Polio vaccinators and law enforcement officials protecting them, have been killed in the line of duty since 2012 in Pakistan. This study was conducted to determine the opinions of university students ...in Islamabad and Rawalpindi, regarding the importance of polio vaccination, and the role of international donor agencies. Nine hundred forty-six students participated in this study; 833 (88.1%) students thought that polio is a public health problem in the country, and 815 (86.2%) thought that polio vaccination prevents polio in children. About a quarter of respondents thought that Pakistanis as well as non-Pakistanis working for either international nongovernmental organizations or United Nations agencies are spies working for the Western governments or their spy agencies. An appalling 300 (31.7%) respondents replied as either affirmatively or 'don't know' to the question whether killing of polio vaccinators is justified.
IntroductionIndividuals with schizophrenia are at a high risk of physical health comorbidities and premature mortality. Cardiovascular and metabolic causes are an important contributor. There are ...gaps in monitoring, documenting and managing these physical health comorbidities. Because of their condition, patients themselves may not be aware of these comorbidities and may not be able to follow a lifestyle that prevents and manages the complications. In many low-income and middle-income countries including Pakistan, the bulk of the burden of care for those struggling with schizophrenia falls on the families.ObjectivesTo determine the rate of self-reported physical health disorders and risk factors, like body mass index (BMI) and smoking, associated with cardiovascular and metabolic disorders in cases of schizophrenia compared with a group of mentally healthy controls.DesignA case-controlled, cross-sectional multicentre study of patients with schizophrenia in Pakistan.SettingsMultiple data collection sites across the country for patients, that is, public and private psychiatric OPDs (out patient departments), specialised psychiatric care facilities, and psychiatric wards of teaching and district level hospitals. Healthy controls were enrolled from the community.ParticipantsWe report a total of 6838 participants’ data with (N 3411 (49.9%)) cases of schizophrenia compared with a group of healthy controls (N 3427 (50.1%)).ResultsBMI (OR 0.98 (CI 0.97 to 0.99), p=0.0025), and the rate of smoking is higher in patients with schizophrenia than in controls. Problems with vision (OR 0.13 (0.08 to 0.2), joint pain (OR 0.18 (0.07 to 0.44)) and high cholesterol (OR 0.13 (0.05 to 0.35)) have higher reported prevalence in controls. The cases describe more physical health disorders in the category ‘other’ (OR 4.65 (3.01 to 7.18)). This captures residual disorders not listed in the questionnaire.ConclusionsParticipants with schizophrenia in comparison with controls report more disorders. The access in the ‘other’ category may be a reflection of undiagnosed disorders.
Introduction:
Clearance of detected somatic mutations at complete response by next-generation sequencing is a prognostic marker for survival in patients with acute myeloid leukemia (AML). However, ...the impact of allelic burden and persistence of clonal hematopoiesis of indeterminate potential (CHIP)-associated mutations on survival remains unclear. The aim of this study is to evaluate the prognostic impact of allelic burden of CHIP mutations at diagnosis, and their persistence within 6 months of therapy.
Methods:
From February 1, 2012 to May 26, 2016, we reviewed 562 patients with newly diagnosed AML. Next-generation sequencing was performed on the bone marrow samples to detect the presence of CHIP-associated mutations defined as DNMT3A, TET2, ASXL1, JAK2 and TP53. Overall survival (OS) was defined as time period from the diagnosis of AML to the date of last follow-up or death. Univariate (UVA) and multivariate Cox proportional hazard regression (MVA) were performed to identify prognostic factors for OS with p value cutoff of 0.020 for the selection of variables for MVA. Landmark analysis at 6 months was performed for the evaluation of the impact of clearance of CHIP, FLT3-ITD, FLT3D835, and NPM1 mutations.
Results:
We identified 378 patients (74%) with AML with CHIP mutations; 134 patients (26%) with AML without CHIP mutations. The overall median follow-up of 23 months (range, 0.1-49.0). The median age at diagnosis was 70 years (range, 17-92) and 66 years (range, 20-87) in CHIP AML and non-CHIP AML, respectively (p =0.001). Of 371 patients and 127 patients evaluable for cytogenetic in CHIP AML and non-CHIP AML, 124 (33%) and 25 patients (20%) had complex karyotype, respectively (p= 0.004). Of 378 patients with CHIP AML, 183 patients (48%) had TET2 mutations; 113 (30%), TP53; 110 (29%), ASXL1; 109 (29%), DNMT3A; JAK2, 46 (12%). Of 378 patients, single CHIP mutations was observed in 225 patients (60%); double, 33 (9%); triple, 28 (7%); quadruple, 1 (0%). Concurrent FLT3-ITD mutations was detected in 47 patients (13%) and 12 patients (9%) in CHIP AML and non-CHIP AML, respectively (p= 0.287); FLT3-D835, 22 (6%) and 8 (6%), respectively (p= 0.932); NPM1 mutations, 62 (17%) and 13 (10%), respectively (p= 0.057). Of 183 patients with TET2-mutated AML, the median TET2 variant allele frequency (VAF) was 42.9% (range, 2.26-95.32); of 113 with TP53-mutated AML, the median TP53 VAF, 45.9% (range, 1.15-93.74); of 109 with ASXL1-mutated AML, the median ASXL1 VAF was 34.5% (range, 1.17-58.62); of 109 with DNMT3A-mutated AML, the median DNMT3A VAF was 41.8% (range, 1.02-91.66); of 46 with JAK2-mutated AML, the median JAK2 VAF was 54.4% (range, 1.49-98.52). Overall, the median OS was 12 months and 11 months in CHIP AML and non-CHIP AML, respectively (p= 0.564); 16 months and 5 months in TET2-mutated AML and non-TET2-mutated AML, respectively (p <0.001); 4 months and 13 months in TP53-mutated and non-TP53-mutated AML, respectively (p< 0.001); 17 months and 11 months in DNMT3A-mutated and non-DNMT3A-mutated AML, respectively (p= 0.072); 16 months and 11 months in ASXL1-mutated AML and non-ASXL1-mutated AML, respectively (p= 0.067); 11 months and 12 months in JAK2-murated and non-JAK2-mutated AML, respectively (p= 0.123). The presence and number of CHIP mutations were not a prognostic factor for OS by univariate analysis (p=0.565; hazard ratio HR, 0.929; 95% confidence interval CI, 0.722-1.194: p= 0.408; hazard ratio, 1.058; 95% confidence interval, 0.926-1.208, respectively). MVA Cox regression identified age (p< 0.001; HR, 1.036; 95% CI, 1.024-1.048), TP53 VAF (p= 0.007; HR, 1.009; 95% CI, 1.002-1.016), NPM1 VAF (p=0.006; HR, 0.980; 95% CI, 0.967-0.994), and complex karyotype (p<0.001; HR, 1.869; 95% CI, 1.332-2.622) as independent prognostic factors for OS. Of 33 patients with CHIP AML who were evaluated for the clearance of VAF by next generation sequencing , landmark analysis at 6 months showed median OS of not reached and 20.3 months in patients with and without CHIP-mutation clearance, respectively (p=0.310).
Conclusion:
The VAF of TP53 and NPM1 mutations by next generation sequencing can further stratify patients with newly diagnosed AML. Approximately, each increment of TP53 and NPM1 VAF by 1% is independently associated with 1% higher risk of death, and 2% lower risk of death, respectively. The presence of CHIP mutations except TP53 does not affect outcome.
Sasaki:Otsuka Pharmaceutical: Honoraria. Short:Takeda Oncology: Consultancy. Ravandi:Macrogenix: Honoraria, Research Funding; Seattle Genetics: Research Funding; Sunesis: Honoraria; Xencor: Research Funding; Jazz: Honoraria; Seattle Genetics: Research Funding; Abbvie: Research Funding; Macrogenix: Honoraria, Research Funding; Bristol-Myers Squibb: Research Funding; Orsenix: Honoraria; Abbvie: Research Funding; Jazz: Honoraria; Xencor: Research Funding; Orsenix: Honoraria; Sunesis: Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Astellas Pharmaceuticals: Consultancy, Honoraria. Kadia:BMS: Research Funding; Abbvie: Consultancy; Takeda: Consultancy; Jazz: Consultancy, Research Funding; Takeda: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Research Funding; Novartis: Consultancy; Amgen: Consultancy, Research Funding; BMS: Research Funding; Jazz: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy; Abbvie: Consultancy; Celgene: Research Funding. DiNardo:Karyopharm: Honoraria; Agios: Consultancy; Celgene: Honoraria; Medimmune: Honoraria; Bayer: Honoraria; Abbvie: Honoraria. Cortes:Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Arog: Research Funding.
•SNPs at promoter directly affect the cytokine production.•Leprosy progression is associated with high producer genotypes of IL-10 and TNFα.•IL-10−1082 GG masks the production of high producer ...genotype of TNFα in leprosy.•TNFα−308GG, IL-10−819TT is predominant genotypes in our studied patients.•Individuals with these genotypes and IL-10−1082 GG are susceptible to leprosy.
Leprosy is an infectious disease caused by M. leprae. We analyzed 48 cytokine polymorphisms in 13 (pro as well as anti-inflammatory) cytokine genes using PCR-SSP assay in 102 leprosy patients and 120 healthy controls with intent to find out a link between cytokine polymorphisms and disease susceptibility. TNF-α (−308) GG, IL-10 (−819) TT, IL-10 (−1082) GG and IL1R (+1970) CC genotypes are found to be predominant (p=0.01, p=0.02, p=0.0001 and p=0.001, respectively) in both tuberculoid as well as lepromatous leprosy patients. This observation suggests these genotypes as play the central role(s) in the progression of disease. CBA assay demonstrates the varied serum concentration of these cytokines with respect to their genotypes. The above genotypes appeared as high producer genotypes in our study. Even in presence of high produce genotypes, TNF-α level are found to be affected/masked by the presence of IL-10 in leprosy patients. Expressional masking of TNF-α is associated with the expression of IL-10 in these patients. This is one the negative impact of SNP–SNP interaction in leprosy patients. Therefore, we can conclude that cytokine gene polymorphisms determine the predisposition to the leprosy progression.
ABSTRACT This research was aimed to explore the helminth parasitic diseases in Schizothorax plagiostomus (the snow trout) from river Swat and river Panjkora, Pakistan. Collection of 360 fish ...specimens have done from the lower, middle and upper reaches of both the rivers through gill nets, cast nets, dragon nets and hooks. All the samples were examined in the University of Malakand, Zoology Department for helminth parasites during the months from January 2015 to December 2016. Of the total examined fish samples 21.9% (n=79) were infected with Rhabdochona spp including 17.7% (n=32/180) in river Swat and 26.6% (n=47/180) in river Panjkora. Highest month-wise prevalence (p=0.09878,p<0.05) was reported in May (30%), then by February and October each (26.6%) while the lowest during August (13.3%). Highest prevalence (p=0.9723, p<0.05) was reported in summer season (26.6%), while lowest in the winter season (20%). Adults were highly infected (p=< 0.0001) in prevalence (63.7%) followed by sub-adults (13.2%) while no infection was found in juvenile specimens. Females fish samples had higher (p=0.0277, p>0.05) prevalence (28.8%) than males (16.6%). Fishes of the lower reaches had highest (p=0.0029, P>0.05) prevalence (31.7%) followed by middle reaches (16.5%) while the lowest prevalence was observed in samples of fish collected from upper reaches (9.87%). Present study address that Rhabdochona spp in the intestine of snow trout has a long term relationship and call as a natural infection in cyprinids and zoonotic risk to human.
The strength of the trade union movement in Pakistan has ebbed and flowed over the course of the country's history, but today, after roughly twenty-five years of liberalization, deregulation, and ...privatization, the movement is arguably at its weakest point in recent memory.
We report a case of a Calcium pyrophosphate dihydrate deposition disease (CPPD) presenting as a mass in the parotid and temporomandibular joint (TMJ) that simulated a parotid tumor. A 35 year-old man ...presented with pain in the left ear area. A CT Scan of the area showed a large, calcified mass surrounding the left condylar head, and extending into the infratemporal fossa. FNA of the mass showed birefringent crystals, most of which were rhomboid with occasional ones being needle shaped, embedded in an amorphous pink substance. Scanning electron microscopy (SEM) with energy dispersive x-ray spectroscopy (EDS) of these crystals showed peaks corresponding to calcium and phosphorus. SEM/EDS is a rapid method of diagnosing calcium pyrophosphate dihydrate deposition disease (CPPD) and an alternative to more commonly used method of special staining of cell block sections coupled with polarizing microscopy.
During winter, different types of sheds were constructed to reduce lamb mortality. A study was conducted to assess the effect of different types of housing on the behavior of Malpura lambs during the ...winter in semiarid tropical condition in terms of suckling, feeding, lying, standing, social interaction, and oral stereotype. Sheds are constructed to reduce winter mortality. This study was carried out for a period of 1 month during winter (January-February). Twenty-one lambs of aged 3-5 weeks were divided into 3 groups of 7 animals each such as G-I (control, n = 7), G-II (bamboo dome, n = 7) and G-III (thermocol-insulated cold-protected shed, n = 7). The G-I lambs were maintained in normal asbestos roofed shed (side wall wire net, curtains at night time), whereas G-II lambs were maintained in a local hand-made bamboo dome structures. G-III lambs were kept in thermocol-insulated (roof and doors were made up of asbestos, thermocol, and polyvinyl chloride sheet, brick side wall) roofed shed from 6:30 pm to 7 am. The lambs were exposed to their mother in the morning (7 am to 7:30 am) and evening (5:30 pm to 6 pm) for suckling. Lambs were provided with ad libitum green fodder, dry roughage, and concentrate in an open area from 8 am to 5:30 pm. Behavioral recording was carried out for 1 animal from each group daily (once weekly for each animal) by 3 people (1 person for 1 lamb). G-III lambs showed higher weekly body weight gain and higher milk intake. Total feeding time was 22.44% higher in G-III compared to G-I lambs. Drinking time was higher in G-I lambs compared with those in the other groups. Standing time was significantly higher (P < 0.05) in G-II lambs, whereas lying time was higher in G-I lambs. The lambs kept in the dome showed a greater frequency of oral stereotypies. The findings from this experiment provide useful information to understand the necessity of adequate space and the effects of temperature requirements for behavioral expression and growth of lambs in semiarid tropical environments.
This study evaluates the possibility of the cyclic use of magnesite by subjecting the reactivated adsorbent to surface area determination and scanning electron microscopy. Both these analyses show ...that the reactivated adsorbent is comparable to the fresh adsorbent, produced from raw magnesite, in porosity that plays the major role in the removal of noxious substances from spent lubricants. The adsorption ability of the reactivated adsorbent has been further testified through spectroscopic analyses of the percolated oil that exhibit marked decrease in polyaromatic hydrocarbons, metal content, and oxygenates that impart rancid odor in spent lubricants.
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