Acquired Vitamin B12 Deficiency in Newborns: Positive Impact on Newborn Health through Early Detection.

The early diagnosis of and intervention in vitamin B12 deficiency in exclusively breastfed infants by mothers with low vitamin B12 is crucial in preventing possible irreversible neurologic damage, megaloblastic anemia, and failure to thrive. We assess the usefulness of the early detection of asymptomatic B12 deficiency related to acquired conditions and highlight the importance of monitoring serum vitamin B12 levels during pregnancy. We describe demographic, clinical, dietary, and biochemical data, including the evolution of a vitamin B12 deficiency's functional biomarkers. We enrolled 12 newborns (5 males) with an age range of 1-2 months old that were exclusively breastfed and asymptomatic. These cases were referred to our metabolic unit due to alterations in expanded newborn screening: high levels of methylmalonic acid and/or total homocysteine (tHcy). All mothers were under a vegetarian diet except three who had abnormal B12 absorption, and all presented low or borderline serum B12 level and high plasma levels of tHcy. Supplementation with oral vitB12 re-established the metabolic homeostasis of the mothers. In infants, therapy with an intramuscular injection of 1.0 mg hydroxocobalamin led to the rapid normalization of the metabolic pattern, and a healthy outcome was observed. Acquired B12 deficiency should be ruled out before proceeding in a differential diagnosis of cobalamin metabolism deficits, methylmalonic acidemia, and homocystinuria.

Effectiveness of hypnosis for pain and health-related quality-of-life among people with hemophilia: Three-month outcomes of a randomized controlled pilot trial.

BACKGROUND AND PURPOSE: Pain is a common condition among people with hemophilia (PWH), negatively impacting quality of life. However, effective treatment remains a challenge. This two-arm, parallel randomized controlled pilot trial aimed to examine the three-month effects of hypnosis intervention on clinical and psychosocial variables, and on the inflammatory profile of PWH. MATERIALS AND METHODS: The study was conducted between January and October 2018, in a Reference Center for Congenital Coagulopathies. Adult (age ≥18) patients were randomized to experimental group (EG) or control group (CG). The EG received four weekly hypnosis sessions plus treatment-as-usual, and the CG maintained treatment-as-usual only. Outcomes were evaluated at one week and three months post-intervention and included pain, joint status, health-related quality of life (HRQoL), emotional state and inflammatory profile (leukocytes, C-reactive protein, cytokines). The randomization sequence was computer-generated, and allocation was concealed until enrolment. The outcome assessor was blind to allocation, but blinding of the participants was not possible due to the differences in procedure. RESULTS: Twenty patients were randomized to EG (n = 10; 8 analyzed) or CG (n = 10; 10 analyzed). Two-way mixed ANOVA showed significant time × group interactions on pain interference with normal work and with relations with other people, and on perception of health status. The EG significantly improved in pain interference with normal work and perception of health status. There was no report of harm. CONCLUSION: Hypnosis may be a promising intervention to manage hemophilia-related pain and promote HRQoL, with benefits lasting up to three months.

Effectiveness of hypnosis for pain management and promotion of health-related quality-of-life among people with haemophilia: a randomised controlled pilot trial.

Joint deterioration and associated chronic pain are common among people with haemophilia (PWH), having an impact on quality-of-life. Though non-pharmacological strategies are recommended, psychological interventions to promote pain control and quality-of-life have scarcely been tested in haemophilia. This randomised controlled pilot trial aimed to assess feasibility, acceptability and effectiveness of hypnosis for pain management and promotion of health-related quality-of-life (HRQoL) among PWH. Twenty adults were randomised either to four weekly hypnosis sessions plus treatment-as-usual (experimental group; EG) or treatment-as-usual only (control group; CG). Participants completed sociodemographic and clinical assessment, measures of pain, HRQoL and emotional distress before (T1) and after (T2) intervention. Changes were analysed by calculating the differences between T1 and T2, and the groups were compared through independent-sample t tests (or chi-squared). Retention rates (90%) and analysis of patient satisfaction showed good acceptability and feasibility of the intervention. The EG (n = 8) had a higher reduction on pain interference than the CG (n = 10) (d = -0.267). A higher improvement on HRQoL (EQ-5D index: d = 0.334; EQ-5D VAS: d = 1.437) and a tendency towards better haemophilia-related quality-of-life (A36-Hemofilia QoL) were also evident in the EG. This is the first study showing the effectiveness of hypnosis to reduce pain interference and promote HRQoL among PWH.

A zebrafish drug screening platform boosts the discovery of novel therapeutics for spinal cord injury in mammals.

Spinal cord injury (SCI) is a complex condition, with limited therapeutic options, that results in sensory and motor disabilities. To boost discovery of novel therapeutics, we designed a simple and efficient drug screening platform. This innovative approach allows to determine locomotor rescue properties of small molecules in a zebrafish (Danio rerio) larval spinal cord transection model. We validated our screening platform by showing that Riluzole and Minocycline, two molecules that are in clinical trials for SCI, promote rescue of the locomotor function of the transected larvae. Further validation of the platform was obtained through the blind identification of D-Cycloserine, a molecule scheduled to enter phase IV clinical trials for SCI. Importantly, we identified Tranexamic acid and further showed that this molecule maintains its locomotor recovery properties in a rodent female contusion model. Our screening platform, combined with drug repurposing, promises to propel the rapid translation of novel therapeutics to improve SCI recovery in humans.

Effectiveness of two psychological interventions for pain management, emotional regulation and promotion of quality of life among adult Portuguese men with haemophilia (PSY-HaEMOPEQ): study protocol for a single-centre prospective randomised controlled trial.

INTRODUCTION: Haemophilia is a bleeding disorder associated with significant pain, emotional distress, quality of life (QoL) impairment and considerable healthcare costs. Psychosocial health and effective pain management are considered essential end points for optimal haemophilia care, but there is a significant gap in evidence-based treatments targeting these outcomes in people with haemophilia (PWH). Psychological interventions are cost-effective in promoting emotional well-being, QoL and pain control, although these have been scarcely used in haemophilia field. This investigation aims to evaluate the effectiveness of two psychological interventions for pain management, emotional regulation and promotion of QoL in PWH. METHODS AND ANALYSIS: This is a single-centre parallel randomised controlled trial conducted at a European Haemophilia Comprehensive Care Centre in Portugal, with five assessment points: baseline (T0), postintervention (T1), 3 (T2), 6 (T3) and 12 (T4) months follow-up. Eligible adult males, with moderate or severe haemophilia A or B will be randomised to experimental (EG) or control (CG) group. Intervention is either cognitive-behavioural therapy (EG1) or hypnosis (EG2), both consisting of four weekly sessions following standardised scripts delivered by trained psychologists. Randomisation will be computer generated, allocation concealment will be guaranteed and outcome assessors will be blind to EG/CG allocation. Main outcomes are pain and haemophilia-related QoL and secondary outcomes include clinical (clotting factor replacement consumption, joint bleeding episodes, analgesic intake) and psychological (pain coping strategies, anxiety, depression, illness perceptions) variables, functional assessment of the joints, inflammatory biomarkers (cytokines, high-sensitivity C reactive protein) and white blood cell count. ETHICS AND DISSEMINATION: This study was approved by the competent authorities and all procedures will comply with international ethical guidelines for clinical studies involving humans. Written informed consent will be obtained from all participants. The dissemination plan includes peer-reviewed scientific publications, conference participation and web and media coverage. TRIAL REGISTRATION NUMBER: NCT02870452.

In vitro screening for estrogenic endocrine disrupting compounds using Mozambique tilapia and sea bass scales.

A wide range of estrogenic endocrine disruptors (EDCs) are accumulating in the environment and may disrupt the physiology of aquatic organisms. The effects of EDCs on fish have mainly been assessed using reproductive endpoints and in vivo animal experiments. We used a simple non-invasive assay to evaluate the impact of estrogens and EDCs on sea bass (Dicentrarchus labrax) and tilapia (Oreochromis mossambicus) scales. These were exposed to estradiol (E2), two phytoestrogens and six anthropogenic estrogenic/anti-estrogenic EDCs and activities of enzymes related to mineralized tissue turnover (TRAP, tartrate-resistant acid phosphatase and ALP, alkaline phosphatase) were measured. Semi-quantitative RT-PCR detected the expression of both membrane and nuclear estrogen receptors in the scales of both species, confirming scales as a target for E2 and EDCs through different mechanisms. Changes in TRAP or ALP activities after 30minute and 24h exposure were detected in sea bass and tilapia scales treated with E2 and three EDCs, although compound-, time- and dose-specific responses were observed for the two species. These results support again that the mineralized tissue turnover of fish is regulated by estrogens and reveals that the scales are a mineralized estrogen-responsive tissue that may be affected by some EDCs. The significance of these effects for whole animal physiology needs to be further explored. The in vitro fish scale bioassay is a promising non-invasive screening tool for E2 and EDCs effects, although the low sensitivity of TRAP/ALP quantification limits their utility and indicates that alternative endpoints are required.

Tissue responsiveness to estradiol and genistein in the sea bass liver and scale.

As in mammals, estrogens in fish are essential for reproduction but also important regulators of mineral homeostasis. Fish scales are a non-conventional target tissue responsive to estradiol and constitute a good model to study mineralized tissues effects and mechanisms of action of estrogenic compounds, including phytoestrogens. The responsiveness to estradiol and the phytoestrogen genistein, was compared between the scales and the liver, a classical estrogenic target, in sea bass (Dicentrarchus labrax). Injection with estradiol and genistein significantly increased circulating vitellogenin (for both compounds) and mineral levels (estradiol only) and genistein also significantly increased scale enzymatic activities suggesting it increased mineral turnover. The repertoire, abundance and estrogenic regulation of nuclear estrogen receptors (ESR1, 2a and 2b) and membrane G-protein receptors (GPER and GPER-like) were different between liver and scales, which presumably explains the tissue-specific changes detected in estrogen-responsive gene expression. In scales changes in gene expression mainly consisted of small rapid increases, while in liver strong, sustained increases/decreases in gene expression occurred. Similar but not overlapping gene expression changes were observed in response to both estradiol and genistein. This study demonstrates for the first time the expression of membrane estrogen receptors in scales and that estrogens and phytoestrogens, to which fish may be exposed in the wild or in aquaculture, both affect liver and mineralized tissues in a tissue-specific manner.

Proteomic approach to skin regeneration in a marine teleost: modulation by oestradiol-17ß.

Skin and scale formation and regeneration in teleosts have mainly been described from a morphological perspective, and few studies of the underlying molecular events exist. The present study evaluates (1) the change in the skin proteome during its regeneration in a marine teleost fish (gilthead sea bream, Sparus aurata) and (2) the impact of oestradiol-17ß (Ε2) on regeneration and the involvement of oestrogen receptor (ER) isoforms. Thirty-five candidate proteins were differentially expressed (p < 0.05) between intact and regenerated skin proteome 5 days after scale removal, and 27 proteins were differentially expressed after E2 treatment. Agglomerative hierarchical clustering of the skin proteome revealed that the skin treated with E2 clustered most closely to intact skin, while regenerating untreated skin formed an independent cluster. Gene Ontology classification associated the differentially expressed proteins in E2-treated skin with developmental processes and cellular morphogenesis. The proteins modified during skin regeneration suggest a balance exists between immune response and anatomical repair. Overall, the results indicate that, even after 5 days regeneration, the composition of mature skin is not attained, and endocrine factors, in particular E2, can accelerate wound repair acting possibly via ERßs expressed in the skin-scales. Several candidate proteins probably involved in scale development, osteoglycin, lipocalin2 and lamin A and the transcription factors PHD and grainyhead were identified. Future studies of fish skin regeneration will be required to provide further insight into this multistage process, and the present study indicates it will be useful to explore immune adaptations of epithelia permanently exposed to an aqueous environment.

2011 Portuguese recommendations for the use of biological therapies in patients with psoriatic arthritis.

OBJECTIVE: To develop recommendations for the treatment of psoriatic arthritis (PsA) with biological therapies, endorsed by the Portuguese Society of Rheumatology. METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. A draft of the recommendations was first circulated to all Portuguese rheumatologists and their suggestions were incorporated in the draft. At a national meeting the recommendations were discussed and all attending rheumatologists voted on the level of agreement for each recommendation. A second draft was again circulated before publication. RESULTS: A consensus was achieved regarding the initiation, assessment of response and switching biological therapies in patients with PsA. Specific recommendations were developed for several disease domains: peripheral arthritis, axial disease, enthesitis and dactylitis. CONCLUSION: These recommendations may be used for guidance in deciding which patients with PsA should be treated with biological therapies. They cover a rapidly evolving area of therapeutic intervention. As more evidence becomes available and more biological therapies are licensed, these recommendations will have to be updated.

Portuguese guidelines for the use of biological agents in rheumatoid arthritis - March 2010 update.

The authors present the revised version of the Portuguese Society of Rheumatology (SPR) guidelines for the treatment of rheumatoid arthritis (RA) with biological therapies. In these guidelines the criteria for introduction and maintenance of biological agents are discussed as well as the contraindications and procedures in the case of non-responders. Biological treatment should be considered in RA patients with a disease activity score 28 (DAS 28) superior to 3.2 despite treatment with 20mg/week of methotrexate (MTX) for at least 3 months or, if such treatment is not possible, after 6 months of other conventional disease modifying drug or combination therapy. A DAS 28 score between 2.6 and 3.2 with a significant functional or radiological deterioration under treatment with conventional regimens could also constitute an indication for biological treatment. The treatment goal should be remission or, if that is not achievable, at least a low disease activity, characterized by a DAS28 lower than 3.2, without significative functional or radiological worsening. The response criteria, at the end of the first 3 months of treatment, are a decrease of 0.6 in the DAS28 score. After 6 months of treatment response criteria is defined as a decrease of more than 1.2 in the DAS28 score. Non-responders, in accordance to the Rheumatologist's clinical opinion, should try a switch to another biological agent (tumour necrosis factor antagonist, abatacept, rituximab or tocilizumab).

Supervisão na formação profissional de agentes indígenas de saúde no Parque Indígena do Xingu / Supervision on the professional training of Indigenous agents of health at the Parque Indígena do Xingu

A supervisão de agentes indígenas de saúde possui desafios específicos, entre eles a busca do diálogo entre os saberes tradicionais dos povos indígenas e os saberes do modelo biomédico ocidental. A supervisão é considerada uma atividade do processo de trabalho em saúde, que demonstra a quais finalidades se presta em função da necessidade de seu contexto histórico-social mais amplo e da saúde pública. O objetivo do estudo foi analisar o processo de supervisão dos agentes indígenas de saúde, seus componentes e especificidades. Procedemos a um estudo de caso do serviço de atenção primária na região do Médio e Baixo Xingu, Mato Grosso. Utilizamos a análise de conteúdo para o tratamento de dados secundários e primários: documentos institucionais sobre a formação de recursos humanos e entrevistas com agentes indígenas de saúde, lideranças indígenas, representantes da medicina tradicional e profissionais de saúde de nível universitário. As análises fundamentam-se no referencial teórico do processo de trabalho em saúde, com destaque para a supervisão de trabalhadores da saúde, e na abordagem da antropologia médica e relações interculturais. Apresentamos três grandes núcleos temáticos: os agentes do processo de trabalho em saúde indígena; concepções e práticas da supervisão; finalidades da supervisão e da formação profissional de agentes indígenas de saúde. A interculturalidade manifestou-se como característica que permeia todos os núcleos temáticos.

The supervision of indigenous agents of health contained specific challenges, among them, the search for the dialogue between the traditional knowledge of the indigenous nations and the knowledge of the west biomedical model. The supervision on health is considered an activity on the work process. It demonstrates which finalities they will work concerning the necessity of a more broaden social-historical context and for the public health. The purpose of this research was to analyze the process of supervising the indigenous agents of health, its components and specificities. We have performed a case study of a primary service attention in the region of Low and Middle Xingu, Mato Grosso. We have used the analysis of content for the treatment of primary and secondary data: institutional documents about the formation of human resources and interviews with indigenous agents of health, indigenous leaderships, representatives of traditional medicine and graduated professionals of health. The analyses are based on the theoretical process of working on health, particularly for the supervision of health workers, and the approach of the medical anthropology and intercultural relationships. Here we present three major thematic areas: the agents in the working process of health itself, the concepts and practices of supervision; and the finalities of the supervision and the professional improvement of indigenous health workers. The articulation of cultures has proved to be a characteristic which are part of all those thematic areas.