Cannabinoid type 2 receptor inhibition enhances the antidepressant and proneurogenic effects of physical exercise after chronic stress.

Chronic stress is a major risk factor for neuropsychiatric conditions such as depression. Adult hippocampal neurogenesis (AHN) has emerged as a promising target to counteract stress-related disorders given the ability of newborn neurons to facilitate endogenous plasticity. Recent data sheds light on the interaction between cannabinoids and neurotrophic factors underlying the regulation of AHN, with important effects on cognitive plasticity and emotional flexibility. Since physical exercise (PE) is known to enhance neurotrophic factor levels, we hypothesised that PE could engage with cannabinoids to influence AHN and that this would result in beneficial effects under stressful conditions. We therefore investigated the actions of modulating cannabinoid type 2 receptors (CB2R), which are devoid of psychotropic effects, in combination with PE in chronically stressed animals. We found that CB2R inhibition, but not CB2R activation, in combination with PE significantly ameliorated stress-evoked emotional changes and cognitive deficits. Importantly, this combined strategy critically shaped stress-induced changes in AHN dynamics, leading to a significant increase in the rates of cell proliferation and differentiation of newborn neurons, overall reduction in neuroinflammation, and increased hippocampal levels of BDNF. Together, these results show that CB2Rs are crucial regulators of the beneficial effects of PE in countering the effects of chronic stress. Our work emphasises the importance of understanding the mechanisms behind the actions of cannabinoids and PE and provides a framework for future therapeutic strategies to treat stress-related disorders that capitalise on lifestyle interventions complemented with endocannabinoid pharmacomodulation.

Artificial light impairs local attraction to females in male glow-worms.

The negative effects of artificial lighting at night (ALAN) on insects are increasingly recognised and have been postulated as one possible cause of declines in insect populations. Yet, the behavioural mechanisms underpinning ALAN effects on insects remain unclear. ALAN interferes with the bioluminescent signal female glow-worms use to attract males, disrupting reproduction. To determine the behavioural mechanisms that underpin this effect of ALAN, we quantified the effect of white illumination on males' ability to reach a female-mimicking LED within a Y-maze. We show that as the intensity of illumination increases, the proportion of males reaching the female-mimicking LED declines. Brighter illumination also increases the time taken by males to reach the female-mimicking LED. This is a consequence of males spending more time: (i) in the central arm of the Y-maze; and (ii) with their head retracted beneath their head shield. These effects reverse rapidly when illumination is removed, suggesting that male glow-worms are averse to white light. Our results show that ALAN not only prevents male glow-worms from reaching females, but also increases the time they take to reach females and the time they spend avoiding exposure to light. This demonstrates that the impacts of ALAN on male glow-worms extend beyond those previously observed in field experiments, and raises the possibility that ALAN has similar behavioural impacts on other insect species that remain undetected in field experiments.

Implementation Status of the Proposal for a Regulation of the European Health Data Space in Portugal: Are We Ready for It?

The European Health Data Space (EHDS) proposal aims to establish a set of rules and governance frameworks to promote the use of electronic health data for both primary and secondary purposes. This study aims at analysing the implementation status of the EHDS proposal in Portugal, particularly the points concerning the primary use of health data. The proposal was scanned for the points that gave member states a direct responsibility to implement actions, and a literature review and interviews were conducted to assess the implementation status of these policies in Portugal This study found that Portugal is well advanced in the implementation of policies concerning the rights of natural persons in relation to the primary use of their personal health data, but also identified challenges, which include the lack of a common interoperability framework for the exchange of electronic health data.

A systematic review of natural products for skin applications: Targeting inflammation, wound healing, and photo-aging.

BACKGROUND: Every day the skin is constantly exposed to several harmful factors that induce oxidative stress. When the cells are incapable to maintain the balance between antioxidant defenses and reactive oxygen species, the skin no longer can keep its integrity and homeostasis. Chronic inflammation, premature skin aging, tissue damage, and immunosuppression are possible consequences induced by sustained exposure to environmental and endogenous reactive oxygen species. Skin immune and non-immune cells together with the microbiome are essential to efficiently trigger skin immune responses to stress. For this reason, an ever-increasing demand for novel molecules capable of modulating immune functions in the skin has risen the level of their development, particularly in the field of natural product-derived molecules. PURPOSE: In this review, we explore different classes of molecules that showed evidence in modulate skin immune responses, as well as their target receptors and signaling pathways. Moreover, we describe the role of polyphenols, polysaccharides, fatty acids, peptides, and probiotics as possible treatments for skin conditions, including wound healing, infection, inflammation, allergies, and premature skin aging. METHODS: Literature was searched, analyzed, and collected using databases, including PubMed, Science Direct, and Google Scholar. The search terms used included "Skin", "wound healing", "natural products", "skin microbiome", "immunomodulation", "anti-inflammatory", "antioxidant", "infection", "UV radiation", "polyphenols", "polysaccharides", "fatty acids", "plant oils", "peptides", "antimicrobial peptides", "probiotics", "atopic dermatitis", "psoriasis", "auto-immunity", "dry skin", "aging", etc., and several combinations of these keywords. RESULTS: Natural products offer different solutions as possible treatments for several skin conditions. Significant antioxidant and anti-inflammatory activities were reported, followed by the ability to modulate immune functions in the skin. Several membrane-bound immune receptors in the skin recognize diverse types of natural-derived molecules, promoting different immune responses that can improve skin conditions. CONCLUSION: Despite the increasing progress in drug discovery, several limiting factors need future clarification. Understanding the safety, biological activities, and precise mechanisms of action is a priority as well as the characterization of the active compounds responsible for that. This review provides directions for future studies in the development of new molecules with important pharmaceutical and cosmeceutical value.

Water quality predictions through linear regression - A brute force algorithm approach.

Linear regression is one of the oldest statistical modeling approaches. Still, it is a valuable tool, particularly when it is necessary to create forecast models with low sample sizes. When researchers use this method and have numerous potential regressors, choosing the group of regressors for a model that fulfills all the required assumptions can be challenging. In this sense, the authors developed an open-source Python script that automatically tests all the combinations of regressors under a brute-force approach. The output displays the best linear regression models, regarding the thresholds set by users for the required assumptions: statistical significance of the estimations, multicollinearity, error normality, and homoscedasticity. Further, the script allows the selection of linear regressions with regression coefficients according to the user's expectations. This script was tested with an environmental dataset to predict surface water quality parameters based on landscape metrics and contaminant loads. Among millions of possible combinations, less than 0.1 % of the regressor combinations fulfilled the requirements. The resulting combinations were also tested in geographically weighted regression, with similar results to linear regression. The model's performance was higher for pH and total nitrate and lower for total alkalinity and electrical conductivity.•A Python script was developed to find the best linear regressions within a dataset.•Output regressions are automatically selected based on regression coefficient expectations set by the user and the linear regression assumptions.•The algorithm was successfully validated through an environmental dataset.

Musical and psychomotor interventions for cognitive, sensorimotor, and cerebral decline in patients with Mild Cognitive Impairment (COPE): a study protocol for a multicentric randomized controlled study.

BACKGROUND: Regular cognitive training can boost or maintain cognitive and brain functions known to decline with age. Most studies administered such cognitive training on a computer and in a lab setting. However, everyday life activities, like musical practice or physical exercise that are complex and variable, might be more successful at inducing transfer effects to different cognitive domains and maintaining motivation. "Body-mind exercises", like Tai Chi or psychomotor exercise, may also positively affect cognitive functioning in the elderly. We will compare the influence of active music practice and psychomotor training over 6 months in Mild Cognitive Impairment patients from university hospital memory clinics on cognitive and sensorimotor performance and brain plasticity. The acronym of the study is COPE (Countervail cOgnitive imPairmEnt), illustrating the aim of the study: learning to better "cope" with cognitive decline. METHODS: We aim to conduct a randomized controlled multicenter intervention study on 32 Mild Cognitive Impairment (MCI) patients (60-80 years), divided over 2 experimental groups: 1) Music practice; 2) Psychomotor treatment. Controls will consist of a passive test-retest group of 16 age, gender and education level matched healthy volunteers. The training regimens take place twice a week for 45 min over 6 months in small groups, provided by professionals, and patients should exercise daily at home. Data collection takes place at baseline (before the interventions), 3, and 6 months after training onset, on cognitive and sensorimotor capacities, subjective well-being, daily living activities, and via functional and structural neuroimaging. Considering the current constraints of the COVID-19 pandemic, recruitment and data collection takes place in 3 waves. DISCUSSION: We will investigate whether musical practice contrasted to psychomotor exercise in small groups can improve cognitive, sensorimotor and brain functioning in MCI patients, and therefore provoke specific benefits for their daily life functioning and well-being. TRIAL REGISTRATION: The full protocol was approved by the Commission cantonale d'éthique de la recherche sur l'être humain de Genève (CCER, no. 2020-00510) on 04.05.2020, and an amendment by the CCER and the Commission cantonale d'éthique de la recherche sur l'être humain de Vaud (CER-VD) on 03.08.2021. The protocol was registered at clinicaltrials.gov (20.09.2020, no. NCT04546451).

Phagocytotic activity and gene expression of leukocytes isolated from Astyanax lacustris.

The constant intensification of aquaculture has considerable increased the stress levels of farmed fish and, consequently, the number and intensity of diseases outbreaks. Thus, studies on fish immune response, especially regarding the interaction of fish leukocytes with potential pathogens and xenobiotics are of great importance in order to develop new prophylactic and curative strategies. We isolated leukocytes from the head kidney of Astyanax lacustris-an important Neotropical fish species for aquaculture and a potential model for Neotropical aquaculture research-using a Percoll centrifugation protocol. The isolated leukocytes were incubated with lipopolysaccharide (LPS), and the expression of genes IL-1ß, IL-8, LysC, and LysG were measured. We assessed the phagocytotic activity of leukocytes using Congo red-dyed yeast, a novel and cost-effective protocol that has been developed in this study. The isolated leukocytes responded to LPS induction, exhibiting strong IL-1ß and IL-8 upregulation, two of the most important pro-inflammatory interleukins for vertebrates immune reponse. The optimal concentration of yeast for the phagocytic assay was 106 cells mL-1, resulting in acceptable phagocytic capacity (PC) but without excess of yeasts during the counting process, ensuring a high precision and accuracy of the method. To the best of our knowledge, the present study is the first to investigate the in vitro gene expression and phagocytic activity of leukocytes isolated from A. lacustris. Our findings will serve as a reference for future studies on the immunology and toxicology of Neotropical fish.

Precision technologies for predictive diagnosis and study of the allometric growth of broiler chickens with breast myopathies.

1. An experiment was carried out to validate techniques as predictive diagnostic tools for breast myopathies and to study the allometric growth of distinct parts of the body and meat quality of broilers.2. Infrared thermography was performed at 35 d of age. The surface temperatures of breasts of 300 birds were recorded, followed by ultrasound imaging.3. The birds were slaughtered and the cuts were made to weigh the body parts. Then, the breasts were evaluated as for the presence and severity of myopathies, from which nine treatments were established represented by the associated degrees of the myopathies white striping and wooden breast and breasts classified as normal.4. There was no difference in surface temperatures and echogenicity values between normal breasts and breasts affected by myopathies. At 35 d of age few fillets classified as normal were found.5. The breast showed late growth in relation to the body, regardless of characteristic lesions of myopathies. The most severe score of wooden breast affected meat quality variables.

Anaesthesia in a parturient with systemic mastocytosis.

Mastocytosis is characterized by clonal expansion of mast cells, with abnormal accumulation in different organs. Perioperatively, numerous stimuli may lead to the release of vasoactive substances by mast cells. Parturients with systemic mastocytosis pose a challenge to the anesthesiologist: on one hand, the pain and stress of labor may lead to greater mast cell activation and, on the other, the administration of drugs that may possibly trigger the release of mast cell mediators. The authors describe a case of a 34-year-old pregnant woman with systemic mastocytosis who requests labor analgesia. An epidural analgesia was performed after induction of labor, after considering anesthetic particularities. The epidural procedure, labor and delivery were uneventful. A review of systemic mastocytosis is provided and its anesthetic considerations are discussed.

Consideraciones anestésicas en una parturienta con mastocitosis sistémica / Anesthetic considerations in a laboring woman with systemic mastocytosis

La mastocitosis se caracteriza por la expansión clónica de mastocitos, con acumulación anormal en diferentes órganos. Perioperatoriamente, numerosos estímulos pueden originar la liberación de sustancias vasoactivas por parte de los mastocitos. Las parturientas con mastocitosis sistémica plantean una dificultad al anestesiólogo: por un lado, el dolor y el estrés del parto pueden causar una mayor activación de los mastocitos y, por otro, la administración de fármacos puede desencadenar posiblemente la liberación de mediadores de los mastocitos. Los autores describen un caso de una embarazada de 34 años de edad con mastocitosis sistémica que solicita analgesia para el parto. Se realizó analgesia epidural tras la inducción del parto, una vez consideradas las particularidades anestésicas. El procedimiento epidural, el parto y la expulsión transcurrieron sin incidentes. Se aporta una revisión de la mastocitosis sistémica y se abordan sus consideraciones anestésicas.(AU)

Mastocytosis is characterized by clonal expansion of mast cells, with abnormal accumulation in different organs. Perioperatively, numerous stimuli may lead to the release of vasoactive substances by mast cells. Parturients with systemic mastocytosis pose a challenge to the anesthesiologist: on one hand, the pain and stress of labor may lead to greater mast cell activation and, on the other, the administration of drugs that may possibly trigger the release of mast cell mediators. The authors describe a case of a 34-year-old pregnant woman with systemic mastocytosis who requests labor analgesia. An epidural analgesia was performed after induction of labor, after considering anesthetic particularities. The epidural procedure, labor and delivery were uneventful. A review of systemic mastocytosis is provided and its anesthetic considerations are discussed.(AU)

Efficacy assessment of different time cycles of nebulized hydrogen peroxide against bacterial and yeast biofilms.

BACKGROUND: The prevention of healthcare-associated infections requires continuous effort. In order to achieve better practical results, the control of environmental microbial biofilms with effective disinfection strategies should be addressed. AIM: To test the efficacy of different time cycles of nebulized hydrogen peroxide (H2O2) against bacterial and yeast dry biofilms. METHODS: The efficacies of a standard cycle (SC) and a fast cycle (FC) of nebulized H2O2 were compared. Microbial biofilms were grown on different material coupons. The metabolic activity of biofilms was determined by XTT assay, and the total biomass of biofilms was determined by crystal violet assay. FINDINGS: Regarding the efficacy of nebulized H2O2 against biofilms, the mean reduction in metabolic activity for the SC was 55.2% [standard deviation (SD) 19.4%], compared with 50.4% (SD 17.7%) for the FC. The mean reduction in total biomass for the SC was 45.5% (SD 22.7%), compared with 46.7% (SD 21.7%) for the FC. No significant differences were found between the tested cycles and materials. CONCLUSION: H2O2 nebulization was found to exhibit good efficacy against healthcare-associated microbial dry biofilms. Moreover, similar efficacies were found between the SC and the FC.

Diretriz Latino-americana sobre o Diagnóstico e Tratamento da Alergia Ocular ­ Em nome da Sociedade Latinoamericana de Alergia, Asma e Imunologia (SLAAI) / Latin American Guideline on the Diagnosis and Treatment of Ocular Allergy ­ On behalf of the Latin American Society of Allergy, Asthma and Immunology (SLAAI)

A alergia ocular, também conhecida como conjuntivite alérgica (CA), é uma reação de hipersensibilidade mediada por imunoglobulina E (IgE) do olho desencadeada por aeroalérgenos, principalmente ácaros da poeira doméstica e pólen de gramíneas. Os sintomas geralmente consistem em prurido ocular ou periocular, lacrimejamento e olhos vermelhos que podem estar presentes durante todo o ano ou sazonalmente. A alergia ocular tem frequência elevada, é subdiagnosticada e pode ser debilitante para o paciente. É potencialmente danosa para a visão, nos casos em que ocasiona cicatrização corneana grave, e na maioria dos pacientes associa-se a outros quadros alérgicos, principalmente rinite, asma e dermatite atópica. É classificada em conjuntivite alérgica perene, conjuntivite alérgica sazonal, ceratoconjuntivite atópica e ceratoconjuntivite vernal. O diagnóstico procura evidenciar o agente etiológico e a confirmação se dá pela realização do teste de provocação conjuntival. O tratamento baseia-se em evitar o contato com os desencadeantes, lubrificação, anti-histamínicos tópicos, estabilizadores de mastócitos, imunossupressores e imunoterapia específica com o objetivo de obter o controle e prevenir as complicações da doença.

Ocular allergy, also known as allergic conjunctivitis, is an immunoglobulin E-mediated hypersensitivity reaction of the eye triggered by airborne allergens, primarily house dust mites and grass pollen. Symptoms usually consist of ocular or periocular itching, watery eyes, and red eyes that may be present year-round or seasonally. Ocular allergy has a high frequency, is underdiagnosed, and can be debilitating for the patient. It is potentially harmful to vision in cases of severe corneal scarring, and in most patients, it is associated with other allergic conditions, especially rhinitis, asthma, and atopic dermatitis. It is classified as perennial allergic conjunctivitis, seasonal allergic conjunctivitis, atopic keratoconjunctivitis, and vernal keratoconjunctivitis. Diagnosis seeks to identify the etiologic agent, and confirmation is given by conjunctival provocation testing. Treatment is based on avoiding contact with triggers, lubrication, topical antihistamines, mast cell stabilizers, immunosuppressants, and specific immunotherapy with the aim of achieving control and preventing disease complications.

Treatment of fruit processing wastewater by electrochemical and activated persulfate processes: Toxicological and energetic evaluation.

A fruit processing wastewater was submitted to different advanced oxidation processes, namely, electro-Fenton (EF), electrochemical oxidation (EO), activated persulfate (PS), and combined EF/PS. The performance of the treatment processes, at different experimental conditions, regarding organic load removal, biodegradability increment, toxicity reduction, and specific energy consumption (Esp), was evaluated. At the experimental conditions studied, EO led to the treated solutions with the highest biodegradability increment, from 0.24 to 0.48, and toxicity reduction towards Daphnia magna, from 5.8 to 1.5 toxic units, without requiring the addition of chemicals. Nevertheless, the highest chemical oxygen demand (COD) removals were obtained for EF and combined EF/PS treatments. For the electrochemical processes, an increase in COD removal rate with applied current density (j) was observed. However, the increase in j substantially raised the Esp. In PS treatment, COD removals above 80% were only achieved for high amounts of added persulfate and iron, which led to less biodegradable and more toxic solutions. Combined EF/PS attained the lowest Esp values, mainly due to the conductivity increase originated by the persulfate and iron salts addition. Besides the disadvantage of the chemicals added, this combined treatment led to treated solutions with very acidic pH and significant iron content.

The power of feeling seen: perspectives of individuals with eating disorders on receiving validation.

BACKGROUND: A common complaint of individuals suffering from mental health conditions is feeling invalidated or misunderstood by care providers. This is notable, given that non-collaborative care has been linked to poor engagement, low motivation and treatment non-adherence. This study examined how receiving validation from care providers is experienced by individuals who have an eating disorder (ED) and the impact of receiving validation on the recovery journey. METHODS: Eighteen individuals who had an eating disorder for an average duration of 19.1 years (two identifying as male, 16 identifying as female), participated in semi-structured interviews on barriers and facilitators to self-compassion. Seven were fully recovered, and 11 were currently participating in recovery-focused residential treatment. Thematic analysis focused on the meaning and impact of receiving validation to participants. RESULTS: Five care provider actions were identified: (i) making time and space for me, (ii) offering a compassionate perspective, (iii) understanding and recognizing my treatment needs, (iv) showing me I can do this, and (v) walking the runway. These were associated with four key experiences (feeling trust, cared for, empowered, and inspired), that participants described as supportive of their recovery. CONCLUSIONS: This research provides insight into patient perspectives of validation and strategies care providers can use, such as compassionate reframing of difficult life experiences, matching interventions to patient readiness, and modeling vulnerability.

Feeling validated (or feeling understood and accepted) is an important aspect of a patient's experience with health care providers. The purpose of this research was to learn about the role of validation in eating disorders treatment from patients' perspectives, and to learn how the experience of validation supports recovery from an eating disorder. In this research, interviews were conducted with eighteen individuals who were either currently seeking intensive treatment for an eating disorder or had recently recovered. Five care provider actions were identified as engendering feelings of validation: (i) making time and space for me, (ii) offering a compassionate perspective, (iii) understanding and recognizing my treatment needs, (iv) showing me I can do this, and (v) walking the runway. These actions were associated with four key patient experiences: feeling trust, cared for, empowered, and inspired. Recommendations for care providers to practice validation are made based on study findings.

Incidence of completed suicide and suicide attempts in a global prospective study of Huntington's disease.

BACKGROUND: Risk of death from suicide in Huntington's disease is notably elevated relative to that in the general population, although the incidence within HD populations has not been precisely defined. Robust incidence estimates of suicidal behavior can serve as references for HD therapeutic research and post-marketing surveillance to help evaluate the suicidality risk of novel therapeutics. AIMS: To estimate the incidence rate of completed suicide and suicide attempt in the global, prospective HD cohort study Enroll-HD that records these events per protocol. METHOD: A total of 20 912 participants were available for analysis (HD gene-expansion carriers (HDGECs) n = 15 924; non-HDGECs n = 4988) representing a collective observation period of 53 390 participant-years. Each observed event was subject to clinical review and evaluation. We generated incidence rates (events per 100 000 person-years) for suicides and suicide attempts using all available data, as well as by year of study and geographical region. Proportionate mortality statistics for suicide and respective 95% confidence intervals were also generated. RESULTS: The overall incidence rate of suicide in HDGECs was 72 per 100 000 person-years, and 8 per 100 000 person-years in non-HDGECs. Proportionate mortality attributable to suicide in HDGECs was 4.6%. For suicide attempts, the global overall incidence rate observed in HDGECs was 306-375 per 100 000 person-years, and 23-38 per 100 000 person-years in non-HDGECs. CONCLUSIONS: The incidence estimates calculated here can be used as a reference to help evaluate drug safety and may also be useful in assessing progress in clinical care for HDGECs once therapeutic interventions become widely available.