natgillin/translations-raw huggingface dataset:
What benefit has Pelzont shown during the studies?
Kakšne koristi je zdravilo Pelzont izkazalo med študijami?
Pelzont is used on its own only in patients who cannot take statins.
Zdravilo Pelzont se samostojno uporablja samo pri bolnikih, ki ne morejo jemati statina.
It should also not be used in patients who have problems with their liver, an active stomach ulcer or bleeding from an artery.
Zdravila prav tako ne smejo uporabljati bolniki, ki imajo težave z jetri, aktivno želodčno razjedo ali krvavenje iz arterije.
The most common side effect with Pelzont (seen in more than 1 patient in 10) is flushing.
Najpogostejši neželeni učinek zdravila Pelzont (opažen pri več kot 1 bolniku od 10) je zardevanje.
Two studies looked at the effectiveness of Pelzont in modifying blood fat levels.
Dve študiji sta preučevali učinkovitost zdravila Pelzont pri uravnavanju ravni maščob v krvi.
The main measure of effectiveness was the change in the blood levels of LDL cholesterol after 12 weeks.
Glavno merilo učinkovitosti je bila sprememba ravni LDL-holesterola v krvi po 12. tednih.
It was first used as a medicine to modify blood fat levels in the mid-1950s, but its use has been limited because of its side effects, particularly flushing (reddening of the skin).
Zdravilo je bilo prvič uporabljeno za zmanjševanje ravni maščob v krvi v sredini petdesetih let, vendar je bila njegova uporaba zaradi neželenih učinkov, še zlasti zardevanja (pordelosti kože), omejena.
Pelzont is a medicine containing two active substances: nicotinic acid (also known as niacin or vitamin B3) and laropiprant.
Pelzont je zdravilo, ki vsebuje dve zdravilni učinkovini: nikotinsko kislino (znano tudi kot niacin ali vitamin B3) in laropiprant.
When the receptors are blocked, PGD2 cannot dilate the vessels in the skin, reducing the frequency and intensity of flushing.
Ko so receptorji blokirani, pa PGD2 ne more razširiti krvnih žil v koži, s čimer se zmanjšuje pogostnost in intenzivnost zardevanja.
What is the risk associated with Pelzont?
Kakšna tveganja so povezana z zdravilom Pelzont?
Patients with combined mixed dyslipidaemia have high blood levels of ‘bad' LDL cholesterol and triglycerides (a type of fat), and low levels of ‘good' HDL cholesterol.
Bolniki s kombinirano mešano dislipidemijo imajo v krvi visoko raven „slabega“ LDL-holesterola in trigliceridov (vrsta maščobe) ter nizko raven „dobrega“ HDLholesterola.
Flushing due to nicotinic acid is thought to occur because of the release of a substance called ‘prostaglandin D2' (PGD2) from cells in the skin, which dilates (widens) the blood vessels in the skin.
Zardevanje zaradi nikotinske kisline naj bi se pojavljalo zaradi sproščanja učinkovine, imenovane prostaglandin D2 (PGD2), iz celic v koži, ki razširja (širi) krvne žile v koži.
They included a total of 2,349 patients who were taking either Pelzont or nicotinic acid.
Študiji sta vključevali vsega skupaj 2349 bolnikov, ki so jemali zdravilo Pelzont ali nikotinsko kislino.
Pelzont was studied in four main studies in patients with hypercholesterolaemia or mixed dyslipidaemia.
Zdravilo Pelzont so raziskovali v štirih glavnih študijah pri bolnikih s hiperholesterolemijo ali mešano dislipidemijo.
It is available as modified-release tablets.
Na voljo je v obliki tablet s prirejenim sproščanjem.
The second study showed that the LDL cholesterol levels were further reduced when Pelzont was taken with simvastatin (48% reduction), compared with Pelzont alone (17% reduction) or simvastatin alone (37% reduction).
V drugi študiji so dokazali, da je prišlo še do večjega znižanja ravni LDL-holesterola v skupini, ki je jemala zdravilo Pelzont skupaj s simvastatinom (48 % znižanje), v primerjavi s tisto, ki je jemala zdravilo Pelzont samostojno (17 % znižanje) ali samo simvastatin (37 % znižanje).
Primary hypercholesterolaemia is when the levels of cholesterol in the blood are high.
Primarna hiperholesterolemija je stanje, pri katerem so ravni obeh holesterolov v krvi visoke.
In the first study, LDL cholesterol levels were reduced by 19% in patients taking Pelzont, compared with 1% in those taking placebo.
V prvi študiji so se ravni LDL pri bolnikih, ki so jemali zdravilo Pelzont, znižale za 19 % v primerjavi z 1 % pri tistih, ki so jemali placebo.
Nicotinic acid is a naturally occurring substance that is used in low doses as a vitamin.
Nikotinska kislina je naravno prisotna spojina, ki se v majhnih odmerkih uporablja kot vitamin.
Pelzont is normally given together with a statin (the standard medicine used to reduce cholesterol) when the effectiveness of a statin taken alone is inadequate.
Zdravilo Pelzont se navadno daje skupaj s statinom (standardno zdravilo za zniževanje holesterola), kadar statin samostojno ni dovolj učinkovit.
The third and fourth studies looked at the effectiveness of laropiprant in reducing the flushing caused by nicotinic acid.
V tretji in četrti študiji so raziskovali učinkovitost laropipranta pri zmanjšanju zardevanja, ki ga povzroča nikotinska kislina.
For the full list of all side effects reported with Pelzont, see the Package Leaflet.
Za celoten seznam neželenih učinkov, o katerih so poročali pri uporabi zdravila Pelzont, glejte navodilo za uporabo.
Pelzont should not be used in people who may be hypersensitive (allergic) to nicotinic acid, laropiprant or any of the other ingredients.
Zdravila Pelzont ne smejo uporabljati osebe, ki utegnejo biti preobčutljive za (alergične na) nikotinsko kislino, laropiprant ali katero koli drugo sestavino zdravila.
Pelzont was effective in reducing the blood levels of LDL cholesterol.
Zdravilo Pelzont je bilo učinkovito pri zniževanju ravni LDL-holesterola.
‘Modified-release' means that the two active substances are released at different rates from the tablet over a few hours.
Prirejeno sproščanje pomeni, da se zdravilni učinkovini iz tablete v obdobju nekaj ur sproščata z različno hitrostjo.
The two active substances in Pelzont, nicotinic acid and laropiprant, have different modes of action.
Zdravilni učinkovini v zdravilu Pelzont, nikotinska kislina in laropiprant, imata različna načina delovanja.
In Pelzont tablets, laropiprant is in one of the layers, and the other layer contains nicotinic acid.
En sloj tablet zdravila Pelzont vsebuje laropiprant, drugi sloj pa vsebuje nikotinsko kislino.
This study also looked at the symptoms of flushing using a specially designed questionnaire.
V tej študiji so s posebnim vprašalnikom raziskovali tudi simptome zardevanja.
Adding laropiprant to nicotinic acid reduced the symptoms of flushing caused by nicotinic acid.
Če so laropiprantu dodali nikotinsko kislino, je prišlo do zmanjšanja simptomov zardevanja, ki jih povzroča nikotinska kislina.
In the first and third studies, fewer patients taking Pelzont reported moderate, severe or extreme flushing than patients taking nicotinic acid alone.
V prvi in tretji študiji je o zmernem, hudem ali skrajnem zardevanju poročalo manj tistih bolnikov, ki so jemali Pelzont, kot tistih, ki so jemali samo nikotinsko kislino.
The first study compared the effectiveness of Pelzont with that of nicotinic acid alone or placebo (a dummy treatment) in reducing the levels of LDL cholesterol in a total of 1,613 patients.
V prvi študiji so primerjali učinkovitost zdravila Pelzont s samostojno nikotinsko kislino ali placebom (zdravilom brez zdravilne učinkovine) pri zniževanju ravni LDL-holesterola pri vsega skupaj 1613 bolnikih.
The Committee for Medicinal Products for Human Use (CHMP) decided that Pelzont's benefits are greater than its risks for the treatment of dyslipidaemia, particularly in patients with combined mixed dyslipidaemia and in patients with primary hypercholesterolaemia.
Odbor za zdravila za uporabo v humani medicini (CHMP) je zaključil, da so koristi zdravila Pelzont pri zdravljenju dislipidemije, zlasti pri bolnikih s kombinirano mešano dislipidemijo in bolnikih s primarno hiperholesterolemijo, večje od z njim povezanih tveganj.
When the patient takes the tablet, laropiprant is released first into the bloodstream and blocks the PGD2 receptors.
Pri zaužitju tablete se tako v krvni obtok najprej sprosti laropiprant, ki blokira receptorje PGD2.
Flushing was measured using the flushing symptom questionnaire.
Zardevanje so merili z vprašalnikom o simptomih zardevanja.
Why has Pelzont been approved?
Zakaj je bilo zdravilo Pelzont odobreno?
In the fourth study, flushing was seen on fewer days in patients taking Pelzont than in those taking nicotinic acid alone.
V četrti študiji je bilo število dni opaženega zardevanja manjše pri tistih bolnikih, ki so jemali zdravilo Pelzont kot pri tistih, ki so jemali samo nikotinsko kislino.
The nicotinic acid is released more slowly from the other layer and has its effect as a fatmodifying agent.
Nikotinska kislina se iz drugega sloja sprošča počasneje in učinkuje kot sredstvo za uravnavanje maščob v krvi.
The full EPAR for Pelzont can be found here.
Celotno evropsko javno poročilo o oceni zdravila (EPAR) za zdravilo Pelzont je na voljo tukaj.
Pelzont is used in addition to diet and exercise in patients with dyslipidaemia (abnormally high levels of fat in the blood), particularly ‘combined mixed dyslipidaemia' and ‘primary hypercholesterolaemia'.
Zdravilo Pelzont se uporablja kot dodatek k prehrani in telesni vadbi pri bolnikih z dislipidemijo (nenormalno visoka raven maščobe v krvi), zlasti pri tistih s kombinirano mešano dislipidemijo in primarno hiperholesterolemijo.
How has Pelzont been studied?
Kako je bilo zdravilo Pelzont raziskano?
The second study compared the combination of Pelzont and simvastatin (a statin) with Pelzont alone or simvastatin alone in 1,398 patients.
V drugi študiji so pri 1398 bolnikih primerjali kombinacijo zdravila Pelzont in simvastatin (vrsta statina) s samostojnim zdravilom Pelzont ali simvastatinom.
It should be used with caution in patients who have problems with their kidneys and should not be used in patients with liver problems.
Pri bolnikih z ledvičnimi težavami je potrebna posebna previdnost pri uporabi zdravila Pelzont , pri bolnikih z jetrnimi težavami pa se zdravilo Pelzont ne sme uporabljati.
How is Pelzont used?
Kako se zdravilo Pelzont uporablja?
What is Pelzont?
Kaj je zdravilo Pelzont?
How does Pelzont work?
Kako zdravilo Pelzont deluje?
What is Pelzont used for?
Zakaj se zdravilo Pelzont uporablja?
and what is it used for?
in za kaj se uporablja?
be approved for use in the EU.
odobri za uporabo v EU.
may be given to adults or children from 3 years of age and weighing at least 15 kg.
se lahko daje odraslim ali otrokom, starejšim od treh let, ki tehtajo najmanj 15 kg.
is available as tablets.
je na voljo v obliki tablet.
can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European public assessment reports.
je na voljo na spletni strani agencije: ema.europa.eu/Find medicine/Human medicines/European public assessment reports.
is a ‘generic medicine'.
je „generično zdravilo“.
is always given with ritonavir.
se vedno daje z ritonavirjem.
This allows effective treatment while avoiding a higher dose of darunavir.
To prispeva k učinkovitemu zdravljenju in hkrati omogoča, da se bolnik izogne prejemanju višjega odmerka darunavirja.
For more information on generic medicines, see the questionand-answer document here.
Za več informacij o generičnih zdravilih si oglejte dokument z vprašanji in odgovori, ki je na voljo tukaj.
is an antiviral medicine used with other HIV medicines to treat patients with human immunodeficiency virus type 1 (HIV-1), a virus that causes acquired immune deficiency syndrome (AIDS).
je protivirusno zdravilo, ki se uporablja v kombinaciji z drugimi zdravili za zdravljenje okužbe z virusom HIV pri bolnikih, okuženih z virusom humane imunske pomanjkljivosti tipa 1 (HIV-1), tj. virusom, ki povzroča sindrom pridobljene imunske pomanjkljivosti (aids).
is a generic medicine and is bioequivalent to the reference medicine, its benefits and risks are taken as being the same as the reference medicine's.
generično zdravilo in je biološko enakovredno referenčnemu zdravilu, so njegove koristi in tveganja enaki kot pri referenčnem zdravilu.
does not cure HIV infection or AIDS, but HIV treatment may hold off the damage to the immune system and the development of infections and diseases associated with AIDS.
ne zdravi okužbe z virusom HIV ali aidsa, lahko pa upočasni slabšanje imunskega sistema ter razvoj okužb in bolezni, povezanih z aidsom.
When the enzyme is blocked, the virus does not reproduce normally, slowing down its multiplication in the body.
Ko je encim zavrt, se virus v telesu ne razmnožuje več normalno, temveč upočasnjeno.
Studies on the benefits and risks of the active substance in the approved use have already been carried out with the reference medicine, Prezista, and do not need to be repeated for Darunavir Krka d.d.
Študije o koristih in tveganjih zdravilne učinkovine pri dovoljenih uporabah so že bile izvedene z referenčnim zdravilom Prezista, zato jih ni treba ponoviti za zdravilo Darunavir Krka d.d.
contains the same active substance and works in the same way as a ‘reference medicine' already authorised in the European Union (EU) called Prezista.
To pomeni, da vsebuje enako zdravilno učinkovino in ima enak način delovanja kot referenčno zdravilo Prezista, ki je že odobreno v Evropski uniji (EU).
The European Medicines Agency concluded that, in accordance with EU requirements, Darunavir Krka d.d.
Evropska agencija za zdravila je zaključila, da je bilo v skladu z zahtevami EU dokazano, da ima zdravilo Darunavir Krka d.d.
approved?
odobreno?
Ritonavir reduces the breakdown of darunavir, increasing the levels of darunavir in the blood.
Ritonavir upočasnjuje hitrost razgradnje darunavirja in s tem povečuje njegove ravni v krvi.
As for every medicine, the company provided studies on the quality of Darunavir Krka d.d.
Kot to velja za vsako zdravilo, je družba zagotovila študije o kakovosti zdravila Darunavir Krka d.d.
Therefore, the Agency's view was that, as for Prezista, the benefit outweighs the identified risk.
Zato je menila, da njegove koristi enako kot pri zdravilu Prezista odtehtajo znana tveganja.
The medicine is to be taken with low-dose ritonavir or, as an alternative in adults, with cobicistat and with other HIV medicines, and should be taken with food.
se jemlje z nizkimi odmerki ritonavirja ali, kot druga možnost pri odraslih, s kobicistatom in drugimi zdravili za zdravljenje okužbe s HIV, jemati pa ga je treba sočasno s hrano.
can only be obtained with a prescription and treatment should be started by a healthcare professional who has experience in the management of HIV.
je le na recept, zdravljenje z njim pa mora uvesti zdravnik specialist, ki ima izkušnje z zdravljenjem okužbe z virusom HIV.
What measures are being taken to ensure the safe and effective use of Darunavir Krka d.d.
Kateri ukrepi se izvajajo za zagotovitev varne in učinkovite uporabe zdravila Darunavir Krka d.d.
This is a summary of the European public assessment report (EPAR) for Darunavir Krka d.d.
To je povzetek evropskega javnega poročila o oceni zdravila (EPAR) za zdravilo Darunavir Krka d.d.
What are the benefits and risks of Darunavir Krka d.d.
Kakšne so koristi in tveganja, povezani z zdravilom Darunavir Krka d.d.
The active substance in Darunavir Krka d.d., darunavir, is a protease inhibitor.
Zdravilna učinkovina zdravila Darunavir Krka d.d., darunavir, je zaviralec proteaze.
It is given with low-dose ritonavir or, in adults, with cobicistat.
Daje se skupaj z nizkimi odmerki ritonavirja ali pri odraslih s kobicistatom.
on 18 January 2018.
EMA/23183/2018
contains the active substance darunavir.
vsebuje zdravilno učinkovino darunavir.
For more information about treatment with Darunavir Krka d.d., read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.
preberite navodilo za uporabo (ki je prav tako del EPAR) ali se posvetujte z zdravnikom ali farmacevtom.
used?
uporablja?
Darunavir Krka d.d., taken in combination with other HIV medicines, reduces the amount of HIV in the blood and keeps it at a low level.
v kombinaciji z drugimi protivirusnimi zdravili zniža količino virusa HIV v krvi in jo vzdržuje na nizki ravni.
been studied?
raziskano?
Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Darunavir Krka d.d.
Priporočila in varnostni ukrepi, ki jih morajo za varno in učinkovito uporabo zdravila Darunavir Krka d.d.
has been shown to have comparable quality and to be bioequivalent to Prezista.
primerljivo raven kakovosti kot referenčno zdravilo Prezista ter da mu je biološko enakovredno.
For practical information about using Darunavir Krka d.d., patients should read the package leaflet or contact their doctor or pharmacist.
naj bolniki preberejo navodilo za uporabo ali se posvetujejo z zdravnikom ali farmacevtom.
Other information about Darunavir Krka d.d.
Druge informacije o zdravilu Darunavir Krka d.d.
It is not intended to provide practical advice on how to use Darunavir Krka d.d.
Povzetek ni namenjen zagotavljanju praktičnih nasvetov o njegovi uporabi.
have been included in the summary of product characteristics and the package leaflet.
upoštevati zdravstveni delavci in bolniki, so vključeni v povzetek glavnih značilnosti zdravila in navodilo za njegovo uporabo.
work?
deluje?
Why is Darunavir Krka d.d.
Zakaj je bilo zdravilo Darunavir Krka d.d.
Because Darunavir Krka d.d.
Ker je zdravilo Darunavir Krka d.d.
What is Darunavir Krka d.d.
Kaj je zdravilo Darunavir Krka d.d.
How does Darunavir Krka d.d.
Kako se zdravilo Darunavir Krka d.d.
The Agency recommended that Darunavir Krka d.d.
Priporočila je, da se zdravilo Darunavir Krka d.d.
How is Darunavir Krka d.d.
Kako je bilo zdravilo Darunavir Krka d.d.
List of the names, pharmaceutical form(s), strength(s) of the medicinal product(s), route(s) of administration, applicant(s) in the Member States
Seznam imen, farmacevtskih oblik, jakosti zdravila, poti uporabe zdravila, predlagatelj v državah članicah na
Didanosine 250 mg gastroresistant capsules, hard
Farmacevtska oblika Pot uporabe zdravila
Spain
Ime
Italy
Predlagatelj
Germany
Jakost
Further information on Verzenios can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European public assessment reports.
Nadaljnje informacije o zdravilu Verzenios so na voljo na spletni strani agencije: ema.europa.eu/Find medicine/Human medicines/European public assessment reports.
Verzenios is available as tablets (50 mg, 100 mg and 150 mg).
Zdravilo Verzenios je na voljo v obliki tablet (50 mg, 100 mg in 150 mg).
What measures are being taken to ensure the safe and effective use of Verzenios?
Kateri ukrepi se izvajajo za zagotovitev varne in učinkovite uporabe zdravila Verzenios?
The European Medicines Agency decided that the benefits of Verzenios are greater than its risks and it can be authorised for use in the EU.
Evropska agencija za zdravila je zaključila, da so koristi zdravila Verzenios večje od z njim povezanih tveganj in da se lahko odobri za uporabo v EU.
Regarding safety, the main risk is diarrhoea, which is considered manageable with dose reduction.
Kar zadeva varnost, je glavno tveganje driska, ki se šteje za obvladljivo z zmanjšanjem odmerka.
Other information about Verzenios
Druge informacije o zdravilu Verzenios
The dose should be reduced if the patient is also taking certain medicines called ‘CYP3A4 inhibitors'.
Odmerek je treba zmanjšati, če bolnik jemlje nekatera zdravila, imenovana „zaviralci CYP3A4“.
Data were considered sufficient to conclude that Verzenios can be of benefit also in women who have not yet been through the menopause.
Podatki so bili ocenjeni kot zadostni za zaključek, da je lahko zdravilo Verzenios koristno tudi pri ženskah, ki še niso preživele menopavze.
It is used together with a hormonal medicine, either an aromatase inhibitor or fulvestrant.
Uporablja se skupaj s hormonskim zdravilom, bodisi zaviralcem aromataze bodisi fulvestrantom.
As for all medicines, data on the use of Verzenios are continuously monitored.
Tako kot za vsako zdravilo se tudi podatki o uporabi zdravila Verzenios stalno spremljajo.
Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Verzenios have been included in the summary of product characteristics and the package leaflet.
Priporočila in previdnostni ukrepi, ki jih morajo za varno in učinkovito uporabo zdravila Verzenios upoštevati zdravstveni delavci in bolniki, so vključeni v povzetek glavnih značilnosti zdravila in navodilo za uporabo.
What is Verzenios and what is it used for?
Kaj je zdravilo Verzenios in za kaj se uporablja?
An overview of Verzenios and why it is authorised in the EU
Pregled zdravila Verzenios in zakaj je odobreno v EU
Side effects reported with Verzenios are carefully evaluated and any necessary action taken to protect patients.
Neželeni učinki, o katerih so poročali pri zdravilu Verzenios, se skrbno ovrednotijo in po potrebi se sprejmejo ukrepi za zaščito bolnikov.
What benefits of Verzenios have been shown in studies?
Kakšne koristi zdravila Verzenios so se pokazale v študijah?
What are the risks associated with Verzenios?
Kakšna tveganja so povezana z zdravilom Verzenios?
Verzenios is a cancer medicine used to treat women with breast cancer that is advanced or has spread to other parts of the body.
Verzenios je zdravilo za zdravljenje raka, ki se uporablja za zdravljenje žensk z rakom dojke, ki je napredoval ali se je razširil v druge dele telesa.
Grapefruit juice should be avoided during treatment with Verzenios as it may affect the way the medicine is absorbed and broken down in the body.
Soku grenivke se je med zdravljenjem z zdravilom Verzenios treba izogibati, saj lahko vpliva na to, kako se zdravilo absorbira in presnavlja v telesu.
Verzenios can only be used when the cancer cells have certain types of receptor (called hormone receptors) on their surface (HR-positive) and do not produce abnormally large quantities of another receptor called HER2 (HER2-negative).
Zdravilo Verzenios se sme uporabljati le, če imajo rakave celice na površini nekatere vrste receptorjev (imenovanih hormonski receptorji - so HR-pozitivne) in ne proizvajajo nenormalno velikih količin receptorja, imenovanega HER2 (so HER2-negativne).
For more information about using Verzenios, see the package leaflet or contact your doctor or pharmacist.
Za več informacij glede uporabe zdravila Verzenios glejte navodilo za uporabo ali se posvetujte z zdravnikom ali farmacevtom.
Why is Verzenios authorised in the EU?
Zakaj je bilo zdravilo Verzenios odobreno v EU?
The most common side effects with Verzenios (which may affect more than 1 in 10 people) are diarrhoea, infections, neutropenia (low levels of neutrophils, a type of white blood cell), anaemia (low red blood cell counts), tiredness, nausea (feeling sick), vomiting and decreased appetite.
Najpogostejši neželeni učinki zdravila Verzenios (ki se lahko pojavijo pri več kot 1 bolnici od 10) so driska, okužbe, nevtropenija (nizke vrednosti nevtrofilcev, vrste belih krvnih celic), anemija (nizka raven rdečih krvnih celic), utrujenost, navzeja (slabost), bruhanje in zmanjšan tek.
Verzenios can only be obtained with a prescription and treatment should be started and supervised by a doctor experienced in the use of cancer medicines.
Predpisovanje in izdaja zdravila Verzenios je le na recept, zdravljenje pa mora začeti in nadzorovati zdravnik, ki ima izkušnje z uporabo zdravil za zdravljenje raka.
A third study, conducted in 132 women who had received previous cancer treatment, failed to demonstrate that Verzenios used on its own was of benefit in the treatment of HR-positive, HER2negative breast cancer that had started to spread.
Tretja študija, izvedena pri 132 ženskah, ki so predhodno prejele zdravljenje proti raku, ni pokazala, da je zdravilo Verzenios kot samostojno zdravilo koristno pri zdravljenju HR-pozitivnega in HER2-negativnega raka dojke, ki se je začel širiti.