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Objectives: Converging evidence indicates that Horticultural Therapy (HT) contributes to significant reductions in stress, loneliness, and depression, notable risk factors for suicidality. This pilot study aimed to assess the initial feasibility and acceptability of HT when virtually administered. Intervention: Telehealth-delivered horticultural therapy (TeleHT) was administered to groups of Veterans, including those with elevated suicide risk over the course of four weeks. Participants were each sent a package through the mail of at-home gardening supplies that were used to facilitate multisensory, nature experiences during weekly HT sessions administered via Zoom. Outcome measures: Participants completed thermometer-based scales for the suicide risk factors of stress, loneliness, depression, and pain before and after each TeleHT session. Post-intervention qualitative assessments were completed upon the conclusion of the four-week intervention. Results: Significant reductions in stress, depression, and loneliness risk were observed from weekly pre- to post-session measures (p

While many studies of intestinal permeability (IP) are focused on those with gastrointestinal (GI) disorders, there is a rising trend to analyze IP among individuals with mental health conditions including posttraumatic stress disorder (PTSD) with and without diagnosed GI conditions. This interest stems from the association between gut dysbiosis and chronic inflammation, which are mechanisms linked to stress-related somatic and mental health conditions. Efforts to date have resulted in the exploration of non-invasive and feasible measures to identify an IP biomarker that could also serve as a treatment target. Additionally, those conducting studies regarding IP often recruit individuals without health problems and compare levels of biomarkers of IP to those obtained from participants with conditions of interest. This study aimed to assess correlations between blood-based biomarkers of IP, as well as examine the association between blood-based biomarkers of IP and PTSD symptoms. Blood was sampled from seventeen United States military Veterans with variable severity of PTSD symptoms per the posttraumatic checklist for DSM-5 (PCL-5) (n = 6 with scores over 31 indicating clinically meaningful symptoms of PTSD; overall range 0–49, mean 20.8, standard deviation 15.7) and analyzed blood biomarkers of IP including citrulline, diamine oxidase, glucagon-like peptide-2, intestinal fatty-acid binding protein, lipopolysaccharide binding protein, lipopolysaccharide, and zonulin. Correlations between the IP blood-based biomarkers ranged from ρ of −0.31 to 0.35. None of the measured biomarkers were significantly correlated to PTSD symptom severity scores (ρ of −0.34 to 0.05). Although based on limited sample size, our results call into question the specificity of blood-based biomarkers of IP when: (1) studying persons with and without PTSD symptoms in whom clinical GI disorders are not necessarily the focus of the study; and (2) comparing IP results among individuals with well-defined disease states to those without the disease (e.g., controls). Further studies are needed to explore the role of external factors (e.g., nutrition, obesity, alcohol use) on IP and to determine if the biomarkers studied are appropriate for measuring IP in people with a range of symptoms related to PTSD.

IntroductionStudies showing associations between inflammation in suicide are typically cross-sectional. Present study investigated how cytokine levels track with suicidal ideation and severity longitudinally.MethodsVeterans with a diagnosis of major depressive disorder (MDD) with or without suicide attempt history (MDD/SA n = 38, MDD/NS n = 41) and non-psychiatric non-attempter controls (HC n = 33) were recruited, MDD/SA and HC groups were followed longitudinally at 3 months and 6 months. Blood plasma was collected and processed using Luminex Immunology Multiplex technology.ResultsSignificant differences in depression severity (BDI) and suicidal ideation severity (SSI) were observed across all groups at study entry, wherein MDD/SA group had the highest scores followed by MDD/NS and HC, respectively. Cytokines IL-1β, IL-4, TNF-α, IFN-γ, and IL-6 were examined at study entry and longitudinally, with IL6 levels differing significantly across the groups (p = 0.0123) at study entry. Significant differences in changes in cytokine levels between depressed attempters and the control group were detected for IL-6 (interaction F1,91.77 = 5.58, p = 0.0203) and TNF-α (F1,101.73 = 4.69, p = 0.0327). However, only depressed attempters showed a significant change, in IL-6 and TNF-α levels, decreasing over time [IL-6: b = −0.04, 95% CI = (−0.08, −0.01), p = 0.0245 and TNF-α: b = −0.02, 95% CI = (−0.04, −0.01), p = 0.0196]. Although IL-6 levels were not predictive of suicidal ideation presence [OR = 1.34, 95% CI = (0.77, 2.33), p = 0.3067], IL-6 levels were significantly associated with suicidal ideation severity (b = 0.19, p = 0.0422).DiscussionIL-6 was not associated with presence of suicidal ideation. IL-6 however, was associated with severity of ideation, suggesting that IL-6 may be useful in clinical practice, as an objective marker of heightened suicide risk.

Background: A repeat dose of Gonadotropin-releasing Hormone (GnRH) agonist could provide long duration of luteinizing hormone (LH) surge and amplitude appropriately. Objective: Improvement in oocyte maturity could be obtained by a repeat dose of GnRH agonist. Materials and Methods: In this randomized double-blinded study, 120 women with polycystic ovarian syndrome and serum estradiol level (E2) > 3000 who were candidate for in vitro fertilization with Antagonist protocol were enrolled between July 2018 and July 2019. Participants were randomized in two groups - and final oocyte maturation was triggered with two doses: In group A, a repeat dose of 0.1 mg, 12 hr. after the first dose and in group B, 0.2 mg SC triptorelin (decapeptyl) 35 hr. prior to oocyte retrieval. Serum Estradiol, LH, and progesterone concentration were measured on the trigger day. Serum LH measurement was done three times in both groups. The outcomes were oocyte yield, meiosis (M) I, MII, Maturity rate, germinal vesicle (GV) rate, 2 pronuclear, embryo yield, ovarian hyper stimulation syndrome rates. Results: Maturity rate (p = 0.89), MI (p = 0.38), MII (p = 0.89), and GV oocytes (p = 0.38) were not statistically different between the two study groups. LH levels measured at 12 hr post-trigger did not relate statistically significant with maturity rate in our participants (p = 0.96). No empty follicular syndrome was reported. Conclusion: Although, the second dose of GnRH agonist after 12 hr since the first dose could provide duration of LH surge and amplitude and as a result no empty follicular syndrome was seen, the maturity rate, MI, MII, and GV oocytes were not different between the two study groups.

Traumatic brain injury (TBI) affects millions of Americans each year, with extremely high prevalence in the Veteran community, and sleep disturbance is one of the most commonly reported symptoms. Reduction in the quality and amount of sleep can negatively impact recovery and result in a wide range of behavioral and physiological symptoms, such as impaired cognition, mood and anxiety disorders, and cardiovascular effects. Thus, to improve long-term patient outcomes and develop novel treatments, it is essential to understand the molecular mechanisms involved in sleep disturbance following TBI. In this effort, we performed transcriptional profiling in an established rodent model of penetrating ballistic brain injury (PBBI) in conjunction with continuous sleep/wake EEG/EMG recording of the first 24 h after injury. Rats subjected to PBBI showed profound differences in sleep architecture. Injured animals spent significantly more time in slow wave sleep and less time in REM sleep compared to sham control animals. To identify PBBI-related transcriptional differences, we then performed transcriptome-wide gene expression profiling at 24 h post-injury, which identified a vast array of immune- related genes differentially expressed in the injured cortex as well as sleep-related genes. Further, transcriptional changes associated with total time spent in various sleep stages were identified. Such molecular changes may underlie the pathology and symptoms that emerge following TBI, including neurodegeneration, sleep disturbance, and mood disorders.

Sampling the live brain is difficult and dangerous, and withdrawing cerebrospinal fluid is uncomfortable and frightening to the subject, so new sources of real-time analysis are constantly sought. Cell-free DNA (cfDNA) derived from glia and neurons offers the potential for wide-ranging neurological disease diagnosis and monitoring. However, new laboratory and bioinformatic strategies are needed. DNA methylation patterns on individual cfDNA fragments can be used to ascribe their cell-of-origin. Here we describe bisulfite sequencing assays and bioinformatic processing methods to identify cfDNA derived from glia and neurons. In proof-of-concept experiments, we describe the presence of both glia- and neuron-cfDNA in the blood plasma of human subjects following mild trauma. This detection of glia- and neuron-cfDNA represents a significant step forward in the translation of liquid biopsies for neurological diseases.

Objectives: Novel approaches to mental health and suicide prevention are lacking. Converging evidence has shown the effectiveness of horticultural therapy (HT) in improving mental health symptoms, but whether it would reduce suicide risk and contributing risk factors is unknown. Design: Using a cohort model, HT was delivered 3.5 h over four weekly, sessions administered by a registered horticultural therapist to veterans with history of suicide ideation or attempt who felt isolated and experienced ongoing environmental stressors with interest in learning new coping strategies. Setting: HT delivery occurred in an urban garden, through a community partnership between the VA (Veterans Administration) and the New York Botanical Garden. Guided by principles of biophilia, participating veterans took part in nature walks, self-reflection and journaling, and planting activities. Outcome measures: Stress, mood, pain, and social isolation levels were measured weekly pre-post HT sessions using thermometer scales, with concordant validity to validated clinical instruments. Results: Of the 20 men and women with a history of suicide attempts/ideation, HT demonstrated immediate improvements after each session across all symptom domains in magnitude of reduction in stress, pain, mood, and loneliness. The effect sizes were in medium to large range (Cohen’s d>.5). Additionally, a single HT session showed a sustained effect over subsequent 2-to-4 weeks as observed by the significantly decreased pre-session thermometer scores in subsequent weeks. Reductions in mood symptoms correlated with decline in suicidal ideation (rs = 0.63). Conclusion: HT intervention maybe a promising therapeutic modality for improving overall wellness in suicide prevention in at-risk veteran populations.

Objective: To examine sociodemographic characteristics and chronic health conditions in veterans across health coverage types including those without coverage. Design: The sample included cross-sectional data from veterans aged 18 years and over, collected in the 2016 National Health Interview Survey (n = 3487). Chronic health conditions and sociodemographic variables were examined across eleven health coverage types and combinations of health coverage types, as follows: No coverage, Medicare, Medicaid, Private, TRICARE (formerly known as the Civilian Health and Medical Program of the Uniformed Services (CHAMPUS)), TRICARE and Medicare, Veteran's Administration, Veteran's Administration and Medicare, Veteran's Administration and Private, Veteran's Administration and Private and Medicare. Results: Approximately 3.9% of veterans did not have coverage. The greatest proportion had private coverage (28.2%), then private coverage plus Medicare (19.6%). Only 5.9% had Veterans Administration coverage solely. Among the veterans not covered, the majority were young, lived alone, had less than a high school education and resided in the South. The most common chronic health conditions among non-covered veterans were obesity and migraine. Regional differences were observed in the types of chronic health conditions. Veterans in the Northeast were less likely to report serious psychological distress. In a logistic regression, younger age (18–44 years), living alone and having less than a high school education were predictive of no coverage, but number of chronic health conditions was not. Conclusion: A population of veterans without health coverage may be undeserved and at risk for poor mental and physical health due to non-health related factors. Keywords: Veterans, Health coverage, Mental health, Suicide, VA

Background: Injuries from exposure to explosions rose dramatically during the Iraq and Afghanistan wars, which motivated investigation of blast-related neurotrauma. We have undertaken human studies involving military “breachers” —exposed to controlled, low-level blast during a 3-days explosive breaching course.Methods: We screened epigenetic profiles in peripheral blood samples from 59 subjects (in two separate U.S. Military training sessions) using Infinium MethylationEPIC BeadChips. Participants had varying numbers of exposures to blast over their military careers (empirically defined as high ≥ 40, and conversely, low < 39 breaching exposures). Daily self-reported physiological symptoms were recorded. Tinnitus, memory problems, headaches, and sleep disturbances are most frequently reported.Results: We identified 14 significantly differentially methylated regions (DMRs) within genes associated with cumulative blast exposure in participants with high relative to low cumulative blast exposure. Notably, NTSR1 and SPON1 were significantly differentially methylated in high relative to low blast exposed groups, suggesting that sleep dysregulation may be altered in response to chronic cumulative blast exposure. In comparing lifetime blast exposure at baseline (prior to exposure in current training), and top associated symptoms, we identified significant DMRs associated with tinnitus, sleep difficulties, and headache. Notably, we identified KCNN3, SOD3, MUC4, GALR1, and WDR45B, which are implicated in auditory function, as differentially methylated associated with self-reported tinnitus. These findings suggest neurobiological mechanisms behind auditory injuries in our military warfighters and are particularly relevant given tinnitus is not only a primary disability among veterans, but has also been demonstrated in active duty medical records for populations exposed to blast in training. Additionally, we found that differentially methylated regions associated with the genes CCDC68 and COMT track with sleep difficulties, and those within FMOD and TNXB track with pain and headache.Conclusion: Sleep disturbances, as well as tinnitus and chronic pain, are widely reported in U.S. military service members and veterans. As we have previously demonstrated, DNA methylation encapsulates lifetime exposure to blast. The current data support previous findings and recapitulate transcriptional regulatory alterations in genes involved in sleep, auditory function, and pain. These data uncovered novel epigenetic and transcriptional regulatory mechanism underlying the etiological basis of these symptoms.

The short and long-term neurological and psychological consequences of traumatic brain injury (TBI), and especially mild TBI (mTBI) are of immense interest to the Veteran community. mTBI is a common and detrimental result of combat exposure and results in various deleterious outcomes, including mood and anxiety disorders, cognitive deficits, and post-traumatic stress disorder (PTSD). In the current study, we aimed to further define the behavioral and molecular effects of blast-related mTBI using a well-established (3 × 75 kPa, one per day on three consecutive days) repeated blast overpressure (rBOP) model in rats. We exposed adult male rats to the rBOP procedure and conducted behavioral tests for anxiety and fear conditioning at 1–1.5 months (sub-acute) or 12–13 months (chronic) following blast exposure. We also used next-generation sequencing to measure transcriptome-wide gene expression in the amygdala of sham and blast-exposed animals at the sub-acute and chronic time points. Results showed that blast-exposed animals exhibited an anxiety-like phenotype at the sub-acute timepoint but this phenotype was diminished by the chronic time point. Conversely, gene expression analysis at both sub-acute and chronic timepoints demonstrated a large treatment by timepoint interaction such that the most differentially expressed genes were present in the blast-exposed animals at the chronic time point, which also corresponded to a Bdnf-centric gene network. Overall, the current study identified changes in the amygdalar transcriptome and anxiety-related phenotypic outcomes dependent on both blast exposure and aging, which may play a role in the long-term pathological consequences of mTBI.

Background: Early diagnosis of breast cancer, the incidence of which among Iranian women is about a decade earlier than in developed countries, is important. Objective: To compare mammography and ultrasonography findings with those of pathology in patients with breast cancer. Methods: This descriptive cross-sectional study was performed using medical records of 79 patients with breast malignancies, who were referred to Imam Reza Hospital and private laboratories of Birjand, Iran, from December 2012 to December 2014. The patients’ information was recorded using a checklist, which included name, code, age, ultrasonography, and mammography results and pathology reports. The results of ultrasonography and mammography were compared with pathology findings as the gold standard. SPSS Version 21 was used for data analysis. Results: The mean age of the patients was 46.94 ± 11.76 years. The results showed that 74.7%, 16.5%, and 7.6% of the patients had ductal carcinoma, lobular carcinoma, and mixed carcinoma, respectively. About 72.5%, 24.6%, and 2.9% of the patients had stage 2, 3, and 1 breast cancer, respectively. In addition, both breasts were involved in 1.3% of the patients. The ultrasound findings were positive and false negative in 97.5% and 2.5% of the cases. Moreover, the mammography results were positive and false negative in 98.7% and 1.3% of the patients. Conclusion: This study showed that mammography is the preferred modality in screening breast cancer patients; the use of complementary tests such as ultrasonography is recommended, especially in high-risk women.

The binding of natural ligands and synthetic drugs to the P2Y12 receptor is of great interest because of its crucial role in platelets activation and the therapy of arterial thrombosis. Up to now, all computational studies of P2Y12 concentrated on the available crystal structures, while the role of intrinsic protein dynamics and the membrane environment in the functioning of P2Y12 was not clear. In this work, we performed all-atom molecular dynamics simulations of the full-length P2Y12 receptor in three different membrane environments and in two possible conformations derived from available crystal structures. The binding of ticagrelor, its two major metabolites, adenosine diphosphate (ADP) and 2-Methylthioadenosine diphosphate (2MeS-ADP) as agonist, and ethyl 6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate (AZD1283)as antagonist were assessed systematically by means of ensemble docking. It is shown that the binding of all ligands becomes systematically stronger with the increase of the membrane rigidity. Binding of all ligands to the agonist-bound-like conformations is systematically stronger in comparison to antagonist-bound-likes ones. This is dramatically opposite to the results obtained for static crystal structures. Our results show that accounting for internal protein dynamics, strongly modulated by its lipid environment, is crucial for correct assessment of the ligand binding to P2Y12.

Background and Aim: Cancer is the second leading cause of death in industrialized countries and the third in developing ones. The present study aimed at assessing prevalence of breast cancer among women over 30 in Birjand between 2009 and 2010. Materials and Methods: In this descriptive-analytical study, 2000 over 30 years women from Birjand city were selected through multiple-stage sampling. A demographic questionnaire was completed by each subject after being justified about the importance of screening and method of examination. Clinical breast examination was performed by a female GP under standard conditions, one week after menstrual ceasing. When there was a palpable mass in the breast, the participant underwent a mammography test for an accurate diagnosis of the type and size of the lesion. Positive cases were referred to a surgeon for open biopsy. The obtained data was analyzed by means of SPSS software (V: 15) using ANOVA test at α = 0.05 as the significance level. Results: Out of 2000 surveyed women, 80 were excluded because of the inappropriateness of their completed questionnaires. Totally, 1920 women were included with the mean age of 44.48±8.56 (range: 30-88) years. Out of 267 women (13.9%) referred for mammography due to positive clinical findings, only 134 (50.2%) cases underwent mammography test and 17 of them (12.7%) had a lesion as observed in their mammography images and, as a result, fibrocystic lesion was the most common diagnosis. Biopsy was performed for 32 patients (1.6% of the total participants) and malignancy was reported in 11 patients (0.5%). Mean age of the cancer patients was 41.18±12.65 years which was similar to other women's situation without malignancy (P=0.11). Conclusion: According to our results and based on the low mean age of patients with breast cancer, it is required to study the causes leading to the early occurrence of breast cancer at young ages in this area.

Blast-related mild traumatic brain injury (mTBI) has been unfortunately common in veterans who served in the recent conflicts in Iraq and Afghanistan. The postconcussion syndrome associated with these mTBIs has frequently appeared in combination with post-traumatic stress disorder (PTSD). The presence of PTSD has complicated diagnosis since clinically PTSD and the postconcussion syndrome of mTBI have many overlapping symptoms. In particular establishing how much of the symptom complex can be attributed to the psychological trauma associated with PTSD in contrast to the physical injury of TBI has proven difficult. Indeed some have suggested that much of what is now being called blast-related postconcussion syndrome is better explained by PTSD. The relationship between the postconcussion syndrome of mTBI and PTSD is complex. Association of the two disorders might be viewed as additive effects of independent psychological and physical traumas suffered in a war zone. However we previously found that rats exposed to repetitive low-level blast exposure in the absence of a psychological stressor developed a variety of anxiety and PTSD-related behavioral traits that were present months following the last blast exposure. Here we show that a single predator scent challenge delivered 8 months after the last blast exposure induces chronic anxiety related changes in blast-exposed rats that are still present 45 days later. These observations suggest that in addition to independently inducing PTSD-related traits, blast exposure sensitizes the brain to react abnormally to a subsequent psychological stressor. These studies have implications for conceptualizing the relationship between blast-related mTBI and PTSD and suggest that blast-related mTBI in humans may predispose to the later development of PTSD in reaction to subsequent psychological stressors.

Background: This study aims to demonstrate the frequency of malignant breast cancer (BC) according to pathologic findings in Birjand during 2011-2013 years. Methods: For this cross-sectional study, the sample consisted of pathologic records from 229 breast biopsies of two hospitals in Birjand. Results: Most of the biopsies in women were malignant cases which nearly 90% of them were detected after lymph node involvement. The mean age of women with malignant BC was 48.8 years. Conclusions: A notable proportion of our cases were diagnosed in metastatic stages as advanced BC. It further highlights the importance of screening and diagnosis at earlier stages.

Suicide and suicide attempts are complex behaviors that result from the interaction of different factors, including genetic variants that increase the predisposition to suicidal behaviors. Copy number variations (CNVs) are deletions or duplications of a segment of DNA usually larger than one kilobase. These structural genetic changes, although quite rare, have been associated with genetic liability to mental disorders, such as autism, schizophrenia, and bipolar disorder. No genome-wide level studies have been published investigating the potential role of CNVs in suicidal behaviors. Based on single-nucleotide polymorphism array data, we followed the Penn-CNV standards to detect CNVs in 1,608 subjects, comprising 475 suicide and suicide attempt cases and 1,133 controls. Although the initial algorithms determined the presence of CNVs on chromosomes 6 and 12 in seven and eight cases, respectively, compared with none of the controls, visual inspection of the raw data did not support this finding. Furthermore we were unable to validate these findings by CNV-specific real-time polymerase chain reaction. Additionally, rare CNV burden analysis did not find an association between the frequency or length of rare CNVs and suicidal behavior in our sample population. Although our findings suggest CNVs do not play an important role in the etiology of suicidal behaviors, they are not inconsistent with the strong evidence from the literature suggesting that other genetic variants account for a portion of the total phenotypic variability in suicidal behavior.

Objective: Some studies have recently focused on the association between TNF-α polymorphisms and cervical cancer; however, results have been inconsistent. In order to drive a more precise estimation, the present systematic review and meta-analysis is performed to investigate the relationship of the TNF-α rs1800629 and s1799724 polymorphisms with cervical cancer risk. Methods: An electronic search was conducted on PubMed, Web of Science, and Google scholar databases, for papers that describe the association between TNF-α polymorphisms and cervical cancer risk. Results: A number of 24 case-control studies in 22 publications were identified according to the inclusion criteria. The results showed that rs1800629 polymorphism was significantly associated with the increased cervical cancer risk under four genetic models (A vs. G: OR = 1.277, 95% CI: 1.104-1.477, p = 0.001; AA vs. GG: OR = 1.333, 95% CI: 1.062-1.674, p = 0.013; AG vs. GG: OR = 1.307, 95% CI: 1.064-1.605, p = 0.011; and AA+AG vs. GG: OR = 1.324, 95% CI: 1.104-1.587, p = 0.002). In stratified analysis, there was a significant association between rs1800629 polymorphism and cervical cancer risk in the subgroup of Caucasians and African, but not in Asians. However, no statistically significant association was observed between the s1799724 and cervical cancer risk under all genetic models. Furthermore, stratification by ethnicity indicated no association between the s1799724 and cervical cancer risk. Conclusion: the present meta-analysis suggests that the rs1800629 polymorphism of the TNF-α gene was significantly associated with cervical cancer risk, but not s1799724.

Background: Due to the high number of women affected by cervical cancer and the importance of an early diagnosis, combined with the frequent incidence of false-negative Papanicolaou (Pap) smear screening results for this disease, several studies have been conducted in recent years in order to find better tests. Liquid-based cytology (LBC) tests, including the liquid-based thin layer method, have demonstrated the highest potential for reducing false-negative cases and improved sample quality. This study aimed to compare the strength of the Pap smear test with fluid cytology and conventional tests in detecting cervical dysplasia. Materials and Methods: This descriptive-analytic study was conducted on 366 women who attended private laboratories for a Pap smear. The Pap smear sampling was conducted simultaneously using two methods: conventional Pap (CP) smear and LBC), from the cervix. Results: The mean age of the participants was 32 ± 8.8 years. Diagnostic results of endocervical cells, epithelial cells, vaginitis cells, and metaplastia were consistent with both conventional and liquid cytology smears, and the kappa coefficient was determined to be significant (P < 0.001). In total, 40.5% of diagnostic cases indicated bacterial inflammation 80.3% of the diagnoses in both methods were P1 and 3.9% of cases diagnosed were P2, the overall diagnostic consistency was 83.9% between the two sampling methods. The inflammation diagnosis was 40.5% and this was consistent in both methods of LBC and CP. There was one case of a false-negative diagnosis in the LBC method and 14 cases in the CP method. Conclusion: Results showed that the LBC may improve the sample's quality and reduce the number of unsatisfactory cases more than with the CP method.

Emerging evidence suggests that DNA methylation plays an expansive role in the central nervous system (CNS). Large-scale whole genome DNA methylation profiling of the normal human brain offers tremendous potential in understanding the role of DNA methylation in brain development and function.Using methylation-sensitive SNP chip analysis (MSNP), we performed whole genome DNA methylation profiling of the prefrontal, occipital, and temporal regions of cerebral cortex, as well as cerebellum. These data provide an unbiased representation of CpG sites comprising 377,509 CpG dinucleotides within both the genic and intergenic euchromatic region of the genome. Our large-scale genome DNA methylation profiling reveals that the prefrontal, occipital, and temporal regions of the cerebral cortex compared to cerebellum have markedly different DNA methylation signatures, with the cerebral cortex being hypermethylated and cerebellum being hypomethylated. Such differences were observed in distinct genomic regions, including genes involved in CNS function. The MSNP data were validated for a subset of these genes, by performing bisulfite cloning and sequencing and confirming that prefrontal, occipital, and temporal cortices are significantly more methylated as compared to the cerebellum.These findings are consistent with known developmental differences in nucleosome repeat lengths in cerebral and cerebellar cortices, with cerebrum exhibiting shorter repeat lengths than cerebellum. Our observed differences in DNA methylation profiles in these regions underscores the potential role of DNA methylation in chromatin structure and organization in CNS, reflecting functional specialization within cortical regions.

For diagnosis of neuropsychiatric disorders, a categorical classification system is often utilized as a simple way for conceptualizing an often complex clinical picture. This approach provides an unsatisfactory model of mental illness, since in practice patients do not conform to these prototypical diagnostic categories. Family studies show notable familial co-aggregation between schizophrenia and bipolar illness and between schizoaffective disorders and both bipolar disorder and schizophrenia, revealing that mental illness does not conform to such categorical models and is likely to follow a continuum encompassing a spectrum of behavioral symptoms.We introduce an analytic framework to dissect the phenotypic heterogeneity present in complex psychiatric disorders based on the conceptual paradigm of a continuum of psychosis. The approach identifies subgroups of behavioral symptoms that are likely to be phenotypically and genetically homogenous. We have evaluated this approach through analysis of simulated data with simulated behavioral traits and predisposing genetic factors. We also apply this approach to a psychiatric dataset of a genome scan for schizophrenia for which extensive behavioral information was collected for each individual patient and their families. With this approach, we identified significant evidence for linkage among depressed individuals with two distinct symptom profiles, that is individuals with sleep disturbance symptoms with linkage on chromosome 2q13 and also a mutually exclusive group of individuals with symptoms of concentration problems with linkage on chromosome 2q35. In addition we identified a subset of individuals with schizophrenia defined by language disturbances with linkage to chromosome 2p25.1 and a group of patients with a phenotype intermediate between those of schizophrenia and schizoaffective disorder with linkage to chromosome 2p21.The findings presented are novel and demonstrate the efficacy of this approach in detection of genes underlying such complex human disorders as schizophrenia and depression.

Background: Many aspects of epidemiological and clinicopathological features of gestational trophoblastic disease (GTD), one of the important subject in gynecology oncology, needs to be defined so as to recommend the best approach and management toward it. In the present study, we evaluated 10-years incidence of throphoblastic diseases in north east of Iran in prospective epidemiological and clinicopathological study. Materials and Methods:We reviewed the registered histopathology database archive (120 records) related to throphoblastic diseases of the Ghaem Hospital, Mashhad University of Medical Sciences from 2001 to 2010. Results:Evaluation of the pathological reports revealed 5 (4.2%) choriocarcinom and 115 (95.8%) of hydatidiform mole (HM), with complete and partial HM diagnosis in 29 (25.2%) and 86 (74.8%) patients, respectively. The pregnancy rate of HM patients (2.72 ± 1.86) and choriocarcinoma patients (3.56 ± 2.8) was not significantly different ( P = 0.61). There was no statistical significant difference between the number of pregnancies in HM (2.90 ± 3.13) and choriocarcinoma (3.84 ± 3.80) patients ( P = 0.46). The ratio of complete to partial mole increased with age, although this correlation was not significant. Most patients in both the groups had no history of abortion. O positive was the predominant blood group among the studied patients. Conclusion:Throphoblastic diseases occur during the fertility age mostly, and there is an increased risk with more previous pregnancies; ultrasound sonography is a useful method for primary diagnosis of this disease. Further pathological studies are needed to define the mole type.