Tactile, Auditory, and Visual Stimulation as Sensory Enrichment for Dairy Cattle.

Several types of enrichment can be used to improve animal welfare. This review summarizes the literature on the use of mechanical brushes, tactile udder stimulation, music, and visual stimuli as enrichment methods for dairy cows. Mechanical brushes and tactile stimulation of the udder have been shown to have a positive effect on milk yield and overall behavioral repertoire, enhancing natural behavior. Classical music reduces stress levels and has similarly been associated with increased milk yield. A slow or moderate tempo (70 to 100 bpm) at frequencies below 70 dB is recommended to have this positive effect. Evidence on the impacts of other types of enrichment, such as visual stimulation through mirrors, pictures, and color lights, or the use of olfactory stimuli, is equivocal and requires further study.

Application of Infrared Thermography in the Rehabilitation of Patients in Veterinary Medicine.

Infrared Thermography (IRT) has become an assistance tool in medicine and is used to noninvasively evaluate heat elimination during and after inflammatory processes or during the recovery period. However, its application in veterinary patients undergoing physiotherapy is a field that requires deep research. This review aims to analyze the application of IRT in the monitoring of animal physiotherapy, using the thermal changes that are present in patients undergoing gait or lameness issues (e.g., inflammation, pain, increased local temperature) as a neurobiological basis. Rehabilitation techniques such as acupuncture, physical therapies, thermotherapy, photo-biomodulation, and electrostimulation have been reported to have an anti-inflammatory effect that decreases the amount of local heat production, which is heat that can be recorded with IRT. Therefore, IRT could be used as a complementary tool to evaluate the effectiveness of the therapy, and it is suggested that further studies evaluate the accuracy, sensibility, and sensitivity of IRT.

Generalized pustular psoriasis: A nationwide population-based study using the National Health Data System in France.

BACKGROUND: GPP is a rare, chronic, neutrophilic skin disease, with limited real-world data characterizing patients with flares and the impact of flares on disease progression and morbidity. OBJECTIVE: Describe the clinical characteristics of patients with GPP, comorbidities, disease epidemiology and frequency and severity of flares, and compare patients with GPP with a matched severe psoriasis population. METHODS: In this population-based real-world cohort study an algorithm was developed to identify patients with GPP flares. Three cohorts were identified using the Système National des Données de Santé (SNDS) database covering almost the entire French population; a prevalent cohort (2010-2018), an incident cohort (2012-2015). A severe psoriasis cohort was compared with the GPP incident cohort using propensity score matching. RESULTS: The prevalent and incident cohorts comprised 4195 and 1842 patients, respectively. In both cohorts, mean age was 58 years; 53% were male. Comorbidities were significantly more common in the incident cohort versus matched psoriasis cohort, respectively, including hypertension (44% vs. 26%), ischaemic heart disease (26% vs. 18%) and hyperlipidaemia (25% vs. 15%). In the incident cohort, the flare rate was 0.1 flares/person-year and 0.4 flares/person-year among the 569 out of 1842 patients hospitalized with flares. These patients had a mean (±SD) stay of 11.6 ± 10.4 days; 25% were admitted to the intensive care unit. In 2017, the cumulative incidence and cumulative GPP age-sex standardized prevalence were 7.1 and 45.2 per million, respectively. CONCLUSIONS: Patients with GPP had a distinct comorbidity profile compared to patients with severe psoriasis, and GPP flares were associated with long hospitalizations.

Light-Responsive and Dual-Targeting Liposomes: From Mechanisms to Targeting Strategies.

In recent years, nanocarriers have played an ever-increasing role in clinical and biomedical applications owing to their unique physicochemical properties and surface functionalities. Lately, much effort has been directed towards the development of smart, stimuli-responsive nanocarriers that are capable of releasing their cargos in response to specific stimuli. These intelligent-responsive nanocarriers can be further surface-functionalized so as to achieve active tumor targeting in a sequential manner, which can be simply modulated by the stimuli. By applying this methodological approach, these intelligent-responsive nanocarriers can be directed to different target-specific organs, tissues, or cells and exhibit on-demand controlled drug release that may enhance therapeutic effectiveness and reduce systemic toxicity. Light, an external stimulus, is one of the most promising triggers for use in nanomedicine to stimulate on-demand drug release from nanocarriers. Light-triggered drug release can be achieved through light irradiation at different wavelengths, either in the UV, visible, or even NIR region, depending on the photophysical properties of the photo-responsive molecule embedded in the nanocarrier system, the structural characteristics, and the material composition of the nanocarrier system. In this review, we highlighted the emerging functional role of light in nanocarriers, with an emphasis on light-responsive liposomes and dual-targeted stimuli-responsive liposomes. Moreover, we provided the most up-to-date photo-triggered targeting strategies and mechanisms of light-triggered drug release from liposomes and NIR-responsive nanocarriers. Lastly, we addressed the current challenges, advances, and future perspectives for the deployment of light-responsive liposomes in targeted drug delivery and therapy.

Real life data: follow-up assessment on Spanish Gaucher disease patients treated with eliglustat. TRAZELGA project.

BACKGROUND: The availability of multiple treatments for type 1 Gaucher disease increases the need for real-life studies to evaluate treatment efficacy and safety and provide clinicians with more information to choose the best personalized therapy for their patients. AIMS: To determine whether treatment with eliglustat produces, in adult GD1 patients, ans optimal response in daily clinical practice. METHODS: We designed a real-life study with 2 years of follow-up (TRAZELGA [GEE-ELI-2017-01]) to uniformly evaluate the response and adverse events to eliglustat treatment. This study, conducted in 30 patients across Spain and previously treated with other therapies, included the evaluation of safety and efficacy by assessing visceral enlargement, bone disease (DEXA and T and Z scores), concomitant treatments and adverse events, as well as a quality of life evaluation (SF-36). In addition, the quantification of classical biomarkers (chitotriosidase activity, CCL18/PARC and glucosylsphingosine (GluSph)) and new candidates for GD biomarkers (YKL-40, cathepsin S, hepcidin and lipocalin-2 determined by immunoassay) were also assessed. Non-parametric statistical analysis was performed and p < 0.05 was considered statistically significant. MAIN RESULTS: Thirty patients were enrolled in the study. The median age was 41.5 years and the male-female ratio was 1.1:1. 84% of the patients had received ERT and 16% SRT as previous treatment. The most common symptoms at baseline were fatigue (42%) and bone pain (38%), no patient had a bone crisis during the study, and two years after switching, 37% had reduced their use of analgesics. Patient-reported outcomes showed a significant increase in physical function scores (p = 0.027) and physical pain scores (p = 0.010). None of the enrolled patients discontinued treatment due to adverse events, which were mild and transient in nature, mainly gastrointestinal and skin dryness. None of the biomarkers show a significant increase or decompensation after switching. CCL18/PARC (p = 0.0012), YKL-40 (p = 0.00004) and lipocalin-2 (p = 0.0155) improved after two years and GluSph after one year (p = 0.0008) and two years (p = 0.0245) of oral therapy. CONCLUSION: In summary, this real-life study, showed that eliglustat maintains stability and can improve quality of life with few side effects. Significant reductions in classic and other novel biomarkers were observed after two years of therapy.

Uterine dynamics, blood profiles, and electronic fetal monitoring of primiparous and multiparous bitches classified according to their weight.

Perinatal mortality occurs in all species. In dogs, mortality rates have been reported to range from 5 to 35%. Electronic fetal and uterine monitoring has recently been used in domestic animals to monitor the mother and newborn before and during parturition. In this way, the fetal heart rate and uterine dynamics can be monitored. This study evaluated the uterine dynamics of bitches with different weights and parity. Ninety-six bitches and their 476 puppies were divided into four experimental groups containing 24 individuals each (12 primiparous bitches and 12 multiparous bitches), according to body weight: G1 (4-8 kg), G2 (8.1-16 kg), G3 (16.1 to 32 kg), and G4 (32.1 to 39.6 kg). The fetal heart rate decelerations (dip 2 patterns), uterine dynamics, and bitches' blood profiles were evaluated, including levels of glucose, lactate, pCO2, pO2, pH, HCO3-, and Ca++. The dam weight can affect the vitality of newborns and the uterine dynamics, with differences in the frequency, intensity, and duration of myometrial contractions. The expulsion interval between puppies was longest in primiparous bitches with low weight and shortest in multiparous bitches with high weight. The expulsion interval and the number of stillborn females were higher in primiparous bitches with high weight. Newborn male puppies were significantly heavier than newborn females.

Caffeine Administration in Piglets with Low Birthweight and Low Vitality Scores, and Its Effect on Physiological Blood Profile, Acid-Base Balance, Gas Exchange, and Infrared Thermal Response.

Intrapartum asphyxia, fetal hypoxia, and their consequences (e.g., acidosis, hypercapnia, hypoglycemia, and hypothermia) are the main factors related to physio-metabolic imbalances that increase neonatal mortality in piglets, particularly in piglets with low birthweight and low vitality scores. This study aimed to evaluate the effect of three different doses of caffeine (10, 20, and 30 mg/kg) administered orally to 480 newborn piglets with low birthweight and low vitality scores. Blood gas parameters (pH, pO2, pCO2, and HCO3-), physio-metabolic profile (Ca++, glucose, and lactate), and the thermal response assessed through infrared thermography in four thermal windows (ocular, auricular, snout, and hindlimb) and rectal temperature were evaluated during the first 24 h of life. Doses of 30 mg/kg resulted in significant differences at 24 h for all evaluated parameters, suggesting that caffeine administration improved the cardiorespiratory function and metabolic activity of piglets by reducing acidosis, restoring glycemia, and increasing surface and rectal temperature. In conclusion, caffeine at 30 mg/kg could be suggested as an appropriate dose to use in piglets with low birthweight and low vitality scores. Future research might need to study the presentation of adverse effects due to higher caffeine concentrations.

Rat Grimace Scale as a Method to Evaluate Animal Welfare, Nociception, and Quality of the Euthanasia Method of Wistar Rats.

Refinement of experimental procedures in animal research has the objective of preventing and minimizing pain/distress in animals, including the euthanasia period. This study aimed to evaluate pain associated with six methods of euthanasia in Wistar rats (injectable, inhalational, and physical), by applying the Rat Grimace Scale (RGS), comparing the scores, and determining the method with the highest score that might indicate pain for laboratory rodents. Sixty adult male and female Wistar rats were used and assigned to six treatments: pentobarbital, CO2, decapitation, isoflurane, ketamine + xylazine, and ketamine + CO2. Video recording to assess the RGS scores was performed in four events: basal: 24 h before the procedure; Ti1: three minutes before the procedure; Ti2: during the application of the euthanasia method; and Ti3: immediately after the application until LORR. The main findings of this study showed that, during Ti2, decapitation and ketamine + xylazine had the highest scores (0.6 ± 0.26 and 0.6 ± 0.16, respectively) (p < 0.0001), while at Ti3, CO2 (0.9 ± 0.18) and isoflurane (1.2 ± 0.20) recorded the highest scores (p < 0.0001). According to the present results, decapitation and ketamine + xylazine elicited short-term acute pain, possibly due to tissue damage caused by both methods (injection and guillotine). In contrast, isoflurane's RGS scores recorded during Ti3 might be associated with nociception/pain due to the pungency of the drug or to the pharmacological muscle relaxant effect of isoflurane. Further research is needed to establish a comprehensive study of pain during euthanasia, where RGS could be used minding the limitations that anesthetics might have on facial expression.

The Challenge of Global Warming in Water Buffalo Farming: Physiological and Behavioral Aspects and Strategies to Face Heat Stress.

Water buffaloes have morphological and behavioral characteristics for efficient thermoregulation. However, their health, welfare, and productive performance can be affected by GW. The objective of this review was to analyze the adverse effects of GW on the productive behavior and health of water buffaloes. The physiological, morphological, and behavioral characteristics of the species were discussed to understand the impact of climate change and extreme meteorological events on buffaloes' thermoregulation. In addition, management strategies in buffalo farms, as well as the use of infrared thermography as a method to recognize heat stress in water buffaloes, were addressed. We concluded that heat stress causes a change in energy mobilization to restore animal homeostasis. Preventing hyperthermia limits the physiological, endocrine, and behavioral changes so that they return to thermoneutrality. The use of fans, sprinklers, foggers, and natural sources of water are appropriate additions to current buffalo facilities, and infrared thermography could be used to monitor the thermal states of water buffaloes.

Clinical Outcomes of Patients with Chronic Neuropathic Form of Gaucher Disease in the Spanish Real-World Setting: A Retrospective Study.

This was a retrospective, multicenter study that aimed to report the characteristics of type 3 Gaucher disease (GD3) patients in Spain, including the genotype, phenotype, therapeutic options, and treatment responses. A total of 19 patients with GD3 from 10 Spanish hospitals were enrolled in the study (14 men, 5 women). The median age at disease onset and diagnosis was 1 and 1.2 years, respectively, and the mean age at follow-up completion was 12.37 years (range: 1-25 years). Most patients exhibited splenomegaly (18/19) and hepatomegaly (17/19) at the time of diagnosis. The most frequent neurological abnormalities at onset were psychomotor retardation (14/19) and extrinsic muscle disorders (11/19), including oculomotor apraxia, supranuclear palsy, and strabismus. The L444P (c.1448T>C) allele was predominant, with the L444P (c.1448T>C) homozygous genotype mainly associated with visceral manifestations like hepatosplenomegaly, anemia, and thrombocytopenia. All patients received enzyme replacement therapy (ERT); other treatments included miglustat and the chaperone (ambroxol). Visceral manifestations, including hepatosplenomegaly and hematological and bone manifestations, were mostly controlled with ERT, except for kyphosis. The data from this study may help to increase the evidence base on this rare disease and contribute to improving the clinical management of GD3 patients.

Breastfeeding and Inborn Errors of Amino Acid and Protein Metabolism: A Spreadsheet to Calculate Optimal Intake of Human Milk and Disease-Specific Formulas.

Human milk (HM) offers important nutritional benefits. However, except for phenylketonuria (PKU), there are little data on optimal levels of consumption of HM and a special formula free of disease-related amino acids (SF-AA) in infants with inborn errors of metabolism of amino acids and proteins (IEM-AA-P). We designed a spreadsheet to calculate the amounts of SF-AA and HM required to cover amino acid, protein, and energy needs in patients with the nine main IEM-AA-P in infants aged under 6 months. Upon entering the infant's weight and the essential amino acid or intact protein requirements for the specific IEM, the spreadsheet calculates the corresponding required volume of HM based on the amino acid concentration in HM. Next, the theoretical daily fluid intake (typical range, 120-200 mL/kg/day) is entered, and the estimated daily fluid intake is calculated. The required daily volume of SF-AA is calculated as the difference between the total fluid intake value and the calculated volume of HM. The spreadsheet allows for the introduction of a range of requirements based on the patient's metabolic status, and includes the option to calculate the required volume of expressed HM, which may be necessary in certain conditions such as MMA/PA and UCD. In cases in which breastfeeding on demand is feasible, the spreadsheet determines the daily amount of SF-AA divided over 6-8 feeds, assuming that SF-AA is administered first, followed by HM as needed. Intake data calculated by the spreadsheet should be evaluated in conjunction with data from clinical and nutritional analyses, which provide a comprehensive understanding of the patient's nutritional status and help guide individualized dietary management for the specific IEM.

Controversial Topics in Animal Welfare in Latin America: A Focus on the Legislation Surrounding the Human-Companion Animal Relationship and Animals Used for Recreational Practices.

Animal welfare is a societally relevant issue that is globally attracting increased attention. This is in addition to the importance placed on welfare for the animals themselves. However, the content and application of laws protecting animals' welfare vary across countries. In Latin America, there are a range of common practices or activities involving certain animal species, many of which are legal, that can impair an animal's quality of life. These include the performance of aesthetic surgical procedures; bull-, cock-, and dog fighting; and the existence of circuses that exhibit animals. The extent and impact of these practices being dependent on the socioeconomic, cultural, territorial, and regulatory landscape of each country. Particularly, Ibero-American regions face welfare challenges that might be influenced by traditions and relevant legal gaps. The objective of this article is to review controversial practices carried out in companion and entertainment animals in Latin America, with a focus on legal aspects, as well as the current efforts being made to address and incorporate global welfare standards into domestic and wild animal practice and regulation.

Advanced or metastatic biliary tract cancer in Japan: a study using the Japan Medical Data Center payer claims database.

Aim: Biliary tract cancers are aggressive, with poor prognosis. This study describes clinical characteristics, treatment patterns and healthcare resource utilization in patients with metastatic biliary tract cancer in Japan. Materials & methods: This cohort-based study collected data from the Japan Medical Data Center claims database (2014-2018). Results: A total of 325 patients were included; 65.2% were male and the mean age was 59.2 years. A 47.6% had an Elixhauser Comorbidity Index score ≥5. Most frequent regimens were gemcitabine + cisplatin (52.9%) for first-line therapy and tegafur + gimeracil + oteracil for second-line therapy (48.6%) and third-line therapy (27.2%). Approximately 77% of patients had ≥1 hospital admission, with a median length of 57 days. Conclusion: This study provides insights on the characteristics and burden of metastatic biliary tract cancer in Japan, highlighting high disease burden in a younger population.

The effect of birth weight and time of day on the thermal response of newborn water buffalo calves.

During the 1st days of life, water buffalo calves, especially those with low birth weight, are susceptible to hypothermic mortality due to scarce energy reserves provided by fats. This means that monitoring the thermal state of newborns is essential. The objectives of the present study were to apply infrared thermography (IRT) in 109 buffalo calves to detect differences in the surface temperatures of six thermal windows -lacrimal gland, lacrimal caruncle, periocular region, nostrils, ear canal, pelvic limbs-, and determine their association to birth weight during the first 6 days of life. The calves were divided into four categories according to their weight (Q1, 37.8-41.25 kg; Q2, 41.3-46.3 kg; Q3, 46.4-56.3 kg; Q4, 56.4-60.3 kg). The thermographic images were recorded in the morning and afternoon. Results showed that the animals in Q4 registered the highest temperatures in all the thermal windows, and that these were higher in the afternoon (p < 0.0001). When considering the thermal windows, those located in the facial region recorded the highest temperatures; in contrast, the temperatures at the pelvic limbs remained below the average values of the other windows (33.41 and 33.76°C in the morning and afternoon, respectively). According to these results, the birth weight of water buffaloes is a factor that alters their thermoregulation during the 1st days of life, a condition that can be partially compensated by colostrum intake to promote development of an efficient thermoregulatory mechanism in water buffalo calves.

Mother-Young Bonding: Neurobiological Aspects and Maternal Biochemical Signaling in Altricial Domesticated Mammals.

Mother-young bonding is a type of early learning where the female and their newborn recognize each other through a series of neurobiological mechanisms and neurotransmitters that establish a behavioral preference for filial individuals. This process is essential to promote their welfare by providing maternal care, particularly in altricial species, animals that require extended parental care due to their limited neurodevelopment at birth. Olfactory, auditory, tactile, and visual stimuli trigger the neural integration of multimodal sensory and conditioned affective associations in mammals. This review aims to discuss the neurobiological aspects of bonding processes in altricial mammals, with a focus on the brain structures and neurotransmitters involved and how these influence the signaling during the first days of the life of newborns.

Clinical Experiences and Mechanism of Action with the Use of Oxytocin Injection at Parturition in Domestic Animals: Effect on the Myometrium and Fetuses.

Oxytocin is a key hormone for parturition and maternal traits in animals. During the peripartum period, the levels of endogenous oxytocin dictate physiological events such as myometrial contractions, prostaglandin production with the subsequent increase in oxytocin receptors, and the promotion of lactation when administered immediately after birth. While this hormone has some benefits regarding these aspects, the exogenous administration of oxytocin has been shown to have detrimental effects on the fetus, such as asphyxia, meconium staining, ruptured umbilical cords, and more dystocia cases in females. This review aims to analyze the main effects of oxytocin on myometrial activity during parturition, and its potential favorable and negative administration effects reflected in the fetus health of domestic animals. In conclusion, it is convenient to know oxytocin's different effects as well as the adequate doses and the proper moment to administrate it, as it can reduce labor duration, but it can also increase dystocia.

Mesenchymal stem cells attenuate the proinflammatory cytokine pattern in a guinea pig model of chronic cigarette smoke exposure.

AIMS: Cigarette smoke often induces pulmonary and systemic inflammation. In animal models, mesenchymal stem cells (MSC) tend to ameliorate these effects. We aimed to explore the local and systemic expression of cytokines in guinea pigs chronically exposed to cigarette smoke, and their modifications by MSC. MAIN METHODS: Concentrations of IL-1ß, IL-6, IL-8, IL-12, TNF-α, INF-É£, TSG-6, MMP-9, TIMP-1, and/or TIMP-2 in serum and bronchoalveolar lavage (BALF) from animals exposed to tobacco smoke (20 cigarettes/day, 5 days/week for 10 weeks) were determined, and mRNA expression of some of them was measured in lung tissue. Intratracheal instillation of allogeneic bone marrow MSC (5x106 cells in 1 ml) was done at week 2. KEY FINDINGS: After cigarette smoke, IL-6 and IFN-γ increased in serum and BALF, while IL-1ß and IL-12 decreased in serum, and TSG-6 and TIMP-2 increased in BALF. IL-1ß had a paradoxical increase in BALF. MSC had an almost null effect in unexposed animals. The intratracheal administration of MSC in guinea pigs exposed to cigarette smoke was associated with a statistically significant decrease of IL-12 and TSG-6 in serum, as well as a decrease of IL-1ß and IFN-γ and an increase in TIMP-1 in BALF. Concerning mRNA expression in lung tissue, cigarette smoke did not modify the relative amount of the studied transcripts, but even so, MSC decreased the IL-12 mRNA and increased the TIMP-1 mRNA. SIGNIFICANCE: A single intratracheal instillation of MSC reduces the pulmonary and systemic proinflammatory pattern induced by chronic exposure to cigarette smoke in guinea pigs. TRIAL REGISTRATION: Not applicable.

Is the Weight of the Newborn Puppy Related to Its Thermal Balance?

Hypothermia, a factor associated with neonatal mortality, can occur immediately after birth as a protective mechanism to prevent hypoxic damage in neonates, or to reduce the metabolic rate to improve the chances of survival in the first hours of life. The heat interchange through the superficial temperature of animals can be evaluated with infrared thermography (IRT). However, to date, there is no information on thermal windows in puppies. This study aimed to evaluate, with the use of IRT, the microcirculatory alterations in 8 different thermal windows identified at 7 different times in 289 newborn puppies assigned to different groups. Three thermograms were taken from four zones of each puppy: the facial, frontal, right lateral, and left lateral regions. Newborn puppies were grouped in 4 quartiles according to their weight: Q1 (126−226 g) n = 73, Q2 (227−330 g) n = 72, Q3 (331−387 g) n = 74, and Q4 (388−452 g) n = 70. A total of 8 thermal windows were considered at 7 evaluation times from Wet at birth until 24 h after birth (AB). Two-way mixed ANOVA within and between subjects' design for each thermal window (eight models) was performed. Results revealed a positive correlation between the puppy's weight and its ability to achieve thermostability in all the evaluated thermal windows. Statistically significant differences (p < 0.0001) between the 4 quartiles (Q1, Q2, Q3, and Q4) were found. The lowest temperatures were recorded when the pups were still wet and the highest at 24 h AB. Thermal windows with the highest temperatures were abdominal (34.234 ± 0.056 °C), thoracic (33.705 ± 0.049 °C), nasal (30.671 ± 0.110 °C), and upper left palpebral (34.066 ± 0.052 °C), while the lowest were thoracic limb brachial biceps (27.534 ± 0.051 °C), thoracic limb elbow (27.141 ± 0.049 °C), thoracic limb metacarpal (27.024 ± 0.062 °C), and femoral pelvic limb (27.654 ± 0.055 °C). Assessing the thermal response in newborn puppies can help identify drastic temperature reductions or deficient thermoregulatory compensation during the first hours of life, preventing the consequences of hypothermia.