Demographic and clinical correlates of suicidal ideation in individuals with at-risk mental state (ARMS): A study from Pakistan.

BACKGROUND: Suicide is a major public health concern and one of the leading causes of mortality worldwide. People with an at-risk-mental-state (ARMS) for psychosis are more vulnerable to psychiatric co-morbidity and suicide, however, there are limited data from low-middle-income countries. The present study aimed to identify the prevalence of depressive symptoms and suicidal ideation along with sociodemographic and clinical correlates of suicidal ideation in individuals with ARMS from Pakistan. METHOD: Participants between the age of 16 and 35 years who met the criteria for ARMS based on the Comprehensive Assessment of At-Risk Mental State (CAARMS), were recruited from the community, general practitioner clinics and psychiatric units across Pakistan (n = 326). Montgomery and Asberg Depression Rating Scale (MADRS) and Social-Occupational-Functional-Assessment-Scale (SOFAS) were administered to participants. RESULTS: The prevalence of depressive symptoms and suicidal thoughts in the sample at baseline were 91.1% (n = 297) and 61.0% (n = 199), respectively. There were significant mean differences between groups (mean difference [95% CI]; p-value) without suicidal ideation and with suicidal ideation on measures of MADRS (-5.47 [-7.14, -3.81]; p < .001), CAARMS non-bizarre ideas (-0.29 [-0.47, -0.11]; p = .002) and perceptual abnormalities (-0.23 [-0.41, -0.04]; p = .015). CONCLUSION: These findings indicate that suicidal ideation and depressive symptoms are highly prevalent in individuals with ARMS in Pakistan. Given the pivotal developmental stages that ARMS presents, and the poor outcomes associated with co-morbid depression, there is an urgent need to prioritize the development of low-cost and scalable evidence-based interventions to address psychiatric comorbidity and suicidality in the ARMS population in Pakistan.

Role of oral vaccines as an edible tool to prevent infectious diseases.

Plants have been as medicinal mediators for centuries. Recent trends in agro-biotechnology however, improved the therapeutic roles of plants to a significant level and introduced plant-based oral vaccine which can arouse an immune response in consumer. Although conventional vaccines against infectious diseases have been administrated for years the discovery of plant-based oral vaccines can potentially replace them completely in the future. The probable limitations in conventional vaccines are found to be overcome by plant-based oral vaccines. Humans and animals will no longer be dependent upon local or systemic administration of vaccines but they will just receive the vaccines as a routine food. For the purpose, gene of interest is introduced into plant through transformation, and expression of specific antigen is obtained in plant products which are then consumed by humans or animals. Therefore, plants can serve as bioreactors or bio-factories for production of edible vaccines. A detailed overview about edible vaccines, methods for edible vaccine production, candidate bioreactors and future perspectives of edible vaccines has been summarized in current article. The future of vaccination seems to be present within plant-based vaccination system. Keywords: vaccine; edible vaccine; infectious diseases; antigen; edible crops; oral immunization.

Correction: An unprecedented tandem synthesis of fluorescent coumarin-fused pyrimidines via copper-catalyzed cross-dehydrogenative C(sp3)-N bond coupling.

Correction for 'An unprecedented tandem synthesis of fluorescent coumarin-fused pyrimidines via copper-catalyzed cross-dehydrogenative C(sp3)-N bond coupling' by Santosh Kumari et al., Org. Biomol. Chem., 2018, 16, 3220-3228.

An unprecedented tandem synthesis of fluorescent coumarin-fused pyrimidines via copper-catalyzed cross-dehydrogenative C(sp3)-N bond coupling.

An efficient, one-pot Cu-catalyzed tandem synthesis of fluorescent 1-benzyl-2-phenyl-1,2-dihydro-5H-chromeno[4,3-d]pyrimidin-5-ones from 4-chloro-3-formylcoumarin and benzylamines was developed by in situ intramolecular cross-dehydrogenative C(sp3)-N bond formation in moderate-to-good yields under ligand-free ambient conditions. This synthesis was easily scalable, and the generality of the substrates was established. These coumarin-fused pyrimidines exhibited interesting photo-physical properties and high quantum yields, and would be potential candidates for facilitating suitable studies in medicinal chemistry and materials science.

Solvent-Driven Iodine-Mediated Oxidative Strategies for the Synthesis of Bis(imidazo[1,2-a]pyridin-3-yl)sulfanes and Disulfanes.

Two efficient iodine-mediated strategies, which are economical and one-pot, are described to access bis(imidazo[1,2-a]pyridin-3-yl)sulfanes and bis(imidazo[1,2-a]pyridin-3-yl)disulfanes in chloroform and acetic acid, respectively, by a direct oxidative homocoupling of imidazo-heterocycles using inexpensive sodium sulfide as a sulfur source. These strategies are scalable, and an array of substrates delivered their corresponding stable sulfur-bridged imidazo-heterocycles in excellent yields.

Secular trends of Streptococcus pyogenes sepsis in Pakistan and analysis of clinical features in a hospitalized cohort.

Streptococcus pyogenes or Group A Streptococcus (GAS) is a re-emerging pathogen of significant public health importance. We present trends in GAS blood cultures over a 10 year period in Pakistan and characteristics of hospitalized patients with GAS sepsis over three years at a tertiary care hospital in Karachi, Pakistan. Blood cultures positive for GAS from 2004 -2014 were recorded at the clinical microbiology laboratory of the Aga Khan University and studied for trends in positivity rates. Medical records of patients hospitalized at the Aga Khan University hospital from 2012-2014 were also examined for clinical features and outcomes. GAS trends show a steady rate of blood culture positivity over 11 years, with higher rates in those >50 years, and seasonality favouring winter months. Case fatality rate in the hospitalized cohort was 34.1% (n= 14; of 41 patients). Malignancy predominated as the underlying predisposing factor among the 15-49 age group. Presence of sepsis was an independent predictor of mortality in GAS bacteremia. Studies of GAS trends in developing regions are important to inform changing epidemiology. GAS septic shock continues to have high case fatality despite antibiotic treatment. Early recognition, aggressive, goal-directed therapy for sepsis and prevention are possible control measures to prevent high mortality.

Ruthenium(II)-Catalyzed Regioselective Ortho Amidation of Imidazo Heterocycles with Isocyanates.

Direct ortho amidation at the phenyl ring of 2-phenylimidazo heterocycles with aryl isocyanates has been achieved via a chelation-assisted cationic ruthenium(II) complex catalyzed mechanism. The methodology provides a straightforward, high-yielding regioselective approach toward the synthesis of an array of ortho-amidated phenylimidazo heterocycles without prior activation of C(sp2)-H. This also reports the first method for coupling of aryl isocyanates with the imidazo[1,2-a]pyridine system via a pentacyclometalated intermediate. The methodology is found to be easily scalable and could be applied toward the selective ortho amidation of 2-heteroarylimidazo[1,2-a]pyridine frameworks.

Fluoroquinolone consumption and -resistance trends in Mycobacterium tuberculosis and other respiratory pathogens: Ecological antibiotic pressure and consequences in Pakistan, 2009-2015.

OBJECTIVE/BACKGROUND: Fluoroquinolones (FQs) are important anti-tuberculous drugs for the treatment of multidrug-resistant (MDR) tuberculosis. Resistance to FQs leads to fewer options for treatment of tuberculosis (TB), and infection with such strains may also require longer treatment duration. Trends of resistance in Mycobacterium tuberculosis (MTB) are indicators of MTB-resistance evolution. Drivers of such resistance need to be understood and studied to inform preventive strategies. METHODS: Here, we present FQ-resistance rates and trends in Pakistan from 2010 to 2015 and compare rates with FQ-consumption data and rates in other community pathogens. RESULTS: Our results reveal a recent decrease in FQ-resistance rates in MTB, but an increase in resistance for Haemophilus influenzae and Shigella spp. Correlation of FQ resistance with FQ consumption at the population level was weak for MTB, although strong associations were noted for H. influenzae and Shigella spp. CONCLUSION: We discuss the possible reasons for the decrease in resistance rates in TB, putative drivers of resistance other than volume of FQ consumption, and the possible impact of the National Tuberculosis Programme and drug regulatory activities.

The development and evaluation of a community-based clinical diagnosis tool and treatment regimen for postpartum sepsis in Bangladesh and Pakistan.

BACKGROUND: Postpartum sepsis accounts for most maternal deaths between three and seven days postpartum, when most mothers, even those who deliver in facilities, are at home. Case fatality rates for untreated women are very high. Newborns of ill women have substantially higher infection risk. METHODS/DESIGN: The objectives of this study are to: (1) create, field-test and validate a tool for community health workers to improve diagnostic accuracy of suspected puerperal sepsis; (2) measure incidence and identify associated risk factors and; (3) describe etiologic agents responsible and antibacterial susceptibility patterns. This prospective cohort study builds on the Aetiology of Neonatal Infection in South Asia study in three sites: Sylhet, Bangladesh and Karachi and Matiari, Pakistan. Formative research determined local knowledge of symptoms and signs of postpartum sepsis, and a systematic literature review was conducted to design a diagnostic tool for community health workers to use during ten postpartum home visits. Suspected postpartum sepsis cases were referred to study physicians for independent assessment, which permitted validation of the tool. Clinical specimens, including urine, blood, and endometrial material, were collected for etiologic assessment and antibiotic sensitivity. All women with puerperal sepsis were given appropriate antibiotics. DISCUSSION: This is the first large population-based study to expand community-based surveillance for diagnoses, referral and treatment of newborn sepsis to include maternal postpartum sepsis. Study activities will lead to development and validation of a diagnostic tool for use by community health workers in resource-poor countries. Understanding the epidemiology and microbiology of postpartum sepsis will inform prevention and treatment strategies and improve understanding of linkages between maternal and neonatal infections.

Current situation and challenges in implementing Malaria control strategies in Pakistan.

Malaria transmission is unstable in Pakistan with the highest number of cases reported during the monsoon season. Despite its high incidence, malaria is still a poorly resourced, poorly funded and an uncontrolled disease especially in far-flung areas. Pakistan's National Malaria Control Program (NMCP), although operational since its inception in 1947, has suffered due to the unstable political, socioeconomic and financial situation prevalent in the country. In Pakistan, more than 300 000 cases of malaria are reported every year with 68% of the cases caused by Plasmodium vivax. It is estimated that about 70-80% of the population accesses the private sector for treatment. As the private sector does not routinely report data to the government, the actual malaria burden could be 4-5 times higher than reported. P. vivax now accounts for more than 85% of all cases requiring hospital admission compared to 54% in 2000. In this review, we have described the saga of poor control of malaria in Pakistan over several years in context of restructuring of the Malaria Control Program, challenges to improvement, and way forward.

The emerging threat of schistosomiasis spread in Pakistan.

Schistosomiasis is among the thirteen neglected tropical diseases of the world. While prevalent in a number of countries, it has only rarely been reported in Pakistan. Here we report a 25 year old male who acquired the infection during travel to Malawi and presented with haematuria and dysuria. He was successfully treated with praziquantel. The possibility of schistosomiasis becoming endemic in the country is discussed. A number of risk factors are present including dams, irrigation, increased travel and geographical proximity to endemic countries. The local presence of at least one snail species of potential hosts for Schistosoma mansoni is confirmed. We see that schistosomiasis endemicity is a possible threat in Pakistan. Solutions to prevent this include reducing travel to endemic areas, prompt recognition and treatment of cases, and health education.

Use of p-nitrobenzoic acid in 7H10 agar for identification of Mycobacterium tuberculosis complex: a field study.

We report the efficiency and cost-effectiveness of p-nitrobenzoic acid (PNB) testing in Middlebrook 7H10 agar medium for the identification of Mycobacterium tuberculosis complex (MTC). PNB-7H10 was compared with PNB-MGIT and BACTEC-NAP using 200 clinical mycobacterial isolates. PNB-7H10 showed 100% agreement with PNB-MGIT and BACTEC-NAP tests, and reduced the cost of PNB-MGIT test by 80%. PNB-7H10 agar is therefore an effective alternative to the costly PNB-MGIT and BACTEC-NAP tests, especially in resource-poor settings.

Gastrointestinal helminthiasis presenting with acute diarrhoea and constipation: report of two cases with a second pathology.

Gastrointestinal helminthiasis in developing countries contributes to malnutrition and anemia. Diagnosis and treatment of helminthiasis, especially with low worm load is an unmet public health need in such settings. The infection may sometimes become manifest when a second pathology leads to purgation of the gastrointestinal tract. Two cases of helminthiasis are presented in which the infections only became amenable to diagnosis due to acute diarrhoea caused by giardiasis and lactulose administration. In the first case, acute giardiasis revealed Ascaris lumbricoides infestation, and in the second case primary helminthiasis (strongyloidiasis) was revealed by lactulose, and also led to Vibrio cholera bacteremia. These cases highlight the need to diagnose helminth infestations especially with low worm burdens by means of public health surveillance programmes. These cases highlight the need to diagnose helminth infestations especially with low worm burdens by means of public health surveillance programmes.

Endothelial progenitor cells in subclinical hypothyroidism: the effect of thyroid hormone replacement therapy.

CONTEXT: Subclinical hypothyroidism (SCH) is associated with cardiovascular (CV) risk factors, and possibly CV disease. However, its management remains controversial. Endothelial progenitor cells (EPC), expressing both endothelial and stem cell markers, are known to offer a novel CV risk marker. OBJECTIVE: The aim of the study was to ascertain whether EPC count or function is reduced in SCH and whether it improves with T(4) therapy. DESIGN AND INTERVENTION: EPC were studied in peripheral blood by fluorescence-activated cell sorter and following in vitro cultures before and after T(4) together with CV risk factors in 20 SCH and healthy controls (HC). MAIN OUTCOME MEASURE: EPC count was measured at baseline and after T(4) replacement in SCH. RESULTS: EPC count was significantly reduced in SCH compared to HC: median (range)-CD133+/VEGFR-2+, 0.09 (0.02-0.44) vs. 0.47 (0.17-2.12), P < 0.001; CD34+/VEGFR-2+, 0.10 (0.04-0.46) vs. 0.39 (0.11-2.13), P < 0.001; whereas EPC function was similar. There was a significant positive correlation between CD133+/VEGFR-2+ with free T(4) levels (r = 0.38; P = 0.02); high-density lipoprotein cholesterol levels (r = 0.51; P = 0.001); and negative correlation with TSH concentrations (r = -0.64; P < 0.001). After adjustment for conventional CV risk factors, SCH predicted lower EPC count, beta coefficient/P value: CD133+/VEGFR-2+ (-0.77/<0.001), and CD34+/VEGFR-2+ (-0.71/<0.001). In SCH participants, EPC count increased and was similar to HC after T(4); CD133+/VEGFR-2+, 0.32 (0.03-0.94) vs. 0.09 (0.02-0.44), P < 0.001; and CD34+/VEGFR-2+, 0.26 (0.06-0.88) vs. 0.10 (0.04-0.46), P < 0.001. CONCLUSION: SCH predicted lower EPC count, which improved with T(4) treatment, independent of other CV risk factors, providing additional evidence that T(4) replacement may improve CV risk in SCH.

Bullying victimization in youths and mental health problems: 'much ado about nothing'?

Bullying victimization is a topic of concern for youths, parents, school staff and mental health practitioners. Children and adolescents who are victimized by bullies show signs of distress and adjustment problems. However, it is not clear whether bullying is the source of these difficulties. This paper reviews empirical evidence to determine whether bullying victimization is a significant risk factor for psychopathology and should be the target of intervention and prevention strategies. Research indicates that being the victim of bullying (1) is not a random event and can be predicted by individual characteristics and family factors; (2) can be stable across ages; (3) is associated with severe symptoms of mental health problems, including self-harm, violent behaviour and psychotic symptoms; (4) has long-lasting effects that can persist until late adolescence; and (5) contributes independently to children's mental health problems. This body of evidence suggests that efforts aimed at reducing bullying victimization in childhood and adolescence should be strongly supported. In addition, research on explanatory mechanisms involved in the development of mental health problems in bullied youths is needed.

Dengue outbreak in Karachi, Pakistan, 2006: experience at a tertiary care center.

This is the first report of the largest epidemic of dengue hemorrhagic fever (DHF) virus infection (2006) with IgM-confirmed cases from Karachi, Pakistan. Medical records of 172 IgM-positive patients were reviewed retrospectively for demographic, clinical and laboratory data. Patients were categorized into dengue fever (DF) and DHF according to the WHO severity grading scale. The mean+/-SD age of the patients was 25.9+/-12.8 years, 55.8% were males and the hemoconcentration was recorded in a small number of patients [10 (7.0%)]. Male gender [odds ratio (OR)=14.7, P=0.003), positive history of vomiting (OR=4.3, P=0.047), thrombocytopenia at presentation (OR=225.2, P<0.001) and monocytosis (OR=5.8, P=0.030) were independently associated with DHF, but not with DF. Five cases (2.9%) had a fatal outcome, with a male-to-female ratio of 1:4. Three were from a pediatric group (<15 years). Pulmonary hemorrhages, disseminated intravascular coagulation and cerebral edema preceded death in these patients. The results have highlighted significant findings, such as adult susceptibility to DHF, pronounced abdominal symptoms and lack of hemoconcentration at time of presentation in the study population. These findings may play an important role in the case definitions of future studies from this part of the world.

The octreotide test dose is not a reliable predictor of the subsequent response to somatostatin analogue therapy in patients with acromegaly.

In many centres, a test dose (TD) of octreotide is administered before commencing somatostatin analogue therapy (SAT), although the merits of this procedure are uncertain. We have analysed the value of the GH response to a TD in predicting the efficacy of subsequent SAT in 47 patients with acromegaly (25 male, median age 51 years, range 20-82). The primary goal of SAT was a mean GH of < 5 mU/l. Median baseline GH was 19.3 mU/l (2.2-233 mU/l) and with the TD fell by 78% (35-98%) to a nadir of 4.2 mU/l (< 0.3-85 mU/l). Optimal predictive power was observed when GH fell to < 5 mU/l after the TD. With this criterion, the TD had a positive predictive value (PPV) of achieving the primary goal on SAT of 82% and a negative predictive value (NPV) of 50%. However, baseline GH was also highly predictive of the likelihood of successful SAT (GH < 5 mU/l). The GH response to the TD had PPV of 83% and NPV of 61% of normalising IGF-I on SAT. In summary, baseline GH and nadir after a TD are highly predictive of a good response to SAT; however, a poor response to a TD does not exclude an optimal response to SAT. Furthermore, failure to achieve biochemical control does not equate to no benefit, as biochemical improvement was seen in every patient; therefore, no patient should be deprived of octreotide therapy because of the result of a TD. In conclusion, our data indicate that the octreotide TD has no place in selecting patients for SAT.

Effects of GH replacement on metabolism and physical performance in GH deficient adults.

GH deficiency (GHD) in adults is associated with abnormalities in body composition, metabolic derangements, sub-optimal physical performance, high incidence of adverse cardiovascular risk factors and poor quality of life. GHD adults are insulin resistant and have reduced hepatic glycogen stores, reduced insulin stimulated glucose utilization and reduced glycogen synthesis in muscle. GH replacement results in either no change or slight reduction in insulin sensitivity. Hence, it is important to monitor for the development of glucose intolerance in patients on long-term GH replacement. GHD is associated with a lipid profile known to predispose to premature atherosclerosis and cardiovascular disease, i.e. increased total and LDL cholesterol, decreased HDL cholesterol, increased small dense LDL particles and increased triglycerides. LDL-cholesterol abnormalities appear to improve with GH replacement even if maintained within physiological dose range; the greatest improvement occurs in those subjects with higher baseline total and LDL cholesterol values and in female patients with adult onset GHD compared with male patients with childhood onset GHD. In contrast, hypertriglyceridaemia is not corrected by GH replacement. The majority of the reports suggest GH replacement increases Lipoprotein-a levels. Long-term observation will be required to determine whether GH replacement reduces cardiovascular morbidity and mortality in GHD adults. The reduced muscle mass and strength associated with GHD has been shown to improve after GH replacement. GH treatment also improves maximal and sub-maximal exercise performance in GHD adults. The effects on protein metabolism, energy expenditure and thyroid metabolism in GHD adults are also critical.