Psychological symptoms and brain activity alterations in women with PCOS and their relation to the reduced quality of life: a narrative review.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common feminine endocrine disorder, characterized by androgen excess, ovulatory dysfunction, and polycystic ovarian morphology. The negative impact of symptoms on the quality of life (QoL) of patients is still not clear. PURPOSE: The present review aimed at studying the impact of the symptoms, the psychological symptoms, and brain alterations in women with PCOS. METHODS: A systematic search was undertaken for studies that assessed the impact of PCOS symptoms on QoL, psychological symptoms, and brain alterations in PCOS patients. RESULTS: Most of the information about QoL came from psychometric studies, which used culture-based questionnaires. Alterations of sleep quality, body image, and mood disorders can negatively affect the QoL of the patients. Sexual satisfaction and desire were affected by PCOS. Brain imaging studies showed functional alterations that are associated with impairments of visuospatial working memory, episodic and verbal memory, attention, and executive function. CONCLUSIONS: Several factors can negatively influence the quality of life of the patients, and they are directly related to hyperandrogenism and the risk of infertility. In particular, obesity, hirsutism, acne, and the fear of infertility can have a direct impact on self-esteem and sexual function. Metabolic and psychiatric comorbidities, such as mood, anxiety, and eating disorders, can affect the well-being of the patients. Moreover, specific cognitive alterations, such as impairments in attention and memory, can limit PCOS patients in a series of aspects of daily life.

Developing a core outcome set for clinical trials in olfactory disorders: a COMET initiative.

STATEMENT OF PROBLEM: Evaluating the effectiveness of the management of Olfactory Dysfunction (OD) has been limited by a paucity of high-quality randomised and/or controlled trials. A major barrier is heterogeneity of outcomes in such studies. Core outcome sets (COS) - standardized sets of outcomes that should be measured/reported as determined by consensus-would help overcome this problem and facilitate future meta-analyses and/or systematic reviews (SRs). We set out to develop a COS for interventions for patients with OD. METHODS: A long-list of potential outcomes was identified by a steering group utilising a literature review, thematic analysis of a wide range of stakeholders' views and systematic analysis of currently available Patient Reported Outcome Measures (PROMs). A subsequent e-Delphi process allowed patients and healthcare practitioners to individually rate the outcomes in terms of importance on a 9-point Likert scale. RESULTS: After 2 rounds of the iterative eDelphi process, the initial outcomes were distilled down to a final COS including subjective questions (visual analogue scores, quantitative and qualitative), quality of life measures, psychophysical testing of smell, baseline psychophysical testing of taste, and presence of side effects along with the investigational medicine/device and patient's symptom log. CONCLUSIONS: Inclusion of these core outcomes in future trials will increase the value of research on clinical interventions for OD. We include recommendations regarding the outcomes that should be measured, although future work will be required to further develop and revalidate existing outcome measures.

Position paper on olfactory dysfunction: 2023

BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

Obesity status and obesity-associated gut dysbiosis effects on hypothalamic structural covariance.

BACKGROUND: Functional connectivity alterations in the lateral and medial hypothalamic networks have been associated with the development and maintenance of obesity, but the possible impact on the structural properties of these networks remains largely unexplored. Also, obesity-related gut dysbiosis may delineate specific hypothalamic alterations within obese conditions. We aim to assess the effects of obesity, and obesity and gut-dysbiosis on the structural covariance differences in hypothalamic networks, executive functioning, and depressive symptoms. METHODS: Medial (MH) and lateral (LH) hypothalamic structural covariance alterations were identified in 57 subjects with obesity compared to 47 subjects without obesity. Gut dysbiosis in the subjects with obesity was defined by the presence of high (n = 28) and low (n = 29) values in a BMI-associated microbial signature, and posthoc comparisons between these groups were used as a proxy to explore the role of obesity-related gut dysbiosis on the hypothalamic measurements, executive function, and depressive symptoms. RESULTS: Structural covariance alterations between the MH and the striatum, lateral prefrontal, cingulate, insula, and temporal cortices are congruent with previously functional connectivity disruptions in obesity conditions. MH structural covariance decreases encompassed postcentral parietal cortices in the subjects with obesity and gut-dysbiosis, but increases with subcortical nuclei involved in the coding food-related hedonic information in the subjects with obesity without gut-dysbiosis. Alterations for the structural covariance of the LH in the subjects with obesity and gut-dysbiosis encompassed increases with frontolimbic networks, but decreases with the lateral orbitofrontal cortex in the subjects with obesity without gut-dysbiosis. Subjects with obesity and gut dysbiosis showed higher executive dysfunction and depressive symptoms. CONCLUSIONS: Obesity-related gut dysbiosis is linked to specific structural covariance alterations in hypothalamic networks relevant to the integration of somatic-visceral information, and emotion regulation.

Digital technologies and implications for Veterinary Services.

The pace of digital disruption over the past few years has been spectacular, transforming every sector of the economy, including animal production, health and welfare. This paper reviews some advanced digital technologies that may shape the future of Veterinary Services. These technologies are all data driven and are illustrated by three examples that fall under the following categories: a) wireless and mobile technologies for animal health monitoring, disease surveillance, reporting and information sharing; b) advanced data-processing technologies, such as big data and data analytics used to detect patterns, make predictions, find correlations and other information; and c) promising technologies such as blockchain applications, used for effective and efficient management of various input supply chains. The authors briefly discuss current challenges to increasing the use of these technologies in the animal health sector, along with some implications for Veterinary Services. Digital technologies will have a profound effect on how animal health services are delivered and how animal health systems are managed. It is therefore crucial for Veterinary Services to be proactive and adapt to the ongoing digital transformation. Investment in new technologies and preparing the current and future veterinary workforce with the necessary digital skills and knowledge to stay up to date and at the centre of digital innovation in animal health should be a priority for the years to come.

L'accélération de la perturbation numérique depuis quelques années est spectaculaire, transformant tous les secteurs de l'économie, y compris la production animale, la santé animale et le bien-être des animaux. Les auteurs s'intéressent à certaines technologies numériques de pointe qui pourraient influencer le devenir des Services vétérinaires. Toutes ces technologies sont orientées données et trouvent leur illustration dans trois exemples qui se répartissent dans les catégories suivantes : a) les technologies sans fil et mobiles appliquées au suivi de la santé animale, à la surveillance des maladies, aux notifications des foyers et à l'échange d'informations ; b) les technologies avancées de traitement des données, dont les mégadonnées et l'analytique de données qui servent à mettre en évidence des structures sous-jacentes, à extraire des schémas prédictifs, à relever des corrélations et à générer d'autres informations ; c) des technologies prometteuses comme les applications « blockchain ¼ (chaînes de blocs) utilisées pour une gestion efficace et efficiente de diverses chaînes d'approvisionnement en intrants. Les auteurs résument brièvement les défis actuels associés au recours accru à ces technologies dans le secteur de la santé animale et en font ressortir certaines répercussions sur les Services vétérinaires. Les technologies numériques vont profondément affecter les modalités de la prestation des services de santé animale ainsi que la gestion des systèmes de santé animale. Par conséquent, il est crucial que les Services vétérinaires anticipent cette évolution et s'adaptent à la transformation numérique en cours. L'investissement dans les nouvelles technologies et les efforts visant à doter les professionnels vétérinaires actuels et futurs des compétences et des connaissances numériques nécessaires pour rester informés et au centre de l'innovation numérique dans le domaine de la santé animale doivent être les priorités des prochaines années.

De unos años a esta parte, el universo digital viene cambiando a un ritmo espectacular y transformando a su estela todos los sectores de la economía, lo que incluye la producción, la sanidad y el bienestar animales. Los autores pasan revista a algunas avanzadas tecnologías digitales que pueden determinar el porvenir de los Servicios Veterinarios. Para ilustrar estas tecnologías, todas ellas basadas en el uso de datos, ofrecen tres ejemplos correspondientes a otras tantas categorías: a) dispositivos móviles e inalámbricos de seguimiento zoosanitario, vigilancia de enfermedades, notificación e intercambio de información; b) tecnologías avanzadas de tratamiento de datos, como las de macrodatos o las de análisis de datos empleadas para descubrir patrones ocultos, efectuar predicciones, determinar correlaciones u obtener otro tipo de información; y c) tecnologías prometedoras, como las aplicaciones de cadena de bloques utilizadas para gestionar con eficacia y eficiencia varias cadenas de suministro de insumos. Los autores examinan someramente las dificultades que existen actualmente para aplicar en mayor medida estas tecnologías en el sector de la sanidad animal, así como algunas de las consecuencias que traen consigo para los Servicios Veterinarios. Las tecnologías digitales tendrán un profundo efecto en los modos de prestación de servicios zoosanitarios y de gestión de los sistemas de sanidad animal. Por ello es crucial que los Servicios Veterinarios tomen la iniciativa y se adapten a la transformación digital que ya está en curso. Para los años venideros la prioridad debería cifrarse en invertir en nuevas tecnologías y en aportar al personal veterinario del presente y del futuro los conocimientos teóricos y prácticos sobre cuestiones digitales que necesita no solo para mantenerse al día, sino también para protagonizar la innovación digital en el terreno de la sanidad animal.

Essential oils from Ocimum basilicum cultivars: analysis of their composition and determination of the effect of the major compounds on Haemonchus contortus eggs.

The continuous use of synthetic anthelmintics against gastrointestinal nematodes (GINs) has resulted in the increased resistance, which is why alternative methods are being sought, such as the use of natural products. Plant essential oils (EOs) have been considered as potential products for the control of GINs. However, the chemical composition and, consequently, the biological activity of EOs vary in different plant cultivars. The aim of this study was to evaluate the anthelmintic activity of EOs from cultivars of Ocimum basilicum L. and that of their major constituents against Haemonchus contortus. The EOs from 16 cultivars as well the pure compound linalool, methyl chavicol, citral and eugenol were used in the assessment of the inhibition of H. contortus egg hatch. In addition, the composition of three cultivars was simulated using a combination of the two major compounds from each. The EOs from different cultivars showed mean Inhibition Concentration (IC50) varying from 0.56 to 2.22 mg/mL. The cultivar with the highest egg-hatch inhibition, Napoletano, is constituted mainly of linalool and methyl chavicol. Among the individual compounds tested, citral was the most effective (IC50 0.30 mg/mL). The best combination of compounds was obtained with 11% eugenol plus 64% linalool (IC50 0.44 mg/mL), simulating the Italian Large Leaf (Richters) cultivar. We conclude that different cultivars of O. basilicum show different anthelmintic potential, with cultivars containing linalool and methyl chavicol being the most promising; and that citral or methyl chavicol isolated should also be considered for the development of new anthelmintic formulations.

Cardiomyocyte nuclearity and ploidy: when is double trouble?

Considerable effort has gone into investigating mechanisms that underlie the developmental transition in which mammalian cardiomyocytes (CMs) switch from being able to proliferate during development, to essentially having lost that ability at maturity. This problem is interesting not only for scientific curiosity, but also for its clinical relevance because controlling the ability of mature CMs to replicate would provide a much-needed approach for restoring cardiac function in damaged hearts. In this review, we focus on the propensity of mature mammalian CMs to be multinucleated and polyploid, and the extent to which this may be necessary for normal physiology yet possibly disadvantageous in some circumstances. In this context, we explore whether the concept of the myonuclear domain (MND) in multinucleated skeletal muscle fibers might apply to cardiomyocytes, and whether cardio-MND size might be related to the transition of CMs to become multinuclear. Nuclei in CMs are almost certainly integrators of not only biochemical, but also-because of their central location within the myofibrils-mechanical information, and this multimodal, integrative function in adult CMs-involving molecules that have been extensively studied along with newly identified possibilities-could influence both gene expression as well as replication of the genome and the nuclei themselves.

Does sequential balloon expulsion test improve the screening of defecation disorders?

BACKGROUND: A defecation disorder (DD) is a difficulty in evacuation documented by physiological exams. However, this physiological evaluation can be cumbersome, inaccessible and costly. Three "low-cost" tools to evaluate DD-a clinical DD score, the balloon expulsion test (BET) and a digital rectal examination (DRE) score were evaluated as separate or combined tests for DD screening. METHODS: This prospective study occurred between January 2015 and March 2019 in the Gastroenterology Department of a tertiary hospital. Besides the gold standard physiological tests, constipated patients answered the clinical DD score and were evaluated by DRE and BET [standard and variable volume (VV)]. RESULTS: From 98 constipated patients, 35 (38.9%) were diagnosed with DD according to Rome IV criteria, mainly female (n = 30, 86%) with a median age of 60 years old. The clinical DD score revealed an AUC of 0.417 (SE = 0.07, p = 0.191). The DRE score displayed an AUC of 0.56 (SE = 0.063, p = 0.301). The standard BET displayed a sensitivity of 86%, specificity of 58%, positive predictive value (PPV) of 57% and negative predictive value (NPV) of 86%. The sequential VVBET followed by standard BET improved the BET performance regarding the evaluation of DD, with a sensitivity of 86%, specificity of 67%, PPV of 63% and NPV of 87%. The sequential BET had an OR 8.942, p > 0.001, CI 3.18-25.14, revealing to be the most significant predictor for DD screening. CONCLUSION: The sequential BET is a low cost, well-performing DD screening tool, appropriate to the Primary Care Setting.

Effect of immersion in distilled water or phosphate-buffered saline on the solubility, volumetric change and presence of voids within new calcium silicate-based root canal sealers.

AIM: To assess the effect of immersion in distilled water or phosphate-buffered saline (PBS) on the solubility, volumetric change and presence of voids of calcium silicate-based root canal sealers (TotalFill BC, Sealer Plus BC and Bio-C), in comparison with the gold standard epoxy resin-based sealer (AH Plus). METHODOLOGY: All properties were evaluated after immersion in distilled water or PBS. Solubility was determined by the percentage of mass loss, whereas volumetric change and presence of voids were evaluated by micro-computed tomography, after 7 days of immersion. The volumetric change and percentage of voids between the baseline (after setting) and the experimental period were calculated. Statistical analysis was performed using one-way anova and Tukey's or Student's t-tests (α = 0.05). RESULTS: The calcium silicate-based sealers had significantly greater solubility and volumetric loss than AH Plus, after immersion in distilled water or PBS (P < 0.05). Bio-C had the greatest solubility (P < 0.05), followed by TotalFill BC and Sealer Plus BC, which were similar (P > 0.05). Regarding the volumetric change, AH Plus had a volume increase, with similar values in distilled water and PBS (P > 0.05). TotalFill BC, Sealer Plus BC and Bio-C had a similar volumetric change (P > 0.05). The calcium silicate-based materials had the greatest solubility and volume loss after immersion in distilled water (P < 0.05). There was no difference in the percentage of voids amongst the sealers, before and after immersion in distilled water or PBS (P > 0.05). CONCLUSIONS: TotalFill BC, Sealer Plus BC and Bio-C had significantly greater solubility and volumetric loss than AH Plus. Although storage in PBS significantly reduced the solubility and volumetric change of calcium silicate-based sealers, their solubility remained above that recommend by ISO 6876. All the sealers evaluated had low and similar voids, even after immersion in distilled water or PBS.

Primary and metastatic brain cancer genomics and emerging biomarkers for immunomodulatory cancer treatment.

Recent studies with immunomodulatory agents targeting both cytotoxic T-lymphocyte protein 4 (CTLA4) and programmed cell death 1 (PD1)/programmed cell death ligand 1 (PDL1) have shown to be very effective in several cancers revealing an unexpected great activity in patients with both primary and metastatic brain tumors. Combining anti-CTLA4 and anti-PD1 agents as upfront systemic therapy has revealed to further increase the clinical benefit observed with single agent, even at cost of higher toxicity. Since the brain is an immunological specialized area it's crucial to establish the specific composition of the brain tumors' microenvironment in order to predict the potential activity of immunomodulatory agents. This review briefly summarizes the basis of the brain immunogenicity, providing the most updated clinical evidences in terms of immune-checkpoint inhibitors efficacy and toxicity in both primary and metastatic brain tumors with the final aim of defining potential biomarkers for immunomodulatory cancer treatment.

Tribo-Charging Behaviour of Inhalable Mannitol Blends with Salbutamol Sulphate.

PURPOSE: The performance of carrier-based dry powder inhaler (DPI) formulations can be critically impacted by interfacial interactions driven by tribo-electrification. Therefore, the aim of the present work was to understand how distinct API particle characteristics affect the charging behaviour of blends intended for DPI delivery. METHODS: Salbutamol sulphate (SBS) particles engineered via spray-drying and jet milling were used as model APIs. D-mannitol was selected as a model carrier. The materials were characterized concerning their different particle properties and their charge was analysed alone and in blends before and after flow over a stainless-steel pipe. RESULTS: The spray-dried SBS (amorphous and spherical) charged positively and to a higher extent than jet milled SBS (crystalline and acicular) that charged negatively and to a lower extent. D-mannitol charged positively and to a higher extent than the APIs. All drug-excipient blends charged negatively and differences were found between the spray-dried and jet milled SBS blends at 2% and 5% drug loads. CONCLUSIONS: It was demonstrated how distinct solid-states, particle shape, size and morphology as well as different water contents of the different materials can affect tribo-charging. For their binary blends, the amount and nature of fines seem to govern inter-particle contacts critically impacting charge evolution.

Identification of Copy Number Variation by Array-CGH in Portuguese Children and Adolescents Diagnosed with Autism Spectrum Disorders.

BACKGROUND: Autism spectrum disorders (ASD) affect many children with an estimated prevalence of 1%. Array-comparative genomic hybridization (CGH) offers significant sensitivity for the identification of submicroscopic chromosomal abnormalities and it is one of the most used techniques in daily practice. The main objective of this study was to describe the usefulness of array-CGH in the etiologic diagnosis of ASD. METHODS: Two-hundred fifty-three patients admitted to a neurogenetic outpatient clinic and diagnosed with ASD were selected for array-CGH (4 × 180K microarrays). Public databases were used for classification in accordance with the American College of Medical Genetics Standards and Guidelines. RESULTS: About 3.56% (9/253) of copy number variations (CNVs) were classified as pathogenic. When likely pathogenic CNVs were considered, the rate increased to 11.46% (29/253). Some CNVs apparently not correlated to the ASD were also found. Considering a phenotype-genotype correlation, the patients were divided in two groups. One group according to previous literature includes all the CNVs related to ASDs (23 CNVs present in 22 children) and another with those apparently not related to ASD (10 CNVs present in 7 children). In 18 patients, a next-generation sequencing (NGS) panel were performed. From these, one pathogenic and 16 uncertain significance variants were identified. CONCLUSION: The results of our study are in accordance with the literature, highlighting the relevance of array-CGH in the genetic of diagnosis of ASD population, namely when associated with other features. Our study also reinforces the need for complementarity between array-CGH and NGS panels or whole exome sequencing in the etiological diagnosis of ASD.

Prevalence of asthma, allergic rhinitis and eczema in 6-7-year-old schoolchildren from Luanda, Angola.

BACKGROUND: Epidemiological data have shown that the prevalence of asthma, rhinoconjunctivitis and eczema in children is still increasing, namely in Africa. However, there are no epidemiological studies on asthma or allergic diseases in Angolan children. OBJECTIVE: To study the prevalence of asthma and other allergic diseases in Angolan children. METHODS: Descriptive, observational, cross-sectional study, using the ISAAC study methodology, in the province of Luanda, Angola in 6-7-year-old children. Forty-six (8.3%) public schools were randomly selected. Data were analysed using the SPSS Statistics version 24.0 software. RESULTS: A total of 3080 children were studied. Results showed that the prevalence of asthma (wheezing in the previous 12 months) was 15.8%, that of rhinitis (sneezing, runny or blocked nose in the previous 12 months) was 19%, and that of eczema (itchy skin lesions in the previous 12 months) was 22%, without differences between sexes. Rhinitis was associated with a higher number of episodes of wheezing episodes, disturbed sleep and night cough, in children with asthma. Rhinitis, eczema, Split-type air conditioning system, antibiotic intake in the child's first year of life, frequent intake (more than once per month) of paracetamol and active maternal smoking were associated with a higher risk of having asthma, whereas electrical cooking was associated with a protective effect. CONCLUSION: Asthma and allergic diseases are highly prevalent in children from Luanda. A strategy for preventive and control measures should be implemented.

One Health operations: a critical component in the International Health Regulations Monitoring and Evaluation Framework.

Under the International Health Regulations (IHR, 2005), a legally binding document adopted by 196 States Parties, countries are required to develop their capacity to rapidly detect, assess, notify and respond to unusual health events of potential international concern. To support countries in monitoring and enhancing their capacities and complying with the IHR (2005), the World Health Organization (WHO) developed the IHR Monitoring and Evaluation Framework (IHR MEF). This framework comprises four complementary components: the State Party Annual Report, the Joint External Evaluation, after-action reviews and simulation exercises. The first two are used to review capacities and the second two to help to explore their functionality. The contribution of different disciplines, sectors, and areas of work, joining forces through a One Health approach, is essential for the implementation of the IHR (2005). Therefore, WHO, in partnership with the Food and Agriculture Organization of the United Nations (FAO), the World Organisation for Animal Health (OIE), and other international and national partners, has actively worked on facilitating the inclusion of the relevant sectors, in particular the animal health sector, in each of the four components of the IHR MEF. Other tools complement the IHR MEF, such as the WHO/OIE IHR-PVS [Performance of Veterinary Services] National Bridging Workshops, which facilitate the optimal use of the results of the IHR MEF and the OIE Performance of Veterinary Services Pathway and create an opportunity for stakeholders from animal health and human health services to work on the coordination of their efforts. The results of these various tools are used in countries' planning processes and are incorporated in their National Action Plan for Health Security to accelerate the implementation of IHR core capacities. The present article describes how One Health is incorporated in all components of the IHR MEF.

En vertu du Règlement sanitaire international (RSI, 2005), instrument juridique ayant force obligatoire pour les 196 États Parties dans le monde, les pays s'engagent à renforcer leurs capacités de détection, d'évaluation, de notification et de réaction en cas d'événements sanitaires inhabituels ou présentant une dimension internationale inquiétante. Le Cadre de suivi et d'évaluation du RSI (2005) a été élaboré par l'Organisation mondiale de la santé (OMS) afin de soutenir les pays souhaitant évaluer et améliorer leurs capacités et leur niveau de conformité avec le RSI (2005). Ce cadre comprend quatre composantes complémentaires : le rapport annuel de l'État Partie, l'Évaluation extérieure conjointe, les examens « après action¼ et les exercices de simulation. Les deux premières composantes permettent de faire le point sur les capacités tandis que les deux dernières visent une connaissance détaillée de leur fonctionnement. La mise en oeuvre du RSI (2005) demande aux différentes disciplines, secteurs et domaines d'activités de fédérer leurs forces dans une approche Une seule santé. Par conséquent, en partenariat avec l'Organisation des Nations Unies pour l'alimentation et l'agriculture (FAO), avec l'Organisation mondiale de la santé animale (OIE) et avec d'autres partenaires internationaux et nationaux, l'OMS a fait en sorte de faciliter l'intégration de tous les secteurs concernés, en particulier celui de la santé animale, dans les diverses composantes du Cadre d'évaluation du RSI. D'autres outils complètent celui-ci, en particulier les ateliers de liaison nationaux OMS/OIE sur le RSI et le Processus d'évaluation des performances des Services vétérinaires (PVS), dont le but est de faciliter l'utilisation optimale des résultats du Cadre d'évaluation du RSI et du Processus PVS de l'OIE et de fournir aux acteurs des services de santé animale et de santé publique la possibilité de se concerter sur les modalités d'une synergie de leur action. Les résultats de ces outils sont ensuite pris en compte par les pays lors des procédures de planification et intégrés dans les Plans d'action nationaux pour la sécurité sanitaire afin d'accélérer la mise en oeuvre des capacités fondamentales décrites dans le RSI. Les auteurs décrivent l'intégration du concept Une seule santé dans chacune des composantes du Cadre d'évaluation du RSI.

Según lo dispuesto en el Reglamento Sanitario Internacional (RSI, 2005), documento jurídicamente vinculante suscrito por 196 Estados Partes, los países están obligados a dotarse de la capacidad necesaria para detectar, evaluar, notificar y afrontar con rapidez todo evento sanitario inusual que pueda revestir importancia internacional. Para ayudar a los países a dotarse de mejores capacidades, a seguir de cerca su evolución al respecto y a dar cumplimiento al RSI (2005), la Organización Mundial de la Salud (OMS) elaboró el marco de seguimiento y evaluación del RSI, que consta de cuatro elementos complementarios: el informe anual que debe presentar cada Estado Parte; la evaluación externa conjunta; exámenes posteriores a las intervenciones; y ejercicios de simulación. Los dos primeros sirven para examinar las capacidades, y los dos segundos para ayudar a estudiar su funcionalidad. Para la aplicación del RSI (2005) es fundamental la contribución de diferentes disciplinas, sectores y ámbitos de trabajo, que aúnen esfuerzos actuando desde los postulados de Una sola salud. Por ello la OMS, en colaboración con la Organización de las Naciones Unidas para la Alimentación y la Agricultura (FAO), la Organización Mundial de Sanidad Animal (OIE) y otros asociados internacionales y nacionales, ha trabajado activamente para facilitar la integración de los sectores pertinentes, en particular el de la sanidad animal, en cada uno de los cuatro componentes del marco de seguimiento y evaluación del RSI. Hay otros dispositivos que vienen a complementar este marco, por ejemplo los talleres nacionales dedicados a la creación de nexos entre el RSI y el proceso PVS (Prestaciones de los Servicios Veterinarios) de la OIE, organizados conjuntamente por la OMS y la OIE, que facilitan un uso idóneo de los resultados del marco de seguimiento y evaluación del RSI y del proceso PVS y brindan a las partes interesadas de los servicios sanitarios y zoosanitarios la oportunidad de trabajar sobre la coordinación de sus respectivas actividades. Los resultados de estas diversas herramientas alimentan después los procesos de planificación de los países y son incorporados a su Plan de acción nacional de seguridad sanitaria para acelerar la implantación de las capacidades básicas prescritas en el RSI. Los autores explican cómo se incorpora la filosofía de Una sola salud a todos los componentes del marco de seguimiento y evaluación del RSI.

Structural and functional impact of troponin C-mediated Ca2+ sensitization on myofilament lattice spacing and cross-bridge mechanics in mouse cardiac muscle.

Acto-myosin cross-bridge kinetics are important for beat-to-beat regulation of cardiac contractility; however, physiological and pathophysiological mechanisms for regulation of contractile kinetics are incompletely understood. Here we explored whether thin filament-mediated Ca2+ sensitization influences cross-bridge kinetics in permeabilized, osmotically compressed cardiac muscle preparations. We used a murine model of hypertrophic cardiomyopathy (HCM) harboring a cardiac troponin C (cTnC) Ca2+-sensitizing mutation, Ala8Val in the regulatory N-domain. We also treated wild-type murine muscle with bepridil, a cTnC-targeting Ca2+ sensitizer. Our findings suggest that both methods of increasing myofilament Ca2+ sensitivity increase cross-bridge cycling rate measured by the rate of tension redevelopment (kTR); force per cross-bridge was also enhanced as measured by sinusoidal stiffness and I1,1/I1,0 ratio from X-ray diffraction. Computational modeling suggests that Ca2+ sensitization through this cTnC mutation or bepridil accelerates kTR primarily by promoting faster cross-bridge detachment. To elucidate if myofilament structural rearrangements are associated with changes in kTR, we used small angle X-ray diffraction to simultaneously measure myofilament lattice spacing and isometric force during steady-state Ca2+ activations. Within in vivo lattice dimensions, lattice spacing and steady-state isometric force increased significantly at submaximal activation. We conclude that the cTnC N-domain controls force by modulating both the number and rate of cycling cross-bridges, and that the both methods of Ca2+ sensitization may act through stabilization of cTnC's D-helix. Furthermore, we propose that the transient expansion of the myofilament lattice during Ca2+ activation may be an additional factor that could increase the rate of cross-bridge cycling in cardiac muscle. These findings may have implications for the pathophysiology of HCM.

Vitamin D levels and risk for periodontal disease: A systematic review.

OBJECTIVE: To evaluate the existing evidence supporting or refuting the following questions: (i) Do patients with lower vitamin D levels have higher risk for periodontal disease? (ii) Are periodontal treatment outcomes improved by the adjuvant supplementation of vitamin D or by elevated serum vitamin D levels? MATERIAL AND METHODS: MEDLINE, SCOPUS, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched up to September 2017. Studies were included if they had measured serum vitamin D levels or vitamin D intake and any periodontal parameter. RESULTS: Overall, 27 studies were included (13 cross-sectional studies, 6 case-control studies, 5 cohort studies, 2 randomized clinical trials and 1 case series study). Sixty-five percent of the cross-sectional studies reported significant associations between low vitamin D levels and poor periodontal parameters. None of the observational longitudinal studies found that periodontal disease progression could be attributed to lower vitamin D levels. No interventional studies that evaluated the use of vitamin D supplementation as a solely adjuvant to periodontal treatment was found. No meta-analysis was performed due to high variability across studies. CONCLUSION: The data to support or refute the association between vitamin D levels and periodontal disease are inconclusive at the moment. More rigorously designed longitudinal studies with standardized definitions of periodontal disease and vitamin D are necessary.

A novel nested polymerase chain reaction assay targeting Plasmodium mitochondrial DNA in field-collected Anopheles mosquitoes.

Sensitive techniques for the detection of Plasmodium (Aconoidasida: Plasmodiidae) sporozoites in field-collected malaria vectors are essential for the correct assessment of risk for malaria transmission. A real-time polymerase chain reaction (RT-PCR) protocol targeting Plasmodium mtDNA proved to be much more sensitive in detecting sporozoites in mosquitoes than the widely used enzyme-linked immunosorbent assay targeting Plasmodium circumsporozoite protein (CSP-ELISA). However, because of the relatively high costs associated with equipment and reagents, RT-PCRs are mostly used to assess the outcomes of experimental infections in the frame of research experiments, rather than in routine monitoring of mosquito infection in the field. The present authors developed a novel mtDNA-based nested PCR protocol, modified from a loop-mediated isothermal amplification (LAMP) assay for Plasmodium recognition in human blood samples, and compared its performance with that of routinely used CSP-ELISAs in field-collected Anopheles coluzzii (Diptera: Culicidae) samples. The nested PCR showed 1.4-fold higher sensitivity than the CSP-ELISA. However, nested PCR results obtained in two laboratories and in different replicates within the same laboratory were not 100% consistent, probably because the copy number of amplifiable Plasmodium mtDNA was close in some specimens to the threshold of nested PCR sensitivity. This implies that Plasmodium-positive specimens should be confirmed by a second nested PCR to avoid false positives. Overall, the results emphasize the need to use molecular approaches to obtain accurate estimates of the actual level of Plasmodium circulation within malaria vector populations.

Wii-based exercise program to improve physical fitness, motor proficiency and functional mobility in adults with Down syndrome.

BACKGROUND: People with Down syndrome (DS) usually display reduced physical fitness (aerobic capacity, muscle strength and abnormal body composition), motor proficiency impairments (balance and postural control) and physical functional limitations. Exergames can be an appealing alternative to enhance exercise engagement and compliance, whilst improving physical fitness and motor function. This study aims to analyse the effects of a Wii-based exercise program on physical fitness, functional mobility and motor proficiency of adults with DS. METHODS: Twenty-seven adults with DS were randomly allocated to an experimental group (Wii; n = 14) or control group (n = 13). Participants in the experimental group completed a 2-month Wii-based exercise program, with three 1-h sessions per week that included training games for aerobic endurance, balance and isometric strength. Participants completed assessments regarding anthropometric measures, physical fitness, functional mobility and motor proficiency. RESULTS: Mixed ANOVA analysis showed a significant group by time interaction for aerobic endurance, explosive leg power and flexibility. Independent samples t-test for change scores indicated significant between-group differences favouring the experimental group regarding speed of limb movement, trunk strength and functional mobility, as well as a trend towards significance on body weight. Mann-Whitney's U test for change scores demonstrated between-group differences favouring the experimental group for visceral fat as well as running speed and agility. Large within-group effect sizes were observed for explosive leg power (d = 1.691), body weight (d = 1.281), functional mobility (d = 1.218), aerobic endurance (d = 1.020), speed of limb movement (d = 0.867) and flexibility (d = 0.818) in the experimental group. CONCLUSIONS: Our findings suggest that Wii-based exercise can be an effective tool to improve physical fitness, functional mobility and motor proficiency of adults with DS, including crucial measures such as aerobic capacity and lower limb strength. Exergames using Wii Fit or other equipment can be appealing alternatives for adults with DS to engage in regular physical activity, preventing sedentary behaviour and decreasing the risk to develop cardiovascular diseases.

International health threats and global early warning and response mechanisms.

The global community continues to incur the high costs of crisis mitigation and emergency response to outbreaks of emerging infectious diseases, such as those caused by the H5N1 highly pathogenic avian influenza virus, Ebola virus, Nipah virus, Zika virus or the Middle East respiratory syndrome coronavirus. These viruses are particularly dangerous in regions associated with poor development indicators and high vulnerability. The drivers of these disease crises include failures in the way that animal diseases are detected and reported and failures in the way in which disease response is implemented by animal health and public health systems. In addition, the lack of a coordinated response hampers disease control efforts. A comprehensive approach for disease prevention, detection and response, however, requires a coordinated and joint effort among governments, communities, donors and international networks to invest effectively in prevention systems that can identify early signals of the emergence, spillover and spread of animal pathogens at the local level. These signals include trade bans, market closures, civil unrest, heavy rains and droughts associated with climate change, and livestock intensification or changes in consumer behaviour. The global community needs to increase its investment in early warning and detection systems that can provide information that enables action to be taken at the national, regional and global levels in the event of an outbreak of a transboundary animal disease (TAD). Like any preventive measure, an early warning system requires financial resources, but these are insignificant when compared to the losses that are avoided. Building a global early warning and effective response system for outbreaks is value for money, as the benefits far outweigh the costs. The goal of the Food and Agriculture Organization of the United Nations (FAO) is to end hunger and poverty, which is a challenging and complex task. Building global capacity to prepare for and respond to TADs is an important element of the FAO's strategic objective to increase the resilience of livelihoods to threats and crises. Each year, livestock, and the people who rely upon them for their livelihoods, are confronted with animal disease and crises. They can strike suddenly, causing obvious illness and death, or emerge insidiously and become well established before becoming apparent. Animal disease emergencies threaten the production of, and access to, food; consequently, one of the FAO's missions is to help countries to prepare for and respond to animal health disasters.

La communauté mondiale continue à supporter le coût élevé de l'atténuation des crises ainsi que des réponses apportées en urgence aux foyers de maladies infectieuses émergentes, par exemple les infections dues au virus H5N1 de l'influenza aviaire hautement pathogène, au virus Ebola, au virus Nipah, au virus Zika ou au coronavirus responsable du syndrome respiratoire du Moyen-Orient. Ces virus sont particulièrement dangereux dans les régions les plus vulnérables et dont les indicateurs de développement sont bas. Les défaillances dans la détection et la notification des maladies animales jouent un rôle déterminant dans ces crises sanitaires, de même que l'incapacité des systèmes de santé animale et publique à mettre en œuvre une réponse sanitaire appropriée. En outre, l'absence de coordination dans les réponses apportées affaiblit les efforts pour lutter contre les maladies. La mise en place d'une méthode de prévention, de détection et de réponse intégrée face aux maladies exige que les gouvernements, les communautés, les donateurs et les réseaux internationaux associent leurs efforts et se concertent afin d'investir efficacement dans des systèmes de prévention capables de détecter à l'échelle locale les tout premiers signes d'émergence d'un agent pathogène chez les animaux, de sa transmission à d'autres espèces et de sa propagation. Parmi ces signes révélateurs on peut citer certaines interdictions d'importer, mais aussi la fermeture des marchés, l'existence de troubles civils, les changements climatiques tels que de fortes précipitations ou une sécheresse prolongée et la modification de certaines tendances en production animale ou du comportement des consommateurs. La communauté mondiale doit investir davantage dans des systèmes d'alerte précoce et de détection afin d'obtenir l'information nécessaire pour prendre des mesures appropriées, à l'échelle nationale, régional et mondiale, en cas d'apparition d'une maladie animale transfrontalière. Comme toute mesure de prévention, les systèmes d'alerte précoce doivent être correctement financés, mais cet effort est insignifiant lorsqu'on le compare aux pertes qu'il permet d'éviter. La création d'un système mondial d'alerte précoce et de réponse en cas de foyers constitue un investissement rentable, qui génère des bénéfices bien supérieurs à ses coûts. L'Organisation des Nations Unies pour l'alimentation et l'agriculture (FAO) a pour objectif de mettre un terme à la faim et à la pauvreté dans le monde, ce qui constitue une tâche complexe et difficile. Le renforcement des capacités mondiales de préparation et de réponse en cas de maladies animales transfrontalières est un aspect important des objectifs stratégiques de la FAO visant à accroître la résilience des moyens d'existence face aux crises et aux menaces. Chaque année, le cheptel domestique et les personnes qui en tirent leur subsistance sont confrontés à des maladies animales et à des crises sanitaires. Celles-ci peuvent se déchaîner brutalement et présenter un tableau clair de morbidité et de mortalité, ou bien émerger de manière insidieuse et se propager avant l'apparition de signes manifestes. Puisque la production et l'accès aux denrées alimentaires sont menacés par les catastrophes sanitaires dues aux maladies animales, l'une des missions de la FAO consiste à aider les pays à répondre à ces catastrophes et à s'y préparer.

La comunidad mundial sigue soportando los elevados costos de las actividades de atenuación de crisis y de respuesta de emergencia ante brotes de enfermedades infecciosas emergentes como los causados por el virus de la influenza aviar altamente patógena H5N1, el del Ébola, el Nipah, el Zika o el coronavirus del síndrome respiratorio de Oriente Medio. Estos virus resultan especialmente peligrosos en regiones que presentan indicadores de desarrollo mediocres y un elevado nivel de vulnerabilidad. Entre los factores que subyacen a estas crisis sanitarias están las deficiencias en la forma de detectar y comunicar estas enfermedades y la inadecuada aplicación de medidas de respuesta por parte de los sistemas de salud pública y sanidad animal. Por añadidura, la ausencia de una respuesta coordinada lastra también las actividades de lucha. Un trabajo integral de prevención y detección de enfermedades y de respuesta a ellas exige sin embargo un esfuerzo coordinado y conjunto de gobiernos, poblaciones, donantes y redes internacionales para invertir eficazmente en sistemas de prevención que sirvan para detectar las señales precoces de aparición, extensión y propagación de patógenos animales a nivel local, señales como prohibiciones comerciales, cierres de mercados, desórdenes civiles, cambios climáticos como lluvias o sequías intensas o modificación de la dinámica de producción ganadera o los patrones de consumo. La comunidad mundial debe invertir en mayor medida en sistemas de alerta y detección rápidas que aporten información que pueda traducirse en acciones de ámbito nacional, regional y mundial en caso de brote de una enfermedad animal transfronteriza. Como toda medida de carácter preventivo, un sistema de alerta rápida requiere recursos económicos, pero su cuantía resulta insignificante en comparación con las pérdidas que se evitan. La construcción de un sistema mundial de alerta rápida y respuesta eficaz en caso de brote ofrece gran rentabilidad, por cuanto los beneficios superan holgadamente los costos. La Organización de las Naciones Unidas para la Alimentación y la Agricultura (FAO) persigue el objetivo de poner fin al hambre y la pobreza, empresa harto difícil y compleja. Dotar al mundo de la capacidad de preparación y respuesta ante enfermedades animales transfronterizas es un elemento importante del objetivo estratégico de la FAO de lograr que los medios de sustento gocen de mayor resiliencia ante crisis y amenazas. Cada año, los rebaños de animales domésticos y las personas que dependen de ellos para vivir hacen frente a enfermedades y crisis zoosanitarias, que pueden golpear de forma súbita y extender abiertamente la enfermedad y la muerte o, por el contrario, surgir insidiosamente y arraigar antes de que su presencia resulte patente. Las emergencias zoosanitarias hacen peligrar la producción de alimentos y el acceso a ellos. Una de las misiones de la FAO, por consiguiente, es la de ayudar a los países a prepararse para episodios de catástrofe zoosanitaria y a responder a este tipo de eventos cuando se produzcan.

Assessment of genetic diversity of a native population of Eplingiella fruticosa: a plant with therapeutic potential.

Eplingiella fruticosa (Salzm. ex Benth.) Harley & J.F.B. Pastore, ex Hyptis fruticosa Salzm. ex Benth. is an aromatic and medicinal plant of the family Lamiaceae, found mainly in regions with intense anthropic activity. Information on the genetic diversity of this species is scarce. However, it can be assessed using molecular markers that identify the level of diversity among phenotypically identical individuals. The present study aimed to characterize the genetic diversity of a native population of E. fruticosa from the State of Sergipe using ISSR molecular markers. Samples of 100 plants were collected in 11 municipalities of the State of Sergipe and analyzed using eight ISSR primers, resulting in 72 informative bands. The cluster analysis obtained using the neighbor joining method resulted in three groups: Group I consisted of 50 plants, mainly from the municipalities of Areia Branca, Estância, Japaratuba, Moita Bonita, Pirambu, and Salgado; Group II was formed by 21 plants, with nine representatives from the municipality of Itaporanga d'Ajuda and 13 representatives from other municipalities; Group III was composed by 29 plants, being represented mainly by the municipalities of Malhada dos Bois and São Cristóvão. The smallest genetic distance occurred between plants EPF94 and EPF96 (0.250), and the greatest distance occurred between plants EPF50 and EPF96 (0.9778). The Shannon index had a mean value of 0.42, and diversity was considered moderate. Heterozygosity had a mean value of 0.267 and was considered low. Polymorphic information content (0.253) was considered moderately informative. Genetic diversity of E. fruticosa plants was intermediate, and the results of the present study can assist in the conservation and use of the genetic resources of this species.