Prenatal aripiprazole induces alterations of rat placenta: a histological, immunohistochemical and ultrastructural study.

Antipsychotic drugs (APDs) are used to treat many psychiatric illnesses as schizophrenia. Typical antipsychotic drugs (TAPDs) are being used; however, they have many side effects. Atypical antipsychotic drugs (AAPDs) are newer medications with known fewer side effects. Aripiprazole (ARI) is an AAPD, recommended by healthcare providers, even during pregnancy. It can cross the placental barrier and enter fetal circulation, so it might be possible that ARI can adversely impair normal placental development and growth, if it is given prenatally. ARI was applied orally to pregnant female rats in two doses (3& 6 mg/kg body weight). On gestation day 20, the mothers were sacrificed, and the placentas were removed and processed for general histological and electron microscopic evaluations. Immunohistochemistry was done using anti-PCNA (proliferating cell nuclear antigen), anti-Bax (for apoptosis) and anti-vascular endothelial growth factor alpha (VEGFA). Morphological evaluation revealed degenerative changes in the placenta as dark nuclei, vacuolization, and cyst formation. Ultra-structurally, there was degeneration of cellular components including organelles and nuclei. These changes were found in different cells of the basal and labyrinth zones and were dose dependent. Immunohistochemistry revealed upregulation of Bax and VEGFA and downregulation of PCNA. Prenatal administration of the AAPD, ARI to pregnant female rats resulted in histological changes in the placenta. Additionally, there was a decrease in cellular proliferation and increase in apoptosis, and vascular impairment. This indicates placental atrophy and dysgenesis and might suggest possible teratogenic effects to ARI, which needs further evaluation.

Postoperative Patient Pain Severity and Its Association With Anxiety, Depression, and Sleep Quality.

Introduction The experience of pain is a complex phenomenon. A patient in the acute postsurgical pain setting may feel a constant bombardment of nociceptive input from the surgical site; this in turn influences psychological factors that determine the overall emotional experience of pain, which is significant. The aim of our study was to investigate the severity of pain in postsurgical patients three days after surgery using the 100 mm visual analog scale (VAS). Methods This was a cross-sectional assessment of postoperative pain. Participants were patients between 18 and 64 years of age who had undergone a surgical procedure (laparoscopic or open surgery), three days prior to the data collection and who were admitted or discharged postoperatively at the Al Salmaniya Complex, Manama, Bahrain. Participants were asked demographic questions about whether they had laparoscopic or open surgeries and completed self-reporting scales. Patient Health Questionnaire-9 (PHQ-9) was utilized to screen for both the presence and severity of depression; Generalized Anxiety Disorder 7-item (GAD-7) was administered to screen for anxiety; the Insomnia Severity Index (ISI) was used to evaluate insomnia; and the VAS was used to evaluate pain.  Results Sixty-seven patients were recruited, with a mean age of 61.53 years (SD = 7.37). Twenty-nine (43%) were females, 38 (57%) were males, 36 (54%) underwent elective surgery, 31 (46%) underwent emergency surgery, 31 (46%) underwent laparoscopic surgery, and 36 (54%) underwent open surgery. The average score on the Brief Pain Inventory Short Form (BPISF) was 8.12 (SD = 1.16), indicating a moderate level of pain. Twenty-six (43%) patients had moderate-severe insomnia, 21 participants (31%) had no insomnia, 17 participants (25%) had subthreshold insomnia, 28 (42%) had moderate depression, five (7%) had moderate-severe depression, and 34 (51%) had severe depression. Eighteen participants (27%) had mild anxiety, 46 (69%) had moderate anxiety, and 3 (4%) had severe anxiety. Six of the participants (9%) reported moderate pain, while 61 participants (91%) reported severe pain.

Hyperthyroidism Masking Depression and Panic Disorder Symptoms During Pregnancy: A Case Report.

Depression occurring during pregnancy, often known as antenatal depression, is a significant mental illness with negative impacts on the mother's health, the health of the unborn baby, and the general welfare of the family. The condition is linked to various negative pregnancy outcomes, such as preterm birth, low birth weight, elevated risks of gestational diabetes, and preeclampsia. The signs and symptoms of depression in pregnancy do not differ from depression at any time. Another condition that may resemble symptoms of antenatal depression is hyperthyroidism, which is characterized by increased levels of thyroid hormones. Excessive levels of thyroid hormones can impact mood, energy levels, and overall well-being. It is crucial to differentiate between symptoms related to thyroid function and clinical depression. This case report could serve as a comprehensive approach addressing the management of antenatal depression with hyperthyroidism. This often involves a multidisciplinary approach, which includes collaboration between obstetricians, endocrinologists, and mental health professionals.

Mitochondrial DNA copy number in autism spectrum disorder and attention deficit hyperactivity disorder: a systematic review and meta-analysis.

Background: Several reports suggest that altered mitochondrial DNA copy number (mtDNA-cn), a common biomarker for aberrant mitochondrial function, is implicated in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), but the results are still elusive. Methods: A meta-analysis was performed to summarize the current indication and to provide a more precise assessment of the mtDNA-cn in ASD and ADHD. A search in the MEDLINE-PubMed, Scopus, and EMBASE databases was done to identify related studies up to the end of February 2023. The meta-analysis was conducted according to recommendations of the Cochrane Handbook of Systematic Reviews. Results: Fourteen studies involving 666 cases with ASD and ADHD and 585 controls were collected and judged relevant for the systematic review and meta-analysis. The pooled results by a random effects meta-analysis was reported as a geometric mean of the estimated average response ratio and 95% confidence interval. Overall analysis of studies reported differences in mtDNA-cn in blood samples (k = 10) and non-blood samples (brain tissues and oral samples; k = 4) suggested significantly higher mtDNA-cn in patients compared to controls (p = 0.0275). Sub-analysis by stratifying studies based on tissue type, showed no significant increase in mtDNA-cn in blood samples among patients and controls (p = 0.284). Conversely, higher mtDNA-cn was observed in non-blood samples in patients than in controls (p = 0.0122). Further stratified analysis based on blood-cell compositions as potential confounds showed no significant difference in mtDNA-cn in peripheral blood samples of patients comparted to controls (p = 0.074). In addition, stratified analysis of aged-matched ASD and ADHD patients and controls revealed no significant difference in mtDNA-cn in blood samples between patients and controls (p = 0.214), whereas a significant increase in mtDNA-cn was observed in non-blood samples between patients and controls (p < 0.001). Finally, when the mtDNA-cn was analyzed in blood samples of aged-matched patients with ASD (peripheral blood, leukocytes, and PBMCs) or ADHD (peripheral blood), no significant difference in mtDNA-cn was observed between ASD patients and controls (p = 0.385), while a significant increase in mtDNA-cn was found between ADHD patients and controls (p = 0.033). Conclusion: In this first meta-analysis of the evaluation of mtDNA-cn in ASD/ADHD, our results show elevated mtDNA-cn in ASD and ADHD, further emphasizing the implication of mitochondrial dysfunction in neurodevelopmental disorders. However, our results indicate that the mtDNA-cn in blood is not reflected in other tissues in ASD/ADHD, and the true relationship between blood-derived mtDNA-cn and ASD/ADHD remains to be defined in future studies. The importance of blood-cell compositions as confounders of blood-based mtDNA-cn measurement and the advantages of salivary mtDNA-cn should be considered in future studies. Moreover, the potential of mtDNA-cn as a biomarker for mitochondrial malfunction in neurodevelopmental disorders deserves further investigations.

The Worldwide Prevalence of Sleep Problems Among Medical Students by Problem, Country, and COVID-19 Status: a Systematic Review, Meta-analysis, and Meta-regression of 109 Studies Involving 59427 Participants.

Purpose of Review: Several studies have found that medical students have a significant prevalence of sleep issues, such as poor sleep quality, excessive daytime sleepiness, and inadequate sleep duration. The purpose of this review is to carefully evaluate the current research on sleep problems among medical students and, as a result, estimate the prevalence of these disturbances. The EMBASE, PsychINFO, PubMed/MEDLINE, ScienceDirect, Scopus, and Web of Science and retrieved article reference lists were rigorously searched and rated for quality. Random effects meta-analysis was performed to compute estimates. Recent Findings: The current meta-analysis revealed an alarming estimated pooled prevalence of poor sleep quality (K = 95, N = 54894) of 55.64% [95%CI 51.45%; 59.74%]. A total of 33.32% [95%CI 26.52%; 40.91%] of the students (K = 28, N = 10122) experienced excessive sleepiness during the day. The average sleep duration for medical students (K = 35, N = 18052) is only 6.5 h per night [95%CI 6.24; 6.64], which suggests that at least 30% of them get less sleep than the recommended 7-9 h per night. Summary: Sleep issues are common among medical students, making them a genuine problem. Future research should focus on prevention and intervention initiatives aimed at these groups. Supplementary Information: The online version contains supplementary material available at 10.1007/s40675-023-00258-5.

Cross-cultural comparison of mental illness stigma and help-seeking attitudes: a multinational population-based study from 16 Arab countries and 10,036 individuals.

BACKGROUND: There is evidence that culture deeply affects beliefs about mental illnesses' causes, treatment, and help-seeking. We aimed to explore and compare knowledge, attitudes toward mental illness and help-seeking, causal attributions, and help-seeking recommendations for mental illnesses across various Arab countries and investigate factors related to attitudes toward help-seeking. METHODS: We carried out a multinational cross-sectional study using online self-administered surveys in the Arabic language from June to November 2021 across 16 Arab countries among participants from the general public. RESULTS: More than one in four individuals exhibited stigmatizing attitudes towards mental illness (26.5%), had poor knowledge (31.7%), and hold negative attitudes toward help-seeking (28.0%). ANOVA tests revealed a significant difference between countries regarding attitudes (F = 194.8, p < .001), knowledge (F = 88.7, p < .001), and help-seeking attitudes (F = 32.4, p < .001). Three multivariate regression analysis models were performed for overall sample, as well as Palestinian and Sudanese samples that displayed the lowest and highest ATSPPH-SF scores, respectively. In the overall sample, being female, older, having higher knowledge and more positive attitudes toward mental illness, and endorsing biomedical and psychosocial causations were associated with more favorable help-seeking attitudes; whereas having a family psychiatric history and endorsing religious/supernatural causations were associated with more negative help-seeking attitudes. The same results have been found in the Palestinian sample, while only stigma dimensions helped predict help-seeking attitudes in Sudanese participants. CONCLUSION: Interventions aiming at improving help-seeking attitudes and behaviors and promoting early access to care need to be culturally tailored, and congruent with public beliefs about mental illnesses and their causations.

Perceptual visual dependence for spatial orientation in patients with schizophrenia.

BACKGROUND: Patients with schizophrenia are reported to have vestibular dysfunction and to weigh vestibular input to a lesser extent compared to healthy controls. Such deficits may increase visual dependence (VD) for spatial orientation at a perceptual level in these patients. The aim of this study is to compare VD levels between healthy control and patients with schizophrenia and to explore associations between VD and clinical measures in these patients. Relation of VD to antipsychotic drug treatment is also discussed. METHOD: 18 patients with schizophrenia and 19 healthy controls participated in this study. The Rod and Disc Test (RDT) was used to create an optokinetic surround around a centrally located rod. Participants aligned the rod to their subjective visual vertical (SVV) in both static and dynamic disc conditions. VD was calculated as the difference in SVV between these two conditions. RESULTS: There was no group difference or gender difference in static or dynamic SVV as well as VD. There was no correlation between VD and any of the Positive and Negative Syndrome Scale (PANSS) scores, however VD was significantly correlated to illness duration in the patient group. CONCLUSIONS: Schizophrenia is not associated with greater VD levels at a perceptual level, compared to controls, indicating adequate visuo-vestibular integration for judging line verticality in these patients. Patients with greater chronicity of the disease are more visually dependent than those less chronically ill, consistent with previous reports of possible vestibular dysfunction in patients with schizophrenia. This may affect their daily functioning in dynamic visual environments.

Symptom severity is associated with leftward lateralization upon contextual modulation of visual vertical in patients with schizophrenia.

Background: Contextual processing dysfunction in patients with schizophrenia (SCZ) is not uniform and task-dependent. In SCZ, studies on the rod and frame test (RFT), which evaluates contextual modulation of verticality perception, are sparse. A main study that utilized a two-alternative forced choice design for judging rod verticality reported equivalent strength of RFT contextual modulation in healthy controls and SCZ. The current study aims to uncover any potential differences in contextual modulation between controls and SCZ with an adjustment method on a computerized RFT. Materials and methods: A total of 17 healthy controls and 15 SCZ aligned an oriented rod to their perceived vertical with a computer mouse under four randomized frame presentations: absent frame, non-tilted (Frame0°), or tilted by 18 degrees leftward (Frame-18°) or rightward (Frame+18°). Rod deviation error was assigned a negative or positive value when aligned leftward or rightward, respectively, of 0°. Signed and absolute errors, the rod and frame effect (RFE), and intra-individual variability (inconsistency) were used for analysis. Results: There was no group difference in rod alignment errors or derived measures, except that SCZ displayed greater inconsistency in rod alignment, compared to controls. The negative symptom scale (PANSS-N) scores correlated positively with the variability measure and with unsigned Frame-18° error. Conclusions: Only the variability measure was sensitive enough to distinguish between controls and SCZ. SCZ with more severe negative symptoms had larger variability in rod alignment, probably reflecting a state of indifference. The larger deviation errors only with a leftward tilted frame, as PANSS-N scores increased, may indicate a lateralized attentional abnormality that is correlated with severity of symptoms in SCZ.

Prevalence of burnout in medical students: A systematic review and meta-analysis.

BACKGROUND: Medical students are at a significant risk of experiencing psychological issues, such as burnout. Over the past few years, more studies have been conducted on this topic, producing different results. AIMS: The purpose of this review was to determine the global pooled prevalence rate and risk factors associated with burnout and its components among undergraduate (pre-intern) medical students. METHOD: From inception until 30 November 2021, nine electronic databases were used for an electronic search. Using random-effects meta-analysis, we pooled the estimates using the DerSimonian-Laird method. The prevalence of burnout in medical students was the primary outcome of interest. Data were analyzed globally, by country, by research measure. Age and sex were examined as confounders using meta-regression analysis. RESULTS: A random-effects meta-analysis of 42 studies involving 26,824 evaluating the prevalence of burnout in medical students showed an overall prevalence rate 37.23% [32.66%; 42.05%], Q = 2,267.15(41), p < .0001, τ2 = .42, τ = .65, I2 = 98.2%; H = 7.5. Prevalence of emotional exhaustion, depersonalization, and personal accomplishment were 38.08% [30.67%; 46.10%], 35.07% [26.74%; 44.41%], and 37.23% [32.66%; 42.05%], respectively. Variations were observed between countries and research measures. Age (older) and sex (female) were both significant predictors of burnout. CONCLUSION: The prevalence of burnout in medical students was estimated to be 37.23%. It is urgent that future studies serve as a basis for the development of prevention and treatment programs to prevent and treat burnout in students.

Evaluation of the Utility of Online Objective Structured Clinical Examination Conducted During the COVID-19 Pandemic.

Background: The COVID-19 pandemic led to profound restrictions on the face-to-face learning and assessment in all educational institutions, particularly the medical schools. The College of Medicine and Medical Sciences of the Arabian Gulf University (CMMS-AGU) conducted the final exams, both theoretical and clinical components, for its MD students online. This study was conducted to evaluate the utility of online clinical exams held at CMMS-AGU. Methods: This is a cross-sectional, mixed method study that included samples from final year medical students, examiners, and heads of clinical departments. Data were collected through surveys, structured interviews, documents' review, and calculation of online examination's psychometrics. Descriptive statistics were used. Quantitative data were presented in the form of means and standard deviations. Responses of heads of clinical departments in the structured interview were transcribed and analyzed thematically based on three pre-established themes. Results: Quantitative and qualitative data on the utility (validity, reliability, acceptability, educational impact, and cost and feasibility) of online objective structured clinical examination (OSCE) were collected. Content validity of the online clinical examination was established through high mean scores of content representativeness, which was confirmed by the heads of clinical departments regarding the proper coverage of clinical skills. Criterion validity was established through a high correlation between clinical and theoretical exam results (r = 0.75). Reliability of the exam was established through an acceptable Cronbach's alpha value (0.70 to 0.78) over the four days of the examinations. The examinations were perceived as highly acceptable by both students and examiners. High educational impact was inferred from students' responses and review of documents. The examination was found to be feasible and of reasonable cost. Conclusion: Online OSCE might be a good alternative of conventional clinical assessments in times of crises and impossibility of having in-person contact between students, examiners, and patients. An important major drawback is still present in such initiatives, which is the inability to assess students' physical examination skills.

Immune reconstitution and clinical recovery following anti-CD28 antibody (TGN1412)-induced cytokine storm.

Cytokine storm can result from cancer immunotherapy or certain infections, including COVID-19. Though short-term immune-related adverse events are routinely described, longer-term immune consequences and sequential immune monitoring are not as well defined. In 2006, six healthy volunteers received TGN1412, a CD28 superagonist antibody, in a first-in-man clinical trial and suffered from cytokine storm. After the initial cytokine release, antibody effect-specific immune monitoring started on Day + 10 and consisted mainly of evaluation of dendritic cell and T-cell subsets and 15 serum cytokines at 21 time-points over 2 years. All patients developed problems with concentration and memory; three patients were diagnosed with mild-to-moderate depression. Mild neutropenia and autoantibody production was observed intermittently. One patient suffered from peripheral dry gangrene, required amputations, and had persistent Raynaud's phenomenon. Gastrointestinal irritability was noted in three patients and coincided with elevated γδT-cells. One had pruritus associated with elevated IgE levels, also found in three other asymptomatic patients. Dendritic cells, initially undetectable, rose to normal within a month. Naïve CD8+ T-cells were maintained at high levels, whereas naïve CD4+ and memory CD4+ and CD8+ T-cells started high but declined over 2 years. T-regulatory cells cycled circannually and were normal in number. Cytokine dysregulation was especially noted in one patient with systemic symptoms. Over a 2-year follow-up, cognitive deficits were observed in all patients following TGN1412 infusion. Some also had signs or symptoms of psychological, mucosal or immune dysregulation. These observations may discern immunopathology, treatment targets, and long-term monitoring strategies for other patients undergoing immunotherapy or with cytokine storm.

Amisulpride augmentation of clozapine for treatment-refractory schizophrenia: a double-blind, placebo-controlled trial.

BACKGROUND: A second antipsychotic is commonly added to clozapine to treat refractory schizophrenia, notwithstanding the limited evidence to support such practice. METHODS: The efficacy and adverse effects of this pharmacological strategy were examined in a double-blind, placebo-controlled, 12-week randomized trial of clozapine augmentation with amisulpride, involving 68 adults with treatment-resistant schizophrenia and persistent symptoms despite a predefined trial of clozapine. RESULTS: There were no statistically significant differences between the amisulpride and placebo groups on the primary outcome measure (clinical response defined as a 20% reduction in total Positive and Negative Syndrome Scale score) or other mental state measures. However, the trial under recruited and was therefore underpowered to detect differences in the primary outcome, meaning that acceptance of the null hypothesis carries an increased risk of type II error. The findings suggested that amisulpride-treated participants were more likely to fulfil the clinical response criterion, odds ratio 1.17 (95% confidence interval 0.40-3.42) and have a greater reduction in negative symptoms, but these numerical differences were not statistically significant and only evident at 12 weeks. A significantly higher proportion of participants in the amisulpride group had at least one adverse event compared with the control group (p = 0.014), and these were more likely to be cardiac symptoms. CONCLUSIONS: Treatment for more than 6 weeks may be required for an adequate trial of clozapine augmentation with amisulpride. The greater side-effect burden associated with this treatment strategy highlights the need for safety and tolerability monitoring, including vigilance for indicators of cardiac abnormalities, when it is used in either a clinical or research setting.

Amisulpride augmentation in clozapine-unresponsive schizophrenia (AMICUS): a double-blind, placebo-controlled, randomised trial of clinical effectiveness and cost-effectiveness.

BACKGROUND: When treatment-refractory schizophrenia shows an insufficient response to a trial of clozapine, clinicians commonly add a second antipsychotic, despite the lack of robust evidence to justify this practice. OBJECTIVES: The main objectives of the study were to establish the clinical effectiveness and cost-effectiveness of augmentation of clozapine medication with a second antipsychotic, amisulpride, for the management of treatment-resistant schizophrenia. DESIGN: The study was a multicentre, double-blind, individually randomised, placebo-controlled trial with follow-up at 12 weeks. SETTINGS: The study was set in NHS multidisciplinary teams in adult psychiatry. PARTICIPANTS: Eligible participants were people aged 18-65 years with treatment-resistant schizophrenia unresponsive, at a criterion level of persistent symptom severity and impaired social function, to an adequate trial of clozapine monotherapy. INTERVENTIONS: Interventions comprised clozapine augmentation over 12 weeks with amisulpride or placebo. Participants received 400 mg of amisulpride or two matching placebo capsules for the first 4 weeks, after which there was a clinical option to titrate the dosage of amisulpride up to 800 mg or four matching placebo capsules for the remaining 8 weeks. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of 'responders', using a criterion response threshold of a 20% reduction in total score on the Positive and Negative Syndrome Scale. RESULTS: A total of 68 participants were randomised. Compared with the participants assigned to placebo, those receiving amisulpride had a greater chance of being a responder by the 12-week follow-up (odds ratio 1.17, 95% confidence interval 0.40 to 3.42) and a greater improvement in negative symptoms, although neither finding had been present at 6-week follow-up and neither was statistically significant. Amisulpride was associated with a greater side effect burden, including cardiac side effects. Economic analyses indicated that amisulpride augmentation has the potential to be cost-effective in the short term [net saving of between £329 and £2011; no difference in quality-adjusted life-years (QALYs)] and possibly in the longer term. LIMITATIONS: The trial under-recruited and, therefore, the power of statistical analysis to detect significant differences between the active and placebo groups was limited. The economic analyses indicated high uncertainty because of the short duration and relatively small number of participants. CONCLUSIONS: The risk-benefit of amisulpride augmentation of clozapine for schizophrenia that has shown an insufficient response to a trial of clozapine monotherapy is worthy of further investigation in larger studies. The size and extent of the side effect burden identified for the amisulpride-clozapine combination may partly reflect the comprehensive assessment of side effects in this study. The design of future trials of such a treatment strategy should take into account that a clinical response may be not be evident within the 4- to 6-week follow-up period usually considered adequate in studies of antipsychotic treatment of acute psychotic episodes. Economic evaluation indicated the need for larger, longer-term studies to address uncertainty about the extent of savings because of amisulpride and impact on QALYs. The extent and nature of the side effect burden identified for the amisulpride-clozapine combination has implications for the nature and frequency of safety and tolerability monitoring of clozapine augmentation with a second antipsychotic in both clinical and research settings. TRIAL REGISTRATION: EudraCT number 2010-018963-40 and Current Controlled Trials ISRCTN68824876. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 49. See the NIHR Journals Library website for further project information.

The role of nutrient-based epigenetic changes in buffering against stress, aging, and Alzheimer's disease.

Converging evidence identifies stress-related disorders as putative risk factors for Alzheimer Disease (AD). This article reviews evidence on the complex interplay of stress, aging, and genes-epigenetics interactions. The recent classification of AD into preclinical, mild cognitive impairment, and AD offers a window for intervention to prevent, delay, or modify the course of AD. Evidence in support of the cognitive effects of epigenetics-diet, and nutraceuticals is reviewed. A proactive epigenetics diet and nutraceuticals program holds promise as potential buffer against the negative impact of aging and stress responses on cognition, and can optimize vascular, metabolic, and brain health in the community.

Proof-of-Concept Randomized Controlled Study of Cognition Effects of the Proprietary Extract Sceletium tortuosum (Zembrin) Targeting Phosphodiesterase-4 in Cognitively Healthy Subjects: Implications for Alzheimer's Dementia.

Introduction. Converging evidence suggests that PDE-4 (phosphodiesterase subtype 4) plays a crucial role in regulating cognition via the PDE-4-cAMP cascade signaling involving phosphorylated cAMP response element binding protein (CREB). Objective. The primary endpoint was to examine the neurocognitive effects of extract Sceletium tortuosum (Zembrin) and to assess the safety and tolerability of Zembrin in cognitively healthy control subjects. Method. We chose the randomized double-blind placebo-controlled cross-over design in our study. We randomized normal healthy subjects (total n = 21) to receive either 25 mg capsule Zembrin or placebo capsule once daily for 3 weeks, in a randomized placebo-controlled 3-week cross-over design. We administered battery of neuropsychological tests: CNS Vital Signs and Hamilton depression rating scale (HAM-D) at baseline and regular intervals and monitored side effects with treatment emergent adverse events scale. Results. 21 subjects (mean age: 54.6 years ± 6.0 yrs; male/female ratio: 9/12) entered the study. Zembrin at 25 mg daily dosage significantly improved cognitive set flexibility (P < 0.032) and executive function (P < 0.022), compared with the placebo group. Positive changes in mood and sleep were found. Zembrin was well tolerated. Conclusion. The promising cognitive enhancing effects of Zembrin likely implicate the PDE-4-cAMP-CREB cascade, a novel drug target in the potential treatment of early Alzheimer's dementia. This trial is registered with ClinicalTrials.gov NCT01805518.

Liposomal-formulated curcumin [Lipocurc™] targeting HDAC (histone deacetylase) prevents apoptosis and improves motor deficits in Park 7 (DJ-1)-knockout rat model of Parkinson's disease: implications for epigenetics-based nanotechnology-driven drug platform.

BACKGROUND: Converging evidence suggests dysregulation of epigenetics in terms of histone-mediated acetylation/deacetylation imbalance in Parkinson's disease (PD). Targeting histone deacetylase (HDAC) in neuronal survival and neuroprotection may be beneficial in the treatment and prevention of neurodegenerative disorders. Few pharmacological studies use the transgenic model of PD to characterize the neuroprotection actions of a lead compound known to target HDAC in the brain. METHODS: In our study, we investigated neuroprotective effects of liposomal-formulated curcumin: Lipocurc™ targeting HDAC inhibitor in the DJ-1(Park 7)-gene knockout rat model of PD. Group I (DJ-1-KO-Lipocurc™) received Lipocurc™ 20 mg/kg iv 3× weekly for 8 weeks; Group II: DJ-1 KO controls (DJ-1 KO-PBS) received i.v. phosphate-buffered saline (PBS). Group III: DJ-1-Wild Type (DJ-1 WT-PBS) received PBS. We monitored various components of motor behavior, rotarod, dyskinesia, and open-field behaviors, both at baseline and at regular intervals. Toward the end of the 8 weeks, we measured neuronal apoptosis and dopamine (DA) neuron-specific tyrosine hydroxylase levels by immunohistochemistry methods at post-mortem. RESULTS: We found that DJ-KO Group I and Group II, as compared with DJ-1 WT group, exhibited moderate degree of motor impairment on the rotarod test. Lipocurc™ treatment improved the motor behavior motor impairment to a greater extent than the PBS treatment. There was marked apoptosis in the DJ-1 WT group. Lipocurc™ significantly blocked neuronal apoptosis: the apoptotic index of DJ-1-KO-Lipocurc™ group was markedly reduced compared with the DJ-KO-PBS group (3.3 vs 25.0, p<0.001). We found preliminary evidence Lipocurc™ stimulated DA neurons in the substantia nigra. The ratio of immature to mature DA neurons in substantia nigra was statistically higher in the DJ-1-KO-Lipocurc™ group (p<0.025). CONCLUSIONS: We demonstrated for the first time Lipocurc™'s anti-apoptotic and neurotrophic effects in theDJ-1-KO rat model of PD. Our promising findings warrant randomized controlled trial of Lipocurc™ in translating the novel nanotechnology-based epigenetics-driven drug discovery platform toward efficacious therapeutics in PD.

Medical education and health care in Iraqi Kurdistan in the last four decades.

Medical education and health care in Iraqi Kurdistan were oppressed by the regime of Saddam Hussein for four decades. There have been efforts to revive them by Kurdish and non-Kurdish professionals in and outside Kurdistan with the assistance of various governmental and non-governmental organisations. However, the health care and medical education systems in Iraqi Kurdistan require ongoing international support. Recent global awareness of the war on terror and attempts to rebuild the health care system should not concentrate only on the immediate effects of the war, but they should also focus on the wide-ranging implications of the previous dictatorship regime.

Clinical correlates of insight in schizophrenia.

111 schizophrenic patients diagnosed in accordance with DSM-III were rated on Landmark's symptom checklist, on demographic variables, and on variables descriptive of the course of illness. Of the 111 patients, 108 (97.3%) showed poor insight into their illness at some time in the past and 65 (58.6%) at the time of assessment. Those presently showing poor insight were significantly (Pearson rs, p< .01, 2-tailed) more frequently rated as currently displaying poor judgement also in other matters (r =.50), as showing social withdrawal (r=.42) and poor rapport (r=.33), and as being preoccupied with their delusions or hallucinations (r=.31) and as being unreliable informants (r=.41). They usually had lower education (r=.33), their income in the last taxation year was lower (r = .47), and their work functioning was less adequate (r = .30).

Sociodemographic correlates of assimilation of refugees from Kurdistan.

Successful assimilation of refugees in their host country is an important prerequisite of psychological well-being. Refugees' satisfaction in the new country is one of key indicators of their assimilation. The satisfaction with their host country was assessed for 54 Kurdish refugees of mean age of 35.8 yr. (SD= 10.9) via an 8-item rating scale partly based on Cernovsky's Assimilation Scale. The 36 men and 18 women had resided in the host country for a mean of 4.5 yr. (SD=4.0). An overall score was calculated from ratings of satisfaction with personal safety, health, employment, food, financial security, social life, and entertainment. This overall score was unrelated to age, sex, and employment status. Those who emigrated at a younger age (r = -.28, p = .03) and those with lower education reported more satisfaction with their host country (r = -.28, p = .03) perhaps because they could more easily and rapidly re-establish social status comparable to what they had in their homeland than could older refugees from Kurdistan's higher educational strata.