17 agosto 2023
News
PF4 elisir nel sangue, può ‘ringiovanire’ cervello che invecchia
Far tornare indietro il tempo, riavvolgendo il nastro del cervello che invecchia. A 70 anni tornare lucidi come a 30-40. Un sogno che potrebbe trovare un alleato più vicino di quanto si pensi: nel sangue potrebbe infatti nascondersi un ‘elisir’, la spiegazione per cui sia l’esercizio fisico, sia l’ormone della longevità ‘klotho’, e sia una trasfusione di sangue ‘giovane’ sembrano essere in grado di portare un miglioramento cognitivo. La chiave del successo? Tre studi diversi portano tutti nella stessa direzione: il fattore PF4 . Su questo prodotto delle piastrine accendono i riflettori due gruppi di ricercatori Usa (entrambi Ucsf, University of California San Francisco) e uno australiano (University of Queensland), in tre articoli comparsi su ‘Nature’, ‘Nature Aging’ e ‘Nature Communications’.
E’ PF4, evidenziano gli autori, il filo rosso che lega i diversi interventi esaminati. Le piastrine sono un tipo di cellula del sangue che allerta il sistema immunitario in presenza di una ferita e aiuta a coagulare il sangue. Ora si scopre che il fattore piastrinico 4 (Pf4) è anche un potenziatore cognitivo. Sotto la sua influenza i topi anziani recuperano l’acume della mezza età e i topi giovani diventano più intelligenti, spiegano gli esperti.
“Sembra che il sangue giovane”, la proteina “klotho e l’esercizio fisico possano in qualche modo dire al cervello: migliora la tua funzione. Con PF4, stiamo iniziando a comprendere il vocabolario alla base di questo ringiovanimento”, evidenzia Saul Villeda dell’Ucsf Bakar Aging Research Institute, autore senior del documento su Nature. Villeda ha guidato lo studio sul sangue giovane. Dena Dubal, professoressa Ucsf, ha guidato lo studio su Klotho, pubblicato su Nature Aging, e Tara Walker, docente di neuroscienze all’Università del Queensland ha guidato lo studio sull’esercizio fisico, uscito su ‘Nature Communications’. “Quando ci siamo resi conto di aver trovato in modo indipendente e fortuito la stessa cosa, siamo rimasti a bocca aperta”, ha detto Dubal. “Il fatto che tre interventi separati siano convergenti sui fattori piastrinici evidenzia la validità e la riproducibilità di questa biologia. È giunto il momento di seguire questa strada nel campo della salute del cervello e del miglioramento cognitivo”.
Il primo punto di vista che viene offerto è quello del team di Villeda, il quale nel 2014 aveva scoperto che il plasma sanguigno di giovani iniettato in animali anziani aveva un effetto riparatore. Quando il suo team ha confrontato il plasma giovane con quello vecchio, ha scoperto che conteneva molto più PF4. Allo stesso modo, un’iniezione di solo PF4 in animali anziani risultava rigenerante quanto il plasma giovane: i roditori trattati ottenevano risultati migliori in una serie di compiti di memoria e apprendimento. “PF4 fa sembrare il sistema immunitario più giovane, diminuendo tutti i fattori pro-invecchiamento, portando a un cervello con meno infiammazione, più plasticità e infine più cognizione”, spiega Villeda. “Stiamo esaminando topi di 22 mesi, equivalenti a un essere umano di 70 anni, e PF4 li riporta a funzionare come se fossero alla fine dei 30 anni, o ai primi dei 40″.
Un secondo punto a favore di PF4 lo segna Dubal. Quando l’esperta un decennio fa ha dimostrato che la proteina Klotho migliora la cognizione negli animali giovani e anziani e rende il cervello più resistente alla degenerazione legata all’età, era conscia del fatto che questi effetti potessero essere indiretti perché le molecole di Klotho, iniettate, non raggiungevano mai il cervello. Il team di Dubal ha scoperto che una connessione era PF4, rilasciato dalle piastrine dopo l’iniezione. Il PF4 ha avuto un effetto importante sull’ippocampo, regione del cervello responsabile della creazione dei ricordi, dove ha potenziato la formazione di nuove connessioni neurali. Ha anche dato agli animali vecchi e giovani una spinta cerebrale nei test comportamentali, suggerendo che “c’è spazio per andare a migliorare la funzione cognitiva anche nei cervelli giovani”.
E poi c’è il capitolo dell’esercizio fisico, e del suo effetto benefico sull’uomo. L’esercizio può mantenere una mente acuta per decenni. Anche in questo caso, hanno dimostrato gli scienziati, la chiave è PF4. Walker e il suo laboratorio hanno infatti scoperto che le piastrine rilasciavano PF4 nel flusso sanguigno dopo l’attività fisica. Testando l’impatto di questo fattore da solo, anche il team australiano ha osservato un miglioramento cognitivo negli animali anziani. “Per molte persone con patologie, problemi di mobilità o di età avanzata, l’esercizio non è possibile, quindi l’intervento farmacologico è un’importante area di ricerca”, conclude Walker. “Ora possiamo mirare alle piastrine per promuovere la neurogenesi, migliorare la cognizione e contrastare il declino legato all’età”.
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Editore: Associazione Reportage - Direttore responsabile: Annamaria Persico
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0:e.pageLoadedCallback,page_method:t.page_method,page_request:t.page_request,page_time:t.page_time,page_url:t.page_url,reportable_channel:t.reportableChannel,reportable_style_id:t.reportableStyleId,tablet:t.tablet,template_id:t.templateId,type:n,user_has_ad_blocker:t.user_has_ad_blocker,uuid:t.uuid,zeroclick:t.zeroClick},browserState())},trackVisit=({callbacks:e,context:t},n,i="")=>{const s=`${i}/${TRACKING_URL}`,a=i?"include":"same-origin",o=buildSignature({callbacks:e,context:t},n);let r={};"click"===n&&(r={click:"true",session:t.uuid,nc:Date.now().toString()}),fetch(s,{method:"POST",headers:{Accept:"application/json","Content-Type":"application/json"},credentials:a,body:JSON.stringify(Object.assign({signature:encode(o)},r))})};var State$1;!function(){if(!window.CustomEvent){function e(e,t){t=t||{bubbles:!1,cancelable:!1,detail:void 0};const n=document.createEvent("CustomEvent");return n.initCustomEvent(e,t.bubbles,t.cancelable,t.detail),n}e.prototype=window.Event.prototype,window.CustomEvent=e}}(),function(e){e[e.Pending=0]="Pending",e[e.Loaded=1]="Loaded",e[e.Failed=2]="Failed"}(State$1||(State$1={}));class Provider{constructor(e){this.timeoutSeconds=5,this.handlePixelEvent=e=>{switch(this.state){case State$1.Failed:break;case State$1.Pending:setTimeout((()=>this.handlePixelEvent(e)),100);break;case State$1.Loaded:this.onPixelEvent(e)}},this.watch=()=>{switch(this.state){case State$1.Loaded:case State$1.Failed:break;case State$1.Pending:this.isLoaded()?this.state=State$1.Loaded:this.isTimedOut()?this.state=State$1.Failed:setTimeout(this.watch,50)}},this.config=e,this.identifier&&this.identifier.length>0?(this.state=State$1.Pending,this.timeoutAt=new Date,this.timeoutAt.setSeconds(this.timeoutAt.getSeconds()+this.timeoutAfter()),this.injectPixel()):this.state=State$1.Failed}get identifier(){var e;return null===(e=this.config)||void 0===e?void 0:e.key}get pixelEvents(){var e;return null===(e=this.config)||void 0===e?void 0:e.pixel_events}injectPixel(){this.injectedAt||(this.injectedAt=new Date,this.inject(),this.watch())}inject(){const e=document.createElement("script");e.text=this.script,document.head.appendChild(e)}isTimedOut(){return+new Date>=+this.timeoutAt}timeoutAfter(){return this.timeoutSeconds}selectPixelEvents(e){if(Array.isArray(this.pixelEvents))return this.pixelEvents.filter((t=>"term-view"===t.trigger&&"visit"===e||(!(!["term-click","ad-view"].includes(t.trigger)||"ctr"!==e)||"ad-click"===t.trigger&&"click"===e)))}}class Facebook extends Provider{get script(){return`!function(f,b,e,v,n,t,s){if(f.fbq)return;n=f.fbq=function(){n.callMethod?n.callMethod.apply(n,arguments):n.queue.push(arguments)};if(!f._fbq)f._fbq=n;n.push=n;n.loaded=!0;n.version='2.0';n.queue=[];t=b.createElement(e);t.async=!0;t.src=v;s=b.getElementsByTagName(e)[0];s.parentNode.insertBefore(t,s)}(window, document,'script','https://connect.facebook.net/en_US/fbevents.js');fbq('init', '${this.identifier}');`}onPixelEvent(e){this.selectPixelEvents(e).forEach((e=>{e&&(e.custom?window.fbq("trackCustom",e.event):window.fbq("track",e.event))}))}isLoaded(){return!!window.fbq}}class Outbrain extends Provider{get script(){return`!function(_window, _document) {var OB_ADV_ID = '${this.identifier}';if (_window.obApi) {var toArray = function(object) {return Object.prototype.toString.call(object) === '[object Array]' ? object : [object];};_window.obApi.marketerId = toArray(_window.obApi.marketerId).concat(toArray(OB_ADV_ID));return;}var api = _window.obApi = function() {api.dispatch ? api.dispatch.apply(api, arguments) : api.queue.push(arguments);};api.version = '1.1';api.loaded = true;api.marketerId = OB_ADV_ID;api.queue = [];var tag = _document.createElement('script');tag.async = true;tag.src = '//amplify.outbrain.com/cp/obtp.js';tag.type = 'text/javascript';var script = _document.getElementsByTagName('script')[0];script.parentNode.insertBefore(tag, script);}(window, document);`}onPixelEvent(e){this.selectPixelEvents(e).forEach((e=>{e&&window.obApi("track",e.event)}))}isLoaded(){return!!window.obApi}}class Revcontent extends Provider{get script(){return""}inject(){const e=document.createElement("script");e.src="https://assets.revcontent.com/master/rev.js",document.head.appendChild(e)}onPixelEvent(e){this.selectPixelEvents(e).forEach((e=>{e&&window.rev("event",e.event)}))}isLoaded(){return!!window.rev}}class Taboola extends Provider{get script(){return"window._tfa = window._tfa || [];!function (t, f, a, x) {if (!document.getElementById(x)) {t.async = 1;t.src = a;t.id=x;f.parentNode.insertBefore(t, f);}}(document.createElement('script'),document.getElementsByTagName('script')[0],'//cdn.taboola.com/libtrc/unip/1451879/tfa.js','tb_tfa_script');"}onPixelEvent(e){this.selectPixelEvents(e).forEach((e=>{e&&window._tfa.push({notify:"event",name:e.event,id:e.pixel_id})}))}isLoaded(){return Array.isArray(window._tfa)}}class Tiktok extends Provider{constructor(e,t){super(e),this.useAltTikTokEventsForAdsPlatformUser=t}get script(){return`!function (w, d, t) {w.TiktokAnalyticsObject=t;var ttq=w[t]=w[t]||[];ttq.methods=["page","track","identify","instances","debug","on","off","once","ready","alias","group","enableCookie","disableCookie"],ttq.setAndDefer=function(t,e){t[e]=function(){t.push([e].concat(Array.prototype.slice.call(arguments,0)))}};for(var i=0;i
{e&&window.ttq.instance(this.identifier).track(e.event)}))}isLoaded(){return!!window.ttq}}const ADS_PARAM$1="?caf",MESSAGE_PREFIX="FSXDC,.aCS:",ALLOWED_ORIGINS=["https://www.google.com","https://www.adsensecustomsearchads.com","https://syndicatedsearch.goog","https://googleadservices.com"];class Pixels{static build(e){const t=unpackPHPArrayObject(e,"pixel_tracking_data");if(t)return t.useAltTikTokEventsForAdsPlatformUser=e.is_ads,new Pixels(t)}constructor(e){this.onPixelEvent=e=>{const{detail:{type:t}}=e;switch(t){case"visit":case"ctr":case"click":this.providers.forEach((e=>e.handlePixelEvent(t)))}},this.providers=[new Facebook(e.facebook),new Tiktok(e.tiktok,e.useAltTikTokEventsForAdsPlatformUser),new Taboola(e.taboola),new Revcontent(e.revcontent),new Outbrain(e.outbrain)]}listenForEvents(){document.addEventListener("pixel",(e=>{this.onPixelEvent(e)}));window.onmessage=e=>{const{origin:t,data:n}=e;ALLOWED_ORIGINS.includes(t)&&(null==n?void 0:n.startsWith(MESSAGE_PREFIX))&&window.location.search.startsWith(ADS_PARAM$1)&&document.dispatchEvent(new CustomEvent("pixel",{detail:{type:"click"}}))}}dispatchEvent(e){document.dispatchEvent(new CustomEvent("pixel",{detail:e}))}}var State;!function(e){e[e.Pending=0]="Pending",e[e.Loaded=1]="Loaded",e[e.Failure=2]="Failure",e[e.TimedOut=3]="TimedOut",e[e.Errored=4]="Errored"}(State||(State={}));const CAF_SCRIPT_SRC=`https://www.google.com/adsense/domains/caf.js?${GOOGLE_MV3_URL_PARAMS}`,TIMEOUT_SCRIPTS=Number(GOOGLE_CAF_TIMEOUT_SCRIPTS),TIMEOUT_CALLBACKS=Number(GOOGLE_CAF_TIMEOUT_CALLBACKS);class StateMachine{constructor(){this.state=State.Pending}transitionTo(e){this.state=e}transitionFromPendingTo(e){this.done||(this.state=e)}get loaded(){return this.state===State.Loaded}get timedOut(){return this.state===State.TimedOut}get done(){return this.state!==State.Pending}}class Ads{constructor(e,t){this.state={script:new StateMachine,blocks:new StateMachine},this.blocksLoaded=[],this.injectScriptTags=()=>__awaiter(this,void 0,void 0,(function*(){return new Promise((e=>{const t=document.createElement("script");t.type="text/javascript",t.src=CAF_SCRIPT_SRC,t.addEventListener("load",(()=>e(!0))),t.addEventListener("error",(()=>e(!1))),document.body.appendChild(t),TIMEOUT_SCRIPTS>0&&setTimeout((()=>e(!1)),TIMEOUT_SCRIPTS)}))})),this.onPageLoaded=(e,t)=>{if(this.pageLoaded={requestAccepted:e,status:t},this.state.script.done)return;const n=null==t?void 0:t.error_code;n?(this.state.script.transitionTo(State.Failure),this.failureReason=`caf_pageloaderror_${n}`):this.state.script.transitionTo(State.Loaded)},this.onBlockLoaded=(e,t,n,i)=>{this.blocksLoaded.push({containerName:e,adsLoaded:t,isExperimentVariant:n,callbackOptions:i}),this.state.blocks.done||(t?this.state.blocks.transitionTo(State.Loaded):this.blocksLoaded.length>=this.blocks.length&&(this.state.blocks.transitionTo(State.Failure),this.failureReason=`caf_adloadfail_${e}`))},this.onTimeout=()=>{this.state.script.transitionFromPendingTo(State.TimedOut),this.state.blocks.transitionFromPendingTo(State.TimedOut)},this.blocks=e,this.options=t}get loaded(){return this.state.script.loaded&&!this.blocksLoaded.map((e=>e.adsLoaded)).includes(!1)}waitForBlocks(){return __awaiter(this,void 0,void 0,(function*(){return new Promise((e=>{const t=()=>{const n=performance.now();if(this.state.blocks.done)return this.cafLoadTime=Math.round(n-this.cafStartTime),void e();const i=this.blocksLoaded.map((e=>e.adsLoaded));i.includes(!1)||i.length>=this.blocks.length?e():setTimeout(t,50)};t()}))}))}inject(){return __awaiter(this,void 0,void 0,(function*(){try{const e=yield this.injectScriptTags();return this.cafStartTime=performance.now(),e&&void 0!==window.google?(new window.google.ads.domains.Caf(Object.assign(Object.assign({},this.options),{pageLoadedCallback:this.onPageLoaded,adLoadedCallback:this.onBlockLoaded}),...this.blocks),TIMEOUT_CALLBACKS>0&&setTimeout(this.onTimeout,TIMEOUT_CALLBACKS),yield new Promise((e=>{const t=()=>{this.state.script.done?e():setTimeout(t,10)};t()}))):void this.state.script.transitionTo(State.Failure)}catch(e){return void(this.error=e.toString())}}))}toCallbacks(){return{adLoadedCallback:this.blocksLoaded.slice(-1)[0],pageLoadedCallback:this.pageLoaded,cafTimedOut:this.state.script.timedOut||this.state.blocks.timedOut,cafLoadedMs:this.cafLoadTime,googleAdsFailure:!!this.failureReason}}toContext(){const e={cafScriptWasLoaded:this.state.script.loaded,cafScriptLoadTime:this.cafLoadTime,callbacks:this.toCallbacks};return this.error&&(e.js_error={message:this.error}),this.state.script.loaded||(e.zeroclick={reason:"googleAdsFailure"}),e}mockFailedState(){this.state.blocks.transitionTo(State.Failure),this.state.script.transitionTo(State.Failure)}}class TagManager{constructor(e){this.injected=!1,this.identifier=e}inject(){if(this.injected)return;if(!this.identifier)return;if("TEST"===this.identifier)return;const e=document.createElement("script");e.setAttribute("src",`https://www.googletagmanager.com/gtag/js?id=${this.identifier}`),document.head.appendChild(e),this.track(),this.injected=!0}track(){this.push("js",new Date),this.push("config",this.identifier)}push(e,t){window.dataLayer||(window.dataLayer=[]),window.dataLayer.push(arguments)}}const ADS_PARAM="caf",ADS_TRACKING_URL="_tr",BLOCKS_TYPE="ads",BLOCKS_CONTAINER="rs",KNOWN_CAF_PARAMS=["caf","query","afdToken","pcsa","nb","nm","nx","ny","is","clkt"];class Google{static build({pageOptions:e,preferredLanguage:t,blocks:n,googleAnalytics:i},s,a,o){let r={};e&&(r=Object.assign({},e),r.hl||(r.hl=t));let d=null==e?void 0:e.resultsPageBaseUrl;d||(d=window.location.origin);return new Google(s.uuid,n,r,i,d,o)}constructor(e,t,n,i,s,a){this._blocks=t,this._pageOptions=n,this.uuid=e,this._baseURL=new URL(s),this._signature=a,this.ads=new Ads(this.blocks,this.pageOptions),this.tagManager=new TagManager(i)}injectTagManager(){this.tagManager.inject()}injectAds(){return __awaiter(this,void 0,void 0,(function*(){yield this.ads.inject()}))}waitForBlocks(){return __awaiter(this,void 0,void 0,(function*(){return this.ads.waitForBlocks()}))}get blocks(){return(this._blocks||[]).filter((e=>this.wantsToServeAds?e.type===BLOCKS_TYPE:e.container===BLOCKS_CONTAINER)).map((e=>{const t=this.baseURL;new URLSearchParams(window.location.search).forEach(((e,n)=>{t.searchParams.has(n)||t.searchParams.append(n,e)}));const n=Object.assign({},e);if(n.resultsPageBaseUrl=t.toString(),this.wantsToServeAds){const e=new URLSearchParams;e.append("click","true"),e.append("session",this.uuid);const t=Object.assign({},this._signature);delete t.ad_loaded_callback,delete t.caf_loaded_ms,delete t.caf_timed_out,delete t.flex_rule,delete t.frame,delete t.js_error,delete t.no_ads_redirect,delete t.page_headers,delete t.page_request,delete t.page_loaded_callback,delete t.popup,delete t.screen_resolution,delete t.user_has_ad_blocker,delete t.user_preference,delete t.user_supports_darkmode,delete t.user_using_darkmode,delete t.zeroclick,e.append("signature",encode(t)),n.clicktrackUrl=`${TRACKING_DOMAIN}${ADS_TRACKING_URL}?${e.toString()}`}return n}))}get baseURL(){const e=new URL(this._baseURL.origin);return e.searchParams.append(ADS_PARAM,"1"),this._baseURL.searchParams.forEach(((t,n)=>{e.searchParams.append(n,t)})),e}get pageOptions(){const e=Object.assign({},this._pageOptions);return Object.keys(this._pageOptions).forEach((t=>{t.startsWith("bodis")&&delete e[t]})),e}get cannotLoadAds(){return!this.ads.loaded}get wantsToServeAds(){return new URLSearchParams(window.location.search).has(ADS_PARAM)}get adsMode(){return this.ads.loaded&&this.wantsToServeAds}get adsReady(){return this.wantsToServeAds&&!this.cannotLoadAds}get noAdsRedirectUrl(){const e=new URLSearchParams(window.location.search);return KNOWN_CAF_PARAMS.forEach((t=>e.delete(t))),`${window.location.origin}?${e.toString()}`}get callbacks(){return this.ads.toCallbacks()}toContext(){return Object.assign({blocks:this.blocks,pageOptions:this.pageOptions},this.ads.toContext())}}class CookieConsentManager{constructor(){this.injectScriptTag=()=>__awaiter(this,void 0,void 0,(function*(){return new Promise((e=>{const t=document.createElement("script");t.setAttribute("src",COOKIE_CONSENT_JS_URL),t.addEventListener("load",(()=>this.awaitConsent(e))),t.addEventListener("error",(()=>e(!1))),document.head.appendChild(t)}))}))}inject(){return __awaiter(this,void 0,void 0,(function*(){this.injected||!COOKIE_CONSENT_JS_URL||isLocal()||(this.injected=yield this.injectScriptTag())}))}awaitConsent(e){let t=0;const n=setInterval((()=>{t+=1,20===t&&(clearInterval(n),e(!0)),void 0!==window.__tcfapi&&(window.addEventListener("ConsentActivity",(t=>{const{detail:{status:n}}=t;n&&e(!0)})),clearInterval(n))}),50)}}class App{main(){var e,t;return __awaiter(this,void 0,void 0,(function*(){if(this.parkResponse=decode(),this.findDomainResponse=yield getFindDomain(),!this.findDomainResponse)throw new Error("Domain failed to load.");this.pixels=Pixels.build(this.findDomainResponse),null===(e=this.pixels)||void 0===e||e.listenForEvents(),this.adblock=new Adblock,yield this.adblock.inject(),this.google=Google.build(this.findDomainResponse,this.parkResponse,this.adblock,buildSignature({context:this.context,callbacks:null===(t=this.google)||void 0===t?void 0:t.callbacks},"click")),this.google.injectTagManager();const n=Parking.build(this.findDomainResponse,this.google);Render.prerender(n),this.cookieConsentManager=new CookieConsentManager,yield this.cookieConsentManager.inject();let i=Failed.cannotPark(this.findDomainResponse);if(i)return void(yield this.transitionToFailed(i));yield this.google.injectAds();let s=Disabled.build(this.findDomainResponse,this.adblock.state);if(s)return void(yield this.transitionToDisabled(s));const a=this.adblock.hasAdblocker();a&&this.adblock.handleAdblocked();const o=Sales.build(this.findDomainResponse);if(o)return void(yield this.transitionToSales(o));this.eligibleForZeroClick&&(this.zeroClickResponse=yield getZeroClick(this.context));const r=Redirect.build(this.findDomainResponse,this.zeroClickResponse,this.google);if(r)yield this.transitionToRedirect(r);else{if(a)return s=Disabled.build(this.findDomainResponse,this.adblock.state),void(yield this.transitionToDisabled(s));i=Failed.noSponsors(this.google),i?yield this.transitionToFailed(i):yield this.transitionToParking(n)}}))}transitionToParking(e){return __awaiter(this,void 0,void 0,(function*(){this.state=e,Render.template(e),Render.revealPage(),yield this.google.waitForBlocks(),yield this.track()}))}transitionToRedirect(e){return __awaiter(this,void 0,void 0,(function*(){this.state=e;const t=this.track();Render.revealPage(),yield waiter(e.delay,(e=>Render.loading(e))),yield t,window.location.href=e.url,log(`➡ Redirecting [${e.url}]`)}))}transitionToFailed(e){return __awaiter(this,void 0,void 0,(function*(){this.state=e,Render.message(e.message),Render.revealPage(),yield this.track()}))}transitionToSales(e){return __awaiter(this,void 0,void 0,(function*(){this.state=e,e.init(this.context),yield this.track()}))}transitionToDisabled(e){return __awaiter(this,void 0,void 0,(function*(){this.state=e,Render.message(e.message),Render.revealPage(),yield this.track()}))}track(){var e;return __awaiter(this,void 0,void 0,(function*(){if(!this.state.track)return Promise.resolve();try{const t=this.state.trackingType;return null===(e=this.pixels)||void 0===e||e.dispatchEvent({type:t}),trackVisit({context:this.context,callbacks:this.google.callbacks},t)}catch(e){return}}))}get eligibleForZeroClick(){const{cannotPark:e,canZeroClick:t,zeroClick:n}=this.findDomainResponse,{cannotLoadAds:i,wantsToServeAds:s}=this.google;return this.adblock.state!==Blocking.BLOCKED&&(!!t&&(!!e||(!(!i||s)||!!(null==n?void 0:n.reason))))}get context(){var e,t,n,i;const s=this.findDomainResponse,a=this.parkResponse,o=null===(e=this.state)||void 0===e?void 0:e.toContext(),r=null===(t=this.adblock)||void 0===t?void 0:t.toContext(),d=null===(n=this.google)||void 0===n?void 0:n.toContext(),c=browserState(),l=Object.assign(Object.assign({},null===(i=this.findDomainResponse)||void 0===i?void 0:i.zeroClick),this.zeroClickResponse);return Object.assign(Object.assign(Object.assign(Object.assign(Object.assign(Object.assign(Object.assign({app_version:APP_VERSION},s),a),r),d),o),c),{zeroClick:l})}init(){return __awaiter(this,void 0,void 0,(function*(){try{window.__parkour=this,yield this.main()}catch(e){console.error("app",e);const t=Failed.fromError(e);this.state=t,Render.message(t.message),Render.revealPage()}}))}}(new App).init(),exports.App=App}));