FrancophonIA/ELRC3.0 huggingface dataset:
English: Therefore, in addition to therapy with valaciclovir, it is recommended that patients use safer sex practices.
Slovenian: Zato je poleg zdravljenja z valaciklovirjem priporočljivo, da bolniki skrbijo za varnejšo spolnost.
English: For AEs identified from spontaneous reporting, the frequency will be referred to as “not known” as requested.
Slovenian: Za spontano prijavljene neželene pojave bo pogostnost navedena kot „ni znana“, kakor je bilo zahtevano.
English: • Do not use Valtrex after the expiry date which is stated on the carton.
Slovenian: • Zdravila Valtrex ne smete uporabljati po datumu izteka roka uporabnosti, ki je naveden na škatli.
English: Furthermore, the safety of the potentially higher intraocular concentrations of aciclovir after valaciclovir use in infected eyes has not been satisfactorily addressed.
Slovenian: Poleg tega varnost potencialno visokih intraokularnih koncentracij aciklovirja po uporabi valaciklovirja v okuženem očesu ni bila zadovoljivo obravnavana.
English: These data give confidence that the potential for development of resistance has not diminished the established benefit/risk profile of valaciclovir.
Slovenian: Ti podatki zagotavljajo, da potencial za razvoj odpornosti ni zmanjšal uveljavljenega profila koristi in tveganj, povezanega z valaciklovirjem.
English: • You will usually start taking Valtrex as soon as possible after your surgery.
Slovenian: • Običajno boste zdravilo Valtrex začeli jemati čimprej po operaciji.
English: Valaciclovir was significantly more effective than placebo in delaying the time to first genital herpes recurrence (Patel, 1997; Reitano, 1998).
Slovenian: Valaciklovir je bil bistveno učinkovitejši od placeba pri odložitvi časa do prve ponovitve genitalnega herpesa (Patel, 1997; Reitano, 1998).
English: This will help to reduce side effects that can affect the kidney or nervous system.
Slovenian: To pomaga zmanjšati neželene učinke, ki lahko prizadenejo ledvice ali živčevje.
English: For recurrent episodes of herpes simplex, this should ideally be during the prodromal period or immediately upon appearance of the first signs or symptoms.
Slovenian: Za ponavljajoče se epizode herpesa simpleksa bi moralo biti to v idealnem primeru med prodromsko fazo ali tik po pojavu prvih znakov ali simptomov.
English: • Don't take a double dose to make up for a forgotten dose.
Slovenian: • Ne vzemite dvojnega odmerka, če ste pozabili vzeti prejšnji odmerek.
English: However, if it is nearly time for your next dose, skip the missed dose.
Slovenian: Če pa je že skoraj čas za naslednji odmerek, izpustite tistega, ki ste ga pozabili vzeti.
English: Undesirable effects are listed below by body system organ class and by frequency.
Slovenian: Neželeni učinki so navedeni spodaj po organskih sistemih in pogostnosti.
English: The bioavailability of aciclovir from 1000 mg valaciclovir is 54%, and is not reduced by food.
Slovenian: Biološka uporabnost aciklovirja iz 1.000 mg valaciklovirja je 54 % in je hrana ne zmanjša.
English: Selectivity is maintained in CMV with phosphorylation, at least in part, being mediated through the phosphotransferase gene product of UL97.
Slovenian: Pri CMV se selektivnost ohrani s fosforilacijo; vsaj deloma je posredovana prek fosfotransferaznega genskega produkta UL97.
English: The included study reports have shown that no additional clinical benefit was found with 2-day vs. 1-day treatment (Spruance, 2003).
Slovenian: Vključena poročila o študijah so pokazala, da 1-dnevno zdravljenje nima večjih kliničnih koristi od 2-dnevnega zdravljenja (Spruance, 2003).
English: • reduction in the number of white blood cells (leucopenia)
Slovenian: • zmanjšanje števila belih krvnih celic (levkopenija),
English: Î If you have an allergic reaction, stop taking Valtrex and see a doctor straight away.
Slovenian: Î Če imate alergijsko reakcijo, nehajte jemati zdravilo Valtrex in takoj pojdite k zdravniku.
English: Very Common (affects more than 1 in 10 people): • headache
Slovenian: Zelo pogosti (pojavijo se pri več kot 1 od 10 oseb): • glavobol.
English: GlaxoSmithKline Latvia SIA, Bruņinieku iela 5, Riga, LV-1001
Slovenian: GlaxoSmithKline Latvija SIA, Bruņinieku iela 5, Riga, LV-1001
English: Results showed significant reductions in risk of transmission: 75 % (symptomatic HSV-2 acquisition), 50 % (HSV-2 seroconversion), and 48 % (overall HSV-2 acquisition) for valaciclovir compared to placebo.
Slovenian: Rezultati so pokazali značilno manjše tveganje prenosa: 75 % (simptomatska pridobitev HSV-2), 50 % (serološka konverzija HSV-2) in 48 % (celotna pridobitev HSV-2) za valaciklovir v primerjavi s placebom.
English: Less than 1% of the administered dose of valaciclovir is recovered in the urine as unchanged drug.
Slovenian: Manj kot 1 % uporabljenega odmerka valaciklovirja se pojavi v urinu kot nespremenjeno zdravilo.
English: Like all medicines, Valtrex can cause side effects in some people.
Slovenian: Kot vsa zdravila lahko tudi zdravilo Valtrex nekaterim ljudem povzroči neželene učinke.
English: For recurrent episodes, treatment should be for three to five days.
Slovenian: Za ponavljajoče se epizode mora zdravljenje trajati od tri do pet dni.
English: • Take Valtrex according to instructions from your doctor or pharmacist.
Slovenian: • Zdravilo Valtrex jemljite po navodilih zdravnika ali farmacevta.
English: They usually get better when Valtrex is stopped or the dose reduced.
Slovenian: Po navadi se izboljšajo po prenehanju uporabe zdravila Valtrex ali zmanjšanju odmerka.
English: Patients should be advised to avoid intercourse when symptoms are present even if treatment with an antiviral has been initiated.
Slovenian: Bolnikom je treba naročiti, naj se izognejo spolnim odnosom, kadar imajo simptome, tudi če se je zdravljenje s protivirusnim zdravilom že začelo.
English: Caution is required to prevent inadvertent overdosing.
Slovenian: Potrebna je previdnost, da bi preprečili naključno preveliko odmerjanje.
English: If you are pregnant, or think you could be, or if you are planning to become pregnant, don't take Valtrex without checking with your doctor.
Slovenian: Če ste noseči oz. mislite, da bi lahko bili noseči, ali če načrtujete nosečnost, ne vzemite zdravila Valtrex, ne da bi se posvetovali z zdravnikom.
English: Æ Don't drive or use machines unless you are sure you're not affected.
Slovenian: Æ Ne vozite ali upravljajte s stroji, če glede vpliva na vas niste prepričani.
English: The dosage of Valtrex is 2000 mg four times a day, to be initiated as early as possible post-transplant.
Slovenian: Odmerek zdravila Valtrex je 2.000 mg štirikrat na dan in ga je treba začeti uporabljati čim prej po presaditvi.
English: The French guidelines recommend valaciclovir 1000 mg 3 times daily (TID) with close follow-up [Yeni, 2008].
Slovenian: Francoska priporočila priporočajo odmerek valaciklovirja 1000 mg 3-krat dnevno s skrbnim spremljanjem [Yeni, 2008].
English: • swelling of the lips, face, neck and throat, causing difficulty in breathing (angiodema)
Slovenian: • oteklost ustnic, obraza, vratu in žrela, ki povzroči težave z dihanjem (angioedem),
English: When using this dosing regimen, treatment should not exceed one day, since this has been shown not to provide additional clinical benefit.
Slovenian: Zdravljenje po tej odmerni shemi ne sme trajati več kot en dan, ker je dokazano, da daljše zdravljenje nima dodatnih kliničnih koristi.
English: • severe allergic reactions (anaphylaxis).
Slovenian: • Hude alergijske reakcije (anafilaksija).
English: A-1140 Wien Austria
Slovenian: A-1140 Wien Avstrija
English: Due to the divergent national decisions taken by Member States concerning the authorisation of the above-mentioned products (and its associated names), the European Commission notified an official referral under Article 30(2) of Directive 2001/83/EC in order to resolve divergences amongst the nationally authorised SPCs and thus to harmonise the SPCs across the EU.
Slovenian: Zaradi različnih nacionalnih odločitev držav članic glede odobritve zgoraj navedenega zdravila (in z njim povezanih imen) je Evropska komisija v skladu s členom 30(2) Direktive 2001/83/ES prijavila uradno napotitev, da se razrešijo razlike med nacionalno odobrenimi povzetki glavnih značilnosti zdravila v EU.
English: Alter, SAEstrada Marco do Grilo
Slovenian: Portugalska Alter, SAEstrada Marco do Grilo
English: A double blind, placebo controlled study was conducted in 1,484 heterosexual, immunocompetent adult couples discordant for HSV-2 infection.
Slovenian: Dvojno slepa, s placebom nadzorovana študija je bila izvedena pri 1.484 heteroseksualnih odraslih parih, diskordantnih glede okužbe s HSV-2.
English: Given that expected peak concentrations in this group appear to be near the low end of the range for subjects with CLcr ≥ 50 mL/min and that only a single dose would be administered, assurance is provided regarding the appropriateness of the proposed regimens.
Slovenian: Glede na to, da so očitno pričakovane najvišje koncentracije v tej skupini blizu spodnji meji razpona za osebe s CLcr ≥ 50 mL/min in da se daje samo en odmerek, je to zagotovilo ustreznosti predlaganih režimov.
English: A-1140 Wien, Austria
Slovenian: A-1140 Wien, Avstrija
English: A unique combination of virus-, host- and drug-related factors explains why resistance has not emerged in the general population and also why the use of valaciclovir is unlikely to increase the prevalence of aciclovir-resistant HSV.
Slovenian: Edinstvena kombinacija dejavnikov, povezanih z virusom, gostiteljem in zdravilom, razloži, zakaj se odpornost ni pojavila v splošni populaciji in tudi zakaj uporaba valaciklovirja verjetno ne bo povečala pogostnosti proti aciklovirju odpornih virusov HSV.
English: Estimations of relationships between aciclovir pharmacokinetics and renal function are obtained from subjects in Studies P66-01, P66-02, P66-09 and P66-10 who received valaciclovir 1000mg doses.
Slovenian: Ocene povezav med farmakokinetiko aciklovirja in ledvično funkcijo so bile pridobljene iz preiskovancev v študijah P66-01, P66-02, P66-09 in P66-10, ki so prejeli odmerke 1000 mg valaciklovirja.
English: • You should take Valtrex for seven days.
Slovenian: • Zdravilo Valtrex morate jemati sedem dni.
English: This requirement for activation of aciclovir by a virusspecific enzyme largely explains its selectivity.
Slovenian: Ta pogoj aktivacije aciklovirja z encimom, specifičnim za virus, v veliki meri pojasni njegovo selektivnost.
English: Based on results from study P66-09, estimates of relative bioavailability of aciclovir from different valaciclovir dose levels were assumed to be independent of renal function.
Slovenian: Na osnovi rezultatov študije P66-09 je bilo predpostavljeno, da so ocene relativne biološke razpoložljivosti aciklovirja iz različnih ravni odmerkov valaciklovirja neodvisne od ledvične funkcije.
English: • Swallow the tablets whole with a drink of water.
Slovenian: • Tablete pogoltnite cele in z vodo.
English: There is limited clinical experience with the use of this combination.
Slovenian: Kliničnih izkušenj s to kombinacijo je malo.
English: refers to the last day of that month.
Slovenian: Datum izteka roka uporabnosti (Uporabno do) se nanaša na zadnji dan navedenega meseca.
English: The first one was a pivotal trial (Study 123-012) in renal transplant patients and the second one was a smaller trial (Study 123-031) in adult heart transplant recipients.
Slovenian: Prva študija je bila ključno preskušanje (študija 123-012) pri prejemnikih ledvic, druga pa manjše preskušanje (študija 123-031) pri odraslih prejemnikih srca.
English: Helping to prevent HSV infections from returning after you have had them
Slovenian: Pomoč za preprečevanje ponovitev okužbe s HSV, če ste jo že kdaj imeli
English: Valaciclovir has not been studied in patients with severe immune deficiency.
Slovenian: Valaciklovir ni raziskan pri bolnikih s hudo imunsko pomanjkljivostjo.
English: The incidence of aciclovir resistance is stable, has not changed in the nearly three decades aciclovir has been available, and is not different between treated patients and untreated subjects.
Slovenian: Pojavnost odpornosti proti aciklovirju je stabilna, saj se ni spremenila v skoraj tridesetih letih razpoložljivosti aciklovirja, in se ne razlikuje med zdravljenimi in nezdravljenimi osebami.
English: • Store below 30°C.
Slovenian: • Shranjujte pri temperaturi do 30°C.
English: Valaciclovir should be used with caution during breast feeding and only when clinically indicated.
Slovenian: Valaciklovir je treba med obdobjem dojenja uporabljati previdno in samo, če je klinično indiciran.
English: Laboratoires BIOGARAN 15, boulevard Charles de Gaulle 92707 COLOMBES Cedex France
Slovenian: Laboratoires BIOGARAN 15, boulevard Charles de Gaulle 92707 COLOMBES Cedex Francija
English: However, the use of valaciclovir in prophylaxis of transplant should be restricted to solid organ transplant.
Slovenian: Vendar je treba uporabo valaciklovirja za profilakso omejiti na presaditve trdnih organov.
English: Some Member States have an additional contraindication for virus resistant to aciclovir.
Slovenian: Določene države članice imajo dodatno kontraindikacijo za viruse, odporne proti aciklovirju.
English: • reduction in the number of blood platelets which are cells that help blood to clot
Slovenian: • zmanjšanje števila krvnih ploščic; to so celice, ki sodelujejo pri strjevanju krvi
English: The CHMP endorsed also contraindications regarding hypersensitivity to ACV, VACV or formulations of VACV.
Slovenian: CHMP je potrdil tudi kontraindikacije v zvezi s preobčutljivostjo za ACV, VACV in formulacije VACV.
English: Pharmacokinetic variability (% CV) in Cmax and AUC are expected to be similar for different doses and degrees of renal impairment.
Slovenian: Pričakuje se, da je farmakokinetična variabilnost (KV %) v vrednostih Cmax in AUC podobna za različne odmerke in stopnje okvare delovanja ledvic.
English: The creatinine clearance should be monitored frequently, especially during periods when renal function is changing rapidly e.g. immediately after renal transplantation or engraftment.
Slovenian: Očistek kreatinina je treba pogosto kontrolirati, zlasti med obdobji hitrega spreminjanja delovanja ledvic, npr. takoj po presaditvi ali vsaditvi ledvice.
English: Clinical response should be closely monitored in these patients.
Slovenian: Pri takšnih bolnikih je treba natančno spremljati klinični odziv.
English: Viral resistance differs from a condition where the drug must not be given for safety reasons and a distinction is to be made between safety risks versus reduced efficacy.
Slovenian: Odpornost virusov ni enaka primeru, ko zdravila ne smemo uporabiti zaradi varnostnih razlogov, zato je treba razlikovati med varnostnimi tveganji in zmanjšano učinkovitostjo.
English: Approximately 88% of the total combined plasma exposure is attributable to aciclovir, 11% to CMMG and 1% to 8-OH-ACV.
Slovenian: Približno 88 % celotne kombinirane izpostavljenosti v plazmi gre na račun aciklovirja, 11 % na račun CMMG in 1 % na račun 8-OH-ACV.
English: Valaciclovir pharmacokinetics is not dose-proportional.
Slovenian: Farmakokinetika valaciklovirja ni sorazmerna odmerku.
English: In situations where there were different incidences across studies, the most conservative approach was taken i.e. frequency category was based on the higher incidence.
Slovenian: Primeri, kjer so bile v študijah drugačne pojavnosti, so izbrali najbolj konzervativen pristop, tj. kategorija pogostnosti na osnovi višje pojavnosti.
English: Neither valaciclovir nor aciclovir is metabolized by cytochrome P450 enzymes.
Slovenian: Niti valaciklovir niti aciklovir se ne presnovita z encimi citokroma P450.
English: Sandoz GmbH Biochemiestraße 10, 6250 Kundl Austria
Slovenian: Sandoz GmbH Biochemiestraße 10, 6250 Kundl Avstrija
English: The benefit and risk assessment of the use of valaciclovir in specific indications and in specific individual pregnant or lactating women falls within the remit of the treating physician.
Slovenian: Presoja koristi in tveganja uporabe valaciklovirja v specifičnih indikacijah in pri specifičnih posameznih nosečnicah ali doječih materah je v rokah lečečega zdravnika.
English: Valtrex can be used to:
Slovenian: Zdravilo Valtrex se lahko uporablja za:
English: Renal impairment, acute renal failure (especially in elderly patients or in patients with renal impairment receiving higher than the recommended doses).
Slovenian: okvara ledvic, akutna odpoved ledvic (zlasti pri starejših bolnikih ali bolnikih z okvaro ledvic, ki prejemajo odmerke, večje od priporočenih)
English: A study of the pharmacokinetics of valaciclovir and aciclovir during late pregnancy indicates that pregnancy does not affect the pharmacokinetics of valaciclovir.
Slovenian: Študija farmakokinetike valaciklovirja in aciklovirja v pozni nosečnosti kaže, da nosečnost ne vpliva na farmakokinetiko valaciklovirja.
English: However, the 1-day valaciclovir regimen offers patients a convenient dosing alternative compared to available topical therapies and longer-course aciclovir and valaciclovir regimens.
Slovenian: Vendar 1-dnevni režim jemanja valaciklovirja bolniku nudi primerno alternativo odmerjanja v primerjavi z razpoložljivimi topičnimi terapijami in dolgotrajnejšimi režimi aciklovirja in valaciklovirja.
English: However, the modelled data presented indicated that the Cmax (suggested to be important for the short-term treatment of herpes labialis) and the AUC will still be sufficient in the group with CLcrea 30-49 ml/min.
Slovenian: Vendar predstavljeni modelni podatki kažejo, da bosta vrednosti Cmax (predlagana kot pomembna za kratkotrajno zdravljenje labialnega herpesa) in AUC še vedno zadostni v skupini bolnikov s CLcrea 30-49 ml/min.
English: Indication 2 - Herpes simplex virus (HSV) infections Regarding herpes simplex there were differences between Member States regarding site of infection and recommendations for treatment, suppression or prevention.
Slovenian: Indikacija 2 - okužbe z virusom herpes simpleks (HSV) V zvezi s herpesom simpleks obstajajo razlike med državami članicami glede mesta okužbe in priporočil za zdravljenje, supresijo in preprečevanje.
English: Herpes labialis infections (HSV-1)
Slovenian: Labialni herpes (HSV-1)
English: The selection of the studies included in this clinical trial database reflects the product safety profile for the general population exposed to valaciclovir.
Slovenian: Izbor študij, vključenih v to zbirko podatkov kliničnih preskušanj, odraža varnostni profil zdravila za splošno populacijo, izpostavljeno valaciklovirju.
English: GlaxoSmithKline Oy Piispansilta 9 A, 02230 Espoo, Finland
Slovenian: GlaxoSmithKline Oy Piispansilta 9 A, 02230 Espoo, Finska
English: The CHMP agreed to include a reference to ocular HSV in section 5.1.
Slovenian: CHMP se je strinjal, da se v poglavje 5.1 vključi sklic na očesni HSV.
English: Aciclovir is eliminated primarily unchanged in the urine via active renal tubular secretion.
Slovenian: Aciklovir se izloči predvsem nespremenjen v urinu z aktivno ledvično tubularno sekrecijo.
English: In transplant recipients receiving valaciclovir 2000 mg 4 times daily, aciclovir peak concentrations are similar to or greater than those in healthy volunteers receiving the same dose.
Slovenian: Pri prejemnikih presadkov, ki so dobivali 2000 mg valaciklovirja 4-krat na dan, je bila največja koncentracija aciklovirja podobna ali večja kot pri zdravih prostovoljcih, ki so dobivali enak odmerek.
English: These include also a Clinical Overview describing safety and efficacy of the pivotal efficacy trials.
Slovenian: V dokumentih je vključen tudi klinični pregled z opisom varnosti in učinkovitosti ključnih preskušanj učinkovitosti.
English: In the case of HSV, VZV and EBV this enzyme is the viral thymidine kinase (TK), which is only present in virus-infected cells.
Slovenian: Pri HSV, VZV in EBV je ta encim virusna timidin-kinaza (TK), ki se nahaja le v celicah, okuženih z virusom.
English: Section 4.6 Pregnancy
Slovenian: Razdelek 4.6 Nosečnost
English: The areas of disharmony mainly pertain to sections 4.1, 4.2, 4.3 and 4.6 of the SPC.
Slovenian: Razlike se nanašajo predvsem na poglavja 4.1, 4.2, 4.3 in 4.6 povzetka glavnih značilnosti zdravila.
English: The MAH gained approval in some Member States for the use of valaciclovir at a higher dose and shorter course (2g twice daily for one day) for the treatment of herpes labialis (Clinical practice recommendation of the International Herpes management Forum (IHMF) [Gilbert, 2007]).
Slovenian: Imetnik dovoljenja za promet z zdravilom je v nekaterih državah članicah dosegel odobritev uporabe večjih odmerkov valaciklovirja ter krajše trajanje zdravljenja (2 g dvakrat dnevno en dan) za zdravljenje labialnega herpesa (Priporočilo klinične prakse Mednarodnega foruma za obvladovanje herpesa - Clinical practice recommendation of the International Herpes management Forum (IHMF) [Gilbert, 2007]).
English: Valaciclovir should only be used in pregnancy if the potential benefits of treatment outweigh the potential risk.
Slovenian: Valaciklovir se sme med nosečnostjo uporabiti le, če možne koristi zdravljenja odtehtajo možna tveganja.
English: The Valtrex dosage should be adjusted accordingly.
Slovenian: Odmerek zdravila Valtrex je treba ustrezno prilagoditi.
English: As requested by the MAH, the Quality Module has been also harmonised.
Slovenian: Na željo imetnika dovoljenja za promet z zdravilom je bil usklajen tudi kakovostni modul.
English: However, the primary safety concerns with aciclovir pertain primarily to reversible acute effects on renal function due to the potential for crystallization in renal tubules.
Slovenian: Vendar se primarni varnostni zadržki za aciklovir prvotno nanašajo na reverzibilne akutne učinke na ledvično funkcijo zaradi možnosti kristalizacije v ledvičnih tubulih.
English: Confusion, hallucinations, decreased consciousness, tremor, agitation
Slovenian: zmedenost, halucinacije, zmanjšanje zavesti, tremor, agitiranost
English: Further, a detrimental effect on such activities cannot be predicted from the pharmacology of the active substance.
Slovenian: Poleg tega iz farmakologije zdravilne učinkovine ni mogoče napovedati škodljivega vpliva na ti dejavnosti.
English: The HSV resistance in the immunocompetent is low; less than 1% and in the immunosuppressed subjects ~5-6% which similarly is considered to be low.
Slovenian: Odpornost HSV pri imunsko kompetentnih osebah je nizka (manj kot 1 %), pri imunsko oslabljenih osebah pa ~5-6 %, ki se podobno šteje za nizko.
English: Cimetidine and probenecid taken together with valaciclovir increased aciclovir AUC by about 65%.
Slovenian: Cimetidin in probenecid, uporabljena skupaj z valaciklovirjem, sta povečala AUC aciklovirja za približno 65 %.
English: Laboratórios Wellcome de Portugal, Lda, Rua Dr António Loureiro Borges, nº3
Slovenian: Portugalska Laboratórios Wellcome de Portugalska, Lda, Rua Dr António Loureiro Borges, nº3
English: The CHMP noted that these findings would support an additional effect of VACV although this can not be addressed as a primary indication for treatment but can be annotated in section 5.1.
Slovenian: CHMP je ugotovil, da ta odkritja lahko podprejo dodatni učinek VACV, čeprav tega ni možno obravnavati kot primarno indikacijo za zdravljenje, vendar se lahko doda v poglavje 5.1.
English: The elimination half-life of aciclovir from breast milk was similar to that for serum.
Slovenian: Eliminacijski razpolovni čas iz materinega mleka je podoben kot za serum.
English: However, minor changes to the text were recommended as such as the amount of experience accumulated with valacicovir and aciclovir in pregnancy was quantified (designated as limited or moderate, respectively), the historical corresponding numbers from the final study report of the Pregnancy Registry were inserted to illustrate the data available.
Slovenian: Vendar so bili predlagani manjši popravki besedila, in sicer je bila količinsko opredeljena količina izkušenj z valaciklovirjem (omejena količina) in aciklovirjem (zmerna količina) v nosečnosti, in vstavljene zgodovinske ustrezne številke iz končnega poročila študije registra nosečnosti, da se prikažejo razpoložljivi podatki.