Pharmacological inhibition of mTORC1 reduces neural death and damage volume after MCAO by modulating microglial reactivity.

Ischemic stroke is a sudden and acute disease characterized by neuronal death, increment of reactive gliosis (reactive microglia and astrocytes), and a severe inflammatory process. Neuroinflammation is an early event after cerebral ischemia, with microglia playing a leading role. Reactive microglia involve functional and morphological changes that drive a wide variety of phenotypes. In this context, deciphering the molecular mechanisms underlying such reactive microglial is essential to devise strategies to protect neurons and maintain certain brain functions affected by early neuroinflammation after ischemia. Here, we studied the role of mammalian target of rapamycin (mTOR) activity in the microglial response using a murine model of cerebral ischemia in the acute phase. We also determined the therapeutic relevance of the pharmacological administration of rapamycin, a mTOR inhibitor, before and after ischemic injury. Our data show that rapamycin, administered before or after brain ischemia induction, reduced the volume of brain damage and neuronal loss by attenuating the microglial response. Therefore, our findings indicate that the pharmacological inhibition of mTORC1 in the acute phase of ischemia may provide an alternative strategy to reduce neuronal damage through attenuation of the associated neuroinflammation.

The genomic footprint of whaling and isolation in fin whale populations.

Twentieth century industrial whaling pushed several species to the brink of extinction, with fin whales being the most impacted. However, a small, resident population in the Gulf of California was not targeted by whaling. Here, we analyzed 50 whole-genomes from the Eastern North Pacific (ENP) and Gulf of California (GOC) fin whale populations to investigate their demographic history and the genomic effects of natural and human-induced bottlenecks. We show that the two populations diverged ~16,000 years ago, after which the ENP population expanded and then suffered a 99% reduction in effective size during the whaling period. In contrast, the GOC population remained small and isolated, receiving less than one migrant per generation. However, this low level of migration has been crucial for maintaining its viability. Our study exposes the severity of whaling, emphasizes the importance of migration, and demonstrates the use of genome-based analyses and simulations to inform conservation strategies.

Delayed-onset posttraumatic stress disorder with response to methylphenidate / Trastorno por estrés postraumático de expresión retardada con respuesta a metilfenidato

Introduction: Posttraumatic stress disorder (PTSD) is extremely frequent in war veterans and has been widely studied. However, the efficacy of currently available pharmacological and psychotherapeutic treatments of war PTSD and other causes of PTSD is very limited. Method We present a case of war PTSD with delayed expression, with a good response to complementation with methylphenidate after a failed treatment with venlafaxine and risperidone. Results We review the role of dopamine in the pathophysiology of PTSD and the scarce studies in the treatment of PTSD with dopaminergic drugs that show an improvement in re-experimentation and in affective symptoms, especially anhedonia and cognitive impairment. Conclusions We conclude that the use of methylphenidate and other dopaminergic drugs can be a promising treatment for PTSD, a high prevalent disease with a high resistance to treatment, for which we encourage the use of large sample studies. (AU)

Introducción: El trastorno por estrés postraumático (TEPT) es extremadamente prevalente en veteranos de guerra y ha sido ampliamente estudiado. Sin embargo, la eficacia de los tratamientos farmacológicos y psicoterapéuticos disponibles es aún muy limitada, tanto en el TEPT de guerra como en el TEPT por otras causas. Método Presentamos un caso de TEPT de guerra con expresión retardada, con una buena respuesta al metilfenidato a su tratamiento con venlafaxina y risperidona, que había resultado ineficaz. Resultados Revisamos el rol de la dopamina en la psicopatología del TEPT y los pocos estudios del tratamiento del TEPT con fármacos dopaminérgicos, en los que se muestra una mejoría en los síntomas de reexperimentación y los síntomas afectivos, especialmente la anhedonia y los déficits cognitivos secundarios. Conclusiones Consideramos que el uso del metilfenidato y de otros fármacos dopaminérgicos podrían ser prometedores el tratamiento del TEPT, un trastorno altamente prevalente y con alta resistencia al tratamiento habitual. Por esto, animamos a realizar estudios con muestras amplias. (AU)

Training Characteristics and Competitive Demands in Women Road Cyclists: A Systematic Review.

PURPOSE: To identify the main training characteristics and competitive demands in women's road cycling. METHODS: A systematic search was conducted on 5 databases according to PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. The articles had to be primary studies, written after 1990 with a sample of competitive women between the ages of 15 and 50. The Quality Assessment Tool for Quantitative Studies and the Oxford Levels of Evidence scales were used. RESULTS: The search yielded 1713 articles, of which 20 were included. Studies on training and competitive demands (n = 5) found that both external and internal loads are higher in women than in men. Studies on strength and endurance training (n = 5) showed that both velocity-based and heavy-load strength training programs performed at least 2 days per week and including 3 to 4 lower-body exercises improved performance. Altitude-training studies (n = 3) found that "Live High-Train Low" was effective to increase performance during the first 9 days after the training camp. The 7 remaining studies focused on a range of topics. The methodological quality was strong for 12 studies and moderate for 8. In contrast, the level of evidence was high in 7 and low in the other 13. CONCLUSIONS: Endurance training and competitive demands in women's road cycling are higher than those of men. Strength training is effective in women when the frequency, intensity, and number of exercises are appropriate, while altitude training should be completed a few days before competing. Further studies are warranted to better define the participants' competitive level, using a methodological design with a higher level of evidence.

Genetic Analysis as a Tool to Improve the Monitoring of Stranded Cetaceans in Chile.

Cetacean strandings are a valuable source of information for several studies from species richness to conservation and management. During the examination of strandings, taxonomic and sex identification might be hindered for several reasons. Molecular techniques are valuable tools to obtain that missing information. This study evaluates how gene fragment amplification protocols can support the records of strandings done in the field in Chile by identifying, corroborating, or correcting the identification of the species and sex of the recorded individuals. Through a collaboration between a scientific laboratory and government institution in Chile, 63 samples were analyzed. Thirty-nine samples were successfully identified to the species level. In total, 17 species of six families were detected, including six species of conservation interest. Of the 39 samples, 29 corresponded to corroborations of field identifications. Seven corresponded to unidentified samples and three to corrected misidentifications, adding up to 28% of the identified samples. Sex was successfully identified for 58 of the 63 individuals. Twenty were corroborations, 34 were previously unidentified, and four were corrections. Applying this method improves the stranding database of Chile and provides new data for future management and conservation tasks.

Trauma infantil en esquizofrenia. Implicaciones en los síntomas psicóticos positivos y negativos / Childhood trauma and schizophrenia. Implications for positive and negative psychotic symptomsresumen

La relación entre trauma infantil (TI) y la psicosis está bien establecida y son diversas las teorías sobre los factores que median en esta relación. También son muchos los estudios que exploran la influencia del TI en el curso de la psicosis en distintas áreas. El objetivo de este estudio fue explorar la influencia del TI en la presencia e intensidad de los síntomas psicóticos positivos (SPP) y negativos (SPN) en pacientes con trastornos del espectro esquizofrénico. Se incluyeron un total de 45 pacientes con diagnóstico de esquizofrenia o trastorno esquizoafectivo. Se valoraron datos sociodemográficos, los antecedentes de TI mediante el Childhood Trauma Questionnaire, Short Form (CTQ-SF), así como la intensidad de los síntomas psicóticos positivos y negativos mediante la Positive and Negative Syndrome Scale (PANSS+ y -).De la totalidad de la muestra, 35 pacientes, el 77,8 %, habían padecido algún tipo trauma infantil; el 55,6%, negligencia emocional; el 48,9%, abuso emocional: el 46,7%, negligencia física y el 40,0%, abuso sexual. No encontramos correlación entre CTQ-SF y PANSS+ y sí una relación inversa ente CTQ-SF v PANSS- (Rho -0.300, p=0.045). A diferencia de otros estudios no encontramos una correlación entre el TI y los SPP, a excepción del abuso físico con el ítem de excitación, tal vez debido a la cronicidad de los pacientes de nuestra muestra. La correlación moderada e inversa entre el TI y los SPN sugerimos que podría deberse a que los síntomas psicóticos positivos y negativos surgirían de diátesis distintas. Los síntomas negativos estarían en relación con déficits de neurodesarrollo y no relacionados con el estrés, como se ha sugerido en los síntomas psicóticos positivos. Sin embargo, dado que es trata de un hallazgo poco replicado, es difícil establecer conclusiones claras.(AU)

The relationship between childhood trauma (CT) and psychosis is well established and theories about the factors mediating this relationship are diverse. CT is associated with a worse prognosis of psychosis The aim of this study was to explore the influence of childhood trauma on the presence and intensity of positive (PPS) and negative psychotic symptoms (NPS) in patients with schizophrenic spectrum disorders. Forty-five patients with a diagnosis of schizophrenia or schizo affective disorder were included. Sociodemographic data, childhood trauma history using the Childhood Trauma Questionnaire Short Form (CTQ-SF) and the intensity of positive and negative psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS + and -), were valued. Of the total sample, 35 patients, 77.8%, had suffered some type of childhood trauma; 55.6%, emotional neglect; 48.9%, emotional abuse: 46.7%, physical neglect and 40.0%, sexual abuse. We did not find a correlation between CTQ-SF and PANSS+ and an inverse relationship between CTQ-SF v PANSS- (Rho -0.300, p=0.045). Unlike other studies, we did not find a correlation between CT and PPS, except for physical abuse with the excitation item, perhaps due to the chronicity of patients in our sample. The inverse corre lation between CT and NPS may be due to positive and negative psychotic symptoms arising from different diameters. NPS could be related to neurological development deficits and not related to stress, as suggested in PPS. However, since it is a finding with little replication, it is difficult to draw clear conclusions.(AU

Relationship between competency for evidence-based practice and level of burnout of physical therapists with the establishment of the therapeutic relationship.

BACKGROUND: Evidence-based practice (EBP) interventions and effective therapeutic alliance (TA) are associated with greater treatment success. Furthermore, burnout syndrome could be detrimental to the development of such TA. OBJECTIVE: To examine the association between EBP competencies and burnout level with the quality of TA among Spanish physiotherapists. METHODS: Cross-sectional research with an electronic survey including the EBP Questionnaire-19, Maslach Burnout Inventory and Working Alliance Inventory-Short (WAI-S) and administered to 471 physiotherapists. RESULTS: Regarding the EBP Questionnaire-19, physiotherapists scored highest on attitude and lowest on knowledge. For WAIS which achieved appropriate results of internal consistency and validity in the sample analyzed, bond scored the highest and goals the lowest. Years of experience was significantly associated with the task (r = 0.5; p = .003) and bond (r = 0.7; p = .002) and the WAIS total score (r = 0.8; p < .001), and all burnout subscales (-0.7 < r > 0.7; p < .001 for all). CONCLUSION: Lower levels of burnout and improved EBP competencies are associated with a TA of greater quality. The association between attitudes toward EBP, a higher level of self-confidence and a lower perception of depersonalization appear to be determinant factors for improving TA.

Artificial Intelligence on FDG PET Images Identifies Mild Cognitive Impairment Patients with Neurodegenerative Disease.

The purpose of this project is to develop and validate a Deep Learning (DL) FDG PET imaging algorithm able to identify patients with any neurodegenerative diseases (Alzheimer's Disease (AD), Frontotemporal Degeneration (FTD) or Dementia with Lewy Bodies (DLB)) among patients with Mild Cognitive Impairment (MCI). A 3D Convolutional neural network was trained using images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The ADNI dataset used for the model training and testing consisted of 822 subjects (472 AD and 350 MCI). The validation was performed on an independent dataset from La Fe University and Polytechnic Hospital. This dataset contained 90 subjects with MCI, 71 of them developed a neurodegenerative disease (64 AD, 4 FTD and 3 DLB) while 19 did not associate any neurodegenerative disease. The model had 79% accuracy, 88% sensitivity and 71% specificity in the identification of patients with neurodegenerative diseases tested on the 10% ADNI dataset, achieving an area under the receiver operating characteristic curve (AUC) of 0.90. On the external validation, the model preserved 80% balanced accuracy, 75% sensitivity, 84% specificity and 0.86 AUC. This binary classifier model based on FDG PET images allows the early prediction of neurodegenerative diseases in MCI patients in standard clinical settings with an overall 80% classification balanced accuracy.

Perspectives on the Ethics of Antibiotic Overuse and on the Implementation of (New) Antibiotics.

The continuing rise in global antimicrobial resistance is seen by many governments and international organizations as a major threat to worldwide health. This means that many publications have already described the problems concerning the overuse of currently available antibiotics and potential solutions to this crisis, including the development of new alternatives to antibiotics. However, in this manuscript, the authors approach the subject of increasing global antimicrobial resistance from two perspectives not normally covered by previous publications, namely the ethical use of antibiotics and potential issues relating to the implementation of new antibiotics.

The association between empathy and the physiotherapy-patient therapeutic alliance: A cross-sectional study.

BACKGROUND: The central component of person-centred care is in having a therapeutic realtionship. Furthermore, the empathy of the physiotherapist is one of the most important attributes in achieving a successful therapeutic alliance. OBJECTIVE: The aim of the research was to determine the association between the constructs of empathy and therapeutic alliance in Spanish physical therapists and the possible influence of socio-professional variables on them. DESIGN: Cross-sectional research. METHODS: An electronic survey including the Working Alliance Inventory-Short Form, the Interpersonal Reactivity Index and sociodemographic data with 473 Spanish physiotherapists. A descriptive, bivariate and simple lineal regression analysis was carried out. RESULTS: Work experience has a positive influence on bonding and the agreement on objectives and tasks (0.04 < B > 0.06; p < 0.01). The perspective taking dimensions and empathic concern positively influence the agreement on achievement (0.14 < B > 0.19; p < 0.001). Personal distress inversely influences bonding and the agreement on achievements and tasks (-0.13 < B > -0.09; p < 0.01). CONCLUSIONS: The dimensions of perspective taking and empathic concern seem to facilitate successful shared decision making in terms of treating objectives. Furthermore, the physiotherapist's personal distress acts as an obstacle to the development of the three subcomponents of the therapeutic alliance analysed.

Dysregulation of mTOR Signaling after Brain Ischemia.

In this review, we provide recent data on the role of mTOR kinase in the brain under physiological conditions and after damage, with a particular focus on cerebral ischemia. We cover the upstream and downstream pathways that regulate the activation state of mTOR complexes. Furthermore, we summarize recent advances in our understanding of mTORC1 and mTORC2 status in ischemia-hypoxia at tissue and cellular levels and analyze the existing evidence related to two types of neural cells, namely glia and neurons. Finally, we discuss the potential use of mTORC1 and mTORC2 as therapeutic targets after stroke.

Fast Energy Dependent Scatter Correction for List-Mode PET Data.

Improvements in energy resolution of modern positron emission tomography (PET) detectors have created opportunities to implement energy-based scatter correction algorithms. Here, we use the energy information of auxiliary windows to estimate the scatter component. Our method is directly implemented in an iterative reconstruction algorithm, generating a scatter-corrected image without the need for sinograms. The purpose was to implement a fast energy-based scatter correction method on list-mode PET data, when it was not possible to use an attenuation map as a practical approach for the scatter degradation. The proposed method was evaluated using Monte Carlo simulations of various digital phantoms. It accurately estimated the scatter fraction distribution, and improved the image contrast in the simulated studied cases. We conclude that the proposed scatter correction method could effectively correct the scattered events, including multiple scatters and those originated in sources outside the field of view.

2D feasibility study of joint reconstruction of attenuation and activity in limited angle TOF-PET.

Several research groups are studying organ-dedicated limited angle positron emission tomography (PET) systems to optimize performance-cost ratio, sensitivity, access to the patient and/or flexibility. Often open systems are considered, typically consisting of two detector panels of various sizes. Such systems provide incomplete sampling due to limited angular coverage and/or truncation, which leads to artefacts in the reconstructed activity images. In addition, these organ-dedicated PET systems are usually stand-alone systems, and as a result, no attenuation information can be obtained from anatomical images acquired in the same imaging session. It has been shown that the use of time-of-flight information reduces incomplete data artefacts and enables the joint estimation of the activity and the attenuation factors. In this work, we explore with simple 2D simulations the performance and stability of a joint reconstruction algorithm, for imaging with a limited angle PET system. The reconstruction is based on the so-called MLACF (Maximum Likelihood Attenuation Correction Factors) algorithm and uses linear attenuation coefficients in a known-tissue-class region to obtain absolute quantification. Different panel sizes and different time-of-flight (TOF) resolutions are considered. The noise propagation is compared to that of MLEM reconstruction with exact attenuation correction (AC) for the same PET system. The results show that with good TOF resolution, images of good visual quality can be obtained. If also a good scatter correction can be implemented, quantitative PET imaging will be possible. Further research, in particular on scatter correction, is required.

Glial Cells as Therapeutic Approaches in Brain Ischemia-Reperfusion Injury.

Ischemic stroke is the second cause of mortality and the first cause of long-term disability constituting a serious socioeconomic burden worldwide. Approved treatments include thrombectomy and rtPA intravenous administration, which, despite their efficacy in some cases, are not suitable for a great proportion of patients. Glial cell-related therapies are progressively overcoming inefficient neuron-centered approaches in the preclinical phase. Exploiting the ability of microglia to naturally switch between detrimental and protective phenotypes represents a promising therapeutic treatment, in a similar way to what happens with astrocytes. However, the duality present in many of the roles of these cells upon ischemia poses a notorious difficulty in disentangling the precise pathways to target. Still, promoting M2/A2 microglia/astrocyte protective phenotypes and inhibiting M1/A1 neurotoxic profiles is globally rendering promising results in different in vivo models of stroke. On the other hand, described oligodendrogenesis after brain ischemia seems to be strictly beneficial, although these cells are the less studied players in the stroke paradigm and negative effects could be described for oligodendrocytes in the next years. Here, we review recent advances in understanding the precise role of mentioned glial cell types in the main pathological events of ischemic stroke, including inflammation, blood brain barrier integrity, excitotoxicity, reactive oxygen species management, metabolic support, and neurogenesis, among others, with a special attention to tested therapeutic approaches.

Simulation Study of a Frame-Based Motion Correction Algorithm for Positron Emission Imaging.

Positron emission tomography (PET) is a functional non-invasive imaging modality that uses radioactive substances (radiotracers) to measure changes in metabolic processes. Advances in scanner technology and data acquisition in the last decade have led to the development of more sophisticated PET devices with good spatial resolution (1-3 mm of full width at half maximum (FWHM)). However, there are involuntary motions produced by the patient inside the scanner that lead to image degradation and potentially to a misdiagnosis. The adverse effect of the motion in the reconstructed image increases as the spatial resolution of the current scanners continues improving. In order to correct this effect, motion correction techniques are becoming increasingly popular and further studied. This work presents a simulation study of an image motion correction using a frame-based algorithm. The method is able to cut the acquired data from the scanner in frames, taking into account the size of the object of study. This approach allows working with low statistical information without losing image quality. The frames are later registered using spatio-temporal registration developed in a multi-level way. To validate these results, several performance tests are applied to a set of simulated moving phantoms. The results obtained show that the method minimizes the intra-frame motion, improves the signal intensity over the background in comparison with other literature methods, produces excellent values of similarity with the ground-truth (static) image and is able to find a limit in the patient-injected dose when some prior knowledge of the lesion is present.

Childhhood Trauma in Schizophrenia Spectrum Disorders: Dissociative, Psychotic Symptoms, and Suicide Behavior.

Current evidence suggests a high prevalence of childhood trauma (CT) among adult patients diagnosed with schizophrenia spectrum disorders. Exposure to CT might lead to clinical differences eventually observed in these patients. We present a cross-sectional study with 54 patients with schizophrenia spectrum disorder (schizophrenia and schizoaffective disorder). We obtained sociodemographic data, as well as data on CT, dissociation, suicide history, and intensity of positive and negative psychotic symptoms. More than 75% of the patients reported a history of CT. We observed a link between CT and suicidal behavior. Patients showed high rates of dissociation. Dissociative experiences were related to CT, both in terms of intensity of trauma and number of traumas experienced. All CT forms except emotional neglect showed direct correlations with dissociative experiences. We found no correlation between intensity of CT and intensity of positive psychotic symptoms, yet we observed a moderate inverse correlation with negative psychotic symptoms.

Musculoskeletal Pain and Teleworking in Times of the COVID-19: Analysis of the Impact on the Workers at Two Spanish Universities.

The special situation brought about by the coronavirus pandemic and the confinement imposed by the Government, has given rise to numerous changes in working habits. The workers at the universities have had to start a period of teleworking that could give rise to consequences for the musculoskeletal system. The objective of this article is to analyze the impact of the confinement on the musculoskeletal health of the staff of two Spanish universities. A cross-sectional, observational study was carried out on the workers. Data was taken in April-May 2020 and included: The Standardized Kuorinka Modified Nordic Questionnaire, the Perceived Stress Scale and another one on sociodemographic data. This study comprised 472 people. The areas of pain noted during the confinement period concluded that it was less in all cases (p < 0.001). The frequency of physical activity carried out increased significantly during the period of confinement (p < 0.04), especially in women. The type of physical activity done was also seen to modify during this period (p < 0.001), with a preference for strength training and stretching exercises. In conclusion, the confinement gave rise to changes in the lifestyle and in the musculoskeletal pain of the workers at the universities. All of this must be taken into account by health institutions and those responsible for the Prevention of Occupational Risks at Spanish universities.

Intimate Partner Violence Among Patients Diagnosed With Severe Mental Disorder.

Intimate partner violence (IPV) has a remarkable impact on mental health and is common in people diagnosed with severe mental disorders (SMDs). Data of 102 outpatients were collected from clinical records and the Traumatic Life Events Questionnaire (TLEQ). Global estimation of lifetime IPV exposure was obtained by combining answers to selected TLEQ questions about physical, psychological, and sexual IPV. Overall, 24.5% of the participants reported at least one lifetime episode of IPV victimization. Female gender (odds ratio [OR] = 3.15, p = 0.016) and childhood trauma (OR = 4.7, p = 0.002) significantly increased the likelihood of IPV victimization. Conversely, posttraumatic stress disorder was not significantly increased in IPV victims. These findings are in line with current literature and suggest a remarkable and transdiagnostic prevalence of lifetime IPV victimization in SMD. Gender, childhood trauma, and SMD are relevant factors in IPV analysis and prevention. Diathesis of trauma, psychosocial vulnerability to revictimization and intersectional feminist theory help explain our results.