Ukungasebenzi kakuhle kwe-Prodromal autonomic kwizifo zomzimba zaseLewy

 Namhlanje, ndonwabile ukuba ndijoyinwe ziingcali ezintathu ezibalaseleyo, uDavid Goldstein ovela kwi-NIH, omsebenzi wakhe ube ngundoqo ekuchazeni indima yokusilela kwe-autonomic kunye nokungabikho kwe-catecholamine kwi-synucleinopathies, kuquka nezifundo ezibalulekileyo kwi-pure autonomic failure njengemeko ye-prodromal.

David, enkosi ngokujoyina [00:01:00] nathi.

 UAbhimanyu Mahajan omsebenzi wakhe wakutshanje ugxile kwi-autonomic dysfunction njenge-biomarker yokuqala kwizifo ze-neurodegenerative, kuquka uphando lwakhe lwakutshanje oluhlola iimpawu ze-autonomic kwi-prodromal synnucleinopathies. Abhi, enkosi ngokuba nathi namhlanje.

UDkt. Abhimanyu Mahajan: Enkosi Michele, kwaye enkosi ngokundibona.

UDkt. Michele Matarazzo: Kunye no-Alison Yarnall, uprofesa wezonyango lwabantu abadala oqatshelwe ngomsebenzi wakhe kwiimpawu zengqondo kunye nezingezizo ezomzimba kwizifo zomzimba zikaLewy, kubandakanya nezifundo zexesha elide malunga ne-prodromal dementia kunye nemizimba kaLewy kunye ne-early non-motor phenotyping. Enkosi, Alison, ngokuba nam namhlanje.

UDkt. Alison Yarnall: Enkosi ngesimemo.

UDkt. Michele Matarazzo: Ngoko ke, David, mandiqale ngawe. Umsebenzi wakho uye wayila indlela esicinga ngayo ngokungasebenzi kakuhle kwe-autonomic njengokubonakaliswa kokuqala kwe-synucleinopathy. Ziziphi ubungqina beklinikhi okanye be-biomarker ezixhasa ukubakho kokungasebenzi kakuhle kwe-autonomic kwisigaba se-prodromal sezifo zomzimba zeLewy?

UDkt. David Goldstein: Ndicinga ukuba ubungqina obunamandla buvela kwi-cardiac sympathetic neuroimaging. [00:02:00] Akunyanzelekanga ukuba kube yi-I-123 MIBG esetyenziswa kwihlabathi liphela. Kwaye singangena kuloo nto kamva kancinci, ukuba kuyimfuneko. Kodwa nge-fluordopamine, [18F]fluordopamine PET scanning, endayiphuhlisa kwi-NIH kudala, kwaye ndiyisebenzise iminyaka engaphezu kwama-30.

Ingxelo yokuqala yayikwiNew England Journal of Medicine ngo-1997 kwaye kuloo ngxelo sichaze okokuqala umahluko phakathi kwezifo zomzimba zikaLewy, ukusilela okuzimeleyo kwisifo sikaParkinson. Kunye ne-non-Lewy body synucleinopathy, iShy-Drager syndrome, eyabizwa ngokuba yi-multiple system atrophy.

Kwiminyaka engamashumi amathathu edlulileyo siqinisekisile ukuxilongwa emva kokufa ngokukhangela i-norepinephrine entliziyweni. Kwaye akukho mathandabuzo ukuba kukho ukusilela okukhulu kwe-cardiac noradrenergic [00:03:00] kwizifo zomzimba zeLewy. Kwaye ngokubanzi akukho nanye kwi-multiple system atrophy.

Ngoko ke le biomarker ayizahlulanga nje kuphela iimeko, kodwa ikwaqinisekiswe yi-postmortem neurochemistry. Kakade ke, umbuzo uyaphakama, kwenzeka nini oku? Kwaye oko kwathatha ixesha elide, kodwa ngoku kucacile ukuba ubuncinane, kwinto ebizwa ngokuba yi-body first form of central synucleinopathies, esinokungena kuyo kamva.

Kodwa ubuncinane kwifomu yokuqala yomzimba, akukho mathandabuzo ukuba isilonda sentliziyo esibangela ukungasebenzi kakuhle kwengqondo siqala ukuqala kweParkinsonism okanye ukungasebenzi kakuhle kwengqondo njengakwi-dementia kwimizimba yeLewy. Iziphumo zentliziyo ze-fluordopamine ziqinisekiswe kukusetyenziswa kwe-catheterization yentliziyo ebonisa ukuba kukho ukwehla okukhulu kwizinga lokungena kwe-norepinephrine kuluhlu lwemithambo yentliziyo kwizifo zomzimba zeLewy kwaye kungekhona kwi-multiple [00:04:00] system atrophy.

Ngoko ke ndicinga ukuba i-autonomic lesion ikhetha intliziyo kwizifo zomzimba zaseLewy. Ekugqibeleni kukho umba wokuba kuthiwani nge-synucleinopathy kwenye indawo, kwaye ndiqinisekile ukuba siza kuthetha nge-skin biopsies kunye nomsebenzi we-synuclein seeding kunye ne-gut kunye ne-vagal afferent traffic njalo njalo kwaye indlela ezi zinto ezinxulumene ngayo isalokhu iyimfihlakalo.

Kwaye ndicinga ukuba oko kubalulekile. Xa une-skin biopsies ebonisa i-alpha-synuclein deposition kunye ne-sympathetic nerves, kwaye une-synucleinopathy efunyenwe kuhlobo oluthile lovavanyo olwenziwe emathunjini, kwaye wenza le cardiac sympathetic imaging. Zinxulumene njani? Kwaye ubukhulu becala, akukho mntu waziyo.

UDkt. Michele Matarazzo: Ewe. Uyilungisile le nto apha ngolwazi oluninzi malunga nokubonakaliswa okuhlukeneyo kunye neendlela ezininzi ezahlukeneyo zokulinganisa oku. Kwaye Abhi, mhlawumbi mandikuxelele apha [00:05:00]. Ngaba kukho naziphi na iindawo ezithile ezizimeleyo ezifana nokungasebenzi kakuhle kwentliziyo kunye nesisu, okanye mhlawumbi iimpawu zomchamo, eziqhele ukungaqhelekanga kwii-cohorts ze-prodromal?

UGqr. Abhimanyu Mahajan: Okokuqala, ndingammamela uGqr. Goldstein ethetha ngale nto kangangeeyure ezimbalwa, kwaye elo lingaba lelona xesha lilungileyo endakha ndalichitha. Amava am ewe, asinalo ukufikelela kwizixhobo ezimangalisayo ezenziwe nguye kwi-NIH kwaye inxalenye enkulu yento endizama ukuyenza kukujonga amaqela ezonyango kunye nokujonga imilinganiselo esekelwe kwisikali ukuze ndibone ukuba anokunceda njani ekunyamekeleni izigulane zethu.

Idatha esiyisebenzisileyo yayiyiPPMI, iParkinson's Progressions Markers Initiative, njengoko sisazi, ingumthombo otyebileyo wedatha kwizigulana, kubantu abanesifo sikaParkinson esingapheliyo. Kakade ke, bekukho nezinye iidatha kwixesha elidlulileyo, nezinye ii-cohorts kwixesha elidlulileyo.

Ndicinga ukuba ndifanele ndiqale ngokuthi elinye lamaphepha amahle kakhulu ngale nto kwasekuqaleni yayingowama-2013 nguNjingalwazi uRon Postuma, apho achaze khona iimpawu ze-autonomic, iimpawu ze-autonomic [00:06:00], kunye nokulinganiswa kweklinikhi ecaleni kwebhedi, njenge-orthostatic hypotension kwiqela lezigulane ezimalunga ne-9, kunye neqela elifanelekileyo lolawulo.

Kwaye waphawula ukuba kukho ubuncinane uphawu olunye kwi-subdomain nganye ezimeleyo. Ngoko ke ukuba uthetha ngentliziyo, amathumbu, isini, umchamo, isini, njalo njalo, uchaze ubuncinane uphawu olunye kwi-subdomain nganye kwinani elikhulu lezi zigulana ezinesifo sikaParkinson esibizwa ngokuba yi-prodromal kunye ne-PPMI. Kuba nzima kuba ufuna ukuxobula itswele kangakanani, akunjalo?

Ngoko ke ukuba ufuna ukuba ibe novakalelo olukhulu kwaye ufuna ukuqwalasela umbuzo omnye, ngoko ke isikali esasetyenziswayo yayiyi-SCOPA-AUT, esisikali esiqinisekisiweyo yi-MDS, kwaye sisetyenziswe iminyaka eliqela. Kwaye icandelo ngalinye, icandelo ngalinye elizimeleyo linemibuzo emininzi. Ukuba uthatha impendulo entle komnye waloo mibuzo kwi-subdomain nganye, ngoko kuyamangalisa ukuba zingaphi kwezi [00:07:00] izigulane ekuthiwa zi-prodromal kwisifo sazo kunye ne-prodromal ezichazwa kukuqala kweempawu zemoto, ewe. Phantse bonke baya kuba nombuzo omnye abawuphendula ngokuthi ewe.

Njengoko uGqr. Goldstein etshilo, eyona mpembelelo inkulu, ubuncinane ngesiphumo esasisiphanda, esikukuba ukuphazamiseka kwengqondo okuncinci, umthwalo weempawu zentliziyo kunye nemithambo yegazi yileyo, esiyifumene inefuthe kakhulu, ngomlinganiselo weengozi eziphezulu we-5.21. Kodwa ewe, bekukho nabanye.

UGqr. Michele Matarazzo: Ngoko ke ucinga ukuba ii-biomarkers zentliziyo nezomeleleyo okwangoku okanye ucinga ukuba sizithatha lula ezinye iindawo ezifana ne-gastrointestinal okanye masithi ukungasebenzi kakuhle kwe-pseudo motor, kukho into esingathethi ngayo.

UGqr. Abhimanyu Mahajan: Ndicinga ukuba kukho into ebalulekileyo kuloo nto. Ndicinga ukuba ukungasebenzi kakuhle kwe-cardiovascular autonomic dysfunction kuye kwenza ukuba ii-biomarkers eziqinileyo ziphuhliswe ngaphandle kwamathandabuzo. Kwaye ndicinga ukuba okukhona sisazi ngakumbi, kokukhona siyazi kancinci kangakanani na. Ngoko ke, andiyi kumangaliswa kukuba ii-biomarkers ezingcono ziphuhliswa kwezinye ii-subdomains size sizifumane.

Kwakhona [00:08:00] iyaziwa, olu phando ndicinga ngalo luphando lomngcipheko we-PD oluvela kwi-NIH, kodwa bekukho namanye amaqela. Nokuba ungayeka ukuthetha ngesifo sikaParkinson esibangelwa yi-prodromal size sijonge iphepha lakutshanje elipapashwe yi-UCL eLondon malunga nokusilela kwe-autonomic. Onke la maqela abalisa ibali elifanayo.

Ngoko ke ukuba ugxila kumthwalo we-cardiovascular autonomic, ewe, uya kufumana unxulumano nokuqonda. Uya kufumana unxulumano nokuguqulwa kwe-pheno, kwanokusinda, kodwa ukuqunjelwa, isini, ukusetyenziswa kwe-catheter yomchamo, njl. njl., kuye kwanxulunyaniswa nokuguqulwa kwe-pheno ukuya kwi-MSA, umzekelo, endaweni ye-PD DLB, akunjalo?

Ndicinga ukuba ukuba sijonga ngakumbi, siya kufumana ulwalamano oluqinileyo kungekuphela nje ngokuphuhlisa ukuguqulwa kwe-pheno, kodwa nokuguqulwa kwe-pheno ukuya kuhlobo oluthile lwesifo.

UDkt. Michele Matarazzo: Kwaye Alison, ndingathanda ukuba uzise umbono wakho apha ingakumbi xa ucinga ngomsebenzi wakho kwi-prodromal dementia ngemizimba kaLewy kunye ne-cognitive first phenotypes. Iimpawu ze-autonomic zithelekiswa njani kwi-sensitivity kunye ne-[00:09:00] specificity kwezinye iimpawu ze-prodromal, ezinje nge-REM sleep behavior disorder, i-cognitive changes kwiimpawu ze-neuropsychiatric?

UGqr. Alison Yarnall: Ndiyazibuza ukuba ndingabuyela umva kuqala ndize ndicinge kancinci ngento u-Abhi ebeyithetha ngoku kwaye sithethe ngamava ethu kwi-prodromal dementia kunye nemizimba yeLewy. Ngoko ke xa sijonga i-mild cognitive impairment kunye nemizimba yeLewy, apho sinee-phenotype cohorts ezinzulu apha eNewcastle esizilandele kangangeminyaka eliqela kwaye sathelekisa oko kunye ne-mild cognitive impairment kunye ne-Alzheimer's kunye ne-controls.

Ngokuqinisekileyo kumava ethu, sifumanise ukuba iimpawu zokuzimela komzimba zazixelwa rhoqo, kwaye oko kwakuqhelekile xa kuthelekiswa nokwaluphala okuqhelekileyo, kodwa eneneni, kwakungaqhelekanga xa kuthelekiswa nezo zine-MCI ezine-Alzheimer's type pathology. Kwaye kwakhona, njengoko u-Abhi esitsho sithengisa ibali elifanayo.

Sifumanise ukuba iimpawu zesisu kunye ne-secretory psychomotor zazixelwa rhoqo, kodwa ezo mpawu zohlobo lwentliziyo zixelwe njengezinzima ngakumbi.

Ngoko ke, ukuya kwinto ondibuze yona ngokukodwa kukuba, singayithelekisa njani into engabonakaliyo kunye ne [00:10:00] specificity? Uninzi lwezi mpawu lunovakalelo oluphezulu, ngoko ke zihlala zikhona. Ngoko ke sizibona kwiimeko ezingaphezu kwesiqingatha ze-prodromal DLB, ingakumbi ukuqunjelwa okanye i-orthostatic hypotension, kodwa inobukrelekrele obuphantsi kakhulu xa kuthelekiswa nezinye iimpawu eziphambili esizibonayo. Ngoko ke, ukubakho kwe-REM sleep behavior disorder okanye i-dopamine transporter imaging engaqhelekanga.

Kwakhona, ndingabuyela kakhulu kwisifundo u-Abhi athethe ngaso, esabeka imeko kwiParkinson's nangona kunjalo, sijonge i-IBD size silandele elo qela kwiminyaka eliqela, nto leyo eye yasigcina sikwindawo efanelekileyo. Ndicinga ukuba kukho nomsebenzi wamva nje ovela kwiqela laseBologna owapapashwa kwi-neurology kunyaka ophelileyo.

Kwaye bajonga ukuba yintoni imilinganiselo yengozi yokuguqulwa, ukuguqulwa kwe-pheno. Kwaye kwakhona, kwavela uhlobo olufanayo lweempawu. Ngoko ke i-neurogenic orthostatic hypotension, iimpendulo ze-regal ezifipheleyo, izinto ezibalulekileyo zomngcipheko wokuqikelela ukuguqulwa kwe-pheno.

UGqr. Michele Matarazzo: Ngoku sithetha ngeempawu ezahlukeneyo [00:11:00] kweminye yemisebenzi yakho, kuquka nezifundo ezijonga iimpawu zokuqala ezingezizo ezomzimba kunye neepateni zokuqhubela phambili, ukungasebenzi kakuhle kwe-autonomic kubonakala kunye neempawu zengqondo yengqondo endaweni yokwahlulwa. Ngoku, ngaba ucinga ukuba ukungasebenzi kakuhle kwe-autonomic okwangoku akunasisindo kwiziseko ezikhoyo?

Okokuqala, xa kuthelekiswa ne-dementia kuqala apho siqwalasela iindlela ezilawulayo ezingezizo ezomzimba. Ucinga ukuba asicingi kangako ngokungasebenzi kakuhle kwe-autonomic? Kwakhona ukuba ufuna ukuphawula, uAlison malunga nezikhokelo ezifana neekhrayitheriya zophando ze-MDS ezivela kwisifo sikaParkinson esibizwa ngokuba yi-prodromal.

Ngoko ke sele ziquka ukungasebenzi kakuhle kwe-autonomic. Kodwa ucinga ukuba le miqathango ibamba ngokupheleleyo uluhlu lwezinto esizibonayo ngoku kwaye siyazi ngakumbi nangakumbi, ingakumbi xa sijonga iintlobo ezahlukeneyo kunye neempawu ezahlukeneyo zezifo zomzimba zikaLewy.

UGqr. Alison Yarnall: Ewe, ndicinga ukuba yindawo eguqukayo kwaye ndicinga ukuba siyayiqonda ngakumbi nangakumbi. Kwaye ndicinga ukuba ukuba sijonga nzulu, siza kuyibona le nto kwaye siyayibona rhoqo. Ndicinga ukuba [00:12:00] kwelinye icala, uninzi lwezi mpawu ludla ngokuxelwa nakubantu abadala kwaye zixhaphakile njengoko sikhula.

Kwaye ke ngoko kukho ukudibana phakathi kokwaluphala kunye nesifo somzimba sikaLewy.

UDkt. Michele Matarazzo: Kulungile, ngoku masingene ekuxilongeni. David, ndiza kubuyela kuwe. Ewe, wonke umntu uzive ekhululekile ukungenelela. Ngoko ke zeziphi iindlela ezintsha zokuvavanya umsebenzi we-autonomic ezithembisa kakhulu ukufumanisa isifo se-prodromal?

UDkt. David Goldstein: Ndicinga ukuba kubalulekile ukwahlula ii-biomarkers zeklinikhi kwii-biomarkers zelebhu ezijolise ngqo. Oku kubalulekile. Ngoko ke xa kufikwa kwi-orthostatic hypotension, umzekelo, endicinga ukuba ayimelwanga ngokwaneleyo. Kungenxa yokuba iingcali ze-neurologists azicingi ngayo ngaphandle kokuba isigulana sinempawu.

Akuqhelekanga ukuba iimpawu ezibalulekileyo ze-orthostatic zihlolwe rhoqo kwiklinikhi ye-neurology. Ngoko ke, uza kuyithatha kancinci i-orthostatic [00:13:00] hypotension ukuba uxhomekeke kwiimpawu. Ndingumlandeli omkhulu wee-biomarkers kwaye kukho ii-physiological, kukho ii-neurochemical, kukho ii-neuroimaging, kukho ii-micro neuroimaging biomarkers, kwaye zonke ziyadibana ngohlobo lwe-Venn diagram.

Xa kufikwa kwi-physiological, ndicinga ngakumbi nge-indices ye-diver reflex, umsebenzi we-sympathetic neural. Xa kufikwa kwi-neurochemical, ndicinga ngamanqanaba e-CSF e-catecholamines kunye ne-metabolites zazo. Andiqinisekanga ukuba kukho okuninzi kakhulu ekufuneka kuthethwe ngako xa kufikwa kumanqanaba e-plasma, masithi nje, e-catecholamines kunye ne-metabolites zazo kwezi meko, ngaphandle kokusilela kwe-autonomic kuphela. Xa kufikwa kwi-neuroimaging, sele sithethe ngento ye-PET scanning kwaye kwihlabathi lokwenyani une-MIBG SPECT scanning yakho, loo nto, ejonga intliziyo. Kwaye xa kufikwa kwi-micro neuroimaging, ke une-skin biopsies yakho. Ukongeza kwi-neurochemistry [00:14:00] malunga ne-catecholamines, ewe kukho into ye-synuclein seeding, ubuncinci kwisifundo sethu yayibikezela kwisifundo se-longitudinal perspective.

Ngoko ke oko kukwabalulekile. Ngoko ke, njengoko ndibona, kukho iindawo ezahlukeneyo zee-biomarkers, kwaye ndinethemba lokuba kwixesha elizayo kuya kubakho utshintsho ekuqwalaselweni kweklinikhi kuba ndicinga ukuba azinamvakalelo kwaye azicaci. Kwaye endaweni yoko kuya kubakho ukugxininiswa ngakumbi kwezi ndawo zahlukeneyo zee-biomarkers.

UGqr. Michele Matarazzo: Kulungile, ngaphambi kokuba ndiye e-Abhi, ndiyazi ukuba ufuna ukongeza into ethile, kodwa mandiqhubeke kancinci ndithethe ngee-biomarkers. Ngoko ke ucinga ukuba sifanele sisebenzise rhoqo ezi biomarkers kwi-clinical practice kwaye ukuba kufuneka uthethe enye okanye ezimbini eziya kuba, okanye ziya kuba nefuthe elikhulu kwikamva le-clinical practice yethu, masithi kwiminyaka emi-5-10 ezayo, ubungakhetha ntoni?

UDkt. David Goldstein: Ndingasebenzisa uhlobo oluthile lwendlela ye-algorithmic [00:15:00]. Uqala ngezinto ezikhawulezayo, ezingabizi kakhulu, ezikhuselekileyo, kodwa ezinobuthathaka ngokwaneleyo. Kwaye ndicinga ukuba ngokombono onjalo unohlalutyo lokuguquguquka kwesantya sentliziyo yakho ngakumbi kwi-frequency domain.

Ndicinga ukuba yiloo nto siyifumene iyinto exelwa kwangaphambili. Kodwa kukho ukutshintshiselana kuba kukho izinto ezininzi ezilungileyo nezingalunganga nezingalunganga. Emva koko, ndicinga ukuba ndingatshintshela kwinto enxulumene ne-synuclein.

Kwaye ndicinga ukuba niyayazi into endithetha ngayo. Emva koko, ndicinga ukuba ndingaya kwi-PET scanning, i-fluorodopa PET scanning yobuchopho. Kwaye ukuba ingenziwa i-fluorodopa PET scanning yentliziyo. Ngoko ke siqala kwi-cheap, elula, ekhawulezayo, nekhuselekileyo ukuya kubani owenza loo nto?

UDkt. Michele Matarazzo: Ewe. Kulungile. Ngoko ke ndiyayithanda ingcamango ye-algorithm. Yingcamango entle kakhulu leyo. Ucinga ntoni ngo-Abhi, kwaye yintoni obufuna ukuyidibanisa kwingxoxo ye-biomarker.

UGqr. Abhimanyu Mahajan: Ngoko ke into ehambelana noko kuthethwe nguGqr. Goldstein, indlela endicinga ngayo ngale nto, ndicinga ukuba ukuba nee-biomarkers ezithile ezinobuchule kakhulu kubaluleke kakhulu kuthi ukuze siqonde i-pathophysiology. Ayisiyo i-pathophysiology kuphela, kodwa i-physiology yendlela esebenza ngayo yonke le nto.

Kwangaxeshanye, ndicinga ukuba kukho into entle ngoluvo lwam ukuba singayithathi lula inzuzo yebhedi kunye noko sinokukwenza ecaleni kwebhedi. Ndiyavuma ngokupheleleyo ukuba noxinzelelo lwegazi oluhambelana ne-orthostatic, umzekelo, olu phononongo lwenzeke kwiYunivesithi yaseCincinnati kwiminyaka embalwa eyadlulayo ngoku. Kwaye sijonge izigulane ezazinemilinganiselo yokulinganisa i-orthostatic hypotension ecaleni kwebhedi.

Emva koko sibabuze ngeempawu ze-orthostatic hypotension. Kwaye malunga nama-30% abantu babengazi ukuba uxinzelelo lwabo lwegazi luyi-orthostatic. Okubalulekileyo kukuba, nokuba babengenalo ulwazi, nokuba babengenazo iimpawu, umngcipheko we-ADLs ezimbi kunye nokuwa wawusephezulu, akunjalo? Ngoko ke ukuba isigulane asikwazi oko akuthethi ukuba akunampembelelo. Kwangaxeshanye, ubuncinci kwikliniki yam, ndizama kangangoko ukuba nomda ophantsi kakhulu wokufumana uxinzelelo lwegazi oluyi-orthostatic.[00:17:00] 

Nangona iimpawu ziphantsi kakhulu, ndisacinga ukuba kubaluleke kakhulu ukuzibamba ecaleni kwebhedi. Ulwazi oluninzi esinalo malunga nempembelelo yomthwalo weempawu ze-orthostatic kunye nempembelelo yayo kwezinye iindawo kwiParkinson's kwizifundo nakwii-cohorts ezilandelwayo eklinikhi lusekelwe kwizikali ezinjalo, njenge-SCOPA kunye nezinye. Kwaye kungekuphela nje kwi-prodromal, ndicinga ukuba ngekhosi yesifo uthetha ngeParkinson's ekhubazekileyo ngokwengqondo, iParkinson's esekwe, kunye nezigulane ze-DLB eziphambili.

Ngoko ke ilandela yonke ikhosi yesifo kwaye kungekuphela nje kwi-prodromal Parkinson's kwaye inokuba nefuthe lonyango. Into yokugqibela endifuna ukuyongeza, ndicinga ukuba ukukwazi ukwenza ezi zikali kunye nolu vavanyo ecaleni kwebhedi kusinika amandla okubamba ulwazi kwiisampulu ezinkulu ezisinceda ukuba sichaze ezinye zezifo ezahlukeneyo esizibonayo.

Nokuba sizama kangakanani na ukwenza la maqoqo abe neenkcukacha ezithile kangangoko, kusekho ubuninzi [00:18:00] bokungafani. Ngoko ke ukuba novavanyo ecaleni kwebhedi kusinceda sonyuse ubungakanani besampulu. Kwaye kusenza sikwazi ukuqukanisa ngakumbi kwiimvavanyo zeklinikhi kunye noko sikwaziyo ngeklinikhi.

Ngoko ke ndicinga ukuba zombini ezi ndlela zokuvavanya ukungasebenzi kakuhle kwe-autonomic kufuneka zisebenze ngaxeshanye. Ziyanceda, ewe.

UGqr. Michele Matarazzo: Ngoku mandibuze nina nobathathu, nicinga ntoni ngee-biomarkers zophando eziphezulu kakhulu nezibiza kakhulu, nize niye ecaleni kwebhedi ukuze nenze into efumaneka lula. Kodwa masihambe inyathelo elinye phambili size sithethe ngokuhlala sijongile. Into esinokuyifumana ngqo kwisigulana sikude. Ucinga ukuba olu hlobo lwezixhobo luza kuba yintoni kwixesha elizayo, kungekuphela nje ngokuxilonga kodwa nokuqonda okwenzekayo kwezi zigulana, nokuba azikho nathi esibhedlele okanye kwikliniki yophando, uAlison.

UDkt. Alison Yarnall: Ewe ndingumlandeli omkhulu wale nto kwaye ndicinga ukuba yindlela ihlabathi elihamba ngayo. Apha e-UK sinesicwangciso seminyaka eli-10 se-NHS yethu, enye yazo kwezi ntsika zintathu [00:19:00] kukuhamba ukusuka esibhedlele ukuya kuluntu, ukugula ukuya ekuthinteleni, ukuya kukhathalelo ekhaya. Kwaye ndicinga ukuba le yindlela esihamba ngayo kuyo nayiphi na kwezi ndlela sithetha ngazo, kunye nezinye iindlela ezininzi zokulinganisa, ukulala, ukudinwa, ukuhambahamba, ukuhambahamba, nokuqonda. Ukulinganisa oku kwindawo yomntu kwixesha leentsuku ezisixhenxe kuthetha ukuba asinawo umfanekiso ongeke ubambe ukuguquguquka okuyinxalenye yesifo sikaParkinson kunye ne-dementia Lewy bodies. Kwaye ndicinga kakhulu ukuba kulapho siya khona kwaye sisiya khona.

Kwaye oku kunokunciphisa umthwalo ngexesha lezonyango. Ukuba sineziphumo zezigulane ngexesha langempela, sinokukwazi ukwenza utshintsho kude ukuze abantu bangabi nakuza eklinikhi. Kuvumela ukubandakanywa. Ngoko ke izigulane ezindala, ezibuthathaka, abantu abakwindawo yasemaphandleni kuya kubavumela ukuba babe nonyango olufanayo nolwabo bahlala kufutshane namaziko amakhulu eyunivesithi [00:20:00] kokubini kwindawo yezonyango nakwindawo yophando.

Kwaye ndicinga kakhulu ukuba le yindlela esihamba ngayo, kwaye mhlawumbi asijongi nto inye, ngoko ke asiyondlela ye-univar kodwa sithatha i-algorithm ethethwe nguDavid. Mhlawumbi ke uninzi lweendlela zokulinganisa, uxinzelelo lwegazi oluhambelanayo, ukuguquguquka kwesantya sentliziyo, njl. Kwaye mhlawumbi amanqaku nokukwazi ukwahlula abo baqhubela phambili ngokukhawuleza, kancinci, kunye nabo bafuna ukungenelela. Ndicinga ukuba le yindlela eya phambili.

UGqr. Michele Matarazzo: Kuhle kakhulu. Ngoko ke umbuzo olandelayo wawumalunga nokusebenzisa olu hlobo lwezixhobo zokwahlulahlula umngcipheko kwaye mhlawumbi ingaba ukungasebenzi kakuhle kokuzimela kungasinceda na ukuchonga abantu abasengozini enkulu yokuguquka kwiiqela ezisele zisengozini yesifo sikaParkinson okanye i-dementia kunye nemizimba kaLewy.

Ingaba ufuna ukongeza enye into kule nto? Mhlawumbi uDavide.

UGqr. David Goldstein: Ndiza kubhekisa kuphononongo lomngcipheko we-PD kuba lolunye lwezifundo ezimbalwa ze-longitudinal perspective zabantu abanee-risk factors ezininzi ukuze babone ukuba ixabiso lokuqikelela lithini [00:21:00] xa kufakwa iintlobo ezahlukeneyo ze-biomarkers. Ndicinga ukuba lelo licandelo eliphambili lophononongo lomngcipheko we-PD elenze ukuba libe yinto eyahlukileyo.

Uqikelelo, olusekelwe kwizinto ezinobungozi, imbali yosapho, ukuziphatha okuphuphayo, ukungasebenzi kakuhle kwevumba, ukunganyamezelani kwe-orthostatic, olo hlobo lwezinto. Ezo zinto zinamandla kakhulu. Ingakumbi xa zidibene. Yandisa kakhulu iziphumo zokuqikelela, uhlobo lokuxela kwangaphambili ngokwemeko yokuguqulwa kwe-pheno kwixesha elizayo. Kodwa xa udibanisa ii-biomarkers, ngoko ke, ngokwenene, akusekho ngxaki yomngcipheko. Unesifo. Lixesha. Kwaye ndicinga ukuba yayililo isifundo esiphambili esivela kwisifundo somngcipheko we-PD. Ezo biomarkers ziya kutshintsha umngcipheko, andazi, ngokuphindwe kahlanu ukuya kwikhulu leepesenti, yiloo nto kanye. Ndicinga ukuba ikamva likwikongeza ii-biomarkers zentliziyo [00:22:00] kwizinto ezinobungozi esele sithethe ngazo. Ndifuna ukukhankanya kwakhona, ndilandela nje ingcamango yokwenza uhlolo olukude okanye kwi-intanethi.

Ndiyavuma, oko kunamandla kakhulu. Kunamandla kakhulu. Kwaye ndingongeza, iindlela zokulinganisa uxinzelelo lwegazi oluqhubekayo okanye ukulinganisa uxinzelelo lwegazi rhoqo, ukujonga uxinzelelo lwegazi oluhambahambayo, loo nto. Kuba uninzi lwezigulane azinazo iimpawu ze-orthostatic, kodwa zine-hypotension emva kokutya onokuzibona.

Ndicinga ukuba kubaluleke kakhulu ukufumanisa kwizigulana ukuba uxinzelelo lwegazi oluphantsi luba mandundu na emini. Kuba amaxesha amaninzi luba mandundu kusasa, kwaye ukuba luba mandundu kusasa, awuyi kumnyanga umntu nge-vasoconstrictor imini nobusuku.

Ukuba novavanyo olunokuvavanywa kude, ndicinga ukuba lelo likamva.

UGqr. Michele Matarazzo: Kulungile, ngoko ke ndiyabona ukuba sinabalandeli abathathu abakhulu bee-biomarkers apha, nto leyo intle. Kwaye ndicinga ukuba umyalezo wokugqibela malunga nokuba olu lwazi lusebenza njani kwizigulane zokwenyani [00:23:00] ezifana nawe ubukhankanya uDavid ngenxa yoxinzelelo lwegazi. Yinto esifanele siyikhumbule ngokwenene leyo.

Emva kokuthetha ngale nto, ndifuna ukuthetha kancinci nge-pathophysiology. Ngoku, mhlawumbi Abhi, ukuba ungaphawula ngale nto, yintoni enokusifundisa yona malunga ne-autonomic dysfunction kwi-prodromal phase of disease malunga ne-pathology esisiseko yezifo zomzimba zaseLewy?

Kakade ungathetha ngayo nantoni na oyithandayo. Kodwa sele sikhankanyile lo mzimba kuqala, ingxoxo yohlobo lokuqala lobuchopho. Ucinga ntoni ngale nto?

UGqr. Abhimanyu Mahajan: Logama nje ndinelayisenisi yokuqikelela ngokugqithisileyo, ndingakwazi ukuqikelela ngokusekelwe kwinto esiyaziyo. Kodwa nje uluvo olufutshane malunga noko uGqr. Yarnall wayekuthethile ngaphambili. Andikwazanga ukuzibamba ndivakalelwa kukuba nomona we-2% kuphela xa ekhankanya ukuba i-NHS inesicwangciso seminyaka eli-10 sokudibanisa ezi zinto kuba ndingakuxelela ukuba okwangoku sinenkqubo yophando malunga nokusebenzisa iimonitha zoxinzelelo lwegazi ezijikelezayo kwiziko lethu. Kutshanje ezimbini zezigulane zethu zilahlekelwe ziimonitha zoxinzelelo lwegazi kwaye oko bekuyi-$6,000. Kwaye ndisanethemba lokuba oko kuza kuphuma kuhlahlo-lwabiwo mali lwethu lophando. Ngoko ke sizama ukwenza oko ngenxa yazo zonke izizathu endizikhankanyileyo. Kodwa kufuneka kuvele kwisibonelelo kungekhona kwinkxaso-mali karhulumente.

Emva kokuba ndithethe ngaloo nto, ndiya kumbuzo wakho. Ndicinga ukuba kukho ubungqina obuninzi obufanelekileyo, ukuba abuyonto kwisifo se-prodromal, ngoko ngokuqinisekileyo kwi-PD yokuqala kunye ne-DLB yokuqala malunga nokuba yintoni enokuba yi-pathophysiology esisiseko.

Uninzi lwazo kuqala, zithetha ngokungasebenzi kakuhle kwe-cardiovascular autonomics kunye nokuqonda. Eyona nto iphantsi endicinga ukuba ndiyikhankanye yi-cerebral autoregulation kunye nokuphazamiseka koko. Ndiyazi ukuba uGqr. Rymans upapashe oku kutshanje kwijenali yeMovement Disorders, kodwa bekukho uphononongo oluhle kakhulu kunye nohlalutyo lwe-meta apho babonise ukuba kukho ulwalamano oluthe ngqo, eneneni, babonise imbangela kuba yayisabela kwidosi, phakathi kokuguquguquka koxinzelelo lwegazi olusecaleni kunye nokuhamba kwegazi lobuchopho kwabo bane-neurogenic orthostatic hypotension. Ngoko ke, ukuba unokuguquguquka koxinzelelo lwegazi [00:25:00], unokuba nokuguquguquka kokuhamba kwegazi lobuchopho, okuya kuchaza ezinye zezi mpawu zengqondo esizibonayo.

Uthotho lwamatyala esiwapapashe kutshanje kwi-MDCP, sibone ukuba kwizigulana ezine kubekho ukwehla koxinzelelo lwegazi kwisithuba seyure ngaphambi kokuba umnakekeli wesigulana axele ukuba kukho ukuguquguquka kwengqondo. Ngoko ke yinxalenye yalo. Ewe i-locus coeruleus ibingumxholo oshushu kakhulu ixesha elide, kwaye ndicinga ukuba iyanda kakhulu kutshanje.

Ngokukhululwa kwe-noradrenaline unokuba nefuthe kungekuphela nje kwiimpawu ze-autonomic, kodwa nakwingqwalasela. Ngendlela, oku kusenokungabi yinto ethile kwizifo zomzimba zikaLewy, kodwa ngokuqinisekileyo kwizifo zomzimba zikaLewy inkqubo ye-cholinergic, endiyaziyo ukuba uGqr. Yarnall uyipapashile ngokulahlekelwa yi-cholinergic drive. Umbuzo wokubekwa kwe-alpha synuclein, nokuba kusembindini okanye ngaphesheya, uhlala uphakathi, kwaye andiqinisekanga ukuba unxulumano luye lwaphandwa ngokupheleleyo. Kwaye ndicinga ukuba ngokuqinisekileyo kufuneka lwenziwe njalo. Kwaye ke ewe, i-sympathetic denervation, akunjalo? Nguwuphi uGqr. [00:26:00] Goldstein awawugubungelayo kwasekuqaleni.

Ngoko ke olu luhlu aluphelelanga. Kusenokwenzeka ukuba ezinye zezi, okanye zonke ezi zibandakanyeka kwi-pathophysiology. Kusenokwenzeka kakhulu ukuba indibaniselwano yokuba zeziphi kwezi zibandakanyekayo yahlukile ngohlobo lwesifo kunye nohlobo lwesigulana. Ngoko ke ndicinga ukuba konke oku kufuneka kuqondwe ukuba kufuneka sithethe ngonyango lwesigulana olusebenzela loo mntu.

UDkt. Michele Matarazzo: Kulungile. Kulungile, Alison noDavid, nikhe nacatshulwa nguAbhi ngexesha lempendulo yakhe. Ngoko ke ukuba nifuna ukongeza into kule nto.

UDkt. David Goldstein: Kaloku, kukho imibuzo emibini esisiseko engakhange iphendulwe xa kufikwa kwi-pathophysiology. Eyokuqala kukuba yintoni ebangela ukunqongophala kwe-catecholamine? Ukunqongophala kwe-putamen dopamine kukhulu kakhulu, njenge-98%. Akukho enye i-neurotransmitter, kukho ezinye ii-transmitters, ewe, ezibandakanyekayo, kodwa akukho nto ifana ne-98%. Yintoni ebangela oko?

Ngaba kukho iindlela ezahlukeneyo zokusabela ezenzeka kwii-dopamine terminals. Zeziphi kuzo eziphazamisekileyo? Isiphumo [00:27:00] kuloo nqanaba lokunqongophala. Umbuzo wesibini ngulo, yintoni edibanisa ukunqongophala kwe-catecholamine kunye nemizimba yeLewy, okanye ngokwemigaqo yanamhlanje ne-alpha synucleinopathy?

Kutheni kunjalo? Oko kwachazwa nguTretiakoff kwiminyaka engaphezu kwekhulu eyadlulayo. Olu nxibelelwano phakathi kwemizimba kaLewy, awayicingayo njengophawu kunye nokususwa kombala kwi-nigral, ngoku okuya kuba kukungabikho kwe-dopamine, ingxaki ye-neurochemical.

Yintoni isiseko saloo bude? Leyo yimibuzo emibini. Ndinempendulo. Kodwa ngoku yonke le nto yingongoma nje. Asingombandela wedatha ecacileyo. Ukuba bekukho idatha ecacileyo, bendiya kufumana amabhaso kuyo yonke indawo. Le yingcinga nje.

Ingcamango kukuba into ebangela ukunqongophala kwe-catecholamine ikakhulu kukungakwazi ukugcina ii-catecholamines kwi-vesicles, [00:28:00] isiphene sokugcina ii-vesicular. Oku kwenzeka, ndicinga, kwangethuba ngaphambi kokuba kubekho i-denervation. Ndiyibiza ngokuba kukugula, kodwa ayisiyonto ifileyo.

Kwaye yintoni edibanisa olu nqongophala ne-alpha synuclein?

Oko ndicinga ukuba kuvela kwimveliso yemetabolism ye-catecholamines ebizwa ngokuba yi-aldehydes, i-catechol aldehydes. I-aldehyde ye-dopamine ibizwa ngokuba yi-DOPAL. Xa i-oxidize ngokuzenzekelayo idibanisa iifom zeproteni ngamandla kwaye ihlanganise i-alpha synuclein. Ndicinga ukuba yiyo leyo ikhonkco.

Izifo zomzimba zikaLewy azizozifo ze-synucleinopathies, kanye kanye. Zizifo apho i-alpha synuclein idibana khona ne-catecholamine metabolites, njenge-DOPAL. Kwaye kukho ubungqina obuninzi ngaphambi konyango njalo njalo. I-DOPAL yakhiwe kwi-putamen postmortem xa ithelekiswa ne-dopamine kwisifo sikaParkinson.

Kodwa ukuze [00:29:00] umeyise ngokwenene umntu othandabuzayo, kuya kufuneka wenze uphando apho uphazamisana nolu nxibelelwano uze ubonise ukuba xa usenza loo nto, awukhuli esi sifo. Kwaye oko akwenzekanga.

UDkt. Michele Matarazzo: Kwakhona, umbuzo ngulo, kutheni oko kwenzeke kwasekuqaleni?

UDkt. David Goldstein: I-DOPAL yenziwa ngalo lonke ixesha. I-Dopamine yenziwa ngalo lonke ixesha. Ngoko ke ithathwa njengetyhefu yemoto. Ayisiyonto evezwa kwindalo esingqongileyo. Ayiyonto yemfuza. Le yinxalenye yobomi. Iyenzeka ngalo lonke ixesha.

Kwabanye abantu, ukuba awukwazi ukuyisusa ityhefu kwi-aldehyde, kuba masithi unengxaki ye-aldehyde dehydrogenase ozalwa nayo, okanye ujongene nesibulali-zinambuzane esiza kuthintela umsebenzi we-aldehyde dehydrogenase. Yiloo nto iguqulela uhlobo oluqhubekayo lomngeni kwi-homeostasis kwinkqubo yesifo.

Konke oku kusekelwe kwingcamango, kodwa yiloo nto ndiyicingayo nge-pathophysiology.

UGqr. Michele Matarazzo: [00:30:00] Kuhle kakhulu. Alison, ngaphambi kokuba sithethe ngempembelelo yonyango, ngaba ufuna ukongeza into ethile kwi-pathophysiology okanye

UDkt. Alison Yarnall: Ewe, ndizonwabele ezi ngxoxo nokuva konke ngazo.

Ndicinga ukuba konke oku kubonisa into yokuba izifo zeParkinson, izifo zomzimba zeLewy, iDLB, zonke zineentlobo ezahlukeneyo zokwahluka kwaye mhlawumbi zezi zingxaki kwii-neurotransmitters ezahlukeneyo ezibangela oko.

Kwaye ndicinga ukuba ukuqhubeka nombuzo olandelayo kubonisa iziphumo zonyango zale nto. Mhlawumbi kwixesha elizayo, kweli hlabathi lihle apho sinala ma-biomarker, isigulane safika ekliniki, ukwazile ukuxelela ukuba abanazo na ii-neurotransmitters ezahlukeneyo, zeziphi iimpawu ze-autonomic abanazo ezinokuthi zichaze unyango lwabo kunye neendlela zonyango lwabo. Ukongeza, ndicinga ukuba zeziphi iimpawu ze-autonomic pro ezinokusixelela ngezifo ze-prodomal. Kwakhona kunokusinika umbono malunga nomngcipheko kunye nokwahlulwahlulwa komngcipheko. Kwaye oko kunokuxhasa lowo umbeke phambili kuvavanyo lweklinikhi.

Kwaye [00:31:00] mhlawumbi uvavanyo lokugqibela lweklinikhi luya kuba yinto ethintela umntu ukuba atshintshele kwisifo se-prodromal abe yi-DLB, PD ebonakalayo. Ngokunokwenzeka ngokufumanisa ezi mpawu zeklinikhi kunye ne-biomarker zesifo esizimeleyo, kunokusinceda sigqibe ukuba ngubani oya kuvavanyo lweklinikhi.

UGqr. Michele Matarazzo: Kulungile, ngoko ke sebenzisa iimpawu zokungasebenzi kakuhle komzimba ukuze uphucule uvavanyo lweklinikhi kwaye, usincede sijonge le ngcamango idumileyo nesetyenziswa kakhulu ngoku yeyeza elichanekileyo, sifumane unyango olufanelekileyo kwisigulana esifanelekileyo.

UDkt. Alison Yarnall: Kulungile. Ewe.

UDkt. Abhimanyu Mahajan: Ndingakongeza inqaku elinye kuloo nto?

UGqr Michele Matarazzo: Ewe, Abhi.

UGqr. Abhimanyu Mahajan: Ewe, ndicinga ukuba ukongeza izilingo zeklinikhi yeyona ndlela ilungileyo, kodwa ndingathi ngoku ekubeni sisazi ukuba ukungasebenzi kakuhle kwe-autonomic kwangoko kunxulunyaniswa nexesha elikhawulezayo lokuguqulwa kwe-pheno, kunxulunyaniswa nokugula okukhulu, ukusinda okuncinci, mhlawumbi umngcipheko omkhulu wokuqonda. Nokuba asisebenzisi [00:32:00] umthwalo we-autonomic njengesiphumo, asisebenzisi umthwalo we-autonomic ukutyebisa izilingo zeklinikhi. Ndicinga ukuba kubaluleke kakhulu ukwahlulahlula isampuli kwiimvavanyo zeklinikhi kuba oko sikucinga njengedatha eqhelekileyo ngokwesantya sokuqhubela phambili nezinto ezinjalo. Kwahlukile kakhulu kwabo banengxaki ye-autonomic.

Kwaye lulwalamano lokuphendula ngedosi. Umzekelo, kwi-autonomic failure kuphela, iqela lokujonga elineminyaka eli-10 elapapashwa kwi-UCL ekuqaleni kwalo nyaka, izigulane ezingama-281. Ngoko ke asiloqela lincinci. Ubunzima be-orthostatic hypotension yayiyenye yezinto ezibangela umngcipheko ekufeni, ekusindeni, nakwisantya sokuqhubela phambili.

Ngoko ke kubalulekile ukuba ezi zinto ziqwalaselwe ukuze kuqondwe ukuba yintoni idatha eqhelekileyo okanye eqhelekileyo kwisigulana sakho esiqhelekileyo esiqeshwe kulo naluphi na kwezi zifundo. Ndicinga ukuba le yingongoma ebalulekileyo ekufuneka uyiqonde.

Ngaphandle koko, ukuqonda ukuguqulwa kwesifo, umzekelo, sidla ngokuthelekisa iigrafu size sijonge ixesha [00:33:00] ukuze sizalise isithuba esingenanto, akunjalo? Kwaye ukuba oko kuyahluka ngenxa yokubakho komthwalo we-autonomic, ndicinga ukuba oko kufuneka kuthathelwe ingqalelo.

UGqr. Michele Matarazzo: Ngoko ke, sisebenzisa ulwazi esinalo malunga nexabiso lokuqikelela la ma-markers size siwabeke kuhlalutyo lweziphumo zovavanyo lweklinikhi. Ndicinga ukuba oko kungaba yinto enomdla kakhulu. Enkosi kakhulu. Sibe nencoko enomdla kakhulu nemangalisayo, ngoko ke ndifuna ukukubulela ngokwenene.

Ngaphambi kokuba sigqibe, ndingathanda ukunibuza umbuzo wokugqibela, umbuzo ofanayo kuni nobathathu. Kwaye kwakhona, ndiza kuqala ngoDavid. Ucinga ntoni okanye yintoni oyibona njengeyona nto iphambili kuphando kweli candelo kwiminyaka emi-5-10 ezayo?

UDkt. David Goldstein: Ukuchonga ii-biomarker zangaphambi kweklinikhi.

Ingcamango kukuba nokuba unesifo sokukhula kwesisu, sele kukho umonakalo omkhulu kakhulu. Ukuba unesifo sengqondo esingasebenzi kakuhle, ukuba unesifo sokuqaqamba kwengqondo esingaxilongwayo, loo nto injalo. Ndicinga ukuba ithemba lekamva [00:34:00] kukuchonga inkqubo yesifo ngaphambi kokuba umntu abe neempawu kwaphela. Kwaye ke injongo ayikokwandisa ixesha lesifo esineempawu. Kukwahlukileyo koko. Injongo kukulibazisa ukuqala kwesifo esineempawu. Wonke umntu uza kufa.

Kodwa ukuba ungandisa ixesha lempilo ubomi obuthile, loo nto ingaba yinjongo yoluntu. 

UGqr. Michele Matarazzo: Ugqibelele. Enkosi. Ngoku, Alison, yintoni eyona nto iphambili kuphando lwakho kweli candelo kwiminyaka emihlanu ukuya kweli-10 ezayo?

UGqr. Alison Yarnall: Ndicinga ukuba ulawulo lwezi mpawu zokuzimela ezinzima ukunyanga lubalulekile. Kukho umntu othandekayo kwisiseko sobungqina okwangoku, kwaye kudla ngokuba kukuphazamiseka okukhulu komgangatho wobomi. Ngoko ke oko kuya kuba yeyona nto iphambili kuphando lwam.

UGqr Michele Matarazzo: Mkhulu, Abhi.

UGqr. Abhimanyu Mahajan: Ndicinga ukuba kum, kwiminyaka emihlanu ukuya kweli-10 ezayo, ukuba kufuneka kuthathwe umthwalo we-autonomic kwisigulana ngasinye esine-synucleinopathy esiza ekliniki, nokuba [00:35:00] sisigulana esizalwa sinesifo somhlaza, i-PD yasekuqaleni, i-DLB ephelileyo, ukuba nje unokusibamba ngokufanelekileyo kwaye unyange ezo mpawu, kungekuphela nje ngenxa yempembelelo yezo mpawu kodwa, kwaye oku kukubonisa ukuthintela iimpawu ezinxulumene nazo kwixesha elizayo. Ndicinga ukuba oko kuya kuba yinto ephambili kum. Ngokukodwa, ndicinga ukuba ukuphazamiseka kwengqondo, asinazo izinto ezaneleyo kwizixhobo zethu zokuhlasela ukuphazamiseka kwengqondo.

Kwaye ndicinga ukuba umthwalo we-autonomic, umthwalo we-cardiovascular autonomic, yenye yezo zinto. Ikhona kanye phambi kwethu. Kufuneka senze umsebenzi ongcono ekuboniseni ukungenelela okukhokelela ekuphuculeni ingqondo. Ngaphandle koko sinokukuqikelela kwizifundo ezinxulumene noko, oko kum yeyona inkulu.

UDkt. Michele Matarazzo: Le ibe yingxoxo enomdla ngokwenene, ngoko ke ndingathanda ukunibulela nobathathu. Enkosi, David. Enkosi, Abhi. Enkosi, Alison, ngokundijoyina namhlanje.

UDkt. Alison Yarnall: Enkosi ngokundibona.

UDkt. David Goldstein: Kumnandi kakhulu.

UDkt. Michele Matarazzo: Kwaye ndifuna ukunibulela ewe, uSephira Ryman kunye neKomiti yeMicimbi yezeSayensi ye-MDS [00:36:00] ngokunceda ekubumbeni esi siqendu. Njengesikhumbuzo, ingxoxo iya kupapashwa njengeposi yebhlog kwiwebhusayithi ye-MDS, ikhethwe kwaye ihlelwe nguSephira.

Kwaye ukuba uyonwabele le nxalenye, ungalibali nokubhalisela i-podcast ye-MDS. Kwaye enkosi nonke ngokumamela.