Survival Bias, Non-Lineal Behavioral and Cortico-Limbic Neuropathological Signatures in 3xTg-AD Mice for Alzheimer's Disease from Premorbid to Advanced Stages and Compared to Normal Aging.

Pre-clinical research in aging is hampered by the scarcity of studies modeling its heterogeneity and complexity forged by pathophysiological conditions throughout the life cycle and under the sex perspective. In the case of Alzheimer's disease, the leading cause of dementia in older adults, we recently described in female wildtype and APP23 mice a survival bias and non-linear chronology of behavioral signatures from middle age to long life. Here, we present a comprehensive and multidimensional (physical, cognitive, and neuropsychiatric-like symptoms) screening and underlying neuropathological signatures in male and female 3xTg-AD mice at 2, 4, 6, 12, and 16 months of age and compared to their non-transgenic counterparts with gold-standard C57BL/6J background. Most variables studied detected age-related differences, whereas the genotype factor was specific to horizontal and vertical activities, thigmotaxis, coping with stress strategies, working memory, and frailty index. A sex effect was predominantly observed in classical emotional variables and physical status. Sixteen-month-old mice exhibited non-linear age- and genotype-dependent behavioral signatures, with higher heterogeneity in females, and worsened in naturalistically isolated males, suggesting distinct compensatory mechanisms and survival bias. The underlying temporal and spatial progression of Aß and tau pathologies pointed to a relevant cortico-limbic substrate roadmap: premorbid intracellular Aß immunoreactivity and pSer202/pThr205 tau phosphorylation in the amygdala and ventral hippocampus, and the entorhinal cortex and ventral hippocampus as the areas most affected by Aß plaques. Therefore, depicting phenotypic signatures and neuropathological correlates can be critical to unveiling preventive/therapeutic research and intervention windows and studying adaptative behaviors and maladaptive responses relevant to psychopathology.

Decreased activation of parvalbumin interneurons in the medial prefrontal cortex in intact inbred Roman rats with schizophrenia-like reduced sensorimotor gating.

Prepulse inhibition (PPI) allows assessing schizophrenia-like sensorimotor gating deficits in rodents. Previous studies indicate that PPI is modulated by the medial prefrontal cortex (mPFC), which is in agreement with our findings showing that PPI differences in the Roman rats are associated with divergences in mPFC activity. Here, we explore whether differences in PPI and mPFC activity in male Roman rats can be explained by (i) differences in the activation (c-Fos) of inhibitory neurons (parvalbumin (PV) interneurons); and/or (ii) reduced excitatory drive (PSD-95) to PV interneurons. Our data show that low PPI in the Roman high-avoidance (RHA) rats is associated with reduced activation of PV interneurons. Moreover, the RHA rats exhibit decreased density of both PV interneurons and PSD-95 puncta on active PV interneurons. These findings point to reduced cortical inhibition as a candidate to explain the schizophrenia-like features observed in RHA rats and support the role of impaired cortical inhibition in schizophrenia.

Riesgo de infección por SARS-CoV-2 en trabajadores sanitarios altamente expuestos / Risk of sars-cov-2 infection in highly exposed health workers

Objetivos: El presente estudio permite establecer el perfil de trabajador más susceptible a la infección por SARS-CoV-2, describir la seroprevalencia y conocer la presencia de anosmia y/o disgeusia. Material y Métodos: Se realizó un estudio epidemiológico descriptivo, transversal y retrospectivo durante 263 días en una UCI de un hospital terciario. Se incluyeron 146 trabajadores de 11 categorías distintas. Se consultaron los resultados de las pruebas diagnósticas de infección y se realizó una entrevista telefónica. Resultados: 56 trabajadores se infectaron (39,4%). El riesgo de infección en sanitarios fue superior (OR 3,38). El personal de enfermería y el trabajo a turnos presentó una tasa de infección más elevada (p= 0, 000). Se detectaron anticuerpos Anti SARS-CoV-2 (AntiN) IgG durante más de 4 meses. El 38,1% desarrolló anosmia y/o disgeusia con una recuperación de 117,41 días de media. Conclusiones: Los datos obtenidos pueden resultar de interés para la evaluación del riesgo ocupacional frente al SARS-CoV-2 en el ámbito sanitario. (AU)

Objectives: The present study makes it possible to establish the profile of the worker most susceptible to SARS-CoV-2 infection, describe seroprevalence and determine the presence of anosmia and / or dysgeusia. Material and Methods: A descriptive, cross-sectional, and retrospective epidemiological study was carried out for 263 days in an ICU of a tertiary hospital. One hundred forty-six workers from 11 different categories were included. The results of the diagnostic tests for infection were consulted, and a telephone interview was carried out. Results: Fifty-six workers were infected (39.4%). The risk of infection in healthcare workers was higher (OR 3.38). Nursing staff and shift workers had a higher infection rate (p = 0, 000). Anti SARS-CoV-2 (AntiN) IgG antibodies were detected for more than four months. 38.1% developed anosmia and/or dysgeusia with a recovery of 117.41 days on average. Conclusions: The data obtained may be of interest for assessing occupational risk against SARS-CoV-2 in the health field. (AU)

Overlapping of Independent SARS-CoV-2 Nosocomial Transmissions in a Complex Outbreak.

SARS-CoV-2 nosocomial outbreaks in the first COVID-19 wave were likely associated with a shortage of personal protective equipment and scarce indications on control measures. Having covered these limitations, updates on current SARS-CoV-2 nosocomial outbreaks are required. We carried out an in-depth analysis of a 27-day nosocomial outbreak in a gastroenterology ward in our hospital, potentially involving 15 patients and 3 health care workers. Patients had stayed in one of three neighboring rooms in the ward. The severity of the infections in six of the cases and a high fatality rate made the clinicians suspect the possible involvement of a single virulent strain persisting in those rooms. Whole-genome sequencing (WGS) of the strains from 12 patients and 1 health care worker revealed an unexpected complexity. Five different SARS-CoV-2 strains were identified, two infecting a single patient each, ruling out their relationship with the outbreak; the remaining three strains were involved in three independent, overlapping, limited transmission clusters with three, three, and five cases. Whole-genome sequencing was key to understand the complexity of this outbreak. IMPORTANCE We report a complex epidemiological scenario of a nosocomial COVID-19 outbreak in the second wave, based on WGS analysis. Initially, standard epidemiological findings led to the assumption of a homogeneous outbreak caused by a single SARS-CoV-2 strain. The discriminatory power of WGS offered a strikingly different perspective consisting of five introductions of different strains, with only half of them causing secondary cases in three independent overlapping clusters. Our study exemplifies how complex the SARS-CoV-2 transmission in the nosocomial setting during the second COVID-19 wave occurred and leads to extending the analysis of outbreaks beyond the initial epidemiological assumptions.

Proximal Ultrasound-Guided Gastrocnemius Recession: A New Ultra-Minimally Invasive Surgical Technique.

Selective proximal recession of the medial gastrocnemius head has clear advantages over other approaches and can be performed as a single or combined open procedure for many indications. The purpose of this study was to evaluate the safety and efficacy of a new technique based on ultrasound-guided ultraminimally invasive proximal gastrocnemius recession. We performed a pilot study with 16 cadavers to ensure that the technique was effective and safe; we then prospectively performed gastrocnemius recession in 12 patients (23 cases) with gastrocnemius contracture associated with other indications. We evaluated pre- and postprocedure dorsiflexion, clinical outcomes (based on the visual analog scale and American Orthopedic Foot and Ankle Society scores), and potential complications. We achieved effective release of the proximal medial gastrocnemius tendon in all cases, with no damage to other tissue. Ankle dorsiflexion increased 12° (range 6° to 18°) (p = .05) and was maintained throughout follow-up. The mean preoperative visual analog scale score was 7 (range 5 to 9), which improved to 1 (range 0 to 2) (p = .01). The American Orthopedic Foot and Ankle Society Ankle-Hindfoot Score improved from a mean of 25 (range 20 to 40) to 85 (range 80 to 100) at 6 months and 90 at 12 months (p = .01). No major complications were observed. We considered the technique to be safe and effective for ultrasound-guided ultraminimally invasive proximal-medial gastrocnemius recession using a 1-mm incision in vivo. This novel technique is an alternative to open techniques, with encouraging results and with the potential advantages of reducing pain and obviating lower limb ischemia and deep anesthesia, thus decreasing complications and contraindications and accelerating recovery, although further studies are required.

Schizophrenia-like reduced sensorimotor gating in intact inbred and outbred rats is associated with decreased medial prefrontal cortex activity and volume.

Prepulse inhibition (PPI) of startle response is a measure of sensorimotor gating that is impaired in schizophrenia and in many other clinical conditions. Rat models using pharmacological or surgical strategies reveal that PPI is modulated by the cortico-striatal-pallido-thalamic (CSPT) circuit. Here, we explore whether spontaneous variation in PPI in intact inbred and outbred rats is associated with functional and structural differences in the CSPT circuit. Inbred Roman High-(RHA) and Low-avoidance (RLA) and outbred heterogeneous stock (HS) rats were assessed for PPI, brain activity, and brain volume. Brain activity was assessed by c-Fos expression and brain volume by magnetic resonance imaging. Relevant structures of the CSPT circuit were evaluated, such as the medial prefrontal cortex (mPFC), cingulate cortex, hippocampus (HPC), amygdala, nucleus accumbens (NAc), and dorsal striatum. RHA showed lower PPI than RLA rats, while HS rats were stratified by their PPI levels in three groups. Reduced PPI was accompanied by decreased mPFC activity in Roman and HS rats and increased NAc shell activity in HS rats. Low PPI was also associated with decreased mPFC and HPC volumes in Roman and HS rats. This study reports a consistent relationship between decreased function and volume of the mPFC and spontaneous low-PPI levels in inbred and outbred intact rats. Moreover, our findings suggest that, apart from a hypoactive and smaller mPFC, a hyperactive NAc and smaller HPC may underlie reduced PPI levels. Our results support the notion that sensorimotor gating is modulated by forebrain structures and highlight the importance of the mPFC in its regulation.

Estado nutricional y grado de actividad física en la población con síndrome de Down. Diseño y aplicación de un programa de Educación Nutricional (Programa NUTRIDOWN) / Nutritional status and physical activity level in the population with Down syndrome. Design and application of a nutrition education program (NUTRIDOWN)

Fundamentos: Las personas con síndrome de Down (SD) tienen mayor riesgo de presentar obesidad. Los objetivos del estudio fueron valorar el estado nutricional y grado de actividad física en el colectivo con SD, y aplicar un programa de educación nutricional (PEN) adaptado, para mejorar sus conocimientos sobre obesidad y alimentación saludable. Métodos: Se realizó un estudio descriptivo observacional sobre 16 personas con SD y discapacidad leve-moderada. Se midió el peso corporal, talla y perímetro abdominal. Se valoró la ingesta mediante un cuestionario de frecuencia de consumo de alimentos, el grado de adherencia a la dieta Mediterránea (DM) y el grado de actividad física. Además, se diseñó y aplicó un PEN. Resultados: La media de edad fue de 21,5 años. El 62,6% presentaba sobrepeso u obesidad y el 43,8% fueron sedentarios. Se observó una baja adherencia a la DM y un aumento de conocimientos mediante el programa. Conclusiones: Se observa un elevado porcentaje de sobrepeso y obesidad que podría ser debido al elevado sedentarismo y a la baja adherencia a la DM observados. Los PEN adaptados al colectivo mejoran sus conocimientos sobre alimentación saludable. Sin embargo, es necesario observar su efectividad a largo plazo (AU)

Background: People with Down syndrome (DS) have higher risk of suffering obesity. The aims of this study were to evaluate the nutritional status and the degree of physical activity in teenagers and adults with DS, as well as designing and applying a nutritional education programme (NEP) adapted in order to improve the knowledge about obesity and healthy dietary habits. Methods: A descriptive observational study was made to 16 people suffering from DS and minor-to-moderate intellectual disability. Body weight, height and waist circumference were measured. We assessed the dietary intake using a food frequency questionnaire, as well as the adherence to the mediterranean diet (MD) and the physical activity level. We designed and applied a NEP. Results: The mean age was 21.5 years. The 62.6 % were overweight or obese and the 43.8 % declared itself as sedentary. Low adherence to MD was observed and the programme increased their knowledge. Conclusions: We observed high rates of overweight and obesity that could be attributed to the high sedentary behaviour, the poor-quality diet and the low adherence to MD observed. NEP adapted to SD people can improve the knowledge about healthy eating. However, it is necessary to observe its long-term effectiveness (AU)

Decreased myeloperoxidase expressing cells in the aged rat brain after excitotoxic damage.

Brain aging is associated to several morphological and functional alterations that influence the evolution and outcome of CNS damage. Acute brain injury such as an excitotoxic insult induces initial tissue damage followed by associated inflammation and oxidative stress, partly attributed to neutrophil recruitment and the expression of oxidative enzymes such as myeloperoxidase (MPO), among others. However, to date, very few studies have focused on how age can influence neutrophil infiltration after acute brain damage. Therefore, to evaluate the age-dependent pattern of neutrophil cell infiltration following an excitotoxic injury, intrastriatal injection of N-methyl-d-aspartate was performed in young and aged male Wistar rats. Animals were sacrificed at different times between 12h post-lesion (hpl) to 14 days post-lesion (dpl). Cryostat sections were processed for myeloperoxidase (MPO) immunohistochemistry, and double labeling for either neuronal cells (NeuN), astrocytes (GFAP), perivascular macrophages (ED-2), or microglia/macrophages (tomato lectin histochemistry). Our observations showed that MPO + cells were observed in the injured striatum from 12 hpl (when maximum values were found) until 7 dpl, when cell density was strongly diminished. However, at all survival times analyzed, the overall density of MPO + cells was lower in the aged versus the adult injured striatum. MPO + cells were mainly identified as neutrophils (especially at 12 hpl and 1 dpl), but it should be noted that MPO + neurons and microglia/macrophages were also found. MPO + neurons were most commonly observed at 12 hpl and reduced in the aged. MPO + microglia/macrophages were the main population expressing MPO from 3 dpl, when density was also reduced in aged subjects. These results point to neutrophil infiltration as another important factor contributing to the different responses of the adult and aged brain to damage, highlighting the need of using aged animals for the study of acute age-related brain insults.