Morphology of placentome in Korean water deer Hydropotes inermis argropus

The placenta of the Korean water deer was anatomically examined to accumulate basic information regarding its reproductive system. The convex placentomes with five to nine well-developed pedicles were observed in the whole uterine horns, and therefore, the placenta was classified as oligocotyledonary. The evidence indicating the migration of binucleate cells (BNCs) from trophectoderm to the uterine epithelium led to the histological classification of the placenta as synepitheliochorial. The number of fetuses was markedly higher than that in other ruminant species. However, the number of placentomes was found to be similar to the other Cervidae species. Therefore, these results suggest that the Korean water deer may possess special mechanisms or structures at the fetus attachment site to maintain this unusally high number of fetuses.     

Immobilization of mink (Mustela vison) with medetomidine-ketamine and remobilization with atipamezole

Four groups of mink were immobilized with medetomidine-HCl (MED) 0.1 mg/kg + ketamine (KET) 5 or 7.5 mg/kg at different ambient temperatures. The induction time, degree of immobilization and analgesia, rectal temperature, heart and respiration rates were recorded at intervals throughout the immobilization period. The animals were then given atipamezole-HCl (ATI) 0.5 mg/kg for reversal at different times after injection of MED/KET and the effects of the antagonist were evaluated.Subcutaneous administration of MED/KET induced complete immobilization in all 20 animals, and the highest dose was considered suitable for major surgery. Prolonged immobilization at low ambient temperatures (–10 to +5°C) caused severe hypothermia in all animals. The mean rectal temperature had dropped to 37.8°C and 32.1°C at 15 and 85 min, respectively, after injection of MED/KET, significantly lower than the corresponding values for animals immobilized at room temperature.Intramuscular administration of ATI 20 or 40 min after injection of MED/KET rapidly remobilized the animals without apparent side-effects. Administration of ATI to animals recovering spontaneously 90 min after injection of MED/KET induced thermogenesis (shivering) in animals immobilized at a low ambient temperature, while no such effect was seen in animals immobilized at room temperature. One hour after injection of ATI, the rectal temperatures of all treated animals had returned to normal and there were no signs of abnormal behaviour.     

Evaluation of the anaesthetic effects of medetomidine and ketamine in rats and their reversal with atipamezole

ObjectivesTo compare the anaesthetic effects of varying doses of medetomidine (MED) combined with ketamine (KET) in rats, and to determine the efficacy of atipamezole (ATI) in the reversal of these effects using electroencephalogram (EEG) and assessment of clinical parameters.Study designProspective, randomized experimental trial.AnimalsTwenty-one male Sprague–Dawley rats weighing 300–398 g and aged 8–11 weeks old.MethodsThree groups received intraperitoneal injections of MED (0.2, 0.4 or 0.8 mg kg^?1) with KET (60 mg kg^?1) (MED-200, MED-400 and MED-800). Atipamezole, at doses five times higher than the previous dose of MED, was then administered intraperitoneally 70 minutes after MED-KET injection. The EEG band powers and spectral edge frequencies (SEFs), respiratory rates, reflex scores to toe-web clamping and behavioural changes were measured. Correlations between EEG parameters and reflex scores were also evaluated.ResultsThe duration of surgical anaesthesia was directly proportional to the dose of MED. Lower frequency bands (δ1 to α2) increased in all groups, and these changes were reversed by ATI. Minimal changes were observed in the higher frequency bands (β1 to γ), but their powers were increased by ATI. The SEFs were decreased in all groups, and they were reversed by ATI. While α1 band power and SEF95 showed strong correlations with the depth of anaesthesia, their changes appeared before the measured decreases in reflex score. Recovery from anaesthesia was extended by increasing the dose of MED.Conclusions and clinical relevanceSpectral EEG parameters may not accurately predict the depth of surgical anaesthesia because they had already changed during the induction of surgical anaesthesia. The ATI dose used in the present study may not be enough for complete reversal of anaesthesia induced by MED-KET.     

Assessment of ketamine and medetomidine anaesthesia in the domestic rabbit

OBJECTIVE: To study the effects of ketamine and two doses of medetomidine administered by two routes of injection in a genetically diverse population of rabbits. STUDY DESIGN: Prospective, randomized, clinical trial. ANIMALS: One hundred and five domestic rabbits of mixed breed, sex and age. MATERIALS AND METHODS: Rabbits undergoing orchiectomy or ovariohysterectomy received ketamine (15 mg kg(-1)) combined with medetomidine at 0.25 or 0.5 mg kg(-1), by subcutaneous (SC) or intramuscular (IM) injection. Anaesthesia was supplemented with 1.5-2% isoflurane when signs of regular jaw movements and/or slight limb twitching indicated inadequate anaesthesia. Heart and respiratory rate, blood oxygen saturation, end-tidal carbon dioxide concentration and rectal temperature were monitored at several time points. Duration of surgical anaesthesia and anaesthesia time were measured. At completion of surgery, atipamezole (1.0 or 0.5 mg kg(-1), IM or SC) was administered. STATISTICAL ANALYSES: MANOVA was used to compare variables over time between males and females, anaesthetic doses and routes of drug administration. RESULTS: All reflexes were lost significantly more rapidly after IM drug administration (p < 0.05). The times (in minutes) from drug injection to loss of reflexes for the respective groups were: righting reflex: 6.3 (15.0 + 0.25, SC), 5.5 (15.0 + 0.5, SC), 2.9 (15.0 + 0.25, IM) and 2.3 (15.0 + 0.5, IM); ear pinch: 9.2, 8.5, 4.8, 3.6; pedal withdrawal: 12.8, 10.4, 6.6, 5.2. Heart and respiratory rates during surgery did not differ between groups, however the highest end-tidal CO(2) concentration during surgery was significantly affected by dose, with the highest concentration occurring in group 15.0 + 0.5 IM. The number of animals requiring isoflurane tended to decrease with increasing dose of anaesthetic and significantly more females required supplementation than males (p < 0.05). Recovery from anaesthesia (return of righting reflex) was not significantly different between dose groups (p > 0.1) but was more rapid in animals given IM atipamezole (13.6 +/- 13 versus 21 +/- 17, p = 0.037). No anaesthetic-related mortality occurred and all but three animals recovered uneventfully. Five animals were killed whilst under anaesthesia because of unrelated disease. CONCLUSION AND CLINICAL RELEVANCE: Ketamine-medetomidine combinations reliably produced surgical anaesthesia in domestic rabbits that could easily be deepened for brief periods with low concentrations of isoflurane. Subcutaneous administration was better tolerated, but the speed of induction was slower compared with IM injection. Atipamezole was an effective antagonist and produced most rapid effects when administered IM.     

Medetomidine-ketamine-isoflurane anaesthesia in pygmy hippopotami (Choeropsis liberiensis)--a case series

History Medical knowledge of pygmy hippopotami is limited. Anaesthesia has been considered a challenge because of the anatomy, semi‐aquatic life style and aggressive behaviour. Polycystic kidney disease (PKD) has been described and can contribute to active kidney disease potentially affecting anaesthesia. Physical examination and Management Fourteen pygmy hippopotami were anaesthetized for general health assessment and reproductive procedures. Animals (estimated bodyweight 250 kg) were darted intramuscularly with 0.08 mg kg^?1 medetomidine and 1.2 mg kg^?1 ketamine. After endotracheal intubation, anaesthesia was maintained with isoflurane delivered either by circle system (100% oxygen) or by Triservice apparatus (air or air/oxygen admixture). Heart rate (HR) respiratory rate (f_R), oxygen saturation (SpO₂) and end tidal CO₂ were recorded at 5‐minute intervals. Atipamezole was administered intramuscularly (0.4 mg kg^?1) at the end of the procedure. Statistical analysis was performed using anova (p < 0.05). Most animals rapidly became recumbent although five hippopotami needed additional drugs to assure acceptable immobilization. There were no statistical differences in mean HR between animals with or without PKD (PKD: 34 ± 8 beats minutes^?1; no PKD: 33 ± 6 beats minutes^?1), f_R (PKD: 15 ± 7 breaths minutes^?1; no PKD; 12 ± 5 breaths minutes^?1) and end tidal CO₂ (PKD: 7.1 ± 1.3 kPa; no PKD: 7.8 ± 1.4 kPa). SpO₂ was higher in animals receiving 100% oxygen or air with oxygen (92 ± 8% and 91 ± 9% respectively) compared with animals receiving air only (77 ± 5%) (p = 0.003). Recovery was uneventful after atipamezole administration. Follow‐up There were no apparent adverse effects after anaesthesia during a 24‐hour follow‐up period. Discussion and conclusions Medetomidine‐ketamine‐isoflurane induced satisfactory anaesthesia in this species. Incremental induction doses were related to remote injection and the animals’ thick skin. There were no differences in anaesthetic parameters in animals with or without PKD. Supplemental oxygen should be mandatory during anaesthesia in this species.     

Xylazine-induced sedation in axis deer (Axis axis) and its reversal by atipamezole

Eight free-ranging axis deer (Axis axis) were captured in drive nets and injected with xylazine (3.4±0.1 mg/kg; mean ±SEM) intramuscularly using a hand-held syringe. Xylazine induced complete immobilization and sedation in three animals, heavy sedation in three, and moderate sedation in two. The mean induction time was 10.4±1.0 min. The mean rectal temperature, heart and respiratory rates of immobilized animals were 39.2±0.4°C, 75.5±6.5 beats/min and 62.1±4.2 breaths/min, respectively.All the animals were given atipamezole intravenously for reversal. The mean time from injection of xylazine to administration of atipamezole was 37.8±4.6 min. A dose ratio (w/w) for xylazine:atipamezole-HCl of 10:1 was used. The mean time from injection of atipamezole to mobility was 2.41±0.58 min.Atipamezole given intravenously effectively antagonized xylazine-induced sedation in axis deer. Only one animal showed signs of overalertness after reversal and no cases of resedation were observed.Abbreviations i.m. intramuscular(ly) - i.v. intravenous(ly) - SEM standard error of the mean     

A specific suppurative epididymitis of rams

On the basis of worm counts in naturally infected Angora-X goats, albendazole at either 3.8mg/kg repeated after 24 hours or as a single dose at 7.6mg/kg, was >99% effective in removing adult Ostertagia and Trichostrongylus spp. Small numbers of adult Haemonchus contortus, Cooperia sp. and Chabertia ovina were present in control but not treated animals. The single dose of 7.6mg/kg removed > 99% of adult Oesophagostomum venulosum whereas the repeated dose of 3.8mg/kg removed only 96%.     

Anaesthesia with medetomidine,midazolam and ketamine in six gorillas after premedication with oral zuclopenthixol dihydrochloride

ObjectiveTo evaluate the effects of medetomidine, midazolam and ketamine (MMK) in captive gorillas after premedication with oral zuclopenthixol.Study designCase series.AnimalsSix gorillas, two males and four females, aged 9–52 years and weighing 63–155 kg.MethodsThe gorillas were given zuclopenthixol dihydrochloride 0.2 ± 0.05 mg kg^?1 per os twice daily for 3 days for premedication. On the day of anaesthesia the dose of zuclopenthixol was increased to 0.27 mg kg^?1 and given once early in the morning. Anaesthesia was induced with medetomidine 0.04 ± 0.004 mg kg^?1, midazolam 0.048 ± 0.003 mg kg^?1 and ketamine 4.9 ± 0.4 mg kg^?1 intramuscularly (IM). Upon recumbency, the trachea was intubated and anaesthesia was maintained on 1–2% isoflurane in oxygen. Physiological parameters were monitored every 10 minutes and arterial blood gas analysis was performed once 30–50 minutes after initial darting. At the end of the procedure, 42–115 minutes after initial darting, immobilisation was antagonized with atipamezole 0.21 ± 0.03 mg kg^?1 and sarmazenil 5 ± 0.4 μg kg^?1 IM.ResultsRecumbency was reached within 10 minutes in five out of six animals. One animal required two additional darts before intubation was feasible. Heart rate ranged from 60 to 85 beats minute^?1, respiratory rate from 17 to 46 breaths minute^?1 and temperature from 36.9 to 38.3 °C. No spontaneous recoveries were observed and anaesthetic level was stable. Blood gas analyses revealed mild respiratory acidosis, and mean PaO₂ was 24.87 ± 17.16 kPa (187 ± 129 mmHg) with all values being above 13.4 kPa (101 mmHg). Recovery was smooth and gorillas were sitting within 25 minutes.Conclusion and clinical relevanceThe drug combination proved to be effective in anaesthetizing captive gorillas of various ages and both sexes, with minimal cardio-respiratory changes.     

獐(Hydropotes inermis)生态学研究进展

獐是一种较为原始的鹿科动物,为东亚地区特有种,被列为国家Ⅱ级重点保护动物.上个世纪以来,过度捕猎和栖息地丧失使獐的种群数量和分布范围经历了急剧的减少,种群数量已不足10000只.迄今,国内外开展了大量关于该物种及其栖息地的生态学研究.本文从獐的分类地位、种群分布、觅食对策、空间利用、活动节律、集群行为、繁殖与寿命等方面对獐的国内外研究现状进行了梳理,旨在归纳已有的研究发现,结合研究和保护管理工作的需要,对未来研究热点进行前瞻.     

Evaluation of butorphanol, medetomidine and midazolam as a reversible narcotic combination in free-ranging African lions (Panthera leo)

ObjectiveTo evaluate the effects of the combination butorphanol, medetomidine and midazolam (BMM) and its reversibility in lions.Study designProspective clinical trial.AnimalsThirty free-ranging lions, 10 male and 20 female, weighing 81-210 kg.MethodsLions were immobilised with butorphanol mean 0.31 ± SD 0.034 mg kg^?1, medetomidine 0.052 ± 0.006 mg kg^?1, midazolam 0.21 ± 0.024 mg kg^?1 and hyaluronidase 1250 IU administered intramuscularly with a dart gun. Upon recumbency, physiological parameters and anaesthetic depth were monitored 10-15 minutes after darting (T1) and repeated every 10 minutes for a further 30 minutes (T2, T3, T4). Arterial blood gas analyses were performed at T1 and T4. At the end of the procedure, 45-60 minutes after initial darting, immobilisation was reversed with naltrexone 0.68 ± 0.082 mg kg^?1, atipamezole 0.26 ± 0.031 mg kg^?1, and flumazenil 0.0032 ± 0.0007 mg kg^?1 administered intravenously and subcutaneously.ResultsThe BMM combination rapidly induced immobilisation and lateral recumbency was reached within 7.25 ± 2.3 minutes. Median induction score [scored 1 (excellent) to 4 (poor)] was 1.4 (range 1-2). Cardio-respiratory parameters were stable. Heart rate varied from 32 to 72 beats per minute, respiratory rate from 14 to 32 breaths minute^?1 and rectal temperature from 36.6 to 40.3 °C. No sudden arousals were observed. Arterial blood gas analyses revealed a mean pH of 7.33, PaCO₂ of 33 mmHg and PaO₂ of 87 mmHg. Mild to moderate hypoxemia was seen in four lions. Recovery was smooth and lions were walking within 4.4 ± 4.25 minutes. Median recovery score [scored 1 (excellent) to 4 (poor)] was 1.3 (range 1-2).Conclusion and clinical relevanceThe drug combination proved to be effective in immobilising free-ranging healthy lions of both sexes with minimal cardio-respiratory changes.     

Comparison of medetomidine-ketamine and dexmedetomidine-ketamine anesthesia in golden-headed lion tamarins

The cardiovascular, respiratory, and anesthetic effects of medetomidine-ketamine (20 microg/kg bodyweight [BW] and 10 mg/kg BW) (MK group) or dexmedetomidine-ketamine (10 microg/kg BW and 10 mg/kg BW) (DK group) were studied in golden-headed lion tamarins. Heart rate decreased after administration of both combinations; this reduction was statistically greater in the DK group than in the MK group after 15 and 45 minutes. Systolic arterial pressure decreased in a similar way in both groups, except at 15 minutes, when systolic arterial pressure was significantly lower in the DK group. Diastolic arterial pressure, mean arterial pressure, respiratory rate, and rectal temperature were progressively reduced in all groups. Sedation time was significantly shorter and anesthesia time was significantly longer in the DK group compared with MK group. Anesthetic quality and analgesia scores were significantly greater at 5 and 15 minutes in the DK group compared with the MK group. The administration of dexmedetomidine-ketamine is as safe and effective as the administration of medetomidine-ketamine in tamarins.     

Evaluation of the anaesthetic effects of combinations of ketamine, medetomidine, romifidine and butorphanol in European badgers (Meles meles)

OBJECTIVE: To evaluate the effects of three anaesthetic combinations in adult European badgers (Meles meles). STUDY DESIGN: Prospective, randomized, blinded, experimental trial. ANIMALS: Sixteen captive adult badgers. METHODS: The badgers were each anaesthetized by intramuscular injection using the three techniques assigned in random order: romifidine 0.18 mg kg(-1), ketamine 10 mg kg(-1) and butorphanol 0.1 mg kg(-1) (RKB); medetomidine 0.1 mg kg(-1), ketamine 9 mg kg(-1) and butorphanol 0.1 mg kg(-1) (MKB); and medetomidine 0.1 mg kg(-1) and ketamine 10 mg kg(-1) (MK). Initial drug doses were calculated based on a body mass of 10 kg. Additional anaesthetic requirements, time to drug effect, duration of action and recovery from anaesthesia were recorded. Heart rate and rhythm, respiratory rate and rhythm, rectal and subcutaneous microchip temperature and oxygen saturation were recorded every 5 minutes. Depth of anaesthesia was assessed using: muscle tone; palpebral and pedal reflexes; and tongue relaxation at these time points. Blood samples and a tracheal aspirate were obtained under anaesthesia. Atipamezole was administered if the badger had not recovered within 60 minutes Parametric data were analysed using anova for repeated measures, and nonparametric data using Friedman's, and Cochran's Q tests: p < 0.05 was considered significant. RESULTS: All combinations produced good or excellent muscle relaxation throughout the anaesthetic period. RKB had the shortest duration of anaesthesia (16.8 minutes compared with MKB 25.9 minutes and MK 25.5 minutes) and antagonism was not required. RKB depressed respiratory rate less than MK and MKB. There was no significant difference between techniques for heart rate and rhythm. CONCLUSIONS AND CLINICAL RELEVANCE: All combinations provided anaesthetic conditions suitable for sampling and identification procedures in adult badgers. The RKB protocol provided a significantly shorter period of anaesthesia when compared with the combinations containing medetomidine.     

Medetomidine immobilisation and atipamezole reversal in large estuarine crocodiles (Crocodylus porosus) using metabolically scaled dosages

Background Restraint of large estuarine crocodiles is potentially dangerous. Neuromuscular blockers and other immobilising drugs have been used with variable results. Medetomidine has been reported as a reliable, repeatable and reversible immobilisation agent in small estuarine crocodilians. Methods and Results Two wild and two farmed male animals, between 3.05 and 4.6 m long, were hand‐injected into a triceps muscle with a metabolically scaled medetomidine dosage. Immobilisation occurred within 30 min. At the conclusion of the procedures, 70 min after medetomidine administration, three animals were injected with atipamezole IM into the opposite triceps muscle at a dosage based on body surface area. Reversal occurred within 5 min. The fourth animal was intubated prior to reversal of medetomidine and maintained on isoflurane anaesthesia for a gastrotomy. All animals were monitored closely post recovery and then regularly for at least 1 week. Conclusions Medetomidine at a metabolically scaled dosage delivered IM into the forelimb was effective for immobilising large estuarine crocodiles for at least 40 min. Atipamezole administered at a dosage calculated as a function of surface area effectively reversed this immobilisation.     

Comparison of three anaesthetic protocols in Bennett’s wallabies (Macropus rufogriseus)

ObjectiveInvestigate physiological and sedative/anaesthetic effects of xylazine, medetomidine or dexmedetomidine combined with ketamine in free-ranging Bennett's wallabies.Study designProspective clinical trial.AnimalsTwenty-six adult free-ranging Bennett's wallabies.MethodsAnimals were darted intramuscularly with one of three treatments: xylazine and ketamine, 2.0 and 15.0 mg kg^?1, respectively (XK): medetomidine and ketamine 0.1 and 5.0 mg kg^?1 (MK) and dexmedetomidine and ketamine 0.05 and 5.0 mg kg^?1 (DMK). Body weights were estimated. If the animal was still laterally recumbent after 45 minutes of anaesthesia, then an alpha-2 adrenoceptor antagonist, atipamezole, was administered (XK: 0.4 mg kg^?1, MK: 5 mg kg^?1, DMK: 2.5 mg kg^?1). Heart rate (HR) and respiratory rate (f_R) were recorded at 5-minute intervals and temperature at 10-minute intervals. Venous blood was taken 30 minutes after initial injection. Statistical analysis utilized anova. p < 0.05 was considered significant.ResultsAnimals became recumbent rapidly in all groups. XK animals had muscle twitches, responded to external stimuli, and three animals required additional dosing; this was not observed in the MK and DMK groups. HR (mean ± SD beats minute^?1) in XK (81 ± 4) was significantly higher than MK (74 ± 2) and DMK (67 ± 4). There were no differences in f_R, temperature, blood-gas and biochemical values between groups. More animals in MK (9/10) and DMK (5/6) needed antagonism of anaesthesia compared with XK (1/10). There were no adverse effects after anaesthesia.Conclusion and clinical relevanceCardio-respiratory effects were similar in all groups. There were fewer muscle twitches and reactions to external stimuli in MK and DMK. Duration of anaesthesia was shorter in XK; most animals in MK and DMK needed atipamezole to assist recovery. All three treatments provided satisfactory sedation/anaesthesia and are suitable for use in Bennett's wallabies.     

Chemical immobilization of chimpanzees (Pan troglodytes) using a combination of detomidine and ketamine

Objective To determine if a combination of detomidine and ketamine can be used for effective chemical immobilization of chimpanzees. Study design Observational study. Animals Twenty‐one adult captive chimpanzees (12 males, nine females), age 8–46 years, weighing 40.4–68.4 kg. Methods The chimpanzees were immobilized with intramuscular (IM) detomidine and ketamine by a darting system. Based on estimated weights, doses administered were 50 μg kg^?1 detomidine and 4 mg kg^?1 ketamine in groups 1 and 2, and 60 μg kg^?1 and 5 mg kg^?1 respectively in group 3. Eight minutes in group 1 and 15 minutes in groups 2 and 3 were allowed from the time of apparent immobilization before removing the animals from their enclosures. Body temperature, arterial haemoglobin saturation and pulse rate were measured. The time from injection to induction (recumbency and absence of voluntary movement), total anaesthetic and recovery times (with or without atipamezole) were recorded. Results Immobilization occurred within 5 minutes after darting in most animals. Early handling of the chimpanzees often resulted in arousal and required further doses of ketamine IM. Most animals were hypoxaemic and hypothermic. Occasionally, bradycardia was observed. Atipamezole resulted in an acceptable quality of recovery 10 minutes after IM injection. The duration of immobilization varied widely when no antagonist was administered. Conclusions and clinical relevance The combination detomidine (60 μg kg^?1) and ketamine (5–6 mg kg^?1) can be used for the immobilization of chimpanzees for non‐ to minimally invasive procedures. A period of 15 minutes should be allowed before handling to avoid unwanted arousal. Oxygen administration is recommended to reduce hypoxaemia. Administration of atipamezole is justified to hasten recovery.     

Comparative morphometrical studies on the skull bones of barking deer (Muntiacus muntjak) and sambar deer (Rusa unicolor)

The present study reports data on the skull bone morphometry of barking and sambar deer. The skulls of adult barking deer (n = 6) and sambar deer (n = 6) of either sex (n = 3 males and n = 3 females) were collected from the Aizawl Zoological Park, Aizawl, Mizoram, India, with official permission from the Government of Mizoram. Anatomically, barking and sambar deer's skulls were elongated, pyramid-like, dolichocephalic and consisted of thirty-two cranial and facial bones. The cranial bones were eleven (three single and four paired), comprising of occipital, sphenoid, ethmoid, frontal, interparietal, parietal and temporal. The facial bones were twenty-one (one single and ten were paired), consisting of the maxilla, premaxilla (incisive), palatine, pterygoid, nasal, lacrimal, zygomatic (malar), vomer, turbinates, mandible and hyoid. In the present study, altogether 41 different measurements were taken morphologically and 6 different indices were applied. The obtained morphometrical parameters were significantly (p < .01, p < .05) higher in males than females of both species. Species wise, all obtained parameters were higher in sambar deer than barking deer. The obtained 41 different skull parameters and 6 indices showed statistically significant differences (p < .01 and p < .05) between both sexes of barking and sambar deer; however, practically these differences were meagre. The present morphometrical study on the skull of both species can help the wildlife professionals and zoo veterinarians determine the sex of these animals and differentiate it from other domestic and wild small ruminants for solving veterolegal cases. This study's findings will also motivate and assist other comparative studies with various domestic and wild small ruminants.