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Uncovering the impact of alcohol on internal organs and reproductive health:Exploring TLR4/NF-kB and CYP2E1/ROS/Nrf2 pathways

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Animal Models and Experimental medicine 2024年第4期7卷 444-459页

作者： Eason Qi Zheng Kong Vetriselvan Subramaniyan Natasha Sura Anak Lubau Pharmacology Unit Jeffrey Cheah School of Medicine and Health SciencesMonash University MalaysiaSubang JayaSelangorMalaysia Center for Global health Research Saveetha Medical CollegeSaveetha Institute of Medical and Technical SciencesChennaiTamil NaduIndia

This review delves into the detrimental impact of alcohol consumption on internal organs and reproductive health,elucidating the underlying mechanisms involving the Toll-like receptor 4(TLR4)/Nuclear factor kappa light chain enhancer of activated B cells(NF-kB)pathway and the Cytochrome P4502E1(CYP2E1)/reactive oxygen spe-cies(ROS)/nuclear factor erythroid 2-related factor 2(Nrf2)*** TLR4/NF-kB pathway,crucial for inflammatory and immune responses,triggers the production of pro-inflammatory agents and type-1 interferon,disrupting the balance between inflammatory and antioxidant responses when tissues are chronically exposed to ***-induced dysbiosis in gut microbes heightens gut wall permeability to pathogen-associated molecular patterns(PAMPs),leading to liver cell infection and subsequent ***,CYP2E1-mediated alcohol metabolism gen-erates ROS,causing oxidative stress and damaging cells,lipids,proteins,and deoxy-ribonucleic acid(DNA).To counteract this inflammatory imbalance,Nrf2 regulates gene expression,inhibiting inflammatory progression and promoting antioxidant *** alcohol intake results in elevated liver enzymes(ADH,CYP2E1,and catalase),ROS,NADH,acetaldehyde,and acetate,leading to damage in vital organs such as the heart,brain,and ***,alcohol negatively affects reproduc-tive health by inhibiting the hypothalamic-pituitary-gonadal axis,causing infertility in both men and *** findings underscore the profound health concerns associated with alcohol-induced damage,emphasizing the need for public awareness regarding the intricate interplay between immune responses and the multi-organ im-pacts of alcohol consumption.

关键词： alcohol health impact inflammation metabolism molecular pathways

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Autophagy and mitophagy as potential therapeutic targets in diabetic heart condition:Harnessing the power of nanotheranostics

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Asian Journal of Pharmaceutical sciences 2024年第3期19卷 79-101页

作者： Sagnik Nag Oishi Mitra Bhanu Maturi Simran Preet Kaur Ankita Saini Muskan Nama Soumik Roy Souvik Samanta Leena Chacko Rohan Dutta Suresh Babu Sayana Vetriselvan Subramaniyan Jasvinder Singh Bhatti Ramesh Kandimalla jeffrey cheah school of medicine and health sciences Monash University MalaysiaJalan Lagoon Selatan47500 Bandar SunwaySelangorMalaysia Department of Bio-sciences School of Bio-Sciences&Technology(SBST)Vellore Institute of Technology(VIT)Tiruvalam RoadVellore 632014Tamil NaduIndia Department of Internal medicine University of Alabama at BirminghamBirminghamALUSA Department of Microbiology University of Delhi(South Campus)Benito Juarez RoadNew Delhi 110021India Department of Biotechnology Indian Institute of TechnologyHyderabad(IIT-H)SangareddyTelangana 502284India BioAnalytical Lab Meso Scale Discovery1601 Research BlvdRockvilleMDUSA Department of Pharmacology Government Medical CollegeSuryapetTelanganaIndia Laboratory of Translational medicine and Nanotherapeutics Department of Human Genetics and Molecular MedicineSchool of Health SciencesCentral University of PunjabBathindaIndia Department of Biochemistry Kakatiya Medical CollegeWarangal 506007India

Autophagy and mitophagy pose unresolved challenges in understanding the pathology of diabetic heart condition(DHC),which encompasses a complex range of cardiovascular issues linked to diabetes and associated *** significant progress in reducing mortality rates from cardiovascular diseases(CVDs),heart failure remains a major cause of increased morbidity among diabetic *** cellular processes are essential for maintaining cellular balance and removing damaged or dysfunctional components,and their involvement in the development of diabetic heart disease makes them attractive targets for diagnosis and *** a variety of conventional diagnostic and therapeutic strategies are available,DHC continues to present a significant ***-of-care diagnostics,supported by nanobiosensing techniques,offer a promising alternative for these complex *** conventional medications have been widely used in DHC patients,they raise several concerns regarding various physiological *** medicine places great emphasis on the application of nanotechnology to target autophagy and mitophagy in DHC,offering a promising approach to deliver drugs beyond the limitations of traditional *** article aims to explore the potential connections between autophagy,mitophagy and DHC,while also discussing the promise of nanotechnology-based theranostic interventions that specifically target these molecular pathways.

关键词： Autophagy Diabetes Diabetic heart condition Mitophagy Nanotheranostics Nanomedicine

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Storylines of family medicine Ⅺ:professional identity formation—nurturing one’s own story

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Family medicine and Community health 2024年第S3期12卷 99-108页

作者： William B Ventres Leslie A Stone Hamish J Wilson Sumi M Sexton David J Doukas Jessica P Cerdena David M Kelley Michael D Fetters jeffrey J Haney John J Frey III Family and Preventive medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA General Practice and Rural health University of Otago Dunedin School of MedicineDunedinNew Zealand Family medicine Georgetown University School of MedicineWashingtonDistrict of ColumbiaUSA Family and Community medicine Tulane University School of MedicineNew OrleansLouisianaUSA Family medicine Residency Program Middlesex HealthMiddletownConnecticutUSA Family medicine University of Michigan Medical SchoolAnn ArborMichiganUSA Medical Education and Clinical sciences Washington State UniversitySpokaneWashingtonUSA Family medicine and Community health University of Wisconsin-Madison School of Medicine and Public HealthMadisonWisconsinUSA

Storylines of Family medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine,as interpreted by individual family physicians and medical educators in the USA and elsewhere around the ***‘Ⅺ:professional identity formation—nurturing one’s own story’,authors address the following themes:‘The social construction of professional identity’,‘On becoming a family physician’,‘What’s on the test?—professionalism for family physicians’,‘The ugly doc-ling’,‘Teachers—the essence of who we are’,‘Family medicine research—it starts in the clinic’,‘Socially accountability in medical education’,‘Personal philosophy and how to find it’and‘Teaching and learning with Storylines of Family medicine’.May these essays encourage readers to find their own creative spark in medicine.

关键词： own becoming professional

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Storylines of family medicine Ⅳ:perspectives on practice—lenses of appreciation

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Family medicine and Community health 2024年第S3期12卷 33-42页

作者： William B Ventres Leslie A Stone Radeeb Akhtar jeffrey M Ring Lucy M Candib Erick Messias Ronald M Epstein Marc Tunzi Amy L Lee Christopher P Morley Carina M Brown David Slawson Jill Konkin David G Campbell Ian Couper Susan Williams Robert Brooks Lucie Walters Family and Preventive medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA Family medicine and Community health Icahn School of Medicine at Mount SinaiNew YorkNew YorkUSA Independent health Psychologist Los AngelesCaliforniaUSA Family medicine and Community health UMass Chan Medical SchoolWorcesterMassachusettsUSA Psychiatry and Behavioral Neurosciences Saint Louis University School of MedicineSaint LouisMissouriUSA Family medicine University of Rochester Medical CenterRochesterNew YorkUSA Family medicine Residency Program Natividad Medical CenterSalinasCaliforniaUSA Family medicine Tufts University School of MedicineBostonMassachusettsUSA Public health and Preventive medicine SUNY Upstate Medical UniversitySyracuseNew YorkUSA Cone health Family medicine Residency The University of North Carolina School of MedicineGreensboroNorth CarolinaUSA Family medicine Atrium HealthCharlotteNorth CarolinaUSA Family medicine University of Alberta Faculty of Medicine&DentistryEdmontonAlbertaCanada Cunninghame Arm Medical Centre Australian College of Rural and Remote MedicineLakes EntranceQueenslandAustralia Ukwanda Centre for Rural health Stellenbosch University Faculty of Medicine and Health SciencesCape TownWestern CapeSouth Africa Adelaide Rural Clinical school The University of AdelaideAdelaideSouth AustraliaAustralia Department of Rural health Broken Hill UniversityBroken HillNew South WalesAustralia Adelaide Rural Clinical school The University of Adelaide Faculty of Health and Medical SciencesMount GambierSouth AustraliaAustralia

Storylines of Family medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine,as interpreted by individual family physicians and medical educators in the USA and elsewhere around the ***‘Ⅳ:perspectives on practice—lenses of appreciation’,authors address the following themes:‘Relational connections in the doctor–patient partnership’,‘Feminism and family medicine’,‘Positive family medicine’,‘Mindful practice’,‘The new,old ethics of family medicine’,‘Public health,prevention and populations’,‘Information mastery in family medicine’and‘Clinical courage.’May readers nurture their curiosity through these essays.

关键词： thematic illustration doctor

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Patients’experiences with‘sludge’(administrative burden)in the cancer screening process and its relationship with screening completion,experience and health system distrust

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Family medicine and Community health 2024年第S2期12卷 8-17页

作者： Michelle S Rockwell Brianna Chang Vivian Zagarese Jamie K Turner Ally Southworth YingXing Wu Paul Yeaton Li Li jeffrey S Stein Sarah H Parker John W Epling Department of Family and Community medicine Virginia Tech Carilion School of MedicineRoanokeVirginiaUSA Department of Family and Community medicine Carilion ClinicRoanokeVirginiaUSA Virginia Tech Carilion school of medicine RoanokeVirginiaUSA Department of health Systems and Implementation Science Virginia Tech Carilion School of MedicineRoanokeVirginiaUSA Graduate Program in Translational Biology Medicineand HealthVirginia TechRoanokeVirginiaUSA health Analytics Research Team Carilion ClinicRoanokeVirginiaUSA Division of Gastroenterology Department of Internal MedicineCarilion ClinicRoanokeVirginiaUSA Department of Family medicine University of Virginia School of MedicineCharlottesvilleVirginiaUSA Center for health Behaviors Research Fralin Biomedical Research Institute at VTCRoanokeVirginiaUSA

Objective‘Sludge’refers to administrative burdens or frictions that preclude people from getting what they want or need(eg,duplicative forms,complicated instructions,long waiting times).This mixed methods study evaluated patients’perceptions of sludge in the colorectal cancer(CRC)screening process and some impacts of this *** We employed an exploratory sequential mixed methods study design that comprised patient interviews and a patient *** interviews informed final survey revisions and captured contextual data about patients’experiences with *** transcripts were inductively and deductively analysed to identify overarching *** survey quantified sludge,delayed or forgone screenings,screening experience(Net Promoter Score)and health system distrust(health System Distrust Scale).We usedχ2 or t-tests for univariable comparisons and logistic or linear regressions to evaluate the association between cumulative sludge score and delayed or forgone screenings,screening experience and health system *** were integrated for *** Southeastern United *** Patients who were 45–75 years of age,at average risk for CRC and had either completed or been referred for CRC screening(colonoscopy or stool-based test)within the previous 12 *** 22 interview participants and 255 survey participants completed the study.38(15%)survey participants rated their screening experience as poor(Net Promoter Score=0–7 out of 10).The mean(SD)health System Distrust Scale score was 22.4(6.3)out of 45 possible points(higher score=greater distrust).Perceptions of sludge in the CRC screening process varied,with long waiting times and burdensome communication being the most common sources(58%and 35%of participants,respectively).Sludge was positively associated with delayed or forgone screenings(OR=1.42,95%CI 1.28,1.57,phealth system distrust(β=0.47,p

关键词： sludge screening burden

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Storylines of family medicine Ⅰ:framing family medicine–history,values and perspectives

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Family medicine and Community health 2024年第S3期12卷 2-11页

作者： William B Ventres Leslie A Stone Kathleen T Rowland Richard H Streiffer Michael D Macechko Julia A Roulier jeffrey M Borkan Larry A Green Family and Preventive medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA Family and Preventive medicine Rush Medical College of Rush UniversityChicagoIllinoisUSA College of Community health sciences University of AlabamaTuscaloosaAlabamaUSA UAMS Northwest Regional Campus Family medicine Residency Program FayettevilleArkansasUSA UAMS North Central Regional Campus Family medicine Residency Program BatesvilleArkansasUSA Family medicine Brown University Warren Alpert Medical SchoolProvidenceRhode IslandUSA University of Colorado school of medicine AuroraColoradoUSA

Storylines of Family medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine,as interpreted by individual family physicians and medical educators in the USA and elsewhere around the ***‘Ⅰ:framing family medicine—history,values,and perspectives’,the authors address the following themes:‘Notes on Storylines of Family medicine’,‘Family medicine—the generalist specialty’,‘Family medicine’s achievements—a glass half full assessment’,‘Family medicine’s next 50 years—toward filling our glasses’,‘Four enduring truths of family medicine’,‘Names matter’,‘Family medicine at its core’and‘The ecology of medical care.’May readers find much food for thought in these essays.

关键词： glasses illustration Notes

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PH-responsive strontium nanoparticles for targeted gene therapy against mammary carcinoma cells

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Asian Journal of Pharmaceutical sciences 2021年第2期16卷 236-252页

作者： Athirah Bakhtiar Ezharul Hoque Chowdhury school of Pharmacy Monash University MalaysiaSelangor 47500Malaysia jeffrey cheah school of medicine and health sciences Monash University MalaysiaSelangor 47500Malaysia

Genetic intervention via the delivery of functional genes such as plasmid DNA(pDNA)and short-interfering RNA(siRNA)offers a great way to treat many single or multiple genetic defects effectively,including mammary *** of naked therapeutic genes or siRNAs is,however,short-lived due to biological clearance by scavenging nucleases and circulating *** cellular internalization of negatively-charged nucleic acids further causes low transfection or silencing *** of safe and effectual gene vectors is therefore undeniably crucial to the success of nucleic acid *** nanoparticles have attracted considerable attention in the recent years due to their high loading capacity and encapsulation *** we introduce strontium salt-based nanoparticles,namely,strontium sulfate,strontium sulfite and strontium fluoride as new inorganic *** strontium salt particles were found to be nanosized with high affinity towards negatively-charged pDNA and *** of the particles was seen with a drop in pH,suggesting their capacity to respond to pH change and undergo dissolution at endosomal pH to release the genetic *** the particles are relatively nontoxic towards the cells,siRNA-loaded SrF 2 and SrSO 3 particles exerted superior transgene expression and knockdown activity of MAPK and AKT,leading to inhibition of their phosphorylation to a distinctive extent in both MCF-7 and 4T1 *** salt nanoparticles have thus emerged as a promising tool for applications in cancer gene therapy.

关键词： Strontium Gene therapy Breast cancer SiRNA Nanoparticles

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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Philip Appleton Lisa J Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala Mark Dixon Timothy J England Kailash Krishnan Grant Mair Keith W Muir John Potter Christopher I Price Marc Randall Thompson G Robinson Christine Roffe Else C Sandset jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena Joanna M Wardlaw Nikola Sprigg Philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied healthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of health and Medical sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular sciences and NIHR Leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway Research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%*** 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital *** IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

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Strategies to assemble therapeutic and imaging molecules into inorganic nanocarriers

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Frontiers of Materials Science 2022年第3期16卷 101-144页

作者： Sheikh Tanzina HAQUE Mark M.BANASZAK HOLL Ezharul Hoque CHOWDHURY jeffrey cheah school of medicine and health sciences Monash University MalaysiaJalan Lagoon SelatanBandar Sunway47500 Subang JayaSelangorMalaysia Department of Chemical and Biological Engineering Monash UniversityClaytonVictoria 3800Australia health and Wellbeing Cluster Global Asia in the 21st Century(GA21)PlatformJeffrey Cheah School of Medicine and Health SciencesMonash University MalaysiaJalan Lagoon SelatanBandar Sunway47500 Subang JayaSelangorMalaysia

Inorganic nanocarriers are potent candidates for delivering conventional anticancer drugs,nucleic acid-based therapeutics,and imaging agents,influencing their blood half-lives,tumor targetability,and *** addition to the high surface area-to-volume ratio,they exhibit excellent scalability in synthesis,controllable shape and size,facile surface modification,inertness,stability,and unique optical and magnetic ***,only a limited number of inorganic nanocarriers have been so far approved for clinical applications due to burst drug release,poor target specificity,and *** overcome these barriers,understanding the principles involved in loading therapeutic and imaging molecules into these nanoparticles(NPs)and the strategies employed in enhancing sustainability and targetability of the resultant complexes and ensuring the release of the payloads in extracellular and intracellular compartments of the target site is of paramount ***,we will shed light on various loading mechanisms harnessed for different inorganic NPs,particularly involving physical entrapment into porous/hollow nanostructures,ionic interactions with native and surface-modified NPs,covalent bonding to surface-functionalized nanomaterials,hydrophobic binding,affinity-based interactions,and intercalation through co-precipitation or anion exchange reaction.

关键词： inorganic nanoparticle cancer ionic interaction covalent bonding affinity interaction intercalation

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Dyslipidemia in Adults with Type 2 Diabetes in a Rural Community in Ganadougou, Mali: A Cross-Sectional Study

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Journal of Diabetes Mellitus 2024年第2期14卷 133-152页

作者： Abdoulaye Diawara Djibril Mamadou Coulibaly Drissa Kone Mama A. Traore Drissa Konaté Dicko S. Bazi Oumar Kassogue Djeneba Sylla Fatoumata Gniné Fofana Oudou Diabaté Mariam Traore Ibrahim Antoine Nieantao Kaly Keїta Mamadou Diarra Olivia Smith Jian Li Cheickna Cisse Talib Yusuf Abbas Crystal Zheng Segun Fatumo Kassim Traore Mamadou Wele Mahamadou Diakité Seydou O. Doumbia jeffrey G. Shaffer University of sciences Techniques and Technologies of Bamako Bamako Mali National Federation of Community health Associations Bamako Mali Department of Tropical medicine Medical Microbiology & Pharmacology John A. Burns School of Medicine University of Hawaii Manoa Honolulu USA Department Biostatistics and Data Science School of Public Health and Tropical Medicine Tulane University New Orleans USA Department of Biotechnology and Computer Science Burhani College Mazgaon Mumbai India school of medicine Tulane University New Orleans USA Medical Research Council Uganda Virus Research Institute Entebbe Uganda London school of Hygiene and Tropical medicine London UK Departement of Biochemistry and Genetics Duquesne University College of Medicine Pittsburgh USA

Dyslipidemia is a disorder where abnormally lipid concentrations circulate in the bloodstream. The disorder is common in type 2 diabetics (T2D) and is linked with T2D comorbidities, particularly cardiovascular disease. Dyslipidemia in T2D is typically characterized by elevated plasma triglyceride and low high-density lipoprotein cholesterol (HDL-C) levels. There is a significant gap in the literature regarding dyslipidemia in rural parts of Africa, where lipid profiles may not be captured through routine surveillance. This study aimed to characterize the prevalence and demo-graphic profile of dyslipidemia in T2D in the rural community of Ganadougou, Mali. We performed a cross-sectional study of 104 subjects with T2D in Ganadougou between November 2021 and March 2022. Demographic and lipid profiles were collected through cross-sectional surveys and serological analyses. The overall prevalence of dyslipidemia in T2D patients was 87.5% (91/104), which did not differ by sex (P = .368). High low-density lipoprotein cholesterol (LDL-C) was the most common lipid abnormality (78.9%, [82/104]). Dyslipidemia was associated with age and hypertension status (P = .013 and.036, respectively). High total and high LDL-C parameters were significantly associated with hypertension (P = .029 and .006, respectively). In low-resource settings such as rural Mali, there is a critical need to improve infrastructure for routine dyslipidemia screening to guide its prevention and intervention approaches. The high rates of dyslipidemia observed in Gandadougou, consistent with concomitant increases in cardiovascular diseases in Africa suggest that lipid profile assessments should be incorporated into routine medical care for T2D patients in African rural settings.

关键词： Cholesterol Cross-Sectional Study Dyslipidemia Lipids Mali Type 2 Diabetes

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