natgillin/translations-raw huggingface dataset:
Reclose the large bottle properly according to the instructions on the cap and shake vigorously for about 15 seconds.
Zaprite stekleničko točno po navodilu na zaporki in močno stresajte približno 15 sekund.
Following concomitant administration of 250 mg ciprofloxacin with clozapine for 7 days, serum concentrations of clozapine and N-desmethylclozapine were increased by 29% and 31%, respectively.
Po sedemdnevni sočasni uporabi ciprofloksacina v odmerku 250 mg so se zvečale serumske koncentracije klozapina in N-desmetilklozapina za 29 % oz. 31 %.
The occurrence of severe and persistent diarrhoea during or after treatment (including several weeks after treatment) may indicate an antibiotic-associated colitis (life-threatening with possible fatal outcome), requiring immediate treatment (see section 4.8).
Če se med zdravljenjem s ciprofloksacinom ali po njem (tudi več tednov po koncu zdravljenja) pojavi huda in trdovratna driska, so ti simptomi lahko povezani s kolitisom, ki nastane zaradi jemanja antibiotikov (življenjsko nevarno stanje z možnim smrtnim izidom), ki zahteva takojšnje zdravljenje (glejte poglavje 4.8).
If you suffer from depression or psychosis, your symptoms may become worse under treatment with Ciprofloxacin Bayer.
Če ste depresivni ali imate psihoze, se simptomi lahko poslabšajo med zdravljenjem z zdravilom Ciprofloksacin Bayer.
6.6 Special precautions for disposal and other handling Since the infusion solution is photosensitive, the infusion bags should be removed from the box only immediately before use.
6.6 Posebni varnostni ukrepi za odstranjevanje in ravnanje z zdravilom Ker je raztopina za infundiranje občutljiva za svetlobo, je treba vreče z raztopino za infundiranje vzeti iz škatle tik pred uporabo.
The infusion solution can be infused either directly or after mixing with other compatible infusion solutions.
Raztopino za infundiranje se lahko infundira neposredno ali v dodatku z drugimi kompatibilnimi raztopinami za infundiranje.
Food and drink does not affect your treatment with Ciprofloxacin Bayer.
Hrana in pijača nimata vpliva na zdravljenje z zdravilom Ciprofloksacin Bayer.
After evaluating the data presented by the Applicant/MAH, the CHMP considered that the therapeutic indication related to the empiric ciprofloxacin treatment of Shigellosis or the traveller's diarrhoea was acceptable with the wording “infections of the gastro-intestinal tract (e.g. travellers' diarrhoea)” and restricted its use in “severe” cases in section 4.2, with the following schedule regimens:
Po ovrednotenju predloženih podatkov predlagatelja/imetnika dovoljenja za promet z zdravilom je CHMP menil, da je terapevtska indikacija v zvezi z empiričnim zdravljenjem šigeloze s ciprofloksacinom ali potovalne driske sprejemljiva z ubeseditvijo „okužbe prebavil (na primer potovalna driska)“ ter omejil uporabo na „hude“ primere v poglavju 4.2 z naslednjim načinom:
Ciprofloxacin has been shown to cause photosensitivity reactions.
Ciprofloksacin povzroča fotosenzitivnostne reakcije.
Indications approved for children and adolescents in most European countries include acute pulmonary exacerbations of patients with cystic fibrosis caused by Pseudomonas aeruginosa, complicated urinary tract infections, pyelonephritis, and post-exposure prophylaxis of inhalational anthrax.
Odobrene indikacije za otroke in mladostnike v večini evropskih držav vključujejo akutne pljučne eksacerbacije pri bolnikih s cistično fibrozo, povzročeno z Pseudomonas aeruginosa, zapletenimi infekcijami sečil, pielonefritisom in zaščito po izpostavljenosti zaradi vdihavanja antraksa.
Non-renal clearance of ciprofloxacin is mainly due to active trans-intestinal secretion and metabolism.
Neledvični očistek ciprofloksacina je v glavnem posledica njegovega aktivnega izločanja skozi črevesje in presnove.
After careful evaluation, the CHMP agreed with the Applicant/MAH to delete the dose regimen “100 mg bid for 3 days” allocated to the treatment of uncomplicated cystitis.
Po natančnem pregledu se je CHMP strinjal s predlagateljem/imetnikom dovoljenja za promet z zdravilom o izbrisu načina odmerjanja „100 mg bid v treh dneh“, določenega za zdravljenje nezapletenih cist.
This will depend on the type of infection you have and how bad it is.
To je odvisno od vrste in resnosti okužbe.
Not authorised
Ni registrirano
It is an often intractable bacterial infection of the ear, mastoid and skull base caused by Pseudomonas aeruginosa.
Pogoste trdovratne bakterijske okužbe ušesa, mastoida in baze lobanje, ki jih povzroča bakterija Pseudomonas aeruginosa.
If you have a severe infection or one that is caused by more than one type of bacterium, you may be given additional antibiotic treatment in addition to Ciprofloxacin Bayer.
Če imate hudo okužbo ali okužbo, ki jo povzroča več vrst bakterij, boste mogoče hkrati z zdravilom Ciprofloksacin Bayer dobili še dodaten antibiotik.
Always use the measuring spoon provided.
Vedno uporabite merilno žličko.
Dose adjustments for patients with impaired renal function The CHMP reviewed the Applicant/MAH's initial proposal for dose adjustment in case of renal impairment and considered it incomplete and poorly substantiated.
Prilagoditev odmerkov bolnikom z oslabljenim delovanjem ledvic CHMP je preučil prvoten predlog predlagatelja/imetnika dovoljenja za promet z zdravilom glede prilagoditve odmerjanja v primeru oslabljenega delovanja ledvic in menil, da je predlog nepopoln in neustrezno utemeljen.
In a study in young beagle dogs, ciprofloxacin caused severe articular changes at therapeutic doses after two weeks of treatment, which were still observed after 5 months.
V študijah na mladih slednih psih, ki so dobivali ciprofloksacin v terapevtskih odmerkih, je le ta po dveh tednih zdravljenja povzročil hude spremembe v sklepih, ki so bile opazne tudi po 5 mesecih.
As it is not compulsory to specify the recommended antibiotic strategy in the wording of the therapeutic indication in the Marketing Authorisation, the CHMP recommended that the proposed 4.1 SPC wording “prophylaxis of invasive infections due to Neisseria meningitidis” remain, and accepted the adult posology: PO: 1 x 500 mg/d (single dose).
Ker v besedilu o terapevtskih indikacijah v dovoljenju za promet z zdravilom natančna opredelitev priporočene strategije z antibiotiki ni obvezna, je CHMP priporočil, da predlagano besedilo poglavja 4.1 povzetka glavnih značilnosti zdravila ostane nespremenjeno in sprejel odmerjanje pri odraslih: PO: 1 x 500 mg/d (enkraten odmerek).
Berkshire RG14 1JA United Kingdom Trading as: Bayer plc, Bayer Schering Pharma
Berkshire RG14 1JA Velika Britanija Ime družbe, ki trži: Bayer plc,
Shake vigorously each time before use for approximately 15 seconds.
Pred vsako uporabo jo močno stresajte približno 15 sekund!
The CHMP raised concerns on the potential uncontrolled use of ciprofloxacin in the empirical treatment of shigellosis or traveller's diarrhoea and questioned its effectiveness, especially in the mild form, pointing out the high risk of resistance induction.
Odbor za zdravila za uporabo v humani medicini je izrazil zadržke o možni nenadzorovani uporabi ciprofloksacina pri empiričnem zdravljenju šigeloze ali potovalne driske ter izpostavil vprašanje o učinkovitosti, zlasti pri zdravljenju zmernih oblik, ki lahko povzroči visoko tveganje nastanka odpornosti.
• have myasthenia gravis (a type of muscle weakness)
− imate miastenijo gravis (vrsta mišične oslabelosti)
During or following a course of treatment with ciprofloxacin bacteria that demonstrate resistance to ciprofloxacin may be isolated, with or without a clinically apparent superinfection.
Med ali po zdravljenju s ciprofloksacinom se lahko izolirajo bakterije odporne na ciprofloksacin, z ali brez klinično izražene superinfekcije.
Ciprofloxacin Bayer should be checked visually prior to use.
ZdraviloCiprofloksacin Bayer je treba pred uporabo vizualno preveriti.
Apart from routine emergency measures, it is recommended to monitor renal function, including urinary pH and acidify, if required, to prevent crystalluria.
Poleg običajnih ukrepov nujne medicinske pomoči se priporoča nadzor ledvičnega delovanja, in če je potrebno za zaščito pred kristalurijo tudi nadzor pH in kislosti seča.
It was shown in a clinical study that concomitant use of ropinirole with ciprofloxacin, a moderate inhibitor of the CYP450 1A2 isozyme, results in an increase of Cmax and AUC of ropinirole by 60% and 84%, respectively.
V kliničnih študijah so ugotovili, da se zaradi sočasne uporabe ropinirola in ciprofloksacina, ki je srednje močni zaviralec izoencima CYP450 1A2, zvečata Cmax in AUC ropinirola za 60 % oz. 84 %.
However, the recommendation of the administration of 750 mg tid and 1g bid by oral route in severe infections (respiratory tract infections, bone and joint infections) was not supported by the data submitted and the CHMP considered that none of the proposed posologies could be included in the Marketing Authorisation.
Predloženi podatki niso utemeljili priporočila za uporabo 750 mg tid in 1 g bid na peroralen način pri hudih okužbah (okužbe dihal, kosti in sklepov) in CHMP je menil, da nobeno od predlaganih odmerjanj ne more biti vključeno v dovoljenje za promet z zdravilom.
The recommended dosage can be higher (750 mg bid) depending on the severity and the microorganism.
Predlagan odmerek je glede na okužbo in mikroorganizme lahko večji (750 mg bid).
Efficacy mainly depends on the relation between the maximum concentration in serum (Cmax) and the minimum inhibitory concentration (MIC) of ciprofloxacin for a bacterial pathogen and the relation between the area under the curve (AUC) and the MIC.
Učinek je odvisen predvsem od razmerja med največjo serumsko koncentracijo (Cmax) in minimalno inhibitorno koncentracijo (MIK) ciprofloksacina proti bakterijam oziroma razmerja med področjem pod krivuljo (AUC) in MIK.
Package Leaflet and Labelling
Navodila za uporabo in označevanje
Ciprofloxacin treatment should be initiated only by physicians who are experienced in the treatment of cystic fibrosis and/or severe infections in children and adolescents.
Zdravljenje s ciprofloksacinom lahko začne le zdravnik, ki ima izkušnje z zdravljenjem cistične fibroze/hudih okužb pri otrocih in mladostnikih.
Spectrum of antibacterial activity:
Spekter protibakterijske učinkovitosti
Pseudomonas aeruginosa* Pseudomonas fluorescens Serratia marcescens* Anaerobic micro-organisms Peptostreptococcus spp.
Pseudomonas aeruginosa* Pseudomonas fluorescens Serratia marcescens * anaerobni mikroorganizmi Peptostreptococcus spp.
Ciprofloxacin should be used in combination with other antimicrobial agents depending on the results of the microbiological documentation.
Ciprofloksacin je treba uporabljati v kombinaciji z drugimi antibakterijskimi zdravili, odvisno od mikrobioloških izvidov.
Ciprofloxacin inhibits CYP1A2 and thus may cause increased serum concentration of concomitantly administered substances metabolised by this enzyme (e.g. theophylline, clozapine, ropinirole, tizanidine).
Ciprofloksacin zavira encimski sistem CYP1A2, kar lahko povzroči zvišanje serumskih koncentracij sočasno danih zdravil, ki se presnavljajo s pomočjo tega encima (npr. teofilin, klozapin, ropinirol, tizanidin).
Any calcium you take as part of a meal will not seriously affect uptake.
Kalcij, ki ga zaužijete kot del obroka, ne bo pomembno vplival na jemanje zdravila.
Treatment of some infections (e.g. pelvic inflammatory disease, intra-abdominal infections, infections in neutropenic patients and infections of bones and joints) may require co-administration with other appropriate antibacterial agents depending on the pathogens involved.
Pri zdravljenju nekaterih okužb (npr. medenične vnetne bolezni, intraabdominalnih okužb, okužb pri bolnikih z nevtropenijo in okužbah kosti in sklepov) je lahko potrebno sočasno zdravljenje z drugimi ustreznimi antibakterijskimi zdravili, odvisno od povzročitelja.
If it becomes severe or persistent or you notice that your stool contains blood or mucus tell your doctor immediately.
Če je huda in trdovratna ali če v blatu opazite kri ali sluz, takoj obvestite svojega zdravnika.
Prophylaxis of invasive infections of adults due to Neisseria meningitides Ciprofloxacin is used in clinical practice in prophylaxis of invasive infections of adults due to Neisseria meningitidis when rifampicin is contra-indicated or after microbiologically documentation when Neisseria meningitidis is resistant to rifampicin, in line with some therapeutic guidelines.
Profilaksa invazivnih okužb pri odraslih zaradi bakterije Neisseria meningitides Ciprofloksacin se uporablja v klinični praksi, v profilaksi invazivnih okužb pri odraslih zaradi bakterije Neisseria meningitidis v primeru, kadar je rifampicin kontraindiciran ali po mikrobiološki dokumentaciji, ko je bakterija Neisseria meningitidis odporna na rifampicin v skladu z nekaterimi terapevtskimi smernicami.
The CHMP asked the applicant/MAH to provide a substantiated discussion on the use of ciprofloxacin in prophylaxis of invasive infections of adults, to harmonize the therapeutic management of patients.
CHMP je predlagatelja/imetnika dovoljenja za promet z zdravilom zaprosil, naj predloži ustrezno utemeljeno razpravo o uporabi ciprofloksacina za profilakso invazivnih okužb pri odraslih za uskladitev terapevtskega vodenja bolnikov.
The changes to the SPC have been taken into account in the amendments to the Package Leaflet and Labelling.
Spremembe v povzetku glavnih značilnosti zdravila so bile upoštevane tudi pri spremembah v navodilih za uporabo in označevanju.
Administering the infusion slowly helps prevent immediate side effects occurring.
Počasno infundiranje zmanjša nevarnost takojšnjih neželenih učinkov.
Patients receiving ciprofloxacin should be well hydrated and excessive alkalinity of the urine should be avoided.
Bolniki, ki jemljejo ciprofloksacin morajo biti primerno hidrirani; izogibati se je treba preveliki alkalnosti seča.
• If you suffer from epilepsy or other neurological conditions such as cerebral ischemia or stroke, you may experience side effects associated with the central nervous system.
− Če imate epilepsijo ali kakšne druge nevrološke motnje (npr. zmanjšana prekrvavitev možganov ali možganska kap), se lahko pojavijo neželeni učinki, ki so povezani z osrednjim živčnim sistemom.
Pour the granules completely into the large bottle with the suspension fluid.
Stresite zrnca v celoti v stekleničko s suspenzijo.
- the CHMP concluded that the Marketing Authorisation could be harmonised on the following indications for oral and intravenous formulations in children and adolescents:
- da je CHMP sklenil, da se dovoljenja za promet z zdravilom lahko uskladijo pri naslednjih indikacijah za peroralne in intravenozne pripravke pri otrocih in mladostnikih:
Diarrhoea caused by Vibrio cholerae
5 dni driska, ki jo povzroča Vibrio cholerae
The resort to combination therapy, however, should be envisaged according to specific factors (including severe neutropenia).
Odločitev za uporabo ciprofloksacina v kombinaciji z drugimi antibiotiki pa mora biti sprejeta upoštevajoč določene specifične dejavnike (vključno s hudo nevtropenijo).
The Applicant/MAH proposed to take the Ciprofloxacin Modified Release Tablets out of this Referral procedure to significantly simplify the exercise of harmonisation.
Predlagatelj/imetnik dovoljenja za promet z zdravilom je predlagal, da se tablete ciprofloksacina s prirejenim sproščanjem izvzamejo iz tega napotitvenega postopka, s čimer bi bilo usklajevanje precej enostavnejše.
Most reported adverse events were not unexpected, mainly gastro-intestinal disorders or cutaneous disorders.
Najpogosteje objavljeni neželeni dogodki so bili pričakovani in so v glavnem vključevali motnje v prebavilih ali motnje na koži.
Therefore, the CHMP asked the applicant/MAH to discuss (PK/PD rational) and make a proposal in this field.
Tako je CHMP predlagatelja/imetnika dovoljenja za promet z zdravilom zaprosil naj predstavi (farmakokinetiko/farmakodinamiko) in na tem področju pripravi predlog.
As a fluoroquinolone antibacterial agent, the bactericidal action of ciprofloxacin results from the inhibition of both type II topoisomerase (DNA-gyrase) and topoisomerase IV, required for bacterial DNA replication, transcription, repair and recombination.
Kot antibakterijsko zdravilo iz skupine fluorokinolonov ciprofloksacin zavira bakterijska encima topoizomerazo II (DNK girazo) in topoizomerazo IV, ki sta potrebna za podvajanje, prepisovanje, popravljanje in rekombinacijo bakterijske DNK.
Importantly, the MR tablet formulation would not gain any new indications.
Tablete s prirejenim sproščanjem pa ne bodo mogle pridobiti nobenih novih indikacij.
If such reaction occurs, ciprofloxacin should be discontinued and an adequate medical treatment is required.
Če se pojavi taka reakcija, je treba zdravljenje s ciprofloksacinom prekiniti in ustrezno ukrepati.
Subsequently, the CHMP reached an agreement with the Applicant/MAH concerning the new proposals for dose adjustments in case of renal impairment.
Posledično je CHMP s predlagateljem/imetnikom dovoljenja za promet z zdravilom dosegel dogovor o novem predlogu prilagoditve odmerjanja v primeru oslabljenega delovanja ledvic.
The mean treatment duration of ciprofloxacin for MEO as reported in the meta-analysis on 13 publications, published by Gehanno (1993) was 3 months (6 months in 3 studies, 2 months in one study).
Meta analiza 13 publikacij, ki jo je objavil Gehanno (1993) je pokazala, da v povprečju trajanje zdravljenja malignega zunanjega otitisa s ciprofloksacinom traja 3 mesece (6 mesecev v treh študijah, 2 meseca v eni študiji).
Diarrhoea caused by Shigella dysenteriae type
1 dan driska, ki jo povzroča Shigella dysenteriae tipa
In its original document the applicant/MAH proposed an oral posology of 500 mg QD and an IV posology of 200 mgx2.
V originalnem dokumentu je predlagatelj/imetnik dovoljenja za promet z zdravilom predlagal peroralno odmerjanje z 500 mg QD (enkrat na dan) in IV odmerjanje z 200 mgx2.
For treatment of febrile neutropenic patients, when an intravenous antibiotic administration is necessary, ciprofloxacin should be administered at a 400 mg bid or tid regimen.
Za zdravljenje bolnikov z vročinsko nevtropenijo, v primeru kadar je potrebna uporaba intravenoznega antibiotika, naj se ciprofloksacin uporablja z odmerkom 400 mg z bid ali tid načinom odmerjanja.
However, 500 mg bid PO was considered inadequate for the treatment of malignant external otitis, and a dose of 750 mg bid PO was recommended for oral administration.
Kljub temu pa odmerjanje s 500 mg bid ni ustrezno pri zdravljenju malignega zunanjega otitisa, medtem ko je odmerjanje s 750 mg bid priporočeno za peroralno uporabo.
In summary, the CHMP was of the opinion that anthrax should remain part of the indications to avoid any confusion for prescribers and to be consistent with EU and international guidelines including a recommendation on ciprofloxacin as a first line treatment.
CHMP je tako menil, da naj antraks ostane del indikacije, saj se lahko tako prepreči kakršna koli zmedenost pri zdravnikih, ki predpisujejo ciprofloksacin in zagotovi skladnost z mednarodnimi smernicami in smernicami EU, vključno z navedbo, da je zdravljenje s ciprofloksacinom primarno.
More limited experience is available in treating children between 1 and 5 years of age.
Izkušnje pri otrocih starih med 1 in 5 let so bolj omejene.
• suffer from epilepsy or other neurological conditions
− imate epilepsijo ali kakšne druge nevrološke težave
If possible, take your tablets or the box with you to show the doctor.
Če je mogoče, vzemite s seboj tablete ali škatlo in jih pokažite zdravniku.
Recommended starting and maintenance doses for patients with impaired renal function:
Priporočeni začetni in vzdrževalni odmerki pri bolnikih z okvarjenim delovanjem ledvic:
Posology for severe respiratory tract infections, severe bone and joint infections In severe respiratory tract infections as well as in severe bone and joint infections, higher doses than that currently recommended (such as 750 mg x 3/day or 1000 mg x 2/day) for oral route are currently used in clinical practice given the known decreased susceptibility of the main pathogens involved (including Pseudomonas aeruginosa, Acinetobacter, Staphylococcus aureus) and the severity of the disease (as well as the difficulties in reaching optimal concentration at the bone level).
Odmerjanje pri hudih okužbah dihal, hudih okužbah kosti in sklepov Pri hudih okužbah dihal in pri hudih okužbah kosti in sklepov se v sodobni klinični praksi uporabljajo večji odmerki od trenutno priporočenih za peroralno uporabo (na primer 750 mg x3/dan ali 1000 mg x 2/dan), upoštevajoč znano zmanjšano občutljivost glavnih sodelujočih patogenov (vključno z Pseudomonas aeruginosa, Acinetobacter, Staphylococcus aureus) in resnost bolezni (ter težave pri doseganju optimalne koncentracije na ravni kosti).
Nevertheless the CHMP noted that consideration should be given to the precautions of use in ciprofloxacin treatment of such infections.
Kljub temu pa je CHMP menil, da je pri zdravljenju takšnih okužb s ciprofloksacinom potrebna posebna previdnost.
2 - Strictly follow the prescription.
Natančno upoštevati navodila.
The ready-to-use suspension is now finished.
Suspenzija je tako pripravljena za uporabo.
Your doctor will decide whether treatment with Ciprofloxacin Bayer needs to be stopped.
Zdravnik se bo odločil, če je treba zdravljenje z zdravilom Ciprofloksacin Bayer prekiniti.
¾ Take the normal dose as soon as possible and then continue as prescribed.
Če ste pozabili vzeti zdravilo, vzemite običajni odmerek takoj, ko se spomnite in nato nadaljujte kot vam je predpisal zdravnik.
Reversible renal toxicity has been reported.
Poročali so tudi o reverzibilni nefrotoksičnosti.
Patients taking ciprofloxacin should be advised to avoid direct exposure to either extensive sunlight or UV irradiation during treatment (see section 4.8).
Bolnikom, ki jemljejo ciprofloksacin, je treba odsvetovati daljše izpostavljanje neposredni sončni svetlobi ali ultravijoličnemu sevanju med zdravljenjem (glejte poglavje 4.8)
Data on photomutagenicity/photocarcinogenicity show a weak photomutagenic or phototumorigenic effect of ciprofloxacin in-vitro and in animal experiments.
Podatki o fotomutagenosti/fotokarcinogenosti kažejo na šibak fotomutageni ali fototumorogeni učinek ciprofloksacina in vitro in v poskusih na živalih.
Non-species-related breakpoints *
Mejne vrednosti za nespecifične vrste*
The Applicant/MAH did not provide any data or scientific discussion to support the single dose oral ciprofloxacin treatment of uncomplicated cystitis.
Predlagatelj/imetnik dovoljenja za promet z zdravilom ni predložil nobenih podatkov ali znanstvenih razprav, ki bi potrdile zdravljenje nezapletenih cist z enkratnim odmerkom peroralnega ciprofloksacina.
Psychiatric reactions may occur even after the first administration of ciprofloxacin.
Psihiatrične reakcije se lahko pojavijo že po prvem odmerku ciprofloksacina.
When a switch down to oral therapy is possible, a 750 mg bid ciprofloxacin regimen is recommended.
Kadar je možna sprememba terapije na peroralno, se priporoča 750 mg odmerek bid odmerjanja ciprofloksacina.
These may appear as local skin reactions which resolve rapidly upon completion of the infusion.
Lokalne kožne reakcije izginejo hitro po koncu infundiranja.
Ciprofloxacin should be used in combination with other antimicrobial agents, such as rifampicin in infections due to Staphylococci, and beta-lactams or aminoglycosides in infections due to Pseudomonas aeruginosa.
Ciprofloksacin naj se uporablja v kombinaciji z drugimi protimikrobnimi snovmi, kot so na primer rifampicin pri okužbah s stafilokoki in beta laktami ali aminoglikozidi pri okužbah s Pseudomonas aeruginosa.
Therefore, the CHMP and the Applicant/MAH were in agreement that a duration up to 3 months with ciprofloxacin was justified for the treatment of malignant external otitis.
CHMP in predlagatelj/imetnik dovoljenja za promet z zdravilom sta soglašala, da je uporaba ciprofloksacina do treh mesecev upravičena pri zdravljenju malignega zunanjega otitisa.