| 1. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- Muhammad, Noor, et al.
(författare)
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Novel mutations in MPT64 secretory protein of Mycobacterium tuberculosis complex
- 2023
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 20:3
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Tidskriftsartikel (refereegranskat)abstract
- Tuberculosis (TB) is a global health problem caused by the Mycobacterium tuberculosis complex (MTBC). These bacteria secrete various proteins involved in the pathogenesis and persistence of MTBC. Among the secretory proteins, MPT64 (Rv1980C) is highly conserved and is also known as a major culture filtrate that is used in rapid diagnosis of MTBC. In the current study, we aimed to find the mutation in this highly conserved protein in isolates from the Pashtun-dominant province of Pakistan. We analyzed 470 M. tuberculosis whole-genome sequences of Khyber Pakhtunkhwa Province. Mutations in the MPT64 gene were screened through TB-Profiler and BioEdit software tools. The DynaMut web server was used to analyze the impact of the mutation on protein dynamics and stability. Among 470 MTB genomes, three non-synonymous mutations were detected in nine isolates, and one synonymous mutation (G208A) was found in four isolates. Mutation G211T (F159L), which was detected at the C-terminal domain of the protein in six isolates, was the most prominent. The second novel mutation, T480C (I70V), was detected in two isolates at the C-terminal side of the protein structure. The third novel mutation, A491C (L66R), was detected in a single isolate at the N-terminal side of the MPT64 protein. The effect of these three mutations was destabilizing on the protein structure. The molecular flexibility of the first two mutations increased, and the last one decreased. MPT64 is a highly conserved secretory protein, harboring only a few mutations. This study provides useful information for better managing the diagnosis of MTB isolates in high TB-burden countries.
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| 5. |
- Salman, Muhammad, et al.
(författare)
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Evaluation of Conspiracy Beliefs, Vaccine Hesitancy, and Willingness to Pay towards COVID-19 Vaccines in Six Countries from Asian and African Regions : A Large Multinational Analysis
- 2022
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Ingår i: Vaccines. - : MDPI. - 2076-393X. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- Vaccination protects people from serious illness and associated complications. Conspiracy theories and misinformation on vaccines have been rampant during the COVID-19 pandemic and are considered significant drivers of vaccine hesitancy. Since vaccine hesitancy can undermine efforts to immunize the population against COVID-19 and interferes with the vaccination rate, this study aimed to ascertain the COVID-19-vaccine-related conspiracy beliefs, vaccine hesitancy, views regarding vaccine mandates, and willingness to pay for vaccines among the general population. A web-based, cross-sectional survey was conducted (April-August 2021) among the adult population in six countries (Pakistan, Saudi Arabia, India, Malaysia, Sudan, and Egypt). Participants were recruited using an exponential, non-discriminate snowball sampling method. A validated self-completed electronic questionnaire was used for the data collection. All the participants responded to questions on various domains of the study instrument, including conspiracy beliefs, vaccine hesitancy, and willingness to pay. The responses were scored according to predefined criteria and stratified into various groups. All data were entered and analyzed using SPSS version 22. A total of 2481 responses were included in the study (Pakistan 24.1%, Saudi Arabia 19.5%, India 11.6%, Malaysia 8.1%, Sudan 19.3%, and Egypt 17.3%). There was a preponderance of participants <= 40 years old (18-25 years: 55.8%, 26-40 years: 28.5%) and females (57.1%). The average score of the COVID-19 vaccine conspiracy belief scale (C19V-CBS) was 2.30 +/- 2.12 (median 2; range 0-7). Our analysis showed that 30% of the respondents were found to achieve the ideal score of zero, indicating no conspiracy belief. The mean score of the COVID-19 vaccine hesitancy scale (C19V-HS) was 25.93 +/- 8.11 (range: 10-50). The majority (45.7%) had C19V-HA scores of 21-30 and nearly 28% achieved a score greater than 30, indicating a higher degree of hesitancy. There was a significant positive correlation between conspiracy beliefs and vaccine hesitancy (Spearman's rho = 0.547, p < 0.001). Half of the study population were against the vaccine mandate. Respondents in favor of governmental enforcement of COVID-19 vaccines had significantly (p < 0.001) lower scores on the C19V-CBS and C19V-HS scale. Nearly 52% reported that they would only take vaccine if it were free, and only 24% were willing to pay for COVID-19 vaccines. A high prevalence of conspiracy beliefs and vaccine hesitancy was observed in the targeted countries. Our findings highlight the dire need for aggressive measures to counter the conspiracy beliefs and factors underlying this vaccine hesitancy.
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| 6. |
- Kassebaum, Nicholas J., et al.
(författare)
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Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015
- 2016
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658
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Tidskriftsartikel (refereegranskat)abstract
- Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
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| 7. |
- Khan, H. R., et al.
(författare)
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Cross-cultural prevalence of sleep quality and psychological distress in healthcare workers during COVID-19 pandemic
- 2021
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Ingår i: Brain and Behavior. - : John Wiley & Sons. - 2162-3279. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Poor quality sleep and emotional disturbances are expected in times of crisis. COVID-19 has severely impacted healthcare worldwide and with that comes the concern about its effects on healthcare workers. The purpose of the present study was to assess sleep quality and psychological distress in healthcare workers during the COVID-19 pandemic.Methods: The present work is a multi-centric cross-sectional study targeting healthcare workers from India, Pakistan, and Nepal. It used an online version of the Pittsburg Sleep Quality Index and the General Health Questionnaire, and data were analyzed using SPSS V.24.Results: A total of 1790 participants completed the questionnaire. Of the 1790 participants, 57% reported poor sleep quality, and 10% reported a high level of psychological distress. A cross-cultural comparison found some differences between the different groups of participants. The details of the differences were further explored in the article.Conclusion: The present study highlights that a significant proportion of healthcare workers are affected by poor sleep quality and psychological distress during the COVID-19 pandemic. It also emphasizes the imperative to provide them with psychosocial support to avoid potential short- and long-term psychological consequences of these troubling times.
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| 8. |
- Khan, Tahir Naeem, et al.
(författare)
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Cenani-Lenz syndrome restricted to limb and kidney anomalies associated with a novel LRP4 missense mutation
- 2013
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Ingår i: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212 .- 1878-0849. ; 56:7, s. 371-374
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Tidskriftsartikel (refereegranskat)abstract
- Cenani-Lenz syndrome (CLS) is a rare autosomal recessive developmental disorder of the limbs. The disorder is characterized by complete syndactyly with metacarpal fusions and/or oligodactyly sometimes accompanied by radioulnar synostosis. The clinical expression is variable and kidney agenesis/hypoplasia, craniofacial dysmorphism and teeth abnormalities are frequent features as well as lower limb involvement. CLS was recently associated with mutations in the low-density lipoprotein receptor-related protein 4 (LRP4) gene and dysregulated canonical WNT signaling. We have identified a large consanguineous Pakistani pedigree with 9 members affected by CLS. The affected individuals present with a consistent expression of the syndrome restricted to the limbs and kidneys. Symptoms from the lower limb are mild or absent and there were no radioulnar synostosis or craniofacial involvement. Genetic analysis using autozygosity mapping and sequencing revealed homozygosity for a novel missense mutation c.2858T > C (p.L953P) in the LRP4 gene. The mutation is located in a region encoding the highly conserved low-density lipoprotein receptor repeat class B domain of LRP4. Our findings add to the genotype-phenotype correlations in CLS and support kidney anomalies as a frequent associated feature.
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| 9. |
- Mushtaq, Iram, et al.
(författare)
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N-acetyl cysteine, selenium, and ascorbic acid rescue diabetic cardiac hypertrophy via mitochondrial-associated redox regulators
- 2021
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Ingår i: Molecules. - : MDPI AG. - 1420-3049. ; 26:23
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic disorders often lead to cardiac complications. Metabolic deregulations during diabetic conditions are linked to mitochondrial dysfunctions, which are the key contributing factors in cardiac hypertrophy. However, the underlying mechanisms involved in diabetes-induced cardiac hypertrophy are poorly understood. In the current study, we initially established a diabetic rat model by alloxan-administration, which was validated by peripheral glucose measurement. Diabetic rats displayed myocardial stiffness and fibrosis, changes in heart weight/body weight, heart weight/tibia length ratios, and enhanced size of myocytes, which altogether demonstrated the establishment of diabetic cardiac hypertrophy (DCH). Furthermore, we examined the expression of genes associated with mitochondrial signaling impairment. Our data show that the expression of PGC-1α, cytochrome c, MFN-2, and Drp-1 was deregulated. Mitochondrial-signaling impairment was further validated by redox-system dysregulation, which showed a significant increase in ROS and thiobarbituric acid reactive substances, both in serum and heart tissue, whereas the superoxide dismutase, catalase, and glutathione levels were decreased. Additionally, the expression levels of pro-apoptotic gene PUMA and stress marker GATA-4 genes were elevated, whereas ARC, PPARα, and Bcl-2 expression levels were decreased in the heart tissues of diabetic rats. Importantly, these alloxan-induced impairments were rescued by N-acetyl cysteine, ascorbic acid, and selenium treatment. This was demonstrated by the amelioration of myocardial stiffness, fibrosis, mitochondrial gene expression, lipid profile, restoration of myocyte size, reduced oxidative stress, and the activation of enzymes associated with antioxidant activities. Altogether, these data indicate that the improvement of mitochondrial dysfunction by protective agents such as N-acetyl cysteine, selenium, and ascorbic acid could rescue diabetes-associated cardiac complications, including DCH.
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| 10. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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