11 ottobre 2024
News
Infarto e ictus possono arrivare dall’intestino: la scoperta italiana
C’è una via diretta che collega l’intestino al cuore e al cervello . Un”autostrada’ lungo la quale, ‘a bordo’ del colesterolo cattivo, viaggia una sostanza che è presente in alcuni batteri del microbiota e che può innescare una trombosi responsabile di infarti e ictus. Lo ha scoperto un gruppo di ricercatori italiani diretto da Francesco Violi, presidente onorario della Simi (Società italiana di medicina interna) e professore emerito dell’università Sapienza di Roma, che ne parlerà durante il 125esimo Congresso Simi in programma a Rimini dall’11 al 13 ottobre. Per contrastare il nuovo meccanismo di malattia, sono allo studio terapie mirate .
“L’arteriosclerosi – ricordano gli internisti della Simi – è una malattia multifattoriale associata a tanti fattori di rischio, i più noti dei quali sono il fumo, il diabete di tipo 2, l’obesità, la sindrome metabolica, l’ipertensione e l’aumento del colesterolo cattivo Ldl”. Il team di Violi ha individuato un nuovo responsabile della patologia.
Cos’è e cosa fa il lipopolisaccaride (Lps)
“Il ‘colpevole’ sul quale si è appuntata la nostra attenzione – illustra lo specialista – è il lipopolisaccaride (Lps), un glicolipide che si trova nella parete dei batteri Gram negativi come l’Escherichia coli. Questa sostanza entra in circolo dopo aver attraversato la parete dell’intestino e si va a localizzare nella parete dell’arterie, dove provoca un’infiammazione cronica di basso grado. Questo danneggia nel tempo le arterie e richiama dal circolo sanguigno le piastrine che provocano la trombosi del vaso interessato. Abbiamo già condotto sperimentazioni sugli animali – riferisce Violi – che hanno dimostrato come l’Lps abbia in effetti questa ‘vocazione’ trombotica”. Ecco quindi “una nuova via attraverso la quale si estrinseca il danno aterosclerotico, la trombosi , ed è una scoperta della ricerca italiana. Ora è necessario capire come bloccare questo meccanismo, per prevenire l’infarto e le altre forme di ostruzione arteriosa causati dall’Lps”.
“Il ‘primum movens’ di questo nuovo meccanismo di malattia - riepilogano gli internisti – è un’alterata permeabilità dell’intestino causata dalla disbiosi, cioè da un’alterazione del microbiota intestinale , che favorisce il passaggio del lipopolisaccaride nella circolazione generale; questo induce uno stato infiammatorio a livello della parete arteriosa, che dà il via alla progressione dell’aterosclerosi coinvolgendo non solo le cellule di rivestimento delle arterie (cellule endoteliali), ma anche i globuli bianchi e le piastrine, rendendole più prone a formare trombi”.
Lps “si muove nel circolo sanguigno a bordo del colesterolo Ldl – precisa Violi – che utilizza come ‘cavallo di Troia’ per penetrare nella parete delle arterie . La capacità del colesterolo di infiammare le arterie potrebbe dunque essere dovuta non a lui direttamente, ma all’Lps che stimola la produzione di radicali liberi dell’ossigeno, ossidanti che vanno a infiammare la parete delle arterie e la danneggiano. Questo danno richiama poi le piastrine che formano un trombo, andando a interrompere il flusso del sangue all’interno di quell’arteria e dando quindi luogo a un infarto o un ictus”.
Chi è più a rischio?
“La presenza di questi batteri pericolosi che possono mandare in circolo l’Lps – prosegue l’esperto – è più probabile nei soggetti classicamente a rischio di infarto, ad esempio le persone con diabete o obesità . Gli individui dismetabolici presentano un’infiammazione intestinale cronica di basso grado che si associa a una disbiosi intestinale con prevalenza di batteri patogeni come l’E. coli. Abbiamo fatto esperimenti sull’animale obeso e” in effetti “siamo arrivati a dimostrare che questa condizione si associa a disbiosi intestinale, ad aumento di Lps e ad aumentato rischio di trombosi”. Commenta il presidente della Simi, Giorgio Sesti: “Questa importante serie di ricerche condotte da un gruppo di ricercatori italiani affiliati alla nostra società scientifica sono la dimostrazione che soltanto il medico internista è capace di avere un approccio olistico clinico e sperimentale in grado di affrontare lo studio di patologie complesse e multifattoriali che richiedono conoscenze mediche trasversali a tante aree specialistiche”.
Ma come intervenire per combattere gli effetti del meccanismo scoperto?
“Per ora – risponde Violi – possiamo fare solo ipotesi. Ci sono varie possibilità di prevenzione del danno da Lps che stiamo esplorando. Una potrebbe essere modulare la composizione della flora batterica intestinale, attraverso la somministrazione di probiotici e prebiotici . Un’altra possibilità è somministrare cicli di antibiotici intestinali non assorbibili per correggere la disbiosi: negli animali abbiamo ottenuto risultati molto interessanti. Un’altra strada ancora potrebbe essere bloccare l’azione dell’Lps una volta entrato in circolo, impedendogli di interagire con il suo recettore sulla parete delle arterie, quindi di attivare tutta la cascata di eventi che porterà alla trombosi: stiamo già lavorando a una possibile terapia farmacologica che sfrutta l’Lps come nuovo target terapeutico anti-trombosi. Potremmo infine anche pensare a una possibile azione favorevole degli analoghi recettoriali del Glp-1″: un’altra applicazione dei nuovi farmaci anti-diabete e anti-obesità, “visto che riducono la permeabilità intestinale e hanno un effetto di protezione cardiovascolare. Ma non ci sono prove in tale senso”, almeno al momento.
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Editore: Associazione Reportage - Direttore responsabile: Annamaria Persico
Reportage è una testata iscritta al n.18 Registro Stampa Tribunale di Lamezia Terme il 27-11-1962. © 2020 - reportage
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Object.assign({ad_loaded_callback:null==e?void 0:e.adLoadedCallback,app_version:version,caf_client_id:null===(i=null==t?void 0:t.pageOptions)||void 0===i?void 0:i.pubId,caf_timed_out:null==e?void 0:e.cafTimedOut,caf_loaded_ms:null==e?void 0:e.cafLoadedMs,channel:null===(s=null==t?void 0:t.pageOptions)||void 0===s?void 0:s.channel,desktop:t.desktop,terms:null===(a=null==t?void 0:t.pageOptions)||void 0===a?void 0:a.terms,fd_server_datetime:t.fd_server_datetime,fd_server:t.fd_server,flex_rule:t.flex_rule,host:t.host,ip:t.ip,ivt:null===(o=null==t?void 0:t.pageOptions)||void 0===o?void 0:o.ivt,js_error:t.js_error,mobile:t.mobile,no_ads_redirect:t.noAdsRedirect,page_headers:t.page_headers,page_loaded_callback:null==e?void 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}));