艾司西酞普兰联合唑吡坦对失眠障碍患者睡眠质量、焦虑抑郁状态及血清神经递质的影响

摘要 目的：探讨艾司西酞普兰联合唑吡坦对失眠障碍患者睡眠质量、焦虑抑郁状态及血清神经递质的影响。方法：选取2018年1月~2020年12月期间我院收治的失眠障碍患者100例为研究对象。根据随机数字表法分为对照组（唑吡坦治疗,n=50）和研究组（对照组的基础上联合艾司西酞普兰治疗,n=50）,比较两组患者睡眠质量、焦虑抑郁状态、血清神经递质及不良反应情况。结果：治疗4周后,研究组睡眠效率高于对照组,睡眠总时间长于对照组,醒觉时间、入睡时间短于对照组（P<0.05）。治疗4周后,研究组匹兹堡睡眠质量指数（PSQI）、汉密顿抑郁评估量表（HAMD）、汉密顿焦虑评估量表(HAMA)低于对照组（P<0.05）。治疗4周后,研究组5-羟色胺（5-HT）、r-氨基丁酸（GABA）水平高于对照组,去甲肾上腺素（NE）水平低于对照组（P<0.05）。两组不良反应发生率比较无差异（P>0.05）。结论：失眠障碍患者接受唑吡坦、艾司西酞普兰联合治疗,可有效改善患者焦虑抑郁状态、睡眠质量以及血清神经递质水平,安全性较好。     

Oral supplementation with carbohydrate- and branched-chain amino acid-enriched nutrients improves postoperative quality of life in patients undergoing hepatic resection

The long-term outcomes of branched-chain amino acid (BCAA) administration in patients undergoing hepatic resection remain unclear. The aim of this study is to assess the impact of oral supplementation with BCAA-enriched nutrients on postoperative quality of life (QOL) in patients undergoing liver resection. A prospective randomized clinical trial was conducted in 96 patients undergoing hepatic resection. Patients were randomly assigned to receive BCAA supplementation (AEN group, n = 48) or a conventional diet (control group, n = 48). Postoperative QOL and short-term outcomes were regularly and continuously evaluated in all patients using a short-form 36 (SF-36) health questionnaire and by measuring various clinical parameters. This study demonstrated a significant improvement in QOL after hepatectomy for liver neoplasm in the AEN group based on the same patients’ preoperative SF-36 scores (P < 0.05). Perioperative BCAA supplementation preserved liver function and general patient health in the short term for AEN group patients compared to those not receiving the nutritional supplement. BCAA supplementation improved postoperative QOL after hepatic resection over the long term by restoring and maintaining nutritional status and whole-body kinetics. This study was registered at (registration number: NCT00945568).     

Social rhythm regularity moderates the relationship between sleep disruption and depressive symptoms in veterans with post-traumatic stress disorder and major depressive disorder

ABSTRACT

Approximately 50% to 80% of individuals with posttraumatic stress disorder (PTSD) also meet criteria for major depressive disorder (MDD). Sleep disturbance is a major concern in both PTSD and MDD, and is associated with poor treatment response, poor functional outcome and increased suicide risk. Social rhythm regularity, or the consistency of daily habitual behaviors, is theoretically linked to circadian rhythms and may be disturbed in both PTSD and MDD. The present study examined the relationship between social rhythm regularity, sleep disruption and MDD and PTSD symptoms in a sample of veterans with comorbid PTSD and MDD. Baseline data were obtained from 56 male veterans who met DSM-IV criteria for PTSD and MDD. Veterans completed the Social Rhythm Metric (SRM), a self-report questionnaire that assesses the regularity of routines by determining how regularly individuals completed 17 different types of activities. In a linear regression model, increased minutes awake after sleep onset (WASO) was a significant predictor of increased depression scores on the Hamilton Rating Scale for Depression (p < .05). SRM scores did not significantly predict depressive symptoms, however the interaction of WASO and SRM significantly predicted depressive symptoms (p = <.05), with significant relationships found at SRM scores less than 3.62. Neither minutes awake after sleep onset, SRM scores, nor their interaction was associated with PTSD symptom severity. Social and possibly circadian rhythm regularity may represent a risk or resilience factor for individuals with comorbid PTSD and MDD. Findings highlight the importance of exploring the interactions of sleep and social/circadian rhythms in depression in order to inform continued treatment development.     

百乐眠胶囊联合艾司西酞普兰片对失眠伴抑郁焦虑患者睡眠质量、不良情绪以及神经递质水平的影响

摘要 目的：探讨百乐眠胶囊联合艾司西酞普兰片对失眠伴抑郁焦虑患者睡眠质量、不良情绪以及神经递质水平的影响。方法：选取2017年7月~2019年12月期间我院收治的失眠伴抑郁焦虑患者117例,将上述患者根据随机数字表法分为对照组（n=58,艾司西酞普兰片治疗）和研究组（n=59,百乐眠胶囊联合艾司西酞普兰片治疗）,比较两组患者睡眠质量、不良情绪、多导睡眠图（PSG）参数、神经递质水平及不良反应。结果：研究组治疗2个月后的临床总有效率为93.22%（55/59）,高于对照组的79.31%（46/58）（P<0.05）。两组治疗2个月后汉密尔顿焦虑量表（HAMA）、汉密尔顿抑郁量表（HAMD）以及匹兹堡睡眠质量指数（PSQI）评分、睡眠潜伏期、P物质（SP）均较治疗前降低,且研究组低于对照组（P<0.05）。两组治疗2个月后睡眠总时间、睡眠效率、神经肽Y（NPY）、5-羟色胺（5-HT）升高,且研究组高于对照组（P<0.05）。治疗期间研究组不良反应发生率较对照组降低（P<0.05）。结论：失眠伴抑郁焦虑患者经百乐眠胶囊联合艾司西酞普兰片治疗后,睡眠质量、不良情绪得到显著改善,同时还可有效改善血清神经递质水平,减少不良反应,临床应用效果确切。     

Chronotype preference matters for depression in youth

Morningness/eveningness (M/E) preference is an important circadian rhythm indicator with strong individual variation. M/E chronotype has been found to be correlated with depression in adults, yet the relationship is less clear in children and adolescents. Additionally, poor sleep quality is another commonly studied risk factor for depression. The aims of the present study are to investigate the independent effects of M/E chronotype on youth depression using both self-report and parental-report questionnaires. We also evaluated how poor sleep quality may affect the relationship through a mediating or moderating effect. In total, 2,139 students attending grades 1 to 7 participated in this study. They completed questionnaires regarding M/E chronotype, depression, and sleep quality. A total of 1,708 parents also participated and filled out parental-reports of emotional and behavioral problems of their children. The prevalence of self- and parental-report depression was 16.8% and 12.8% among young students, respectively. Overall, 15.4% of the students were the eveningness type. Being an eveningness type was independently associated with self-report depression after adjustment for poor sleep quality (OR = 1.86, 95% CI = 1.07–3.24). We also observed that poor sleep quality mediated the influence of M/E chronotype on self-report depression among students aged 7–13 years (p < 0.001). On the other hand, being an eveningness type was associated with a number of parental-report emotional and behavioral problems in the students, in addition to depression, although these associations become non-significant after adjusted for poor sleep quality. Our results demonstrate the importance of M/E chronotype on youth depression and poor sleep quality partly mediates this effect.     

Yoga Ameliorates Performance Anxiety and Mood Disturbance in Young Professional Musicians

Yoga and meditation can alleviate stress, anxiety, mood disturbance, and musculoskeletal problems, and can enhance cognitive and physical performance. Professional musicians experience high levels of stress, performance anxiety, and debilitating performance-related musculoskeletal disorders (PRMDs). The goal of this controlled study was to evaluate the benefits of yoga and meditation for musicians. Young adult professional musicians who volunteered to participate in a 2-month program of yoga and meditation were randomized to a yoga lifestyle intervention group (n = 15) or to a group practicing yoga and meditation only (n = 15). Additional musicians were recruited to a no-practice control group (n = 15). Both yoga groups attended three Kripalu Yoga or meditation classes each week. The yoga lifestyle group also experienced weekly group practice and discussion sessions as part of their more immersive treatment. All participants completed baseline and end-program self-report questionnaires that evaluated music performance anxiety, mood, PRMDs, perceived stress, and sleep quality; many participants later completed a 1-year followup assessment using the same questionnaires. Both yoga groups showed a trend towards less music performance anxiety and significantly less general anxiety/tension, depression, and anger at end-program relative to controls, but showed no changes in PRMDs, stress, or sleep. Similar results in the two yoga groups, despite psychosocial differences in their interventions, suggest that the yoga and meditation techniques themselves may have mediated the improvements. Our results suggest that yoga and meditation techniques can reduce performance anxiety and mood disturbance in young professional musicians.     

Para‐psychobiotic Lactobacillus gasseri CP2305 ameliorates stress‐related symptoms and sleep quality

Aims

To confirm the stress‐relieving effects of heat‐inactivated, enteric‐colonizing Lactobacillus gasseri CP2305 (paraprobiotic CP2305) in medical students taking a cadaver dissection course.

Methods and Results

Healthy students (21 males and 11 females) took paraprobiotic CP2305 daily for 5 weeks during a cadaver dissection course. The General Health Questionnaire and the Pittsburgh Sleep Quality Index were employed to assess stress‐related somatic symptoms and sleep quality respectively. The aggravation of stress‐associated somatic symptoms was observed in female students (P = 0·029). Sleep quality was improved in the paraprobiotic CP2305 group (P = 0·038), particularly in men (P = 0·004). Among men, paraprobiotic CP2305 shortened sleep latency (P = 0·035) and increased sleep duration (P = 0·048). Diarrhoea‐like symptoms were also effectively controlled with CP2305 (P = 0·005) in men. Thus, we observed sex‐related differences in the effects of paraprobiotic CP2305. In addition, CP2305 affected the growth of faecal Bacteroides vulgatus and Dorea longicatena, which are involved in intestinal inflammation.

Conclusions

CP2305 is a potential paraprobiotic that regulates stress responses, and its beneficial effects may depend on specific cell component(s).

Significance and Impact of the Study

This study characterizes the effects of a stress‐relieving para‐psychobiotic in humans.     

Resilience,sleep quality and morningness as mediators of vulnerability to depression in medical students with sleep pattern alterations

The medical career is considered highly stressful, especially during internships when academic and clinical demands, combined with changes in sleep patterns, increase students’ likelihood to develop depression. Resilience, which is considered as opposite vulnerability to stress and, along with another protective factor, namely morningness, may cause a student to be less reactive to stimuli and, therefore, less prone to depression. The objective of this study was to evaluate the role of resilience and morningness facing to sleep quality and main risk factors, on the development of depression symptoms in a group of students with sleep pattern alterations. To this end, an observational and longitudinal study was performed with 30 undergraduate interns, with an average age of 22.63 years (SE ± 0.13), 33% men and 67% women. A survey was conducted in three different times during the year of internship: at the beginning (T₁), in the middle (T₂) and the end (T₃). The instruments were the Brief Resilience Scale, Composite Scale of Morningness, Pittsburgh Sleep Quality Index and Patient Health Questionnaire. The path analysis examined the roles of morningness, sleep quality and resilience as potential mediators between family history of depression and depression symptoms at different times. The results showed that resilience had a protective effect on depression symptoms at T₂ (β = ?0.18, p < 0.05) and with greater power at T₃ (β = ?0.41, p < 0.05), as did morningness, although less strongly, on the symptoms at T₃ (β = ?0.13, p < 0.05). A relationship between these two mediating variables was also observed (β = 0.30, p < 0.05). The initial sleep quality had an effect on the increase of depression symptoms at T₁ (β = 0.61, p < 0.05) and T₃ (β = 0.21, p < 0.05), while family history of depression had a direct effect on the measures of depression at T₂ (β = 0.49, p < 0.05) and T₃ (β = 0.19, p < 0.05). Aside from personal risk factors, it is possible to conclude that the levels of resilience, morningness and sleep quality manifested by students at the beginning of their internship may explain the decrease in depression symptoms at the end of the course.     

A DNA mini‐barcode for land plants

Small portions of the barcode region – mini‐barcodes – may be used in place of full‐length barcodes to overcome DNA degradation for samples with poor DNA preservation. 591,491,286 rbcL mini‐barcode primer combinations were electronically evaluated for PCR universality, and two novel highly universal sets of priming sites were identified. Novel and published rbcL mini‐barcode primers were evaluated for PCR amplification [determined with a validated electronic simulation (n = 2765) and empirically (n = 188)], Sanger sequence quality [determined empirically (n = 188)], and taxonomic discrimination [determined empirically (n = 30 472)]. PCR amplification for all mini‐barcodes, as estimated by validated electronic simulation, was successful for 90.2–99.8% of species. Overall Sanger sequence quality for mini‐barcodes was very low – the best mini‐barcode tested produced sequences of adequate quality (B₂₀ ≥ 0.5) for 74.5% of samples. The majority of mini‐barcodes provide correct identifications of families in excess of 70.1% of the time. Discriminatory power noticeably decreased at lower taxonomic levels. At the species level, the discriminatory power of the best mini‐barcode was less than 38.2%. For samples believed to contain DNA from only one species, an investigator should attempt to sequence, in decreasing order of utility and probability of success, mini‐barcodes F (rbcL1/rbcLB), D (F52/R193) and K (F517/R604). For samples believed to contain DNA from more than one species, an investigator should amplify and sequence mini‐barcode D (F52/R193).     

Correlation Between Dietary Zinc Intakes and Its Serum Levels with Depression Scales in Young Female Students

It has been suggested that mood disorders and depressive status may be accompanied by lowered zinc status in the body, and adequate consumption of zinc increases a general perceived well-being. The main objective of this study was to assess the correlation between serum zinc concentrations and dietary zinc intakes with depression scores in university female students. In the first phase, Beck's depression questionnaire was applied in a random sampling of 308 selected 20–25-year-old female students (one third of total students in Ahvaz Jondi-Shapour University of Medical Sciences Golestan dormitories) to assess the major depressive disorder (MDD) scales. Then, in the second phase, 23 students who identified as having moderate and severe depression were selected as the case group, and 23 healthy age matched were chosen as the controls. Each of them completed a 12-item semiquantitative food frequency questionnaire containing the main food sources of zinc in the usual dietary patterns and also a 24-h food recall questionnaire to assure the daily zinc intakes. Daily zinc intakes were obtained by multiplying each portion size by its zinc content using food tables. A 5-ml blood sample was taken for further serum zinc status using flame atomic absorption spectrophotometry technique. Pearson's r was used to show the correlation between quantitative variables. Both daily zinc intake and serum zinc concentrations of MDD group were about two thirds of healthy index (p < 0.01). Depressed individuals used to eat lower servings of red meats and chicken as the main food sources of zinc in students' usual diets (p < 0.001). Consumption of other foods as the sources of zinc was not significantly different in two groups. A linear significant correlation between dietary zinc intakes and its serum levels was seen in samples (r = 0.62; p < 0.001) and MDD students (r = 0.55; p < 0.001). There was a linear inverse correlation between Beck questionnaire scores and serum zinc concentrations in all of the investigated students(r = -0.65; p < 0.001) and MDD girls (r = −0.71; p < 0.001). Beck questionnaire scores and diatary zinc intakes were also inversly correlated (r = −0.58; p < 0.001). However, no statistical correlation was seen between these two variables in MDD cases. In depressed female students, dietary zinc intake is correlated to its serum concentrations; however, the serum zinc levels are inversely correlated to depression scales. Consumption of the main dietary sources of zinc such as red meats and chicken should be encouraged in young depressed girls.     

Effects of Venlafaxine and Escitalopram Treatments on NMDA Receptors in the Rat Depression Model

Depression may relate to neurocognitive impairment that results from alteration of N-methyl-D: -aspartate receptor (NMDAR) levels. Venlafaxine and escitalopram are two drugs commonly used to treat depression. The drugs may affect expression of NMDARs, which mediate learning and memory formation. The aim of the study was to examine whether the effects of venlafaxine and escitalopram treatments are associated with NMDARs in a rat model of depression. Forty male Wistar albino rats were randomly divided into four groups (n?=?10) as follows: control group, chronic mild stress group (CMS), venlafaxine (20?mg/kg body weight per day)?+?CMS, and escitalopram (10?mg/kg body weight per day)?+?CMS. After induction of depression, a decrease in the concentration of NR2B was observed; venlafaxine treatment prevented the reduction of NR2B expression. Escitalopram treatment did not effect the reduced levels of NR2B resulting from depression. There was no significant difference in NR2A concentration among groups. The present data support the notion that venlafaxine plays a role in maintaining NR2B receptor in experimental depression. It may be possible that treatment with escitalopram has no effect on NMDARs in experimental depression.     

Neuro-protective effects of carbamazepine on sleep patterns and head and body shakes in kainic acid-treated rats

The aim of this work was to analyze the effect of carbamazepine (CBZ) on sleep patterns and on “head and body shakes” and to determine the role of serotonin (5-HT) in a model of kainic-induced seizures. Thirty male Wistar rats (280–300 g) were used for polygraphic sleep recording. After a basal recording, the rats were allocated into three groups: kainic acid-treated animals (KA; 10 mg/kg; n = 10), carbamazepine-treated animals (CBZ; 30 mg/kg; n = 10) and animals injected with KA 30 min after pretreatment with CBZ (CBZ + KA; n = 10). Polygraphic recordings were performed for 10 h for 3 days, with the exception of the CBZ group, which were observed for 1 day. In order to measure the head and body shakes that occurred over that time, a behavioral assessment was performed in two additional groups of KA (n = 10) and CBZ + KA (n = 10) animals. After 10 h of behavioral assessment, the rats were sacrificed, and the levels of 5-HT and 5-hydroxy-indol-acetic acid (5-HIAA) were analyzed. We compared these findings with the results from a group of rats without pharmacological intervention (n = 10). All of the recordings were performed from 08:00 to 18:00 h. Data analysis: the electrographic parameters, head and body shake counting and monoamine concentrations were analyzed by an ANOVA test. Differences of *p ≤ 0.01 and **p ≤ 0.001 were considered statistically significant. Our results showed that CBZ exerted a protective effect on sleep pattern alterations induced by KA, which when administered alone caused a complete inhibition of sleep for the first 10 h after administration. Although there was a reduction in the amount of sleep after the administration of KA in CBZ-pretreated animals, sleep inhibition was incomplete. In addition, CBZ decreased the frequency of head and body shakes by 60% as compared to KA. The 5-HT and 5-HIAA levels in the pons were increased in the KA and KA + CBZ groups. Our conclusion is that in addition to decreasing seizure intensity, CBZ facilitates the partial recovery of sleep. These results suggest that CBZ provides neuro-protective effects on sleep and against seizures.     

A Genetic Variant in 12q13, a Possible Risk Factor for Bipolar Disorder,Is Associated with Depressive State,Accounting for Stressful Life Events

Genome-wide association studies (GWASs) have identified a number of susceptibility genes for schizophrenia (SCZ) and bipolar disorder (BD). However, the identification of risk genes for major depressive disorder (MDD) has been unsuccessful because the etiology of MDD is more influenced by environmental factors; thus, gene–environment (G×E) interactions are important, such as interplay with stressful life events (SLEs). We assessed the G×E interactions and main effects of genes targeting depressive symptoms. Using a case–control design, 922 hospital staff members were evaluated for depressive symptoms according to Beck Depressive Inventory (BDI; “depression” and “control” groups were classified by scores of 10 in the BDI test), SLEs, and personality. A total of sixty-three genetic variants were selected on the basis of previous GWASs of MDD, SCZ, and BD as well as candidate-gene (SLC6A4, BDNF, DBH, and FKBP5) studies. Logistic regression analysis revealed a marginally significant interaction (genetic variant × SLE) at rs4523957 (P_uncorrected = 0.0034) with depression and a significant association of single nucleotide polymorphism identified from evidence of BD GWAS (rs7296288, downstream of DHH at 12q13.1) with depression as the main effect (P_uncorrected = 9.4×10⁻⁴, P_corrected = 0.0424). We also found that SLEs had a larger impact on depression (odds ratio∼3), as reported previously. These results suggest that DHH plays a possible role in depression etiology; however, variants from MDD or SCZ GWAS evidence or candidate genes showed no significant associations or minimal effects of interactions with SLEs on depression.     

Seed and pollen dispersal distances in two African legume timber trees and their reproductive potential under selective logging

The natural regeneration of tree species depends on seed and pollen dispersal. To assess whether limited dispersal could be critical for the sustainability of selective logging practices, we performed parentage analyses in two Central African legume canopy species displaying contrasted floral and fruit traits: Distemonanthus benthamianus and Erythrophleum suaveolens. We also developed new tools linking forward dispersal kernels with backward migration rates to better characterize long‐distance dispersal. Much longer pollen dispersal in D. benthamianus (mean distance d_p = 700 m, m_p = 52% immigration rate in 6 km² plot, s = 7% selfing rate) than in E. suaveolens (d_p = 294 m, m_p = 22% in 2 km² plot, s = 20%) might reflect different insect pollinators. At a local scale, secondary seed dispersal by vertebrates led to larger seed dispersal distances in the barochorous E. suaveolens (d_s = 175 m) than in the wind‐dispersed D. benthamianus (d_s = 71 m). Yet, seed dispersal appeared much more fat‐tailed in the latter species (15%–25% seeds dispersing >500 m), putatively due to storm winds (papery pods). The reproductive success was correlated to trunk diameter in E. suaveolens and crown dominance in D. benthamianus. Contrary to D. benthamianus, E. suaveolens underwent significant assortative mating, increasing further the already high inbreeding of its juveniles due to selfing, which seems offset by strong inbreeding depression. To achieve sustainable exploitation, seed and pollen dispersal distances did not appear limiting, but the natural regeneration of E. suaveolens might become insufficient if all trees above the minimum legal cutting diameter were exploited. This highlights the importance of assessing the diameter structure of reproductive trees for logged species.     

艾司西酞普兰联合心理疗法对焦虑症患者睡眠质量、生活质量和血清神经递质水平的影响

目的:探讨艾司西酞普兰联合心理疗法对焦虑症患者睡眠质量、生活质量和血清神经递质水平的影响.方法:选取2017年7月～2020年3月期间我院收治的焦虑症患者117例,随机分为对照组58例和研究组59例,对照组给予艾司西酞普兰治疗,研究组在对照组的基础上联合心理疗法,对比两组疗效、汉密尔顿焦虑量表(HAMA)、匹兹堡睡眠质...     

Zinc and Fatty Acids in Depression

Polyunsaturated Fatty acids (PUFAs) seem to be helpful in the therapy of depression. Zinc (Zn) may be one co-factor contributing to their antidepressive effect. Zn acts lipid protective and is a constituent of fatty acid metabolism enzymes. In animals, an antidepressive effect of Zn was already demonstrated. Therefore, if and how Zn and PUFAs correlate in depressive patients or in individuals from the general population was investigated. Blood samples were collected from 88 depressive in-patients and 88 volunteers from the general population matched for age-group and gender (each 32 men and 56 women, 21–70 years) for measurement of Zn (colorimetric) and of 12 fatty acids (FAs) (by capillary gas-chromatography). Severity of depression in patients was assessed by Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). Zn concentration was independent of age, gender and body-mass-index and significantly correlated with the severity of depression measured by BDI (r = 0.26; P = 0.034) in depressive patients,. HDRS was inversely correlated with gammalinolenic acid concentration (r = −0.24; P = 0.029). Median serum Zn concentration in depressive patients did not differ from control individuals. Zn was correlated with myristic acid concentration (r = 0.22; P < 0.05) in controls from the general population; and a negative correlation between Zn and dihomogammalinolenic acid concentration (r = −0.26; P < 0.05) was found in depressive inpatients. FA composition in serum significantly differed between depressive and healthy persons: Depressive patients had higher stearic and arachidonic acid (AA) concentration. Relative to AA, their eicosapentaenoic and docosapentaenoic acid concentration were diminished compared to the general populations group. These results do not confirm the hypothesis of a general lack of Zn in depressive disorders, but Zn concentrations differed dependent on comorbid disorders and severity of depression. In depressive patients and control persons Zn concentration is associated with different FAs indicating diverging metabolic pathways.     

Intercellular adhesion molecule-1 gene K469E polymorphism and ischemic stroke: a case-control study in a Chinese population

Background Intercellular adhesion molecule-1 (ICAM-1) was involved in the pathogenetic mechanisms responsible for ischemic stroke (IS). Population-based sample have revealed gene-gender interaction in blood pressure which is major risk for IS. We sought to evaluate whether ICAM-1 K469E polymorphism was involved in the causation of IS and whether it was different between female and male. Methods A 1:1 case-control study was conducted. The K469E polymorphism of ICAM-1 gene were analyzed by polymerase chain reaction (PCR) and restriction enzyme analysis in Chinese patients with IS (n = 309) and elderly subjects without IS (n = 309). Results ICAM-1 K469E polymorphism was significantly associated with IS. Interestingly, a further analysis stratified by sex found that there was significance between 469E genotypes and IS in female, but not in male. Multiple regression analysis revealed that ICAM-1 K469E polymorphism was still significantly associated with IS, compared with ICAM-1 KK genotype in all population (OR = 1.60, P = 0.030). Stratified by sex, EE combined EK was contributory factor to IS in female (OR = 3.03, P = 0.004), but not in male. After adjustment for confounding factors, the interaction between female and ICAM-1 EK/EE genotypes was found (OR = 3.54, P = 0.001). Conclusions It is suggested that the ICAM-1 469E allele may be important in the pathogenesis of ischemic stroke, especially in female but not in male. Xiao-Xia Li and Jian-Ping Liu have contributed equally.     

Effect of early adverse events on response and survival outcomes of advanced melanoma patients treated with vemurafenib or vemurafenib plus cobimetinib: A pooled analysis of clinical trial data

This study aimed to evaluate the impact of early adverse events on overall survival (OS), progression‐free survival (PFS) and objective response within a pooled secondary analysis of participants treated with first‐line vemurafenib or vemurafenib plus cobimetinib in the clinical trials BRIM3 and coBRIM. The study included 583 participants who received vemurafenib monotherapy and 247 who received vemurafenib plus cobimetinib. Adverse events requiring vemurafenib/cobimetinib dose adjustment within the first 28 days of therapy were significantly associated with OS (hazard ratio (HR) [95% CI]: dose reduced/interrupted = 0.79 [0.65–0.96]; drug withdrawn = 1.18 [0.71–1.96]; p = 0.032), PFS (HR [95% CI]: dose reduced/interrupted = 0.82 [0.67–0.99]; drug withdrawn = 1.58 [0.97–2.58]; p = 0.017) and objective response (odds ratio (OR) [95% CI]: dose reduced/interrupted = 1.35 [0.99–1.85]; drug withdrawn = 0.17 [0.06–0.43]; p = <0.001). Arthralgia occurring within the first 28 days of vemurafenib or vemurafenib plus cobimetinib therapy was also significantly associated with favourable OS (p = 0.026), PFS (p = 0.042) and objective response (p = 0.047).     

The Mechanism and Characterization of Learning and Memory Impairment in Sleep-Deprived Mice

Objectives are to examine the effects of sleep deprivation (SD) on spatial learning and memory in mice, to determine how SD effects the expression of phosphorylated cyclic AMP responsive element binding protein (pCREB) in mouse hippocampus, and to explore the mechanism of influence of sleep deprivation on cognitive function. Twenty, 3-month-old female C57BL/6J mice were randomly assigned into two groups, the sleep deprivation group (SD, n = 10) and control group with normal sleep (CC, n = 10). The mice in SD group were deprived sleep by “gentle touch” for 20 days and then all the mice were subjected for Morris Water Maze test to determine the mean latency of escape (LE). Percentage of time spent in the target quadrant was calculated. Mouse hippocampus pCREB levels were quantified by western blot. Compared with CC group, SD mice had a significantly longer mean LE time (P < 0.05) and spent less time in the target quadrant (P < 0.05). Western blot revealed that hippocampus pCREB levels in the SD group were significantly lower than that in control group (0.71 ± 0.03 vs 0.82 ± 0.06, P < 0.01). The impairment in spatial learning and memory in sleep-deprived animals may be associated with the reduction of pCREB in the hippocampus.     

Psychometric properties and accuracy of the European Portuguese version of the Pittsburgh Sleep Quality Index in clinical and non-clinical samples

To assess the reliability and validity concerning the formal European Portuguese version of the Pittsburgh Sleep Quality Index [PSQI (EP)], its accuracy, and optimal cut-off point. N = 564 volunteers (18–80 years old) recruited in several settings (e.g., university campuses; work place; home; sleep consultations), agreed to complete the PSQI (EP). Subgroups completed additional measures: Insomnia Severity Index (ISI), STOP-Bang, Glasgow Sleep Effort Scale, or responded to a supplementary question about perceived sleep problems. As to internal consistency, Cronbach’s α = 0.75. Principal component analysis revealed a unidimensional structure. Six PSQI (EP) components and total scores were able to discriminate individuals who did versus did not describe having any sleep problem; all PSQI (EP) scores were significantly higher (denoting poorer quality) in participants suffering from a sleep disorder. Most Cohen’s d values showed large magnitude associations. PSQI (EP) and ISI scores were highly correlated, but no significant correlations were found considering STOP-Bang. ROC analysis confirmed an optimal cut-off point > 5 of the PSQI (EP) to detect self-reported poor/good sleepers in non-clinical settings. To discriminate non-clinical from clinical sleep patients, the optimal cutoff was > 7, and AUC = 0.94. The European Portuguese version of the PSQI performs as a reliable, valid, and accurate measure of overall sleep quality in Portuguese participants. Furthermore, results suggest that PSQI (EP) can discriminate poor sleepers in non-clinical settings, in addition to demonstrating high clinical accuracy in signaling potential sleep-disorder cases. In conclusion, the PSQI (EP) is a suitable tool to assess general sleep quality in Portuguese participants, both for clinical or non-clinical applications.