-induced preference/abstinence behaviors. As brain incorporation of trans and n-6 PUFA modifies its physiological functions, it may facilitate drug addiction.     

Protocol digest of randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel combination therapy for locally advanced pancreatic cancer: Japan clinical oncology group study (JCOG1407)

Gemcitabine is one of the standard treatments for locally advanced pancreatic cancer. Recent studies on metastatic pancreatic cancer have shown that combination chemotherapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP) prolonged the overall survival compared with gemcitabine alone. To select the most promising chemotherapy, a randomized phase II selection design trial was started in July 2016 to compare between modified FOLFIRINOX and GnP for patients with locally advanced pancreatic cancer. A total of 124 patients will be enrolled from 36 Japanese institutions within 2.5 years. The primary endpoint is the proportion of 1-year overall survival, and secondary endpoints are progression-free survival, distant metastasis-free survival, response rate in patients with target lesions, CA19-9 response, adverse events, treatment-related death, early death, grade 4 non-hematological toxicity, and dose intensity. This trial has been registered with the UMIN Clinical Trials Registry [http://www.umin.ac.jp/ctr/index.htm], and the registration number is UMIN000023143.     

Features of “ET plus” correlate with age and tremor duration: “ET plus” may be a disease stage rather than a subtype of essential tremor

BackgroundEssential tremor (ET) is characterized by considerable clinical heterogeneity. In 2018, the term “ET plus” was introduced to mark a potential stratification point for dividing ET into subtypes – ET vs ET plus (i.e., ET cases with neurological features other than action tremor). However, as ET progresses, patients often develop increasingly severe tremor, spread of tremor, tremor under different activation conditions, and other features. Given this situation, ET plus may represent a disease stage rather than a disease classification or subtype. In theory, if the defining characteristics of a disease subtype fluctuate with age or disease duration, it raises the distinct possibility the “subtype” is a disease stage.MethodsA cohort of 241 prospectively enrolled ET cases underwent a detailed motor and cognitive assessment in which the features of ET plus including cerebellar signs (intention tremor, tandem gait difficulty), rest tremor, dystonia, and cognitive performance were evaluated. We determined whether these features of ET plus correlated with action tremor duration and age.ResultsWe demonstrated that numerous ET plus features were significantly correlated with both age and action tremor duration (numerous p values < 0.05). The same relationships were observed in a series of sensitivity analyses.ConclusionWe observed that the component parts of ET plus are highly age- and stage-dependent. These features are yearly-changing features conditional on a demographic and disease stage variable. These data support the notion that ET plus may represent a disease stage rather than a distinct disease subtype or disease classification.     

MEBO治疗慢性难愈性皮肤溃疡的临床疗效观察

目的观察湿润烧伤膏(Moist Exposed Burn Ointment,MEBO)治疗慢性难愈性皮肤溃疡的临床疗效。方法对2010年1月-2014年12月收治的344例慢性难愈性皮肤溃疡患者创面采用"药刀结合"的方法治疗,药即MEBO,刀即外科清创术、植皮术等。患者初诊时尽量清除创面坏死组织,不能耐受一次性清创者行蚕食疗法;清创后创面均匀涂抹MEBO并外敷MEBO药纱包扎治疗,存在潜腔的创面用MEBO药纱填塞引流,待肉芽组织填满创面后行肉芽创面游离植皮术。观察患者创面愈合时间及愈合情况。结果344例患者中除38例患者好转后自动出院,3例患者死于基础疾病外,其余303例患者创面均完全愈合,愈合率达88.1%,创面平均愈合时间为80.4 d±15.8 d。其中,193例患者经MEBO换药治疗后创面自行愈合(56.1%);48例合并趾骨坏死的糖尿病足患者进行了坏死组织剜除术(14.0%);34例骨外露创面进行了钻孔术(9.9%);54例患者进行了肉芽创面植皮术(包括接受趾骨剜除术及骨钻孔术后的创面)。89例烧伤残余创面愈合较快,最短为7 d,最长为29 d,平均愈合时间为18.8 d±4.9 d。结论MEBO可有效控制创面感染,促进坏死组织液化脱落及肉芽组织生长,缩短创面愈合时间,减轻患者疼痛,适时配合"刀法"还可进一步加速坏死组织脱落,促进肉芽组织生长,及时封闭创面,减少瘢痕增生,是治疗慢性难愈性皮肤溃疡的理想方法。     

Novel B3GALTL mutations in classic Peters plus syndrome and lack of mutations in a large cohort of patients with similar phenotypes

Peters plus syndrome (PPS) is a rare autosomal‐recessive disorder characterized by Peters anomaly of the eye, short stature, brachydactyly, dysmorphic facial features, developmental delay, and variable other systemic abnormalities. In this report, we describe screening of 64 patients affected with PPS, isolated Peters anomaly and PPS‐like phenotypes. Mutations in the coding region of B3GALTL were identified in nine patients; six had a documented phenotype of classic PPS and the remaining three had a clinical diagnosis of PPS with incomplete clinical documentation. A total of nine different pathogenic alleles were identified. Five alleles are novel including one frameshift, c.168dupA, p.(Gly57Argfs*11), one nonsense, c.1234C>T, p.(Arg412*), two missense, c.1045G>A, p.(Asp349Asn) and c.1181G>A, p.(Gly394Glu), and one splicing, c.347+5G>T, mutations. Consistent with previous reports, the c.660+1G>A mutation was the most common mutation identified, seen in eight of the nine patients and accounting for 55% of pathogenic alleles in this study and 69% of all reported pathogenic alleles; while two patients were homozygous for this mutation, the majority had a second rare pathogenic allele. We also report the absence of B3GALTL mutations in 55 cases of PPS‐like phenotypes or isolated Peters anomaly, further establishing the strong association of B3GALTL mutations with classic PPS only.     

静脉溶栓后神经功能恶化的治疗观察

目的 探讨抗凝和抗血小板聚集治疗脑梗死静脉溶栓后神经功能恶化的疗效。方法 收集自2015年1月至2019年12月在石家庄市第一医院神经内科经静脉溶栓后神经功能恶化的62例急性脑梗死患者,行头颅CT除外出血转化后随机分为治疗组和对照组,各31例,治疗组采用单抗加抗凝,即阿加曲班联合氯吡格雷治疗,对照组采用双抗,即阿司匹林联合氯吡格雷治疗,比较两组治疗静脉溶栓后神经功能恶化的临床疗效及不良反应情况。结果 治疗14天后治疗组NIHSS评分较对照组偏低（P<0.05）,治疗组mRS评分亦低于对照组（P<0.05）。治疗组发生消化道出血1例,恶心、呕吐1例,对照组发生消化道出血1例,恶心、呕吐2例,对照组和治疗组不良反应的差异不显著。结论 采用阿加曲班联合氯吡格雷治疗,减轻静脉溶栓后神经功能恶化症状,减轻残疾程度,疗效显著,且不会出现严重不良反应,安全可靠。     

“互联网+”健康教育在体检中心中的应用

目的:探讨"互联网+"健康教育在体检中心中的应用效果。方法:在湖北省十堰市人民医院体检中心2017年9-12月进行体检的患者中抽取510例,按照随机数字表法1:1比例分组为干预组(255例)和对照组(255例),对照组采用常规健康教育,干预组通过体检中心的护士采用微信、App,进行为期6个月的院外健康教育的方式,为患者推送精准、个性化的健康教育内容。评价两组患者饮食、运动、血压、血脂达标情况和护理满意度。结果:干预组在干预后6个月饮食、运动、血压、血脂达标率显著高于对照组,护理满意度高于对照组,差异有统计学意义(P<0.05)。结论:对体检人员实施"互联网+"健康教育模式,可有效改善体检者的生活方式,有助于体检者建立良好的生活行为习惯。     

Sex differences in circadian timing systems: Implications for disease

Virtually every eukaryotic cell has an endogenous circadian clock and a biological sex. These cell-based clocks have been conceptualized as oscillators whose phase can be reset by internal signals such as hormones, and external cues such as light. The present review highlights the inter-relationship between circadian clocks and sex differences. In mammals, the suprachiasmatic nucleus (SCN) serves as a master clock synchronizing the phase of clocks throughout the body. Gonadal steroid receptors are expressed in almost every site that receives direct SCN input. Here we review sex differences in the circadian timing system in the hypothalamic–pituitary–gonadal axis (HPG), the hypothalamic–adrenal–pituitary (HPA) axis, and sleep–arousal systems. We also point to ways in which disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease. Understanding sex differentiated circadian timing systems can lead to improved treatment strategies for these conditions.     

Impact de la modification des prescriptions chez les sujets âgés hospitalisés en service de court séjour gériatrique en termes de coût

Purpose

Polypharmacy in the elderly increases the risk of adverse drug reactions and leads to increased medical costs. There is little data currently available on drug modification and cost reduction during hospitalization in a geriatric unit. The aims of this study were to analyse drug modification during hospitalization in a geriatric care unit and to evaluate the repercussions in terms of cost reduction.

Methods

This monocentric study included 691 patients over a period of 3.5 years. The drugs and their daily costs were counted and classified (10 classes, 37 subclasses) upon admission and upon discharge. The modifications in the number of drugs in each class and subclass, as well as their costs, were analysed. Predictive factors in drug modification between admission and discharge were investigated.

Results

Our study showed a significant decrease in the number of drugs (mean  ±  standard error [SE], 5.2 ± 0.11 to 4.5 ± 0.07), as well as in the daily medical costs (4.4 ± 0.18 to 3.67 ± 0.12 €) between admission and discharge. The higher the number of drugs was upon admission, the greater the reduction was upon discharge. Cardiovascular, metabolic, analgesic and pulmonary drugs were significantly reduced, whereas gastrointestinal and anti-osteoporotic treatments increased. Diabetes, adverse drug events and the one-leg balance were predictive factors in drug modification.

Conclusion

Hospitalization in a geriatric unit allows a re-evaluation of drug management with a significant reduction in the number and cost of treatments between admission and discharge. Given the multiple consequences of polypharmacy and its serious financial impact, research to develop optimal care of the elderly and to improve medication intervention is warranted.     

Deep brain stimulation affects conditioned and unconditioned anxiety in different brain areas

Deep brain stimulation (DBS) of the nucleus accumbens (NAc) has proven to be an effective treatment for therapy refractory obsessive–compulsive disorder. Clinical observations show that anxiety symptoms decrease rapidly following DBS. As in clinical studies different regions are targeted, it is of principal interest to understand which brain area is responsible for the anxiolytic effect and whether high-frequency stimulation of different areas differentially affect unconditioned (innate) and conditioned (learned) anxiety. In this study, we examined the effect of stimulation in five brain areas in rats (NAc core and shell, bed nucleus of the stria terminalis (BNST), internal capsule (IC) and the ventral medial caudate nucleus (CAU)). The elevated plus maze was used to test the effect of stimulation on unconditioned anxiety, the Vogel conflict test for conditioned anxiety, and an activity test for general locomotor behaviour. We found different anxiolytic effects of stimulation in the five target areas. Stimulation of the CAU decreased both conditioned and unconditioned anxiety, while stimulation of the IC uniquely reduced conditioned anxiety. Remarkably, neither the accumbens nor the BNST stimulation affected conditioned or unconditioned anxiety. Locomotor activity increased with NAc core stimulation but decreased with the BNST. These findings suggest that (1) DBS may have a differential effect on unconditioned and conditioned anxiety depending on the stimulation area, and that (2) stimulation of the IC exclusively reduces conditioned anxiety. This suggests that the anxiolytic effects of DBS seen in OCD patients may not be induced by stimulation of the NAc, but rather by the IC.