Sex-Related Effect of Aging in Gingival Gamma-Delta T Cells.

Aging affects the number and function of gamma-delta (γδ) T cells in a tissue-specific manner, modifying the risk for inflammatory disease. These aging-related γδT-cell variations in gingival tissues that could increase the risk for inflammation and periodontal disease remain unknown. Here we sought to identify quantitative and qualitative variations in gingival γδT cells associated with aging that could have an impact in oral immunoinflammatory responses. For this, gingival tissues from young (4 mo) and aged (24 mo) male and female mice were collected and analyzed by flow cytometry. Cell suspensions were stimulated and stained with eFluor450 (cell viability), anti-CD45 (hematopoietic cells), anti-CD3 (lymphocytes), anti-TCRγδ (γδT cells), anti-IL-15rα (cell proliferation), and anti-Notch-3 (senescence marker). Detection of intracellular cytokines IL-17A and interferon γ (IFNγ) was performed. Gingival expression of specific γ- and δ-chains and cytokines was evaluated by quantitative reverse transcription polymerase chain reaction. A significantly higher number of IL-17A-producing γδT cells and IL-17A expression levels were observed in gingival tissues from aged females but not males. Similarly, the number of gingival Notch-3+ γδT cells increased with aging only in females. IL-15rα was not detected in gingival γδT cells. Chains γ1, 2, 4, 5, 6, and 7 as well as δ1, 2, 4, and 6 were detected. Detection levels of all γ chains except γ1 as well as δ1 and δ2 changed with aging in males, females, or both. Interestingly, number of IL-17A-producing conventional T cells similarly increased with aging only in females. Both sexes showed increased IFNγ+ conventional T-cell numbers with aging; however, it reached significance only in females. In conclusion, the number of gingival IL-17A-producing γδT cells and IL-17A expression increase naturally with aging specifically in females. This sexual dimorphism in gingival γδT and conventional Th17 cell numbers and phenotypes suggests distinct aging-related mechanisms of periodontitis in males and females.

[Clinical and radiographic factors associated with the severity of paraspinal fatty infiltration in patients with degenerative low back disease]. / Factores clínicos y radiográficos asociados a la severidad de infiltración grasa paraespinal en pacientes con enfermedad lumbar degenerativa.

INTRODUCTION: Degenerative lumbar disease (DLE) is a spectrum of pathological changes from disc degeneration, herniated disc, spondylolisthesis and lumbar canal stenosis. The pain associated with it is multifactorial. Muscle cramps are among the most frequent causes. The relationship between muscle degeneration and DLE has already been studied in the past in multiple studies, highlighting the one carried out by Kjaer & cols. OBJECTIVE: to determine the prevalence and severity of fatty degeneration in mutifidus spinae, and to study its relationship with clinical and radiographic factors. MATERIAL AND METHODS: observational and analytical study. Patients diagnosed with: herniated disc, lumbar canal stenosis or degenerative scoliosis were included. They were classified according to the Kjaer scale for paraspinal fatty infiltration in one of three groups. Clinical variables were analyzed: age, smoking, obesity, the presence of axial pain, temporality of pain, severity expressed with a visual analog scale (VAS); and radiographic: number of diseased segments, involved segments, diagnostic imaging and the presence of spondylolisthesis. RESULTS: 56 patients with an average age of 52.5 years (16 to 80) with a predominance of females with 62.5% were included. The diagnoses were nonspecific low back pain (1.8%), herniated disc (42.9%), narrow lumbar duct (46.4%) and lumbar duct with degenerative scoliosis deformity (8.9%). The distribution among the three groups described by Kjaer was as follows: 44.6% were classified with a fat infiltration score of 2. In groups 1 and 0, 39.3% and 16.1% were classified respectively. The variables significantly related to greater fat infiltration were: age > 60 years, diagnoses of lumbar canal stenosis and herniated disc; obesity, spondylolisthesis < 2 vertebral segments involved. Axial pain and VAS > 8 points were not related to greater muscle degeneration. CONCLUSIONS: fatty infiltration is present in all patients with some of the forms of DLE. Most patients > 60 years of age with advanced degenerative processes have a greater severity of infiltration. Other related variables are: obesity, spondylolisthesis and disease of < 2 vertebral segments. There is no relationship between a higher percentage of fatty infiltration and axial pain or higher VAS scores.

INTRODUCCIÓN: la enfermedad lumbar degenerativa (ELD) es un espectro de cambios patológicos desde la degeneración discal, la hernia discal, la espondilolistesis y el conducto lumbar estrecho. El dolor que se le asocia es multifactorial. Los espasmos musculares son de las causas más frecuentes. La relación que guarda la degeneración muscular y la ELD ya ha sido estudiada en múltiples trabajos, destacando el realizado por Kjaer y colaboradores. OBJETIVO: determinar la prevalencia y severidad de la degeneración grasa en el mutifidus spinae, y estudiar su relación con variables clínicas y radiográficas. MATERIAL Y MÉTODOS: estudio observacional y analítico. Se incluyeron pacientes diagnosticados con: hernia discal, conducto lumbar estrecho o escoliosis degenerativa. Se clasificaron de acuerdo con escala de Kjaer para infiltración grasa paraespinal en alguno de tres grupos. Se analizaron variables clínicas: edad, tabaquismo, obesidad, presencia de dolor tipo axial, temporalidad del dolor, severidad del dolor expresada con escala visual análoga (EVA); y radiográficas: número de segmento enfermos, segmentos involucrados, diagnóstico por imagen y presencia de espondilolistesis. RESULTADOS: se incluyeron 56 pacientes con edad promedio de 52.5 años (rango 16 a 80) con predominio del sexo femenino (62.5%). Los diagnósticos fueron lumbalgia inespecífica (1.8%), hernia discal (42.9%), conducto lumbar estrecho (46.4%) y conducto lumbar con deformidad en escoliosis degenerativa (8.9%). La distribución entre los tres grupos descritos por Kjaer fue la siguiente: 44.6% fueron clasificados con un puntaje de infiltración grasa de 2. En los grupos 1 y 0, se clasificaron 39.3 y 16.1%, respectivamente. Las variables relacionadas con mayor infiltración grasa fueron: edad > 60 años, diagnósticos de conducto lumbar estrecho y hernia discal; obesidad, espondilolistesis < 2 segmentos vertebrales involucrados. El dolor mecánico y EVA > 8 puntos no se relacionaron con mayor degeneración muscular. CONCLUSIONES: la infiltración grasa está presente en todos los pacientes con alguna de las formas de ELD. La mayoría de los pacientes > 60 años con procesos degenerativos avanzados tienen mayor severidad de infiltración. Otras variables relacionadas son: obesidad, espondilolistesis y enfermedad < 2 segmentos vertebrales. No hay relación entre mayor porcentaje de infiltración grasa y dolor axial o puntajes más altos de dolor.

DAMPs and alarmin gene expression patterns in aging healthy and diseased mucosal tissues.

Introduction: Periodontitis is delineated by a dysbiotic microbiome at sites of lesions accompanied by a dysregulated persistent inflammatory response that undermines the integrity of the periodontium. The interplay of the altered microbial ecology and warning signals from host cells would be a critical feature for maintaining or re-establishing homeostasis in these tissues. Methods: This study used a nonhuman primate model (Macaca mulatta) with naturally-occurring periodontitis (n = 34) and experimental ligature-induced periodontitis (n = 36) to describe the features of gene expression for an array of damage-associate molecular patterns (DAMPs) or alarmins within the gingival tissues. The animals were age stratified into: ≤3 years (Young), 7-12 years (Adolescent), 12-15 years (Adult) and 17-23 years (Aged). Gingival tissue biopsies were examined via microarray. The analysis focused on 51 genes representative of the DAMPs/alarmins family of host cell warning factors and 18 genes associated with tissue destructive processed in the gingival tissues. Bacterial plaque samples were collected by curette sampling and 16S rRNA gene sequences used to describe the oral microbiome. Results: A subset of DAMPs/alarmins were expressed in healthy and naturally-occurring periodontitis tissues in the animals and suggested local effects on gingival tissues leading to altered levels of DAMPs/alarmins related to age and disease. Significant differences from adult healthy levels were most frequently observed in the young and adolescent animals with few representatives in this gene array altered in the healthy aged gingival tissues. Of the 51 target genes, only approximately ⅓ were altered by ≥1.5-fold in any of the age groups of animals during disease, with those increases observed during disease initiation. Distinctive positive and negative correlations were noted with the DAMP/alarmin gene levels and comparative expression changes of tissue destructive molecules during disease across the age groups. Finally, specific correlations of DAMP/alarmin genes and relative abundance of particular microbes were observed in health and resolution samples in younger animals, while increased correlations during disease in the older groups were noted. Conclusions: Thus, using this human-like preclinical model of induced periodontitis, we demonstrated the dynamics of the activation of the DAMP/alarmin warning system in the gingival tissues that showed some specific differences based on age.

[Hidden posterior tibial tendon dislocation after ankle sprain: case report]. / Luxación del tendón tibial posterior oculta tras un esguince de tobillo: reporte de caso.

INTRODUCTION: traumatic posterior tibial tendon dislocation is a rare entity that can go unnoticed in our usual clinical practice. MATERIAL AND METHODS: a 31-year-old man, with no relevant medical history, suffered a high-energy traffic accident. He presented a dislocation of the posterior tibial tendon that went unnoticed. After an early diagnosis, a primary repair of the flexor retinaculum was performed and the anatomical reduction of the tendon was achieved. RESULTS: the patient was able to resume sports activity three months after the injury with good functional results. CONCLUSIONS: we should suspect this entity after high-energy trauma with ankle sprains. Surgical treatment of this lesion offers good functional results.

INTRODUCCIÓN: la luxación traumática del tendón tibial posterior es una entidad poco frecuente que puede pasar desapercibida en nuestra práctica clínica habitual. MATERIAL Y MÉTODOS: un hombre de 31 años, sin antecedentes médicos de interés, sufrió un accidente de tráfico de alta energía. Presentaba una luxación del tendón tibial posterior que pasó desapercibida. Tras un diagnóstico precoz se consiguió realizar una reparación primaria del retináculo flexor y se logró la reducción anatómica del tendón. RESULTADOS: el paciente pudo retomar la actividad deportiva a los tres meses de la lesión con buen resultado funcional. CONCLUSIONES: debemos sospechar esta entidad tras un traumatismo de alta energía con entorsis de tobillo. El tratamiento quirúrgico de esta lesión ofrece buenos resultados funcionales.

Periodontitis-resistant and -susceptible matriline regulation of gingival transcriptome in nonhuman primates.

OBJECTIVE: This report identified if gingival gene expression transcriptomes demonstrated unique profiles that discriminated periodontitis-susceptible (PDS) and periodontitis-resistant (PDR) animals in health and disease. BACKGROUND: Nonhuman primates generally organize their social groups based upon matriline origin. We have used a multi-generational colony of rhesus macaques to identify matrilines presenting with significant differences in periodontitis (e.g., earlier age onset, greater prevalence, and severity). METHODS: Animals from 12 to 23 years of age (n = 17; 8 - PDR, 9 - PDS) were entered into a ligature-induced periodontitis trial. Gingival biopsies were taken at baseline and 0.5, 1, 3, and 5 months post-ligation, and microarray analysis was used to quantify gene expression in samples at each time point. RESULTS: Over 1000 genes showed significant (p < .01) differences in the PDR versus PDS animals at baseline. The frequency of differences generally decreased during the disease process, and increased with resolution (i.e., 5 months). A nearly 2:1 ratio of elevated gene levels was noted in baseline PDR samples that included up-regulated MMPs, Fc receptors, chemokines, interleukins, and innate immune receptors, and down-regulated genes particularly related to epithelial biology. Most dramatically, there was a skewed differential expression of adaptive immune response genes in the PDR and epithelial cell structure/function genes in PDS samples. CONCLUSIONS: The results demonstrate substantive differences in gingival tissue response capacity/programming in PDR and PDS samples that may contribute to the differences in clinical outcomes related to the heritability of disease risk through matrilines.

Macrophage-related gingival transcriptomic patterns and microbiome alterations in experimental periodontitis in nonhuman primates.

OBJECTIVE: This study examined the microbiome features specifically related to host macrophage polarization in health, initiation and progression of periodontitis, and in resolution samples using a nonhuman primate model of ligature-induced periodontitis. BACKGROUND: The oral microbiome is a complex of bacterial phyla, genera, and species acquired early in life into the individual autochthonous oral ecology. The microbiome changes overtime in response to both intrinsic and extrinsic stressors, and transitions to a dysbiotic ecology at sites of periodontal lesions. METHODS: Comparisons were made between the microbial and host features in young (≤7 years) and adult (≥12 years) cohorts of animals. Footprints of macrophage-related genes in the gingival tissues were evaluated using expression profiles including M0, M1, and M2 related genes. RESULTS: Within the gingival tissues, similar macrophage-related gene patterns were observed with significant increases with disease initiation and continued elevation throughout disease in both age groups. Approximately, 70% of the taxa were similar in relative abundance between the two groups; however, the adults showed a large number of OTUs that were significantly altered compared with the younger animals. Developing a correlation map identified three major node levels of interactions that comprised approximately ⅓ of the Operational Taxonomic Units (OTUs) that dominated the microbiomes across the samples. Also noted was a much greater frequency of significant correlations of individual OTUs with the macrophage phenotype markers, compared with disease and resolution samples in both age groups, with a greater frequency in the younger group. Moreover, these correlations were assigned to differentially expressed genes representing M0, M1, and M2-related phenotypes. A cluster analyses across the macrophage-related transcriptome and the OTUs demonstrated multiple somewhat distinct bacterial consortia, incorporating both commensal and putative pathogens, linked to the gene responses that differed in health, disease, and resolution samples. Finally, there were minimal alterations in the OTUs in individual clusters with specific macrophage-related responses in the younger group, while in the adult samples substantial variations were noted with genes from all macrophage phenotypes. CONCLUSIONS: The results confirmed important features that could reflect macrophage polarization in periodontal lesions, and provided some initial data supporting specific members of the oral microbiome feature prominently related to specific gene response patterns consistent with macrophages in the gingival tissues.

[Professional and psychological impact of second victims among hospital healthcare professionals]. / Impacto laboral y psicológico de las segundas víctimas entre los profesionales sanitarios hospitalarios.

OBJECTIVE: To analyze the occupational and psychological consequences suffered by healthcare workers who are considered second victims (SV). MATERIAL AND METHODS: Observational, descriptive and cross-sectional study among the healthcare workers of a university hospital. The answers collected in a specifically designed questionnaire about psychological consequences at work and the result of a post-traumatic stress scale, "Impact of Event Scale-Revised (IES-R, spanish version)" were evaluated. The variables between the groups were compared using the Chi square test (or Fisher's exact test) when both were qualitative and with the Student's T (or the Mann-Whitney U test for independent data), when one of them was quantitative. The level of statistical significance was P<.05. RESULTS: 75.5% (148/207) of the participants in the study suffered some adverse event (AE) and, of these, 88.5% (131/148) were considered SV. Physicians had a 2.2 times higher risk of feeling SV than nurses (95% CI: 1.88-2.52). The impact on the patient related to the AE explained why the professionals involved in it felt SV (P=.037). 80.6% (N=104) of the SVs presented post-traumatic stress. Women were 2.4 times more likely to suffer from it (OR: 2.4; 95% CI: 1.5-4.0). Intrusive thoughts in the SV were almost three times more frequent when the damage suffered by the patient was permanent or death (OR: 2.5; 95% CI: 0.2-3.6). CONCLUSIONS: Many healthcare workers, especially physicians, considered themselves to be SV, and many of them suffered from post-traumatic stress. The impact on the patient related to the AE was a risk factor for being SV and for suffering psychological consequences.

Sex and Age Effects on Healthy Gingival Transcriptomic Patterns.

Many chronic inflammatory diseases demonstrate demographic associations such as sex, age, and race-ethnicity. Periodontitis has been found to be increased with age and in males. This study used nonhuman primates representing a human-like model for periodontitis and examined the gingival transcriptome stratified on sex and age. Thirty-six Macaca mulatta in 4 age groups-young (<3 y), adolescent (3-7 y), adult (12-15 y), and aged (>17 y)-with a healthy periodontium were used to characterize gene expression in healthy gingival tissues. Gene expression was compared to clinical measures of bleeding on probing (BOP) and probing pocket depth (PPD). The results demonstrated sex differences in number of up- and downregulated genes that increased with age. Female animals generally showed elevated expression of genes related to host immunoinflammatory responses, and males showed increased expression of tissue structural genes. Gene expression correlations with BOP and/or PPD showed minimal overlap between the sexes, while male animals demonstrated substantial overlap in genes that correlated with both BOP and PPD clinical features. A cluster analysis of genes significantly different between sexes showed a clear sex and age discrimination in the young and adolescent animals. In the older groups, the genes clustered predominately by sex, irrespective of age group. A pathway analysis identified that significant gene expression patterns were quite similar in adolescent and adult animals, while the young and aged samples were quite distinct. The results confirmed substantial sex related variations in gingival tissue biology that were affected by age and observed even in adolescent animals. This suggests that "programming" of the gingival tissues related to sex can occur rather early in life and presage variations in future risk for periodontitis.

Luxación del tendón tibial posterior oculta tras un esguince de tobillo: reporte de caso / Hidden posterior tibial tendon dislocation after ankle sprain: case report

Resumen: Introducción: la luxación traumática del tendón tibial posterior es una entidad poco frecuente que puede pasar desapercibida en nuestra práctica clínica habitual. Material y métodos: un hombre de 31 años, sin antecedentes médicos de interés, sufrió un accidente de tráfico de alta energía. Presentaba una luxación del tendón tibial posterior que pasó desapercibida. Tras un diagnóstico precoz se consiguió realizar una reparación primaria del retináculo flexor y se logró la reducción anatómica del tendón. Resultados: el paciente pudo retomar la actividad deportiva a los tres meses de la lesión con buen resultado funcional. Conclusiones: debemos sospechar esta entidad tras un traumatismo de alta energía con entorsis de tobillo. El tratamiento quirúrgico de esta lesión ofrece buenos resultados funcionales.

Abstract: Introduction: traumatic posterior tibial tendon dislocation is a rare entity that can go unnoticed in our usual clinical practice. Material and methods: a 31-year-old man, with no relevant medical history, suffered a high-energy traffic accident. He presented a dislocation of the posterior tibial tendon that went unnoticed. After an early diagnosis, a primary repair of the flexor retinaculum was performed and the anatomical reduction of the tendon was achieved. Results: the patient was able to resume sports activity three months after the injury with good functional results. Conclusions: we should suspect this entity after high-energy trauma with ankle sprains. Surgical treatment of this lesion offers good functional results.

Terapia cognitivo conductual para pacientes con riesgo clínico de psicosis / Cognitive behavior therapy for young patients at clinical risk for psychosis

INTRODUCCIÓN. Los estudios de tratamiento indican que el riesgo de transición a un trastorno psicótico puede al menos retrasarse en la población clínica de alto riesgo de psicosis (CHR), además de mejorar variables relacionadas con la calidad de vida de los pacientes, existiendo evidencia a favor de la terapia cognitivo conductual (TCC). MÉTODOS. Se realizó una síntesis narrativa, basada en la búsqueda de artículos originales, que abordasen la efectividad de la TCC en pacientes CHR, publicados en los últimos cinco años, incluidos en esta síntesis. RESULTADOS. Se incluyeron un total de 10 artículos que evalúan la TCC en CHR, siendo un tratamiento efectivo y ampliamente utilizado, lo que se asocia a una disminución en las consecuencias psicosociales que conlleva el retraso en la presentación del cuadro clínico y/o la disminución de síntomas comórbidos. CONCLUSIÓN. Actualmente, la TCC se ha convertido en el tratamiento de primera elección para CHR, existiendo una gran variedad de estrategias psicoterapéuticas específicas dentro de este grupo de intervención.

INTRODUCTION. Treatment studies indicate that the risk of transition to a psychotic disorder can at least be delayed in the clinical population at high risk for psychosis (CHR), in addition to improving variables related to the quality of life of patients, with evidence in favor of cognitive behavioral therapy (CBT). METHODS. A narrative synthesis was carried out, based on the search for original articles, which addressed the effectiveness of CBT in CHR patients, published in the last five years, included in this synthesis. RESULTS. A total of 10 articles that evaluate CBT in CHR were included, being an effective and widely used treatment, which is associated with a decrease in the psychosocial consequences that the delay in the presentation of the clinical picture and/or the decrease in symptoms entails. comorbid. CONCLUSION. Currently, CBT has become the treatment of first choice for CHR, with a wide variety of specific psychotherapeutic strategies within this intervention group.

Microencapsulation of Renealmia alpinia (Rottb.) Maas pulp pigment and antioxidant compounds by spray-drying and its incorporation in yogurt.

Renealmia alpinia (Rottb.) Maas pulp was processed by spray drying using Maltodextrin (MDX), and Gum Arabic (GA), and the mixture of both encapsulating agents (MDX-GA). Yield, moisture, water activity (a w ), apparent and bulk densities, size and morphology of capsules, color, and antioxidant potential (antioxidant activity, total carotenoids, and phenolic compounds) were analyzed. The encapsulates were incorporated as pigments in yogurt and the stability of antioxidant compounds (1, 7, 14, 21, and 28 days of storage) and the sensory properties were evaluated. The yields of all formulations (MDX, GA, MDX-GA) were around 17.86% with low moisture and a w range values (2.62-3.29% and 0.276-0.309, respectively). The microcapsules presented multiples particle sizes (0.67-27.13 µm) with irregular and smooth surfaces. Furthermore, these capsulates preserved yellow color and the retention of carotenoids was significantly higher with MDX (34.12 mg/100 g of powder), while the phenolic compounds and antioxidant activity increased with GA (474.17 mg GAE/100 g and 552.63 mg TE/100 g of powder, respectively). The main compounds ß-carotene and gallic acid were identified and quantified in positive and negative mode respectively using LC-MS/MS. Finally, the addition of the encapsulated pigments to yogurt allowed to obtain a yellow coloration and the yogurt added with MDX-GA presented the best formulation with not significant changes in antioxidant activity and acceptable sensory attributes up 28 days of storage.

Study of antifungal agent caspofungin adsorption to laboratory materials.

Treatment of invasive fungal infections with Caspofungin is used as the first-line antifungal agents. The minimum inhibitory concentration value is a test which indicates the degree of sensitivity of a strain regarding a drug. However, no value of minimum inhibitory concentration for caspofungin is available because very variable value is obtained. In this work, we study the link with the adsorption phenomenon of CSF previously described in literature and the lack of minimum inhibitory concentration value. A systematic study of the impact of different parameters on CSF adsorption is reported. The effect of the nature of container material, the aqueous solution pH and the organic solvent proportion was studied. In addition, the possibility of using a coating agent to minimize the adsorption was assayed and evaluated. Results obtained showed the importance of the material used during the manipulation of CSF. The use of acidic pH aqueous solution or the addition of acetonitrile or methanol proportions (50 % and 70 %, respectively) were found efficient to avoid adsorption of CSF on glassware material, which is the relevant strategy for analytical samples of caspofungin. The treatment of HPLC glass vials and 96-well plates with N-(2-aminoethyl)-3-aminopropyltrimethoxysilane reduced the adsorption. The significant adsorption observed in this work especially with plastic materials, questions the results obtained before in different assays and explained the absence of MIC value.

Epidemiology and characteristics of ischaemic stroke in young adults in Aragon.

INTRODUCTION: Stroke affects around 15 million people per year, with 10%-15% occurring in individuals under 50 years old (stroke in young adults). The prevalence of different vascular risk factors and healthcare strategies for stroke management vary worldwide, making the epidemiology and specific characteristics of stroke in each region an important area of research. This study aimed to determine the prevalence of different vascular risk factors and the aetiology and characteristics of ischaemic stroke in young adults in the autonomous community of Aragon, Spain. METHODS: A cross-sectional, multi-centre study was conducted by the neurology departments of all hospitals in the Aragonese Health Service. We identified all patients aged between 18 and 50 years who were admitted to any of these hospitals with a diagnosis of ischaemic stroke or TIA between January 2005 and December 2015. Data were collected on demographic variables, vascular risk factors, and type of stroke, among other variables. RESULTS: During the study period, 786 patients between 18 and 50 years old were admitted with a diagnosis of ischaemic stroke or TIA to any hospital of Aragon, at a mean annual rate of 12.3 per 100 000 population. The median age was 45 years (IQR: 40-48 years). The most prevalent vascular risk factor was tobacco use, in 404 patients (51.4%). The majority of strokes were of undetermined cause (36.2%), followed by other causes (26.5%). The median NIHSS score was 3.5 (IQR: 2.0-7.0). In total, 211 patients (26.8%) presented TIA. Fifty-nine per cent of the patients admitted with a diagnosis of ischaemic stroke (10.3%) were treated with fibrinolysis. CONCLUSIONS: Ischaemic stroke in young adults is not uncommon in Aragon, and is of undetermined aetiology in a considerable number of cases; it is therefore necessary to implement measures to improve study of the condition, to reduce its incidence, and to prevent its recurrence.

Association between antibiotic pressure and the risk of colonization/infection by multidrug-resistant Acinetobacter baumannii complex: a time series analysis.

OBJECTIVE: To analyze the association between antibiotic pressure and the risk of colonization/infection by Acinetobacter baumannii complex (AB), evaluating both the individual and general prescriptions of antibiotics. METHODS: This is an analytical, observational, case-control study on patients admitted to an Intensive Care Unit (ICU) during an AB outbreak (14 months). A five-year time series was constructed with the monthly incidence of cases of infection/colonization with strains of AB resistant to each antibiotic administered and with the monthly consumption of these antibiotics in the ICU. RESULTS: We identified 40 patients either infected (23) or colonized (17) by AB and 73 controls. We found an epidemic multidrug-resistant clone of AB in 75% of cases. Risk factors associated with the development of AB infection/colonization were: greater use of medical instruments, the presence of a tracheostomy, cutaneous ulcers, surgical lesions and prior antibiotic therapies. The regression analysis of individual use of antibiotics showed that prior treatment with ceftazidime, ceftriaxone, amoxicillin/clavulanate, imipenem, levofloxacin, linezolid, and vancomycin was a risk factor for acquiring AB. ARIMA models showed that the relationship were greatest and statistically significant when the treatment occurred between 6 months (ceftazidime) and 9 months (imipenem and levofloxacin) prior. CONCLUSIONS: The dynamic and aggregate relationship between the incidence of infection/colonization by multidrug-resistant strains of AB and prior antibiotic treatment was statistically significant for intervals of 6 to 9 months.

Mutations in the John Cunningham virus VP1 gene could predispose to the development of progressive multifocal leukoencephalopathy in multiple sclerosis patients undergoing treatment with natalizumab.

BACKGROUND: Patients with Multiple Sclerosis (MS) undergoing treatment with natalizumab (NTZ) are at risk of developing progressive multifocal leukoencephalopathy (PML) due to the reactivation of John Cunningham (JC) virus. A relevant characteristic among PML cases is the development of single nucleotide mutations in the VP1 gene of the causal JC virus. The identification of such mutations in timely manner can provide valuable information for MS management. OBJECTIVE: To identify mutations along the JC virus VP1 gene in MS patients undergoing treatment with NTZ, and correlate them with anti-JC virus antibody index. METHODS: Eighty-eight MS patients, one hundred twenty controls, and six patients with diagnosis of Human Immunodeficiency Virus (HIV) with and without secondary PML were included. JC virus was identified in peripheral blood mononuclear cells and cerebrospinal fluid by PCR. Amplification and sequencing of the entire length of the VP1 gene were performed in all positive clinical samples. RESULTS: In MS cases no mutations were observed in the JC virus VP1 gene, but it was positive in HIV controls with PML. Interestingly, the JC virus VP1 gene sequence derived from the HIV patients exhibited a non-silent substitution in position 186 (G â†’ C), leading to an amino acid change (Lys â†’ Asp). We did not find correlation between anti-JC virus antibody index and DNA viral detection. CONCLUSIONS: . The identification of single nucleotide mutants in the JC virus VP1 gene might be an early predictive marker to PML for efficient patient treatment and follow-up.

Three-month functional prognosis of patients hospitalised due to acute ischaemic stroke in Aragon: regional analysis of the impact of COVID-19.

INTRODUCTION: The COVID-19 pandemic has had an impact on ischaemic stroke management, with a reported decrease in hospital admissions, and even disruptions in healthcare and increased in-hospital mortality. However, there is a lack of evidence on the impact of the pandemic on functional prognosis. The aim of this study is to analyse the effect of the COVID-19 pandemic on the 3-month functional outcomes of patients hospitalised due to acute ischaemic stroke in Aragon (Spain). METHODS: We reviewed the data of all patients admitted due to ischaemic stroke to any hospital in our regional healthcare system between 30 December 2019 and 3 May 2020. We compared modified Rankin Scale scores and mortality at 3 months in patients hospitalised before and after the declaration of a state of emergency due to the COVID-19 pandemic. RESULTS: In total, 318 patients with acute ischaemic stroke met our inclusion criteria. No differences were observed between periods in global or specific characteristics, with the exception of a higher proportion of patients older than 80 years during the first period (42.2% vs 29.0%, P = .028). In the comparative analysis, we found no significant differences in mortality (12.3 vs 7.9, P = .465) or in the proportion of patients with modified Rankin Scale scores ≤ 2 (57.7% vs 57.1%, P = .425) at 3 months. CONCLUSION: To our knowledge, this is the first study to analyse the impact of COVID-19 pandemic on the 3-month functional outcomes of patients with ischaemic stroke. In our region, there has been no increase in rates of mortality or disability at 3 months in patients admitted due to ischaemic stroke during the pandemic.

Gingival transcriptomics of follicular T cell footprints in progressing periodontitis.

Follicular helper T cells (Tfh) cells have been identified in the circulation and in tertiary lymphoid structures in chronic inflammation. Gingival tissues with periodontitis reflect chronic inflammation, so genomic footprints of Tfh cells should occur in these tissues and may differ related to aging effects. Macaca mulatta were used in a ligature-induced periodontitis model [adult group (aged 12-23 years); young group (aged 3-7 years)]. Gingival tissue and subgingival microbiome samples were obtained at matched healthy ligature-induced disease and clinical resolution sites. Microarray analysis examined Tfh genes (n = 54) related to microbiome characteristics documented using 16S MiSeq. An increase in the major transcription factor of Tfh cells, BCL6, was found with disease in both adult and young animals, while master transcription markers of other T cell subsets were either decreased or showed minimal change. Multiple Tfh-related genes, including surface receptors and transcription factors, were also significantly increased during disease. Specific microbiome patterns were significantly associated with profiles indicative of an increased presence/function of Tfh cells. Importantly, unique microbial complexes showed distinctive patterns of interaction with Tfh genes differing in health and disease and with the age of the animals. An increase in Tfh cell responsiveness occurred in the progression of periodontitis, affected by age and related to specific microbial complexes in the oral microbiome. The capacity of gingival Tfh cells to contribute to localized B cell activation and active antibody responses, including affinity maturation, may be critical for controlling periodontal lesions and contributing to limiting and/or resolving the lesions.