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Clinical pharmacology relevant to older adults with cardiovascular disease

Journal of Geriatric Cardiology 2015年第3期12卷 192-195页

作者： Jorge A Brenes-Salazar Laith Alshawabkeh Kenneth E Schmader joseph t hanlon Daniel E Forman Department of Medicine Division of Cardiovascular Diseases Mayo Clinic Rochester MN USA Department of Medicine Division of Cardiovascular Medicine University of lowa Iowa City IA USA Department of Medicine Division of Geriatrics Duke University School of Medicine Durham NC USA Departments of Medicine (Division of Geriatric Medicine) Pharmacy and Epidemiology University of Pittsburgh Geriatric Research Education and Clini- cal Center and Center for Health Equity Research and Promotion VA Pittsburgh Health System Pittsburgh PA USA Department of Medicine (Divisions of Geriatric Medicine and Cardiology) University of Pittsburgh Medical Center Geriatric Research Education and Clinical Center VA Pittsburgh Health System Pittsburgh PA USA

Although older adults are generally among the highest users of cardiovascular medications, they are typically underrepresented or excluded from most efficacy and safety trials. Drug developers are usually reluctant to include many senior adults in randomized controlled clinical trials in part due to their high prevalence of multiple comorbidities, frailty, and polypharmacy; and to age-related pharmacokinetic and pharmacodynamic complexities. Consequently, there is often insufficient high quality evidence-based data to inform pharmacologic management of common cardiovascular conditions on older adults. In the absence of data, clinicians often rely on conceptual principles regarding metabolism and drug-drug interactions to minimize adverse drug events, but this is often not well-substantiated or standardized. A related challenge is poor cardiovascular medication adherence among older adults, and its detrimental impact on their health outcomes. In this brief review we highlight some aspects of these topics.

关键词：临床药理学心血管疾病老年人

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Management of male obesity-related secondary hypogonadism:A clinical update

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World Journal of Experimental Medicine 2024年第2期14卷 11-28页

作者： Mohan t Shenoy Sunetra Mondal Cornelius James Fernandez joseph M Pappachan Department of Endocrinology Sree Gokulam Medical Collegeand Research FoundationTrivandrum 695607KeralaIndia Department of Endocrinology NRS Medical College and HospitalKolkata 700014West BengalIndia Department of Endocrinology&Metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Department of Endocrinology and Metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine&HealthThe University of ManchesterManchester M139PLUnited Kingdom

the global obesity pandemic has resulted in a rise in the prevalence of male obesity-related secondary hypogonadism(MOSH)with emerging evidence on the role of testosterone *** aim to provide an updated and practical approach towards its *** did a comprehensive literature search across MEDLINE(via PubMed),Scopus,and Google Scholar databases using the keywords“MOSH”OR“Obesity-related hypogonadism”OR“testosterone replacement therapy”OR“Selective estrogen receptor modulator”OR“SERM”OR“Guidelines on male hypogonadism”as well as a manual search of references within the articles.A narrative review based on available evidence,recommendations and their practical implications was *** weight loss is the ideal therapeutic strategy for patients with MOSH,achievement of significant weight reduction is usually difficult with lifestyle changes alone in real-world ***,androgen administration is often necessary in the management of hypogonadism in patients with MOSH which also improves many other comorbidities related to ***,there is conflicting evidence for the appropriate use of testosterone replacement therapy(tRt),and it can also be associated with *** evidence-based review updates the available evidence including the very recently published results of the tRAVERSE trial and provides comprehensive clinical practice pearls for the management of patients with *** starting testosterone replacement in functional hypogonadism of obesity,it would be desirable to initiate lifestyle modification to ensure weight *** should be coupled with the management of other comorbidities related to obesity in MOSH *** the risks and benefits of tRt should be considered in every patient before and during longterm management.

关键词： Male obesity-related secondary hypogonadism Androgen therapy testosterone replacement therapy Obesity Cardiovascular benefits

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Periodontitis:An often-neglected complication of diabetes

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World Journal of Diabetes 2024年第3期15卷 318-325页

作者： Marina G Kudiyirickal joseph M Pappachan Primary Care Dental Practice The Smile ClinicPreston PR16PZUnited Kingdom Department of Endocrinology and Metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

the bidirectional association between type 2 diabetes mellitus(t2DM)and periodontitis is now well established,resulting in periodontal disease being considered as the 6th major complication of diabetes mellitus(DM)after cardiovascular disease,eye disease,neuropathy,nephropathy,and peripheral vascular *** can worsen the virulence and invasiveness of pathogenic oral microbial flora aggravating the local inflammation and infection in those with periodontal *** the other hand,the chemical and immunological mediators released into the circulation as part of periodontal inflammation worsen the systemic insulin resistance with worsening of *** if undiagnosed or left untreated can also result in eventual tooth loss.A study by Xu et al in the World Journal of Diabetes examined the predictive factors associated with periodontitis in Chinese patients with *** prevalence of periodontitis was found to be 75.7%in this *** on logistic regression analysis,the predictive factors for higher risk were low tooth brushing frequency[odds ratio(OR)=4.3],high triglycerides(tG;OR=3.31),high total cholesterol(tC;OR=2.87),higher glycated hemoglobin(HbA1c;OR=2.55),and higher age(OR=1.05)while higher education level was protective(OR=0.53).However,the most influential variables were HbA1c followed by age,tC,tG,low education level,brushing frequency,and sex on the random forest model(this model showed higher sensitivity for predicting the risk).A good understanding of the predictors for periodontitis in t2DM patients is important in prevention,early detection of susceptible patients,and intervention to improve periodontal health and enable long-term glycaemic control as observed by Xu et al.

关键词： Diabetes mellitus Periodontitis Predictive factors Cardiovascular disease Glycaemic control

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Advances in discovery of novel investigational agents for functional cure of chronic hepatitis B:A comprehensive review of phases II and III therapeutic agents

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World Journal of Hepatology 2024年第3期16卷 331-343页

作者： Robert Lam joseph K Lim Section of Digestive Diseases Yale University School of MedicineNew HavenCT 06520United States

Chronic hepatitis B virus(HBV)infection affects over 295 million people globally and an estimated 1.6 million people in the United *** is associated with significant morbidity and mortality due to cirrhosis,liver failure,and liver *** therapy with oral nucleos(t)ide analogues is associated with high rates of virologic suppression,which in turn has been associated with a decreased risk of liver ***,current antiviral regimens are limited by concerns with adverse effects,adherence,resistance,long-term treatment,and ongoing risk for liver *** investigational agents are currently in development and are targeted at achieving functional cure with sustained hepatitis B surface antigen(HBsAg)loss and suppression of HBV *** we review key evidence from phases II and III trials defining the efficacy and safety profiles for key investigational agents for functional cure of chronic hepatitis B,including core/capsid inhibitors,entry inhibitors,RNA interference(siRNA/ASO),HBsAg inhibitors,toll-like receptor agonists,checkpoint inhibitors,and therapeutic vaccines.

关键词： Hepatitis B virus treatment Clinical trials RNA interference Entry inhibitors Core inhibitors Immunomodulators

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Correlation of periodontal inflamed surface area with glycated hemoglobin,interleukin-6 and lipoprotein(a)in type 2 diabetes with retinopathy

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World Journal of Diabetes 2024年第4期15卷 686-696页

作者： Nusreen Jamal thazhe Poyil Rosamma joseph Vadakkekuttical Chandni Radhakrishnan Department of Periodontics Government Dental College(Affiliated to Kerala University of Health Sciences)Calicut 673008KeralaIndia Department of Medicine Government Medical College(Affiliated to Kerala University of Health Sciences)Calicut 673008KeralaIndia

BACKGROUND the two-way relationship between periodontitis and type 2 diabetes mellitus(t2DM)is well *** hyperglycemia contributes to increased periodontal destruction and severe periodontitis,accentuating diabetic *** inflammatory link exists between diabetic retinopathy(DR)and periodontitis,but the studies regarding this association and the role of lipoprotein(a)[Lp(a)]and interleukin-6(IL-6)in these conditions are scarce in the *** to determine the correlation of periodontal inflamed surface area(PISA)with glycated Hb(HbA1c),serum IL-6 and Lp(a)in t2DM subjects with *** this cross-sectional study comprised 40 t2DM subjects with DR and 40 t2DM subjects without *** subjects were assessed for periodontal parameters[bleeding on probing(BOP),probing pocket depth,clinical attachment loss(CAL),oral hygiene index-simplified,plaque index(PI)and PISA],and systemic parameters[HbA1c,fasting plasma glucose and postprandial plasma glucose,fasting lipid profile,serum IL-6 and serum Lp(a)].RESULtS the proportion of periodontitis in t2DM with and without DR was 47.5%and 27.5%*** of periodontitis,CAL,PISA,IL-6 and Lp(a)were higher in t2DM with DR group compared to t2DM without DR *** difference was observed in the mean percentage of sites with BOP between t2DM with DR(69%)and t2DM without DR(41%),but there was no significant difference in PI(P>0.05).HbA1c was positively correlated with CAL(r=0.351,P=0.001),and PISA(r=0.393,P≤0.001)in study subjects.A positive correlation was found between PISA and IL-6(r=0.651,Ptudy *** Despite both groups having poor glycemic control and comparable plaque scores,the periodontal parameters were higher in DR as compared to t2DM without *** a bidirectional link exists between periodontitis and DM,the presence of DR may have contr

关键词： type 2 diabetes mellitus Periodontitis Periodontal inflamed surface Area Glycated Hb Diabetic retinopathy

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the timing of Primary Neurosurgical Repair and Wound-Site Infection in Children with Myelomeningocele

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Open Journal of Modern Neurosurgery 2024年第2期14卷 137-148页

作者： joseph O. Obande Paul t. Bitrus Elizabeth I. Obande Division of Neurosurgery Department of Surgery University of Abuja Teaching Hospital Abuja Nigeria Post-Basic School of Critical Care Nursing University of Abuja Teaching Hospital Abuja Nigeria

Background: the optimal time to closure of a newborn with a myelomeningocele has been the focus of a number of evaluations. the timing of primary surgery has received significant attention due to its relationship to repair-site infection that can lead to increased morbidity and prolonged hospital stays. It is on this basis that recommendations have utilized 48 - 72 hours post birth as ideal time of closure. this is not only prevent infection at the site but also prevent ventriculitis and neural structure damage. We therefore, hypothesized an increase in wound infection rates in those patients with delays in myelomeningocele repair. Methods: We retrospectively reviewed the records of 103 children with myelomeningocele treated between 2016 and 2023. At discharge the patients were followed up at the post-operative clinic visit 2 weeks later. Children were assigned to 1 of 2 groups, those who underwent primary neurosurgical repair within 72 hours of delivery (Group 1) and those undergoing repair after 72 hours (Group 2). We compared the infection rates. Results: 103 children who underwent myelomeningocele repair were identified, with a median time from birth to treatment of 1 day. Eight (7.8 %) patients were noted to have post-repair surgical site complications. there was no significant difference in rates of infection between Group 1 and Group 2 repair times. the presence of infection was associated increased length of stay when compared to neonates without infection. Conclusion: In children with myelomeningocele, the timing of primary neurosurgical repair appears not to have a significant impact on surgical site infection. Closure of the spinal lesion within the first 72 hours of life may be more favorable for neural damage prevention. these results suggest that early myelomeningocele repair may not impart significantly on the rate of wound-site infection.

关键词： Spina Bifida Surgical timing Excision and Repair Surgical Site Infection Myelomeningocele

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Comparisons of oxbow lake fish assemblages in relation to bigheaded carp establishment in the lower White River, Arkansas

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Ecological Processes 2024年第1期13卷 188-205页

作者： Michael A.Eggleton Cody J.Salzmann joseph E.Kaiser Shannon C.F.Smith Department of Aquaculture and Fisheries University of Arkansas at Pine Bluff Arkansas Game and Fish Commission Virginia Institute of Marine Science

Background Since the late 1990s, bigheaded carps(largely silver carp [Hypophthalmichthys molitrix] but also bighead carp [H. nobilis]) have established throughout the lower Mississippi River basin. Using previously studied oxbow lakes in the lower White River basin, Arkansas, we compared current(2017, “post-carp” establishment) fish assemblages to historical(2002, “pre-carp” establishment) fish assemblages. Fish assemblages were comprehensively assessed using multiple gears, including boat electrofishing, mini-fyke nets, and experimental small-mesh gill *** t-tests suggested that fish assemblage indices of richness, diversity, evenness, and dominance were often greater(P the post-carp period as reflected by boat electrofishing and experimental gill nets. However, all indices were generally similar(P > 0.05) between the pre-carp and post-carp period with fish assemblages depicted using mini-fyke nets. Nonmetric multidimensional scaling analyses indicated that fish assemblages differed structurally between pre-carp and post-carp periods. Assemblage differences were linked to both small and large abundance changes for more than 20 species. Abundances of gizzard shad(Dorosoma cepedianum), emerald shiner(Notropis atherinoides), pugnose minnow(Opsopoeodus emiliae), crappies(Pomoxis spp.), bluegill(Lepomis macrochirus), orangespotted sunfish(L. humilis), and yellow bass(Morone mississippiensis) declined between the pre-carp and postcarp periods. Conversely, abundances of weed shiner(N. texanus), pallid shiner(Hybopsis amnis), longear sunfish(L. megalotis), buffalofishes(Ictiobus spp.), and gars(Lepisosteus spp.) generally increased during the same *** Although not possible to conclude assemblage shifts were entirely related to bigheaded carps due to the absence of an appropriate reference system where carps did not establish, the wide establishment of these carps is one of the most pervasive changes to have occurred in the lower White

关键词： Bigheaded carp Silver carp Aquatic nuisance species Fish assemblage Oxbow lake Large river

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Recovery rates of persistent post-COVID-19 olfactory dysfunction using psychophysical assessment:A longitudinal cohort study

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 79-87页

作者： Jeremy P.tervo Patricia t.Jacobson Brandon J.Vilarello tiana M.Saak Francesco F.Caruana Liam W.Gallagher joseph B.Gary David A.Gudis Paule V.joseph D.P.Devanand terry E.Goldberg Jonathan B.Overdevest Columbia University Vagelos College of Physicians and Surgeons New YorkNew YorkUSA Department of Otolaryngology-Head and Neck Surgery New York-Presbyterian/Columbia University Irving Medical CenterNew YorkNew YorkUSA Department of Otolaryngology-Head and Neck Surgery University of PittsburghPittsburghPennsylvaniaUSA Department of Otolaryngology-Head and Neck Surgery University of MinnesotaMinneapolisMinnesotaUSA National Institute of Alcohol Abuse and Alcoholism Section of Sensory Science and Metabolism&National Institute of Nursing ResearchBethesdaMarylandUSA New York-Presbyterian/Columbia University Irving Medical Center New YorkNew YorkUSA

Objectives:Persistent olfactory dysfunction(OD)following loss of smell associated with SARS-CoV-2 infection is a major feature of long *** on the prevalence of persistent OD predominantly rely on self-reported olfactory *** studies have tracked longitudinal rates of recovery using psychophysical assessment among patients presenting for evaluation of persistent OD beyond a window of acute *** anchored in standardized testing methods are needed to counsel patients who fail to acutely regain their sense of *** study aims to quantify the degree of persistent OD in post-COVID-19 patients who experience subjective and psychophysical ***:We grouped participants presenting for OD evaluation into cohorts based on both subjective and psychophysical olfactory status at a baseline assessment and assessed their olfactory abilities with a visual analogue scale and the Sniffin'Sticks extended test at baseline and 1-year time *** had confirmed a history of COVID-19 by lab evaluation or clinical diagnosis if lab evaluation was not ***:Baseline olfactory evaluation was completed by 122 participants,53 of whom completed the 1-year follow-up *** participants presenting with perceived OD,74.5%had confirmed psychophysical OD at baseline,with 55.1%at 1-year *** had reliable trends in self-rated versus psychophysically tested olfactory function at both time *** total threshold,discrimination,and identification(tDI)score improved by+3.25 points in the cohort with psychophysical OD(p=0.0005),with this improvement largely attributable to an increase in median threshold scores(+2.75 points;p=0.0004).Conclusions:OD persists in a significant number of patients who fail to acutely recovery their sense of smell after COVID-19,with many demonstrating lingering deficits at *** in threshold,but not discrimination or identification,most significantly mediate improvement

关键词： long COVID olfaction post-COVID condition smell dysfunction

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Cardiac differentiation is modulated by anti-apoptotic signals in murine embryonic stem cells

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World Journal of Stem Cells 2024年第5期16卷 551-559页

作者： Amani Yehya joseph Azar Mohamad Al-Fares Helene Boeuf Wassim Abou-Kheir Dana Zeineddine Ola Hadadeh Department of Anatomy Cell Biology and Physiological SciencesAmerican University of BeirutBeirut 1107-2020Lebanon Inserm BiotisU1026University BordeauxBordeaux F-33000France Rammal Rammal Lab Physio-Toxicity Environmental TeamFaculty of SciencesLebanese UniversityNabatieh 0000Lebanon

BACKGROUND Embryonic stem cells(ESCs)serve as a crucial ex vivo model,representing epiblast cells derived from the inner cell mass of blastocyst-stage *** exhibit a unique combination of self-renewal potency,unlimited proliferation,and *** latter is evident by the ability of the isolated cells to differ-entiate spontaneously into multiple cell lineages,representing the three primary embryonic germ *** regulatory networks guide ESCs,directing their self-renewal and lineage-specific ***,or programmed cell death,emerges as a key event involved in sculpting and forming various organs and structures ensuring proper embryonic ***-ever,the molecular mechanisms underlying the dynamic interplay between diffe-rentiation and apoptosis remain poorly *** to investigate the regulatory impact of apoptosis on the early differentiation of ESCs into cardiac cells,using mouse ESC(mESC)models-mESC-B-cell lym-phoma 2(BCL-2),mESC-PIM-2,and mESC-metallothionein-1(MEt-1)-which overexpress the anti-apoptotic genes Bcl-2,Pim-2,and Met-1,*** mESC-t2(wild-type),mESC-BCL-2,mESC-PIM-2,and mESC-MEt-1 have been used to assess the effect of potentiated apoptotic signals on cardiac *** hanging drop method was adopted to generate embryoid bodies(EBs)and induce terminal differentiation of *** size of the generated EBs was measured in each condition compared to the wild *** the functional level,the percentage of cardiac differentiation was measured by calculating the number of beating cardiomyocytes in the manipulated mESCs compared to the *** the molecular level,quantitative reverse transcription-polymerase chain reaction was used to assess the mRNA expression of three cardiac markers:troponin t,GAtA4,and ***,troponin t protein expression was evaluated through immunofluorescence and western blot *** Our findings showed that the upregulation of Bcl-

关键词： Mouse embryonic stem cells Self-renewal Apoptosis Cardiac differentiation B-cell lymphoma 2 PIM-2 Metallothionein-1

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Understanding the oxidation chemistry of ti_(3)C_(2)t_(x)(MXene)sheets and their catalytic performances

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Journal of Energy Chemistry 2024年第1期88卷 437-445,I0010页

作者： Suvdanchimeg Sunderiya Selengesuren Suragtkhuu Solongo Purevdorj tumentsereg Ochirkhuyag Munkhjargal Bat-Erdene Purevlkham Myagmarsereejid Ashley DSlattery Abdulaziz SRBati joseph GShapter Dorj Odkhuu Sarangerel Davaasambuu Munkhbayar Batmunkh Department of Chemistry Division of Natural SciencesSchool of Arts and SciencesNational University of MongoliaUlaanbaatar 14200Mongolia Queensland Micro-and Nanotechnology Centre School of Environment and ScienceGriffith UniversityNathan campusBrisbaneQueensland 4111Australia Department of Physics Incheon National UniversityIncheon 22012Republic of Korea Australian Institute for Bioengineering and Nanotechnology The University of QueenslandSt LuciaBrisbaneQueensland 4072Australia Adelaide Microscopy The University of AdelaideAdelaideSouth Australia 5005Australia Centre for Organic Photonics&Electronics School of Chemistry and Molecular BiosciencesThe University of QueenslandSt LuciaBrisbaneQueensland 4072Australia

transition metal carbides and nitrides(MXenes)nanosheets are attractive two-dimensional(2D)materials,but they suffer from oxidation/degradation issues during storage and/or applications due to their sensitivity to water and *** the great research progress,the exact oxidation kinetics of ti_(3)C_(2)t_(x)(MXene)and their final products after oxidation are not fully ***,we systematically tracked the oxidation process of few-layer ti_(3)C_(2)t_(x) nanosheets in an aqueous solution at room temperature over several *** also studied the oxidation effects on the electrocatalytic properties of ti_(3)C_(2)t_(x) for hydrogen evolution reaction and found that the overpotential to achieve a current density of 10 mA cm^(-2)increases from 0.435 to 0.877 V after three weeks of degradation,followed by improvement to stabilized values of around 0.40 V after eight *** results suggest that severely oxidized MXene could be a promising candidate for designing efficient *** to our detailed experimental characterization and theoretical calculations,unlike previous studies,black titanium oxide is formed as the final product in addition to white ti(IV)oxide and disordered carbons after the complete oxidation of ti_(3)C_(2)t_(x).this work presents significant advancements in better understanding of 2D ti_(3)C_(2)t_(x)(MXene)oxidation and enhances the prospects of this material for various applications.

关键词： 2D materials MXene Chemical degradation Catalysis Hydrogen evolution reaction

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