Wildfire smoke impacts lake ecosystems.

Wildfire activity is increasing globally. The resulting smoke plumes can travel hundreds to thousands of kilometers, reflecting or scattering sunlight and depositing particles within ecosystems. Several key physical, chemical, and biological processes in lakes are controlled by factors affected by smoke. The spatial and temporal scales of lake exposure to smoke are extensive and under-recognized. We introduce the concept of the lake smoke-day, or the number of days any given lake is exposed to smoke in any given fire season, and quantify the total lake smoke-day exposure in North America from 2019 to 2021. Because smoke can be transported at continental to intercontinental scales, even regions that may not typically experience direct burning of landscapes by wildfire are at risk of smoke exposure. We found that 99.3% of North America was covered by smoke, affecting a total of 1,333,687 lakes ≥10 ha. An incredible 98.9% of lakes experienced at least 10 smoke-days a year, with 89.6% of lakes receiving over 30 lake smoke-days, and lakes in some regions experiencing up to 4 months of cumulative smoke-days. Herein we review the mechanisms through which smoke and ash can affect lakes by altering the amount and spectral composition of incoming solar radiation and depositing carbon, nutrients, or toxic compounds that could alter chemical conditions and impact biota. We develop a conceptual framework that synthesizes known and theoretical impacts of smoke on lakes to guide future research. Finally, we identify emerging research priorities that can help us better understand how lakes will be affected by smoke as wildfire activity increases due to climate change and other anthropogenic activities.

Runway extinction in terrestrial toads (Rhinella arenarum): Instrumental or Pavlovian?

Instrumental appetitive extinction involves the reduction of a previously reinforced response when its occurrence is no longer rewarded. Two experiments with terrestrial toads (Rhinella arenarum) tested whether the occurrence of a nonreinforced response is necessary for response extinction by varying the time of exposure to nonrewarded goal-box stimuli across groups. In Experiment 1, toads that received the same acquisition training (15 sessions, 1 session/day, 300 s of access to water in the goal box) were randomly assigned to two groups. In Group 600 (n=12), animals spent 600 s in the goal box in 8 daily extinction sessions (water present but inaccessible). In Group 0 (n=11), toads performed the runway response (i.e., walking from the start to the goal box) but were removed as soon as they entered the goal box, thus having minimal exposure to nonrewarded goal-box stimuli. The runway response was weakened in Group 600 across extinction trials, but exhibited little change in Group 0. In Experiment 2, toads were randomly assigned to two groups after the same acquisition training. Group 0 (n=7) was treated the same as Group 0 in the previous experiment. In Group RI (retention interval, n=7), toads remained in their home cage for 13 days. Finally, all animals received 4 extinction sessions with 300 s in the empty goal box. There was little behavioral change in Group 0 during the 13 sessions with minimal exposure to the goal box. In extinction, both groups reduced their runway response at similar rates. Although the procedures were instrumental, extinction of the runway response in toads can be accounted for in terms of a Pavlovian approach response to stimuli paired with reward and nonreward in the goal box.

ApTOLL: A new therapeutic aptamer for cytoprotection and (re)myelination after multiple sclerosis.

BACKGROUND AND PURPOSE: ApTOLL is an aptamer selected to antagonize toll-like receptor 4 (TLR4), a relevant actor for innate immunity involved in inflammatory responses in multiple sclerosis (MS) and other diseases. The currently available therapeutic arsenal to treat MS is composed of immunomodulators but, to date, there are no (re)myelinating drugs available in clinics. In our present study, we studied the effect of ApTOLL on different animal models of MS. EXPERIMENTAL APPROACH: The experimental autoimmune encephalomyelitis (EAE) model was used to evaluate the effect of ApTOLL on reducing the inflammatory component. A more direct effect on oligodendroglia was studied with the cuprizone model and purified primary cultures of murine and human oligodendrocyte precursor cells (OPCs) isolated through magnetic-activated cell sorting (MACS) from samples of brain cortex. Also, we tested these effects in an ex vivo model of organotypic cultures demyelinated with lysolecithin (LPC). KEY RESULTS: ApTOLL treatment positively impacted the clinical symptomatology of mice in the EAE and cuprizone models, which was associated with better preservation plus restoration of myelin and oligodendrocytes in the demyelinated lesions of animals. Restoration was corroborated on purified cultures of rodent and human OPCs. CONCLUSION AND IMPLICATIONS: Our findings reveal a new therapeutic approach for the treatment of inflammatory and demyelinating diseases such as MS. The molecular nature of the aptamer exerts not only an anti-inflammatory effect but also neuroprotective and remyelinating effects. The excellent safety profile demonstrated by ApTOLL in animals and humans opens the door to future clinical trials in MS patients.

Ratiometric gibberellin biosensors for the analysis of signaling dynamics and metabolism in plant protoplasts.

Gibberellins (GAs) are major regulators of developmental and growth processes in plants. Using the degradation-based signaling mechanism of GAs, we have built transcriptional regulator (DELLA)-based, genetically encoded ratiometric biosensors as proxies for hormone quantification at high temporal resolution and sensitivity that allow dynamic, rapid and simple analysis in a plant cell system, i.e. Arabidopsis protoplasts. These ratiometric biosensors incorporate a DELLA protein as a degradation target fused to a firefly luciferase connected via a 2A peptide to a renilla luciferase as a co-expressed normalization element. We have implemented these biosensors for all five Arabidopsis DELLA proteins, GA-INSENSITIVE, GAI; REPRESSOR-of-ga1-3, RGA; RGA-like1, RGL1; RGL2 and RGL3, by applying a modular design. The sensors are highly sensitive (in the low pm range), specific and dynamic. As a proof of concept, we have tested the applicability in three domains: the study of substrate specificity and activity of putative GA-oxidases, the characterization of GA transporters, and the use as a discrimination platform coupled to a GA agonists' chemical screening. This work demonstrates the development of a genetically encoded quantitative biosensor complementary to existing tools that allow the visualization of GA in planta.

Instrumental successive negative contrast in rats: Trial distribution, reward magnitude, and prefrontal cortex activation.

Successive negative contrast (SNC) has been used to study reward relativity, reward loss, and frustration for decades. In instrumental SNC (iSNC), the anticipatory performance of animals downshifted from a large reward to a small reward is compared to that of animals always reinforced with the small reward. iSNC involves a transient deterioration of anticipatory behavior in downshifted animals compared to unshifted controls. There is scattered information on the optimal parameters to produce this effect and even less information about its neural basis. Five experiments with rats trained in a runway to collect food pellets explored the effects of trial distribution (massed or spaced), amount of preshift training, reward disparity, and reward magnitude on the development of an iSNC effect. Start, run, and goal latencies were measured. Using spaced trials (one trial per day), evidence of the iSNC effect was observed with 24 preshift trials and a 32-to-4 pellet disparity. With massed trials (4 trials per session separated by 30-s intertrial intervals), evidence of iSNC was found with 12 preshift sessions (a total of 48 trials) and a 16-to-2 pellet disparity. The massed-training procedure was then used to assess neural activity in three prefrontal cortex areas using c-Fos expression in animals perfused after the first downshift session. There was evidence of increased activation in the anterior cingulate cortex and a trend toward increased activation in the infralimbic and prelimbic cortices. These procedures open a venue for studying the neural basis of the instrumental behavior of animals that experience reward loss.

Transcription-driven DNA supercoiling counteracts H-NS-mediated gene silencing in bacterial chromatin.

In all living cells, genomic DNA is compacted through interactions with dedicated proteins and/or the formation of plectonemic coils. In bacteria, DNA compaction is achieved dynamically, coordinated with dense and constantly changing transcriptional activity. H-NS, a major bacterial nucleoid structuring protein, is of special interest due to its interplay with RNA polymerase. H-NS:DNA nucleoprotein filaments inhibit transcription initiation by RNA polymerase. However, the discovery that genes silenced by H-NS can be activated by transcription originating from neighboring regions has suggested that elongating RNA polymerases can disassemble H-NS:DNA filaments. In this study, we present evidence that transcription-induced counter-silencing does not require transcription to reach the silenced gene; rather, it exerts its effect at a distance. Counter-silencing is suppressed by introducing a DNA gyrase binding site within the intervening segment, suggesting that the long-range effect results from transcription-driven positive DNA supercoils diffusing toward the silenced gene. We propose a model wherein H-NS:DNA complexes form in vivo on negatively supercoiled DNA, with H-NS bridging the two arms of the plectoneme. Rotational diffusion of positive supercoils generated by neighboring transcription will cause the H-NS-bound negatively-supercoiled plectoneme to "unroll" disrupting the H-NS bridges and releasing H-NS.

Utility of ultrasound in the diagnostic approach to lymphoma with splenic involvement.

This paper describes the clinical case of a patient diagnosed with diffuse large B-cell lymphoma with splenic involvement, focusing on the role of abdominal ultrasound (US) in this context. The patient experienced dyspepsia and progressive asthenia over several months so an abdominal US was performed. The US showed multiple heterogeneous and hypoechogenic focal splenic lesions together with a moderate left pleural effusion. Lymphoma was suspected due to these findings and the diagnosis was then confirmed with the performance of a CT scan and a biopsy that revealed the presence of a diffuse large B-cell lymphoma with metastatic disease. Chemotherapy containing rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone was administered and the patient is currently on clinical remission. This study highlights the role of abdominal ultrasound as a useful technique in the non-invasive assessment of this entity, considering an appropriate clinical context and mainly after detecting multiple hypoechogenic splenic lesions in the US.

Mitophagy curtails cytosolic mtDNA-dependent activation of cGAS/STING inflammation during aging.

Macroautophagy decreases with age, and this change is considered a hallmark of the aging process. It remains unknown whether mitophagy, the essential selective autophagic degradation of mitochondria, also decreases with age. In our analysis of mitophagy in multiple organs in the mito-QC reporter mouse, mitophagy is either increased or unchanged in old versus young mice. Transcriptomic analysis shows marked upregulation of the type I interferon response in the retina of old mice, which correlates with increased levels of cytosolic mtDNA and activation of the cGAS/STING pathway. Crucially, these same alterations are replicated in primary human fibroblasts from elderly donors. In old mice, pharmacological induction of mitophagy with urolithin A attenuates cGAS/STING activation and ameliorates deterioration of neurological function. These findings point to mitophagy induction as a strategy to decrease age-associated inflammation and increase healthspan.

Efficacy of a benzothiazole-based LRRK2 inhibitor in oligodendrocyte precursor cells and in a murine model of multiple sclerosis.

AIMS: Multiple sclerosis (MS) is a chronic neurological disease that currently lacks effective curative treatments. There is a need to find effective therapies, especially to reverse the progressive demyelination and neuronal damage. Oligodendrocytes form the myelin sheath around axons in the central nervous system (CNS) and oligodendrocyte precursor cells (OPCs) undergo mechanisms that enable spontaneously the partial repair of damaged lesions. The aim of this study was to discover small molecules with potential effects in demyelinating diseases, including (re)myelinating properties. METHODS: Recently, it has been shown how LRRK2 inhibition promotes oligodendrogliogenesis and therefore an efficient repair or myelin damaged lesions. Here we explored small molecules inhibiting LRRK2 as potential enhancers of primary OPCs proliferation and differentiation, and their potential impact on the clinical score of experimental autoimmune encephalomyelitys (EAE) mice, a validated model of the most frequent clinical form of MS, relapsing-remitting MS. RESULTS: One of the LRRK2 inhibitors presented in this study promoted the proliferation and differentiation of OPC primary cultures. When tested in the EAE murine model of MS, it exerted a statistically significant reduction of the clinical burden of the animals, and histological evidence revealed how the treated animals presented a reduced lesion area in the spinal cord. CONCLUSIONS: For the first time, a small molecule with LRRK2 inhibition properties presented (re)myelinating properties in primary OPCs cultures and potentially in the in vivo murine model. This study provides an in vivo proof of concept for a LRRK2 inhibitor, confirming its potential for the treatment of MS.

Biosynthesis of chlorophyll c in a dinoflagellate and heterologous production in planta.

Chlorophyll c is a key photosynthetic pigment that has been used historically to classify eukaryotic algae. Despite its importance in global photosynthetic productivity, the pathway for its biosynthesis has remained elusive. Here we define the CHLOROPHYLL C SYNTHASE (CHLCS) discovered through investigation of a dinoflagellate mutant deficient in chlorophyll c. CHLCSs are proteins with chlorophyll a/b binding and 2-oxoglutarate-Fe(II) dioxygenase (2OGD) domains found in peridinin-containing dinoflagellates; other chlorophyll c-containing algae utilize enzymes with only the 2OGD domain or an unknown synthase to produce chlorophyll c. 2OGD-containing synthases across dinoflagellate, diatom, cryptophyte, and haptophyte lineages form a monophyletic group, 8 members of which were also shown to produce chlorophyll c. Chlorophyll c1 to c2 ratios in marine algae are dictated in part by chlorophyll c synthases. CHLCS heterologously expressed in planta results in the accumulation of chlorophyll c1 and c2, demonstrating a path to augment plant pigment composition with algal counterparts.

Compassion Fatigue Syndrome in Social Workers and Its relationship with Emotional Intelligence.

A study was conducted on how emotional intelligence and compassion fatigue (CF) interact in social workers. The hypothesis was that social workers with higher emotional intelligence were less likely to suffer/develop CF. A sample of 264 subjects was selected from among 2,014 active social workers in Seville (Spain). They were administered a sociodemographic questionnaire (α = .710), the Emotional Intelligence Questionnaire-Short Form (α = .790), and the Compassion Fatigue Scale (α = .770). Authors carried out a reliability analysis (Cronbach's alpha), a frequency study, contingency tables, a Pearson-type correlations analysis, a linear regression analysis, and analysis of variance-type significance tests (with values between p = .001 and p = .005). The social workers who participated in this study presented high emotional intelligence, yet high rates of CF were found. Specifically, the lower the social worker's manifest level of emotional intelligence, the greater the suffering of CF. Overall, social workers with higher emotional intelligence were less likely to suffer or develop CF.

Mitophagy in the retina: Viewing mitochondrial homeostasis through a new lens.

Mitochondrial function is key to support metabolism and homeostasis in the retina, an organ that has one of the highest metabolic rates body-wide and is constantly exposed to photooxidative damage and external stressors. Mitophagy is the selective autophagic degradation of mitochondria within lysosomes, and can be triggered by distinct stimuli such as mitochondrial damage or hypoxia. Here, we review the importance of mitophagy in retinal physiology and pathology. In the developing retina, mitophagy is essential for metabolic reprogramming and differentiation of retina ganglion cells (RGCs). In basal conditions, mitophagy acts as a quality control mechanism, maintaining a healthy mitochondrial pool to meet cellular demands. We summarize the different autophagy- and mitophagy-deficient mouse models described in the literature, and discuss the potential role of mitophagy dysregulation in retinal diseases such as glaucoma, diabetic retinopathy, retinitis pigmentosa, and age-related macular degeneration. Finally, we provide an overview of methods used to monitor mitophagy in vitro, ex vivo, and in vivo. This review highlights the important role of mitophagy in sustaining visual function, and its potential as a putative therapeutic target for retinal and other diseases.

Analysis of Salmonella lineage-specific traits upon cell sorting.

Microbial cell individuality is receiving increasing interest in the scientific community. Individual cells within clonal populations exhibit noticeable phenotypic heterogeneity. The advent of fluorescent protein technology and advances in single-cell analysis has revealed phenotypic cell variant in bacterial populations. This heterogeneity is evident in a wide range of phenotypes, for example, individual cells display variable degrees of gene expression and survival under selective conditions and stresses, and can exhibit differing propensities to host interactions. Last few years, numerous cell sorting approaches have been employed for resolving the properties of bacterial subpopulations. This review provides an overview of applications of cell sorting to analyze Salmonella lineage-specific traits, including bacterial evolution studies, gene expression analysis, response to diverse cellular stresses and characterization of diverse bacterial phenotypic variants.

Influencia del SARS-CoV-2 en la progresión de infección a enfermedad tuberculosa. A propósito de 3 casos / Influence of SARS-CoV-2 On the Progression of Infection to Tuberculous Disease. About 3 cases

Introducción: Es probable que el SARS-CoV-2 favorezca el paso de infección a enfer medad tuberculosa. Si bien la información es limitada, existen avances en la comprensión de la interacción COVID-19 y tuberculosis. Nuevas investigaciones arrojaron similitudes inesperadas en la patogenia y evolución de la coinfección. Linfopenia prolongada, hipe rinflamación, lesión del tejido pulmonar y desequilibrio en los subconjuntos de células T CD4+ asociados con COVID-19 podrían propagar la infección por M. tuberculosis y progresión de la enfermedad. Casos clínicos: Presentamos tres pacientes jóvenes, sin comorbilidades, con factores de riesgo para infección tuberculosa latente, diagnosticados de tuberculosis pulmonar posterior cursado COVID-19 leve, de tratamiento sintomático (no corticoideo). Discusión: Estos casos plantean el probable impacto del SARS-CoV-2 en el paso de infección tuberculosa latente a enfermedad, excluida la ya demostrada influencia de los corticoides y formas graves de COVID-19. Existe cada vez más evidencia que refuerza esta idea.

Introduction: SARS-CoV-2 is likely to favor the transition from infection to tuberculosis disease. Although information is limited, there is progress in understanding the inter action between COVID-19 and Tuberculosis. New investigations yielded unexpected similarities in the pathogenesis and evolution of the coinfection. Prolonged lymphopenia, hyperinflammation, lung tissue injury, and imbalance in CD4+ T-cell subsets associated with COVID-19 could propagate M. tuberculosis infection and disease progression. Clinical cases: we present three young patients, without comorbidities, with risk factors for Latent Tuberculous Infection, diagnosed with pulomonary Tuberculosis post mild COVID-19, treated symptomatically (not corticosteroids). Discussion: These cases raise the probable impact of SARS-CoV-2 in the transition from Latent Tuberculous Infection to disease, excluding the already proven influence of corticosteroids and severe forms of COVID-19. There is increasing evidence to sup port this idea.

A Four-Year Survey of Hemoparasites from Nocturnal Raptors (Strigiformes) Confirms a Relation between Leucocytozoon and Low Hematocrit and Body Condition Scores of Parasitized Birds.

Most hemoparasites hosted by wild birds appear to be harmless, but most of the blood parasite studies in avian wildlife are mainly focused on passerines or migratory species. This study aimed to assess the occurrence of blood parasites in nocturnal raptors (Strigiformes order) and their effect on hematological parameters. A total of 134 blood samples were collected during a four-year period for hematological analysis and hemoparasite detection and quantification by microscopical examination of the samples. Overall, the occurrence of hemoparasites was 35.1%, with Leucocytozoon being the most frequently detected (32.1%), followed by Haemoproteus (11.2%), Trypanosoma and Plasmodium (2.2% each). Among the different bird species, the Eurasian eagle-owl (Bubo bubo) showed the highest blood parasite positivity (94.7%). In barn owls, the positive birds displayed a lower hematocrit measurement and body condition score than the non-parasitized ones (p = 0.007 and p = 0.005, respectively), especially those parasitized by Leucocytozoon. Moreover, the analysis of the magnitude of this association revealed that the presence of hemoparasites is five times more frequent in barn owls with a 2/5 body condition score. Despite the host-parasite coevolution in Strigiformes, our results show a correlation between the presence of hemoparasites and some health parameters, including blood parameters.

Manejo de las gestantes durante la pandemia COVID-19 y experiencia en un hospital de A Coruña / Management of pregnant women during the COVID-19 pandemic and experience in a Coruña’s hospital

Objetivo: Describir el seguimiento y la atención al parto de las gestantes durante la pandemia por Covid- 19 en el Complejo Hospitalario de A Coruña. Recopilar evidencia y recomendaciones científicas en el seguimiento de la mujer gestante durante la pandemia Covid-19. Método: Se ha realizado una búsqueda bibliográfica en bases de datos como Medline, Cochrane y CUIDEN, además de en sitios web: OMS, el Ministerio de Sanidad y el SERGAS. Se han utilizado los términos MeSH: “Covid-19”, “Pregnancy”, “Pregnant women”, “lactation”, “vaccination in pregnant and lactating women”, “obstetrics”, “midwife” y “vertical transmission”. No se establecieron límites temporales ya que se trata de una enfermedad reciente. Se han filtrado por artículos publicados en español, inglés y gallego. Resultados: Se explica el circuito de control de atención primaria y hospitalaria del embarazo, parto y posparto en el hospital de A Coruña durante la pandemia. Conclusiones: Tras comparar la experiencia en hospital de A Coruña y atención primaria con los artículos y guías encontradas sobre el manejo y recomendaciones de las gestantes durante la pandemia de la covid-19, se observó que las actuaciones llevadas a cabo se ajustaron a las recomendaciones en ese momento y tras investigaciones posteriores del Covid se modificaron para dar una mejor asistencia a las gestantes. Es necesario la realización de nuevos estudios para corroborar que el manejo y las recomendaciones actuales son adecuadas. (AU)

Objective: To describe the follow-up and delivery care of pregnant women during the Covid-19 pandemic at the Hospital of A Coruña. Compile evidence and scientific recommendations in the follow-up of pregnant women during the Covid-19 pandemic Method: A bibliographic search has been carried out in databases such as Medline, Cochrane and CUIDEN, as well as in websites: WHO, the Ministry of Health and SERGAS. The MeSH terms have been used: “Covid-19”, “Pregnancy”, “Pregnant women”, “lactation”, “vaccination in pregnant and lactating women”, “obstetrics”, “midwife” and “vertical transmission”. We have not established time limits because it is a recent illness. They have been filtered by articles published in Spanish, English and Galician. Results: The primary and hospital care control circuit for pregnancy, childbirth and postpartum in the A Coruña hospital during the pandemic is explained. Conclusions: After comparing the experience in the A Coruña hospital and primary care with the articles and guides found on the management and recommendations of pregnant women during the covid-19 pandemic, it was observed that the actions carried out were in line with the recommendations in that time and after subsequent investigations of the Covid, they were modified to provide better assistance to pregnant women. It is necessary to carry out new studies to corroborate that the current management and recommendations are adequate. (AU)

Radix entomolaris: A morphological variable of human dentition with anthropological relevance. A study on a Chilean population.

The existence of a third root in the mandibular first molars may have implications for certain dental treatments; however, its greatest relevance could be in anthropological and forensic sciences, because its prevalence varies significantly according to ethnic groups. The purpose of this research was to determine the prevalence of radix entomolaris (RE) in a sample of Chilean people. A random sample of 1330 digital periapical radiographs of endodontically treated mandibular first molars (551 males and 779 females, aged between 18 and 87 years) were evaluated. The prevalence of RE, its distribution by sex and root canal lengths were determined. Evidence demonstrated that the formation of RE is associated with ancestry and its frequency is variable according to populations studied, being more frequent in Asians and Native Americans. The prevalence of RE in the studied people was 3.16%, similar to frequencies reported in European individuals (3.4%-4.2%). The 61.90% of RE were located at the right side of the mandible and 38.10% at the left side. The average working length of RE was 19.52 mm. No statistically significant differences in frequencies were observed by sex (p = 0.19). The prevalence of RE varies among continental population groups. However, due to human migration, the frequency of this physical trait could be modified in specific geographic regions. The observed prevalence of RE in the study group was similar to the prevalence ranges observed for European ancestry populations and it was considerably lower than the data reported for non-Europeans. The absence of sexual dimorphism is consistent with results of previous studies performed worldwide.

Intervención basada en mindfulness a través de una app móvil para personas con cáncer colorrectal en espera de cirugía: ensayo clínico aleatorizado / Mindfulness based intervention through mobile app for colorectal cancer people awaiting surgery: A randomized clinical trial

Introducción: El cáncer colorrectal representa el tercer cáncer con mayor incidencia en ambos sexos. Un tercio de los pacientes con cáncer experimentan sintomatología ansiosa o depresiva. El objetivo de este estudio fue evaluar la eficacia de una intervención de reducción de estrés basada en mindfulness a través de una aplicación móvil (En calma en el quirófano). Método: Es un ensayo controlado, aleatorizado, con evaluador ciego y multicéntrico, que compara la eficacia de una aplicación de entrenamiento en mindfulness para móviles (rama experimental) con tratamiento habitual (rama control), en 3tiempos de medida (T0 o línea base, T1 o alta a domicilio, T2 o un mes tras cirugía). Se evaluó la sintomatología ansiosa y depresiva (HADS), la calidad de vida (WHOQOL), la escala de dolor (EVA) y la escala de satisfacción (CSQ). Resultados: Hubo un total de 270 derivaciones. Fueron analizadas 82 personas: 39 personas utilizaron la app y 43 continuaron su tratamiento habitual. No hubo cambios significativos entre grupos ni tiempos de medida. Se observó una ligera tendencia en la que el grupo experimental tuvo menos síntomas de depresión y ansiedad entre T0 y T2 (B?= −0,2; IC 95%: 8,8-9,2). Conclusiones: Nuestra población mostraba una edad media alta (65 años), niveles bajos de ansiedad y depresión, y niveles medios de calidad de vida en T0. Estos factores podrían haber interactuado y limitado la eficacia de la app. Nuevas líneas de investigación tienen que ir dirigidas a evaluar la eficacia de las apps para pacientes con enfermedades quirúrgicas en poblaciones más jóvenes. (AU)

Introduction: Colorectal cancer is the third most common cancer worldwide that occurs both in men and women. Around one-third of patients with cancer will suffer from anxiety or depression symptoms. The aim of this study was to evaluate the effectiveness of a mindfulness-based stress reduction intervention through a mobile application («en calma en el quirófano»). Method: This study is a multicenter, single-blind (evaluator), controlled, randomized trial that compares the effectiveness of a mindfulness training through a mobile application (intervention group) and treatment as usual (control group) in 3different moments (T0 or baseline, T1 or hospital discharge and T2 or one month after surgery). Hospital Anxiety and depression Scale (HADS), quality of life (WHOQOL), pain (VAS) and satisfaction (CSQ) were assessed. Results: In all, there were 270 referred patients. Among them, 39 and 43 were assigned to the intervention and control groups respectively; 82 patients were analyzed: 39 patients used the app, and 43 patients continued with the treatment as usual. There were no significant changes between groups and time. We observed a slight trend in which intervention group had less depression and anxiety symptoms since T0 and T2 (B=−0.2; 95% CI: 8.8-9.2). Conclusions: The sample of this study had a high mean age (65 years old), and low levels of anxiety and depression and medium levels of pre-surgery quality of life in baseline. These factors could have influenced limiting the effectiveness of the app. Prospective research lines should focus on evaluating the effectiveness of mobile applications for younger patients with surgical pathologies. (AU)

The Dual PDE7-GSK3ß Inhibitor, VP3.15, as Neuroprotective Disease-Modifying Treatment in a Model of Primary Progressive Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic, inflammatory, autoimmune and degenerative disease with axonal damage and demyelination as its main features. Its dual neurological and autoimmune nature makes it a disease that is difficult to treat. Treatments that simultaneously stop the immune response while protecting and repairing the nervous system are urgent. That is of utmost importance for the primary progressive multiple sclerosis (PPMS), a rare and severe variant of MS, characterized by worsening neurological function from the onset of symptoms. In this sense, inhibitors of glycogen synthase kinase 3ß (GSK3ß) and phosphodiesterase 7 (PDE7) have recently shown great therapeutic potential for the treatment of demyelinating diseases. Here we investigated a dual inhibitor of these two targets, the small molecule VP3.15, in a preclinical model, which resembles primary-progressive MS (PPMS), the Theiler's mouse encephalomyelitis virus-induced demyelinated disease (TMEV-IDD). In our study, VP3.15 ameliorates the disease course improving motor deficits of infected mice. Chronic treatment with VP3.15 also showed significant efficacy in the immunomodulation process, as well as in the proliferation and differentiation of oligodendroglial precursors, improving the preservation of myelin and axonal integrity. Therefore, our results support a treatment with the safe VP3.15 as an integrative therapeutic strategy for the treatment of PPMS.