Transcriptional Profiling of PRKG2-Null Growth Plate Identifies Putative Down-Stream Targets of PRKG2

Kinase activity of cGMP-dependent, type II, protein kinase (PRKG2) is required for the proliferative to hypertrophic transition of growth plate chondrocytes during endochondral ossification. Loss of PRKG2 function in rodent and bovine models results in dwarfism. The objective of this study was to identify pathways regulated or impacted by PRKG2 loss of function that may be responsible for disproportionate dwarfism at the molecular level. Microarray technology was used to compare growth plate cartilage gene expression in dwarf versus unaffected Angus cattle to identify putative downstream targets of PRGK2. Pathway enrichment of 1284 transcripts (nominal p \u3c 0.05) was used to identify candidate pathways consistent with the molecular phenotype of disproportionate dwarfism. Analysis with the DAVID pathway suite identified differentially expressed genes that clustered in the MHC, cytochrome B, WNT, and Muc1 pathways. A second analysis with pathway studio software identified differentially expressed genes in a host of pathways (e.g. CREB1, P21, CTNNB1, EGFR, EP300, JUN, P53, RHOA, and SRC). As a proof of concept, we validated the differential expression of five genes regulated by P53, including CEBPA, BRCA1, BUB1, CD58, and VDR by real-time PCR (p \u3c 0.05). Known and novel targets of PRKG2 were identified as enriched pathways in this study. This study indicates that loss of PRKG2 function results in differential expression of P53 regulated genes as well as additional pathways consistent with increased proliferation and apoptosis in the growth plate due to achondroplastic dwarfism

Metabolic Syndrome, Sleep Quality and Lung Function in Persons With Schizophrenia: A Cross-Sectional Study

Aims Persons with schizophrenia typically have a 20% shorter lifespan and mortality rates two times higher than the general population. More than 2/3 of this is due to different forms of physical diseases, like cardiovascular and metabolic syndrome. Systematic meta-analyses and various studies in schizophrenic patients revealed the prevalence of metabolic syndrome to range from 11 to 69%, poor sleep quality 30% to 80%, and impaired lung function ~30%. Both in the general population and in persons with schizophrenia, poor sleep quality and impaired lung function are associated with a heightened risk of metabolic and cardiovascular diseases. Hence, this study aimed to look for the magnitude of metabolic syndrome, poor sleep quality, and impaired lung function, and any association among them, if proven, may be helpful in better management. Methods We included sixty cooperative patients through purposive sampling with an age range of 18 to 65 years, meeting the DSM–5 criteria for schizophrenia, and excluded patients with co-morbid substance use disorder except for smokeless tobacco and caffeine. Harmonized criteria were used to diagnose metabolic syndrome; the Pittsburgh Sleep Quality Index (PSQI) for sleep quality and lung function was interpreted as per the Spirometry for Health Care Providers, Global Initiative for Chronic Obstructive Lung Disease. Results 55% were found to have metabolic syndrome. Poor sleep quality (PSQI > 5) was found in 60% of cases, with the most common sleep abnormality being increased sleep latency (95%). Restrictive Lung Dysfunction (RLD) was found in 46.7% of cases. 66.7% of the participants with metabolic syndrome had RLD, whereas only 22.2% without metabolic syndrome had RLD. The difference was statistically significant. No statistically significant difference was found between metabolic syndrome and sleep quality or sleep quality and RLD. Conclusion From the results obtained, it is clear that the prevalence of metabolic syndrome in people with schizophrenia is twice that of the general population, which also contributes to their increased mortality. Thereby, early identification of metabolic disturbances and correcting poor sleep quality and impaired lung function that are associated with an increased risk of metabolic syndrome will lead to increased life expectancy and a decrease in the mortality rate. Since lung function is studied in only a very few studies all over the world and ours being a novel approach in India showing significant association, it needs to be replicated in a larger sample size

Alexithymia governing neurosis: A comparative study between patients and caregivers

Context: Individuals with neurotic disorders are believed to have alexithymia, which not only acts as a substrate for neurosis but also poses difficulties in delivering psychotherapeutic intervention to these patients. Aims: This study aims to study and compare alexithymia among patients of neurosis and their caregivers. Settings and Design: This descriptive cross-sectional study was carried out at the Department of Psychiatry of a Tertiary Government Hospital in Delhi. Materials and Methods: Fifty consecutive patients of neurosis (as per ICD-10) and their caregivers were assessed using Hindi versions of Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7) and Toronto alexithymia scale (TAS-20) after taking written informed consent. Statistical Analysis: Data were analyzed using descriptive statistics, independent t-test, ANOVA, and multiple linear correlation. Results: The mean age of patient and caregiver groups was comparable (35.86 ± 10.6 and 36.04 ± 10.6 years) with no significant difference on socio-demographic parameters. The patient group had significantly higher scores of total TAS and also on parameters of difficulty identifying feelings, difficulty describing feelings and externally oriented thinking (P < 0.000). Total PHQ-9 and GAD-7 scores were significantly correlated to TAS scores (total and 3 domains) in both groups. Females scored higher than males (P = 0.022, PC = 0.324) and age showed negative correlation (P = 0.036, PC = −0.297) with total TAS scores in the patient group. Conclusion: The study shows that alexithymia is more common in patients with neurosis as compared to their caregivers. Besides, it is closely related to neurotic traits in the caregivers who scored high on PHQ-9 and GAD-7 despite being free of a diagnosable illness

Clinicosocial profile of people who inject drugs receiving opioid substitution therapy at New Delhi

Introduction: Injecting drug use is a public health concern due to its clinical, social, economic, and legal consequences. Objective: (1) To evaluate the prevalence of infections associated with injecting drug use; and (2) To assess the social profile of substance users and high-risk behaviors among people who inject drugs (PWID) receiving opioid substitution therapy (OST). Materials and Methods: A cross-sectional study was conducted among 100 PWID who were deemed eligible using inclusion and exclusion criteria. Data were collected through an interviewer-administered structured questionnaire after obtaining informed written consent. Results: The results revealed that 14% of PWID had human immunodeficiency virus (HIV), 7% had tuberculosis, and 2% had hepatitis B virus (HBV). None of the PWID self-reported hepatitis C virus (HCV) infection. Importantly, 71% of PWID were living on the streets (i.e. homeless), and 41% of PWID had a history of sharing needles with other users in the preceding 3 months. Unmarried or single PWID had significantly increased risk of homelessness (χ2 = 4.570; P = 0.032) and reported high-risk sexual practices with commercial sexual partners in the preceding 3 months (χ2 = 4.163; P = 0.041). Homeless PWID had significantly increased frequency of injecting practices (P = 0.020). Conclusion: Despite the higher global prevalence of HCV compared with HBV and HIV among PWID, HCV testing is not currently conducted at most OST centers in India. Access to free needles and syringes should be enhanced to reduce the morbidity associated with injecting drug use

Pseudocyesis Versus Delusion of Pregnancy: Differential Diagnoses to be Kept in Mind

Pseudocyesis is a condition in which the patient has all signs and symptoms of pregnancy except for the confirmation of the presence of a fetus. The literature on delusions of pregnancy in schizophrenia is however scanty. We hereby present a case of delusion of pregnancy. The case highlights the possibility of delusion of pregnancy if a patient presents with features suggestive of pseudocyesis. The obstetricians being more familiar with pseudocyesis might tend to overlook the other possibility in such cases. This would be especially true if there are no associated clearcut psychotic features

A study of treatment-seeking behavior in psychiatric patients at a tertiary care hospital in Delhi

Background and Aims: Patients with mental disorders often do not seek professional help for a multitude of reasons. These issues need to be highlighted and addressed. This cross-sectional study aims to collect and to analyze treatment-seeking behavior in psychiatric patients. Subjects and Methods: Five hundred patients presenting to psychiatry Outpatient Department of a tertiary hospital in Delhi, were recruited after obtaining written informed consent. Patients were diagnosed based on the International Classification of Disease-10 criteria, and sociodemographic details were collected. Treatment-seeking behavior schedule was applied. Results: Patients between 18 and 35 years of age constituted around 60% of the total treatment-seeking patients and only 2% were above the age of 65 years. More than 60% of the sample belonged to an urban, middle socioeconomic background from nuclear families. Depression and anxiety disorders were the most common psychiatric morbidities followed by psychotic disorders and substance use disorders. Up to half of the sample had sought treatment before coming for consultation. Of these 55% visited nonpsychiatric doctors, 30% of psychiatrists and others consulted faith healers, alternate medicine, and psychologists before visiting our facility. Easy accessibility, faith, and good reputation were the reasons for going to a doctor while belief in the supernatural causation of mental illness was the major reason for seeing a faith healer. Mostly, a family member had given information about our facility. Previous ineffective treatment and cost concerns regarding medications were the predominant reasons to visit after prior visits elsewhere. Conclusion: Factors determining treatment-seeking behavior can help address problems and delay in early identification and optimal management of mental disorders

Significance of vascular endothelial growth factor and CD31 and morphometric analysis of microvessel density by CD31 receptor expression as an adjuvant tool in diagnosis of psoriatic lesions of skin

Background: Pathogenesis of psoriasis is a debated issue. Several mechanisms have been proposed to identify the etiology and pathogenesis so that specific treatments can be given to patients with psoriasis. Aims: (1) To compare pattern and distribution of vascular endothelial growth factor (VEGF) and CD31 in patients with psoriasis and other psoriasiform lesions of skin. (2) To study the correlation between VEGF and CD31 expression, clinical severity, and histopathology of psoriasiform lesions of skin. (3) Evaluation of microvessel density (MVD) by using computer-assisted quantitative image analysis in psoriatic skin lesions. Materials and Methods: This study was conducted on eighty cases, out of which forty were diagnosed cases of psoriasis and forty cases of clinically suspected psoriasiform lesions, submitted in the Department of Pathology, Pt. B.D. Sharma, University of Health Sciences, Rohtak, for histopathological examination. Histopathological sections were stained by routine hematoxylin and eosin staining, and these biopsies were further subjected to immunohistochemical staining with VEGF and CD31 as per standard technique. Results: Assessment of various histopathological features revealed strong correlation between epidermal hyperplasia, suprapapillary thinning, and elongation of rete ridges. Suprabasilar keratinocytes in psoriatic lesions stained intensely for VEGF. The difference for number of microvessels and MVD in psoriasis and psoriasiform lesions was statistically significant. Correlation between intensity of VEGF staining by suprabasilar keratinocytes and MVD was found to be highly significant in psoriatic lesions. Conclusion: The present study concluded that psoriatic lesions exhibit potent angiogenic activity. Early lesions show increased MVD along with other histomorphological parameters such as hypogranulosis, parakeratosis and Munro's microabscesses. Overexpression of VEGF by suprabasilar keratinocytes correlated with increased MVD in papillary dermis

Glioprotective Effects of Ashwagandha Leaf Extract against Lead Induced Toxicity

Withania somnifera (Ashwagandha), also known as Indian Ginseng, is a well-known Indian medicinal plant due to its antioxidative, antistress, antigenotoxic, and immunomodulatory properties. The present study was designed to assess and establish the cytoprotective potential of Ashwagandha leaf aqueous extract against lead induced toxicity. Pretreatment of C6 cells with 0.1% Ashwagandha extract showed cytoprotection against 25 μM to 400 μM concentration of lead nitrate. Further pretreatment with Ashwagandha extract to lead nitrate exposed cells (200 μM) resulted in normalization of glial fibrillary acidic protein (GFAP) expression as well as heat shock protein (HSP70), mortalin, and neural cell adhesion molecule (NCAM) expression. Further, the cytoprotective efficacy of Ashwagandha extract was studied in vivo. Administration of Ashwagandha extract provided significant protection to lead induced altered antioxidant defense that may significantly compromise normal cellular function. Ashwagandha also provided a significant protection to lipid peroxidation (LPx) levels, catalase, and superoxide dismutase (SOD) but not reduced glutathione (GSH) contents in brain tissue as well as peripheral organs, liver and kidney, suggesting its ability to act as a free radical scavenger protecting cells against toxic insult. These results, thus, suggest that Ashwagandha water extract may have the potential therapeutic implication against lead poisoning

Transcriptional Profiling of PRKG2-Null Growth Plate Identifies Putative Down-Stream Targets of PRKG2

Kinase activity of cGMP-dependent, type II, protein kinase (PRKG2) is required for the proliferative to hypertrophic transition of growth plate chondrocytes during endochondral ossification. Loss of PRKG2 function in rodent and bovine models results in dwarfism. The objective of this study was to identify pathways regulated or impacted by PRKG2 loss of function that may be responsible for disproportionate dwarfism at the molecular level. Microarray technology was used to compare growth plate cartilage gene expression in dwarf versus unaffected Angus cattle to identify putative downstream targets of PRGK2. Pathway enrichment of 1284 transcripts (nominal p CEBPA, BRCA1, BUB1, CD58, and VDR by real-time PCR (p This article is from BMC Research Notes 8 (2015): 177, doi:10.1186/s13104-015-1136-6. Posted with permission.</p