Serie de 22 casos de ictus isquémico arterial perinatal: factores de riesgo, manejo clínico y secuelas neurológicas / A series of 22 cases of perinatal arterial ischaemic stroke: risk factors, clinical management and neurological sequelae

Introduction. Perinatal arterial ischaemic stroke (PAIS) is almost as common as in adulthood and causes significant neurological sequelae. Aim. The aim is to describe the risk situations surrounding these neonates, the clinical manifestations, the management, the cost-effectiveness of diagnostic tests and the neurological sequelae. Patients and methods. We conducted an observational study of a cohort of patients consisting of neonates with a gestational age = 35 weeks diagnosed with PAIS in our hospital between 2010 and 2021. Results. Twenty-two cases of PAIS were included, and the incidence in our centre was 1/1,869 live newborns. The data showed that 81.8% had some intrapartum risk factor and 40.9% had a combination of several risk factors. It started with seizures (mean age 27.3 hours) in 77.3% of cases. Patients with a stroke in the left hemisphere had more sequelae (77.8%) than those with a stroke on the right-hand side (16.6%) (p = 0.041), with the exception of infantile cerebral palsy (p = 0.04), while we found no difference between hemispheres in the frequency of language impairment (p = 0.06). The mean follow-up time was 6.13 ± 3.06 years. A total of 63.6% of infants had neurological sequelae: infantile cerebral palsy (40.9%), language disorders (22.7%) and intellectual disability (9%). Moreover, 18.2% developed epilepsy (between 0.25 and 1.8 years) and antiseizure treatment was maintained after discharge in 37.5% of cases in the last years of the study. Conclusions. If a newborn infant presents seizures, it is necessary to rule out the possibility of a stroke. PAIS causes neurological sequelae in over 60% of cases. Early identification is essential to improve the neurological prognosis and avoid the prolonged use of antiseizure drugs where possible. (AU)

Introducción: El ictus cerebral isquémico arterial perinatal (IIAP) es una entidad casi tan frecuente como en la época adulta, que ocasiona secuelas neurológicas importantes.ObjetivoDescribir las situaciones de riesgo que rodean a estos neonatos, la clínica que manifiestan, el manejo, la rentabilidad de las pruebas diagnósticas y las secuelas neurológicas.Pacientes y métodosEstudio observacional de una cohorte de pacientes formada por neonatos = 35 semanas de edad gestacional diagnosticados de IIAP entre 2010 y 2021 en nuestro hospital.ResultadosSe incluyeron 22 casos de IIAP, y su incidencia en nuestro centro fue de 1/1.869 recién nacidos vivos. El 81,8% tuvo algún factor de riesgo intraparto y en el 40,9% se aglutinaron varios. Comenzó con convulsiones (edad media 27,3 horas) el 77,3% de casos. Los pacientes con ictus del hemisferio izquierdo tuvieron más secuelas (77,8%) en comparación con los derechos (16,6%) (p = 0,041), a expensas de la parálisis cerebral infantil (p = 0,04), mientras no encontramos diferencia en la frecuencia de alteraciones del lenguaje (p = 0,06) entre hemisferios. El tiempo medio de seguimiento fue de 6,13 años ± 3,06. El 63,6% de los neonatos tuvo secuelas neurológicas: parálisis cerebral infantil (40,9%), trastornos del lenguaje (22,7%) y discapacidad intelectual (9%). Desarrolló epilepsia el 18,2% (entre 0,25 y 1,8 años) y se mantuvo el tratamiento anticrisis tras el alta en el 37,5% de los casos en los últimos años del estudio.ConclusionesAnte un neonato con convulsiones hay que descartar un ictus cerebral. El IIAP ocasiona secuelas neurológicas en más del 60% de los casos. Su identificación precoz es fundamental para mejorar el pronóstico neurológico y evitar el uso prolongado de fármacos anticrisis cuando resulte posible. (AU)

[A series of 22 cases of perinatal arterial ischaemic stroke: risk factors, clinical management and neurological sequelae]. / Serie de 22 casos de ictus isquémico arterial perinatal: factores de riesgo, manejo clínico y secuelas neurológicas.

INTRODUCTION: Perinatal arterial ischaemic stroke (PAIS) is almost as common as in adulthood and causes significant neurological sequelae. AIM: The aim is to describe the risk situations surrounding these neonates, the clinical manifestations, the management, the cost-effectiveness of diagnostic tests and the neurological sequelae. PATIENTS AND METHODS: We conducted an observational study of a cohort of patients consisting of neonates with a gestational age = 35 weeks diagnosed with PAIS in our hospital between 2010 and 2021. RESULTS: Twenty-two cases of PAIS were included, and the incidence in our centre was 1/1,869 live newborns. The data showed that 81.8% had some intrapartum risk factor and 40.9% had a combination of several risk factors. It started with seizures (mean age 27.3 hours) in 77.3% of cases. Patients with a stroke in the left hemisphere had more sequelae (77.8%) than those with a stroke on the right-hand side (16.6%) (p = 0.041), with the exception of infantile cerebral palsy (p = 0.04), while we found no difference between hemispheres in the frequency of language impairment (p = 0.06). The mean follow-up time was 6.13 ± 3.06 years. A total of 63.6% of infants had neurological sequelae: infantile cerebral palsy (40.9%), language disorders (22.7%) and intellectual disability (9%). Moreover, 18.2% developed epilepsy (between 0.25 and 1.8 years) and antiseizure treatment was maintained after discharge in 37.5% of cases in the last years of the study. CONCLUSIONS: If a newborn infant presents seizures, it is necessary to rule out the possibility of a stroke. PAIS causes neurological sequelae in over 60% of cases. Early identification is essential to improve the neurological prognosis and avoid the prolonged use of antiseizure drugs where possible.

TITLE: Serie de 22 casos de ictus isquémico arterial perinatal: factores de riesgo, manejo clínico y secuelas neurológicas.Introducción. El ictus cerebral isquémico arterial perinatal (IIAP) es una entidad casi tan frecuente como en la época adulta, que ocasiona secuelas neurológicas importantes. Objetivo. Describir las situaciones de riesgo que rodean a estos neonatos, la clínica que manifiestan, el manejo, la rentabilidad de las pruebas diagnósticas y las secuelas neurológicas. Pacientes y métodos. Estudio observacional de una cohorte de pacientes formada por neonatos = 35 semanas de edad gestacional diagnosticados de IIAP entre 2010 y 2021 en nuestro hospital. Resultados. Se incluyeron 22 casos de IIAP, y su incidencia en nuestro centro fue de 1/1.869 recién nacidos vivos. El 81,8% tuvo algún factor de riesgo intraparto y en el 40,9% se aglutinaron varios. Comenzó con convulsiones (edad media 27,3 horas) el 77,3% de casos. Los pacientes con ictus del hemisferio izquierdo tuvieron más secuelas (77,8%) en comparación con los derechos (16,6%) (p = 0,041), a expensas de la parálisis cerebral infantil (p = 0,04), mientras no encontramos diferencia en la frecuencia de alteraciones del lenguaje (p = 0,06) entre hemisferios. El tiempo medio de seguimiento fue de 6,13 años ± 3,06. El 63,6% de los neonatos tuvo secuelas neurológicas: parálisis cerebral infantil (40,9%), trastornos del lenguaje (22,7%) y discapacidad intelectual (9%). Desarrolló epilepsia el 18,2% (entre 0,25 y 1,8 años) y se mantuvo el tratamiento anticrisis tras el alta en el 37,5% de los casos en los últimos años del estudio. Conclusiones. Ante un neonato con convulsiones hay que descartar un ictus cerebral. El IIAP ocasiona secuelas neurológicas en más del 60% de los casos. Su identificación precoz es fundamental para mejorar el pronóstico neurológico y evitar el uso prolongado de fármacos anticrisis cuando resulte posible.

Frequency of lipid-poor adrenal adenomas in magnetic resonance imaging examinations of the abdomen.

Objective: To estimate the frequency of lipid-poor adenomas (LPAs) in magnetic resonance imaging (MRI) examinations. Materials and Methods: We retrospectively investigated adrenal lesions on MRI examinations performed in a total of 2,014 patients between January 2016 and December 2017. After exclusions, the sample comprised 69 patients with 74 proven adenomas. Two readers (reader 1 and reader 2) evaluated lesion size, laterality, homogeneity, signal drop on out-of-phase (OP) images, and the signal intensity index (SII). An LPA was defined as a lesion with no signal drop on OP images and an SII < 16.5%. For 68 lesions, computed tomography (CT) scans (obtained within one year of the MRI) were also reviewed. Results: Of the 69 patients evaluated, 42 (60.8%) were women and 27 (39.2%) were men. The mean age was 59.2 ± 14.1 years. Among the 74 confirmed adrenal adenomas evaluated, the mean lesion size was 18.5 ± 7.7 mm (range, 7.0-56.0 mm) for reader 1 and 21.0 ± 8.3 mm (range, 7.0-55.0 mm) for reader 2 (p = 0.055). On the basis of the signal drop in OP MRI sequences, both readers identified five (6.8%) of the 74 lesions as being LPAs. When determined on the basis of the SII, that frequency was three (4.0%) for reader 1 and four (5.4%) for reader 2. On CT, 21 (30.8%) of the 68 lesions evaluated were classified as LPAs. Conclusion: The prevalence of LPA was significantly lower on MRI than on CT. That prevalence tends to be even lower when the definition of LPA relies on a quantitative analysis rather than on a qualitative (visual) analysis.

Objetivo: Estimar a frequência de adenomas pobres em lipídios (APLs) em exames de ressonância magnética (RM). Materiais e Métodos: Investigaram-se, retrospectivamente, as lesões adrenais em exames de RM realizados de janeiro de 2016 a dezembro de 2017. Um total de 2.014 pacientes foi submetido a exames abdominais e, após exclusões, 69 pacientes com 74 adenomas foram recuperados. Determinaram-se o tamanho da lesão, a lateralidade, a homogeneidade, a queda do sinal em imagens fora-de-fase (FF) e o índice de intensidade do sinal (IIS). Foram utilizadas as seguintes definições para APLs: sem queda de sinal nas imagens FF e IIS < 16,5%. Para 68 lesões, havia imagens de tomografia computadorizada (TC), com intervalo de até um ano da RM, que também foram analisadas. Resultados: Sessenta e nove pacientes foram incluídos, sendo 42 mulheres (60,8%) e 27 homens (39,2%). A média de idade foi 59,2 ± 14,1 anos. O tamanho médio do adenoma adrenal foi 18,5 ± 7,7 mm para o leitor 1 (7,0-56,0 mm) e 21,0 ± 8,3 mm (7,0-55,0 mm) para o leitor 2 (p = 0,055). A queda de sinal nas imagens FF mostrou que a frequência de APLs para ambos os leitores foi 6,8% (5/74). Para a análise quantitativa, a frequência foi 4,0% (3/74) para o leitor 1 e 5,4% (4/74) para o leitor 2. A frequência de APLs nas imagens de TC foi 21/68 lesões (30,8%). Conclusão: A prevalência de APLs em imagens de RM foi significativamente menor do que em exames de TC. Essa prevalência tende a ser ainda menor quando a definição de APL é baseada na análise quantitativa (IIS < 16,5%), em vez da análise visual.

Frequency of lipid-poor adrenal adenomas in magnetic resonance imaging examinations of the abdomen / Frequência de adenomas adrenais pobres em lipídios em exames de ressonância magnética abdominal

Abstract Objective: To estimate the frequency of lipid-poor adenomas (LPAs) in magnetic resonance imaging (MRI) examinations. Materials and Methods: We retrospectively investigated adrenal lesions on MRI examinations performed in a total of 2,014 patients between January 2016 and December 2017. After exclusions, the sample comprised 69 patients with 74 proven adenomas. Two readers (reader 1 and reader 2) evaluated lesion size, laterality, homogeneity, signal drop on out-of-phase (OP) images, and the signal intensity index (SII). An LPA was defined as a lesion with no signal drop on OP images and an SII < 16.5%. For 68 lesions, computed tomography (CT) scans (obtained within one year of the MRI) were also reviewed. Results: Of the 69 patients evaluated, 42 (60.8%) were women and 27 (39.2%) were men. The mean age was 59.2 ± 14.1 years. Among the 74 confirmed adrenal adenomas evaluated, the mean lesion size was 18.5 ± 7.7 mm (range, 7.0-56.0 mm) for reader 1 and 21.0 ± 8.3 mm (range, 7.0-55.0 mm) for reader 2 (p = 0.055). On the basis of the signal drop in OP MRI sequences, both readers identified five (6.8%) of the 74 lesions as being LPAs. When determined on the basis of the SII, that frequency was three (4.0%) for reader 1 and four (5.4%) for reader 2. On CT, 21 (30.8%) of the 68 lesions evaluated were classified as LPAs. Conclusion: The prevalence of LPA was significantly lower on MRI than on CT. That prevalence tends to be even lower when the definition of LPA relies on a quantitative analysis rather than on a qualitative (visual) analysis.

Resumo Objetivo: Estimar a frequência de adenomas pobres em lipídios (APLs) em exames de ressonância magnética (RM). Materiais e Métodos: Investigaram-se, retrospectivamente, as lesões adrenais em exames de RM realizados de janeiro de 2016 a dezembro de 2017. Um total de 2.014 pacientes foi submetido a exames abdominais e, após exclusões, 69 pacientes com 74 adenomas foram recuperados. Determinaram-se o tamanho da lesão, a lateralidade, a homogeneidade, a queda do sinal em imagens fora-de-fase (FF) e o índice de intensidade do sinal (IIS). Foram utilizadas as seguintes definições para APLs: sem queda de sinal nas imagens FF e IIS < 16,5%. Para 68 lesões, havia imagens de tomografia computadorizada (TC), com intervalo de até um ano da RM, que também foram analisadas. Resultados: Sessenta e nove pacientes foram incluídos, sendo 42 mulheres (60,8%) e 27 homens (39,2%). A média de idade foi 59,2 ± 14,1 anos. O tamanho médio do adenoma adrenal foi 18,5 ± 7,7 mm para o leitor 1 (7,0-56,0 mm) e 21,0 ± 8,3 mm (7,0-55,0 mm) para o leitor 2 (p = 0,055). A queda de sinal nas imagens FF mostrou que a frequência de APLs para ambos os leitores foi 6,8% (5/74). Para a análise quantitativa, a frequência foi 4,0% (3/74) para o leitor 1 e 5,4% (4/74) para o leitor 2. A frequência de APLs nas imagens de TC foi 21/68 lesões (30,8%). Conclusão: A prevalência de APLs em imagens de RM foi significativamente menor do que em exames de TC. Essa prevalência tende a ser ainda menor quando a definição de APL é baseada na análise quantitativa (IIS < 16,5%), em vez da análise visual.

Una vista a la tasa de mortalidad por enfermedad de alzheimer en Chile en el periodo de 2017 a 2021 / A view of the mortality rate due to alzheimer's disease in Chile in the period from 2017 to 2021

Introducción: La enfermedad de Alzheimer (EA) es la principal causa de demencia, caracterizada por pérdida progresiva de memoria. Principal fuente de morbimortalidad en mayores de 65 años. En los últimos 20 años las muertes por EA han aumentado un 145% en el mundo. En Chile no hay estudios actuales que describan mortalidad por EA. El objetivo del presente trabajo es analizar y comparar las tasas de mortalidad (TM) por EA según sexo y grupo etario en Chile entre 2017-2021. Materiales y métodos: Estudio descriptivo, ecológico, sobre defunciones por EA entre 2017-2021 en Chile según sexo y grupo etario (n=10.223). Información obtenida de la base de datos del Departamento de Estadísticas e Información de Salud. Se realizó estadística descriptiva y cálculo de TM. No se requiere comité de ética. Resultados: La máxima TM del periodo fue 11,74 por cada 100.000 habitantes en 2021. El sexo femenino logró la mayor TM en este periodo. El grupo etario con mayor cantidad de defunciones fue el de 81 o más años con 76.6% (7.829) de las defunciones totales. Discusión: Se evidenció mantención y luego ascenso de TM por EA, podría deberse al aumento en la esperanza de vida. La mayor frecuencia de defunciones según sexo y edad, podría explicarse por mayor vulnerabilidad femenina a desarrollar EA y a cambios fisiológicos del envejecimiento. En conclusión, la TM por EA en Chile ha aumentado, probablemente secundario al aumento en la esperanza de vida. Se hace un llamado a continuar el estudio de la patología.

Introduction: Alzheimer's disease (AD) is the most common cause of dementia, characterized by progressive memory loss. It is the main source of morbidity and mortality in individuals over 65 years of age, with age being its primary non-modifiable risk factor. In the last 20 years, deaths from AD have increased by 145% worldwide. However, there are no current studies in Chile that describe mortality from AD. The objective of this study is to analyze and compare mortality rates due to AD according to sex and age group in the Chilean population during the years 2017-2021. Material and Methods: Descriptive, ecological study on deaths from AD between 2017-2021 in Chile, categorized by sex and age group (n=10,223). The database was obtained from the Department of Health Statistics and Information. Descriptive statistics and mortality rate calculations were performed. No ethics committee approval was required. Results: The maximum mortality rate (MR) was observed in 2021 with a value of 11.74 per 100,000 inhabitants. Women had the highest MR in this period. The age group with the highest number of deaths was 81 years or older, accounting for 76.6% (7,829) of the total deaths. Discussion: A plateau and subsequent increase in MR due to AD were observed, possibly explained by the increase in life expectancy. The higher frequency of deaths in women and specific age groups may be attributed to the higher vulnerability of women to developing AD and physiological changes related to aging. In conclusion, the MR from AD has increased in Chile, likely due to the rise in life expectancy, emphasizing the importance of continued research on this pathology.

Dopamine denervation in the functional territories of the striatum: a new MR and atlas-based 123I-FP-CIT SPECT quantification method.

Current quantification methods of 123I-FP-CIT SPECT rely on anatomical parcellation of the striatum. We propose here to implement a new method based on MRI segmentation and functional atlas of the basal ganglia (MR-ATLAS) that could provide a reliable quantification within the sensorimotor, associative, and limbic territories of the striatum. Patients with Parkinson's disease (PD), idiopathic rapid eye movement sleep behavioral disorder (iRBD), and healthy controls underwent 123I-FP-CIT SPECT, MRI, motor, and cognitive assessments. SPECT data were corrected for partial volume effects and registered to a functional atlas of the striatum to allow quantification in every functional region of the striatum (nucleus accumbens, limbic, associative, and sensorimotor parts of the striatum). The MR-ATLAS quantification method is proved to be reliable in every territory of the striatum. In addition, good correlations were found between cognitive dysexecutive tests and the binding within the functional (limbic) territories of the striatum using the MR-ATLAS method, slightly better than correlations found using the anatomical quantification method. This new MR-ATLAS method provides a robust and useful tool for studying the dopaminergic system in PD, particularly with respect to cognitive functions. It may also be relevant to further unravel the relationship between dopaminergic denervation and cognitive or behavioral symptoms.

High power continuous laser at 461 nm based on a compact and high-efficiency frequency-doubling linear cavity.

A Watt-level continuous and single frequency blue laser at 461 nm is obtained by frequency-doubling an amplified diode laser operating at 922 nm via a LBO crystal in a resonant Fabry-Pérot cavity. We achieved a best optical conversion efficiency equal to 87% with more than 1 W output power in the blue, and limited by the available input power. The frequency-converted beam is characterized in terms of long term power stability, residual intensity noise, and geometrical shape. The blue beam has a linewidth of the order of 1 MHz, and we used it to magneto-optically trap 88Sr atoms on the 5s2 1S0 - 5s5p 1P1 transition. The low-finesse, linear-cavity doubling system is very robust, maintains the lock for several days, and is compatible with a tenfold increase of the power levels which could be obtained with fully-fibered amplifiers and large mode area fibers.

[Difficult-to-engage patients: What evolution after discharge from Assertive Community Programs?] / Patients réfractaires aux soins : quelle évolution après le suivi intensif d'une équipe mobile de psychiatrie ?

OBJECTIVES: Beneficial effects of Assertive Community Treatment (ACT) programs on patients with severe mental disorders are well established over short or medium term. However, studies that investigate long term clinical and psychosocial outcomes are remarkably scarce, and it is not known whether the support and intensive care delivered by these programs maintain their benefits over time, especially after discharge. Thus, the present study sought further understanding on this issue by evaluating long term clinical and psychosocial evolution of patients who had been treated by an ACT team in 2007. We investigated the nature of treatment interventions and the level of care since discharge from ACT, especially in terms of adherence to care and number of psychiatric hospitalizations. We also examined factors, at inclusion in the ACT program and after six months of treatment, that could predict better long-term outcomes. METHODS: Twenty-nine patients with severe mental disorders, characterized by the heavy use of inpatient facilities and refusal of care, were treated by an ACT team which was implmented between 2007 and 2009. They participated at that time in an initial study on the effect of the program and were therefore assessed at inclusion and again after six months of treatment. Between 2016 and 2017, the present follow up took place and patients were assessed again on their current psychosocial functioning, quality of life and intensity of symptoms, using the same scales as those administered in the initial study. This design allowed us to compare baseline with "early" (after six months) and "late" (after a mean of 8.7 years) effects of ACT program on patients. In order to assess adherence to care since discharge from ACT, data on nature and level of psychiatric treatment was systematically reviewed, including all public and private inpatient and outpatient treatments since the end of the ACT program. RESULTS: Detailed tables on hospitalizations before, during and after ACT treatment are reported, as well as tables summarizing the level of care and nature of treatment since discharge from ACT. During the mean of 8.7 years of evolution and 6.3 years after discharge from ACT, these patients, characterized by severe mental disorders, heavy use of inpatient facilities and refusal of care, sustained a reduced rate of hospitalizations and a minor rate of disengagement from outpatient care (6.9 %). Both severity of symptoms, poorer quality of life and worst functioning in the community at inclusion (baseline) as well as early improvements (after six month of ACT treatment) of the same outcomes were significantly associated with long term improvements. Results also show other baseline predictors of long term improvement: fewer years since disorder onset was associated with improvement of functioning in the community; further advancement in the recovery process predicted better enhancement in quality of life, and a better initial functioning in the community was associated with a better improvement of symptomatology. CONCLUSIONS: This study provides insight on the sustainability of the benefits of ACT programs, suggesting that these interventions can help patients who are refractory to care to gain clinical and psychosocial improvement in the long term. Our results also suggest that baseline severity as well as early improvements after six months of treatment were associated with larger improvement at follow up. These clinical predictors provide some help to distinguish which patients are more likely to benefit from an ACT approach.

Vitamin D status and latent tuberculosis infection: conversion in nursing homes, Spain.

OBJECTIVE: To examine the potential association between vitamin D (VitD) deficiency and latent tuberculosis infection (LTBI) and its effect on TB infection conversion (TBIC) incidence.MATERIAL AND METHODS: We carried out a cross-sectional and prospective cohort study of nine pulmonary TB cases that occurred in 2015-2016 in five nursing homes and one mental disability institution in Castellon, Spain. QuantiFERON®-TB Gold and the tuberculin skin test were used to detect LTBI and TBIC, respectively. Serum 25-hydroxyvitamin D was measured using chemiluminescence immunoassay. Poisson regression and inverse probability weighting were used for statistical analyses.RESULTS: The study included 448 residents, 341 staff members with 48 relatives of TB cases (participation rate 82%): of these, respectively 122 (27.2%), 37 (10.9%) and 7 (14.6%) were LTBI-positive; and respectively 22 (7.7%), 10 (3.8%) and 1 (3.7%) were TBIC-positive. LTBI was not associated with VitD status. Severe VitD deficiency (SVDD; defined as VitD level < 10 ng/ml), found in 45.1% of residents, as well as VitD levels of <30 ng/ml (aRR 10.41 95% CI 1.48-73.26), were associated with increased TBIC risk (adjusted relative risk [aRR] 12.1, 95% CI 1.51-97.10), suggesting SVDD as a threshold effect. CONCLUSION: Severe VitD deficiency is a TBIC risk factor.

On the Relationship between Mechanical Properties and Crystallisation of Chemically Post-Processed Additive Manufactured Polylactic Acid Pieces.

Nowadays, improvement of the surface finish of parts manufactured by fused deposition modelling is a well-studied topic. Chemical post-treatments have proven to be the best technique in terms of time consumption and smoothness improvement. However, these treatments modify the structure of the material and, consequently, its mechanical properties. This relationship was studied in this work. In this case, on the basis of a previous study on crystallisation, polylactic acid pieces were subjected to different post-treatments to evaluate their effects on the sample's mechanical properties, i.e., tensile strength and hardness. Models were obtained according to their percentage of crystallisation, which was related to the different treatments, as well as immersion time. Dramatic changes were obtained within a wide range of material behaviour with some treatments. Specifically, changes were obtained in the maximum stress (from 55 to 20 MPa), in elongation (from 3% to 260%), and in the hardness scale (Shore D to A).

Impact of the early-life skin microbiota on the development of canine atopic dermatitis in a high-risk breed birth cohort.

Canine atopic dermatitis (CAD) is a prevalent inflammatory skin disease of dogs worldwide. Certain breeds such as the West Highland White Terriers (WHWT) are predisposed to suffer from CAD. Microbial dysbiosis is known to play a significant role in the pathogenesis of the disease, which is similar to its human counterpart, atopic dermatitis (AD). To date, no large cohort-study has been conducted in a predisposed dog breed to study the impact of the early-life microbiota on the development of CAD, as well as the possible implication of factors such as hygiene and access to the outdoors. In this study skin samples of 143 WHWT, including 109 puppies up to three weeks old and 34 parent dogs, from 17 breeders, were subjected to 16S rRNA gene and ITS2 amplicon sequencing to disclose the bacterial and fungal oral and skin microbiota, respectively. The oral samples served as a control group to confirm differences between haired and mucosal surfaces. The cutaneous microbiota differed between sample sites and age of the dogs. The season of sampling, geographical origin as well as hygiene status of the household and the access to the outdoors shaped the skin microbiota of the puppies significantly. However, we found that the individual early-life microbiota did not predispose for the later development of CAD.

[Biliary microbiote in cholecystectomized patients: Review of empirical antibiotherapy]. / Microbiota biliar en pacientes colecistectomizados: Revisión de la antibioterapia empírica.

OBJECTIVE: Cholecystitis is an important cause of hospital admission. In moderate or severe cholecystitis, the delay in treatment can lead to serious complications. Our objective is to analyze the microorganisms isolated in bile from cholecystectomized patients and their sensitivity pattern, to evaluate the empirical treatment in those cases in which the surgical removal of the gallbladder should be delayed. METHODS: Prospective descriptive study of biliary cultures of patients undergoing cholecystectomy from May 2013 to February 2015, in the Surgery Department of the Hospital General Universitari de Castelló. RESULTS: We studied 196 patients, 83 women (42.3%) and 113 men (57.7%), with an average age of 61.5 years. The most used antibiotics as empiric treatment were piperacillin/tazobactam (77.8%) and amoxicillin/clavulanic (14.8%). In 46.4% of patients (91/196) bile cultures were positive. 165 microorganisms were isolated. The majority were Gram-negative bacilli (60.5%), mainly of the Enterobacterales order (91/54.5%), with Escherichia coli being the most frequent microorganism (24%) followed by Klebsiella spp. (12.5%). 3 E. coli with extended-spectrum beta-lactamase (ESBL) and 1 K. pneumoniae with ESBL were isolated. Microorganisms producing carbapenemase and methicillin-resistant Staphylococcus aureus were not isolated. CONCLUSIONS: The bile microbiota, with a predominance of Enterobacterales is similar to that found in european studies..

The most recurrent monogenic disorders that overlap with the phenotype of Rett syndrome.

Rett syndrome (RTT) is an early-onset neurodevelopmental disorder that is caused by mutations in the MECP2 gene; however, defects in other genes (CDKL5 and FOXG1) can lead to presentations that resemble classic RTT, although they are not completely identical. Here, we attempted to identify other monogenic disorders that share features of RTT. A total of 437 patients with a clinical diagnosis of RTT-like were studied; in 242 patients, a custom panel with 17 genes related to an RTT-like phenotype was run via a HaloPlex-Target-Enrichment-System. In the remaining 195 patients, a commercial TruSight-One-Sequencing-Panel was analysed. A total of 40 patients with clinical features of RTT had variants which affect gene function in six genes associated with other monogenic disorders. Twelve patients had variants in STXBP1, nine in TCF4, six in SCN2A, five in KCNQ2, four in MEF2C and four in SYNGAP1. Genetic studies using next generation sequencing (NGS) allowed us to study a larger number of genes associated with RTT-like simultaneously, providing a genetic diagnosis for a wider group of patients. These new findings provide the clinician with more information and clues that could help in the prevention of future symptoms or in pharmacologic therapy.

Aggrecan-like biomimetic proteoglycans (BPGs) composed of natural chondroitin sulfate bristles grafted onto a poly(acrylic acid) core for molecular engineering of the extracellular matrix.

Biomimetic proteoglycans (BPGs) were designed to mimic the three-dimensional (3D) bottlebrush architecture of natural extracellular matrix (ECM) proteoglycans, such as aggrecan. BPGs were synthesized by grafting native chondroitin sulfate bristles onto a synthetic poly(acrylic acid) core to form BPGs at a molecular weight of approximately ∼1.6 MDa. The aggrecan mimics were characterized chemically, physically, and structurally, confirming the 3D bottlebrush architecture as well as a level of water uptake, which is greater than that of the natural proteoglycan, aggrecan. Aggrecan mimics were cytocompatible at physiological concentrations. Fluorescently labeled BPGs were injected into the nucleus pulposus of the intervertebral disc ex vivo and were retained in tissue before and after static loading and equilibrium conditioning. BPGs infiltrated the tissue, distributed and integrated with the ECM on a molecular scale, in the absence of a bolus, thus demonstrating a new molecular approach to tissue repair: molecular matrix engineering. Molecular matrix engineering may compliment or offer an acellular alternative to current regenerative medicine strategies. STATEMENT OF SIGNIFICANCE: Aggrecan is a natural biomolecule that is essential for connective tissue hydration and mechanics. Aggrecan is composed of negatively charged chondroitin sulfate bristles attached to a protein core in a bottlebrush configuration. With age and degeneration, enzymatic degradation of aggrecan outpaces cellular synthesis resulting in a loss of this important molecule. We demonstrate a novel biomimetic molecule composed of natural chondroitin sulfate bristles grafted onto an enzymatically-resistant synthetic core. Our molecule mimics a 3D architecture and charge density of the natural aggrecan, can be delivered via a simple injection and is retained in tissue after equilibrium conditioning and loading. This novel material can serve as a platform for molecular repair, drug delivery and tissue engineering in regenerative medicine approaches.

Bacterial, fungal, parasitological and pathological analyses of abortions in small ruminants from 2012-2016.

INTRODUCTION: Abortion in small ruminants presents a clinical and economic problem with legal implications regarding animal health and zoonotic risk by some of the abortive pathogens. Several bacteria, fungi and parasites can cause abortion, but cost-orientated routine diagnostics only cover the most relevant epizootic agents. To cover a broad-range of common as well as underdiagnosed abortifacients, we studied 41 ovine and 36 caprine abortions by Stamp's modification of the Ziehl-Neelsen stain, culture for classical and opportunistic abortive agents, real-time PCR for C. burnetii, C. abortus, pathogenic Leptospira spp., Toxoplasma gondii and Neospora caninum. When the dam's serum was available detection of antibodies against B. melitensis, C. burnetii, C. abortus and Leptospira spp. was performed. In 37 cases sufficient placental tissue was available for pathological and histopathological examination. From the 77 cases 11 (14.3%) were positive by staining whereas real-time PCR detected C. burnetii and C. abortus in 49.3% and 32.5% of the cases. Antibodies against C. abortus and Leptospira spp. (33.3 and 26.7%) were detected. In 23.4% a bacterial culturable pathogen was isolated. Fungal abortion was confirmed in 1.3% of cases. A single abortive agent was identified in 44.2% of the cases and in 31.2% multiple possible abortifacients were present. Our study shows that the highest clarification rate can only be achieved by a combination of methods and evidences the role that multi-infections play as cause of abortion.

INTRODUCTION: Les avortements représentent un problème à la fois clinique et économique avec des conséquences en matière d'épizooties et un risque de zoonose pour certains agents. Diverses bactéries, champignons et parasites peuvent causer des avortements mais le diagnostic de routine, orienté sur les coûts, se concentre sur les principaux agents épizootiques. Afin d'avoir une vision large sur les agents d'avortements les plus fréquents et sur ceux qui sont sous-diagnostiqués, nous avons examinés 41 avortements de moutons et 36 de chèvres au moyen d'une coloration de Ziehl-Neelsen modifiée selon Stamp, de cultures ciblant les agents d'avortements classiques et opportunistes, d'une PCR en temps réel ciblant C. burnetii, C. abortus, les leptospires pathogènes, Toxoplasma gondii et Neospora caninum. Lorsque du sérum de la mère était disponible, nous avons procédé à une recherche d'anticorps contre B. melitensis, C. burnetii, C. abortus et Leptospira spp. Dans 37 cas, on disposait d'assez de tissu placentaire pour des examens pathologiques. Sur les 77 cas, 11 (14.3%) étaient positifs à la coloration alors que la PCR en temps réel démontrait la présence de C. burnetii et de C. abortus dans 49.3% respectivement 32.5% des cas. On a trouvé des anticorps contre C. abortus und Leptospira spp. dans 33.3% respectivement 26.7% des cas. Dans 23.4% des cas, on a pu mettre en évidence des pathogènes bactériens cultivables. Un avortement mycotique a été confirmé dans 1.3% des cas. Dans 44.2% des cas, un seul agent abortif était présent et dans 31.2% des cas, on trouvait plusieurs agents potentiels. Notre étude indique que le plus haut taux de diagnostic ne peut être atteint qu'en combinant diverses méthodes et montre le rôle possible de multi infections dans l'origine des avortements.