Animal board invited review: Improving animal health and welfare in the transition of livestock farming systems: Towards social acceptability and sustainability.

The need to integrate more clearly societal expectations on livestock farming has led the authors of this article to consider that livestock farming systems must be redesigned to position health and welfare at the heart of their objectives. This article proposes a vision of the advances in knowledge required at different scales to contribute to this transformation. After defining health and welfare of animals, the article emphasises the need to consider health in a broader perspective, to deepen the question of positive emotional experiences regarding welfare, and raises the question of how to assess these two elements on farms. The positive interactions between health and welfare are presented. Some possible tensions between them are also discussed, in particular when improving welfare by providing a more stimulating and richer environment such as access to outdoor increases the risk of infectious diseases. Jointly improving health and welfare of animals poses a number of questions at various scales, from the animal level to the production chain. At the animal level, the authors highlight the need to explore: the long-term links between better welfare and physiological balance, the role of microbiota, the psycho-neuro-endocrine mechanisms linking positive mental state and health, and the trade-off between the physiological functions of production, reproduction and immunity. At the farm level, in addition to studying the relationships at the group level between welfare, health and production, the paper supports the idea of co-constructing innovative systems with livestock farmers, as well as analysing the cost, acceptability and impact of improved systems on their working conditions and well-being. At the production chain or territory levels, various questions are raised. These include studying the best strategies to improve animal health and welfare while preserving economic viability, the labelling of products and the consumers' willingness to pay, the consequences of heterogeneity in animal traits on the processing of animal products, and the spatial distribution of livestock farming and the organisation of the production and value chain. At the level of the citizen and consumer, one of the challenges is to better inter-relate sanitary and health perspectives on the one hand, and welfare concerns on the other hand. There is also a need to improve citizens' knowledge on livestock farming, and to develop more intense and constructive exchanges between livestock farmers, the livestock industry and citizens. These difficult issues plead for interdisciplinary and transdisciplinary research involving various scientific disciplines and the different stakeholders, including public policy makers through participatory research.

SARS-CoV-2 infection in children with cystic fibrosis: A cross-sectional multicenter study in Spain. New waves, new knowledge.

INTRODUCTION: The association between viral infections and pulmonary exacerbations in children with cystic fibrosis (cwCF) is well established. However, the question of whether cwCF are at a higher risk of COVID-19 or its adverse consequences remains controversial. METHODS: We conducted an observational, multicenter, cross-sectional study of cwCF infected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) between March 2020 and June 2022, (first to sixth COVID-19 pandemic waves) in Spain. The study aimed to describe patients' basal characteristics, SARS-CoV-2 clinical manifestations and outcomes, and whether there were differences across the pandemic waves. RESULTS: During study time, 351 SARS-CoV2 infections were reported among 341 cwCF. Median age was 8.5 years (range 0-17) and 51% were female. Cases were unevenly distributed across the pandemic, with most cases (82%) clustered between November 2021 and June 2022 (sixth wave, also known as Omicron Wave due to the higher prevalence of this strain in that period in Spain). Most cwCF were asymptomatic (24.8%) or presented with mild Covid-19 symptoms (72.9%). Among symptomatic, most prevalent symptoms were fever (62%) and increased cough (53%). Infection occurring along the sixth wave was the only independent risk factor for being symptomatic. Just eight cwCF needed hospital admission. No multisystem inflammatory syndrome, persisting symptoms, long-term sequelae, or deaths were reported. CONCLUSIONS: Spanish current data indicate that cwCF do not experience higher risks of SARS-CoV-2 infection nor worse health outcomes or sequelae. Changes in patients' basal characteristics, clinical courses, and outcomes were detected across waves. While the pandemic continues, a worldwide monitoring of COVID-19 in pediatric CF patients is needed.

An unexpected high-pressure stability domain for a lower density polymorph of benzophenone.

For over a century, it was thought that the crystalline polymorph II of benzophenone does not possess a stable domain in the pressure-temperature phase diagram. With a combination of new experimental results and literature data, this case of crystalline dimorphism has finally been solved and it is shown that form II possesses a stable domain at high pressure and high temperature, even though its density is lower than that of form I, the stable form under ordinary pressure and temperature conditions. The phase diagram of benzophenone is a clear demonstration of the fact that to understand the phase behaviour of a chemical substance both the exchange of heat (due to the change in intermolecular interactions) and work (due to the change of volume at a given pressure) need to be taken into account.

Using Machine Learning for Predicting the Effect of Mutations in the Initiation Codon.

The effect of mutations has been traditionally predicted by studying what may happen due to the substitution of one amino acid for another one. This approach may be effective for mutations with impact in the function of the protein, but ineffective for mutations in the translation initiation codon. Such mutation might avoid the generation of the protein. Consequently, specific methods for predicting the effect of mutations in the translation initiation codon are needed. We propose a method for predicting the effect of mutations in the canonical translation initiation codon based on a biological model that considers specific features of such mutations, like the distance to a potential alternative initiation codon. Our predictor has been developed using tree-based machine learning algorithms and data extracted from Ensembl. Our final model is able to detect whether a mutation in the canonical initiation codon is deleterious or benign with a precision of 44.28% and an accuracy of 98.32%, which improves the results of state of the art tools such as PolyPhen, SIFT, or CADD for this type of mutation.

On the dimorphism of prednisolone: The topological pressure-temperature phase diagram involving forms I and II.

The dimorphism of the corticosteroid anti-inflammatory drug prednisolone has been investigated by the construction of a topological pressure-temperature phase diagram, using crystallographic and calorimetric data. The system is enantiotropic, because the temperature of the I-II equilibrium under atmospheric conditions (400-463 K) is lower than that of the two melting equilibria (518.7 K for form II and 526.3 K for form I). The slope of the I-II equilibrium in the pressure-temperature phase diagram is negative and relatively steep; therefore, form II, which is the stable form at room temperature, will not easily encounter conditions where form I will become stable even under industrial processing conditions. On the other hand, extreme small amounts of form I have been observed to spontaneously transform into form II in a time interval of about six years at room temperature and it can be concluded that although form I is very persistent under ambient conditions, it does slowly convert into form II. Moreover, the system does not obey the density rule.

Effects of two alveolar recruitment manoeuvres (sustained inflation and stepwise) followed by positive end-expiratory pressure on cardiac output (measured with lithium dilution), invasive blood pressure and arterial oxygen tension in isoflurane-anaesthetised goats.

Alveolar recruitment manoeuvres (ARM) performed during general anaesthesia improve oxygenation; however cardiovascular depression may be observed. The aim of the study was to compare the effects of sustained inflation (SI) and stepwise ARMs on cardiac output (CO), mean arterial blood pressure and arterial oxygen tension (PaO2) in ten mechanically ventilated goats anaesthetised with isoflurane. In the SI ARM, peak inspiratory presure (PIP) was increased to 30 cmH2O and sustained for 20 s. In the stepwise ARM, the PIP was increased by 5 cmH2O each minute for three minutes from 10 to 25 cmH2O. Both ARMs were followed by positive end-expiratory pressure of 5 cmH2O. Paired lithium dilution CO measurements and arterial blood samples were obtained before and after each ARM. The order of the ARM was randomised and each goat was subjected to both techniques. Data was reported as median and interquartile range (IQR). Significance was set at 0.05. The median change in CO (measured by subtracting values after and before ARM) was -0.15 L min-1 (IQR -0.51; 0.03) and - 0.90 L min-1 (IQR -1.69; -0.58) for SI and stepwise ARM respectively (p = 0.04). The median change in PaO2 was 3 kPa (IQR -2.7; 7.6) and 0.4 kPa (IQR -3.4; 5.5) for SI and stepwise ARM respectively (p = 0.03). In conclusion, SI ARM causes less impact on CO and provides a better improvement in PaO2 compared to stepwise ARM in goats.

[ACNES syndrome, exploring the abdominal wall as source of abdominal pain]. / Síndrome de ACNES, explorando la pared abdominal como noxa del dolor abdominal.

Abdominal wall pain, specifically ACNES syndrome (Anterior Cutaneous Nerve Entrapment Syn drome), is part of the differential diagnosis of chronic abdominal pain. This syndrome is frequently overlooked and therefore underdiagnosed. OBJECTIVES: To describe the clinical and evolutionary cha racteristics of patients diagnosed with ACNES and to draw attention to this pathology. PATIENTS AND METHOD: A retrospective descriptive study was carried out in a reference center, between October 2016 and July 2021, in patients under 17 years of age, diagnosed with ACNES, who met at least two of four of the following findings: Carnett's sign, Pinch test, dysesthesia at the point of maximum pain, improvement after infiltration of local anesthetic, having ruled out visceral or functional abdo minal pathology. Epidemiological variables, symptoms, physical examination, complementary tests, treatment, and evolution data were collected. Descriptive statistics were used. RESULTS: 20 patients diagnosed with ACNES, 75% women, median age 12.85 years. The abdominal examination revea led Carnett's sign in 95%, Pinch test sign in 65%, and dysesthesia in 90% of patients. 65% reported pseudovisceral symptoms. 7 patients were overweight or obese. The most frequent location (50%) was the right iliac fossa, at T10-T11 level. One patient reported spontaneous improvement; 7 impro ved with oral analgesia; 9 patients were referred to the pain unit, of which 5 attended, and improved with anesthetic infiltration with bupivacaine-triamcinolone. The remaining 4 were lost to follow-up. CONCLUSION: ACNES should be considered in patients with chronic pain. A combination of typical findings in medical history and physical examination allows its diagnosis, therefore, avoiding unne cessary complementary tests. A step-up treatment strategy should be applied, beginning with oral analgesia, followed by anesthetic infiltration, and, finally, anterior neurectomy.

Morfea lineal en golpe de sable: a propósito de un caso / Linear morphea in saber coup: about a case

La morfea lineal en golpe de sable es una entidad dermatológica caracterizada por la inflamación esclerosante y progresiva del tejido cutáneo en la región frontal y/o en el cuero cabelludo. La cefalea y las crisis convulsivas son dos de los síntomas extracutáneos más frecuentes y están causados por el crecimiento subyacente de la lesión. Es importante un diagnóstico temprano para frenar la progresión e intentar evitar las complicaciones secundarias, principalmente neurológicas. El diagnóstico se basa en el cuadro clínico y el estudio histológico, que permite la confirmación definitiva. El tratamiento de elección es la terapia combinada con corticoides orales y metotrexato. Aun con el tratamiento farmacológico adecuado, esta patología puede presentar un curso recidivante y dejar secuelas a largo plazo. Se presenta el caso de una niña en quien se realizó un diagnóstico rápido de esta enfermedad, a pesar de un cuadro clínico inespecífico. Fue tratada con metotrexato oral con buena respuesta, sin efectos secundarios.

Linear morphea in coup de sabre is a dermatological entity characterized by progressive, sclerosing inflammation of the skin tissue in the frontal region and on the scalp. Headache and seizures are two of the most frequent extracutaneous symptoms and they are caused by the growth of the lesion towards underlying structures. An early diagnosis is important to stop cranial progression and try to avoid secondary complications, mainly neurological. The diagnosis is relied on compatible clinical signs and a pathological study that allows a definitive confirmation. The treatment of choice is combination therapy with oral corticosteroids and methotrexate. Despite an adequate pharmacological treatment, this pathology can present a recurrent course and cause long-term sequelae. We present the case of a girl who was diagnosed quickly, despite a not very noticeable symptoms. She has been treated with oral methotrexate with a good response, without side effect

[Linear morphea in saber coup: about a case]. / Morfea lineal en golpe de sable: a propósito de un caso.

Linear morphea in coup de sabre is a dermatological entity characterized by progressive, sclerosing inflammation of the skin tissue in the frontal region and on the scalp. Headache and seizures are two of the most frequent extracutaneous symptoms and they are caused by the growth of the lesion towards underlying structures. An early diagnosis is important to stop cranial progression and try to avoid secondary complications, mainly neurological. The diagnosis is relied on Morfea lineal en golpe de sable: a propósito de un caso Linear morphea in saber coup: about a case compatible clinical signs and a pathological study that allows a definitive confirmation. The treatment of choice is combination therapy with oral corticosteroids and methotrexate. Despite an adequate pharmacological treatment, this pathology can present a recurrent course and cause long-term sequelae. We present the case of a girl who was diagnosed quickly, despite a not very noticeable symptoms. She has been treated with oral methotrexate with a good response, without side effects.

La morfea lineal en golpe de sable es una entidad dermatológica caracterizada por la inflamación esclerosante y progresiva del tejido cutáneo en la región frontal y/o en el cuero cabelludo. La cefalea y las crisis convulsivas son dos de los síntomas extracutáneos más frecuentes y están causados por el crecimiento subyacente de la lesión. Es importante un diagnóstico temprano para frenar la progresión e intentar evitar las complicaciones secundarias, principalmente neurológicas. El diagnóstico se basa en el cuadro clínico y el estudio histológico, que permite la confirmación definitiva. El tratamiento de elección es la terapia combinada con corticoides orales y metotrexato. Aun con el tratamiento farmacológico adecuado, esta patología puede presentar un curso recidivante y dejar secuelas a largo plazo. Se presenta el caso de una niña en quien se realizó un diagnóstico rápido de esta enfermedad, a pesar de un cuadro clínico inespecífico. Fue tratada con metotrexato oral con buena respuesta, sin efectos secundarios.

Nueva forma de entender las pruebas de condición física en relación con la salud / New Approach to Health-Related Physical Fitness Tests

El objetivo de este trabajo es mostrar una nueva forma de entender la evaluación de la “condición física en relación con la salud”, para evitar la inactividad y el sedentarismo. Los antecedentes se encuentran en las baterías de test utilizadas desde 1976 hasta la actualidad. Se utiliza el concepto de salud de la OMS. Se analizan pruebas con criterios de funcionalidad, economía, validez, fiabilidad y especificidad. Se eligen las siguientes pruebas y se calculan los umbrales: 1425 s UKK Walk test (P75), 6 s en sprint test 20 m (P75), 19 repeticiones en Chair Stand Test (P25), 11 repeticiones Arm Curl Test (P25), -10,5 cm Back Scratch Test (P25), -17,5 cm en Chair Sit and Reach Test. Se propugna la elaboración de una batería de test universal e inclusiva y elaborar percentiles mundiales ayudados por el big data. (AU)

The aim of this research was to propose a new way of understanding health-related physical fitness assessment in order to prevent inactivity and sedentarism. The background lies in the test batteries used from 1976 to the present. WHO's health concept was used. Tests were analysed based on functionality, economy, validity, reliability and specificity criteria. The following tests were chosen and the thresholds were calculated: 1,425s in the UKK walk test (P75), 6s in the 20-m sprint test (P75), 19 repetitions in the chair stand test (P25), 11 repetitions in the arm curl test (P25), -10.5cm in the back scratch test (P25), -17.5cm in the chair sit-and-reach test (P25). It was proposed that a universal and inclusive test battery be developed and the percentiles for the world population are determined with the help of big data. (AU)

Successful deprescribing of proton pump inhibitors with a patient-centered process: the DESPIBP Project.

BACKGROUND: Proton-pump inhibitors (PPIs) are among the most frequently prescribed drugs, but they are being overprescribed. OBJECTIVE: To evaluate the applicability of a deprescription algorithm in hospitalized patients with chronic PPI use. METHODS: A prospective study including consecutive gastroenterology department hospitalized patients with chronic PPI use. The prescription was reassessed and a deprescribing algorithm was applied. Follow-up was carried out at 4, 12, and 24 weeks. RESULTS: A total of 513 (44.22%) of 1160 had chronic PPI use; 371 met inclusion criteria and were evaluated: 285 (76.82%) with appropriate prescription and 86 (23.18%) with inappropriate, mainly (52.30%) due to polypharmacy. Seventy-five patients accepted the deprescribing process. Sixty-one (81.33%) maintained deprescription at week 4, 56 (74.66%) at week 12, and 54 (72.00%) at week 24. Eleven of 21 restarted the PPI because of symptoms. No differences were found between the successful deprescription group and the unsuccessful one, regarding sex (p = 0.877), age (p = 0.635), PPI indication (p = 0.663), or deprescription regimen (p = 0.805). No patient had any adverse event attributable to deprescription. CONCLUSION: There is a high inappropriate indication for PPIs in patients admitted to the gastroenterology department. The application of a patient-centered deprescribing algorithm is a safe and effective strategy to reduce their inappropriate consumption in the medium term.

Thrombin in the Activation of the Fluid Contact Phase in Patients with Hereditary Angioedema Carrying the F12 P.Thr309Lys Variant.

Hereditary angioedema due to pathogenic FXII variants (HAE-FXII) is a rare dominant disease caused by increased activation of the plasma contact system. The most prevalent HAE-FXII variant, c.1032C > A p.Thr309Lys (FXII309Lys), results in a smaller FXII protein with increased sensitivity to fluid-phase activation by poorly understood mechanisms. We aimed to investigate the functionality of the FXII309Lys variant in 33 HAE-FXII patients, 25 healthy controls and 46 patients with congenital disorders of glycosylation (CDG). Activation of the plasma contact system was assessed by western blot and amidolytic assay in basal conditions or after treatment with either artificial or physiological activators. Recombinant wild-type and FXII309Lys variants were expressed in S2 insect (Drosophila) cells. Amidolytic and fibrin generation assays were performed in fresh plasma samples. FXII309Lys samples exhibited an increased electrophoretic mobility comparable with N-glycan-deficient FXII from CDG patients and asialo-FXII generated by neuraminidase treatment. They presented increased sensitivity to activation by dextran sulphate and silica which resulted in the generation of an aberrant 37-kDa heavy chain. We did not observe increased susceptibility of FXII309Lys to proteolysis by exogenous or tPA-generated plasmin. However, both exogenous and endogenous thrombin cleaved the FXII309Lys variant, releasing a 37-kDa fragment and resulting in enhanced proteolytic activation on the fluid phase. This model supports a sequential proteolytic activation process involving thrombin priming of FXII309Lys, followed by kallikrein cleavage and generation of active ßFXIIa. The present results and the observation that angioedema episodes in HAE-FXII patients occur predominantly during hypercoagulable situations suggest a key role for thrombin.

Connections between the internal and the external capsules and the globus pallidus in the sheep: A dichromate stain X-ray microtomographic study.

Sheep are recognized as useful species for translational neurodegeneration research, in particular for the study of Huntington disease. There is a lack of information regarding the detailed anatomy and connections of the basal ganglia of sheep, in normal myeloarchitectonics and in tract-tracing studies. In this work, the organization of the corticostriatal projections at the level of the putamen and globus pallidus (GP) are explored. For the first time, the myeloarchitectonic pattern of connections between the internal (IC) and the external (EC) capsules with the GP have been investigated in the sheep. Formaldehyde-fixed blocks of the striatum were treated with a metallic stain containing potassium dichromate and visualized using micro-CT (µ-CT). The trivalent chromium (Cr3+), attached to myelin phospholipids, imparts a differential contrast to the grey and white matter compartments, which allows the visualization of myelinated fascicles in µ-CT images. The fascicles were classified according to their topographical location in dorsal supreme fascicles (X, Y, apex) arising from the IC and EC; pre-commissurally, basal fascicles connecting the ventral part of the EC with the lateral zone of the ventral pallidum (VP) and, post-commissurally, superior (Z1 ), middle (Z2 ) and lower (Z3 ) fascicles, connecting at different levels the EC with the GP. The results suggest that the presumptive cortical efferent and afferent fibres to the pallidum could be organized according to a dorsal to ventrolateral topography in the sheep, similar to that seen in other mammals. The proposed methodology has the potential to delineate the myeloarchitectonic patterns of nervous systems and tracts.

Impact of SARS-CoV-2 infection in patients with cystic fibrosis in Spain: Incidence and results of the national CF-COVID19-Spain survey.

BACKGROUND: Given the high incidence of confirmed infection by SARS-CoV-2 and mortality by COVID-19 in the Spanish population, its impact was analysed among persons with Cystic Fibrosis (CF) as a group at risk of a worse evolution. The possible causes of the incidence observed in them are explained and how CF Units have faced this health challenge is detailed. METHODS: Retrospective descriptive observational study, for which a Spanish CF Patients with Confirmed COVID-19 Registry is created, requesting information on number of people affected between 8 March-16 May 2020 and their clinical-demographic characteristics from the CF Units participating in the European Cystic Fibrosis Society Patient Registry (ECFSPR). The accumulated incidence is calculated, compared with that of the general population. Additionally, a survey (CF-COVID19-Spain) is carried out on prevention of SARS-CoV-2 infection, workings of CF Units and possible reasons for the incidence observed. RESULTS: COVID-19 was diagnosed in eight CF patients, one of whom had received a lung transplant. The accumulated incidence was 32/10000 in CF patients and 49/10000 in the general population. General death rate was 5.85/10000 while no CF patients included in the ECFSPR died. The characteristics of those affected and the results of the survey are described. CONCLUSIONS: Despite being considered a disease at high risk of severe COVID-19, the low incidence and mortality in CF patients in Spain contrasts with the figures for the general population. The possible factors that would explain such findings are discussed, with the help of the results of the CF-COVID19-Spain survey.

When genetic and surname analyses meet historical sources: The C56R mutation associated with factor XI deficiency as a marker of human migration during the Spanish Reconquista.

The C56R mutation associated with factor XI deficiency has been first evidenced in individuals from the French Basque Country. Genetic investigations revealed that this mutation occurred about 5400 years ago as a founder effect in this zone. Other cases were subsequently described in Southwestern Europe. Noticeably a cluster of cases was evidenced in Yecla, a small city from the province of Murcia, in Southeastern Spain. In correlation with historical sources our genetic data and surname analysis argue for associating this mutation with the migration of people from Western Pyrenees (and more probably from the Navarra province) toward Southeastern Spain during the Reconquista period.

Successful desensitization to oxaliplatin after a single initial dose of omalizumab in a patient with elevated IgE levels

No disponible

Experimental and topological determination of the pressure-temperature phase diagram of racemic etifoxine, a pharmaceutical ingredient with anxiolytic properties.

Information about the solid-state properties of etifoxine has been lacking, even if the active pharmaceutical ingredient has been used for its anxiolytic properties for decennia. The crystal structure of the racemic compound possesses a monoclinic space group P21/n with cell parameters a = 8.489(2) Å, b = 17.674(2) Å, c = 20.883(3) Å, ß = 98.860(10)° and a unit-cell volume of 3095.8(9) Å3 at 293 K. The unit cell contains 8 molecules, while 2 independent molecules with different conformations are present in the asymmetric unit. The density of the crystal is 1.291 g/cm3 and its melting point was found at 362.6 ±â€¯0.3 K with a melting enthalpy of 85.6 ±â€¯3.0 J g-1. Its thermal expansion in the liquid and the solid state and the change in volume on melting and between the vitreous state and the crystalline solid have been studied. The results confirm the tendency of small organic molecules to increase about 11% in volume on melting, while the volume difference between the glass and the crystal at the glass transition temperature is about half this value at 6%. These values can be used in the construction of phase diagrams in the case that the experimental data for a given system is incomplete.