Chronic full-band recordings with graphene microtransistors as neural interfaces for discrimination of brain states.

Brain states such as sleep, anesthesia, wakefulness, or coma are characterized by specific patterns of cortical activity dynamics, from local circuits to full-brain emergent properties. We previously demonstrated that full-spectrum signals, including the infraslow component (DC, direct current-coupled), can be recorded acutely in multiple sites using flexible arrays of graphene solution-gated field-effect transistors (gSGFETs). Here, we performed chronic implantation of 16-channel gSGFET arrays over the rat cerebral cortex and recorded full-band neuronal activity with two objectives: (1) to test the long-term stability of implanted devices; and (2) to investigate full-band activity during the transition across different levels of anesthesia. First, we demonstrate it is possible to record full-band signals with stability, fidelity, and spatiotemporal resolution for up to 5.5 months using chronic epicortical gSGFET implants. Second, brain states generated by progressive variation of levels of anesthesia could be identified as traditionally using the high-pass filtered (AC, alternating current-coupled) spectrogram: from synchronous slow oscillations in deep anesthesia through to asynchronous activity in the awake state. However, the DC signal introduced a highly significant improvement for brain-state discrimination: the DC band provided an almost linear information prediction of the depth of anesthesia, with about 85% precision, using a trained algorithm. This prediction rose to about 95% precision when the full-band (AC + DC) spectrogram was taken into account. We conclude that recording infraslow activity using gSGFET interfaces is superior for the identification of brain states, and further supports the preclinical and clinical use of graphene neural interfaces for long-term recordings of cortical activity.

Habitat selection of resident and non-resident gray wolves: implications for habitat connectivity.

Habitat selection studies facilitate assessing and predicting species distributions and habitat connectivity, but habitat selection can vary temporally and among individuals, which is often ignored. We used GPS telemetry data from 96 Gray wolves (Canis lupus) in the western Great Lakes region of the USA to assess differences in habitat selection while wolves exhibited resident (territorial) or non-resident (dispersing or floating) movements and discuss implications for habitat connectivity. We used a step-selection function (SSF) to assess habitat selection by wolves exhibiting resident or non-resident movements, and modeled circuit connectivity throughout the western Great Lakes region. Wolves selected for natural land cover and against areas with high road densities, with no differences in selection among wolves when resident, dispersing, or floating. Similar habitat selection between resident and non-resident wolves may be due to similarity in environmental conditions, when non-resident movements occur largely within established wolf range rather than near the periphery or beyond the species range. Alternatively, non-resident wolves may travel through occupied territories because higher food availability or lower human disturbance outweighs risks posed by conspecifics. Finally, an absence of differences in habitat selection between resident and non-resident wolf movements may be due to other unknown reasons. We recommend considering context-dependency when evaluating differences in movements and habitat use between resident and non-resident individuals. Our results also provide independent validation of a previous species distribution model and connectivity analysis suggesting most potential wolf habitat in the western Great Lakes region is occupied, with limited connectivity to unoccupied habitat.

Intensive cholesterol-lowering treatment reduces synovial inflammation during early collagenase-induced osteoarthritis, but not pathology at end-stage disease in female dyslipidemic E3L.CETP mice.

INTRODUCTION: The association between metabolic syndrome (MetS) and osteoarthritis (OA) development has become increasingly recognized. In this context, the exact role of cholesterol and cholesterol-lowering therapies in OA development has remained elusive. Recently, we did not observe beneficial effects of intensive cholesterol-lowering treatments on spontaneous OA development in E3L.CETP mice. We postulated that in the presence of local inflammation caused by a joint lesion, cholesterol-lowering therapies may ameliorate OA pathology. MATERIALS AND METHODS: Female ApoE3∗Leiden.CETP mice were fed a cholesterol-supplemented Western type diet. After 3 weeks, half of the mice received intensive cholesterol-lowering treatment consisting of atorvastatin and the anti-PCSK9 antibody alirocumab. Three weeks after the start of the treatment, OA was induced via intra-articular injections of collagenase. Serum levels of cholesterol and triglycerides were monitored throughout the study. Knee joints were analyzed for synovial inflammation, cartilage degeneration, subchondral bone sclerosis and ectopic bone formation using histology. Inflammatory cytokines were determined in serum and synovial washouts. RESULTS: Cholesterol-lowering treatment strongly reduced serum cholesterol and triglyceride levels. Mice receiving cholesterol-lowering treatment showed a significant reduction in synovial inflammation (P = 0.008, WTD: 95% CI: 1.4- 2.3; WTD + AA: 95% CI: 0.8- 1.5) and synovial lining thickness (WTD: 95% CI: 3.0-4.6, WTD + AA: 95% CI: 2.1-3.2) during early-stage collagenase-induced OA. Serum levels of S100A8/A9, MCP-1 and KC were significantly reduced after cholesterol-lowering treatment (P = 0.0005, 95% CI: -46.0 to -12.0; P = 2.8 × 10-10, 95% CI: -398.3 to -152.1; P = 2.1 × 10-9, -66.8 to -30.4, respectively). However, this reduction did not reduce OA pathology, determined by ectopic bone formation, subchondral bone sclerosis and cartilage damage at end-stage disease. CONCLUSION: This study shows that intensive cholesterol-lowering treatment reduces joint inflammation after induction of collagenase-induced OA, but this did not reduce end stage pathology in female mice.

Fármacos modificadores de la enfermedad en la esclerosis múltiple durante la lactancia: revisión de la evidencia actual / Disease-modifying drugs in multiple sclerosis during breastfeeding: a review of current evidence

Introducción: La esclerosis múltiple afecta principalmente a mujeres en edad fértil, y el período de gestación y posparto es de especial interés por las peculiaridades que comporta en cuanto a evolución de la enfermedad y por las consecuencias terapéuticas que se derivan. En el período de lactancia materna (LM), la elección de la estrategia de tratamiento debe poner en una balanza, por un lado, los beneficios bien establecidos de la LM para el recién nacido y su madre y, por el otro, el perfil de seguridad y potenciales efectos adversos en el lactante derivados de la exposición a los fármacos modificadores de la enfermedad, por transferencia a través de leche materna. Desarrollo: Se realiza una revisión de la evidencia actual acerca de la seguridad de los fármacos modificadores de la enfermedad disponibles para el tratamiento de la esclerosis múltiple durante el período de LM, y se recogen datos de transferencia de los diferentes fármacos a la leche materna, así como los potenciales efectos adversos descritos en el lactante. Los fármacos considerados de primera elección durante este período son el interferón beta y el acetato de glatiramer. El resto de los fármacos modificadores de la enfermedad no están aceptados para su utilización en el período de LM por ficha técnica. Sin embargo, en los últimos años, se han publicado datos de estudios de práctica clínica y series de casos que indican que algunos de estos fármacos podrían utilizarse con seguridad durante este período. Conclusiones: Teniendo en cuenta los beneficios reconocidos de la LM para la salud tanto de la madre como del lactante, se debe recomendar la LM exclusiva a las pacientes con esclerosis múltiple siempre que sea posible. Es fundamental realizar una evaluación individualizada previa al embarazo y valorar las diferentes opciones de tratamiento en función de cada paciente.(AU)

Introduction: Multiple sclerosis mainly affects women of childbearing age, and the pregnancy and postpartum period is of special interest because of the peculiarities of the disease course and the therapeutic consequences that derive from it. During the period of breastfeeding (BF), the choice of treatment strategy must weigh up the well-established benefits of BF for both the newborn and the mother against the safety profile and potential adverse effects on the infant resulting from exposure to disease-modifying drugs transferred through breast milk. Development: The study reviews the current evidence on the safety of disease-modifying drugs available for the treatment of multiple sclerosis during the BF period, and gathers data on the transfer of the different drugs into breast milk, as well as the potential adverse effects described in the infant. The drugs of first choice during this period are interferon beta and glatiramer acetate. The rest of the disease modifying drugs are not accepted for use in the BF period according to their summary of product characteristics. However, in recent years, data from studies of clinical practice and case series have been published suggesting that some of these drugs could be used safely during this period. Conclusions: Given the recognised health benefits of BF for both mother and infant, exclusive breastfeeding is recommended whenever possible. It is essential to carry out an individualised assessment prior to pregnancy and to evaluate the different treatment options depending on each patient.(AU)

IL-1ß inhibition combined with cholesterol-lowering therapies decreases synovial lining thickness and spontaneous cartilage degeneration in a humanized dyslipidemia mouse model.

INTRODUCTION: Both systemic inflammation and dyslipidemia contribute to osteoarthritis (OA) development and have been suggested as a possible link between metabolic disease and OA development. Recently, the CANTOS trial showed a reduction in knee and hip replacements after inhibition of IL-1ß in patients with a history of cardiovascular disease and high inflammatory risk. In this light, we investigated whether inhibition of IL-1ß combined with cholesterol-lowering therapies can reduce OA development in dyslipidemic APOE∗3Leiden mice under pro-inflammatory dietary conditions. MATERIALS AND METHODS: Female ApoE3∗Leiden mice were fed a cholesterol-supplemented Western-Type diet (WTD) for 38 weeks. After 14 weeks, cholesterol-lowering and anti-inflammatory treatments were started. Treatments included atorvastatin alone or with an anti-IL1ß antibody, and atorvastatin combined with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor alirocumab without or with the anti-IL1ß antibody. Knee joints were analyzed for cartilage degradation, synovial inflammation and ectopic bone formation using histology at end point. RESULTS: Cholesterol-lowering treatment successfully decreased systemic inflammation in dyslipidemic mice, which was not further affected by inhibition of IL-1ß. Synovial thickening and cartilage degeneration were significantly decreased in mice that received cholesterol-lowering treatment combined with inhibition of IL-1ß (P < 0.01, P < 0.05, respectively) compared to mice fed a WTD alone. Ectopic bone formation was comparable between all groups. CONCLUSION: These results indicate that inhibition of IL-1ß combined with cholesterol-lowering therapy diminishes synovial thickening and cartilage degeneration in mice and may imply that this combination therapy could be beneficial in patients with metabolic inflammation.

[Esclerosis multiple. Lactancia. Lactante. Planificacion familiar. Posparto. Tratamiento modificador de la enfermedad.] / Fármacos modificadores de la enfermedad en la esclerosis múltiple durante la lactancia: revisión de la evidencia actual.

INTRODUCTION: Multiple sclerosis mainly affects women of childbearing age, and the pregnancy and postpartum period is of special interest because of the peculiarities of the disease course and the therapeutic consequences that derive from it. During the period of breastfeeding (BF), the choice of treatment strategy must weigh up the well-established benefits of BF for both the newborn and the mother against the safety profile and potential adverse effects on the infant resulting from exposure to disease-modifying drugs transferred through breast milk. DEVELOPMENT: The study reviews the current evidence on the safety of disease-modifying drugs available for the treatment of multiple sclerosis during the BF period, and gathers data on the transfer of the different drugs into breast milk, as well as the potential adverse effects described in the infant. The drugs of first choice during this period are interferon beta and glatiramer acetate. The rest of the disease modifying drugs are not accepted for use in the BF period according to their summary of product characteristics. However, in recent years, data from studies of clinical practice and case series have been published suggesting that some of these drugs could be used safely during this period. CONCLUSIONS: Given the recognised health benefits of BF for both mother and infant, exclusive breastfeeding is recommended whenever possible. It is essential to carry out an individualised assessment prior to pregnancy and to evaluate the different treatment options depending on each patient.

TITLE: Fármacos modificadores de la enfermedad en la esclerosis múltiple durante la lactancia: revisión de la evidencia actual.Introducción. La esclerosis múltiple afecta principalmente a mujeres en edad fértil, y el período de gestación y posparto es de especial interés por las peculiaridades que comporta en cuanto a evolución de la enfermedad y por las consecuencias terapéuticas que se derivan. En el período de lactancia materna (LM), la elección de la estrategia de tratamiento debe poner en una balanza, por un lado, los beneficios bien establecidos de la LM para el recién nacido y su madre y, por el otro, el perfil de seguridad y potenciales efectos adversos en el lactante derivados de la exposición a los fármacos modificadores de la enfermedad, por transferencia a través de leche materna. Desarrollo. Se realiza una revisión de la evidencia actual acerca de la seguridad de los fármacos modificadores de la enfermedad disponibles para el tratamiento de la esclerosis múltiple durante el período de LM, y se recogen datos de transferencia de los diferentes fármacos a la leche materna, así como los potenciales efectos adversos descritos en el lactante. Los fármacos considerados de primera elección durante este período son el interferón beta y el acetato de glatiramer. El resto de los fármacos modificadores de la enfermedad no están aceptados para su utilización en el período de LM por ficha técnica. Sin embargo, en los últimos años, se han publicado datos de estudios de práctica clínica y series de casos que indican que algunos de estos fármacos podrían utilizarse con seguridad durante este período. Conclusiones. Teniendo en cuenta los beneficios reconocidos de la LM para la salud tanto de la madre como del lactante, se debe recomendar la LM exclusiva a las pacientes con esclerosis múltiple siempre que sea posible. Es fundamental realizar una evaluación individualizada previa al embarazo y valorar las diferentes opciones de tratamiento en función de cada paciente.

Impacto de la vacunación de las embarazadas frente a la tosferina en las hospitalizaciones de menores de un año en un hospital de tercer nivel de Cataluña / Impact of vaccinating pregnant women against pertussis on hospitalizations of children under one year of age in a tertiary hospital in Catalonia

Introducción: La recomendación de la vacunación frente a la tosferina en embarazadas se instauró en Cataluña en febrero del 2014. El objetivo del presente estudio fue comparar la tasa de hospitalización por tosferina en niños menores de un año de edad antes y después de la implantación del programa de vacunación. Métodos: Estudio observacional y retrospectivo de pacientes menores de un año ingresados con diagnóstico de tosferina. Se comparó la tasa de hospitalización del periodo previo al programa de vacunación (2008-2013) con la del periodo con programa de vacunación (2014-2019) en el total de menores de un año y en 2subgrupos: en menores de 3 meses y en lactantes de 3 a 11 meses. Resultados: La tasa de hospitalización fue significativamente menor en el periodo con programa de vacunación en menores de un año y en menores de 3 meses (2,43 vs. 4,72 por 1.000 personas-año y 6,47 vs. 13,11 por 1.000 personas-año, respectivamente). Las razones de tasas entre períodos fueron: 0,51 (IC del 95%, 0,36-0,73) para los menores de un año; 0,49 (IC del 95%, 0,32-0,75) para los menores de 3 meses y 0,56 (IC del 95%, 0,30-1,03) para los de 3-11 meses. No se observaron diferencias estadísticamente significativas en la gravedad de los cuadros clínicos de los pacientes entre ambos periodos. Conclusión: La instauración del programa de vacunación contra la tosferina en embarazadas se ha asociado a una menor tasa de hospitalización por tosferina de forma global en los menores de un año de edad y específicamente en los menores de 3 meses.(AU)

Introduction: The recommendation for pertussis vaccination in pregnancy was established in Catalonia in February 2014. The objective of this study was to compare the hospitalization rate for pertussis in children under one year of age before and after the implementation of the vaccination program. Methods: Observational and retrospective study of patients under one year of age admitted to hospital with a diagnosis of pertussis. The hospitalization rate of patients under one year of age of the period prior to the vaccination program (2008-2013) was compared with the period with vaccination program (2014-2019) in the total of children under one year of age and in 2subgroups: children under 3 months and between 3-11 months. Results: Hospitalization rate was significantly lower in the period with vaccination program in children under one year of age and specifically in children under 3 months (2.43 vs. 4.72 per 1,000 person-years and 6.47 vs. 13.11 per 1,000 person-years, respectively). The rate ratios were: 0.51 (95% CI 0.36-0.73) for children under one year of age; 0.49 (95% CI 0.32-0.75) for those younger than 3 months and 0.56 (95% CI 0.30-1.03) for those with 3-11 months. No statistically significant differences were observed in the clinical severity between both periods. Conclusion: The introduction of the pertussis vaccination program in pregnancy was associated with a global lower hospitalization rate for pertussis in children under one year of age and specifically in those under 3 months of age.(AU)

Impact of vaccinating pregnant women against pertussis on hospitalizations of children under one year of age in a tertiary hospital in Catalonia.

INTRODUCTION: The recommendation for pertussis vaccination in pregnancy was established in Catalonia in February 2014. The objective of this study was to compare the hospitalisation rate for pertussis in children under one year of age before and after the implementation of the vaccination programme. METHODS: Observational and retrospective study of patients under one year of age admitted to hospital with a diagnosis of pertussis. The hospitalisation rate of patients under one year of age of the period prior to the vaccination programme (2008-2013) was compared with the period with vaccination programme (2014-2019) in the total of children under one year of age and in 2 subgroups: children under 3 months and between 3-11 months. RESULTS: Hospitalization rate was significantly lower in the period with vaccination programme in children under one year of age and specifically in children under 3 months (2.43 vs. 4.72 per 1000 person-years and 6.47 vs. 13.11 per 1000 person-years, respectively). The rate ratios were: 0.51 (95% CI 0.36-0.73) for children under one year of age; 0.49 (95% CI 0.32-0.75) for those younger than 3 months and 0.56 (95% CI 0.30-1.03) for those with 3-11 months. No statistically significant differences were observed in the clinical severity between both periods. CONCLUSION: The introduction of the pertussis vaccination programme in pregnancy was associated with a global lower hospitalisation rate for pertussis in children under one year of age and specifically in those under 3 months of age.

Scapular notching in reverse shoulder arthroplasty. Relationship with surgeon's experience and clinical outcomes / Notching escapular en las prótesis invertidas de hombro. Su relación con la experiencia del cirujano y con los resultados clínicos

Background: Scapular Notching is a problem frequently seen in Reverse shoulder arthroplasties (RSAs), produced by a collision between the humeral component and the scapula. The main objective of this study is to analyze whether this problem decreases with the surgeons experience. As secondary objectives, assessing whether there is a relationship between its appearance and the clinical and functional outcome of patients. Methods: We retrospectively reviewed 101 patients with 105 RSAs; we analyzed complications, focusing on scapular notching. Main follow-up time was 36 month (12-72). The clinical and functional outcomes were evaluated with the Constant scale and the QuickDash questionnaire. Results: Forty-two patients (40%) had some degree of scapular notching. Of these, 25 patients had grade I, 14 had grade II and 3 had grade III notching. The average postoperative Constant score for the entire series was 60.72. A tendency toward a reduced incidence of notching was observed with increasing numbers of operated cases and experience of the surgeon (p=0.04). In the group of patients who had notching, the average postoperative Constant score was 56, and in the group that developed notching, the average score was 63. Patients with notching had significantly lower pain scores (p=0.012). Conclusions: Scapular notching is a common problem of RSA. In RSA, the experience of the surgeon reduces the appearance of problems and complications. Scapular notching is related to poorer clinical outcomes with respect to pain.(AU)

Introducción: La erosión o muesca escapular (notching escapular) es un problema que se observa con frecuencia en las prótesis invertidas de hombro, producido por un choque entre el componente humeral y el cuello de la escápula. El objetivo principal de nuestro trabajo es analizar si disminuye el notching escapular con el aumento de la experiencia del cirujano. Como objetivos secundarios, el valorar si existe una relación entre su aparición y el resultado funcional y clínico en los pacientes. Material y método: Se realiza una revisión retrospectiva de 101 pacientes con 105 prótesis invertidas de hombro, valorando radiográficamente la aparición de notching escapular. El tiempo medio de seguimiento fue de 36 meses (rango, 12-72). Se objetivan los resultados clínico-funcionales con la escala Constant y el cuestionario QuickDash. Resultados: Cuarenta y dos pacientes (40%) presentaron algún grado de notching escapular. De ellos, 25 pacientes tenían un grado I, 14 un grado II y tres un grado III. El Constant postoperatorio medio para toda la serie fue de 60,72. Se observó una tendencia a disminuir la incidencia de notching conforme aumentaba el número de casos intervenidos y la experiencia del cirujano (p = 0,04). En el grupo de los pacientes que presentaban notching escapular, el Constant postoperatorio fue de 56 y en el grupo que no desarrolló notching fue del 63. Los pacientes con notching presentaban puntuaciones inferiores en cuanto al dolor siendo la diferencia estadísticamente significativa (p = 0,012). Conclusiones: El notching escapular es un problema frecuente en las prótesis invertidas de hombro, en las cuales la curva de aprendizaje influye positivamente en la diminución de su aparición. La aparición de notching escapular está relacionado con peores resultados clínicos en cuanto al dolor se refiere.(AU)

Notching escapular en las prótesis invertidas de hombro. Su relación con la experiencia del cirujano y con los resultados clínicos / Scapular notching in reverse shoulder arthroplasty. Relationship with surgeons experience and clinical outcomes

Introducción: La erosión o muesca escapular (notching escapular) es un problema que se observa con frecuencia en las prótesis invertidas de hombro, producido por un choque entre el componente humeral y el cuello de la escápula. El objetivo principal de nuestro trabajo es analizar si disminuye el notching escapular con el aumento de la experiencia del cirujano. Como objetivos secundarios, el valorar si existe una relación entre su aparición y el resultado funcional y clínico en los pacientes. Material y métodos: Se realiza una revisión retrospectiva de 101 pacientes con 105 prótesis invertidas de hombro, valorando radiográficamente la aparición de notching escapular. El tiempo medio de seguimiento fue de 36 meses (rango, 12-72). Se objetivan los resultados clínico-funcionales con la escala Constant y el cuestionario QuickDash. Resultados: Cuarenta y dos pacientes (40%) presentaron algún grado de notching escapular. De ellos, 25 pacientes tenían un grado I, 14 un grado II y tres un grado III. El Constant postoperatorio medio para toda la serie fue de 60,72. Se observó una tendencia a disminuir la incidencia de notching conforme aumentaba el número de casos intervenidos y la experiencia del cirujano (p = 0,04). En el grupo de los pacientes que presentaban notching escapular, el Constant postoperatorio fue de 56 y en el grupo que no desarrolló notching fue del 63. Los pacientes con notching presentaban puntuaciones inferiores en cuanto al dolor siendo la diferencia estadísticamente significativa (p = 0,012). Conclusiones: El notching escapular es un problema frecuente en las prótesis invertidas de hombro, en las cuales la curva de aprendizaje influye positivamente en la diminución de su aparición. La aparición de notching escapular está relacionado con peores resultados clínicos en cuanto al dolor se refiere.(AU)

Background: Scapular Notching is a problem frequently seen in Reverse shoulder arthroplasties (RSAs), produced by a collision between the humeral component and the scapula. The main objective of this study is to analyze whether this problem decreases with the surgeons experience. As secondary objectives, assessing whether there is a relationship between its appearance and the clinical and functional outcome of patients. Methods: We retrospectively reviewed 101 patients with 105 RSAs; we analyzed complications, focusing on scapular notching. Main follow-up time was 36 month (12-72). The clinical and functional outcomes were evaluated with the Constant scale and the QuickDash questionnaire. Results: Forty-two patients (40%) had some degree of scapular notching. Of these, 25 patients had grade I, 14 had grade II and 3 had grade III notching. The average postoperative Constant score for the entire series was 60.72. A tendency toward a reduced incidence of notching was observed with increasing numbers of operated cases and experience of the surgeon (p=0.04). In the group of patients who had notching, the average postoperative Constant score was 56, and in the group that developed notching, the average score was 63. Patients with notching had significantly lower pain scores (p=0.012). Conclusions: Scapular notching is a common problem of RSA. In RSA, the experience of the surgeon reduces the appearance of problems and complications. Scapular notching is related to poorer clinical outcomes with respect to pain.(AU)

Scapular notching in reverse shoulder arthroplasty. Relationship with surgeon̈s experience and clinical outcomes. / Notching escapular en las prótesis invertidas de hombro. Su relación con la experiencia del cirujano y con los resultados clínicos.

BACKGROUND: Scapular Notching is a problem frequently seen in Reverse shoulder arthroplasties (RSAs), produced by a collision between the humeral component and the scapula. The main objective of this study is to analyze whether this problem decreases with the surgeons experience. As secondary objectives, assessing whether there is a relationship between its appearance and the clinical and functional outcome of patients. METHODS: We retrospectively reviewed 101 patients with 105 RSAs; we analyzed complications, focusing on scapular notching. Main follow-up time was 36 month (12-72). The clinical and functional outcomes were evaluated with the Constant scale and the QuickDash questionnaire. RESULTS: Forty-two patients (40%) had some degree of scapular notching. Of these, 25 patients had grade I, 14 had grade II and 3 had grade III notching. The average postoperative Constant score for the entire series was 60.72. A tendency toward a reduced incidence of notching was observed with increasing numbers of operated cases and experience of the surgeon (p=0.04). In the group of patients who had notching, the average postoperative Constant score was 56, and in the group that developed notching, the average score was 63. Patients with notching had significantly lower pain scores (p=0.012). CONCLUSIONS: Scapular notching is a common problem of RSA. In RSA, the experience of the surgeon reduces the appearance of problems and complications. Scapular notching is related to poorer clinical outcomes with respect to pain.

Schools as a Framework for COVID-19 Epidemiological Surveillance of Children in Catalonia, Spain: A Population-Based Study.

Objective: We describe and analyze the childhood (<18 years) COVID-19 incidence in Catalonia, Spain, during the first 36 weeks of the 2020-2021 school-year and to compare it with the incidence in adults. Methods: Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests were obtained from the Catalan Agency for Quality and Health Assessment. Overall, 7,203,663 SARS-CoV-2 tests were performed, of which 491,819 were positive (6.8%). We collected epidemiological data including age-group incidence, diagnostic effort, and positivity rate per 100,000 population to analyze the relative results for these epidemiological characteristics. Results: Despite a great diagnostic effort among children, with a difference of 1,154 tests per 100,000 population in relation to adults, the relative incidence of SARS-CoV-2 for <18 years was slightly lower than for the general population, and it increased with the age of the children. Additionally, positivity of SARS-CoV-2 in children (5.7%) was lower than in adults (7.2%), especially outside vacation periods, when children were attending school (4.9%). Conclusions: A great diagnostic effort, including mass screening and systematic whole-group contact tracing when a positive was detected in the class group, was associated with childhood SARS-CoV-2 incidence and lower positivity rate in the 2020-2021 school year. Schools have been a key tool in epidemiological surveillance rather than being drivers of SARS-CoV-2 incidence in Catalonia, Spain.

Microbiological assessment of arterial allografts processed in a tissue bank.

The transmission of microbial infection through tissue allografts is one of the main risks that must be controlled in tissue banks. Therefore, microbiological monitoring controls and validated protocols for the decontamination of tissues during processing have been implemented. This study is based on the evaluation of data from microbiological cultures of arteries (mainly long peripheral arteries) processed in the tissue bank of Valencia (Spain). Donors' profile, pre- and post-disinfection tissue samples were assessed. The presence of residual antibiotics in disinfected tissues was determined and the antimicrobial potential of these tissues was tested. Our overall contamination rate was 23.69%, with a disinfection rate (after antibiotic incubation) of 87.5%. Most (76.09%) of the microbial contaminants were identified as Gram positive. Arterial allografts collected from body sites affected by prior organ removal showed higher risk of contamination. Only vancomycin was detected as tissue release. The antimicrobial effect on Candida albicans was lower than that for bacterial species. Risk assessment for microbial contamination suggested the donor's skin and the environment during tissue collection as the main sources for allograft contamination. Antibiotic-disinfected arterial allografts showed antimicrobial potential.

El rol del sistema renina angiotensina a nivel cerebral / The renin-angiotensin system and the brain

El sistema renina-angiotensina-aldosterona (SRAA) y sus efectos en el flujo sanguíneo e hidrosalino han sido estudiados a nivel cardiovascular y renal. La activación del SRAA en otros órganos tiene efectos tanto locales como sistémicos, alterando la macro y microvascultura de los órganos periféricos. En el cerebro, el SRAA regula la presión arterial (PA) a través del sistema nervioso simpático. El eje enzima convertidora de angiotensina/angiotensina II/receptor de angiotensina 1 (ECA/Ang II/AT1), vía clásica, y enzima convertidora de angiotensina tipo 2/angiotensina (1-7)/receptor Mas (ECA2/Ang [1-7]/MasR), vía no clásica, modulan la respuesta simpática. Su descompensación y acumulación de Ang II propician la hipertensión neurogénica (HTN) y otras patologías vasculares. El eje aminopeptidasa/angiotensina IV/receptor de angiotensina 4 (AMN/Ang IV/AT4), exclusivo del cerebro, condiciona la microvasculatura cerebral e interviene en la cognición, la memoria y el aprendizaje. Esta revisión propone descifrar los mecanismos de regulación de la PA por el SRAA central, así como revisar sus funciones y su contribución en la neuroprotección y la cognición. (AU)

The renin-angiotensin-aldosterone (RAAS) system and its effects on blood pressure and the regulation of water and electrolyte balance have been studied focusing on the cardiovascular and renal system. The activation of RAAS in other organs has local and systemic repercussions by modeling the macro- and microvasculture of peripheral organs. The brain RAAS influence on systemic blood pressure through the sympathetic nervous system. The angiotensin converting enzyme/angiotensin II/angiotensin 1 receptor axis (ACE/AngII/AT1), classical pathway, and angiotensin converting enzyme type 2/angiotensin (1-7)/Mas receptor (ACE2/Ang (1-7)/MasR), non-classical pathway, are involved in the modulation of the sympathetic response. The imbalance of these two axes with subsequently Ang II accumulation promote neurogenic hypertension and other vascular pathologies. The aminopeptidase/angiotensin IV/angiotensin 4 receptor (AMN/Ang IV/AT4) axis, which is exclusive of the brain, acts on cerebral microvasculature and participates in cognition, memory, and learning. The aim of this review is to decipher the major central RAAS mechanisms involved in blood pressure regulation. In addition, paracrine functions of brain RAAS and its role in neuroprotection and cognition are also described in this review. (AU)

A single dose of anti-IL-1ß antibodies prevents Western diet-induced immune activation during early stage collagenase-induced osteoarthritis, but does not ameliorate end-stage pathology.

OBJECTIVE: Metabolic dysfunction can cause IL-1ß mediated activation of the innate immune system, which could have important implications for the therapeutic efficacy of IL-1ß neutralizing drugs as treatment for OA in the context of metabolic syndrome (MetS). In the present study, we investigated whether early treatment with a single dose of IL-1ß blocking antibodies could prevent Western diet (WD) induced changes to systemic monocyte populations and their cytokine secretion profile and herewith modulate collagenase induced osteoarthritis (CiOA) pathology. METHODS: CiOA was induced in female C57Bl/6 mice fed either a standard diet (SD) or WD and treated with a single dose of either polyclonal anti-IL-1ß antibodies or control. Monocyte subsets and granulocytes in bone marrow and blood were analyzed with flow cytometry, and cytokine expression by bone marrow cells was analyzed using qPCR. Synovial cellularity, cartilage damage and osteophyte formation were assessed on histology. RESULTS: WD feeding of C57Bl/6 mice led to increased serum levels of low-density lipoprotein (LDL) and innate immune activation in the form of an increased number of Ly6Chigh cells in bone marrow and blood and increased cytokine expression of IL-6 and TNF-α by bone marrow cells. The increase in monocyte number and activity was ameliorated by anti-IL-1ß treatment. However, anti-IL-1ß treatment did not significantly affect synovial lining thickness, cartilage damage and ectopic bone formation during WD feeding. CONCLUSIONS: Single-dose systemic anti-IL-1ß treatment prevented WD-induced innate immune activation during early stage CiOA in C57Bl/6 mice, but did not ameliorate joint pathology.

Impact of vaccinating pregnant women against pertussis on hospitalizations of children under one year of age in a tertiary hospital in Catalonia. / Impacto de la vacunación de las embarazadas frente a la tosferina en las hospitalizaciones de menores de un año en un hospital de tercer nivel de Cataluña.

INTRODUCTION: The recommendation for pertussis vaccination in pregnancy was established in Catalonia in February 2014. The objective of this study was to compare the hospitalization rate for pertussis in children under one year of age before and after the implementation of the vaccination program. METHODS: Observational and retrospective study of patients under one year of age admitted to hospital with a diagnosis of pertussis. The hospitalization rate of patients under one year of age of the period prior to the vaccination program (2008-2013) was compared with the period with vaccination program (2014-2019) in the total of children under one year of age and in 2subgroups: children under 3 months and between 3-11 months. RESULTS: Hospitalization rate was significantly lower in the period with vaccination program in children under one year of age and specifically in children under 3 months (2.43 vs. 4.72 per 1,000 person-years and 6.47 vs. 13.11 per 1,000 person-years, respectively). The rate ratios were: 0.51 (95% CI 0.36-0.73) for children under one year of age; 0.49 (95% CI 0.32-0.75) for those younger than 3 months and 0.56 (95% CI 0.30-1.03) for those with 3-11 months. No statistically significant differences were observed in the clinical severity between both periods. CONCLUSION: The introduction of the pertussis vaccination program in pregnancy was associated with a global lower hospitalization rate for pertussis in children under one year of age and specifically in those under 3 months of age.

Mapping evidence on the effects of gender-affirming hormone therapy on the hard and soft tissues of the craniofacial complex in transgender people: a protocol for a scoping review.

BACKGROUND: Gender-affirming hormone (GAH) therapy aims to support the transition of transgender people to their gender identity. GAHs can induce changes in their secondary sex characteristics such as the development of breasts in transgender females and increased muscle mass in transgender males. The face and its surrounding tissues also have an important role in gender confirmation. The aim of this scoping review is to systematically map the available evidence in order to provide an overview of the effects of GAH therapy on the hard and soft tissues of the craniofacial complex in transgender people. METHODS/DESIGN: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA) extension for Scoping Reviews was consulted for reporting this protocol. The methods were based on the Arksey and O'Malley's framework and the Reviewer's Manual of the Joanna Briggs Institute for conducting scoping reviews. Ten transgender people were involved in the development of the primary research question through short interviews. The eligibility criteria were defined for transgender people undergoing GAH therapy and for quantitative and qualitative outcomes on the hard and soft tissues of the craniofacial complex. Eligible sources of evidence include observational, experimental, qualitative, and mixed method studies. No exclusion criteria will be applied for the language of publication and the setting. To identify eligible sources of evidence, we will conduct searches from inception onwards in PubMed, Embase.com , the Cochrane Library, Web of Science Core Collection, Scopus, CINAHL, LIVIVO, and various grey literature sources such as Google Scholar. Two reviewers will independently select eligible studies in these information sources and will subsequently conduct data extraction. The same operators will chart, categorize, and summarize the extracted data. A narrative summary of findings will be conducted. Frequency counts of quantitative and qualitative data on items such as concepts, populations, interventions, and other characteristics of the eligible sources will be given. Where possible, these items will be mapped descriptively. DISCUSSION: We chose the scoping review over the systematic review approach, because the research questions are broad-spectrum and the literature is expected to be widely scattered. No systematic review has previously assessed this topic. Identifying knowledge gaps in this area and summarizing and disseminating research findings are important for a wide spectrum of stakeholders, in particular, for transgender people who want to undergo additional interventions such as plastic or orthognathic surgery or orthodontics. SYSTEMATIC REVIEW REGISTRATION: This protocol was registered in the Open Science Framework: https://osf.io/e3qj6.

Novel high-intensive cholesterol-lowering therapies do not ameliorate knee OA development in humanized dyslipidemic mice.

OBJECTIVE: High systemic cholesterol levels have been associated with osteoarthritis (OA) development. Therefore, cholesterol lowering by statins has been suggested as a potential treatment for OA. We investigated whether therapeutic high-intensive cholesterol-lowering attenuated OA development in dyslipidemic APOE∗3Leiden.CETP mice. METHODS: Female mice (n = 13-16 per group) were fed a Western-type diet (WTD) for 38 weeks. After 13 weeks, mice were divided into a baseline group and five groups receiving WTD alone or with treatment: atorvastatin alone, combined with PCSK9 inhibitor alirocumab and/or ANGPTL3 inhibitor evinacumab. Knee joints were analysed for cartilage degradation, synovial inflammation and ectopic bone formation using histology. Aggrecanase activity in articular cartilage and synovial S100A8 expression were determined as markers of cartilage degradation/regeneration and inflammation. RESULTS: Cartilage degradation and active repair were significantly increased in WTD-fed mice, but cholesterol-lowering strategies did not ameliorate cartilage destruction. This was supported by comparable aggrecanase activity and S100A8 expression in all treatment groups. Ectopic bone formation was comparable between groups and independent of cholesterol levels. CONCLUSIONS: Intensive therapeutic cholesterol lowering per se did not attenuate progression of cartilage degradation in dyslipidemic APOE∗3Leiden.CETP mice, with minor joint inflammation. We propose that inflammation is a key feature in the disease and therapeutic cholesterol-lowering strategies may still be promising for OA patients presenting both dyslipidemia and inflammation.