Engineering buffer layers to improve temperature resilience of magnetic tunnel junction sensors.

Improving the thermal resilience of magnetic tunnel junctions (MTJs) broadens their applicability as sensing devices and is necessary to ensure their operation under harsh environments. In this work, we are address the impact of temperature on the degradation of the magnetic reference in field sensor stacks based on MgO-MTJs. Our study starts by simple MnIr/CoFe bilayers to gather enough insights into the role of critical morphological and magnetic parameters and their impact in the temperature dependent behavior. The exchange bias coupling field (Hex), coercive field (Hc), and blocking temperature (Tb) distribution are tuned, combining tailored growth conditions of the antiferromagnet and different buffer layer materials and stackings. This is achieved by a unique combination of ion beam deposition and magnetron sputtering, without vaccum break. Then, the work then extends beyond bilayers into more complex state-of-the-art MgO MTJ stacks as those employed in commercial sensing applications. We systematically address their characteristic fields, such as the width of the antiferromagnetic coupling plateau ΔH, and study their dependence on temperature. Although, [Ta/CuN] buffers showed higher key performance indications (e.g.Hex) at room temperature in both bilayers and MTJs, [Ta/Ru] buffers showed an overall wider ΔHup to 200 °C, more suitable to push high temperature operations. This result highlights the importance of properly design a suitable buffer layer system and addressing the complete MTJ behavior as function of temperature, to deliver the best stacking design with highest resilience to high temperature environments.

Evaluation of bone repair with platelet-rich fibrin following the extraction of impacted third molars - randomized clinical trial.

BACKGROUND: The aim of the present study was to evaluate postoperative effects of platelet-rich fibrin (PRF) in wound and bone healing, pain, swelling and periodontal complications outcomes after impacted third molars extraction. MATERIAL AND METHODS: A prospective, randomized, split-mouth, double-blind clinical trial was conducted. PRF was placed within sockets following tooth removal and before suturing mucoperiosteal flap while no treatment was performed on control group's sockets. Patients were evaluated considering bone volume which was obtained in the 90-day postoperative period. Other variables included trabecular thickness, trabecular distance and grey values, pain, swelling, and wound healing. A Wilcoxon test and a t-Student test were used at a 5% significance level and a Friedman test was used to multiple comparisons. RESULTS: Forty-four surgeries were performed in the present study. The patients' mean age was 22.41 (± 2.75 years) and 72.73% were women. PRF was associated to increased trabecular thickness and bone volume means (p < 0.001). The experimental group had significantly lower pain scores at 4h, 6h, 8h, 16h, 24h, and 72h (p ˂ 0.05). Mean swelling was lower on the experimental group (p < 0.001). The PRF group showed significant higher wound healing (p ˂ 0.001). CONCLUSIONS: Alveolar filling with PRF improves wound and bone healing after extractions while also decreasing pain and swelling in the postoperative period.

Aberrant hippocampal transmission and behavior in mice with a stargazin mutation linked to intellectual disability.

Mutations linked to neurodevelopmental disorders, such as intellectual disability (ID), are frequently found in genes that encode for proteins of the excitatory synapse. Transmembrane AMPA receptor regulatory proteins (TARPs) are AMPA receptor auxiliary proteins that regulate crucial aspects of receptor function. Here, we investigate a mutant form of the TARP family member stargazin, described in an ID patient. Molecular dynamics analyses predicted that the ID-associated stargazin variant, V143L, weakens the overall interface of the AMPAR:stargazin complex and impairs the stability of the complex. Knock-in mice harboring the V143L stargazin mutation manifest cognitive and social deficits and hippocampal synaptic transmission defects, resembling phenotypes displayed by ID patients. In the hippocampus of stargazin V143L mice, CA1 neurons show impaired spine maturation, abnormal synaptic transmission and long-term potentiation specifically in basal dendrites, and synaptic ultrastructural alterations. These data suggest a causal role for mutated stargazin in the pathogenesis of ID and unveil a new role for stargazin in the development and function of hippocampal synapses.

Nontuberculous Mycobacteria in Portugal: Trends from the last decade.

INTRODUCTION AND OBJECTIVES: Nontuberculous mycobacteria (NTM) are opportunistic human pathogens found in the environment. The transmission seems to be associated with inhalation of aerosol droplets, ingestion or trauma events. Recent studies indicate that NTM disease is increasing worldwide, however, the true clinical impact of NTM infections is difficult to determine due to challenges in discriminating between disease and colonization as they are ubiquitous in the environment. In addition, understanding the epidemiology of NTM is difficult and has not yet been established. In this work, we used a country NTM representative collection from the National Reference Laboratory for Tuberculosis (NRL-TB) of the National Institute of Health (INSA), to characterize the circulation trends of NTM species in Portugal and the most affected regions, contributing to a better understanding of the NTM epidemiology. MATERIAL AND METHODS: We conducted a nationwide retrospective study where all individuals with positive NTM cultures at the NRL-TB of the INSA from 2014 to December 2020 were included. Positive cultures were identified using GenoType Mycobacterium CM/AS® (Hain Lifescience) according to manufacturer's instructions, or hsp65 DNA sequencing as previously described. Social-demographic data from patients were also analyzed and patients classified into 3 groups according only to microbiological data, "definite NTM disease", "NTM colonization" and, "possible NTM disease". RESULTS: In the period 2014-2020, the NRL-TB performed 50397 cultures. Among these, 1118 cultures were NTM positive retrieved from 944. Most of our cases were in patients whose mean age was 64±15.9 years, and no significant differences between gender was observed, although more frequent in male patients. Overall, from the 944 cases, we were able to identified 93 "definite NTM disease" cases and 79 "possible NTM disease". Mycobacterium avium complex (MAC) (40,8%), Mycobacterium abscessus-chelonae complex (MABC) (9,6%) and Mycobacterium fortuitum (6,3%) were responsible for most of the infections. The geographical distribution of NTM cases varied significantly and was possible to observe that was independent of population density. The region were most cases occurred was Lisbon Metropolitan Area (31,9%), followed by North (25,3%) and Centre (24,4%), however North region has the highest number of "definite NTM disease" cases (n=33). CONCLUSIONS: This is the first national wide epidemiological study on this subject, contributing to a better understanding of NTM dynamics in Portugal. MAC was the NTM species responsible for the majority of infections and, LMA the region with the highest number of cases. It was also possible to conclude that the number of NTM isolates is independent of the demography of the region.

Discovery of serum biomarkers for diagnosis of tuberculosis by NMR metabolomics including cross-validation with a second cohort.

BACKGROUND: Tuberculosis (TB) is a disease with worldwide presence and a major cause of death in several developing countries. Current diagnostic methodologies often lack specificity and sensitivity, whereas a long time is needed to obtain a conclusive result. METHODS: In an effort to develop better diagnostic methods, this study aimed at the discovery of a biomarker signature for TB diagnosis using a Nuclear Magnetic Resonance based metabolomics approach. In this study, we acquired 1H NMR spectra of blood serum samples of groups of healthy subjects, individuals with latent TB and of patients with pulmonary and extra-pulmonary TB. The resulting data were treated with uni- and multivariate statistical analysis. RESULTS: Six metabolites (inosine, hypoxanthine, mannose, asparagine, aspartate and glutamate) were validated by an independent cohort, all of them related with metabolic processes described as associated with TB infection. CONCLUSION: The findings of the study are according with the WHO Target Product Profile recommendations for a triage test to rule-out active TB.

Examining the Coach Motivation Questionnaire in Fitness Professionals (CMQ-FP): Factor Structure, Invariance, and Predictive Analysis.

Purpose: To date, most research on the assessment of motivation has been exerciser-focused and has not considered how fitness professionals' motivations impact their behaviors toward exercisers during training sessions. The purpose of this study was to examine the factor structure of the Coach Motivation Questionnaire in a sample of fitness professionals (CMQ-FP) to ascertain its usefulness for this vocational grouping. Measurement invariance analysis was conducted between female and male fitness professionals, and predictive validity was tested considering need-supportive and need-thwarting behaviors as outcomes. Methods: Participants were 799 fitness professionals (female = 412) aged between 20 and 56 years (M = 28.71, SD = 3.24), who completed a multi-section survey assessing their motivation toward work and their interpersonal behaviors when engaging with exercisers. Results: The results of this research supported all three hypotheses. First, the hypothesized 6-factor measurement model showed acceptable fit to the data. Second, the factor structure of the CMQ-FP was invariant across gender (male and female fitness professionals). Third, fitness professionals' (autonomous or controlled) motivation was a valid predictor of need-supportive or need-thwarting behaviors. Conclusion: This study supported the factor structure of the CMQ-FP, presenting as a valid measure of motivation in fitness professionals. Understanding fitness professionals' perceptions of their coaching motivation can inform professional development activities to assist fitness professionals to increase understanding of what motivates these professionals and how they might be more need-supportive and less need-thwarting in their pedagogical behaviors.

Tropical grass and legume pastures may alter lamb meat physical and chemical characteristics.

The present study assessed the influence of the type of the tropical pastures on lamb body weight (BW) gain and meat quality. Fifty-four lambs were allocated to three grazing pastures: (1) AG - Aruana grass (Panicum maximum cv. IZ-5); (2) PP - pigeon pea legume (Cajanus cajan cv. Anão); and (3) CS - contiguous swards, half of the paddock with AG and half with PP. After 92 days of grazing, the lambs were slaughtered. Carcasses were evaluated and the longissimus muscle was collected to determine color, lipid profile, tocopherol concentrations, and lipid oxidation. Although the pastures present differences in the characteristics of nutritional quality, the animals did not show difference in BW gain. The results show that all forage presented similar concentration of alpha-tocopherol (137 ± 14.37 mg kg-1 of fresh matter), whereas total and condensed tannin contents were greater in PP, intermediate in CS, and the lowest in AG treatment (P = 0.0001). Meat α-tocopherol content was similar among treatments (P = 0.1392), with an average concentration close to the optimal level to reduce the meat oxidation. Meat from AG treatment had 45 and 25% lower n-6/n-3 ratio than meat from PP and CS treatments, respectively. The legume increases the unsaturated fatty acids and the grass can reduce the n6/n3 ratio. The level of condensed tannin concentration did show to have important effect on meat characteristics. Both tropical pastures studied can provide a high amount of alpha-tocopherol, generating a great potential to increase the concentration of this antioxidant in lamb's meat.

Calvarial graft resorption index in the reconstruction of the maxillary sinus in patients with atrophic maxillas: a prospective clinical study.

The objective of this study was to assess the resorption index of particulate calvarial grafts in maxillary sinuses of patients undergoing total reconstruction of an atrophic maxilla with residual alveolar bone that was less than, or equal to, 3mm thick. Twenty-one maxillary sinus floor elevations were carried out using particulate calvarial grafts in 11 individuals with totally edentulous maxillas. All patients had computed tomography (CT) before (T0), and 48hours (T1) and six months after surgery (T2). For each CT scan, linear measurements were taken of sections of the anterior, medial, and posterior regions of the maxillary sinus. There was a significant increase in the height of the maxillary sinus floor when T0 was compared with T1 (p=0.001). There was a statistically significant reduction in all maxillary sinus measurements when T1 was compared with T2; the mean height reduction being 2.36mm (16.87%) in the anterior region, 3.53mm (22.47%) in the medial region, and 2.21mm (22.78%) in the posterior region (p=0.001). Mean resorption was 20.7%. Autogenous calvarial bone used alone is an option for graft material in pneumatised maxillary sinuses and in cases where there is limited alveolar bone.

Thermally Switchable Electrically Conductive Thermoset rGO/PK Self-Healing Composites.

Among smart materials, self-healing is one of the most studied properties. A self-healing polymer can repair the cracks that occurred in the structure of the material. Polyketones, which are high-performance thermoplastic polymers, are a suitable material for a self-healing mechanism: a furanic pendant moiety can be introduced into the backbone and used as a diene for a temperature reversible Diels-Alder reaction with bismaleimide. The Diels-Alder adduct is formed at around 50 °C and broken at about 120 °C, giving an intrinsic, stimuli-responsive self-healing material triggered by temperature variations. Also, reduced graphene oxide (rGO) is added to the polymer matrix (1.6-7 wt%), giving a reversible OFF-ON electrically conductive polymer network. Remarkably, the electrical conductivity is activated when reaching temperatures higher than 100 °C, thus suggesting applications as electronic switches based on self-healing soft devices.

IL-22 increases the production of sFRP3 by FLS in inflammatory joint diseases.

Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) are inflammatory diseases with different bone remodeling patterns. Fibroblast-like synoviocytes (FLS) are cells involved in the transition from an acute and reparable phase to a chronic and persistent stage in these diseases. The distinction of joint phenotypes involves inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-17, and IL-22 directly or through key signaling pathways such as Wnt. To evaluate the role of FLS as the source of Wnt antagonists (sFRP3/FRZB and Dkk1) in the synovia, levels of TNF- α, IL-17, IL-22, Dkk1, and sFRP3 were measured by ELISA directly in the synovial fluid of patients with RA, PsA, or AS. Dkk1 and sFRP3 were also measured in the FLS culture supernatants after different inflammatory stimulus. sFRP3 and Dkk1 are constitutively expressed by FLS. IL-22 and sFRP3 were positively correlated (r=0.76; P<0.01) in synovial fluid. The stimulation of FLS with IL-22, but not TNF-alpha and IL-17, increased the production of sFRP3. No stimulus altered the basal expression of Dkk1. These results showed, for the first time, the ability of IL-22 to increase the expression of sFRP3/FRZB by human FLS in both in vitro and ex vivo models. This finding linked IL-22 to local inhibition of Wnt signaling and possibly to blockade of osteogenesis. Furthermore, FLS presented as a source of this inhibitor in synovial fluid, assigning to this cell a bone injury mechanism.

Sex Differences in Relationships Between Perceived Coach-Induced Motivational Climates, Basic Psychological Needs, and Behavior Regulation Among Young Swimmers.

This study analyzed independent and codependent effects of task- and ego-involving motivational climates on basic psychological need satisfaction and behavioral regulation (i.e., autonomous and controlled motivation) among young athletes. Participants were young Portuguese female (n = 114) and male (n = 324) swimmers, nested within four different clubs. Participants completed a multisection survey, assessing motivational climates, basic psychological needs satisfaction, and behavioral regulation. We used polynomial regression analysis with surface response methodology to analyze the interactions between these constructs. We found that perceived task- and ego-involving motivational climates were not mutually exclusive; rather, their relationship depended on how athletes perceived coaches' behaviors and how coaches emphasized one or both climates. Coaches who fostered both motivational climates promoted positive outcomes among male (but not female) athletes.

Magnetic field induced vortices in graphene quantum dots.

The energy spectrum and local current patterns in graphene quantum dots (QD) are investigated for different geometries in the presence of an external perpendicular magnetic field. Our results demonstrate that, for specific geometries and edge configurations, the QD exhibits vortex and anti-vortex patterns in the local current density, in close analogy to the vortex patterns observed in the probability density current of semiconductor QD, as well as in the order parameter of mesoscopic superconductors.

High fructose-containing drinking water-induced steatohepatitis in rats is prevented by the nicotinamide-mediated modulation of redox homeostasis and NADPH-producing enzymes.

An imbalance in the redox state, increased levels of lipid precursors and overactivation of de novo lipogenesis determine the development of fibrosis during nonalcoholic steatohepatitis (NASH). We evaluated the modulation of NADPH-producing enzymes associated with the antifibrotic, antioxidant and antilipemic effects of nicotinamide (NAM) in a model of NASH induced by excess fructose consumption. Male rats were provided drinking water containing 40% fructose for 16 weeks. During the last 12 weeks of fructose administration, water containing NAM was provided to some of the rats for 5 h/day. The biochemical profiles and the ghrelin, leptin, lipoperoxidation and TNF-α levels in serum and the glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME) and NADP+-dependent isocitric dehydrogenase (IDP) levels, the reduced/oxidized glutathione (GSH/GSSG) and reduced/oxidized nicotinamide adenine dinucleotide (phosphate) (NAD(P)H/NAD(P)+) ratios, and the levels of various lipogenic and fibrotic markers in the liver were evaluated. The results showed that hepatic fibrosis induced by fructose consumption was associated with weight gain, hunger-satiety system dysregulation, hyperinsulinemia, dyslipidemia, lipoperoxidation and inflammation. Moreover, increased levels of hepatic G6PD and ME activity and expression, the NAD(P)H/NAD(P)+ ratios, and GSSG concentration and increased expression of lipogenic and fibrotic markers were detected, and these alterations were attenuated by NAM administration. Specifically, NAM diminished the activity and expression of G6PD and ME, and this effect was associated with a decrease in the NADPH/NADP+ ratios, increased GSH levels and decreased lipoperoxidation and inflammation, ameliorating fibrosis and NASH development. NAM reduces liver steatosis and fibrosis by regulating redox homeostasis through a G6PD- and ME-dependent mechanism.

IL-22 increases the production of sFRP3 by FLS in inflammatory joint diseases

Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) are inflammatory diseases with different bone remodeling patterns. Fibroblast-like synoviocytes (FLS) are cells involved in the transition from an acute and reparable phase to a chronic and persistent stage in these diseases. The distinction of joint phenotypes involves inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-17, and IL-22 directly or through key signaling pathways such as Wnt. To evaluate the role of FLS as the source of Wnt antagonists (sFRP3/FRZB and Dkk1) in the synovia, levels of TNF- α, IL-17, IL-22, Dkk1, and sFRP3 were measured by ELISA directly in the synovial fluid of patients with RA, PsA, or AS. Dkk1 and sFRP3 were also measured in the FLS culture supernatants after different inflammatory stimulus. sFRP3 and Dkk1 are constitutively expressed by FLS. IL-22 and sFRP3 were positively correlated (r=0.76; P<0.01) in synovial fluid. The stimulation of FLS with IL-22, but not TNF-alpha and IL-17, increased the production of sFRP3. No stimulus altered the basal expression of Dkk1. These results showed, for the first time, the ability of IL-22 to increase the expression of sFRP3/FRZB by human FLS in both in vitro and ex vivo models. This finding linked IL-22 to local inhibition of Wnt signaling and possibly to blockade of osteogenesis. Furthermore, FLS presented as a source of this inhibitor in synovial fluid, assigning to this cell a bone injury mechanism.

Emotional and behavioral problems in children and adolescents with lower urinary tract dysfunction: a population-based study.

BACKGROUND: An association has been found between lower urinary tract dysfunction (LUTD) and emotional and behavioral problems, particularly in cases of urinary incontinence. Other associated symptoms and the coexistence of functional constipation require further investigation. OBJECTIVE: To assess whether emotional and behavioral problems are more common in children and adolescents with LUTD. STUDY DESIGN: A multicenter, cross-sectional, population-based study conducted in public places. Parents answered questions on urinary and psychological symptoms in their children aged 5-14 years. Children/adolescents with neurological problems or anatomical urinary tract abnormalities were excluded. The Dysfunctional Voiding Scoring System was used for assessing urinary symptoms, the Rome III Diagnostic Criteria for evaluating bowel symptoms, and the Strengths and Difficulties Questionnaire (SDQ) for evaluating emotional and behavioral problems. RESULTS: Of the 806 children/adolescents included, 53% were female. The mean age was 9.1 ± 2.7 years. The prevalence of LUTD was 16.4%. Overall, 26.2% had abnormal scores in the overall SDQ scale, 29.2% in the emotional problems subscale, and 30% in the conduct problems subscale. Of the children with LUTD, 40.5% screened positive for emotional/behavioral problems, with a significant association being found for the overall SDQ scale (P < 0.001) and for the emotional problems (P < 0.001), conduct problems (P < 0.001), and hyperactivity (P = 0.037) subscales. Urinary urgency, urinary incontinence, and voiding postponement were significantly associated with a greater prevalence of abnormalities in the overall SDQ score (P = 0.05; P = 0.004, and P = 0.012, respectively). Bladder and bowel dysfunction was an aggravator of emotional and behavioral problems, with more intense symptoms, both in the overall SDQ scale and in the subscales. In the multivariate analysis, the factors independently associated with the presence of emotional and behavioral problems were LUTD (odds ratio [OR] = 1.91), constipation (OR = 1.7), studying in a government-funded school (OR = 2.2), and poor education of the head of the family (OR = 1.9). CONCLUSIONS: Children and adolescents with LUTD have more emotional and behavioral problems, with bladder and bowel dysfunction being an aggravating factor for this association.

Better Selection Criteria With Prognostic Factors for Liver Transplantation.

BACKGROUND: Liver transplantation has evolved significantly in recent years, with each advancement part of the effort toward increasing patient and graft survival as well as quality of life. The objective of this study was to evaluate the prognostic factors and selection criteria for liver transplantation. METHODS: Our study was a statistical analysis, logistic regression, and survival evaluation of a total of 80 liver transplants that were performed between June 1, 2016 and September 24, 2016. Recipient factors evaluated included age, retransplantation, hemodialysis, cardiac risk, portal vein thrombosis, hospitalization, fulminant hepatitis, previous surgery, renal failure, and Model for End-stage Liver Disease (MELD) score. Donor factors included age, cardiac arrest, acidosis, days in the intensive care unit, steatosis, and vasoactive drug use. RESULTS: Of the 80 patients transplanted, 65 deceased donor liver transplants (DDLTs) and 15 living donor liver transplants (LDLTs) were performed. LDLT overall 1-year patient survival was 77.5% and graft survival 75%, and DDLT overall patient survival was 89.23% and graft survival was 86.15%. On evaluated score criteria analyzed we observed a significant score on recipient (P = .01) and not significant on donor (P =.45). Isolated factors evaluated included recipient age (relative risk [RR] 3.15, 95% confidence interval [CI] 0.89 to 11.09; P = .074), retransplant (RR 4.22, 95% CI 1.36 to 13.1; P = .013), and hemodialysis (RR 4.23, 95% CI 1.45 to 12.31, P = .008). On donor evaluation, we observed moderate and severe steatosis (RR 3.8, 95% CI 0.86 to 16.62; P = .06). CONCLUSION: In conclusion, we demonstrate a relevant model of criteria selection of liver transplant patients that is able to make a better match between the donor and recipient allocation for a better graft and patient survival.

Preclinical evaluation of mRNA trimannosylated lipopolyplexes as therapeutic cancer vaccines targeting dendritic cells.

Clinical trials with direct administration of synthetic mRNAs encoding tumor antigens demonstrated safety and induction of tumor-specific immune responses. Their proper delivery to dendritic cells (DCs) requires their protection against RNase degradation and more specificity for dose reduction. Lipid-Polymer-RNA lipopolyplexes (LPR) are attractive mRNA delivery systems and their equipment with mannose containing glycolipid, specific of endocytic receptors present on the membrane of DCs is a valuable strategy. In this present work, we evaluated the capacity of LPR functionalized with a tri-antenna of α-d-mannopyranoside (triMN-LPR) concerning (i) their binding to CD209/DC-SIGN and CD207/Langerin expressing cell lines, human and mouse DCs and other hematopoietic cell populations, (ii) the nature of induced immune response after in vivo immunization and (iii) their therapeutic anti-cancer vaccine efficiency. We demonstrated that triMN-LPR provided high induction of a local inflammatory response two days after intradermal injection to C57BL/6 mice, followed by the recruitment and activation of DCs in the corresponding draining lymph nodes. This was associated with skin production of CCR7 and CXCR4 at vaccination sites driving DC migration. High number of E7-specific T cells was detected after E7-encoded mRNA triMN-LPR vaccination. When evaluated in three therapeutic pre-clinical murine tumor models such as E7-expressing TC1 cells, OVA-expressing EG7 cells and MART-1-expressing B16F0 cells, triMN-LPR carrying mRNA encoding the respective antigens significantly exert curative responses in mice vaccinated seven days after initial tumor inoculation. These results provide evidence that triMN-LPR give rise to an efficient stimulatory immune response allowing for therapeutic anti-cancer vaccination in mice. This mRNA formulation should be considered for anti-cancer vaccination in Humans.