Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features.

Mutations that cause neurological phenotypes are highly informative with regard to mechanisms governing human brain function and disease. We report autosomal recessive mutations in the enzyme glutamate pyruvate transaminase 2 (GPT2) in large kindreds initially ascertained for intellectual and developmental disability (IDD). GPT2 [also known as alanine transaminase 2 (ALT2)] is one of two related transaminases that catalyze the reversible addition of an amino group from glutamate to pyruvate, yielding alanine and α-ketoglutarate. In addition to IDD, all affected individuals show postnatal microcephaly and ∼80% of those followed over time show progressive motor symptoms, a spastic paraplegia. Homozygous nonsense p.Arg404* and missense p.Pro272Leu mutations are shown biochemically to be loss of function. The GPT2 gene demonstrates increasing expression in brain in the early postnatal period, and GPT2 protein localizes to mitochondria. Akin to the human phenotype, Gpt2-null mice exhibit reduced brain growth. Through metabolomics and direct isotope tracing experiments, we find a number of metabolic abnormalities associated with loss of Gpt2. These include defects in amino acid metabolism such as low alanine levels and elevated essential amino acids. Also, we find defects in anaplerosis, the metabolic process involved in replenishing TCA cycle intermediates. Finally, mutant brains demonstrate misregulated metabolites in pathways implicated in neuroprotective mechanisms previously associated with neurodegenerative disorders. Overall, our data reveal an important role for the GPT2 enzyme in mitochondrial metabolism with relevance to developmental as well as potentially to neurodegenerative mechanisms.

Prospective study of avian influenza H9 infection in commercial poultry farms of Punjab Province and Islamabad Capital Territory, Pakistan.

A prospective study was conducted from November 2013 to February 2014 to estimate the spatial clustering; cumulative incidence and risk factors associated with avian influenza (AI) subtype H9 infection on commercial poultry farms of Pakistan. A total of 400 farms were enrolled and followed during the study period. Among these, 109 farms submitted samples suspected for AI to the laboratory, and only 47 farms were confirmed positive by hemagglutinin inhibition (HI) test. Data was collected from these 109 farms about their demography, management, and biosecurity practices. The cumulative incidence of H9N2 was 11.75 % (95 % confidence interval (CI) 8.76-15.23). The highest number of cases (40.42 %) was reported in January. One most likely cluster (p = 0.009, radius = 4.61 km) occurred in the Kasur district. Multivariable logistic regression analyses showed that the presence of wild birds on the farms (odds ratio (OR) = 16.18; 95 % CI 3.94-66.45) was independently associated with H9N2 infection. Cleaning of cages before delivery on farm (OR = 0.16; 95 % CI = 0.06-0.47), presence of a footbath at the entrance of farm (OR = 0.24; 95 % CI 0.08-0.79), and changing of gloves (OR = 0.33; 95 % CI 0.11-0.99) were protective factors against H9N2 infection. Reducing the exposure to risk factors and adapting biosecurity measures may reduce the risk of AI H9N2 infection on commercial poultry farms in Pakistan.

Cross Sectional Study and Risk Factors Analysis of Francisella tularensis in Soil Samples in Punjab Province of Pakistan.

Tularemia is an endemic zoonotic disease in many parts of the world including Asia. A cross-sectional study was conducted to determine genome-based prevalence of Francisella tularensis (Ft) in soil, assess an association between its occurrence in soil and likely predictors i.e., macro and micro-nutrients and several categorical variables, and determine seroconversion in small and large ruminants. The study included a total of 2,280 soil samples representing 456 villages in eight districts of the Punjab Province of Pakistan followed by an analysis of serum antibodies in 707 ruminants. The genome of Ft was detected in 3.25% (n = 74, 95% CI: 2.60-4.06) of soil samples. Soluble salts (OR: 1.276, 95% CI: 1.043-1.562, p = 0.015), Ni (OR: 2.910, 95%CI: 0.795-10.644, p = 0.106), Mn (OR:0.733, 95% CI:0.565-0.951, p = 0.019), Zn (OR: 4.922, 95% CI:0.929-26.064, p = 0.061) and nutrients clustered together as PC-1 (OR: 4.76, 95% CI: 2.37-9.54, p = 0.000) and PC-3 (OR: 0.357, 95% CI: 0.640, p = 0.001) were found to have a positive association for the presence of Ft in soil. The odds of occurrence of Ft DNA in soil were higher at locations close to a water source, including canals, streams or drains, [χ2 = 6.7, OR = 1.19, 95% CI:1.05-3.09, p = 0.004] as well as places where animals were present [χ2 = 4.09, OR = 2.06, 95% CI: 1.05-4.05, p = 0.02]. The seroconversion was detected in 6.22% (n = 44, 95% CI: 4.67-8.25) of domestic animals. An occurrence of Ft over a wide geographical region indicates its expansion to enzootic range, and demonstrates the need for further investigation among potential disease reservoirs and at-risk populations, such as farmers and veterinarians.

Psychiatric care in Asia: spirituality and religious connotations.

Throughout the history of humanity it has been said that the individual ego, is a very limited form of identity. Spirituality is shaped by larger social circumstances and by the beliefs and values present in the wider culture. In Asia, as compared to other regions, people fall back on spiritualism. Mental health professionals, laymen and patients have great interest in spirituality and religious activities but still it is one of the most neglected fields of life. Spirituality and religion often are used interchangeably and it has also been described as an individual search for meaning. In psychiatry, religion and spirituality play a vital role in an individual's personal and social life. They are part of a very powerful medium to help in the healing process. Spiritual people know the meaning and goal of their life, have strong belief and firm faith in God or themselves, they can easily cope with stress and have the ability to adjust in every situation. They have satisfaction and contentment. They are less anxious and depressed and if they feel so, they try to overcome it through religious activities or rituals. Patients who depend heavily on their religious faith are significantly less depressed than those who don't. Spiritual practices foster an awareness that serves to identify and promote values such as creativity, patience, perseverance, honesty, kindness, compassion, wisdom, equanimity, hope and joy, all of which support good healthcare practice. Spirituality and religion form a bridge of contact between human, a composite of body and soul, and the Creator. Realizing this need, mental health professionals working in this field need to understand the spiritual values of patients and incorporate them in assessment and treatment.

Seroprevalence and risk factors of glanders in working equines - Findings of a cross-sectional study in Punjab province of Pakistan.

Glanders is an infectious and contagious bacterial disease of equines. A little is known about its seroprevalence and risk factors in working equines in countries where the disease is endemic. Also, there are no reports on prevalence of the disease in areas where there is a prior evidence of Burkholderia (B.) mallei detection in soil. A cross-sectional study was conducted in selected districts (n=09) of Punjab province of Pakistan during 2014-2015. A total of 1008 serum samples were screened for detection of antibodies to B. mallei with complement fixation test followed by western blot. The overall seroprevalence was found to be 3.17% (95% CI: 2.25-4.44). The seropositivity was significantly higher from the sampling sites where B. mallei was detected in soil [OR: 10.66 (95% CI: 4.42-31.66), p=0.00]. Other risk factors significantly associated with animal seropositivity were: age group [OR: 1.78 (95% CI: 4.58-15.56), p=0.00], location in urban area [OR: 2.99 (95% CI: 1.46-6.51), p=0.00],body condition [OR: 3.47 (95% CI: 1.64-7.99), p=0.00], presence of farcy lesion[OR: 7.71 (95% CI: 3.47-19.50), p=0.00], proximity to water bodies [OR: 7.71 (95% CI: 3.47-19.50), p=0.00]; domestic animal population [OR: 3.20 (95% CI: 1.24-10.87), p=0.03] and number of households in sampling area [OR: 4.18 (95%CI: 1.82-11.30), p=0.00]. The study provides an estimate of prevalence of glanders and a potential link between animal seropositivity and presence of B. mallei in soil. The risk factors identified in this study can be used in surveillance and disease awareness. The high prevalence of disease in draught horses and contact of infected animals with their care-takers in developing countries signify need to initiate progressive control of the disease using one health approach.

Asian outpatients with schizophrenia: a double-blind randomized comparison of quality of life and clinical outcomes for patients treated with olanzapine or haloperidol.

To examine the quality of life (QoL) and clinical outcomes for Asian schizophrenic outpatients treated with olanzapine or haloperidol. Patients were randomized to 24-weeks' treatment with either olanzapine (n = 144) or haloperidol (n = 132) in a double-blind, prospective, multi-country study. The QLS and WHO-BREF were assessed for QoL; the PANSS, BPRS and CGI scales for clinical status; the BAS, AIMS and SAS scales for physical dysfunction. Regardless of antipsychotic, QoL improved significantly at 8 weeks and maintained this improvement at 24 weeks. Compared with haloperidol, olanzapine treatment was associated with significantly better QoL in the WHO-BREF physical and social relationship domains, better improvements in extrapyramidal symptoms in BAS and SAS scores, as well as lower incidence of adverse events. Patients taking haloperidol were more likely to be co-prescribed anticholinergics. The comparatively superior side-effect profile and tolerability of olanzapine may have contributed to enhance domain-specific QoL for these Asian outpatients.

Significant variables associated with epilepsy.

OBJECTIVE: To study the characteristics of the epileptics and the risk factors contributing to the development of epilepsy. DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Epilepsy Clinic at Ahbab Hospital, Lahore, from June 2002 to August 2002. SUBJECTS AND METHODS: Data was collected from 158 subjects, 89 males and 69 females, suffering from epilepsy. The information about socio-demographic characteristics and family history of illness, perinatal morbidity, birth place and mother s age at the time of delivery was obtained using a pre-tested questionnaire. Data was analyzed on SPSS version 10. RESULTS: Majority of the subjects were single (77.84%), 1st born among their siblings (25.95%), belonged to low social class (50.63%), and unemployed (25.31%). The major risk factors were family history of illness (23.52%) and positive medical problem around birth (12.66%). The presence of family history of illness, positive medical problem around birth and advanced maternal age at birth were associated with early onset of epilepsy. Vulnerability for the epilepsy also increases among hospital deliveries. CONCLUSION: Although the present study has identified various risk factors, yet the results need to be further confirmed through case-control studies.

Indian psychiatry and research in Pakistan.

In Asian culture, there is much stigmatization attached on having mental health problems and seeking help from a mental health expert. It is therefore, not surprising, that this stigmatization results in the refutation of the subsistence of a psychiatric problem in an individual and his family but also produces obstruction to help-seeking desires. To get a clear picture of the existence of psychiatric issues in the population, various research projects addressing psychiatric issues in children, women, and elderly are conducted both in Pakistan and India. A significant input has been taken from research conducted in India combating disaster management. In addition, public awareness programs are organized to provide information about common psychiatric disorders in children, adults, women, and the elderly.-Furthermore, psychiatric patients and their families are educated for the management of mental heath problems related to marriage, pregnancy, birth and hazards of smoking & substance abuse in young adults. Keeping in view the similarity in cultural background, treatment models, family structure, and psychosocial factors, collaborative research studies should be encouraged leading to improvement in psychiatric care of the patients both in India and Pakistan.

Frequency of psychological and somatic symptoms in patients with major depressive disorder.

Major depressive disorder (MDD) is one of the most commonly encountered psychiatric disorders in primary care. Depression is primarily a psychological illness; however, patients usually present with somatic symptoms. This pattern of presentation quite often poses a risk for patients with MDD due to the fact that general practitioners commonly attribute the cause of somatic symptoms to organic illnesses, thereby misdiagnosing patients. The current study focuses on the frequency of psychological and somatic symptoms in patients with major depressive disorder. The study is a cross-sectional survey using non-probability purposive sampling technique. The authors administered a self-developed questionnaire on 900 patients (male and female) diagnosed with major depressive disorder based on Diagnostic and Statistical Manual of Mental Disorders-IV-TR (DSM-IV-TR). The data was analyzed using Statistical Package for Social Sciences-10 (SPSS-10). Females presented with a higher frequency of somatic symptoms as compared to psychological symptoms, whereas males presented with a higher frequency of psychological symptoms as compared to somatic symptoms. These findings emphasize the imperative need for health care professionals to have a thorough understanding of major depressive disorder. The disabling effects of depression can be minimized and prognosis of such patients improved to the point of remission if depression is promptly diagnosed without ambiguity, and intensively treated based on the physician's comprehensive knowledge of the symptomatology of major depressive disorder.

Comparison of risperidone, olanzapine and quetiapine: effects on body weight, serum blood glucose and prolactin.

Schizophrenia is a chronic illness with a lifetime prevalence of 1% and with serious physical, social and economic consequences. Over the past decade, atypical antipsychotic medications have become the first-line treatment for schizophrenia (Breier et al, 2005).

Psychosocial responses to disaster: An Asian perspective.

The psychological and psychiatric impact of great natural disasters are beginning to be understood leading to new methods of prevention, intervention and mitigation. There is limited data from the Asian continent, however, which has been the location of some of the greatest disasters of recent times. In this paper, we outline the psychosocial intervention efforts from nine Asian nations when confronted with large-scale natural catastrophic events. These include reports from situations where local services have some capacity to respond as well as those where services are destroyed or overwhelmed. From this it is possible to draw some general principles of psychosocial disaster intervention: (1) Assessment of disaster, extant service systems and incoming resources. (2) Assessment of help-seeking pathways and cultural models of illness. (3) Facilitation and support for family reunion, identification of the dead and cultural and religious practices to address death and grief. (4) Foster and bolster community group activities where possible. (5) Psychosocial training of community, aid and health workers using a train the trainer model to promote case identification, psychoeducation and intervention, with specific emphasis on vulnerable groups, especially children. (6) Promote general community psychoeducation. (7) Train medical and health staff in basic psychiatric and psychological assessment and intervention for post-traumatic stress, mood and anxiety disorders. (8) Minimise risk factors for psychiatric morbidity such as displacement and loss of gainful activity. (9) Reshape mental health systems recognising the long-term psychiatric sequelae of disaster. The collective learnt experience from Asian natural disasters may be constructively used to plan strategies to respond appropriately to the psychosocial consequences of disaster both within Asia and in the rest of the world.

A 12-year follow-up of a sample of patients dependent upon heroin.

Heroin addiction is a chronic, relapsing and remitting condition. Each year 2-5% of addicts discontinue drug use permanently and 1-2% die, mostly of overdose (Robins, 1993). A study of 129 opiate-addicted patients on a monthly maintenance regimen found that those with a family history of opium use had an earlier age at onset (Chaudhry et al, 1991). Long-term follow-up studies of people who misuse opiates have revealed that opioid dependence appears to run a chronic, relapsing and remitting course with a significant mortality (10-15%) over 10 years (Robson, 1992). Metrebian et al (1998) reported that long-term heroin abstinence was associated with less criminality, psychological distress and morbidity; Hser et al (2001) reported it was associated with higher employment rates.

Asian outpatients with schizophrenia: a double-blind randomized comparison of quality of life and clinical outcomes for patients treated with olanzapine or haloperidol.

To examine the quality of life (QoL) and clinical outcomes for Asian schizophrenic outpatients treated with olanzapine or haloperidol. Patients were randomized to 24-weeks' treatment with either olanzapine (n = 144) or haloperidol (n = 132) in a double-blind, prospective, multi-country study. The QLS and WHO-BREF were assessed for QoL; the PANSS, BPRS and CGI scales for clinical status; the BAS, AIMS and SAS scales for physical dysfunction. Regardless of antipsychotic, QoL improved significantly at 8 weeks and maintained this improvement at 24 weeks. Compared with haloperidol, olanzapine treatment was associated with significantly better QoL in the WHO-BREF physical and social relationship domains, better improvements in extrapyramidal symptoms in BAS and SAS scores, as well as lower incidence of adverse events. Patients taking haloperidol were more likely to be co-prescribed anticholinergics. The comparatively superior side-effect profile and tolerability of olanzapine may have contributed to enhance domain-specific QoL for these Asian outpatients.