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IMPORTANCE: Functional movement disorders (FMDs) are frequent and disabling neurological disorders with a substantial socioeconomic impact. Few randomized studies have analyzed the effectiveness of combined physiotherapy and psychotherapy in patients’ quality of life. OBJECTIVE: To assess the efficacy of multidisciplinary treatment (physiotherapy plus cognitive behavioral therapy) in FMDs. DESIGN, SETTING, AND PARTICIPANTS: This was a parallel, rater-blinded, single-center, randomized clinical trial. Recruitment took place from June 2022 to April 2023, and follow-up visits were performed at months 3 and 5, concluding in October 2023. Participants were recruited from a national referral center for movement disorders: the Movement Disorders Unit from the Hospital Universitario Virgen Rocio in Seville, Spain. Patients had to be 18 years or older with a confirmed FMD diagnosis and capable of giving consent to participate. Patients who did not meet eligibility criteria or refused to participate were excluded. Any uncontrolled psychiatric disorder was considered an exclusion criterion. INTERVENTIONS: Patients were randomly assigned, in a ratio of 1:1 to multidisciplinary treatment (physiotherapy plus cognitive behavioral therapy), or a control intervention (psychological support intervention). MAIN OUTCOMES AND MEASURES: Primary outcomes: between-group differences in changes from baseline to month 3 and month 5 in patients’ quality of life (EQ-5D-5L score: EQ Index and EQ visual analog scale [EQ VAS]; and 36-Item Short-Form Survey Physical Component Summary [SF-36 PCS] and SF-36 Mental Component Summary [MCS]). Linear mixed models were applied, controlling by baseline severity and applying Bonferroni correction. RESULTS: Of 70 patients screened with an FMD, 40 were enrolled (mean [SD] age, 43.5 [12.8] years; age range, 18-66 years; 32 female [80%]; mean [SD] age at FMD onset, 38.4 [12.1] years), and 38 completed all the follow-up visits and were included in the analysis for primary outcomes. Multidisciplinary treatment improved SF-36 PCS with a mean between-group difference at 3 months of 4.23 points (95% CI, −0.9 to 9.4 points; P = .11) and a significant mean between-group difference at 5 months of 5.62 points (95% CI, 2.3-8.9 points; P < .001), after multiple-comparisons adjustment. There were no significant differences in other quality-of-life outcomes such as SF-36 MCS (mean between-group difference at 3 and 5 months: 0.72 points; 95% CI, −5.5 to 7.0 points; P = .82 and 0.69 points; 95% CI, 2.3-8.9 points; P = .83, respectively), EQ VAS (9.34 points; 95% CI, −0.6 to 19.3 points; P = .07 and 13.7 points; 95% CI, −1.7 to 29.0 points; P = .09, respectively) and EQ Index (0.001 point; 95% CI, −0.1 to 0.1 point; P = .98 and 0.08 points; 95% CI, 0-0.2 points; P = .13, respectively). At months 3 and 5, 42% and 47% of patients, respectively, in the multidisciplinary group reported improved health using the EQ-5D system, compared with 26% and 16% of patients, respectively, in the control group. CONCLUSIONS AND RELEVANCE: Results show that multidisciplinary treatment (physiotherapy plus cognitive behavioral therapy) effectively improves FMD symptoms and physical aspects of patients’ quality of life. Further studies must be performed to evaluate the potential cost-effectiveness of this approach in FMD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05634486

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We characterized bovine viral diarrhea virus (BVDV)-related abortions in cattle and identified the species and subgenotypes in the state of Santa Catarina, southern Brazil. Our RT-PCR assay was positive for BVDV in 5 fetuses from different farms; however, 3 of the 5 fetuses were also PCR-positive for Neospora caninum. In the 5 BVDV-positive fetuses, gross lesions included fetal mummification (1), hepatomegaly (1), subcutaneous edema (1), and perirenal edema (1). Predominant histologic lesions included epicarditis and mild-to-moderate lymphoplasmacytic myocarditis (5), mild multifocal lymphoplasmacytic interlobular pneumonia (4), nephrosis associated with moderate multifocal interstitial nephritis (1), moderate multifocal lymphoplasmacytic necrotic hepatitis (1), and mild multifocal lymphoplasmacytic meningitis (1). The amplification products from the Pestivirus5′UTR region of 4 of the 5 fetuses had 96.3–100% similarity between fetal strains and reference strains. The samples were distributed into 2 branches of the phylogenetic tree; strains UDESC:01, UDESC:02, and UDESC:05 clustered in the BVDV-1e branch, uncommon in the Americas, and strain UDESC:04 clustered in the BVDV-2b branch. The three 1e strains had 96.9–97.4% similarity.

Fluid-filled cavities within the brain are well-recognized in human and veterinary medicine. Congenital or acquired brain cystic lesions could be isolated or associated with other diseases. Clinical signs related to cysts depend on their size and the mass effect they exert on surrounding neuroanatomical structures. We present a case of a 5-month-old Belgian Malinois dog with cervical pain and right head tilt. The dog had a normal haematochemical profile and negative infectious disease tests. A contrast enhancement Computed Tomography scan revealed the presence of a thin-walled cystic lesion in the caudal cranial fossa at the level of the right pontine-cerebellar junction. A cerebrospinal fluid tap was performed by lumbar puncture, revealing a monocytic pleocytosis. After initial improvement following corticosteroid and antibiotic therapy, clinical signs worsened, and the dog underwent a second clinical evaluation and magnetic resonance imaging examination. After euthanasia a complete postmortem examination was performed. Histological and immunohistochemical findings were suggestive of an ependymal cyst.

•Ante un paciente que consulta por múltiples lesiones pigmentadas, los diagnósticos a tener en cuenta en primer lugar son nevus melanocíticos en un paciente joven y lentigos solares, angiomas seniles o queratosis seborreicas en personas mayores de 50 años. Si las lesiones son únicas o escasas probablemente se trate de un melanoma, un carcinoma basocelular, un granuloma piógeno o un dermatofibroma.•Lo difícil es diferenciar la lesión maligna del resto de lesiones, para lo que nos regimos muchas veces del signo del «patito feo» (ugly duck), aquella lesión que llama la atención, que es diferente del resto por la forma, el color, el tacto o la consistencia.•Para el análisis de las lesiones pigmentadas se suele seguir la regla del ABCDE (Asimetría, Borde irregular, poliCromía, Diámetro ≥ 0,6cm y Evolución o crecimiento). Cualquier lesión con 3 o más criterios puede ser un nevus clínicamente atípico o un melanoma y debería ser remitida al dermatólogo para ser biopsiada.•También es muy útil valerse de un dermatoscopio. El reconocimiento de los patrones característicos facilita la diferenciación de la naturaleza de las lesiones y permite reconocer los cambios precoces de un melanoma.•Los nevus melanocíticos comunes se inician normalmente en la infancia y siguen aumentando en número y tamaño hasta el final de la edad adulta. No es muy frecuente detectar muchos nevus en el anciano, y los que se ven suelen ser intradérmicos o compuestos. La aparición de un nevus en una persona mayor de 50 años nos ha de hacer pensar en la posibilidad de un melanoma.•La mayoría de los nevos en la infancia son junturales, máculas fuertemente pigmentadas, planas, con patrón dermatoscópico globular, reticular o pigmentado homogéneo. Con el tiempo, muchos se sobreelevan y pierden parte de la coloración (nevos compuestos) adoptando patrones combinados retículo-globular o retículo-homogéneo (hiper o hipopigmentación central homogénea y retículo periférico). Algunos de estos cambios se producen con la exposición solar.•Los nevus clínicamente atípicos y los nevos displásicos son una variedad de nevus mayores de 0,5cm, en muchas ocasiones maculopapulares, que tienen al menos 3 de las características ABCDE. Con el dermatoscopio se pueden objetivar retículo atípico, velo azul blanquecino e hiper o hipopigmentación central o parcheada, cambios muy similares a los del melanoma in situ, aunque no tan marcados.•Los dermatofibromas se manifiestan como pápulas pigmentadas de consistencia firme, estables en el tiempo, que se localizan preferentemente en las extremidades inferiores. La dermatoscopia más característica consiste en una zona central blanca, cicatricial, y una periferia con reticulado fino.•Las queratosis seborreicas suelen aparecer después de los 50 años. Hasta el 90% de la población mayor de 70 años tiene de promedio una quincena de queratosis seborreicas. Son pápulas pigmentadas y queratósicas, de tacto ligeramente rasposo, con comedones y tapones córneos y pequeños quistes de millium, hallazgos que se hacen más evidentes con el dermatoscopio.•El melanoma más común es el de extensión superficial. Suele ser una lesión que cumple 2 o más criterios del ABCDE, situada en cualquier localización, que suele cambiar en pocos meses y presenta por lo general un patrón dermatoscópico multicomponente que combina pigmentación irregular, red de pigmento atípica, seudópodos y estructuras de regresión como las estructuras blancas brillantes y las rayas blancas o el velo azul blanquecino con puntos que recuerdan la pimienta.

•Los nevus melanocíticos son tumores benignos que derivan de los melanocitos. Se caracterizan histológicamente por nidos y cordones de células melánicas en la unión dermoepidérmica y/o la dermis. Su importancia estriba en distinguirlos del melanoma, su contrapartida maligna. El principal factor de riesgo de los nevus es la exposición al sol en edades tempranas pero también existe una predisposición genética.•Pueden ser congénitos o adquiridos. Algunas variantes de los primeros son los nevus de Spilus, los nevus de Ota y los nevus de Ito. Entre los segundos destacan el nevus azul, el nevus de Sutton y el nevus de Spitz y de Reed.•Los nevus melanocíticos congénitos se originan durante la vida fetal y suelen estar presentes en el nacimiento. Se localizan principalmente en el tronco y en las extremidades. Se presentan como máculas de bordes irregulares, de color marrón claro a marrón oscuro, casi negro. Con los años pueden evolucionar y presentar hipertricosis o adoptar un aspecto verrugoso. Según el tamaño se pueden clasificar en: pequeños, medianos y gigantes.•El riesgo de desarrollar un melanoma de los nevus melanocíticos congénitos varía según su tamaño. Es de menos del 1% en los pequeños, mientras que se considera de casi el 5% en los gigantes. Por ello se recomienda realizar controles clínicos periódicos en todos los casos, principalmente en los de mayor tamaño, y practicar exéresis-biopsia en los casos que manifiesten signos de atipia clínica (policromía, bordes irregulares, cambios en el tamaño, desarrollo de nódulos en superficie).•Se denomina nevus de Spilus a una lesión pigmentada congénita, habitualmente de color café con leche, sobre la que se asientan múltiples nevus junturales o compuestos, que suele localizarse en tronco y extremidades. El nevus de Ota consiste en una mácula pigmentada, azul-grisácea, en la región oftálmica y maxilar del nervio trigémino. El nevus de Ito es clínicamente idéntico al nevus de Ota, pero afecta la parte superior de la espalda y el hombro.•Los nevus melanocíticos comunes adquiridos aparecen desde los 6 meses de vida hasta la cuarta década. Son más frecuentes en personas de piel clara y predominan en tronco y extremidades. Se presentan como máculas o pápulas simétricas, menores de 6mm, con pigmentación homogénea y bordes definidos. Según la localización de los nidos de melanocitos, se clasifican en junturales, compuestos e intradérmicos, con lo que varía su aspecto clínico. Se tienen que realizar controles periódicos de aquellos casos con más de 50 nevus y, de forma más estricta, cuando presenten atipia clínica (2 o más criterios ABCDE).•Los nevus azules consisten en máculas o pápulas gris-azuladas que presentan esta coloración por el fenómeno Tyndall. El nevus de Sutton se observa como una mácula o pápula central marrón-rosada rodeada de un halo de hipopigmentación y es frecuente en la espalda. El nevus de Spitz aparece como una pápula semiesférica, lisa, de color desde rosado a marrón oscuro. Suele afectar a los niños o a menores de 20 años y suele localizarse en la cabeza o el cuello y, más raramente, en las extremidades. Existe una variante del adulto que suele ser más pigmentada y se conoce como nevus de Reed. Los 3 tipos de lesiones son simuladores del melanoma.•Los nevus atípicos suelen estar presentes en el inicio de la edad adulta y se caracterizan por tener 3 o más características del acrónimo ABCDE: (A) asimetría, (B) bordes irregulares, (C) coloración heterogénea, (D) diámetro mayor de 6mm y (E) evolución: cambios de forma, color o tamaño. Además de considerarse un marcador de riesgo de desarrollar melanoma, la propia lesión puede ser asiento de melanoma. Es muy importante la revisión periódica y seguimiento estrecho de estos pacientes, así como biopsiar las lesiones que puedan ser sospechosas.•Los factores de riesgo principales de melanoma son tener un número elevado de nevus, especialmente si son atípicos, el grado de fotoexposición, el número de quemaduras solares en la infancia, el antecedente personal o familiar de melanoma. Otros factores de riesgo son el fenotipo claro (fototipo i-ii) y, en especial, el fenotipo pelirrojo.•Los nevus melanocíticos son lesiones precursoras directas y marcadores de un mayor riesgo de melanoma cutáneo. Sin embargo, el riesgo de transformación de una lesión concreta en melanoma se considera bajo. Las estrategias recientes para reducir la carga de la enfermedad avanzada se han centrado en la detección temprana y la vigilancia continua de los nevus en busca de signos de alarma según el ABDCE. También es fundamental evitar las quemaduras solares en la infancia y el uso adecuado de fotoprotector con factor de protección solar ≥30.

Latest studies in patients with first episode psychosis (FEP) have shown alterations in cardiovascular, immune and endocrinological systems. These findings could indicate a systemic onset alteration in the metabolic disease as opposed to justifying these findings exclusively by antipsychotics’ side effects and long-term lifestyle consequences. In any case, this population is considered at higher risk for developing cardiometabolic disorders than their age-matched peers.

In the last decades, non-thermal plasma has been extensively investigated as a relevant tool for various biomedical applications, ranging from tissue decontamination to regeneration and from skin treatment to tumor therapies. This high versatility is due to the different kinds and amount of reactive oxygen and nitrogen species that can be generated during a plasma treatment and put in contact with the biological target. Some recent studies report that solutions of biopolymers with the ability to generate hydrogels, when treated with plasma, can enhance the generation of reactive species and influence their stability, resulting thus in the ideal media for indirect treatments of biological targets. The direct effects of the plasma treatment on the structure of biopolymers in water solution, as well as the chemical mechanisms responsible for the enhanced generation of RONS, are not yet fully understood. In this study, we aim at filling this gap by investigating, on the one hand, the nature and extent of the modifications induced by plasma treatment in alginate solutions, and, on the other hand, at using this information to explain the mechanisms responsible for the enhanced generation of reactive species as a consequence of the treatment. The approach we use is twofold: (i) investigating the effects of plasma treatment on alginate solutions, by size exclusion chromatography, rheology and scanning electron microscopy and (ii) study of a molecular model (glucuronate) sharing its chemical structure, by chromatography coupled with mass spectrometry and by molecular dynamics simulations. Our results point out the active role of the biopolymer chemistry during direct plasma treatment. Short-lived reactive species, such as OH radicals and O atoms, can modify the polymer structure, affecting its functional groups and causing partial fragmentation. Some of these chemical modifications, like the generation of organic peroxide, are likely responsible for the secondary generation of long-lived reactive species such as hydrogen peroxide and nitrite ions. This is relevant in view of using biocompatible hydrogels as vehicles for storage and delivery reactive species for targeted therapies.

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD)1. However, achieving stable recovery is unpredictable2, typically requiring trial-and-error stimulation adjustments due to individual recovery trajectories and subjective symptom reporting3. We currently lack objective brain-based biomarkers to guide clinical decisions by distinguishing natural transient mood fluctuations from situations requiring intervention. To address this gap, we used a new device enabling electrophysiology recording to deliver SCC DBS to ten TRD participants (ClinicalTrials.gov identifier NCT01984710). At the study endpoint of 24 weeks, 90% of participants demonstrated robust clinical response, and 70% achieved remission. Using SCC local field potentials available from six participants, we deployed an explainable artificial intelligence approach to identify SCC local field potential changes indicating the patient’s current clinical state. This biomarker is distinct from transient stimulation effects, sensitive to therapeutic adjustments and accurate at capturing individual recovery states. Variable recovery trajectories are predicted by the degree of preoperative damage to the structural integrity and functional connectivity within the targeted white matter treatment network, and are matched by objective facial expression changes detected using data-driven video analysis. Our results demonstrate the utility of objective biomarkers in the management of personalized SCC DBS and provide new insight into the relationship between multifaceted (functional, anatomical and behavioural) features of TRD pathology, motivating further research into causes of variability in depression treatment.

Health care workers (HCW) have been identified as a risk group to suffer psychological burden derived from Coronavirus Disease 19 (COVID-19) pandemic. In addition, possible gender differences in the emotional reactions derived from COVID-19 pandemic have been suggested in this population. The aims of the study were to explore the impact of COVID-19 as well as possible gender differences on mental health status and suicidality in a cohort of HCW.

All-electron basis sets of quintuple and sextuple zeta valence qualities plus polarization functions (5ZP and 6ZP) for the elements from H to Ar, to be used together with the zero-order regular approximation (ZORA), have been developed. To describe electrons distant from the nuclei, diffuse functions were added to the 6ZP non-relativistic set, giving rise to the set designated as augmented 6ZP (A6ZP). A5ZP-ZORA, A6ZP-ZORA, and A6ZP-DKH (Douglas–Kroll–Hess) basis sets were also generated. In order to have a better description of some molecular properties, d-symmetry functions with high exponents were added to the ZORA basis sets for the elements of the second-row. Using these basis sets together with the couple cluster method, ionization energies and static mean dipole polarizabilities of some atoms and geometric parameters, harmonic vibrational frequencies, atomization energies, and electric dipole moments of a set of molecules were calculated and compared with recommended and experimental values found in the literature. The performances of the ZORA and DKH Hamiltonians were evaluated.

In this study, phylogenetic and evolutionary analyses of cattle pestiviruses (BVDV-1, 2 and HoBiPeV) originating in Brazil were used to investigate the temporal diversification of subgenotypes in the country. Inferred dated phylogeny and time of the most recent common ancestor (tMRCA) demonstrated that some BVDV subgenotypes (1a, 1b, 1d, 1e, and 2b) and HoBi-like sequences clustered according to the region in which they were collected and that the diversification of subgenotypes appears to have occurred around the introduction of first Bos taurusand then Bos indicus, followed by expansion to form the adapted Brazilian breeds. The present results help to elucidate the temporal facts that led to diversification of ruminant pestiviruses in cattle in Brazil.

Visna-maedi is a multisystemic and progressive inflammatory disease caused by a non-oncogenic retrovirus (Visna-maedi virus, VMV). An outbreak of visna-maedi occurred in Southern Brazil in sheep with clinical signs of blindness and stumbling gait. At post-mortem examination, all animals had similar lesions, including heavy non-collapsed lungs and multifocal yellow areas in the cerebral white matter, affecting mainly the periventricular region. These lesions corresponded histologically to lymphocytic interstitial pneumonia and histiocytic periventricular encephalitis surrounding areas of necrosis, in addition to significant demyelination in the brain. Serology was performed in all the sheep from the flock and 14% were seropositive for VMV. The presence of VMV was confirmed through PCR and partial sequencing of the 5′LTR. Sequencing demonstrated that the virus had 89.7 to 90.0% of nucleotide identity with VMV strains reported in the USA. This is the first description of clinical disease related to VMV in Brazil leading to economic losses. This study calls for the need to implement control measures to prevent the spread of small ruminant lentiviruses in Brazil.

Natural history studies in neuromuscular disorders are vital to understand the disease evolution and to find sensitive outcome measures. We performed a longitudinal assessment of quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (31P MRS) outcome measures and evaluated their relationship with function in lower limb skeletal muscle of dysferlinopathy patients. Quantitative MRI/31P MRS data were obtained at 3 T in two different sites in 54 patients and 12 controls, at baseline, and three annual follow‐up visits. Fat fraction (FF), contractile cross‐sectional area (cCSA), and muscle water T2in both global leg and thigh segments and individual muscles and 31P MRS indices in the anterior leg compartment were assessed. Analysis included comparisons between patients and controls, assessments of annual changes using a linear mixed model, standardized response means (SRM), and correlations between MRI and 31P MRS markers and functional markers. Posterior muscles in thigh and leg showed the highest FF values. FF at baseline was highly heterogeneous across patients. In ambulant patients, median annual increases in global thigh and leg segment FF values were 4.1% and 3.0%, respectively (P< 0.001). After 3 years, global thigh and leg FF increases were 9.6% and 8.4%, respectively (P< 0.001). SRM values for global thigh FF were over 0.8 for all years. Vastus lateralis muscle showed the highest SRM values across all time points. cCSA decreased significantly after 3 years with median values of 11.0% and 12.8% in global thigh and global leg, respectively (P< 0.001). Water T2values in ambulant patients were significantly increased, as compared with control values (P< 0.001). The highest water T2values were found in the anterior part of thigh and leg. Almost all 31P MRS indices were significantly different in patients as compared with controls (P< 0.006), except for pHw, and remained, similar as to water T2, abnormal for the whole study duration. Global thigh water T2at baseline was significantly correlated to the change in FF after 3 years (ρ= 0.52, P< 0.001). There was also a significant relationship between the change in functional score and change in FF after 3 years in ambulant patients (ρ= −0.55, P= 0.010). This multi‐centre study has shown that quantitative MRI/31P MRS measurements in a heterogeneous group of dysferlinopathy patients can measure significant changes over the course of 3 years. These data can be used as reference values in view of future clinical trials in dysferlinopathy or comparisons with quantitative MRI/S data obtained in other limb‐girdle muscular dystrophy subtypes.

We investigate the observed muon deficit in air shower simulations when compared to ultrahigh-energy cosmic ray (UHECR) data. Based upon the observed enhancement of strangeness production in high-energy hadronic collisions reported by the ALICE Collaboration, the concomitant π↔Kswap is considered as the keystone to resolve the muon anomaly through its corresponding impact on the shower development. We construct a toy model in terms of the π↔Kswapping probability Fs. We present a parametrization of Fsin terms of the pseudorapidity that can accommodate the UHECR data. Looking to the future, we explore potential strategies for model improvement using the massive amounts of data to be collected by LHC neutrino detectors, such as FASERνand experiments at the Forward Physics Facility. We calculate the corresponding sensitivity to Fsand show that these experiments will be able to probe the model phase space.

AbstractPerinatal light exposure predisposes towards health and behaviour in adulthood. Season of birth is associated with psychiatric, allergic, cardiovascular and metabolic problems. It has been proposed that early-life environmental light disrupts the development of biological rhythms which, in turn, influence later-life health. However, the mechanisms linking perinatal seasonal light to later-life biological rhythm and health in humans are unknown. In this study, we investigated the association between season of birth and epigenome-wide DNA methylation of two postmortem human brain regions (16 hypothalamus, 14 temporal cortex). We did not find statistically significant differences at the whole epigenome level, either because we lacked statistical power or that no association exists. However, when we examined 24 CpG sites that had the highest significance or differential methylation, we identified regions which may be associated with circadian rhythm entrainment, cholinergic neurotransmission and neural development. Amongst methylation of the core clock genes, we identified that hypothalamus Neuronal PAS Domain Protein 2(NPAS2) gene has hypermethylated regions in long photoperiod-born individuals. In addition, we found nominal associations between season of birth and genes linked to chronotype and narcolepsy. Season of birth-related brain DNA methylation profile was different than a previously reported blood methylation profile, suggesting a tissue-specific mechanism of perinatal light programming. Overall, we are the first to analyse the relationship between season of birth and human brain DNA methylation. Further studies with larger sample sizes are required to confirm an imprinting effect of perinatal light on the circadian clock.

Nail involvement in psoriasis is common. It is seen in up to 80% of patients with psoriatic lesions and may be the only manifestation in 6% of cases. Nail psoriasis is correlated with more severe disease, characterized by earlier onset and a higher risk of psoriatic arthritis. Accordingly, it can also result in significant functional impairment and reduced quality of life. Psoriasis involving the nail matrix causes pitting, leukonychia, red lunula and nail dystrophy, while nail bed involvement causes splinter hemorrhages, onycholysis, oil spots (salmon patches), and subungual hyperkeratosis. Common evaluation tools are the Nail Psoriasis Severity Index (NAPSI), the modified NAPSI, and the f-PGA (Physician's Global Assessment of Fingernail Psoriasis). Treatment options include topical therapy, intralesional injections, and systemic and biologic agents. Treatment should therefore be assessed on an individualized basis according to the number of nails involved, the part of the nail or nails affected, and the presence of concomitant nail and/or joint involvement.

L’insuline est un médicament à risque (MAR) pourvoyeur d’effets indésirables graves (EIG). Les professionnels de santé doivent être vigilants du stockage à l’administration de l’insuline. Dans le cadre de la préparation de la certification, la réalisation de traceurs ciblés sur le circuit d’utilisation des stylos à insuline a mis en évidence un non-respect des bonnes pratiques.

Le sémaglutide, analogue du GLP1, régule l’appétit et l’apport calorique. Il est indiqué en accès précoce (AP) dans la perte de poids chez les personnes adultes ayant un indice de masse corporelle ≥40 kg/m2avec comorbidités. Son instauration est réalisée par paliers de doses pour améliorer la tolérance.

La contamination interne des professionnels de santé par les médicaments anticancéreux (MAC) reste un problème actuel de santé au travail, notamment parce que ces composés sont classés dangereux à manipuler par le NIOSH et certains comme agents CMR par le CIRC et la FDA. Afin d’améliorer les actions de prévention, une étude des facteurs associés à cette contamination interne a été menée auprès du personnel infirmier de deux établissements de soins.

Les médicaments anticancéreux (MAC) présentent un danger pour la santé des personnels qui les manipulent. Une contamination interne peut avoir lieu lors de la manipulation directe des MAC et lors de contacts indirects via le patient traité ou des surfaces contaminées. La principale voie d’exposition est la voie cutanée. C’est sur cette dernière que pourrait s’appuyer en partie la prévention. L’objectif de ce travail était d’évaluer, selon les recommandations de l’Anses, la contamination interne du personnel par les MAC dans un hôpital oncologique, d’investiguer ces résultats par la métrologie de surface et d’adapter la prévention.

Porcine circovirus type 3 (PCV3) is widely distributed worldwide, and its association with clinical disease in pigs has been studied in recent years. This study describes a novel PCV3-associated clinical disease in piglets from Brazil. Since September 2020, we received 48 piglets with large caudally rotated ears, weakness, and dyspnea. Most piglets were from gilts and died 1–5 days after birth. Two piglets that presented similar clinical signs and survived until 35–60 days had a marked decrease in growth rate. At post-mortem examination, the lungs did not collapse due to marked interlobular edema. Microscopically, the main feature was multisystemic vasculitis characterized by lymphocytes and plasma cells infiltrating and disrupting the wall of vessels, lymphohistiocytic interstitial pneumonia, myocarditis, and encephalitis. Viral replication was confirmed in these lesions through in situ hybridization (ISH-RNA). Seventeen cases were positive for PCV3 in PCR analysis, and all samples tested negative for porcine circovirus (PCV1, and PCV2); porcine parvovirus (PPV1, 2, 5, and 6); atypical porcine pestivirus (APPV); porcine reproductive and respiratory syndrome (PRRSV); and ovine herpesvirus-2 (OvHV-2). Phylogenetic analysis of the ORF2 sequence from five different pig farms showed that the PCV3a clade is circulating among Brazil’s swineherds and causing neonatal piglet losses. This is the first report of PCV3a-associated disease in neonatal pigs from farms in Brazil.

From ab initio simulations of liquid water, the time-dependent friction functions and time-averaged nonlinear effective bond potentials for the OH stretch and HOH bend vibrations are extracted. The obtained friction exhibits not only adiabatic contributions at and below the vibrational time scales but also much slower nonadiabatic contributions, reflecting homogeneous and inhomogeneous line broadening mechanisms, respectively. Intermolecular interactions in liquid water soften both stretch and bend potentials compared to the gas phase, which by itself would lead to a red-shift of the corresponding vibrational bands. In contrast, nonadiabatic friction contributions cause a spectral blue shift. For the stretch mode, the potential effect dominates, and thus, a significant red shift when going from gas to the liquid phase results. For the bend mode, potential and nonadiabatic friction effects are of comparable magnitude, so that a slight blue shift results, in agreement with well-known but puzzling experimental findings. The observed line broadening is shown to be roughly equally caused by adiabatic and nonadiabatic friction contributions for both the stretch and bend modes in liquid water. Thus, the quantitative analysis of the time-dependent friction that acts on vibrational modes in liquids advances the understanding of infrared vibrational frequencies and line shapes.

The detection of distribution patterns of genetic diversity of plant and animal species has contributed to the understanding of biodiversity and evolutionary history of the Atlantic Forest. We used microsatellite markers to access the genetic diversity and structure of 26 populations and 527 adult individuals of Euterpe edulis, a native palm which is an important food resource for fauna and is intensively exploited due to economic reasons. We found high genetic diversity and inbreeding in all populations analyzed. We report highest rates of inbreeding for this species, which could reflect the anthropic impacts of selective cutting, fragmentation, and change in foraging behavior from pollinators and less availability and mobility of large dispersers. We detected by STRUCTURE, two genetic groups, Northern and Southern, which divide the Brazilian Atlantic Forest geographically. These groups have low genetic admixtures, but we found a region of lineage hybridization in the contact zone with low recent gene flow. Distribution pattern of this species corroborates results from previous studies reporting the Last Glacial Maximum (LGM) have shaped the structuring of the species through movements of forests’ expansion and contraction. The STRUCTURE analysis of each group revealed the presence of genetic subgroups with low rates of recurrent gene flow. Southern subgroups have higher rates of admixtures than the Northern subgroups, revealing greater historical connectivity of forests in this region.

El trauma infantil ha sido descrito como un factor de riesgo para la psicosis. Diferentes tipos de experiencias traumáticas en la infancia podrían conducir a distintas manifestaciones clínicas en los trastornos psicóticos.

Hydrogels have been recently proposed as suitable materials to generate reactive oxygen and nitrogen species (RONS) upon gas-plasma treatment, and postulated as promising alternatives to conventional cancer therapies. Acting as delivery vehicles that allow a controlled release of RONS to the diseased site, plasma-treated hydrogels can overcome some of the limitations presented by plasma-treated liquids in in vivotherapies. In this work, we optimized the composition of a methylcellulose (MC) hydrogel to confer it with the ability to form a gel at physiological temperatures while remaining in the liquid phase at room temperature to allow gas-plasma treatment with suitable formation of plasma-generated RONS. MC hydrogels demonstrated the capacity for generation, prolonged storage and release of RONS. This release induced cytotoxic effects on the osteosarcoma cancer cell line MG-63, reducing its cell viability in a dose-response manner. These promising results postulate plasma-treated thermosensitive hydrogels as good candidates to provide local anticancer therapies.

Kratom alkaloids have mostly been evaluated for their opioid activity but less at other targets that could contribute to their physiological effects. Here, we investigated the in vitro and in vivo activity of kratom alkaloids at serotonin receptors (5-HTRs). Paynantheine and speciogynine exhibited high affinity for 5-HT1ARs and 5-HT2BRs, unlike the principal kratom alkaloid mitragynine. Both alkaloids produced antinociceptive properties in rats via an opioid receptor-independent mechanism, and neither activated 5-HT2BRs in vitro. Paynantheine, speciogynine, and mitragynine induced lower lip retraction and antinociception in rats, effects blocked by a selective 5-HT1AR antagonist. In vitro functional assays revealed that the in vivo 5-HT1AR agonistic effects may be due to the metabolites 9-O-desmethylspeciogynine and 9-O-desmethylpaynantheine and not the parent compounds. Both metabolites did not activate 5-HT2BR, suggesting low inherent risk of causing valvulopathy. The 5-HT1AR agonism by kratom alkaloids may contribute to the mood-enhancing effects associated with kratom use.

The interaction between COVID-19, non-communicable diseases, and chronic infectious diseases such as HIV and tuberculosis is unclear, particularly in low-income and middle-income countries in Africa. South Africa has a national HIV prevalence of 19% among people aged 15–49 years and a tuberculosis prevalence of 0·7% in people of all ages. Using a nationally representative hospital surveillance system in South Africa, we aimed to investigate the factors associated with in-hospital mortality among patients with COVID-19.

SARS‐CoV‐2 infection has produced high mortality in kidney transplant (KT) recipients, especially in the elderly. Until December 2020, 1011 KT with COVID‐19 have been prospectively included in the Spanish Registry and followed until recovery or death. In multivariable analysis, age, pneumonia, and KT performed ≤6 months before COVID‐19 were predictors of death, whereas gastrointestinal symptoms were protective. Survival analysis showed significant increasing mortality risk in four subgroups according to recipient age and time after KT (age <65 years and posttransplant time >6 months, age <65 and time ≤6, age ≥65 and time >6 and age ≥65 and time ≤6): mortality rates were, respectively, 11.3%, 24.5%, 35.4%, and 54.5% (p< .001). Patients were significantly younger, presented less pneumonia, and received less frequently specific anti‐COVID‐19 treatment in the second wave (July–December) than in the first one (March–June). Overall mortality was lower in the second wave (15.1 vs. 27.4%, p< .001) but similar in critical patients (66.7% vs. 58.1%, p= .29). The interaction between age and time post‐KT should be considered when selecting recipients for transplantation in the COVID‐19 pandemic. Advanced age and a recent KT should foster strict protective measures, including vaccination. Older recipients diagnosed with COVID‐19 in the first 6 months after transplantation present the highest risk for a fatal outcome during the second wave of the COVID‐19 pandemic.

SARS-CoV-2 infection has produced high mortality in kidney transplant (KT) recipients, especially in the elderly. Until December 2020, 1011 KT with COVID-19 have been prospectively included in the Spanish Registry and followed until recovery or death. In multivariable analysis, age, pneumonia, and KT performed ≤6 months before COVID-19 were predictors of death, whereas gastrointestinal symptoms were protective. Survival analysis showed significant increasing mortality risk in four subgroups according to recipient age and time after KT (age <65 years and posttransplant time >6 months, age <65 and time ≤6, age ≥65 and time >6 and age ≥65 and time ≤6): mortality rates were, respectively, 11.3%, 24.5%, 35.4%, and 54.5% (p< .001). Patients were significantly younger, presented less pneumonia, and received less frequently specific anti-COVID-19 treatment in the second wave (July–December) than in the first one (March–June). Overall mortality was lower in the second wave (15.1 vs. 27.4%, p< .001) but similar in critical patients (66.7% vs. 58.1%, p= .29). The interaction between age and time post-KT should be considered when selecting recipients for transplantation in the COVID-19 pandemic. Advanced age and a recent KT should foster strict protective measures, including vaccination.

Flaviviruses as West Nile virus (WNV), Saint Louis encephalitis virus (SLEV), Ilhéus virus (ILHV), and Rocio virus (ROCV) are previously reported in different Brazilian regions, but studies in Southern Brazil are still scarce. To improve the information regarding flaviviruses in Southern Brazil, horse serum samples were analyzed using RT-qPCR and a commercial ELISA-Ab against WNV followed by PRNT75. All 1000 samples analyzed by real-time RT-PCR resulted negative. The 465 subsampled samples were analyzed by a commercial ELISA-Ab against WNV, and the 18.5% (86/465) positive samples were further analyzed by PRNT75. In the PRNT75, 13/86 and 2/86 horses were positive for SLEV and WNV, respectively. It was observed that 5.8% (13/226) of the farms presented at least one positive animal for SLEV in PRNT75, whereas 0.9% (2/226) for WNV. Apart from the lower seroprevalences identified when compared to data previously reported in other Brazilian regions, our results suggest that public health professionals must be aware of the presence of these potential zoonotic pathogens.

HO radicals are the most important reactive species generated during water treatment by non-thermal plasma devices. In this letter, we report the first quantification of the steady-state concentration and lifetime of plasma-produced hydroxyl radicals in water solutions at pH 3 and 7, and we discuss the differences based on their reactivity with other plasma-generated species. Finally, we show to what extent the use of chemical probes to quantify short-lived reactive species has an influence on the results and that it should be taken into account.

•There was no influence of the training status of the appendectomy procedure on complication rates and in-hospital mortality.•However, the teaching group showed longer duration of surgery (+ 11%).•The advantages of teaching in the surgical setting are superior and justifiable.

Different iron oxide catalysts supported on mesoporous silica were prepared by several techniques including assembly of pre-synthesized nanoparticles, coprecipitation in the presence of the support or impregnation. Characterization showed that iron oxide nanoparticles were dispersed either at the surface of the SiO2material or within the pores when prepared by dry impregnation. The catalytic performance of these materials for Fenton chemistry was evaluated through kinetic tests in the presence of coumarin as a radical trap for the quantification of the HO radicals produced. The first tests concerned the production of HO radicals from H2O2by a Fenton-like reaction. The results show that catalysts prepared by dry impregnation in an ethanolic solution show the highest activity toward the production of HO radicals. These catalysts were also engaged in a reaction without external H2O2using a cold atmospheric pressure plasma jet treatment with the successful purpose of increasing the production of HO radicals in aqueous solution at room temperature and near-neutral pH. Our best catalysts outperformed others reported in the literature in reactions carried out with soluble species or at acidic pH. Moreover, a synergetic effect between the heterogeneous catalyst and the plasma for HO radical production was highlighted. These radicals could be easily used for biomedical or wastewater treatment applications.

Previous research has documented that, when investing abroad, emerging market multinationals (EMMs) have a higher tolerance for risk than developed country multinationals (DCMs), highlighting their propensity to make bold acquisitions and to form alliance networks. In this paper we examine the differences between EMMs and DCMs when it comes to choosing between these options of external growth. We argue that EMMs have a higher propensity than DCMs to choose joint ownership options and, among them, those involving complex partnerships, so as to leverage their routines and imprinted capabilities to deal with partners. In order to carry out the study, we consider the differences in entry mode patterns in emerging markets by multinationals from USA, European Union, BRIC, and Next-Eleven countries between 1996 and 2012. Our results supported our hypotheses.

AbstractThis paper aims to research whether the varieties of capitalism impact the relationship between social capital and inequality in developed economies (coordinated and liberal economies) and Latin America (hierarchical economies) in the period from 2000 to 2016. To do that, the study uses a panel analysis of developed economies and Latin America, that is, a fixed effect panel static analysis. The model includes one dependent variable (Gini index) and ten independent variables (generalised trust, informal economy, years of schooling, union density, market capitalization, annual gross domestic product, gross domestic product per capita, health expenditure, feminine labour force, and gross capital). The findings show that the relationship between inequality and social capital is negative and significant and that hierarchical economies (Latin America) amplified such a relationship.

Establish recommendations for the management of UTIs in MS patients.

Describir las actividades formativas en participación comunitaria en salud que se realizan en España.

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin‐6 (IL‐6) release. The IL‐6‐receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID‐19) . In this pandemic, kidney transplant (KT) recipients are a high‐risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID‐19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P= .039). IL‐6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D‐dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C‐reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004‐1.024], P= .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID‐19 but randomized trials are needed. This multicenter study reports the outcomes of kidney transplant patients treated with tocilizumab for COVID‐19, showing a mortality rate of 32.5% and higher levels of C‐reactive protein early after tocilizumab administration for patients with poor outcomes.

Atmospheric pressure plasma jets generate reactive oxygen and nitrogen species (RONS) in liquids and biological media, which find application in the new area of plasma medicine. These plasma-treated liquids were demonstrated recently to possess selective properties on killing cancer cells and attracted attention toward new plasma-based cancer therapies. These allow for local delivery by injection in the tumor but can be quickly washed away by body fluids. By confining these RONS in a suitable biocompatible delivery system, great perspectives can be opened in the design of novel biomaterials aimed for cancer therapies. Gelatin solutions are evaluated here to store RONS generated by atmospheric pressure plasma jets, and their release properties are evaluated. The concentration of RONS was studied in 2% gelatin as a function of different plasma parameters (treatment time, nozzle distance, and gas flow) with two different plasma jets. Much higher production of reactive species (H2O2and NO2–) was revealed in the polymer solution than in water after plasma treatment. The amount of RONS generated in gelatin is greatly improved with respect to water, with concentrations of H2O2and NO2–between 2 and 12 times higher for the longest plasma treatments. Plasma-treated gelatin exhibited the release of these RONS to a liquid media, which induced an effective killing of bone cancer cells. Indeed, in vitro studies on the sarcoma osteogenic (SaOS-2) cell line exposed to plasma-treated gelatin led to time-dependent increasing cytotoxicity with the longer plasma treatment time of gelatin. While the SaOS-2 cell viability decreased to 12%–23% after 72 h for cells exposed to 3 min of treated gelatin, the viability of healthy cells (hMSC) was preserved (∼90%), establishing the selectivity of the plasma-treated gelatin on cancer cells. This sets the basis for designing improved hydrogels with high capacity to deliver RONS locally to tumors.

Three-dimensional macroporous scaffolds are commonly used in bone tissue engineering applications since they provide sufficient space for cell migration and proliferation, facilitating bone ingrowth and implant vascularisation. The aim of this work was to combine two simple methods, freeze-drying and gas-foaming, in order to fabricate highly macroporous bone scaffolds made of chitosan/agarose matrix reinforced with nanohydroxyapatite. The secondary goal of this research was to comprehensively assess biomedical potential of developed biomaterials. In this work, it was demonstrated that simultaneous application of freeze-drying and gas-foaming technique allows to obtain hybrid (as proven by ATR-FTIR) macroporous bone scaffolds (pore diameter > 50 μm) characterized by high open (70 %) and interconnected porosity. Novel scaffolds were non-toxic, favoured osteoblasts adhesion and growth and induced apatite formation on their surfaces, indicating their high bioactivity that is essential for good implant osseointegration. Biomaterials were also prone to enzymatic degradation, degradation in acidified microenvironment (e.g. osteoclast-mediated), and slow degradation under physiological pH of 7.4. Moreover, the scaffolds revealed microstructure (70 % open porosity, SSA approx. 30 m2/g, high share of macropores with diameter in the range 100−410 μm) and compressive strength (1–1.4 MPa) comparable to cancellous bone, indicating that they are promising implants for cancellous bone regeneration. [ABSTRACT FROM AUTHOR]

•La escabiosis o sarna humana es un trastorno pruriginoso causado por la infestación por el ácaro específico del huésped Sarcoptes scabieivar. hominis. Suele transmitirse a través del contacto directo con una persona infestada, aunque también es posible la transmisión por fómites, especialmente en la variante costrosa.•El diagnóstico debe sospecharse ante toda persona con prurito generalizado y progresivo de predominio nocturno, en el que predominen las excoriaciones por rascado. El diagnóstico definitivo se basa en la detección de ácaros, huevos o escíbalos (residuos fecales) de sarna al examen microscópico.•El tratamiento de primera línea para la sarna clásica consiste en la aplicación de permetrina tópica en crema al 5%.•La aparición de los síntomas de la sarna puede retrasarse varias semanas después de la infestación. Las personas que han estado en contacto personal cercano con un paciente con sarna pueden tener sarna activa incluso en ausencia de síntomas. Por ello, es aconsejable tratar simultáneamente a los individuos que hayan tenido contacto prolongado con pacientes con sarna clásica.•La pediculosis pubis es una infestación principalmente transmitida por vía sexual. Pthirus pubises el organismo causante.•La pediculosis pubis generalmente involucra las áreas púbica y perianal, pero también puede afectar a la axila u otras áreas corporales con vello. El prurito en las áreas afectadas es el síntoma principal.•El diagnóstico se realiza mediante la identificación visual de piojos y liendres.•Las personas con pediculosis pubis deben someterse a pruebas de detección de otras enfermedades de transmisión sexual.•Aunque la mayoría de los niños con pediculosis ciliar adquieren la infestación por contacto no sexual, se debe considerar la posibilidad de abuso sexual.•Como tratamiento de primera elección se utiliza permetrina tópica al 1%. Se recomienda repetir el tratamiento después de una semana para asegurar la curación. Las parejas sexuales de individuos con escabiosis y con pediculosis pubis deben tratarse simultáneamente.