简介:Parkinsonsdisease(PD)isacommon,progressiveneurodegenerativediseasecharacterisedbydegenerationofnigrostriataldopaminergicneurons,aggregationofα-synucleinandmotorsymptoms.Currentdopamine-replacementstrategiesprovidesymptomaticrelief,howevertheireffectivenesswearoffovertimeandtheirprolongeduseleadstodisablingside-effectsinPDpatients.ThereisthereforeacriticalneedtodevelopnewdrugsanddrugtargetstoprotectdopaminergicneuronsandtheiraxonsfromdegenerationinPD.Overrecentyears,therehasbeenrobustevidencegeneratedshowingthatepigeneticdysregulationoccursinPDpatients,andthatepigeneticmodulationisapromisingtherapeuticapproachforPD.Thisarticlefirstdiscussesthepresentevidenceimplicatingglobal,anddopaminergicneuron-specific,alterationsinthemethylomeinPD,andthetherapeuticpotentialofpharmacologicallytargetingthemethylome.Itthenfocusesonanothermechanismofepigeneticregulation,histoneacetylation,anddescribeshowthehistoneacetyltransferase(HAT)andhistonedeacetylase(HDAC)enzymesthatmediatethisprocessareattractivetherapeutictargetsforPD.Itdiscussestheuseofactivatorsand/orinhibitorsofHDACsandHATsinmodelsofPD,andhowtheseapproachesfortheselectivemodulationofhistoneacetylationelicitneuroprotectiveeffects.Finally,itoutlinesthepotentialofemployingsmallmoleculeepigeneticmodulatorsasneuroprotectivetherapiesforPD,andthefutureresearchthatwillberequiredtodetermineandrealisethistherapeuticpotential.
简介:AbstractBackground:Many Parkinson disease (PD) patients complain about chronic fatigue and sleep disturbances during the night. The objective of this study is to determine the relationship between fatigue and sleep disturbances by using polysomnography (PSG) in PD patients.Methods:Two hundred and thirty-two PD patients (152 with mild fatigue and 80 with severe fatigue) were recruited in this study. Demographic information and clinical symptoms were collected. Fatigue severity scale (FSS) was applied to evaluate the severity of fatigue, and PSG was conducted in all PD patients. FSS ≥4 was defined as severe fatigue, and FSS <4 was defined as mild fatigue. Multivariate logistic regression and linear regression models were used to investigate the associations between fatigue and sleep disturbances.Results:Patients with severe fatigue tended to have a longer duration of disease, higher Unified Parkinson Disease Rating Scale score, more advanced Hoehn and Yahr stage, higher daily levodopa equivalent dose, worse depression, anxiety, and higher daytime sleepiness score. In addition, they had lower percentage of rapid eye movement (REM) sleep (P = 0.009) and were more likely to have REM sleep behavior disorder (RBD) (P = 0.018). Multivariate logistic regression analyses found that the presence of RBD and proportion of REM sleep were the independent predictors for fatigue. After the adjustment of age, sex, duration, body mass index, severity of disease, scores of Hamilton Rating Scale for Depression, Hamilton Anxiety Rating Scale, and other sleep disorders, proportion of REM sleep and degree of REM sleep without atonia in patients with PD were still associated with FSS score.Conclusion:Considering the association between fatigue, RBD, and the altered sleep architecture, fatigue is a special subtype in PD and more studies should be focused on this debilitating symptom.
简介:Thedeveloppercutaneoustreatmentsformitralregurgitation(MR)havebeenbasedonestablishedsurgicalprocedures.Mostarebasedinsomewayonmitralannuloplasty.IndirectangioplastyutilizingcoronarysinusandleafletrepairwiththeMitraClipdevicehavethemostdevelopmentandclinicalapplication.Morerecently,afterthesuccessoftranscatheteraorticvalvereplacement,transcathetermitralvalvereplacementhasemerged.Acriticalunansweredquestioniswhattherelativerolesofvalverepairandvalvereplacementwillbe.ThelargestexperienceinpracticeiswithMitraClipleafletrepair.Theevidencebaseforthedevelopmentofthesenoveltherapiesincludessomedatainsurgicalcandidates,andregistrystudiesthathavebeendonepredominantlyinhighriskpopulations.
简介:AbstractThe current literature lacks strong guidelines regarding surgical management of patients with aspirin-exacerbated respiratory disease (AERD), who present with the clinical triad of chronic rhinosinusitis with nasal polyposis (CRSwNP), bronchial asthma, and aspirin/nonsteroidal anti-inflammatory drug intolerance. To further define the effectiveness of sinus surgery in treating AERD patients, this review article discusses current evidence regarding outcomes associated with more extensive surgery, the benefits of frontal sinus surgery on polyposis, and the role of Draf III intervention. Numerous studies suggest that Draf III frontal sinusotomy may be an efficacious early intervention due to increased neo-ostial patency and subsequent distribution of topical therapies. Future studies that further investigate the efficacy and safety of extensive surgery in AERD patients are warranted.
简介:AbstractThere is considerable epidemiological evidence indicating that air pollution has adverse effects on human health and is closely related to respiratory diseases, including chronic obstructive pulmonary disease (COPD). These effects, which can be divided into short- and long-term effects, can manifest as an exacerbation of existing symptoms, impaired lung function, and increased hospitalization and mortality rates. Long-term exposure to air with a high concentration of pollutants may also increase the incidence of COPD. The combined effects of different pollutants may become more complex in the future; hence, there is a need for more intensive research on specific at-risk populations, and formulating corresponding protective strategies is crucial. We aimed to review the epidemiological evidence on the effect of air pollution on COPD, the possible pathophysiological mechanisms underlying this effect, as well as protective measures against the effects of air pollutants in patients with COPD.
简介:煽动性的肠疾病(IBD)经常与象眼的神经炎那样的extraintestinal表明(EIM)被联系(在上)尽管这到目前为止在仅仅一些成年病人被描述了,所有谁与Crohns疾病(CD)被影响。而且,在上并且demyelinating疾病比的被表明了在IBD病人更经常在控制人口。在我们的当前的案例报告,我们与活跃CD描述一个孩子开发了突然的盲目由于在那上双边不与任何已知的原因有关,并且那即时对类固醇的高剂量作出回应。调查和临床的后续到目前为止在这个病人排除了demyelinating疾病的发展。到我们的知识,这是第一份报告在上在有CD的一个小儿科的病人。对这个案例的可能的解释包括活跃的肠疾病的阵发性的EIM,联系自体免疫的混乱例如一周期性孤立在上,多重硬化的第一表明,或能出现在以后的后续的另一demyelinating疾病。
简介:ObjectiveTostudyconcomitantsymptomsanddiseaseconditionsinsuddendeafness.MethodsClinicaldataof418casesofsuddendeafnesstreatedinthisdepartmentfrom2000to2007werereviewed.ResultsOfthe418cases,201weremalesand217werefemales.Rightearwasinvolvedin184casesandleftearin191cases.Bilateralinvolvementwasseenin43cases.Theaverageagewas44.1years.Tinnituswasreportedin369cases(88.3%)eitherbeforeorafterhearingloss,ofwhich64.5%wasoflowpitch,27.1%ofhighpitchand8.4%ofmixedtones.Constanttinnituswasreportedin83%ofthecases,andmuffledfeelingsin33.3%ofthecases.Hearinglosswastheonlycomplaintin221cases(52.9%).Dizzinesswasreportedin77cases(18.4%)andvertigoattacksin120cases(28%).Hypertension,coronaryarterydiseaseanddiabeteswerefoundin19.6%of418casesandhyperlipidemiain54.5%of211cases.CTand/orMRIdatawereavailablein147cases,withpositivefindingsin18cases(12.3%):2withacousticneuroma(1.36%);4withemphraxisinthebasalganglia,cerebellum,temporallobeorparietallobe,and12withpoorpneumatizationofipsiorcontralateralmastoidcells.ConclusionInthiscaseseriesofsuddendeafness,low-pitchconstanttinnituswasacommoncomplaint.Mostofthestudiedcasespresentedwithsimplehearingloss.Vertigoattacksweremorecommonthandizzinessinthisgroupofpatients.Themostcommonconcomitantdisorderwashyperlipidemia,especiallyhightriglycerides.Imagingstudiesareimportantinmanagingsuddendeafnessinrulingoutacousticneuromaandotherintracranialdiseases.
简介:ObstructiveSleepApnea(OSA)isacommonchronicdisorderthataffects5–10%oftheUSpopulationwithahigherprevalenceinmencomparedtowomenby2:1inpopulationstudies.Bycontrast,inpatientswithcardiovasculardisease,itsprevalencecanexceed50%dependingonthespecificdisordersurveyed.Althoughsexdifferenceshavebeenwelldescribedforcardiovascularriskfactors;existingdataregardingtheimpactofsexontherelationshipbetweenOSAandcardiovascularoutcomesiscontroversial.Similarly,whilethereisstrongevidenceforincreasedprevalenceofcardiovascularconditions,suchassystemichypertension,atrialfibrillation,aswellasheartfailureamongstpatientssufferingfromOSA;conflictingevidenceexistsregardingtheincidenceandbidirectionalrelationshipbetweenthemaswellastheimpactoftreatmentofOSAoncardiovascularoutcomes.Inthispaper,wewillreviewtheassociationsbetweenOSAandcardiovasculardiseasesinwomen.Thedataonsexdifferencesislimited,duetoanumberofreasons,including,butnotlimitedtolatepresentationofOSAinwomen,difficultiesindiagnosingbothOSAandcardiovasculardiseasesinwomenandstillsuboptimalinclusionofadequatenumberofwomeninclinicaltrials.MorestudiesareneededtobetterdelineatesexdifferencesintheclinicalpresentationaswellasthepathophysiologyoftheassociationsbetweenOSAandcardiovasculardiseasessothatwecanprovidepatientswithmorepersonalizedcare.
简介:AIM:ToInvestigatethegeneticfindingsandphenotypiccharacteristicsofaChinesefamilywithNorriedisease(ND).METHODS:MoleculargeneticanalysisandclinicalexaminationswereperformedonaChinesefamilywithND.MutationsintheNorriediseasepseudoglioma(NDP)geneweredetectedbydirectsequencing.Haplotypeswereconstructedandcomparedwiththephenotypesinthefamily.Evolutionarycomparisonsandmutantopenreadingframe(ORF)predictionwerealsoundertaken.RESULTS:TwofamilymemberswithocularmanifestationswerediagnosedwithND.Nosignsofsensorineuralhearinglosswereobservedineitherpatient,whileoneofthemshowedsignsofmildmentalretardation.AnovelheterozygousmutationintheNDPgene,c.-12delAAT,wasdetectedinbothpatients.ThemutationandthemutationbearinghapiotypecosegregatedwiththeNDphenotypeinmalesandwastransmittedfromtheirmothersand/orgrandmothers(Ⅱ:2).ThemalewithoutNDdidnotharborthemutation.Themutationoccurredatthehighlyconservednucleotides.DRFfinderpredictedthatthemutationwouldleadtotheproductionofatruncatedproteinthatlacksthefirst11N-terminalaminoacids.CONCLUSION:Anovelmutation,c.-12delAATintheNDPgene,wasidentifiedinaChinesefamilywithND.ThismutationcausedNDwithoutobvioussensorineuralhearingloss.Mentaldisorderwasfoundinonebutnottheotherpatients.Theclinicalheterogeneityinthefamilyindicatedthatothergeneticvariantsandepigeneticfactorsmayalsoplayaroleinthediseasepresentation.
简介:AbstractBackground:Hepatitis B is a viral infection that attacks the liver and can cause both potentially life-threatening acute and chronic liver disease. China has the world’s largest burden of hepatitis B and is considered to be a major contributor toward the goal of World Health Organization (WHO) of eliminating hepatitis B virus (HBV) as a global health threat by 2030. This study aimed to analyze data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to determine the trends in mortality of liver disease due to hepatitis B in China between 1990 and 2019 and the gap with the WHO’s goal.Methods:Annual deaths and age-standardized mortality rates (ASMRs) of liver disease due to hepatitis B in China between 1990 and 2019 were collected from GBD 2019. We calculated the percentage changes in deaths and estimated annual percentage changes (EAPCs) of ASMRs of liver disease due to hepatitis B.Results:In China, deaths of total liver disease due to hepatitis B decreased by 29.13% from 229 thousand in 2016 to 162 thousand in 2019, and ASMR decreased by an average of 4.92% (95% confidence interval [CI]: 4.45–5.39%) per year in this period. For the spectrum of liver disease due to hepatitis B, deaths decreased by 74.83%, 34.71%, and 23.34% for acute hepatitis, cirrhosis and other chronic liver diseases, and liver cancer from 1990 to 2019, respectively, and ASMRs of acute hepatitis (EAPC = –7.63; 95% CI: –8.25, –7.00), cirrhosis and other chronic liver diseases (EAPC= –4.15; 95% CI: –4.66, –3.65), and liver cancer (EAPC = –5.17; 95% CI: –6.00, –4.33) decreased between 1990 and 2019. The proportions of older adults aged ≥70 years among all deaths of the spectrum of liver disease due to hepatitis B increased from 1990 to 2019. Deaths of liver cancer due to hepatitis B increased by 7.05% from 2015 to 2019.Conclusions:Although a favorable trend in the mortality of liver disease due to hepatitis B was observed between 1990 and 2019, China still faces challenges in achieving the WHO’s goal of eliminating HBV as a public threat by 2030. Therefore, efforts to increase the coverage of diagnosis and treatment of liver disease due to hepatitis B, especially of liver cancer due to hepatitis B, are warranted in China.