MyMedR

Displaying publications 1 - 20 of 43 in total

Abstract:

Sort:

Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1

Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.

Autophagy, 2021 Jan;17(1):1-382.
PMID: 33634751 DOI: 10.1080/15548627.2020.1797280

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
Fulltext Identification of common genetic risk variants for autism spectrum disorder

Grove J, Ripke S, Als TD, Mattheisen M, Walters RK, Won H, et al.

Nat Genet, 2019 03;51(3):431-444.
PMID: 30804558 DOI: 10.1038/s41588-019-0344-8

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.
Fulltext The Burden of Mental Disorders in the Eastern Mediterranean Region, 1990-2013

Charara R, Forouzanfar M, Naghavi M, Moradi-Lakeh M, Afshin A, Vos T, et al.

PLoS One, 2017;12(1):e0169575.
PMID: 28095477 DOI: 10.1371/journal.pone.0169575

The Eastern Mediterranean Region (EMR) is witnessing an increase in chronic disorders, including mental illness. With ongoing unrest, this is expected to rise. This is the first study to quantify the burden of mental disorders in the EMR. We used data from the Global Burden of Disease study (GBD) 2013. DALYs (disability-adjusted life years) allow assessment of both premature mortality (years of life lost-YLLs) and nonfatal outcomes (years lived with disability-YLDs). DALYs are computed by adding YLLs and YLDs for each age-sex-country group. In 2013, mental disorders contributed to 5.6% of the total disease burden in the EMR (1894 DALYS/100,000 population): 2519 DALYS/100,000 (2590/100,000 males, 2426/100,000 females) in high-income countries, 1884 DALYS/100,000 (1618/100,000 males, 2157/100,000 females) in middle-income countries, 1607 DALYS/100,000 (1500/100,000 males, 1717/100,000 females) in low-income countries. Females had a greater proportion of burden due to mental disorders than did males of equivalent ages, except for those under 15 years of age. The highest proportion of DALYs occurred in the 25-49 age group, with a peak in the 35-39 years age group (5344 DALYs/100,000). The burden of mental disorders in EMR increased from 1726 DALYs/100,000 in 1990 to 1912 DALYs/100,000 in 2013 (10.8% increase). Within the mental disorders group in EMR, depressive disorders accounted for most DALYs, followed by anxiety disorders. Among EMR countries, Palestine had the largest burden of mental disorders. Nearly all EMR countries had a higher mental disorder burden compared to the global level. Our findings call for EMR ministries of health to increase provision of mental health services and to address the stigma of mental illness. Moreover, our results showing the accelerating burden of mental health are alarming as the region is seeing an increased level of instability. Indeed, mental health problems, if not properly addressed, will lead to an increased burden of diseases in the region.
Fulltext An international multidisciplinary consensus statement on MAFLD and the risk of CVD

Zhou XD, Targher G, Byrne CD, Somers V, Kim SU, Chahal CAA, et al.

Hepatol Int, 2023 Aug;17(4):773-791.
PMID: 37204656 DOI: 10.1007/s12072-023-10543-8

BACKGROUND: Fatty liver disease in the absence of excessive alcohol consumption is an increasingly common condition with a global prevalence of ~ 25-30% and is also associated with cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies its pathogenesis, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been proposed for this condition. MAFLD is closely intertwined with obesity, type 2 diabetes mellitus and atherogenic dyslipidemia, which are established cardiovascular risk factors. Unlike CVD, which has received attention in the literature on fatty liver disease, the CVD risk associated with MAFLD is often underestimated, especially among Cardiologists.
METHODS AND RESULTS: A multidisciplinary panel of fifty-two international experts comprising Hepatologists, Endocrinologists, Diabetologists, Cardiologists and Family Physicians from six continents (Asia, Europe, North America, South America, Africa and Oceania) participated in a formal Delphi survey and developed consensus statements on the association between MAFLD and the risk of CVD. Statements were developed on different aspects of CVD risk, ranging from epidemiology to mechanisms, screening, and management.
CONCULSIONS: The expert panel identified important clinical associations between MAFLD and the risk of CVD that could serve to increase awareness of the adverse metabolic and cardiovascular outcomes of MAFLD. Finally, the expert panel also suggests potential areas for future research.
The rubber tree genome reveals new insights into rubber production and species adaptation

Tang C, Yang M, Fang Y, Luo Y, Gao S, Xiao X, et al.

Nat Plants, 2016 05 23;2(6):16073.
PMID: 27255837 DOI: 10.1038/nplants.2016.73

The Para rubber tree (Hevea brasiliensis) is an economically important tropical tree species that produces natural rubber, an essential industrial raw material. Here we present a high-quality genome assembly of this species (1.37 Gb, scaffold N50 = 1.28 Mb) that covers 93.8% of the genome (1.47 Gb) and harbours 43,792 predicted protein-coding genes. A striking expansion of the REF/SRPP (rubber elongation factor/small rubber particle protein) gene family and its divergence into several laticifer-specific isoforms seem crucial for rubber biosynthesis. The REF/SRPP family has isoforms with sizes similar to or larger than SRPP1 (204 amino acids) in 17 other plants examined, but no isoforms with similar sizes to REF1 (138 amino acids), the predominant molecular variant. A pivotal point in Hevea evolution was the emergence of REF1, which is located on the surface of large rubber particles that account for 93% of rubber in the latex (despite constituting only 6% of total rubber particles, large and small). The stringent control of ethylene synthesis under active ethylene signalling and response in laticifers resolves a longstanding mystery of ethylene stimulation in rubber production. Our study, which includes the re-sequencing of five other Hevea cultivars and extensive RNA-seq data, provides a valuable resource for functional genomics and tools for breeding elite Hevea cultivars.
Fulltext The Tsinghua-Lancet Commission on Healthy Cities in China: unlocking the power of cities for a healthy China

Yang J, Siri JG, Remais JV, Cheng Q, Zhang H, Chan KKY, et al.

Lancet, 2018 05 26;391(10135):2140-2184.
PMID: 29678340 DOI: 10.1016/S0140-6736(18)30486-0
Fulltext Rapid Targeted Next-Generation Sequencing Platform for Molecular Screening and Clinical Genotyping in Subjects with Hemoglobinopathies

Shang X, Peng Z, Ye Y, Asan, Zhang X, Chen Y, et al.

EBioMedicine, 2017 Sep;23:150-159.
PMID: 28865746 DOI: 10.1016/j.ebiom.2017.08.015

Hemoglobinopathies are among the most common autosomal-recessive disorders worldwide. A comprehensive next-generation sequencing (NGS) test would greatly facilitate screening and diagnosis of these disorders. An NGS panel targeting the coding regions of hemoglobin genes and four modifier genes was designed. We validated the assay by using 2522 subjects affected with hemoglobinopathies and applied it to carrier testing in a cohort of 10,111 couples who were also screened through traditional methods. In the clinical genotyping analysis of 1182 β-thalassemia subjects, we identified a group of additional variants that can be used for accurate diagnosis. In the molecular screening analysis of the 10,111 couples, we detected 4180 individuals in total who carried 4840 mutant alleles, and identified 186 couples at risk of having affected offspring. 12.1% of the pathogenic or likely pathogenic variants identified by our NGS assay, which were undetectable by traditional methods. Compared with the traditional methods, our assay identified an additional at-risk 35 couples. We describe a comprehensive NGS-based test that offers advantages over the traditional screening/molecular testing methods. To our knowledge, this is among the first large-scale population study to systematically evaluate the application of an NGS technique in carrier screening and molecular diagnosis of hemoglobinopathies.
Prevalence, complete genome, and metabolic potentials of a phylogenetically novel cyanobacterial symbiont in the coral-killing sponge, Terpios hoshinota

Chen YH, Chen HJ, Yang CY, Shiu JH, Hoh DZ, Chiang PW, et al.

Environ Microbiol, 2021 Oct 27.
PMID: 34708512 DOI: 10.1111/1462-2920.15824

Terpios hoshinota is an aggressive, space-competing sponge that kills various stony corals. Outbreaks of this species have led to intense damage to coral reefs in many locations. Here, the first large-scale 16S rRNA gene survey across three oceans revealed that bacteria related to the taxa Prochloron, Endozoicomonas, SAR116, Ruegeria, and unclassified Proteobacteria were prevalent in T. hoshinota. A Prochloron-related bacterium was the most dominant and prevalent cyanobacterium in T. hoshinota. The complete genome of this uncultivated cyanobacterium and pigment analysis demonstrated that it has phycobiliproteins and lacks chlorophyll b, which is inconsistent with the definition of Prochloron. Furthermore, the cyanobacterium was phylogenetically distinct from Prochloron, strongly suggesting that it should be a sister taxon to Prochloron. Therefore, we proposed this symbiotic cyanobacterium as a novel species under the new genus Candidatus Paraprochloron terpiosi. Comparative genomic analyses revealed that 'Paraprochloron' and Prochloron exhibit distinct genomic features and DNA replication machinery. We also characterized the metabolic potentials of 'Paraprochloron terpiosi' in carbon and nitrogen cycling and propose a model for interactions between it and T. hoshinota. This study builds a foundation for the study of the T. hoshinota microbiome and paves the way for better understanding of ecosystems involving this coral-killing sponge.
Everolimus-Eluting Stents or Bypass Surgery for Multivessel Coronary Artery Disease: Extended Follow-Up Outcomes of Multicenter Randomized Controlled BEST Trial

Ahn JM, Kang DY, Yun SC, Ho Hur S, Park HJ, Tresukosol D, et al.

Circulation, 2022 Nov 22;146(21):1581-1590.
PMID: 36121700 DOI: 10.1161/CIRCULATIONAHA.122.062188

BACKGROUND: Long-term comparative outcomes after percutaneous coronary intervention (PCI) with everolimus-eluting stents and coronary artery bypass grafting (CABG) are limited in patients with multivessel coronary artery disease.
METHODS: This prospective, multicenter, randomized controlled trial was conducted in 27 international heart centers and was designed to randomly assign 1776 patients with angiographic multivessel coronary artery disease to receive PCI with everolimus-eluting stents or CABG. After inclusion of 880 patients (438 in the PCI group and 442 in the CABG group) between July 2008 and September 2013, the study was terminated early because of slow enrollment. The primary end point was the composite of death from any cause, myocardial infarction, or target vessel revascularization.
RESULTS: During a median follow-up of 11.8 years (interquartile range, 10.6-12.5 years; maximum, 13.7 years), the primary end point occurred in 151 patients (34.5%) in the PCI group and 134 patients (30.3%) in the CABG group (hazard ratio [HR], 1.18 [95% CI, 0.88-1.56]; P=0.26). No significant differences were seen in the occurrence of a safety composite of death, myocardial infarction, or stroke between groups (28.8% and 27.1%; HR, 1.07 [95% CI, 0.75-1.53]; P=0.70), as well as the occurrence of death from any cause (20.5% and 19.9%; HR, 1.04 [95% CI, 0.65-1.67]; P=0.86). However, spontaneous myocardial infarction (7.1% and 3.8%; HR, 1.86 [95% CI, 1.06-3.27]; P=0.031) and any repeat revascularization (22.6% and 12.7%; HR, 1.92 [95% CI, 1.58-2.32]; P<0.001) were more frequent after PCI than after CABG.
CONCLUSIONS: In patients with multivessel coronary artery disease, there were no significant differences between PCI and CABG in the incidence of major adverse cardiac events, the safety composite end point, and all-cause mortality during the extended follow-up.
REGISTRATION: URL: https://www.
CLINICALTRIALS: gov; Unique identifiers: NCT05125367 and NCT00997828.
Decadal stability in coral cover could mask hidden changes on reefs in the East Asian Seas

Chan YKS, Affendi YA, Ang PO, Baria-Rodriguez MV, Chen CA, Chui APY, et al.

Commun Biol, 2023 Jun 10;6(1):630.
PMID: 37301948 DOI: 10.1038/s42003-023-05000-z

Coral reefs in the Central Indo-Pacific region comprise some of the most diverse and yet threatened marine habitats. While reef monitoring has grown throughout the region in recent years, studies of coral reef benthic cover remain limited in spatial and temporal scales. Here, we analysed 24,365 reef surveys performed over 37 years at 1972 sites throughout East Asia by the Global Coral Reef Monitoring Network using Bayesian approaches. Our results show that overall coral cover at surveyed reefs has not declined as suggested in previous studies and compared to reef regions like the Caribbean. Concurrently, macroalgal cover has not increased, with no indications of phase shifts from coral to macroalgal dominance on reefs. Yet, models incorporating socio-economic and environmental variables reveal negative associations of coral cover with coastal urbanisation and sea surface temperature. The diversity of reef assemblages may have mitigated cover declines thus far, but climate change could threaten reef resilience. We recommend prioritisation of regionally coordinated, locally collaborative long-term studies for better contextualisation of monitoring data and analyses, which are essential for achieving reef conservation goals.
Everolimus-Eluting Stents or Bypass Surgery for Multivessel Disease in Diabetics: The BEST Extended Follow-Up Study

Kim H, Kang DY, Ahn JM, Lee J, Choi Y, Hur SH, et al.

JACC Cardiovasc Interv, 2023 Oct 09;16(19):2412-2422.
PMID: 37821187 DOI: 10.1016/j.jcin.2023.07.028

BACKGROUND: Diabetes mellitus is associated with more complex coronary artery diseases. Coronary artery bypass grafting (CABG) is a preferred revascularization strategy over percutaneous coronary intervention (PCI) in diabetics with multivessel coronary artery disease (MVD).
OBJECTIVES: This study sought to examine the different prognostic effects of revascularization strategies according to the diabetes status from the randomized BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease) trial.
METHODS: Patients (n = 880) with MVD were randomly assigned to undergo PCI with an everolimus-eluting stent vs CABG stratified by diabetics (n = 363) and nondiabetics (n = 517). The primary endpoint was the composite of death, myocardial infarction, or target vessel revascularization during a median follow-up of 11.8 years (IQR: 10.6-12.5 years).
RESULTS: In diabetics, the primary endpoint rate was significantly higher in the PCI group than in the CABG group (43% and 32%; HR: 1.53; 95% CI: 1.12-2.08; P = 0.008). However, in nondiabetics, no significant difference was found between the groups (PCI group, 29%; CABG group, 29%; HR: 0.97; 95% CI: 0.67-1.39; P = 0.86; Pinteraction= 0.009). Irrespective of the presence of diabetes, no significant between-group differences were found in the rate of a safety composite of death, myocardial infarction, or stroke and mortality rate. However, the rate of any repeat revascularization was significantly higher in the PCI group than in the CABG group.
CONCLUSIONS: In diabetics with MVD, CABG was associated with better clinical outcomes than PCI. However, the mortality rate was similar between PCI and CABG irrespective of diabetes status during an extended follow-up. (Ten-Year Outcomes of Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease [BEST Extended], NCT05125367; Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease [BEST], NCT00997828).
Fulltext Report on hematopoietic cell transplantations performed in 2018/2019 focusing on the trends of selection of stem cell sources in the Asia-Pacific region: APBMT Activity Survey

Iida M, Liu K, Huang XJ, Huang H, Kuwatsuka Y, Moon JH, et al.

Blood Cell Ther, 2023 Nov 25;6(4):114-123.
PMID: 38149021 DOI: 10.31547/bct-2023-015

The number of hematopoietic stem cell transplantations (HCTs) is increasing annually worldwide, and the Asia-Pacific (AP) region is no exception. We report on the absolute number of HCTs in 2018 and 2019 and the trends in graft selection and disease indication in the past few decades. In 2018, 24,292 HCTs were performed in the AP region, of which 8,754 (36.0%) were autologous and 15,538 (64.0%) were allogeneic. Among the allogeneic HCTs, 10,552 (67.9%) of the recipients were related to their donors, whereas 4,986 (32.1%) were unrelated. In 2019, 27,583 HCTs were reported, of which 17,613 (63.9%) were allogeneic and 9,970 (36.1%) were autologous. Although, in 2010, there was a nearly equal number of related and unrelated HCTs, the difference has shown an annual increase, with more than double (2.05) the number of related than unrelated HCTs in 2019. Recent trends in the AP region show that peripheral blood has overwhelmingly surpassed the bone marrow as a graft source for both related and unrelated HCTs, with the haploidentical donor type being preferred; however, their trends in each country/region were quite different among countries/regions. In 2019, the main conditions requiring HCT were acute myelogenous leukemia (n=6,629 [24.0%]), plasma cell disorders (PCD) (n=4,935 [17.9%]), malignant lymphoma (ML) (n=4,106 [14.9%]), acute lymphoblastic leukemia (AML) (n=3,777 [13.7%]), myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm (n=1,913 [6.9%]), severe aplastic anemia (n=1,671 [6.1%]), and hemoglobinopathy (n=910 [3.3%]). PCD and ML were the main indications for autologous HCT, and the number of PCD cases has grown more prominent than the corresponding of ML. The increased number of allogeneic transplants for hemoglobinopathy remains prominent, as well as that of AML and acute lymphocytic leukemia for the past 5 years. There was a significant regional variation in the number of facilities performing HCTs, ranging from one in Mongolia and Nepal to 313 in Japan, and differing regional densities varying from 0.1 in Indonesia and Pakistan to 24.7 in Japan. The total transplant density per 10 million population in each country/region also differed (0.2 in Indonesia and 627 in New Zealand). This annual Activity Survey aims to help all participating countries/regions understand the changes in HCT, serve as an asset in promoting HCT activities in the AP region, and be used as a reference for comparison with other registries from Europe and the United States.
Fulltext Population genetics and demography of the coral-killing cyanobacteriosponge, Terpios hoshinota, in the Indo-West Pacific

Chow SW, Keshavmurthy S, Reimer JD, de Voogd N, Huang H, Wang JT, et al.

PeerJ, 2022;10:e13451.
PMID: 35669953 DOI: 10.7717/peerj.13451

The first occurrence of the cyanobacteriosponge Terpios hoshinota was reported from coral reefs in Guam in 1973, but was only formally described in 1993. Since then, the invasive behavior of this encrusting, coral-killing sponge has been observed in many coral reefs in the West Pacific. From 2015, its occurrence has expanded westward to the Indian Ocean. Although many studies have investigated the morphology, ecology, and symbiotic cyanobacteria of this sponge, little is known of its population genetics and demography. In this study, a mitochondrial cytochrome oxidase I (COI) fragment and nuclear ribosomal internal transcribed spacer 2 (ITS2) were sequenced to reveal the genetic variation of T. hoshinota collected from 11 marine ecoregions throughout the Indo-West Pacific. Both of the statistical parsimony networks based on the COI and nuclear ITS2 were dominated by a common haplotype. Pairwise F ST and Isolation-by-distance by Mantel test of ITS2 showed moderate gene flow existed among most populations in the marine ecoregions of West Pacific, Coral Triangle, and Eastern Indian Ocean, but with a restricted gene flow between these regions and Maldives in the Central Indian Ocean. Demographic analyses of most T. hoshinota populations were consistent with the mutation-drift equilibrium, except for the Sulawesi Sea and Maldives, which showed bottlenecks following recent expansion. Our results suggest that while long-range dispersal might explain the capability of T. hoshinota to spread in the IWP, stable population demography might account for the long-term persistence of T. hoshinota outbreaks on local reefs.
Fulltext Inflammatory bowel disease and associated cardiovascular disease outcomes: A systematic review

Jaiswal V, Batra N, Dagar M, Butey S, Huang H, Chia JE, et al.

Medicine (Baltimore), 2023 Feb 10;102(6):e32775.
PMID: 36820570 DOI: 10.1097/MD.0000000000032775

BACKGROUND: There is limited and conflicting data available regarding the cardiovascular disease outcomes associated with inflammatory bowel disease (IBD).
OBJECTIVE: We aim to perform a systematic review to evaluate the cardiovascular outcomes and mortality associated with IBD patients.
METHODS: A systematic literature search has been performed on PubMed, Embase, Cochrane, and Scopus from inception till May 2022 without any language restrictions.
RESULTS: A total of 2,029,941 patients were included in the analysis from 16 studies. The mean age of the patients was 45.6 years. More females were found compared with males (57% vs 43%). The most common risk factors for cardiovascular disease (CVD) included smoking (24.19%) and alcohol (4.60%). The most common comorbidities includes hypertension (30%), diabetes mellitus (14.41%), dyslipidemia (18.42%), previous CVD (22%), and renal disease (10%). Among outcomes, all-cause mortality among IBD patients was 1.66%; ulcerative colitis (UC): 15.92%; and Crohn disease (CD): 0.30%. Myocardial Infarction (MI) among IBD patients were 1.47%, UC: 30.96%; and CD: 34.14%. CVD events among IBD patients were 1.95%. Heart failure events among IBD patients were 5.49%, stroke events among IBD patients were 0.95%, UC: 2.63%, and CD: 2.41%, respectively.
CONCLUSION: IBD patients are at higher risk for adverse cardiovascular outcomes, especially in women. Although there remains a lack of concrete treatment algorithms and assessment parameters that better characterize IBD risk factors, nutritional modifications and physical activity should be at the forefront of CVD prevention in IBD.
Fulltext Circadian rhythm in systemic autoimmune conditions: Potential of chrono-immunology in clinical practice: A narrative review

Awuah WA, Huang H, Kalmanovich J, Mehta A, Mikhailova T, Ng JC, et al.

Medicine (Baltimore), 2023 Aug 11;102(32):e34614.
PMID: 37565922 DOI: 10.1097/MD.0000000000034614

The circadian rhythm (CR) is a fundamental biological process regulated by the Earth's rotation and solar cycles. It plays a critical role in various bodily functions, and its dysregulation can have systemic effects. These effects impact metabolism, redox homeostasis, cell cycle regulation, gut microbiota, cognition, and immune response. Immune mediators, cycle proteins, and hormones exhibit circadian oscillations, supporting optimal immune function and defence against pathogens. Sleep deprivation and disruptions challenge the regulatory mechanisms, making immune responses vulnerable. Altered CR pathways have been implicated in diseases such as diabetes, neurological conditions, and systemic autoimmune diseases (SADs). SADs involve abnormal immune responses to self-antigens, with genetic and environmental factors disrupting self-tolerance and contributing to conditions like Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Inflammatory Myositis. Dysregulated CR may lead to increased production of pro-inflammatory cytokines, contributing to the systemic responses observed in SADs. Sleep disturbances significantly impact the quality of life of patients with SADs; however, they are often overlooked. The relationship between sleep and autoimmune conditions, whether causal or consequential to CR dysregulation, remains unclear. Chrono-immunology investigates the role of CR in immunity, offering potential for targeted therapies in autoimmune conditions. This paper provides an overview of the connections between sleep and autoimmune conditions, highlighting the importance of recognizing sleep disturbances in SADs and the need for further research into the complex relationship between the CR and autoimmune diseases.
Catalysis by Glomerella cingulata cutinase requires conformational cycling between the active and inactive states of its catalytic triad

Nyon MP, Rice DW, Berrisford JM, Hounslow AM, Moir AJ, Huang H, et al.

J Mol Biol, 2009 Jan 9;385(1):226-35.
PMID: 18983850 DOI: 10.1016/j.jmb.2008.10.050

Cutinase belongs to a group of enzymes that catalyze the hydrolysis of esters and triglycerides. Structural studies on the enzyme from Fusarium solani have revealed the presence of a classic catalytic triad that has been implicated in the enzyme's mechanism. We have solved the crystal structure of Glomerella cingulata cutinase in the absence and in the presence of the inhibitors E600 (diethyl p-nitrophenyl phosphate) and PETFP (3-phenethylthio-1,1,1-trifluoropropan-2-one) to resolutions between 2.6 and 1.9 A. Analysis of these structures reveals that the catalytic triad (Ser136, Asp191, and His204) adopts an unusual configuration with the putative essential histidine His204 swung out of the active site into a position where it is unable to participate in catalysis, with the imidazole ring 11 A away from its expected position. Solution-state NMR experiments are consistent with the disrupted configuration of the triad observed crystallographically. H204N, a site-directed mutant, was shown to be catalytically inactive, confirming the importance of this residue in the enzyme mechanism. These findings suggest that, during its catalytic cycle, cutinase undergoes a significant conformational rearrangement converting the loop bearing the histidine from an inactive conformation, in which the histidine of the triad is solvent exposed, to an active conformation, in which the triad assumes a classic configuration.
Fulltext Molecular epidemiology demonstrates that imported and local strains circulated during the 2014 dengue outbreak in Guangzhou, China

Li G, Pan P, He Q, Kong X, Wu K, Zhang W, et al.

Virol Sin, 2017 Feb;32(1):63-72.
PMID: 28120220 DOI: 10.1007/s12250-016-3872-8

The dengue virus (DENV) is a vital global public health issue. The 2014 dengue epidemic in Guangzhou, China, caused approximately 40,000 cases of infection and five deaths. We carried out a comprehensive investigation aimed at identifying the transmission sources in this dengue epidemic. To analyze the phylogenetics of the 2014 dengue strains, the envelope (E) gene sequences from 17 viral strains isolated from 168 dengue patient serum samples were sequenced and a phylogenetic tree was reconstructed. All 17 strains were serotype I strains, including 8 genotype I and 9 genotype V strains. Additionally, 6 genotype I strains that were probably introduced to China from Thailand before 2009 were widely transmitted in the 2013 and 2014 epidemics, and they continued to circulate until 2015, with one affinis strain being found in Singapore. The other 2 genotype I strains were introduced from the Malaya Peninsula in 2014. The transmission source of the 9 genotype V strains was from Malaysia in 2014. DENVs of different serotypes and genotypes co-circulated in the 2014 dengue outbreak in Guangzhou. Moreover, not only had DENV been imported to Guangzhou, but it had also been gradually exported, as the viruses exhibited an enzootic transmission cycle in Guangzhou.
Fulltext Artificial Intelligence in Pediatric Cardiology: A Scoping Review

Sethi Y, Patel N, Kaka N, Desai A, Kaiwan O, Sheth M, et al.

J Clin Med, 2022 Nov 29;11(23).
PMID: 36498651 DOI: 10.3390/jcm11237072

The evolution of AI and data science has aided in mechanizing several aspects of medical care requiring critical thinking: diagnosis, risk stratification, and management, thus mitigating the burden of physicians and reducing the likelihood of human error. AI modalities have expanded feet to the specialty of pediatric cardiology as well. We conducted a scoping review searching the Scopus, Embase, and PubMed databases covering the recent literature between 2002-2022. We found that the use of neural networks and machine learning has significantly improved the diagnostic value of cardiac magnetic resonance imaging, echocardiograms, computer tomography scans, and electrocardiographs, thus augmenting the clinicians' diagnostic accuracy of pediatric heart diseases. The use of AI-based prediction algorithms in pediatric cardiac surgeries improves postoperative outcomes and prognosis to a great extent. Risk stratification and the prediction of treatment outcomes are feasible using the key clinical findings of each CHD with appropriate computational algorithms. Notably, AI can revolutionize prenatal prediction as well as the diagnosis of CHD using the EMR (electronic medical records) data on maternal risk factors. The use of AI in the diagnostics, risk stratification, and management of CHD in the near future is a promising possibility with current advancements in machine learning and neural networks. However, the challenges posed by the dearth of appropriate algorithms and their nascent nature, limited physician training, fear of over-mechanization, and apprehension of missing the 'human touch' limit the acceptability. Still, AI proposes to aid the clinician tomorrow with precision cardiology, paving a way for extremely efficient human-error-free health care.
Multilevel Pharmacological Effects of Antipsychotics in Potential Glioblastoma Treatment

Awuah WA, Kalmanovich J, Mehta A, Huang H, Abdul-Rahman T, Cheng Ng J, et al.

Curr Top Med Chem, 2023;23(5):389-402.
PMID: 36593538 DOI: 10.2174/1568026623666230102095836

Glioblastoma Multiforme (GBM) is a debilitating type of brain cancer with a high mortality rate. Despite current treatment options such as surgery, radiotherapy, and the use of temozolomide and bevacizumab, it is considered incurable. Various methods, such as drug repositioning, have been used to increase the number of available treatments. Drug repositioning is the use of FDA-approved drugs to treat other diseases. This is possible because the drugs used for this purpose have polypharmacological effects. This means that these medications can bind to multiple targets, resulting in multiple mechanisms of action. Antipsychotics are one type of drug used to treat GBM. Antipsychotics are a broad class of drugs that can be further subdivided into typical and atypical classes. Typical antipsychotics include chlorpromazine, trifluoperazine, and pimozide. This class of antipsychotics was developed early on and primarily works on dopamine D2 receptors, though it can also work on others. Olanzapine and Quetiapine are examples of atypical antipsychotics, a category that was created later. These medications have a high affinity for serotonin receptors such as 5- HT2, but they can also act on dopamine and H1 receptors. Antipsychotic medications, in the case of GBM, also have other effects that can affect multiple pathways due to their polypharmacological effects. These include NF-B suppression, cyclin deregulation, and -catenin phosphorylation, among others. This review will delve deeper into the polypharmacological, the multiple effects of antipsychotics in the treatment of GBM, and an outlook for the field's future progression.
NeuroVerse: neurosurgery in the era of Metaverse and other technological breakthroughs

Kundu M, Ng JC, Awuah WA, Huang H, Yarlagadda R, Mehta A, et al.

Postgrad Med J, 2023 May 22;99(1170):240-243.
PMID: 36892407 DOI: 10.1093/postmj/qgad002

The tremendous evolution in modern technology has led to a paradigm shift in neurosurgery. The latest advancements such as augmented reality, virtual reality, and mobile applications have been incorporated into neurosurgical practice. NeuroVerse, representing the application of the metaverse in neurosurgery, brings enormous potential to neurology and neurosurgery. Implementation of NeuroVerse could potentially elevate neurosurgical and interventional procedures, enhance medical visits and patient care, and reshape neurosurgical training. However, it is also vital to consider the challenges that may be associated with its implementation, such as privacy issues, cybersecurity breaches, ethical concerns, and widening of existing healthcare inequalities. NeuroVerse adds phenomenal dimensions to the neurosurgical environment for patients, doctors, and trainees, and represents an incomparable advancement in the delivery of medicine. Therefore, more research is needed to encourage widespread use of the metaverse in healthcare, particularly focusing on the areas of morality and credibility. Although the metaverse is expected to expand rapidly during and after the COVID-19 pandemic, it remains to be seen whether it represents an emerging technology that will revolutionize our society and healthcare or simply an immature condition of the future.

Filters

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

External Links