MyMedR

Displaying publications 3061 - 3080 of 5425 in total

Abstract:

Sort:

Prospective, large-scale multicenter trial for the use of drug-coated balloons in coronary lesions: The DCB-only All-Comers Registry

Rosenberg M, Waliszewski M, Chin K, Ahmad WAW, Caramanno G, Milazzo D, et al.

Catheter Cardiovasc Interv, 2019 02 01;93(2):181-188.
PMID: 30280482 DOI: 10.1002/ccd.27724

OBJECTIVES: This prospective, observational all-comers registry assessed the safety and efficacy of a Drug Coated Balloon-only strategy (DCB-only) in patients with coronary lesions.
BACKGROUND: Data regarding the performance of a DCB-only approach, especially in patients with previously untreated de-novo coronary artery disease (CAD), are still limited.
METHODS: This study was conducted as an international, multicenter registry primarily enrolling patients with de-novo CAD. However, it was also possible to include patients with in-stent restenosis (ISR). The primary endpoint was the rate of clinically driven target lesion revascularization (TLR) after 9 months.
RESULTS: A total of 1,025 patients with a mean age of 64.0 ± 11.2 years were enrolled. The majority of treated lesions were de-novo (66.9%), followed by drug-eluting-stent ISR (DES-ISR; 22.6%) and bare-metal-stent ISR (BMS-ISR; 10.5%). The TLR rate was lower in the de-novo group (2.3%) when compared to BMS- (2.9%) and DES-ISR (5.8%) (P = 0.049). Regarding MACE, there was a trend toward fewer events in the de-novo group (5.6%) than in the BMS- (7.8%) and DES-ISR cohort (9.6%) (P = 0.131). Subgroup analyses revealed that lesion type (95% CI 1.127-6.587); P = 0.026) and additional stent implantation (95% CI 0.054-0.464; P = 0.001) were associated with higher TLR rates.
CONCLUSIONS: Our results show that DCB-only angioplasty of de-novo coronary lesions is associated with low MACE and TLR rates. Thus, DCBs appear to be an attractive alternative for the interventional, stentless treatment of suitable de-novo coronary lesions.

Matched MeSH terms: Coronary Artery Disease/therapy*
Emerging neuroprotective effect of metformin in Parkinson's disease: A molecular crosstalk

Paudel YN, Angelopoulou E, Piperi C, Shaikh MF, Othman I

Pharmacol Res, 2020 02;152:104593.
PMID: 31843673 DOI: 10.1016/j.phrs.2019.104593

Parkinson's disease (PD) is a devastating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and Lewy pathology. PD is a major concern of today's aging population and has emerged as a global health burden. Despite the rapid advances in PD research over the past decades, the gold standard therapy provides only symptomatic relief and fails to halt disease progression. Therefore, exploring novel disease-modifying therapeutic strategies is highly demanded. Metformin, which is currently used as a first-line therapy for type 2 diabetes mellitus (T2DM), has recently demonstrated to exert a neuroprotective role in several neurodegenerative disorders including PD, both in vitro and in vivo. In this review, we explore the neuroprotective potential of metformin based on emerging evidence from pre-clinical and clinical studies. Regarding the underlying molecular mechanisms, metformin has been shown to inhibit α-synuclein (SNCA) phosphorylation and aggregation, prevent mitochondrial dysfunction, attenuate oxidative stress, modulate autophagy mainly via AMP-activated protein kinase (AMPK) activation, as well as prevent neurodegeneration and neuroinflammation. Overall, the neuroprotective effects of metformin in PD pathogenesis present a novel promising therapeutic strategy that might overcome the limitations of current PD treatment.

Matched MeSH terms: Parkinson Disease/drug therapy*
Stopping anti-tumour necrosis factor therapy in patients with perianal Crohn's disease

Mak JWY, Tang W, Yip TCF, Ran ZH, Wei SC, Ahuja V, et al.

Aliment Pharmacol Ther, 2019 12;50(11-12):1195-1203.
PMID: 31638274 DOI: 10.1111/apt.15547

BACKGROUND: Little is known of the outcome of patients with perianal Crohn's disease after stopping anti-tumour necrosis factor (TNF) therapy.
AIM: To evaluate the rate of relapse in perianal Crohn's disease (CD) after stopping anti-TNF therapy.
METHODS: Consecutive perianal CD patients treated with anti-TNF therapy with subsequent discontinuation were retrieved from prospective inflammatory bowel disease database of institutes in Hong Kong, Shanghai, Taiwan, Malaysia, Thailand and Singapore from 1997 to June 2019. Cumulative probability of perianal CD relapse was estimated using Kaplan-Meier method.
RESULTS: After a median follow-up of 89 months (interquartile range [IQR]: 65-173 months), 44 of the 78 perianal CD patients (56.4%) relapsed after stopping anti-TNF, defined as increased fistula drainage or recurrence of previously healed fistula, after stopping anti-TNF therapy. Cumulative probabilities of perianal CD relapse were 50.8%, 72.6% and 78.0% at 12, 36 and 60 months, respectively. Younger age at diagnosis of CD [adjusted hazard ratio (HR): 1.04; 95% CI 1.01-1.09; P = .04] was associated with a higher chance of perianal CD relapse. Among those with perianal CD relapse (n = 44), retreatment with anti-TNF induced remission in 24 of 29 patients (82.8%). Twelve (27.3%) patients required defunctioning surgery and one (2.3%) required proctectomy. Maintenance with thiopurine was not associated with a reduced likelihood of relapse [HR = 1.10; 95% CI: 0.58-2.12; P = .77]. Among the 17 patients who achieved radiological remission of perianal CD, five (35.3%) developed relapse after stopping anti-TNF therapy after a median of 6 months.
CONCLUSIONS: More than half of the perianal CD patients developed relapse after stopping anti-TNF therapy. Most regained response after resuming anti-TNF. However, more than one-fourth of the perianal CD patients with relapse required defunctioning surgery. Radiological assessment before stopping anti-TNF is crucial in perianal CD.

Matched MeSH terms: Crohn Disease/drug therapy*
Fulltext Smoking prevalence and attributable disease burden in 195 countries and territories, 1990-2015: a systematic analysis from the Global Burden of Disease Study 2015

GBD 2015 Tobacco Collaborators

Lancet, 2017 May 13;389(10082):1885-1906.
PMID: 28390697 DOI: 10.1016/S0140-6736(17)30819-X

BACKGROUND: The scale-up of tobacco control, especially after the adoption of the Framework Convention for Tobacco Control, is a major public health success story. Nonetheless, smoking remains a leading risk for early death and disability worldwide, and therefore continues to require sustained political commitment. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) offers a robust platform through which global, regional, and national progress toward achieving smoking-related targets can be assessed.
METHODS: We synthesised 2818 data sources with spatiotemporal Gaussian process regression and produced estimates of daily smoking prevalence by sex, age group, and year for 195 countries and territories from 1990 to 2015. We analysed 38 risk-outcome pairs to generate estimates of smoking-attributable mortality and disease burden, as measured by disability-adjusted life-years (DALYs). We then performed a cohort analysis of smoking prevalence by birth-year cohort to better understand temporal age patterns in smoking. We also did a decomposition analysis, in which we parsed out changes in all-cause smoking-attributable DALYs due to changes in population growth, population ageing, smoking prevalence, and risk-deleted DALY rates. Finally, we explored results by level of development using the Socio-demographic Index (SDI).
FINDINGS: Worldwide, the age-standardised prevalence of daily smoking was 25·0% (95% uncertainty interval [UI] 24·2-25·7) for men and 5·4% (5·1-5·7) for women, representing 28·4% (25·8-31·1) and 34·4% (29·4-38·6) reductions, respectively, since 1990. A greater percentage of countries and territories achieved significant annualised rates of decline in smoking prevalence from 1990 to 2005 than in between 2005 and 2015; however, only four countries had significant annualised increases in smoking prevalence between 2005 and 2015 (Congo [Brazzaville] and Azerbaijan for men and Kuwait and Timor-Leste for women). In 2015, 11·5% of global deaths (6·4 million [95% UI 5·7-7·0 million]) were attributable to smoking worldwide, of which 52·2% took place in four countries (China, India, the USA, and Russia). Smoking was ranked among the five leading risk factors by DALYs in 109 countries and territories in 2015, rising from 88 geographies in 1990. In terms of birth cohorts, male smoking prevalence followed similar age patterns across levels of SDI, whereas much more heterogeneity was found in age patterns for female smokers by level of development. While smoking prevalence and risk-deleted DALY rates mostly decreased by sex and SDI quintile, population growth, population ageing, or a combination of both, drove rises in overall smoking-attributable DALYs in low-SDI to middle-SDI geographies between 2005 and 2015.
INTERPRETATION: The pace of progress in reducing smoking prevalence has been heterogeneous across geographies, development status, and sex, and as highlighted by more recent trends, maintaining past rates of decline should not be taken for granted, especially in women and in low-SDI to middle-SDI countries. Beyond the effect of the tobacco industry and societal mores, a crucial challenge facing tobacco control initiatives is that demographic forces are poised to heighten smoking's global toll, unless progress in preventing initiation and promoting cessation can be substantially accelerated. Greater success in tobacco control is possible but requires effective, comprehensive, and adequately implemented and enforced policies, which might in turn require global and national levels of political commitment beyond what has been achieved during the past 25 years.
FUNDING: Bill & Melinda Gates Foundation and Bloomberg Philanthropies.
Malaysian Collaborators: Southern University College, Skudai, Malaysia (Y J Kim PhD); University of Science Malaysia, Kubang Kerian, Malaysia (K I Musa MD); International Medical University, Kuala Lumpur, Malaysia (C T Sreeramareddy MD)

Matched MeSH terms: Global Burden of Disease*
TP53 Gene 72 Arg/Pro (rs1042522) Single Nucleotide Polymorphism Contribute to Increase the Risk of B-Chronic Lymphocytic Leukemia in the Sudanese Population

Mohammed Basabaeen AA, Abdelgader EA, Babekir EA, Abdelrahim SO, Eltayeb NH, Altayeb OA, et al.

Asian Pac J Cancer Prev, 2019 May 25;20(5):1579-1585.
PMID: 31128065

Objective: This study aimed at exploring the association of TP53 72Arg/Pro polymorphism and Risk of Chronic
Lymphocytic Leukemia and to assess the correlation between TP53 72Arg/Pro polymorphism and clinical parameter,
hematological profile and some biological prognostic markers among Sudanese patients with chronic lymphocytic
leukemia. Methods: A case-control study was conducted in Khartoum state, Sudan, during the period from April 2017 to
April 2018, involved 110 B-CLL patients and 80 healthy volunteers as a control group. Physical examination, Complete
Blood Count and Immunophenotype were performed in all patients to confirm the diagnosis. Clinical staging such as
Rai and Binet were studied. CD38 and ZAP70 were performed by Flow Cytometry. Blood samples were collected from
all participants; DNA was extracted by using ANALYTIKJENA Blood DNA Extraction Kit (Germany) and analyzed
TP53 codon 72Arg/Pro Polymorphism by using AS-PCR. The statistical analysis was performed using SPSS version
23.0 software (Chicago, IL, USA). Results: the Arg/Pro was the most frequent genotype in B-CLL patients(50%),
followed by Arg/Arg (25.5%) and Pro/Pro (24.5%), whereas in healthy control group Arg/Pro was the most frequent
(47.5%), followed by Arg/Arg (45%) and Pro/Pro (7.5%). Our data indicate a higher frequency of homozygous Pro/
Pro in the B-CLL patients as compared to controls with an OR of 4.01 for the Pro/Pro genotype and lower frequency
of Arg/Arg genotype in CLL patients as compared to controls with an OR of .42 for the Arg/Arg genotype. Also, the
Pro allele showed higher risk than Arg allele (P value=0.000, OR 2.23, 95% CI=1.45-3.41). No significant association
between gender, clinical staging systems (Rai, Binet), biological prognostic markers (CD38 expression or ZAP70
expression), and TP53 codon 72Arg/Pro polymorphisms, except Arg/Arg genotype tended to be associated with younger
age (P =0.04). Conclusion: Our data suggested that Pro/Pro genotype contribute to increased susceptibility to B-Chronic
Lymphocytic Leukemia risk in our population tenfold higher than those had Arg/Arg genotype.

Matched MeSH terms: Genetic Predisposition to Disease/genetics*
Fulltext Passengers' destinations from China: low risk of Novel Coronavirus (2019-nCoV) transmission into Africa and South America

Haider N, Yavlinsky A, Simons D, Osman AY, Ntoumi F, Zumla A, et al.

Epidemiol Infect, 2020 02 26;148:e41.
PMID: 32100667 DOI: 10.1017/S0950268820000424

Novel Coronavirus (2019-nCoV [SARS-COV-2]) was detected in humans during the last week of December 2019 at Wuhan city in China, and caused 24 554 cases in 27 countries and territories as of 5 February 2020. The objective of this study was to estimate the risk of transmission of 2019-nCoV through human passenger air flight from four major cities of China (Wuhan, Beijing, Shanghai and Guangzhou) to the passengers' destination countries. We extracted the weekly simulated passengers' end destination data for the period of 1-31 January 2020 from FLIRT, an online air travel dataset that uses information from 800 airlines to show the direct flight and passengers' end destination. We estimated a risk index of 2019-nCoV transmission based on the number of travellers to destination countries, weighted by the number of confirmed cases of the departed city reported by the World Health Organization (WHO). We ranked each country based on the risk index in four quantiles (4th quantile being the highest risk and 1st quantile being the lowest risk). During the period, 388 287 passengers were destined for 1297 airports in 168 countries or territories across the world. The risk index of 2019-nCoV among the countries had a very high correlation with the WHO-reported confirmed cases (0.97). According to our risk score classification, of the countries that reported at least one Coronavirus-infected pneumonia (COVID-19) case as of 5 February 2020, 24 countries were in the 4th quantile of the risk index, two in the 3rd quantile, one in the 2nd quantile and none in the 1st quantile. Outside China, countries with a higher risk of 2019-nCoV transmission are Thailand, Cambodia, Malaysia, Canada and the USA, all of which reported at least one case. In pan-Europe, UK, France, Russia, Germany and Italy; in North America, USA and Canada; in Oceania, Australia had high risk, all of them reported at least one case. In Africa and South America, the risk of transmission is very low with Ethiopia, South Africa, Egypt, Mauritius and Brazil showing a similar risk of transmission compared to the risk of any of the countries where at least one case is detected. The risk of transmission on 31 January 2020 was very high in neighbouring Asian countries, followed by Europe (UK, France, Russia and Germany), Oceania (Australia) and North America (USA and Canada). Increased public health response including early case recognition, isolation of identified case, contract tracing and targeted airport screening, public awareness and vigilance of health workers will help mitigate the force of further spread to naïve countries.

Matched MeSH terms: Disease Outbreaks*
Inherited metabolic disorders presenting as hypoxic ischaemic encephalopathy: A case series of patients presenting at a tertiary care hospital in Pakistan

Zahid M, Khan AH, Yunus ZM, Chen BC, Steinmann B, Johannes H, et al.

J Pak Med Assoc, 2019 Mar;69(3):432-436.
PMID: 30890842

In spite of the efforts and interventions by the Government of Pakistan and The World Health Organization, the neonatal mortality in Pakistan has declined by only 0.9% as compared to the global average decline of 2.1% between 2000 and 2010. This has resulted in failure to achieve the global Millennium Development Goal 4. Hypoxic-ischaemic encephalopathy, still birth, sepsis, pneumonia, diarrhoea and birth defects are commonly attributed as leading causes of neonatal mortality in Pakistan. Inherited metabolic disorders often present at the time of birth or the first few days of life. The clinical presentation of the inherited metabolic disorders including hypotonia, seizure and lactic acidosis overlap with clinical features of hypoxic-ischaemic encephalopathy and sepsis. Thus, these disorders are often either missed or wrongly diagnosed as hypoxicischaemic encephalopathy or sepsis unless the physicians actively investigate for the underlying inherited metabolic disorders. We present 4 neonates who had received the diagnosis of hypoxic-ischaemic encephalopathy and eventually were diagnosed to have various inherited metabolic disorders. Neonates with sepsis and hypoxic-ischaemic encephalopathy-like clinical presentation should be evaluated for inherited metabolic disorders.

Matched MeSH terms: Pyruvate Carboxylase Deficiency Disease/diagnosis*
Fulltext Public perception and attitude towards dengue prevention activity and response to dengue early warning in Malaysia

Zaki R, Roffeei SN, Hii YL, Yahya A, Appannan M, Said MA, et al.

PLoS One, 2019;14(2):e0212497.
PMID: 30818394 DOI: 10.1371/journal.pone.0212497

An early warning system for dengue is meant to predict outbreaks and prevent dengue cases by aiding timely decision making and deployment of interventions. However, only a system which is accepted and utilised by the public would be sustainable in the long run. This study aimed to explore the perception and attitude of the Malaysian public towards a dengue early warning system. The sample consisted of 847 individuals who were 18 years and above and living/working in the Petaling District, an area adjacent to Kuala Lumpur, Malaysia. A questionnaire consisting of personal information and three sub-measures of; i) perception, ii) attitude towards dengue early warning and iii) response towards early warning; was distributed to participants. We found that most of the respondents know about dengue fever (97.1%) and its association with climate factors (90.6%). Most of them wanted to help reduce the number of dengue cases in their area (91.5%). A small percentage of the respondents admitted that they were not willing to be involved in public activities, and 64% of them admitted that they did not check dengue situations or hotspots around their area regularly. Despite the high awareness on the relationship between climate and dengue, about 45% of respondents do not know or are not sure how this can be used to predict dengue. Respondents would like to know more about how climate data can be used to predict a dengue outbreak (92.7%). Providing more information on how climate can influence dengue cases would increase public acceptability and improve response towards climate-based warning system. The most preferred way of communicating early warning was through the television (66.4%). This study shows that the public in Petaling District considers it necessary to have a dengue warning system to be necessary, but more education is required.

Matched MeSH terms: Disease Outbreaks/prevention & control
Fulltext X-chromosome association study reveals genetic susceptibility loci of nasopharyngeal carcinoma

Zuo XY, Feng QS, Sun J, Wei PP, Chin YM, Guo YM, et al.

Biol Sex Differ, 2019 03 25;10(1):13.
PMID: 30909962 DOI: 10.1186/s13293-019-0227-9

BACKGROUND: The male predominance in the incidence of nasopharyngeal carcinoma (NPC) suggests the contribution of the X chromosome to the susceptibility of NPC. However, no X-linked susceptibility loci have been examined by genome-wide association studies (GWASs) for NPC by far.
METHODS: To understand the contribution of the X chromosome in NPC susceptibility, we conducted an X chromosome-wide association analysis on 1615 NPC patients and 1025 healthy controls of Guangdong Chinese, followed by two validation analyses in Taiwan Chinese (n = 562) and Malaysian Chinese (n = 716).
RESULTS: Firstly, the proportion of variance of X-linked loci over phenotypic variance was estimated in the discovery samples, which revealed that the phenotypic variance explained by X chromosome polymorphisms was estimated to be 12.63% (non-dosage compensation model) in males, as compared with 0.0001% in females. This suggested that the contribution of X chromosome to the genetic variance of NPC should not be neglected. Secondly, association analysis revealed that rs5927056 in DMD gene achieved X chromosome-wide association significance in the discovery sample (OR = 0.81, 95% CI 0.73-0.89, P = 1.49 × 10-5). Combined analysis revealed rs5927056 for DMD gene with suggestive significance (P = 9.44 × 10-5). Moreover, the female-specific association of rs5933886 in ARHGAP6 gene (OR = 0.62, 95%CI: 0.47-0.81, P = 4.37 × 10-4) was successfully replicated in Taiwan Chinese (P = 1.64 × 10-2). rs5933886 also showed nominally significant gender × SNP interaction in both Guangdong (P = 6.25 × 10-4) and Taiwan datasets (P = 2.99 × 10-2).
CONCLUSION: Our finding reveals new susceptibility loci at the X chromosome conferring risk of NPC and supports the value of including the X chromosome in large-scale association studies.

Matched MeSH terms: Genetic Predisposition to Disease*
Fulltext Defining the ecological and evolutionary drivers of Plasmodium knowlesi transmission within a multi-scale framework

Davidson G, Chua TH, Cook A, Speldewinde P, Weinstein P

Malar J, 2019 Mar 08;18(1):66.
PMID: 30849978 DOI: 10.1186/s12936-019-2693-2

Plasmodium knowlesi is a zoonotic malaria parasite normally residing in long-tailed and pig-tailed macaques (Macaca fascicularis and Macaca nemestrina, respectively) found throughout Southeast Asia. Recently, knowlesi malaria has become the predominant malaria affecting humans in Malaysian Borneo, being responsible for approximately 70% of reported cases. Largely as a result of anthropogenic land use changes in Borneo, vectors which transmit the parasite, along with macaque hosts, are both now frequently found in disturbed forest habitats, or at the forest fringes, thus having more frequent contact with humans. Having access to human hosts provides the parasite with the opportunity to further its adaption to the human immune system. The ecological drivers of the transmission and spread of P. knowlesi are operating over many different spatial (and, therefore, temporal) scales, from the molecular to the continental. Strategies to prevent and manage zoonoses, such as P. knowlesi malaria require interdisciplinary research exploring the impact of land use change and biodiversity loss on the evolving relationship between parasite, reservoir hosts, vectors, and humans over multiple spatial scales.

Matched MeSH terms: Disease Transmission, Infectious*
Fulltext School-based health education for dengue control in Kelantan, Malaysia: Impact on knowledge, attitude and practice

AhbiRami R, Zuharah WF

PLoS Negl Trop Dis, 2020 03;14(3):e0008075.
PMID: 32218580 DOI: 10.1371/journal.pntd.0008075

The massive flood in Malaysia's east coast in December 2014 has placed Kelantan in a possible dengue outbreak risk. At this point, community awareness is essential in preventing disease spread. However, no data on knowledge, attitude, and practice (KAP) of dengue in Kelantan have existed in relevance to flood disaster, although such information is necessary for the vector control programs. The purpose of this study is to assess the KAP regarding dengue among school children from flooded and unflooded areas and to evaluate the effectiveness of the dengue health education program in improving their KAP level. A school-based pre- and post-tests design was utilized in this study whereby a booklet on dengue was distributed during the interphase of the tests. The information collected was on the socio-demographic, KAP and the source of dengue information. We statistically compared the KAP between the two study sites and the pre- and post-test scores to evaluate the health education program. A total of 203 students participated in the survey, and 51.7% of them were flood victims. When comparing the baseline KAP, the respondents from the unflooded area had higher knowledge scores compared to those from the flooded area (P<0.05), while non-significant differences were observed in the attitude and practice between the two study areas (P>0.05). The health education program significantly improved knowledge and practice in the flooded area and knowledge only in the unflooded area (P<0.05). The multinomial regression analysis suggests that age and dengue history are the primary determinants that influence the high practice level in both areas. We suggest the need to increase routine dengue health education programs to all age groups targeting both high and low dengue risk areas, and the necessity to ensure the translation of positive knowledge and attitude changes into real dengue preventive practices.

Matched MeSH terms: Communicable Disease Control/methods*
Fulltext Comprehensive Genetic Results for Primary Immunodeficiency Disorders in a Highly Consanguineous Population

Al-Herz W, Chou J, Delmonte OM, Massaad MJ, Bainter W, Castagnoli R, et al.

Front Immunol, 2018;9:3146.
PMID: 30697212 DOI: 10.3389/fimmu.2018.03146

Objective: To present the genetic causes of patients with primary immune deficiencies (PIDs) in Kuwait between 2004 and 2017. Methods: The data was obtained from the Kuwait National Primary Immunodeficiency Disorders Registry. Genomic DNA from patients with clinical and immunological features of PID was sequenced using Sanger sequencing (SS), next generation sequencing (NGS) of targeted genes, whole exome sequencing (WES), and/or whole genome sequencing (WGS). Functional assays were utilized to assess the biologic effect of identified variants. Fluorescence in situ hybridization (FISH) for 22q11.2 deletion and genomic hybridizations arrays were performed when thymic defects were suspected. Results: A total of 264 patients were registered during the study period with predominance of patients with immunodeficiencies affecting cellular and humoral immunity (35.2%), followed by combined immunodeficiencies with associated syndromic features (24%). Parental consanguinity and family history suggestive of PID were reported in 213 (81%) and 145 patients (55%), respectively. Genetic testing of 206 patients resulted in a diagnostic yield of 70%. Mutations were identified in 46 different genes and more than 90% of the reported genetic defects were transmitted by in an autosomal recessive pattern. The majority of the mutations were missense mutations (57%) followed by deletions and frame shift mutations. Five novel disease-causing genes were discovered. Conclusions: Genetic testing should be an integral part in the management of primary immunodeficiency patients. This will help the delivery of precision medicine and facilitate proper genetic counseling. Studying inbred populations using sophisticated diagnostic methods can allow better understanding of the genetics of primary immunodeficiency disorders.

Matched MeSH terms: Genetic Predisposition to Disease*
Fulltext Growth Hormone Promotes Motor Function after Experimental Stroke and Enhances Recovery-Promoting Mechanisms within the Peri-Infarct Area

Sanchez-Bezanilla S, Åberg ND, Crock P, Walker FR, Nilsson M, Isgaard J, et al.

Int J Mol Sci, 2020 Jan 17;21(2).
PMID: 31963456 DOI: 10.3390/ijms21020606

Motor impairment is the most common and widely recognised clinical outcome after stroke. Current clinical practice in stroke rehabilitation focuses mainly on physical therapy, with no pharmacological intervention approved to facilitate functional recovery. Several studies have documented positive effects of growth hormone (GH) on cognitive function after stroke, but surprisingly, the effects on motor function remain unclear. In this study, photothrombotic occlusion targeting the motor and sensory cortex was induced in adult male mice. Two days post-stroke, mice were administered with recombinant human GH or saline, continuing for 28 days, followed by evaluation of motor function. Three days after initiation of the treatment, bromodeoxyuridine was administered for subsequent assessment of cell proliferation. Known neurorestorative processes within the peri-infarct area were evaluated by histological and biochemical analyses at 30 days post-stroke. This study demonstrated that GH treatment improves motor function after stroke by 50%-60%, as assessed using the cylinder and grid walk tests. Furthermore, the observed functional improvements occurred in parallel with a reduction in brain tissue loss, as well as increased cell proliferation, neurogenesis, increased synaptic plasticity and angiogenesis within the peri-infarct area. These findings provide new evidence about the potential therapeutic effects of GH in stroke recovery.

Matched MeSH terms: Disease Models, Animal*
Fulltext View of Pakistani Residents toward Coronavirus Disease (COVID-19) during a Rapid Outbreak: A Rapid Online Survey

Hayat K, Rosenthal M, Xu S, Arshed M, Li P, Zhai P, et al.

Int J Environ Res Public Health, 2020 05 12;17(10).
PMID: 32408528 DOI: 10.3390/ijerph17103347

BACKGROUND: Coronavirus disease (COVID-19) is a deadly disease that is affecting most of the countries worldwide. Public understanding, including knowledge about signs and symptoms, mode of transmission, and hygiene of COVID-19, is vital for designing effective control strategies during a public health crisis. The current study is aimed at investigating the public's perspective about COVID-19, including their knowledge, attitude, and practices.
METHODS: A rapid online survey comprising 22 items was administered during the rapid outbreak of COVID-19 in Pakistan. Questions were focused on the prevention, transmission, clinical features, and control of COVID-19. In addition, the attitudes and practices of the participants were explored. Descriptive statistics, Mann-Whitney tests, Kruskal-Wallis tests, and regression analysis were carried out during data analysis.
RESULTS: A total of 1257 respondents participated in this study. Most of the respondents had good knowledge (good = 64.8%, average = 30.5%, poor = 4.7%) of COVID-19. Gender, marital status, education, and residence were observed to have a significant association with the knowledge score. A vast majority of the survey respondents (77.0%) believed that COVID-19 would be controlled successfully in Pakistan. The practices of wearing a mask (85.8%) and handwashing (88.1%) were common among the participants.
CONCLUSION: The participants demonstrated good knowledge and reasonable attitudes and practices toward most aspects of the COVID-19 outbreak. Improvements in certain areas could be made by mass-level education.

Matched MeSH terms: Disease Outbreaks/prevention & control*
Fulltext CNPase, a 2',3'-Cyclic-nucleotide 3'-phosphodiesterase, as a Therapeutic Target to Attenuate Cardiac Hypertrophy by Enhancing Mitochondrial Energy Production

Tan KS, Wang D, Lu Z, Zhang Y, Li S, Lin Y, et al.

Int J Mol Sci, 2021 Oct 06;22(19).
PMID: 34639145 DOI: 10.3390/ijms221910806

Heart failure is the end-stage of all cardiovascular diseases with a ~25% 5-year survival rate, and insufficient mitochondrial energy production to meet myocardial demand is the hallmark of heart failure. Mitochondrial components involved in the regulation of ATP production remain to be fully elucidated. Recently, roles of 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) in the pathophysiological processes of heart diseases have emerged, implicated by evidence that mitochondrial CNPase proteins are associated with mitochondrial integrity under metabolic stress. In this study, a zebrafish heart failure model was established, by employing antisense morpholino oligonucleotides and the CRISPR-Cas9 gene-editing system, which recapitulates heart failure phenotypes including heart dysfunction, pericardial edema, ventricular enlargement, bradycardia, and premature death. The translational implications of CNPase in the pathophysiological process of heart failure were tested in a pressure overload-induced heart hypertrophy model, which was carried out in rats through transverse abdominal aorta constriction (TAAC). AAV9-mediated myocardial delivery of CNPase mitigated the hypertrophic response through the specific hydrolysis of 2'-3'-cyclic nucleotides, supported by the decrease of cardiac hypertrophy and fibrosis, the integrity of mitochondrial ultrastructure, and indicators of heart contractility in the AAV9-TAAC group. Finally, the biometrics of a mitochondrial respiration assay carried out on a Seahorse cellular energy analyzer demonstrated that CNPase protects mitochondrial respiration and ATP production from AngII-induced metabolic stress. In summary, this study provides mechanistic insights into CNPase-2',3'-cyclic nucleotide metabolism that protects the heart from energy starvation and suggests novel therapeutic approaches to treat heart failure by targeting CNPase activity.

Matched MeSH terms: Disease Models, Animal*
Fulltext Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

Fachal L, Aschard H, Beesley J, Barnes DR, Allen J, Kar S, et al.

Nat Genet, 2020 01;52(1):56-73.
PMID: 31911677 DOI: 10.1038/s41588-019-0537-1

Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.

Matched MeSH terms: Genetic Predisposition to Disease*
Antiviral activities of Cholistani plants against common poultry viruses

Shahzad MI, Anwar S, Ashraf H, Manzoor A, Naseer M, Rani U, et al.

Trop Biomed, 2020 Dec 01;37(4):1129-1140.
PMID: 33612765 DOI: 10.47665/tb.37.4.1129

Herbal medicines are becoming more popular and acceptable day by day due to their effectiveness, limited side effects, and cost-effectiveness. Cholistani plants are reported as a rich source of antibacterial, antifungal, antiprotozoal, antioxidant, and anticancer agents. The current study has evaluated antiviral potential of selected Cholistani plants. The whole plants were collected, ground and used in extract formation with n-hexane, ethyl acetate and n-butanol. All the extracts were concentrated by using a rotary evaporator and concentrate was finally dissolved in an appropriate vol of the same solvent. All of the extracts were tested for their antiviral potential by using 9-11 days old chick embryonated eggs. Each extract was tested against the Avian Influenza virus H9N2 strain (AIV), New Castle Disease virus Lasoota strain (NDV), Infectious bronchitis virus (IBV) and an Infectious bursal disease virus (IBDV). Hemagglutination test (HA) and Indirect Hemagglutination (IHA) tests were performed for different viruses. The overall order of the antiviral potential of Cholistani plants against viruses was NDV>IBV>IBDV>AIV. In terms of antiviral activity from extracts, the order of activity was n-butanol>ethyl acetate>n-hexane. The medicinal plants Achyranthes aspera, Neuroda procumbens, Panicum antidotale, Ochthochloa compressa and Suaeda fruticose were very effective against all four poultry viruses through their extracts. The low IC50 values of these extracts confirm the high antiviral potential against these viruses. It is worth to mention that Achyranthes aspera was found positive against IBDV through all its extracts which overcome the problem of unavailability of any known drug against IBDV. In short, the study proved that Cholistani plants are rich source of antiviral agent and their extracts can be used as good source of antiviral drugs both in crude and in purified form.

Matched MeSH terms: Infectious bursal disease virus/drug effects*
Metabolically Healthy Obesity and the Development of Nonalcoholic Fatty Liver Disease

Chang Y, Jung HS, Cho J, Zhang Y, Yun KE, Lazo M, et al.

Am J Gastroenterol, 2016 08;111(8):1133-40.
PMID: 27185080 DOI: 10.1038/ajg.2016.178

OBJECTIVES: The risk of nonalcoholic fatty liver disease (NAFLD) among obese individuals without obesity-related metabolic abnormalities, a condition referred to as metabolically healthy obese (MHO), is largely unexplored. Therefore, we examined the association between body mass index (BMI) categories and the development of NAFLD in a large cohort of metabolically healthy men and women.
METHODS: A cohort study was conducted in 77,425 men and women free of NAFLD and metabolic abnormalities at baseline, who were followed-up annually or biennially for an average of 4.5 years. Being metabolically healthy was defined as not having any metabolic syndrome component and having a homeostasis model assessment of insulin resistance <2.5. The presence of fatty liver was determined using ultrasound.
RESULTS: During 348,193.5 person-years of follow-up, 10,340 participants developed NAFLD (incidence rate, 29.7 per 1,000 person-years). The multivariable adjusted hazard ratios (95% confidence intervals) for incident NAFLD comparing overweight and obese with normal-weight participants were 2.15 (2.06-2.26) and 3.55 (3.37-3.74), respectively. In detailed dose-response analyses, increasing baseline BMI showed a strong and approximately linear relationship with the incidence of NAFLD, with no threshold at no risk. This association was present in both men and women, although it was stronger in women (P for interaction <0.001), and it was evident in all clinically relevant subgroups evaluated, including participants with low inflammation status.
CONCLUSIONS: In a large cohort of strictly defined metabolically healthy men and women, overweight and obesity were strongly and progressively associated with an increased incidence of NAFLD, suggesting that the obese phenotype per se, regardless of metabolic abnormalities, can increase the risk of NAFLD.

Matched MeSH terms: Non-alcoholic Fatty Liver Disease/epidemiology*
Fulltext Differential polarization and the expression of efferocytosis receptor MerTK on M1 and M2 macrophages isolated from coronary artery disease patients

Mohd Idrus FN, Ahmad NS, Hoe CH, Azlan M, Norfuad FA, Yusof Z, et al.

BMC Immunol, 2021 03 24;22(1):21.
PMID: 33761885 DOI: 10.1186/s12865-021-00410-2

BACKGROUND: Differential polarization of macrophage into M1 and M2 mediates atherosclerotic plaque clearance through efferocytosis. Higher expression of Mer proto-oncogene tyrosine kinase (MerTK) on M2 macrophage helps in maintaining macrophage efferocytic efficiency. In healthy individuals, macrophage polarization into M1 and M2 occurs in tissues in concomitance with the acquisition of functional phenotypes depending on specific microenvironment stimuli. However, whether the macrophage differential polarization and MerTK expression vary in coronary artery disease (CAD) patients remain unknown.
OBJECTIVE: This study aimed to elucidate the polarization of M1 and M2 macrophage from CAD patients as well as to investigate the expression of MerTK in these macrophage phenotypes.
METHODS: A total of 14 (n) CAD patients were recruited and subsequently grouped into "no apparent CAD", "non-obstructive CAD" and "obstructive CAD" according to the degree of stenosis. Thirty ml of venous blood was withdrawn to obtain monocyte from the patients. The M1 macrophage was generated by treating the monocyte with GMCSF, LPS and IFN-γ while MCSF, IL-4 and IL-13 were employed to differentiate monocyte into M2 macrophage. After 7 days of polarization, analysis of cell surface differentiation markers (CD86+/CD80+ for M1 and CD206+/CD200R+ for M2) and measurement of MerTK expression were performed using flow cytometry.
RESULTS: Both M1 and M2 macrophage expressed similar level of CD86, CD80 and CD206 in all groups of CAD patients. MerTK expression in no apparent CAD patients was significantly higher in M2 macrophage compared to M1 macrophage [12.58 ± 4.40 vs. 6.58 ± 1.37, p = 0.040].
CONCLUSION: Differential polarization of macrophage into M1 and M2 was highly dynamic and can be varied due to the microenvironment stimuli in atherosclerotic plaque. Besides, higher expression of MerTK in patients with the least coronary obstructive suggest its vital involvement in efferocytosis.

Matched MeSH terms: Coronary Artery Disease/immunology*
Fulltext The prevalence of sexually transmitted diseases among prostitutes in Malaysia

Ramachandran S, Ngeow YF

Genitourin Med, 1990 Oct;66(5):334-6.
PMID: 2245980 DOI: 10.1136/sti.66.5.334

The prevalence of sexually transmitted diseases was determined among 370 prostitutes in Kuala Lumpur, Malaysia. Chlamydial cervicitis (26.5%) was detected more frequently than gonorrhoea (14.25%) and was associated more often with pelvic inflammatory disease. Concurrent infections and asymptomatic infections were common. Seropositivity to hepatitis B and syphilis were 66.3% and 13.6% respectively. Women under 20 years of age had significantly higher rates of infection with Chlamydia trachomatis and hepatitis B virus than older women.
Study site: private clinic, Kuala Lumpur, Malaysia

Matched MeSH terms: Pelvic Inflammatory Disease/microbiology

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links