Calcium (Ca2+) hemostasis, mitochondria, autophagy, and mitophagy contribute to Alzheimer's disease as early moderators.

This review rigorously investigates the early cerebral changes associated with Alzheimer's disease, which manifest long before clinical symptoms arise. It presents evidence that the dysregulation of calcium (Ca2+) homeostasis, along with mitochondrial dysfunction and aberrant autophagic processes, may drive the disease's progression during its asymptomatic, preclinical stage. Understanding the intricate molecular interplay that unfolds during this critical period offers a window into identifying novel therapeutic targets, thereby advancing the treatment of neurodegenerative disorders. The review delves into both established and emerging insights into the molecular alterations precipitated by the disruption of Ca2+ balance, setting the stage for cognitive decline and neurodegeneration.

Traumatic Events Exposure and Post Traumatic Stress Disorder in Caregivers of Patients with Bipolar Disorder, Bipolar Disorder and Comorbid Post Traumatic Stress Disorder and Multiple Sclerosis.

Background: Chronic diseases affect the lives of the patient and caregiver. Caring for a patient with a chronic psychiatric illness, such as bipolar disorder, is a stressful and challenging activity. Caregivers of severe psychiatric patients are the primary victims of violence by patients. Caring for these patients can be very stressful for the caregiver to the extent of experiencing post-traumatic stress symptoms. This study compares the frequency of trauma exposure and PTSD in the caregivers of patients with bipolar disorder type 1(BD-1), bipolar disorder type 1, comorbid post-traumatic stress disorder (BD-1+PTSD), and multiple sclerosis (MS).The MS group served as the control group. Methods: This cross-sectional study with convenient sampling was conducted at three hospitals in Tehran, Iran, from April 2020 to January 2022. One hundred eighty caregivers answered a clinical demographic questionnaire. We then used the Trauma History Questionnaire (THQ) to assess the frequency of exposure to different types of trauma. Then, the Persian version of the SCID-5, a valid and reliable instrument for psychiatric diagnoses, was used to diagnose PTSD. Chi-square was used for analyzing data. Results: Exposure to trauma has a significant difference between the groups. BD-1 + PTSD patients' caregivers were exposed to more physical assaults than others (P < 0.0001) There was a significant difference between sexual harassment in the MS group (P = 0.010). There was a significant difference between the three groups in the development of PTSD (P = 0.003). PTSD prevalence in the BD-1 + PTSD caregiver group is more than in other groups. In the caregivers of BD-1+PTSD, the caregiving experience caused traumatic exposure and the development of PTSD in all caregivers. Conclusion: This study shows that the prevalence of exposure to traumatic events and PTSD is higher in the caregivers of BD-1 patients, especially if the patient has comorbid PTSD. Detecting these symptoms early and using intervention can make the caregiving burden more tolerable.

P38 initiates degeneration of midbrain GABAergic and glutamatergic neurons in diabetes models.

Diabetes mellitus may cause tau protein hyperphosphorylation and neurodegeneration, but the exact mechanism by which diabetic conditions induce tau pathology remains unclear. Tau protein hyperphosphorylation is considered a major pathological hallmark of neurodegeneration and can be triggered by diabetes. Various tau-directed kinases, including P38, can be activated upon diabetic stress and induce tau hyperphosphorylation. Despite extensive research efforts, the exact tau specie(s) and kinases driving neurodegeneration in diabetes mellitus have not been clearly elucidated. We herein employed different techniques to determine the exact molecular mechanism of tau pathology triggered by diabetes in in vivo and in vitro models. We showed that diabetes-related stresses and glucose metabolism deficiency could induce cis P-tau (an early driver of the tau pathology) accumulation in the midbrain and corpus callosum of the diabetic mice models and cells treated with 2-deoxy-D-glucose, respectively. We found that the active phosphorylated level of P38 was increased in the treated cells and diabetic mice models. We observed that oxidative stress activated P38, which directly and indirectly drove tau pathology in the GABAergic and glutamatergic neurons of the midbrain of the diabetic mice after 96 h, which accumulated in the other neighboring brain areas after 2 months. Notably, P38 inhibition suppressed tau pathogenicity and risk-taking behaviors in the animal models after 96 h. The data establish P38 as a central mediator of diabetes mellitus-induced tau pathology. Our findings provide mechanistic insight into the consequences of this metabolic disorder on the nervous system.

Safety and efficacy of melatonin, clonazepam, and trazodone in patients with Parkinson's disease and sleep disorders: a randomized, double-blind trial.

BACKGROUND: Sleep disturbances are common non-motor symptoms of Parkinson's disease (PD). We aimed to compare the safety and efficacy of trazodone with melatonin and clonazepam in patients with PD and sleep complaints. METHODS: This single-center, double-blind, randomized clinical trial was conducted on PD patients with subjective sleep complaints. Eligible patients were randomized 1:1:1 to receive melatonin 3 mg/day, clonazepam 1 mg/day, or trazodone 50 mg/day for 4 weeks. The primary outcome measure was the changes in Pittsburgh Sleep Quality Index (PSQI) scores. The mean change in Epworth Sleepiness Scale (ESS) and RBD screening questionnaire (RBDSQ) was considered as the secondary outcome measures. RESULTS: A total of 112 eligible patients were randomized and 93 participants, melatonin (n = 31), trazodone (n = 31), and clonazepam (n = 31), completed the study. There was a significant decrease in PSQI scores after 4 weeks of treatment in all groups. The mean changes of PSQI from baseline were similar among the treatment arms (P = 0.325). Mean changes of RBDSQ and ESS from baseline were significantly different between study arms (P < 0.05). Melatonin intake was associated with a higher decrease in RBDSQ score compared to trazodone (P = 0.011) and clonazepam (P = 0.004). Trazodone intake was associated with a higher decrease in ESS score compared to clonazepam (P = 0.010). Mild adverse events were reported in three patients in the clonazepam, two patients in the trazodone group, and none in the melatonin group. CONCLUSIONS: Trazodone 50 mg/day, clonazepam 1 mg/day, and melatonin 3 mg/day were all tolerable and effective in improving sleep quality in patients with PD. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (registration number; IRCT20170821035819N2).

Systematic review and meta-analysis of the placebo effect in panic disorder: Implications for research and clinical practice.

OBJECTIVE: This review aimed to measure the degree of placebo response in panic disorder. DATA SOURCES: We searched major databases up to 31 January 2021, for randomized pharmacotherapy trials published in English. STUDY SELECTION: A total of 43 studies met inclusion criteria to be in the analysis (with 174 separate outcome measurements). DATA EXTRACTION: Changes in outcome measures from baseline in the placebo group were used to estimate modified Cohen's d effect size. RESULTS: A total of 43 trials (2392 subjects, 174 outcomes using 27 rating scales) were included in the meta-analysis. Overall placebo effect size was 0.57 (95% confidence interval = [0.50, 0.64]), heterogeneity (I2: 96.3%). Higher placebo effect size was observed among clinician-rated scales compared to patient reports (0.75 vs 0.35) and among general symptom and anxiety scales compared to panic symptoms and depression scales (0.92 and 0.64 vs 0.56 and 0.54, respectively). There was an upward trend in effect size over the publication period (r = 0.02, p = 0.002) that was only significant among clinician-rated scales (r = 0.02, p = 0.011). There was no significant publication bias, Egger's test (p = 0.08). CONCLUSION: We observed a substantial placebo effect size in panic disorder. This effect was more prominent for some aspects of panic disorder psychopathology than for others and was correlated with the source of the assessment and publication year. This finding has implications both for research design, to address the heterogeneity and diversity in placebo responses, and for clinical practice to ensure optimal quality of care. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO, CRD42019125979.

α-synuclein abnormalities trigger focal tau pathology, spreading to various brain areas in Parkinson disease.

Parkinson disease (PD) is the second most common neurodegenerative disorder, whose prevalence is 2~3% in the population over 65. α-Synuclein aggregation is the major pathological hallmark of PD. However, recent studies have demonstrated enhancing evidence of tau pathology in PD. Despite extensive considerations, thus far, the actual spreading mechanism of neurodegeneration has remained elusive in a PD brain. This study aimed to further investigate the development of α-synuclein and tau pathology. We employed various PD models, including cultured neurons treated with either 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or with recombinant α-synuclein. Also, we studied dopaminergic neurons of cytokine Interferon-ß knock-out. Moreover, we examined rats treated with 6-hydroxydopamine, Rhesus monkeys administrated with MPTP neurotoxin, and finally, human post-mortem brains. We found the α-synuclein phosphorylation triggers tau pathogenicity. Also, we observed more widespread phosphorylated tau than α-synuclein with prion-like nature in various brain areas. We optionally removed P-tau or P-α-synuclein from cytokine interferon-ß knock out with respective monoclonal antibodies. We found that tau immunotherapy suppressed neurodegeneration more than α-synuclein elimination. Our findings indicate that the pathogenic tau could be one of the leading causes of comprehensive neurodegeneration triggered by PD. Thus, we can propose an efficient therapeutic target to fight the devastating disorder.

Discharge of psychiatric patients against psychiatrist's advice.

Background: Discharge from the hospital against the doctor's advice and refusal of receiving treatment is one of the significant issues at the time of hospitalization, which is especially crucial in relation to psychiatric patients. It can exacerbate the disorder and the subsequent complications and increase further hospital admissions. The present study was designed to evaluate the causes of discharge from the hospital and the refusal of receiving treatment against medical advice in hospitalized patients in Iran Psychiatric Hospital. Methods: The present study was a descriptive cross-sectional study. One hundred patients hospitalized in Iran Psychiatric Hospital discharged with personal consent against medical advice from July to December 2018 were studied. Two methods were used for assessment; the fulfillment of a routine ministry-approved checklist by the dischargers themselves and the face-to-face interview with both the patient and discharger based on a researcher-made checklist. Cohen's Kappa coefficient was used to assess the agreement of the answers of patients to both routine ministry-approved and researcher-made checklists by SPSS software version 16.0 with an overall accuracy of 95%. Results: Based on the results extracted from the researcher-made checklist, 43 (43%) of the discharges were generally based on patient-related factors. The personal insistence to discharge by the patient was cited as the main reason for discharge. Cohen's Kappa coefficient showed no significant agreement between the patient's answers to the interview and what they have previously filled in the routine ministry-approved checklist. More specifically, the measure of agreement for answers of patients to questions in the standard checklist and the questions asked by the interviewer was 0.078 (p=0.167). Conclusion: From the results of this study, it can be concluded that the face-to-face interview based on the researcher-made checklist can more effectively determine the reasons for discharge of patients due to the accuracy of the interview.

Wnt signalling pathway and tau phosphorylation: A comprehensive study on known connections.

The Wnt pathway is the most important cascade in the nervous system; evidence has indicated that deregulation of the Wnt pathway induced pathogenic hallmarks of neurodegenerative diseases. Glycogen synthase kinase-3ß (GSK-3ß) as the main member of the Wnt pathway increases tau inclusions, the main marker in the neurodegenerative diseases. Phosphorylated tau is observed in the pre-tangle of the neurons in the early stage of neurodegenerative diseases. The researchers always try to improve pharmacological approaches of new therapeutic strategies to the treatment of neurodegenerative diseases that are required to represent a significant entry point by understanding the theoretical interactions of the molecular pathways. In this review, we have discussed the recent knowledge about the canonical and non-canonical Wnt signalling pathway, GSK-3ß, Wnt/ß-catenin antagonists, tau phosphorylation, and their important roles in the neurodegenerative diseases.

First line in psychiatric emergency: pre-hospital emergency protocol for mental disorders in Iran.

INTRODUCTION: This article is a report of designing a rapid and effective guide for paramedics who take care of patients in a pre-hospital setting to answer developing demands. METHODS: The relevant literature was reviewed, and the topics were extracted. Then, the extracted items were discussed in an expert panel. Finally, items were discussed in a meeting including emergency technicians and emergency technical assistants to identify implementation problems. RESULTS: Important topics for managing psychiatric patients were categorized at three levels: 1) Patient safety and security issues, 2) Patient status assessment and diagnosis, and 3) Patient management (medical, behavioral management, and referral to a treatment center). DISCUSSION: This protocol can be a solution to improve emergency technician training. Such summarized protocols can be used for rapid review immediately before exposing a patient with an acute psychiatric condition. Due to specific cultural and different access to medicines in Iran, some issues are different.

Spirituality as a sociocultural determinant of health in the context of medical curriculum: A call for action.

Background: This study aimed to investigate the state of spirituality in the general medicine curricula in Iran. Methods: Reference books for general medicine were reviewed and data were analyzed according to the qualitative content analysis method. Results: After reviewing references, it was found that only 35 paragraphs of the educational reference pages dealt with this subject. Related topics to spirituality had 2 major themes: (a) spirituality and care (assessment, treatment, palliative care, and bereavement); (b) spirituality and professionalism (considering culture and medical ethics). Conclusion: This study showed that despite the importance of the subject and much evidence on spirituality and medicine, medical references have limitations. The authors suggested some strategies to develop a specific course and integrate all educational references with the objectives of the general medical education course in Iran.

Predictors of physical restraint in a psychiatric emergency setting.

BACKGROUND: Considering the negative consequences of using physical restraints, we conducted this study to identify patients who are more frequently restrained in a psychiatric emergency ward as an initial step to limit the use of restraint to the minimum possible. METHODS: This was a retrospective case control study conducted in Iran Psychiatric Hospital in Tehran, Iran. We reviewed the files of 607 patients who were admitted during a one year period using convenience sampling; of them, 186 were in the restrained group and 421 in the unrestrained group. RESULTS: Surprisingly, no significant difference was found between the restrained and unrestrained groups in demographic characteristics. The patients who were referred because of violence were diagnosed as having methamphetamine induced psychotic disorder or bipolar I disorder in manic 1episode and had a higher odds of being restrained (OR=2.51, OR=1.61, and OR=1.57 respectively). Being restrained was also associated with a longer duration of hospitalization and duration of staying in the emergency ward. Moreover, patients in their first admission were more frequently restrained. CONCLUSION: Medical and nursing staff should consider special measures for the patients who are at a higher risk for being restrained. More frequent visits and education for both patients and staff may be effective in reducing the number of physical restraints for these groups of patients.

Evaluation of the Cutoff Point and Diagnostic Value of the Neutrophil-to-Lymphocyte Ratio in Predicting Ovarian Cancer Compared to Pathological Findings.

PURPOSE: This research aims to establish a neutrophil-to-lymphocyte ratio (NLR) threshold and evaluate its diagnostic accuracy compared to pathological criteria for diagnosing Epithelial Ovarian Cancer (EOC). METHODS: We conducted a cross-sectional study at Imam Hossein Hospital involving 204 women aged 18 and older with confirmed ovarian mass based on pathology. We recorded clinical, pathological, and preoperative blood count data, including neutrophil-to-lymphocyte ratio (NLR). Patients were categorized into malignant and benign ovarian mass groups based on postoperative pathology. The power of NLR to diagnosis of EOC was evaluated using ROC curve. RESULTS: At total, 204 patients (Benign 75.5% vs. Malignant 24.5%) were included in the analysis with mean age of 54.26 ±12.04 yrs in malignant and 46.31±13.21 in benign. In all cases, the proportion of patients with the following tumor markers HE4 (>140 Pm), CA 125 (> 35U/Ml) and CEA (>5 ng/Ml) were 52.45%, 41.67% and 3.43%, respectively, and proportion of abnormal tumor markers was statistically higher in malignant group compared to benign mass (p <0.05).  Odds of having higher NLR levels in the malignancy group was higher than benign group (e.g., OR of 4.45 for NLR in quartile 4 vs. quartile 1).  According to model selection criteria, the full model with including NLR level and age, BMI and tumor markers has best performance for diagnosis of malignancy (AUC =0.87). CONCLUSION: High NLR in combination with tumor markers including CA125, HE4 and CEA were associated with malignancy in patients with ovarian mass. More attention and further examinations should be devoted for patients with ovarian mass having high NLR and abnormal tumor markers levels to detect the probable malignancy as soon as possible.

Knowledge, attitude, and practice regarding child maltreatment amongst Iranian medical students through internship course: an 18-month longitudinal study.

BACKGROUND: Child maltreatment has been a major worldwide problem and has remained a persistent public health challenge in all countries. Physicians have a significant role in the prevention and intervention of child maltreatment. An educated physician that can effectively identify and report child maltreatment can fill one of the most significant gaps in reducing child abuse. This study was performed to examine the knowledge, attitude, and practice regarding child maltreatment among Iranian medical students through an internship course. METHOD: All the medical students (235 students) of the Iran University of Medical Sciences who passed the internship entrance exam in the 2019-2020 academic year participated in this study. The participants completed a 49-item scale questionnaire built by combining three other validated questionnaires that evaluate their attitude, knowledge, and practice skills in the first month of their internship course and then completed the same questionnaire 18 months later, at the end-point of the internship period. RESULTS: One-hundred thirty nine (59.1%) participants were female, and 96 (40.9%) were male. The mean age of the subjects was 24.35 ± 0.76. Only 7 (3%) of them formerly received any education about child maltreatment. There was a significant improvement in scores of the knowledge of prevention (p-value = 0.001), the practice of prevention (p-value < 0.001) and the general subscale of the practice section (p-value < 0.001) during the internship course. However, the performance of participants decreased significantly in the subscales of the attitude towards diagnosis (p-value = 0.001) and the attitude towards reporting (p-value < 0.001) of child maltreatment. At the end of the study, the result of graduated physicians was: The total knowledge and attitude of participants were satisfactory, and the majority were at reasonable levels. Although in the practice subscale, 70.6% of the participants didn't identify, 84.7% didn't refer, and 86.4% didn't report a child abuse case in the past year. CONCLUSION: The knowledge and attitude of Iranian physicians regarding child maltreatment are at a satisfactory level. Although, the practice level has deficiencies. In addition, our findings show that Iranian interns have a shallow experience regarding child maltreatment, particularly despite the higher scores in attitude and knowledge, which can be the reason for deficiencies in the practice level.

The COVID-19 pandemic and mental health in pregnant women: A review article.

A rapid spreading of the COVID-19 virus in recent years had a great impact on every single aspect of live and the world faced with unexpected and unpredictable crisis in both physical and mental condition. As with any crisis, vulnerable individuals like pregnant women were the concern of societies. Several physiological and psychological changes occur during pregnancy which put individuals in a risk of mental health problems. During the outbreak of the COVID-19, pregnant women have experienced more psychological stresses, fear, anxiety, and depression. The prenatal mental distresses and psychiatric disorders may cause poor compliance, reduce help-seeking behaviors, and neglect to take the follow up screening visits and risk of harm for mother and others. Addressing the mental health in pregnant women is crucial to prevent the consequences. The purpose of this narrative review was to investigate the available literature on the impact of the COVID-19 pandemic on mental health in pregnant women and provide some recommendations to improve mental health in them. It also shed some light on providing mental health services for women during pregnancy and can be used by health professionals and policymakers.

The Comparison Between Positive and Negative Symptoms Severity in Prolonged Methamphetamine-induced Psychotic Disorder and Schizophrenia.

Introduction: This study aims to compare the positive and negative symptoms of schizophrenia in patients who had psychotic symptoms more than one month after discontinuation of methamphetamine abuse. These factors were analyzed by the positive and negative syndrome scale (PANSS) questionnaire. Methods: Sixty participants were selected from patients referred to Iran Psychiatric Hospital with psychotic symptoms (delusions or hallucinations, disorganized behavior, and speech). The control group was 30 patients with schizophrenia based on a semi-structured interview according to DSMIV-TR (SCID). Thirty patients with a prolonged methamphetamine-induced psychotic disorder were also placed in the case group. For both groups of patients, questionnaires of PANSS, Brief Psychiatric Rating Scale (BPRS), and Global Assessment Of Functioning (GAF) were filled out after obtaining the companions' consent. The scale scores were compared between groups. We used the Mann-Whitney and the Chi-square test to evaluate the mean values of PANSS, BPRS, and GAF scores between the two groups. Results: here was an insignificant difference in positive and general pathology scores between the two groups, but the total score of negative symptoms in the schizophrenia group was significantly higher than in the group of prolonged methamphetamine psychotic disorders (P=0.034). Average scores of uncooperativeness (0.008), difficulty in abstract thinking (0.004), motor retardation (0.002), unusual thought content (0.001), and hostility (0.011) in the schizophrenia group were significantly higher than those in the prolonged methamphetamine psychosis. Conclusion: The results showed that most of the disturbances in patients with schizophrenia might be more influenced by the expression of cognitive disabilities than those with methamphetamine psychosis. The difference in negative symptom scores suggests that schizophrenia and prolonged methamphetamine psychotic disorder can be two different disorders. Highlights: General and positive symptoms scores don't have significant differences.Negative symptoms are much more in schizophrenia.Uncooperativeness, unusual thought content and, motor retardation have more scores in schizophrenia. Plain Language Summary: In clinical practice, Schizophrenia and prolonged methamphetamine-induced psychotic disorder have some similar mental presentations. Additionally, in scientific literature, there is scarce evidence about these similarities. In this regard, this research was designed to investigate the aforementioned obscurity. Determination of similarities and differences between them helps us to address these disorders in terms of treatment and follow-up and awareness of their prognosis of them. This research is a case-control study in which we examine positive and negative psychotic symptoms in schizophrenia and prolonged methamphetamine-induced psychotic disorder. Researchers investigated psychotic symptoms with positive and negative syndrome scale (PANSS), brief psychiatric rating scale (BPRS), and global assessment of functioning (GAF) questionnaires. Moreover, results demonstrate general and positive symptoms scores don't have many differences but negative symptoms are much more in patients with schizophrenia than in patients with a prolonged methamphetamine-induced psychotic disorder. Also, other features like uncooperativeness, unusual thought content, motor retardation, difficulty in abstract thinking, and hostility have higher scores in schizophrenia than the others. In conclusion, this research showed that these disorders are two distinct disorders with some similarities in positive symptoms but not in all features. So, some studies can be designed about why there are similarities between them?

Online Sexual Activity among Iranian Clients with Borderline Personality Disorder and Its Correlation with Severity of Symptoms.

Objective: Clients with borderline personality disorder (BPD) often engage in high-risk sexual behaviors. Online sexual platforms convey abusive and harmful themes, especially for this group of sexually impulsive patients. We hypothesized a correlation between their online sexual activities and the severity of BPD symptoms. Method : Fifty clients with BPD who were referred to Iran psychiatric hospital and Tehran Psychiatric Institute in 2020 participated in this research. The Borderline Evaluation of Severity over Time (BEST) questionnaire was used to assess the severity of BPD symptoms, and the Internet Sex Screening Test (ISST) was used to evaluate online sexual behaviors. A psychiatric interview considered substance abuse and other confounding factors. Results: The mean ISST and BEST scores were 7.82 ± 5.74 and 41.7 ± 12.5, respectively. There was a positive and significant correlation between the severity of BPD symptoms and online sexual activities (P < 0.001, r = 0.480). There was also a significant relationship between online sexual activities and a history of substance abuse (P = 0.003, F = 25.06). Conclusion: Online sexual activity can harm clients with BPD who are more vulnerable to high-risk sexual behaviors. More severe borderline personality traits were associated with more online sexual activity, which underlines the importance of providing education about and managing such activities in clients with BPD.

Comparison of Online Sexual Activity Among Iranian Individuals With and Without Substance Use Disorder: A Case-Control Study.

The most important practical concerns in addiction medicine are the non-substance addiction and related addictive behaviors among individuals with substance use disorder. On the other hand, technological advances, and easy access have increased the frequency of online sexual activities (OSAs) as one of these behaviors. This study aimed to compare the prevalence of OSAs, based on the Internet Sex Screening Test (ISST) scores, among 60 patients with substance use disorder referred to Iran Psychiatric Hospital and 60 non-dependent individuals. The results showed significant negative correlations between the ISST scores and age, age at the onset of substance use, and substance use duration. There was a significant difference between the ISST scores of the case and control groups (P = 0.001). Patients who start using substances at an early age and have a great duration of substance use are more likely to engage in other addictive behaviors such as OSAs. Therefore, it is critical to consider OSAs and other addictive behaviors in patients with substance use disorder to provide better care for this vulnerable community.

Impact of Baseline Estimated Glomerular Filtration Rate Using CKD-EPI Equation on Long-term Prognosis of STEMI Patients: A Matter of Small Increments!

BACKGROUND: Baseline biomarkers including glomerular filtration rate (GFR) guide the management of patients with ST-segment elevation myocardial infarction (STEMI). GFR is a tool for prediction of adverse outcomes in these patients. OBJECTIVES: We aimed to determine the prognostic utility of estimated GFR using Chronic Kidney Disease Epidemiology Collaboration in a cohort of STEMI patients. METHODS: A retrospective cohort was designed among 5953 patients with STEMI. Primary endpoint of the study was major adverse cardiovascular events. GFR was classified into 3 categories delineated as C1 (<60 mL/min), C2 (60-90), and C3 (≥ 90). RESULTS: Mean age of the patients was 60.38 ± 5.54 years and men constituted 78.8% of the study participants. After a median of 22 months, Multivariate Cox-regression demonstrated that hazards of major averse cardiovascular event, all-cause mortality, cardiovascular mortality, and nonfatal myocardial infarction were significantly lower for subjects in C3 as compared with those in C1. Corresponding hazard ratios (HRs) for mentioned outcomes regarding C3 versus C1 were (95% confidence interval) were (HR = 0.852 [0.656-0.975]; P = 0.035), (HR = 0.425 [0.250-0.725]; P = 0.002), (HR = 0.425 [0.242-0.749]; P = 0.003), and (0.885 [0.742-0.949]; P = 0.003), respectively. Normal GFR was also associated with declined in-hospital mortality with HR of C3 versus C1: 0.299 (0.178-0.504; P < 0.0001). CONCLUSIONS: Baseline GFR via Chronic Kidney Disease Epidemiology Collaboration is associated with long-term cardiovascular outcomes following STEMI.

Glutamatergic medications as adjunctive therapy for moderate to severe obsessive-compulsive disorder in adults: a systematic review and meta-analysis.

BACKGROUND: Obsessive-compulsive disorder (OCD) is among the most disabling neuropsychiatric conditions characterized by the presence of repetitive intrusive thoughts, impulses, or images (obsessions) and/or ritualized mental or physical acts (compulsions). Serotonergic medications, particularly Selective Serotonin Reuptake Inhibitors (SSRIs), are the first-line treatments for patients with OCD. Recently, dysregulation of glutamatergic system has been proposed to be involved in the etiology of OCD. We designed this systematic review and meta-analysis to evaluate clinical efficacy of glutamatergic medications in patients with OCD, according to the guidelines of Cochrane collaboration. METHOD: We searched Medline, Scopus, and Cochrane library without applying any language filter. Two of the authors independently reviewed search results for irrelevant and duplicate studies and extracted data and assessed methodological quality of the studies. We transformed data into a common rubric and calculated a weighted treatment effect across studies using Review Manager. RESULTS: We found 476 references in 3 databases, and after exclusion of irrelevant and duplicate studies, 17 studies with total number of 759 patients with OCD were included. In the present review we found evidence for several drugs such as memantine, N-acetylcysteine (NAC), Minocycline, L-carnosine and riluzole. Glutamaterigic drug plus SSRIs were superior to SSRI+ Placebo with regard to Y-BOCS scale [standardized mean difference (SMD = - 3.81 95% CI = - 4.4, - 3.23). CONCLUSION: Augmentation of glutamatergic medications with SSRIs are beneficial in obsessive-compulsive patients, no harmful significant differences in any safety outcome were found between the groups.

Dopamine-loaded poly (butyl cyanoacrylate) nanoparticles reverse behavioral deficits in Parkinson's animal models.

Aim: Parkinson's disease (PD) is a neurological disorder resulting from decreased dopamine (DA) secretion in the brain, which reflects impaired motor function. Thus, a drug-delivery system for releasing DA into the brain would be of crucial importance. Materials & methods: We herein examined the in vivo drug efficiency of novel poly-butyl-cyanoacrylate nanoparticles loaded with DA (DA-PBCA NPs). Results & conclusion: The NPs were able to pass through the blood-brain barrier and improve brain structure and function in the PD animal models. Moreover, we found a reduced α-synucleinopathy in the animal model brains after the NPs administration. Thus, the NPs seem to be a reliable DA delivery system for treating PD patients.