A taxonomy of threat and soothing influences in rheumatic and musculoskeletal diseases and central sensitivity syndromes / Una taxonomía de amenazas e influencias calmantes en enfermedades reumáticas y musculoesqueléticas y síndromes de sensibilidad central

Background: An imbalance in affect regulation, reflected by a hyperactive threat system and hypoactive soothing system, may impact physical symptoms in people with rheumatic and musculoskeletal diseases (RMD) and central sensitivity syndromes (CSS), including chronic fatigue syndrome, fibromyalgia, and irritable bowel syndrome. This study aimed to identify and structure comprehensive overviews of threat and soothing influences that may worsen or alleviate physical symptoms in people with RMD or CSS. Method: A concept mapping procedure was used. An online open-question survey (N = 686, 641 [93.4%] women) yielded comprehensive sets of 40 threats and 40 soothers that were individually sorted by people with RMD or CSS (N = 115, 112 [97.4%] women). Results: Hierarchical cluster analyses generated eight threat clusters: environmental stimuli, physical symptoms, food and drugs, inactivity, demands, effort, invalidation, and emotional stress. Ten soother clusters were identified: social emotional support, rest and balance, pleasant surroundings, illness understanding, positive mindset and autonomy, spirituality, leisure activity, wellness, treatment and care, and nutrition and treats. Conclusions: Our study provided a comprehensive taxonomy of threats and soothers in people with RMD or CSS. The results can be used in experimental research to label threat and soothing stimuli and in clinical practice to screen and monitor relevant treatment targets.(AU)

A taxonomy of threat and soothing influences in rheumatic and musculoskeletal diseases and central sensitivity syndromes.

Background: An imbalance in affect regulation, reflected by a hyperactive threat system and hypoactive soothing system, may impact physical symptoms in people with rheumatic and musculoskeletal diseases (RMD) and central sensitivity syndromes (CSS), including chronic fatigue syndrome, fibromyalgia, and irritable bowel syndrome. This study aimed to identify and structure comprehensive overviews of threat and soothing influences that may worsen or alleviate physical symptoms in people with RMD or CSS. Method: A concept mapping procedure was used. An online open-question survey (N = 686, 641 [93.4%] women) yielded comprehensive sets of 40 threats and 40 soothers that were individually sorted by people with RMD or CSS (N = 115, 112 [97.4%] women). Results: Hierarchical cluster analyses generated eight threat clusters: environmental stimuli, physical symptoms, food and drugs, inactivity, demands, effort, invalidation, and emotional stress. Ten soother clusters were identified: social emotional support, rest and balance, pleasant surroundings, illness understanding, positive mindset and autonomy, spirituality, leisure activity, wellness, treatment and care, and nutrition and treats. Conclusions: Our study provided a comprehensive taxonomy of threats and soothers in people with RMD or CSS. The results can be used in experimental research to label threat and soothing stimuli and in clinical practice to screen and monitor relevant treatment targets.

Acute effects of drinks containing blackcurrant and citrus (poly)phenols and dietary fibre on postprandial glycaemia, gut hormones, cognitive function and appetite in healthy adults: two randomised controlled trials.

(Poly)phenol (PP)-rich blackcurrant (BC) extracts reduce postprandial glucose concentrations. Combinations with other fruit (poly)phenols and fruit fibre may enhance the effect. This study investigated the acute effects of combinations of BC extracts, high (H-BC) and low (L-BC) (poly)phenol concentrations, sweet orange extracts (SO) and fibre-rich orange pulp (F) in reducing postprandial glycaemia. In two randomised, double-blind, crossover design studies, healthy participants consumed seven types of 200 mL beverages: in the GLU-FX trial, H-BC (1600 mg PP); L-BC (800 mg PP); SO (800 mg PP); BC + SO (1600 mg PP) or CON (placebo); in the GLU-MIX trial, BC + F (800 mg PP), F (1.5 g fibre), or CON2 (placebo), immediately followed by consumption of 75 g available carbohydrate (starch and sugars). Blood was sampled at baseline and postprandially to measure changes in glucose, insulin, and gut hormones; appetite changes were assessed by visual analogue scales and, in GLU-MIX, ad libitum food intake and cognitive function were assessed. Twenty-nine and thirty-seven adults completed GLU-FX and GLU-MIX, respectively. L-BC reduced early postprandial glycaemia (0-30 min) with no differences in glucose incremental Cmax or total glycaemic response. No significant effect was observed following other drinks relative to CON. L-BC and H-BC drinks inhibited insulin secretion up to 30 min and GIP up to 120 min. In GLU-MIX, BC + F improved some indicators of cognitive function but not all. Measures of appetite were unaffected. The impact of (poly)phenol-rich BC extracts on total postprandial glycaemia in healthy participants was minimal and not enhanced when administered in combination with an orange (poly)phenol extract or orange pulp. Clinical Trials registered at https://www.clinicaltrials.gov: NCT03184064 (GLU-FX) and NCT03572296 (GLU-MIX).

MITIG.RA: study protocol of a tailored psychological intervention for managing fatigue in rheumatoid arthritis randomized controlled trial.

BACKGROUND: Despite remarkable medical advances in the treatment of rheumatoid arthritis (RA), a subset of patients fails to achieve complete clinical remission, as the Patient Global Assessment (PGA) of disease activity remains above 1, even after the inflammatory process is brought under control. This so-called state of 'PGA-near-remission' negatively impacts individuals' functioning and potentiates inadequate care. Fatigue is a distressing and disabling symptom frequently reported by patients in PGA-near-remission, and its management remains challenging. While classic cognitive-behavioural interventions show some benefits in managing fatigue, there is potential for improvement. Recently, contextual-cognitive behavioural therapies (CCBT), like mindfulness, acceptance, and compassion-based interventions, have shown promising results in fatigue-associated disorders and their determinants. This study primarily aims to examine the efficacy of the Compassion and Mindfulness Intervention for RA (MITIG.RA), a novel intervention combining different components of CCBT, compared to treatment-as-usual (TAU) in the management of RA-associated fatigue. Secondary aims involve exploring whether MITIG.RA produces changes in the perceived impact of disease, satisfaction with disease status, levels of depression, and emotion-regulation skills. METHODS: This is a single center, two-arm parallel randomized controlled trial. Patients will be screened for eligibility and willingness to participate and will be assessed and randomized to the experimental (MITIG.RA + TAU) or control condition (TAU) using computer randomization. MITIG.RA will be delivered by a certified psychologist and comprises eight sessions of 2 h, followed by two booster sessions. Outcomes will be assessed through validated self-report measures, including fatigue (primary outcome), perceived impact of disease, depressive symptoms, mindfulness, self-compassion, safety, and satisfaction (secondary outcomes). Assessment will take place at baseline, post-intervention, before the first and second booster sessions (weeks 12 and 20, respectively), and at 32 and 44 weeks after the interventions' beginning. DISCUSSION: We expect MITIG.RA to be effective in reducing levels of RA-associated fatigue. Secondarily, we hypothesize that the experimental group will show improvements in the overall perceived impact of disease, emotional distress, and emotion regulation skills. Our findings will contribute to determine the benefits of combining CCBT approaches for managing fatigue and associated distress in RA. TRIAL REGISTRATION: ClinicalTrials.gov NCT05389189. Registered on May 25, 2022.

Enhanced secretion of satiety-promoting gut hormones in healthy humans after consumption of white bread enriched with cellular chickpea flour: A randomized crossover study.

BACKGROUND: Dietary intake of pulses is associated with beneficial effects on body weight management and cardiometabolic health, but some of these effects are now known to depend on integrity of plant cells, which are usually disrupted by flour milling. Novel cellular flours preserve the intrinsic dietary fiber structure of whole pulses and provide a way to enrich preprocessed foods with encapsulated macronutrients. OBJECTIVES: This study aimed to determine the effects of replacing wheat flour with cellular chickpea flour on postprandial gut hormones, glucose, insulin, and satiety responses to white bread. METHODS: We conducted a double-blind randomized crossover study in which postprandial blood samples and scores were collected from healthy human participants (n = 20) after they consumed bread enriched with 0%, 30%, or 60% (wt/wt) cellular chickpea powder (CCP, 50 g total starch per serving). RESULTS: Bread type significantly affected postprandial glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) responses (time × treatment, P = 0.001 for both). The 60% CCP breads elicited significantly elevated and sustained release of these anorexigenic hormones [between 0% and 60% CPP-GLP-1: mean difference incremental area under the curve (iAUC), 3101 pM/min; 95% CI: 1891, 4310; P-adjusted < 0.001; PYY: mean difference iAUC, 3576 pM/min; 95% CI: 1024, 6128; P-adjusted = 0.006] and tended to increase fullness (time × treatment, P = 0.053). Moreover, bread type significantly influenced glycemia and insulinemia (time × treatment, P < 0.001, P = 0.006, and P = 0.001 for glucose, insulin, and C-peptide, respectively), with 30% CCP breads eliciting a >40% lower glucose iAUC (P-adjusted < 0.001) than the 0% CCP bread. Our in vitro studies revealed slow digestion of intact chickpea cells and provide a mechanistic explanation for the physiologic effects. CONCLUSIONS: The novel use of intact chickpea cells to replace refined flours in a white bread stimulates an anorexigenic gut hormone response and has potential to improve dietary strategies for prevention and treatment of cardiometabolic diseases. This study was registered at clinicaltrials.gov as NCT03994276.

In vitro protein bioaccessibility and human serum amino acid responses to white bread enriched with intact plant cells.

The cell structure and low glycaemic benefits of pulses are compromised by conventional flour-milling. Cellular chickpea powders ('CCPs') are a new alternative to pulse flours. Here we investigated the in vitro bioaccessibility of essential amino acids ('EAAs') from CCP-enriched bread products and determined the effect of their consumption on serum amino acid responses in healthy humans (n = 20, randomised cross-over design). Breads were prepared with 0, 30 and 60 % of the wheat flour replaced by CCP (intact cells containing encapsulated protein). We found that significant proportion of EAAs from encapsulated protein became bioaccessible during in vitro duodenal digestion, and that in vivo serum EAA responses from healthy human participants were significantly higher following consumption of CCP-enriched breads. Furthermore, the EAA profile of in vitro digestion products were well-correlated with in vivo peak serum EAAs responses. We conclude that CCP-enrichment of wheat bread improved the amount and diversity of bioavailable EAAs.

A Study on a Cast Steel Reinforced with WC-Metal Matrix Composite.

This study seeks to investigate the local reinforcement of low carbon cast steel specimens with WC-metal matrix composites (WC-MMCs), to obtain a new material effective in competing with hard alloy steels. For this purpose, a powder compact of tungsten carbide (WC) and iron (Fe) was prepared and placed in the mold cavity before casting. The reactions that occurred with the molten steel led to the formation of the WC-MMC and, consequently, to the local reinforcement of the steel. The microstructure of the WC-MMC reinforcement was characterized by scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), and electron backscatter diffraction (EBSD). The results showed a microstructural variation throughout the depth of the reinforcement. In the surface region, most of the original WC particles retain their polygonal morphology, but towards the base metal, the dissolution of the WC particles increased with the formation of (Fe,W)6C carbides. Closer to the base metal, dendritic eutectic carbides of (Fe,W)6C and fine (Fe,W)23C6 precipitates in a matrix of martensite were formed. The mechanical properties of the reinforcement were evaluated by hardness and ball-cratering abrasion tests. The results revealed a significant increase in hardness, being three times harder than the base metal, and a decrease of 39% in the wear rate.

Global RNAseq of ocular cells reveals gene dysregulation in both asymptomatic and with Congenital Zika Syndrome infants exposed prenatally to Zika virus.

In 2015, Brazil reported an outbreak identified as Zika virus (ZIKV) infection associated with congenital abnormalities. To date, a total of 86 countries and territories have described evidence of Zika infection and recently the appearance of the African ZIKV lineage in Brazil highlights the risk of a new epidemic. The spectrum of ZIKV infection-induced alterations at both cellular and molecular levels is not completely elucidated. Here, we present for the first time the gene expression responses associated with prenatal ZIKV infection from ocular cells. We applied a recently developed non-invasive method (impression cytology) which use eye cells as a model for ZIKV studies. The ocular profiling revealed significant differences between exposed and control groups, as well as a different pattern in ocular transcripts from Congenital Zika Syndrome (CZS) compared to ZIKV-exposed but asymptomatic infants. Our data showed pathways related to mismatch repair, cancer, and PI3K/AKT/mTOR signaling and genes probably causative or protective in the modulation of ZIKV infection. Ocular cells revealed the effects of ZIKV infection on primordial neuronal cell genes, evidenced by changes in genes associated with embryonic cells. The changes in gene expression support an association with the gestational period of the infection and provide evidence for the resulting clinical and ophthalmological pathologies. Additionally, the findings of cell death- and cancer-associated deregulated genes raise concerns about the early onset of other potential pathologies including the need for tumor surveillance. Our results thus provide direct evidence that infants exposed prenatally to the Zika virus, not only with CZS but also without clinical signs (asymptomatic) express cellular and molecular changes with potential clinical implications.

Production and Characterization of Austenitic Stainless Steel Cast Parts Reinforced with WC Particles Fabricated by Ex Situ Technique.

In this work, austenitic stainless steel specimens were locally reinforced with WC particles. The reinforcements were fabricated via an ex situ technique based on powder technology. Mixtures of WC, Fe, and M0101 binder were cold-pressed to obtain powder compacts. After debinding and sintering, the porous WC-Fe inserts were fixed in a mold cavity, where they reacted with liquid metal. Microstructural analysis was conducted for characterization of the phases constituting the produced reinforcement zone and the bonding interface. The results revealed that the reinforcement is a graded material with compositional and microstructural gradients throughout its thickness. The zone nearest to the surface has a ferrous matrix with homogeneously distributed WC particles and (Fe,W,Cr)6C and (Fe,W,Cr)3C carbides, formed from the liquid metal reaction with the insert. This precipitation leads to austenite destabilization, which transforms into martensite during cooling. A vast dissolution of the WC particles occurred in the inner zones, resulting in more intense carbides formation. Cr-rich carbides ((Fe,Cr,W)7C3, and (Fe,Cr,W)23C6) formed in the interdendritic regions of austenite; this zone is characterized by coarse dendrites of austenite and a multi-phase interdendritic network composed of carbides. An interface free of discontinuities and porosities indicates good bonding of the reinforcement zone to stainless steel.

Heart Rate Variability and Long Chain n-3 Polyunsaturated Fatty Acids in Chronic Kidney Disease Patients on Haemodialysis: A Cross-Sectional Pilot Study.

Low heart rate variability (HRV) is independently associated with increased risk of sudden cardiac death (SCD) and all cardiac death in haemodialysis patients. Long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) may exert anti-arrhythmic effects. This study aimed to investigate relationships between dialysis, sleep and 24 h HRV and LC n-3 PUFA status in patients who have recently commenced haemodialysis. A cross-sectional study was conducted in adults aged 40-80 with chronic kidney disease (CKD) stage 5 (n = 45, mean age 58, SD 9, 20 females and 25 males, 39% with type 2 diabetes). Pre-dialysis blood samples were taken to measure erythrocyte and plasma fatty acid composition (wt % fatty acids). Mean erythrocyte omega-3 index was not associated with HRV following adjustment for age, BMI and use of ß-blocker medication. Higher ratios of erythrocyte eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) were associated with lower 24 h vagally-mediated beat-to-beat HRV parameters. Higher plasma EPA and docosapentaenoic acid (DPAn-3) were also associated with lower sleep-time and 24 h beat-to-beat variability. In contrast, higher plasma EPA was significantly related to higher overall and longer phase components of 24 h HRV. Further investigation is required to investigate whether patients commencing haemodialysis may have compromised conversion of EPA to DHA, which may impair vagally-mediated regulation of cardiac autonomic function, increasing risk of SCD.

The impact of replacing wheat flour with cellular legume powder on starch bioaccessibility, glycaemic response and bread roll quality: A double-blind randomised controlled trial in healthy participants.

The global rise in obesity and type 2 diabetes has generated significant interest in regulating the glycaemic impact of staple foods. Wheat breads (white or wholemeal) are popular staples, but have a high-glycaemic index, due to the highly digestible wheat starch. Reducing the glycaemic potency of white bread is challenging because the bread-making conditions are mostly conducive to starch gelatinisation. Cellular legume powders are a new source of type 1 resistant starch, where the starch is encapsulated by dietary fibre in the form of intact plant cell walls. The starch in these cell powders is less susceptible to gelatinisation and digestion than starch in conventional legume flours. However, legume cell resilience to baking conditions and the effects of this ingredient on glycaemic responses and product quality are unknown. Here we show that the integrity of cell wall fibre in chickpea powder was preserved on baking and this led to a ~40% reduction in in vivo glycaemic responses (iAUC120) to white bread rolls (~50 g available carbohydrate and 12 g wheat protein per serving) when 30% or 60% (w/w) of the wheat flour was replaced with intact cell powder. Significant reductions in glycaemic responses were achieved without adverse effects on bread texture, appearance or palatability. Starch digestibility analysis and microscopy confirmed the importance of cell integrity in attenuating glycaemic responses. Alternative processing methods that preserve cell integrity are a new, promising way to provide healthier low glycaemic staple foods; we anticipate that this will improve dietary options for diabetes care.

Preparation and Microstructural Characterization of a High-Cr White Cast Iron Reinforced with WC Particles.

High-chromium white cast iron (WCI) specimens locally reinforced with WC-metal matrix composites were produced via an ex situ technique: powder mixtures of WC and Fe cold-pressed in a pre-form were inserted in the mold cavity before pouring the base metal. The microstructure of the resulting reinforcement is a matrix of martensite (α') and austenite (γ) with WC particles evenly distributed and (Fe,W,Cr)6C carbides that are formed from the reaction between the molten metal and the inserted pre-form. The (Fe,W,Cr)6C precipitation leads to the hypoeutectic solidification of the matrix and the final microstructure consists of martensite, formed from primary austenite during cooling and eutectic constituent with (Fe,Cr)7C3 and (Fe,W,Cr)6C carbides. The presence of a reaction zone with 200 µm of thickness, between the base metal and the composite should guarantee a strong bonding between these two zones.

Bacteriophages for Chronic Wound Treatment: from Traditional to Novel Delivery Systems.

The treatment and management of chronic wounds presents a massive financial burden for global health care systems, with significant and disturbing consequences for the patients affected. These wounds remain challenging to treat, reduce the patients' life quality, and are responsible for a high percentage of limb amputations and many premature deaths. The presence of bacterial biofilms hampers chronic wound therapy due to the high tolerance of biofilm cells to many first- and second-line antibiotics. Due to the appearance of antibiotic-resistant and multidrug-resistant pathogens in these types of wounds, the research for alternative and complementary therapeutic approaches has increased. Bacteriophage (phage) therapy, discovered in the early 1900s, has been revived in the last few decades due to its antibacterial efficacy against antibiotic-resistant clinical isolates. Its use in the treatment of non-healing wounds has shown promising outcomes. In this review, we focus on the societal problems of chronic wounds, describe both the history and ongoing clinical trials of chronic wound-related treatments, and also outline experiments carried out for efficacy evaluation with different phage-host systems using in vitro, ex vivo, and in vivo animal models. We also describe the modern and most recent delivery systems developed for the incorporation of phages for species-targeted antibacterial control while protecting them upon exposure to harsh conditions, increasing the shelf life and facilitating storage of phage-based products. In this review, we also highlight the advances in phage therapy regulation.

Microstructural Characterization of TiC-White Cast-Iron Composites Fabricated by In Situ Technique.

High-chromium white cast-iron specimens locally reinforced with TiC-metal matrix composites were successfully produced via an in situ technique based on combustion synthesis. Powder mixtures of Ti, Al, and graphite were prepared and compressed to fabricate green powder compacts that were inserted into the mold cavity before the casting. The heat of the molten iron causes the ignition of the combustion reaction of the reactant powders, resulting in the formation of the TiC by self-propagating high-temperature synthesis. The microstructure of the resultant composites and the bonding interfaces was characterized by scanning electron microscopy and energy dispersive spectroscopy (SEM/EDS), X-ray diffraction (XRD), and transmission electron microscopy (TEM). The microstructural results showed a good adhesion of the composite, suggesting an effective infiltration of the metal into the inserted compact, yet a non-homogeneous distribution of the TiC in the martensite matrix was observed. Based on the results, the in situ synthesis appears to be a great potential technique for industrial applications.

Intermittent energy restriction is comparable to continuous energy restriction for cardiometabolic health in adults with central obesity: A randomized controlled trial; the Met-IER study.

BACKGROUND & AIMS: Short bouts of severe energy restriction may have additional, beneficial cardiometabolic effects beyond that of weight loss. We aimed to assess the short-term effects of intermittent fasting on insulin sensitivity and related cardiometabolic mechanisms. METHODS: This parallel arm, randomized controlled trial compared the short-term effects of intermittent and continuous energy restriction (IER and CER) diets on markers of cardiometabolic health in individuals with central obesity, aiming for equivalent weight loss on both diets. Outcomes were assessed in non-smoking men and women (35-75 y), following 4-wk IER (48 h 600 kcal/d followed by 5-day healthy eating advice) or CER diets (-500 kcal/d healthy eating advice). The primary outcome was the revised quantitative insulin sensitivity check index (R-QUICKI), an indirect estimate of insulin sensitivity. Secondary outcomes included ambulatory blood pressure (ABP), indicators of sympathetic activity (heart rate variability (HRV) and normetanephrine), and markers of glucose homeostasis/insulin resistance, adiposity, lipids and inflammation. RESULTS: Forty-three participants completed the study. Reductions in body weight were equivalent in both groups: mean loss (%) -2.6; 95% CI -3.3, -1.9 and -2.9; -3.6, -2.1 for CER and IER, respectively, P = 0.464). R-QUICKI increased following IER and CER, with no between-diet differences (overall mean increase (%) 6.6; 3.6, 9.6). Fasting plasma glucose concentrations decreased after CER but not after IER (mean difference CER-IER - 4.8% (0.7, 8.9), P < 0.05) and fasting plasma non-esterified fatty acid concentrations were lower after IER compared to CER (mean difference CER-IER 0.15 mmol/L (0.06, 0.24), P < 0.005). There were no differences in lipids, adipokine/inflammatory markers, ABP or HRV between diets. CONCLUSIONS: Short-term CER or IER diets are comparable in their effects on most markers of cardiometabolic risk, although adaptive changes in glucose and fatty acid metabolism occur. This study is registered at clinicaltrials.gov as NCT02679989.

Impression Cytology Is a Non-invasive and Effective Method for Ocular Cell Retrieval of Zika Infected Babies: Perspectives in OMIC Studies.

IMPORTANCE: Non-invasive techniques for retrieving ocular surface cells from babies infected by zika virus (ZIKV) during the gestational period remain to be determined. OBJECTIVES: The aim of this study was to describe an optimized impression cytology method for the isolation of viable cells from Zika infected babies with and without Congenital Zika Syndrome (CZS) in satisfactory amount and quality to enable easy adoption in the field and application in the context of genomic and molecular approaches. DESIGN SETTINGS AND PARTICIPANTS: Ocular surface samples were obtained with a hydrophilic nitrocellulose membrane (through optimized impression cytology method) from twelve babies referred to the Pediatric Service of the Antonio Pedro Hospital, Universidade Federal Fluminense (UFF), Niteroi, Rio de Janeiro, Brazil. After an authorized written informed consent from the parents, samples were collected from both eyes of 12 babies (4 babies with maternal ZIKV exposure during gestation and presence of clinical signs which included ocular abnormalities and microcephaly; 4 babies with maternal ZIKV exposure during gestation but no clinical signs; and 4 unaffected control babies with negative PCR for Zika virus and without clinical signs). Cells were used for microscopy analyses and evaluated for their suitability for downstream molecular applications in transcriptomic and proteomic experiments. RESULTS: Our optimized impression cytology protocol enabled the capture of a considerable number of viable cells. The microscopic features of the conjunctival epithelial cells were described by both direct analysis of the membrane-attached cells and analysis of cytospinned captured cells using several staining procedures. Epithelial basal, polyhedral and goblet cells were clearly identified in all groups. All cases of ZIKV infected babies showed potential morphological alterations (cell keratinization, pyknosis, karyolysis, anucleation, and vacuolization). Molecular approaches were also performed in parallel. Genomic DNA and RNA were successfully isolated from all samples to enable the establishment of transcriptomic and proteomic studies. CONCLUSIONS AND RELEVANCE: Our method proved to be a suitable, fast, and non-invasive tool to obtain ocular cell preparations from babies with and without Zika infection. The method yielded sufficient cells for detailed morphological and molecular analyses of samples. We discuss perspectives for the application of impression cytology in the context of ZIKV studies in basic and clinical research.

Long-term Negative Psychological Impact of Presymptomatic Testing on Familial Amyloid Polyneuropathy / Efecto psicológico negativo a largo plazo de las pruebas genéticas presintomáticas en la polineuropatía amiloide familiar

This study addresses the profile of at-risk subjects whose long-term psychological impact of presymptomatic testing (PST) for Familial Amyloid Polyneuropathy (FAP) TTR V30M is negative. The sample consisted of 177 subjects, aged over 20 years that were 50% at-risk for FAP, and performed the PST at least three years ago. Participants were contacted by mail, one time only, to answer the sociodemographic questionnaire and the Brief Symptom Inventory (BSI), the Self-Rating Anxiety Scale of Zung (SAS), and the Beck Depression Inventory (BDI). From the sample, 22.6% (BSI), 16.4% (SAS), and 9% (BDI) subjects presented negative psychological impact, after having performed the PST for more than 3 years. Subjects with clinically significant values in BSI, SAS, and BDI have an overlapping profile concerning the total sample, except regarding age, since clinically depressed subjects have a higher mean age. Married women or living in unmarried unions, aged between 30 and 45 years, employed, carriers, and having performed the PST test for 6-7 years are a group raising higher concern and requiring a more active role with respect to the psychological impact of the PST for FAP. The role of the clinical and health psychologist with these patients is critical in the adjustment to the presymptomatic test result as well as in adherence to the available treatments conducive to a better quality of life, in carriers

Este estudio aborda el perfil de sujetos en riesgo cuyo impacto psicológico a largo plazo de las pruebas presintomáticas (PST) para la polineuropatía amiloide familiar (FAP) TTR V30M es negativo. La muestra consistió en 177 sujetos mayores de 20 años que tenían un 50% de riesgo de FAP, que habían realizado el PST hacía al menos tres años. Se contactó con los participantes por correo, solo una vez, para responder el cuestionario sociodemográfico y el Inventario de síntomas breves (BSI), la Escala de ansiedad de autoclasificación de Zung (SAS) y el Inventario de depresión de Beck (BDI). El 22.6% (BSI), el 16.4% (SAS) y el 9% (BDI) de los sujetos de la muestra presentaron un impacto psicológico negativo después de haber realizado el PST durante más de 3 años. Los sujetos con valores clínicamente significativos en BSI, SAS y BDI tienen un perfil superpuesto con respecto a la muestra total, excepto con respecto a la edad, ya que los sujetos clínicamente deprimidos tienen una edad media más alta. Las mujeres casadas o que viven en pareja, con edades entre 30 y 45 años, que trabajan, son portadoras y han realizado la prueba PST durante 6-7 años son un grupo que suscita una mayor preocupación y requiere un papel más activo con respecto al impacto psicológico del PST para FAP. El papel del psicólogo clínico y de la salud con estos pacientes es decisivo en el ajuste del resultado de la prueba presintomática, así como en la adhesión a los tratamientos disponibles que conducen a una mejor calidad de vida en los portadores

Exposure effects of endotoxin-free titanium-based wear particles to human osteoblasts.

Titanium-based materials are widely employed by the biomedical industry in orthopedic and dental implants. However, when placed into the human body, these materials are highly susceptible to degradation processes, such as corrosion, wear, and tribocorrosion. As a consequence, metallic ions or particles (debris) may be released, and although several studies have been conducted in recent years to better understand the effects of their exposure to living cells, a consensual opinion has not yet been obtained. In this work, we produced metallic-based wear particles by tribological tests carried out on Ti-6Al-4V and Ti-15Zr-15Mo alloys. They were posteriorly physicochemically characterized according to their crystal structure, size, morphology, and chemical composition and compared to Ti-6Al-4V commercially available particles. Finally, adsorbed endotoxins were removed (by applying a specific thermal treatment) and endotoxin-free particles were used in cell experiments to evaluate effects of their exposure to human osteoblasts (MG-63 and HOb), namely cell viability/metabolism, proinflammatory cytokine production (IL-6 and PGE2), and susceptibility to internalization processes. Our results indicate that tribologically-obtained wear particles exhibit fundamental differences in terms of size (smaller) and morphology (irregular shapes and rough surfaces) when compared to the commercial ones. Consequently, both Ti-6Al-4V and Ti-15Zr-15Mo particles were able to induce more pronounced effects on cell viability (decrease) and cytokine production (increase) than did Ti-6Al-4V commercial particles. Furthermore, both types of wear particles penetrated osteoblast membranes and were internalized by the cells. Influences on cytokine production by endotoxins were also demonstrated.

Multifactorial explanatory model of depression in patients with rheumatoid arthritis: a structural equation approach.

OBJECTIVES: Depressive symptoms are common among patients with rheumatoid arthritis (RA). This study was aimed at developing a multifactorial explanatory model that evaluated the influence of personality traits, disease activity, perceived disease impact, and comorbidities. METHODS: This cross-sectional study used structural equation modelling estimation to analyse the associations between these dimensions, pursuing three hypotheses. Depressive symptoms were assessed using the Hospital Anxiety and Depression Scale, disease impact by the Rheumatoid Arthritis Impact of Disease score, personality by the Ten Item Personality Inventory and the disease activity through the Disease Activity Score 28 joints. The influence of comorbidities was investigated by multigroup analysis. RESULTS: The final model derived from data of 254 patients presented a good fit. Disease activity had an indirect relation with depressive symptoms mediated by disease impact (ß=0.17, p<0.001), but the direct relationship between disease activity and depressive symptoms was not significant (ß=0.09; p=0.07). "Positive" personality had a strong negative direct relation with depressive symptoms as well as an indirect relationship mediated by disease impact (total effect ß=-0.61, p<0.001). The final proposed model explained 58% of the variance of depressive symptoms. Multigroup analysis showed an invariant model when comparing patients with and without comorbidities (dχ2=9.03; df=12; p=0.70). CONCLUSIONS: Personality characteristics seem to have a major influence upon the impact of disease and the patient's adjustment to RA, including the vulnerability or resilience to depression. Individual personality traits deserve attention in tailored assessment and treatment of patients with RA, in order to optimise outcomes.