Retinal migraine.

Retinal migraine is usually characterized by attacks of fully reversible monocular visual loss associated with migraine headache. Retinal migraine is most common in women of child-bearing age who have a history of migraine with aura. In the typical attack, monocular visual features consist of partial or complete visual loss lasting less than 1h. Although the current diagnostic criteria for retinal migraine require fully reversible visual loss, our findings suggest that irreversible visual loss is part of the retinal migraine spectrum. Nearly half of reported cases with recurrent transient monocular visual loss subsequently experienced permanent monocular visual loss.

Maternal and neonatal cortisol and catecholamines throughout vaginal eutocia and C-section in dogs.

Increased fetal cortisol is associated with catecholamine release, a primary factor for neonatal adaptive responses. However, relationship between canine peripartum cortisol and catecholamine is unknown. We aimed to compare serum adrenaline, noradrenaline and cortisol during peripartum in bitches and neonates of distinct obstetric conditions and to assess amniotic fluid cortisol concentration. Twenty females and maximum of three puppies per litter were allocated into Vaginal Eutocia (10 females; 17 neonates) and Elective C-section (10 females; 20 neonates) groups. Amniotic fluid was collected at delivery for cortisol concentration. Maternal and neonatal blood were collected prepartum, intrapartum, postpartum and 1h postpartum, and at birth, 30 and 60min, 12hs and 24hs, respectively, for cortisol, adrenaline and noradrenaline assessment. C-section determined higher noradrenaline throughout delivery and cortisol concentration from intrapartum through 1h postpartum, compared to vaginal birth. C-section maternal cortisol showed progressive increase from intrapartum onwards, while neonatal cortisol remained unchanged. No difference of maternal cortisol concentration occurred along whelping, whereas a significant decrease was verified for vaginal delivery puppies from birth until the 12hs. Puppies delivered vaginally had higher cortisol concentration at birth and 30min, compared to c-section puppies. There was a higher concentration of amniotic fluid cortisol in vaginal eutocia. In conclusion, c-section induces higher maternal stress during and after surgery, whilst vaginal delivery is a more neonatal physiologically stressful condition, contributing to better adaptation during transition.

Does Placental Efficiency and Vascularization Affect Puppy Health? A Study in Boxer and Dobermann Dogs.

BACKGROUND: The anatomical and functional characteristics of the placenta influence the adaptive ability of the fetus to the extrauterine environment. Placental efficiency, measured as the gram of neonate produced by each gram of placenta, summarizes these characteristics. In the present study, placental efficiency and its impact on the 7-day postpartum life of the puppies were studied in canine large breeds. METHODS: Placental efficiency (PE) was computed using chorioallantois weight (WPE) and surface (SPE) efficiency for puppies born from natural delivery or elective cesarean section. Capillary density was also histologically determined. Neonate viability was estimated by the APGAR score and the daily weight gain (DWG) was recorded on day 7 after delivery. RESULTS: from 15 large-breed bitches, 69 live puppies were born by natural delivery (24 puppies) and elective cesarean section (45 puppies). Cluster analysis detected a group of neonates for which reduced placental efficiency (8 for the WPE, 9 for the SPE) was identified, despite a placental weight and surface within the mean and no difference in capillary density. In this group, the DWG was lower and the mortality within 7 days was higher. CONCLUSIONS: the results suggest that placental efficiency could be an additional tool for the evaluation of a puppy in the first 7 days after delivery.

Apgar Score for Newborn Dog Viability Assessment: Differences between English and French Bulldogs Born via Cesarean Section.

Even if largely used in canine neonatology, some questions about the Apgar Score (AS) arose. Notably, considering the breed-oriented modifications of the score are needed, slight changes of the score were reported for English (EBs) and French bulldogs (FBs). The present study aimed to evaluate the possible differences between neonatal viability of the two breeds assessed by AS in puppies born via cesarean section. The results obtained from 99 puppies born alive and without malformations (EB = 47, FB = 52) showed significant (p < 0.001) differences in the median AS (seven in EB vs. eight in FB), with Grimace (p < 0.05 for sub-score 0 and p < 0.001 for sub-score 2) and Attitude (p < 0.05) being differently sub-scored between the two breeds. In the 89 alive puppies at 7 days of age, the same difference in the median AS was observed (p < 0.001), and only Grimace was differently sub-scored between the two breeds (p < 0.05 for sub-score 0 and p < 0.01 for sub-score 2). These results suggest that low Grimace could be an intrinsic characteristic of EB newborns, but it could negatively affect the neonatal adaptation process of EBs, providing an indication for focused neonatal assistance. Neonatal mortality at 7 days of age was higher in EBs than in FBs (17 vs. 3.8%, respectively), which deserves further investigations. The study provides further evidence that breed-oriented ASs are needed for a better evaluation and assistance of purebred puppies at birth.

Peripubertal Testosterone, 17ß-Estradiol and Progesterone Concentrations in Hair and Nails in Dobermann Dogs.

Studies about puberty in dogs are few, probably because many factors are involved in the delicate process of puberty onset, leading to difficulties in the proper enrollment of subjects. Moreover, the use of blood for monitoring hormonal changes can be problematic, and not feasible for long-term studies. Hair and nails proved to be suitable matrices for the retrospective evaluation of hormones' long-term accumulation. This study was performed using hair and nails for the evaluation of testosterone (T), 17ß-estradiol (E2) and progesterone (P4) concentrations to assess possible sexual steroid changes during the peripubertal period in dogs. The results, obtained on five males and five females, showed a significant increase in T in hair and nails of males immediately before puberty. In females, a significant increase in E2 at puberty and a marked increase in P4 after puberty was found in both biological specimens. Sex-related differences were detected only for T hair concentrations, but when the sex and sampling time were considered together, hair and nails T and nails P4 concentrations allowed us to discern between male and female dogs at specific sampling times. The results from this study showed that hair and nails are useful biological specimens for the retrospective evaluation of changes in T, E2 and P4 concentrations in peripubertal dogs.

Postnatal morpho-functional development of a dog's meniscus.

This study evaluates the morpho-functional modifications that characterize meniscal development from neonatal to adult dogs. Even if menisci are recognized as essential structures for the knee joint, poor information is available about their morphogenesis, in particular in dog models. Menisci from a group of Dobermann Pinchers aged 0, 10, 30 days, and 4 years (T0, T10, T30, adult, respectively) were analyzed by SEM, histochemistry (Safranin O and Picro Sirius Red Staining analyzed under a polarized light microscope), immunofluorescences (collagen type I and II), biomechanical (compression) and biochemical analyses (glycosaminoglycans, GAGs, and DNA content). SEM analyses revealed that the T0 meniscus is a bulgy structure that during growth tends to flatten, firstly in the inner zone (T10) and then even in the outer zone (T30), until the achievement of the completely smooth adult final shape. These results were further supported by the histochemistry analyses in which the deposition of GAGs started from T30, and the presence of type I birefringent collagen fibers was observed from T0 to T30, while poorly refringent type III collagen fibers were observed in the adult dogs. Double immunofluorescence analyses also evidenced that the neonatal meniscus contains mainly type I collagen fibers, as well as the T10 meniscus, and demonstrated a more evident regionalization and crimping in the T30 and adult meniscus. Young's elastic modulus of the meniscus in T0 and T10 animals was lower than the T30 animals, and this last group was also lower than adult ones (T0-T10 vs T30 vs adult). Biochemical analysis confirmed that cellularity decreases over time from neonatal to adult (p < 0.01). The same decreasing trend was observed in GAGs deposition. These results may suggest that the postnatal development of canine meniscus may be related to the progressive functional locomotory development: after birth, the meniscus acquires its functionality over time, through movement, load, and growth itself.

Effect of a subcutaneous implant of deslorelin acetate on serum testosterone concentrations in male Hermann's (Testudo hermanni sp.) and Greek (Testudo graeca sp.) tortoises.

Deslorelin acetate is a gonadotropin-releasing hormone agonist formulated in a controlled-release subcutaneous implant and designed for reversible suppression of testosterone production in dogs. It has also been demonstrated to be effective in other animal species, but no data on its effectiveness in male land tortoises are available. This study aimed to evaluate the effect of a 4.7-mg deslorelin acetate implant on serum testosterone concentrations in male Hermann's (Testudo hermanni sp.) and Greek (Testudo graeca sp.) tortoises. Twenty adult male tortoises housed under the same environmental conditions were enrolled for the study and randomly assigned to a treatment (D, n = 10) or a control (C, n = 10) group. Starting in May, males from the D group were implanted with a 4.7-mg deslorelin acetate device, whereas males from the C group did not receive any treatment. Blood samples were collected once immediately before implant application (S0-May) and at 15 days (S1-June), 2 (S2-July), and 5 (S3-October) months after application. Serum testosterone at each sampling time was measured through a solid-phase, enzyme-labeled, competitive chemiluminescent immunoassay. Median serum testosterone concentrations were not significantly different between the two groups in all sampling times, and no interaction between treatment and sampling time was observed. The present study, therefore, suggests that a single treatment with a 4.7-mg deslorelin acetate implant has no effect on testosterone circulation in male Hermann's and Greek tortoises during the following 5 months.

Coat, Claw and Dewclaw 17-ß-Estradiol and Testosterone Concentrations in Male and Female Postpubertal Cats: Preliminary Results.

In the recent past, tissue materials such as hair/coat and nails/claws have proved to be useful for the study of long-term hormonal changes in humans and animals and shown to be advantageous in terms of being collectable without invasiveness, with a benefit in terms of animal welfare. However, studies using these tissue materials in cats are scarce, especially on sexual hormone measurement. In this study, the concentrations of 17-ß-estradiol (E2) and testosterone (T) were assessed in 20 male and 18 female domestic postpubertal cats at the time of neutering/spaying during the breeding season. Hormones were measured in coat shaved from the forearm (ACOAT) and from the surgical area (SCOAT); claws were collected from the forearms (CLAWS) and the dewclaws (DCLAWS). Although all these tissue materials were shown to be useful for E2 and T long-term measurement, only T concentrations were higher (p < 0.001) in males from both ACOAT and SCOAT samples when compared to females and therefore useful for distinguishing between the two sexes. Within each sex, E2 and T concentrations can be assessed on coat, but also on the dewclaws, providing an alternative, practical, matrix for sexual steroid measurement in postpubertal cats during the breeding season.

Migraine treatment in pregnancy: A survey of comfort and treatment practices of women's healthcare providers.

OBJECTIVE: The objective of this study was to assess women's healthcare providers' treatment practices for pregnant women with migraine. BACKGROUND: Migraine is associated with several maternal and fetal complications during pregnancy, including preeclampsia and preterm birth. Migraine treatment during pregnancy can present significant challenges due to lack of controlled clinical trials and risks associated with specific medications. METHODS: Women's healthcare providers were queried regarding practice patterns and comfort with use of acute and preventive migraine treatments during pregnancy. The survey was distributed online. RESULTS: The survey was completed by 92 women's healthcare providers (response rate 22.9% [92/402]), with most specializing in general obstetrics and gynecology (91% [83/92]). Approximately one-fourth (26% [24/92]) of respondents indicated they counseled women on migraine treatment in pregnancy as early as before pregnancy contemplation, while over one-third (35% [32/92]) counseled on migraine treatment once the patient became pregnant. The majority of respondents reported feeling somewhat or very comfortable with recommending (63% [58/92]) or continuing (64% [59/92]) acute treatments for pregnant patients with migraine, with highest comfort levels for acetaminophen (100% [92/92] for prescribing or continuing) and caffeine (94% [85/90] prescribing, 91% [82/90] continuing). Higher levels of discomfort were reported with triptans (88% [80/91] rarely or never prescribe during pregnancy). Survey respondents felt less comfortable with recommending preventive migraine treatments to pregnant patients (40% [37/92] somewhat or very comfortable), compared with a higher comfort level with continuing preventive medications (63% [58/92] somewhat or very comfortable). Highest comfort levels were reported with use of magnesium (69% [63/91] comfortable prescribing, 82% [75/92] comfortable continuing) and non-pharmacologic approaches (70% [62/89] comfortable prescribing, 84% [75/89] comfortable continuing). Nearly 40% (35/92) of respondents reported that they typically refer to neurologists or headache specialists for migraine treatment during pregnancy. CONCLUSION: This survey of women's healthcare providers revealed varying levels of comfort regarding migraine management during pregnancy, and highlights the need for additional education regarding migraine treatment safety data during pregnancy.

Biochemical factors affecting newborn survival in dogs and cats.

The importance and implications of small animal neonatology were underestimated until recent times. Despite the recent increasing interest for this branch of veterinary medicine, however, perinatal mortality rates in canine and feline species remain high, representing an important challenge for the clinician. In this perspective, the prompt identification of newborns requiring additional and tailored assistance becomes a key to reduce the perinatal losses in small animals. To achieve this goal, clinical and laboratory findings must be carefully evaluated. This paper focuses on biochemical parameters and their reported influence on neonatal survival, guiding through the evaluation of canine and feline newborn laboratory analyses, with a thorough discussion about the use of different biological material in these subjects. Beside blood, other biological material, such as urines and fetal fluids proved to be interesting for the identification of possible prognostic markers, thanks also to their easy and safe collection. However, the correct reading-through the results must consider many variables such as type of delivery, anesthesia protocol in case of Caesarean section, age of the newborn at samples collection, and for blood analysis, also the type of blood, site of collection, modality of collection and storage must be considered. Notwithstanding the recent progress in literature, for most of the parameters more research is needed to define cut-off values with certainty.

Management of Vaginal Hyperplasia in Bitches by Bühner Suture.

Vaginal hyperplasia in bitch is an exaggerated response of the vaginal mucosa to estrogens during the proestral-estral phase of the cycle that can protrude through the vulvar lips. The present study refers to the management of vaginal hyperplasia in bitches by Bühner vulvar suture. Fourteen private-owners animals were refereed for spontaneous vaginal hyperplasia and complete protrusion of the mucosa, without ischemic or necrotic areas, which occurred during the proestral-estral phase. Under general anesthesia, prolapsed mass was cleaned with 50% glucose solution to reduce oedema and gently repositioned; the Bühner suture was applied using a Gerlach needle and a sterile vaginal suture tape, maintaining a minimal opening to allow urination in order to avoid possible recurrence in the same estrus. None of the bitches showed recurrence during the current cycle, proving the effectiveness of the Bühner suture. To prevent the possible recurrence of vaginal hyperplasia at the subsequent estrus, all the bitches underwent an ovariectomy 2 months later, when the Bühner suture was removed. In conclusion, the Bühner suture proved to be useful for the conservative treatment of vaginal hyperplasia in medium- or large-sized bitches. However, this approach should be considered only for cases in which the prolapsed mass does not show trauma, ulceration, ischemic or necrotic areas.

Clinical Scoring Systems in the Newborn Calf: An Overview.

A scoring system is an instrument that enables the scorers, including farmers, technicians, and veterinarians, to adopt a systematic approach for diagnosis or monitoring, as it decreases bias and confounding and increases objectivity. Practically, it is a number assigned to a patient that correlates with a probability that a diagnosis can be confirmed or that a specific outcome will follow. This article examines the clinical scores designed or adapted to bovine medicine that aim to assess newborn calf viability and to diagnose and monitor neonatal calf diarrhea and respiratory diseases, helping the clinician promptly recognize calves needing medical assistance. Despite the large number of clinical scores described in the literature, these are still barely used in farm animal practice; possibly, the complexity of the scores and missing recommendations for intervention are reasons for their lack of popularity as well as the crosswise lack of consistency among scores designed for the same purpose. Further research is needed in this regard to increase scores validation and encourage their application in bovine calf neonatology.

Hair and Claw Dehydroepiandrosterone Concentrations in Newborn Puppies Spontaneously Dead within 30 Days of Age.

The latest intrauterine fetal developmental stage and the neonatal period represent the most challenging phases for mammalian offspring. Toward the term of pregnancy, during parturition, and after birth, the hypothalamic−pituitary−adrenal axis (HPA) is a key system regulating several physiologic processes, through the production of cortisol and dehydroepiandrosterone (DHEA). This study was aimed to assess DHEA concentrations in hair and claws of 126 spontaneously dead newborn puppies, classified as premature puppies (PRE-P), stillborn puppies (STILL-P) and puppies that died from the 1st to the 30th day of life (NEON-P). The possible influence of newborn sex, breed body size, and timing of death on DHEA concentrations in both matrices was evaluated. Claw DHEA concentrations were higher in the PRE-P group when compared to STILL-P and NEON-P puppies (p < 0.05), whilst no significant differences were found in hair for all the studied factors. The results confirm the hypothesis that higher amounts of DHEA are produced during the intrauterine life in dogs, also in puppies that will die soon after birth.

Refining the APGAR Score Cutoff Values and Viability Classes According to Breed Body Size in Newborn Dogs.

The Apgar score (AS) represents a key tool for neonate assessment, but the possible breed effect on AS in newborn puppies has never been investigated. Therefore, data from 234 dog litters born by caesarean section, grouped according to breed body size (BBS) (small, medium, large), were evaluated. Live-birth puppies were assessed through AS within 5 min of delivery, and classified in viability classes: 0−3 severely distressed, 4−6 moderately distressed, 7−10 not distressed. Statistical analysis evaluated possible differences of AS and viability class according to BBS, and between BBS and puppies' mortality. Results showed no differences in the distribution of mortalities among BBSs. However, an effect of BBS on the AS was found, with small-sized puppies being the most represented in the severely distressed class, but having the best survival chance compared to large-sized newborns. Through receiver-operating-characteristics analysis, the AS new cutoff values for survival and for death <24 h and 24 h−7 days of age were identified, and the viability classes were redefined, with a narrower class of moderately distressed puppy specific for each BBS. In conclusion, the refining of the AS in dog species is imperative, with cutoff values and viability classifications that must be adapted to the BBS.

Feline neonatology: From birth to commencement of weaning - what to know for successful management.

PRACTICAL RELEVANCE: Despite considerable interest in the field of companion animal reproduction, feline neonatology remains largely unstudied. This contrasts with the need for a more professional veterinary approach to newborn kittens and feline husbandry, across the pet, breeding cattery and rescue shelter settings, to reduce kitten mortality. GLOBAL IMPORTANCE: Feline neonatology has relevance for veterinarians around the world as cats are continuing to become established as popular companion animals. CLINICAL CHALLENGES: Perinatal mortality in cats is remarkably high. Therefore, adequate neonatal evaluation and assistance at birth, careful monitoring of kittens in the vulnerable period until weaning begins, assessment of maternal factors and well-informed management of orphans are crucial in helping to reduce kitten losses. AIM: This review aims to deepen the basic knowledge of the veterinary clinical team regarding the characteristics of feline newborns under normal conditions at birth through to the commencement of weaning. Much of the information is also relevant to breeders and rescue/shelter caregivers. EVIDENCE BASE: In compiling the present review, the authors have drawn on specific feline research data, where available, complemented by data extrapolated from scientific publications on newborn dogs, and also their own and their colleagues' professional clinical experience.

How Stressful Is Maternity? Study about Cortisol and Dehydroepiandrosterone-Sulfate Coat and Claws Concentrations in Female Dogs from Mating to 60 Days Post-Partum.

In dogs, the phase from mating to the end of weaning lasts about 120 days and encompasses many aspects that, interacting, contribute to increase the allostatic load. The coat and claws, useful for long-term change assessments, have the advantage of being collectable without invasiveness. In the present study, the Cortisol (C) and Dehydroepiandrosterone-sulfate (DHEA-S) concentration monthly changes in the coat and claws were studied in female dogs from mating to the end of weaning to assess Hypothalamic-Pituitary-Adrenal (HPA) axis activation during pregnancy and the post-partum period. The results from 15 Dobermann Pinscher female dogs showed a trend of increase of the coat C from mating to 60 days post-partum, with significant changes between mating and parturition-60 days post-partum (p < 0.01) and between the 30-day pregnancy diagnosis (PD) and 30-60 days post-partum (p < 0.05). The claws C trend showed significant increases between mating and 30-60 days post-partum (p < 0.05) and between the PD and 60 days post-partum (p < 0.01). DHEA-S in both matrices showed non-significant changes. The results suggest that maternity could play a pivotal role in the HPA axis activation, with a subsequent chronic secretion of C determining an increase in the allostatic load in the mothers. Neither maternal parity nor litter size played a significant role in the accumulation of C and DHEA-S in both matrices.

Effect of Delivery by Emergency or Elective Cesarean Section on Nitric Oxide Metabolites and Cortisol Amniotic Concentrations in at Term Normal Newborn Dogs: Preliminary Results.

The neonatal response to stress was reported to be related to the type of delivery, that is elective or emergency cesarean sections (ELCS and EMCS, respectively). Nitric oxide (NO) is also reported to be related to uterine inertia, and high levels of NO metabolites (NOs) are associated with physical and emotional stress. The study aimed to assess the concentrations of cortisol (C) and NOs in the amniotic fluid of puppies delivered by ELCS or EMCS. In total, 32 puppies were delivered by ELCS and 22 by EMCS. ANCOVA showed an effect of the ELCS vs. EMCS on both amniotic NOs (p < 0.001) and C (p < 0.001) concentrations. Lower amniotic C concentrations were found at increasing Apgar score (p < 0.001). Higher amniotic NOs concentrations were associated to increasing mother's parity (p < 0.001), puppies' birthweight (p < 0.001), and time of labor within the EMCS group (p < 0.05). A positive correlation between birthweight and amniotic NOs concentrations was also found (p < 0.05) in the EMCS group. Due to the possible concurrence of several compartments (maternal, maybe placental, and fetal) to the final amniotic fluid composition, the definition of the role played by the three compartments in the higher C and NOs concentrations found in amniotic fluids collected from puppies delivered by EMCS than ELCS needs further clarification.

Hind limb ossification centre hypoplasia and deformities induced by quadriceps contracture: Radiographic and Computed Tomographic study in 13 Doberman Pinscher littermates.

Quadriceps contracture (QC) is reported in dogs mainly as a complication of trauma or parasitic infection. QC causes progressive hind limb deviation, muscular hypotrophy and degenerative joint disease and, in puppies, bone hypoplasia. The aim of this clinical case series is to describe the radiographic and computed tomographic (CT) changes in hind limb ossification centres in thirteen 55 to 57-days-old Doberman Pinscher related littermates induced by QC after repeated intramuscular injections. The presence, size, and shape of ossification centres of affected and unaffected hind limbs were compared. Affected limbs were hyperextended and externally rotated, with genu recurvatum and proximo-medial patellar luxation. QC had no influence on the time of appearance of ossification centres however, it was associated with femoral head flattening, hip subluxation, flattening of the femoral distal epiphysis. The tibial plateau was tilted caudoproximally-craniodistally and wedged into the growth plate. Thirty-two out of fifty-five ossification centres (including diaphyseal and epiphyseal centres, such as femoral head and tibial plateau) were significantly smaller in affected limbs (p < 0.05). Lack of weight-bearing could account for the smaller size of ossification centres in affected tarsi and metatarsi. Progressive limb hyperextension and external rotation might have induced gradual loading withdrawal on the medial aspect of the foot justifying the reduced size observed only for the medial ossification centres of the digits of affected limbs. To the best of our knowledge, this is the first study describing CT findings of hind limb ossification centre changes in puppies with QC contracture.

Clinical Trial on the Usefulness of On-Site Evaluation of Canine Fetal Fluids by Reagent Test Strip in Puppies at Elective Caesarean Section.

The reagent urinary test strips (TS) marketed for urines represent the first-line diagnostic tool in many instances. Therefore, the aim of the study was to assess the usefulness of TS for the on-field evaluation of fetal fluids' composition in newborn dogs at elective caesarean section. Of a total of 137 puppies born at term, 127 survived and 10 did not survive. One hundred and thirteen amniotic and 107 allantoic samples from surviving newborns were collected, and 8 amniotic and allantoic fluids were collected from the non-surviving newborns and assessed by strips. Significantly lower amounts of amniotic glucose and higher amounts of amniotic and allantoic nitrites, amniotic protein, allantoic urobilinogen, and amniotic bilirubin concentrations were found in non-surviving when compared to surviving newborns. In the surviving ones, higher specific gravity and bilirubin concentrations, and lower pH, were found in allantoic than in amniotic fluids. Higher amniotic and allantoic glucose concentrations, higher amniotic and allantoic pH, and lower amniotic and allantoic protein concentrations were found in medium/large- than in small-sized puppies. The TS allowed the quick evaluation of fetal fluids in puppies at birth. The differences between surviving and non-surviving puppies seem to suggest that the on-site analysis of fetal fluids' composition by TS could represent a first-line diagnostic tool in the field of canine neonatology, allowing the quick recognition of puppies needing assistance as a complementary tool for clinical evaluation.

Gluten-Free Diet and Migraine.

Migraine is common in celiac disease (CD) and usually improves on a gluten-free diet (GFD). The benefit for people impacted by migraine without CD is poorly evidenced. A GFD may have adverse health consequences and is expensive.