Neuropathic Pain in Dogs and Cats: Current Evaluation and Treatment Perspectives: Review

Abstract: During the past decade, the number of scientific papers on the recognition and multimodal management of pain in small animals increased exponentially. However, the variable of neuropathic pain, or adaptive disorder, has not yet been characterized completely. Its genesis is related to several diseases and injuries of the nervous system that change the neuroanatomical structures that participate in pain processing. Finding novel neurobiological mechanisms and the development of techniques for diagnosis and treatment in Human Medicine, are opening great opportunities for research and the understanding of neuropathic pain in pets

Feline Leukemia Virus and Other Pathogens as Important Threats to the Survival of the Critically Endangered Iberian Lynx (Lynx pardinus)

BACKGROUND: The Iberian lynx (Lynx pardinus) is considered the most endangered felid species in the world. In order to save this species, the Spanish authorities implemented a captive breeding program recruiting lynxes from the wild. In this context, a retrospective survey on prevalence of selected feline pathogens in free-ranging lynxes was initiated. METHODOLOGY/ PRINCIPAL FINDINGS: We systematically analyzed the prevalence and importance of seven viral, one protozoan (Cytauxzoon felis), and several bacterial (e.g., hemotropic mycoplasma) infections in 77 of approximately 200 remaining free-ranging Iberian lynxes of the Doñana and Sierra Morena areas, in Southern Spain, between 2003 and 2007. With the exception of feline immunodeficiency virus (FIV), evidence of infection by all tested feline pathogens was found in Iberian lynxes. Fourteen lynxes were feline leukemia virus (FeLV) provirus-positive; eleven of these were antigenemic (FeLV p27 positive). All 14 animals tested negative for other viral infections. During a six-month period in 2007, six of the provirus-positive antigenemic lynxes died. Infection with FeLV but not with other infectious agents was associated with mortality (p<0.001). Sequencing of the FeLV surface glycoprotein gene revealed a common origin for ten of the eleven samples. The ten sequences were closely related to FeLV-A/61E, originally isolated from cats in the USA. Endogenous FeLV sequences were not detected. CONCLUSIONS/SIGNIFICANCE: It was concluded that the FeLV infection most likely originated from domestic cats invading the lynx's habitats. Data available regarding the time frame, co-infections, and outcome of FeLV-infections suggest that, in contrast to the domestic cat, the FeLV strain affecting the lynxes in 2007 is highly virulent to this species. Our data argue strongly for vaccination of lynxes and domestic cats in and around lynx's habitats in order to prevent further spread of the virus as well as reduction the domestic cat population if the lynx population is to be maintained

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Optimum timing for assessing phenotypic resistance against gastrointestinal nematodes in Pelibuey ewes

The objective was to identify the optimal stage of production to evaluate the resistance of Pelibuey ewes against gastrointestinal nematodes (GIN). Faecal egg count (FEC) was used to classify the ewes as resistant, sensible or intermediate against GIN. Forty-seven ewes were mating during 30 d. The gestation was verified by ultrasonography, and the breeding date was used to calculate the productive stages. Faeces were taken weekly to determine the FEC. Blood samples were taken to determine the packed cell volume (PCV), the peripheral eosinophils count (PEC), plasma protein concentration (PP), and Immunoglobulin A (IgA) against Haemonchus contortus. The body condition score (BCS) was recorded at each visit. Six moments during the study (early, mid and late gestation; early, mid and late lactation) were considered. The ewes were classified according to FEC (mean FEC ± three standard errors). The higher FEC occurred during all lactation stages than during early and mid-gestation stages (P<0.05). PCV, PP, and BCS during early gestation stage were higher than shown during the lactation stages (P<0.01). The PEC and IgA were higher during all lactation stages than early and mid-gestation stages (P<0.05). Concerning the type of birth, double births showed higher FEC than single birth (P<0.01). The highest values of accuracy (100 %) and concordance (Youden's J = 1.0) were found during early lactation. Therefore, it is concluded that the optimal stage of production to evaluate phenotypic resistance against GIN infections in Pelibuey ewes was during the early lactation

Molecular detection of Dirofilaria immitis in dogs and mosquitoes in Tabasco, Mexico

Background & objectives: Dirofilaria immitis is a filarial nematode that causes heartworm disease in domestic as well as wild canines and felines; and cutaneous or pulmonary infections in humans. The purpose of the study was to estimate the prevalence of D. immitis in domestic dogs in Tabasco, Mexico and to assay mosquitoes temporally and spatially associated with dogs for evidence of infection. Methods: Blood was collected from 1050 dogs in 1039 houses during a random household survey performed in 2016 and 2017. Genomic DNA was extracted and assayed by polymerase chain reaction (PCR) using pan-filarial primers and various species-specific primers. Dog owners were interviewed using a structured questionnaire designed to collect information on factors that may impact the occurrence of filarial infection. The association between canine dirofilariasis prevalence and factors likely to impact infection was determined by univariate logistic regression analysis, followed by multivariate binomial logistic regression analysis. Indoor and outdoor resting mosquitoes were collected from houses by manual aspiration. Mosquitoes were identified according to species, homogenized and tested by PCR for filarial nematodes. Results: A total of 84 (8%) dogs were positive for D. immitis DNA, while 3 (0.3%) dogs contained Acanthocheilonema reconditum DNA. Several factors were significantly associated with D. immitis infection. For example, dogs that lived <100 m from a large source of open standing water were significantly more likely (p = 0.002) to become infected with D. immitis than other dogs. Additionally, dogs with infrequent or no anthelmintic treatment were significantly more likely (p = 0.0) to become infected than dogs that were regularly treated. The entomologic investigation yielded 2618 female mosquitoes from 14 species. Four pools of Culex quinquefasciatus were positive for D. immitis DNA and the minimum infection rate, calculated as the number of positive pools per 1000 mosquitoes tested, was 2.9. Interpretation & conclusion: The study identified several factors positively associated with an increased risk of D. immitis infection in domestic dogs in Tabasco and provides evidence that Cx. quinquefasciatus is potentially an important vector in this region. This information can be used by local veterinarians and dog owners to reduce the burden of D. immitis on canine health

Fascioliasis in relatives of patients with Fasciola hepatica infection in Peru Fasciolosis en familiares de pacientes con infección por Fasciola hepatica en el Perú

High prevalence rates of human fascioliasis have been described in several regions of Peru. We surveyed 20 families in an endemic area of Peru in order to determine the proportion of infection with F. hepatica in relatives of diagnosed subjects and in order to identify associated risk factors. The study included feces and blood samples of 93 subjects. Ages ranged from one to 53 (mean = 18.6; SD = 14.2). The overall prevalence of fascioliasis by fecal examinations was 33.3% (n = 83) and by serology, 51.9% (n = 86). The prevalence in age group I (< 19 years old) by coprological and serological tests was 61.4% and 75.9%, respectively; in group II (> 19 years old) 15.4% and 37.5%. The main associated risk factor with fascioliasis was eating salads (OR = 3.29, CI = 1.2 - 9.0, p = 0.02). In conclusion, human fascioliasis is highly prevalent in the relatives of index cases and the most significant risk factor of acquiring fascioliasis in the family is eating salads in endemic areas.<br>Altas tasas de fasciolosis humana han sido descritas en varias regiones del Perú. Estudiamos 20 familias en una área endémica del Perú para determinar la proporción de infección con F. hepatica en los familiares de los sujetos diagnosticados y para identificar factores de riesgo asociados. El estudio incluyó un total de 93 sujetos, quienes contribuyeron con muestras de heces y sangre. Las edades comprendieron desde 1 a 53 años (media = 18.6; DS = 14.2). La prevalencia general de fasciolosis por exámenes de heces fue 33.3% (n = 83) y por serología, 51.9% (n = 86). La prevalencia en el grupo de edad I (< 19 años de edad) por pruebas coprológicas y serológicas fueron 61.4% y 75.9%, respectivamente; en el grupo II (> 19 años de edad) 15.4% y 37.5%. El principal factor de riesgo asociado con fasciolosis fue comer ensaladas (OR = 3.29, IC = 1.2-9.0, p = 0.02). En conclusión, la fasciolosis humana es altamente prevalente en familiares de los casos índices y el factor de riesgo más significante para adquirirla en la familia es comer ensaladas en las áreas endémicas