Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8+ T cells in tumors.

A common metabolic alteration in the tumor microenvironment (TME) is lipid accumulation, a feature associated with immune dysfunction. Here, we examined how CD8+ tumor infiltrating lymphocytes (TILs) respond to lipids within the TME. We found elevated concentrations of several classes of lipids in the TME and accumulation of these in CD8+ TILs. Lipid accumulation was associated with increased expression of CD36, a scavenger receptor for oxidized lipids, on CD8+ TILs, which also correlated with progressive T cell dysfunction. Cd36-/- T cells retained effector functions in the TME, as compared to WT counterparts. Mechanistically, CD36 promoted uptake of oxidized low-density lipoproteins (OxLDL) into T cells, and this induced lipid peroxidation and downstream activation of p38 kinase. Inhibition of p38 restored effector T cell functions in vitro, and resolution of lipid peroxidation by overexpression of glutathione peroxidase 4 restored functionalities in CD8+ TILs in vivo. Thus, an oxidized lipid-CD36 axis promotes intratumoral CD8+ T cell dysfunction and serves as a therapeutic avenue for immunotherapies.

Macrophage phenotypes and functions: resolving inflammation and restoring homeostasis.

Inflammation must be tightly regulated to both defend against pathogens and restore tissue homeostasis. The resolution of inflammatory responses is a dynamic process orchestrated by cells of the immune system. Macrophages, tissue-resident innate immune cells, are key players in modulating inflammation. Here, we review recent work highlighting the importance of macrophages in tissue resolution and the return to homeostasis. We propose that enhancing macrophage pro-resolution functions represents a novel and widely applicable therapeutic strategy to dampen inflammation, promote repair, and restore tissue integrity and function.

The conundrum of differentiating Cushing's syndrome from non-neoplastic hypercortisolism: a systematic review and meta-analysis.

CONTEXT: Once hypercortisolemia is confirmed, differential diagnosis between Cushing's syndrome (CS) due to neoplastic endogenous hypercortisolism and non-neoplastic hypercortisolism (NNH, pseudo-Cushing's syndrome) is crucial. Due to worldwide corticotropin-releasing hormone (CRH) unavailability, accuracy of alternative tests to dexamethasone (Dex)-CRH, is clearly needed. OBJECTIVE: Assess the diagnostic accuracy of Dex-CRH test, desmopressin stimulation test, midnight serum cortisol (MSC), and late-night salivary cortisol (LNSC) levels to distinguish CS from NNH. METHODS: Articles through March 2022 were identified from Scopus, Web of Science, MEDLINE, EMBASE, and PubMed. All steps through the systematic review were performed independently and in duplicate and strictly adhered to the updated PRISMA-DTA checklist. DATA SYNTHESIS: A total of 24 articles (1900 patients) were included. Dex-CRH had a pooled sensitivity and specificity of 91% (95%CI 87-94%; I2 0%) and 82% (73-88%; I2 50%), desmopressin test 86% (81-90%; I2 28%) and 90% (84-94%; I2 15%), MSC 91% (85-94%; I2 66%) and 81% (70-89%; I2 71%), and LNSC 80% (67-89%; I2 57%) and 90% (84-93%; I2 21%), respectively. Summary receiver operating characteristics areas under the curve were Dex-CRH 0.949, desmopressin test 0.936, MSC 0.942, and LNSC 0.950 without visual or statistical significance. The overall risk of studies bias was moderate. CONCLUSION: Dex-CRH, the desmopressin stimulation test, and MSC have similar diagnostic accuracy, with Dex-CRH and MSC having slightly higher sensitivity, and the desmopressin test being more specific. LNSC was the least accurate, probably due to high heterogeneity, intrinsic variability, different assays, and lack of consistent reported cutoffs. When facing this challenging differential diagnosis, the results presented here should increase clinicians' confidence when deciding which test to perform.

Experimental evaluation of the impact of sEMG interfaces in enhancing embodiment of virtual myoelectric prostheses.

INTRODUCTION: Despite recent technological advances that have led to sophisticated bionic prostheses, attaining embodied solutions still remains a challenge. Recently, the investigation of prosthetic embodiment has become a topic of interest in the research community, which deals with enhancing the perception of artificial limbs as part of users' own body. Surface electromyography (sEMG) interfaces have emerged as a promising technology for enhancing upper-limb prosthetic control. However, little is known about the impact of these sEMG interfaces on users' experience regarding embodiment and their interaction with different functional levels. METHODS: To investigate this aspect, a comparison is conducted among sEMG configurations with different number of sensors (4 and 16 channels) and different time delay. We used a regression algorithm to simultaneously control hand closing/opening and forearm pronation/supination in an immersive virtual reality environment. The experimental evaluation includes 24 able-bodied subjects and one prosthesis user. We assess functionality with the Target Achievement Control test, and the sense of embodiment with a metric for the users perception of self-location, together with a standard survey. RESULTS: Among the four tested conditions, results proved a higher subjective embodiment when participants used sEMG interfaces employing an increased number of sensors. Regarding functionality, significant improvement over time is observed in the same conditions, independently of the time delay implemented. CONCLUSIONS: Our work indicates that a sufficient number of sEMG sensors improves both, functional and subjective embodiment outcomes. This prompts discussion regarding the potential relationship between these two aspects present in bionic integration. Similar embodiment outcomes are observed in the prosthesis user, showing also differences due to the time delay, and demonstrating the influence of sEMG interfaces on the sense of agency.

The SoftHand Pro platform: a flexible prosthesis with a user-centered approach.

BACKGROUND: Among commercially-available upper-limb prostheses, the two most often used solutions are simple hook-style grippers and poly-articulated hands, which present a higher number of articulations and show a closer resemblance to biological limbs. In their majority, the former type of prostheses is body-powered, while the second type is controlled by myoelectric signals. Body-powered grippers are easy to control and allow a simple form of force feedback, frequently appreciated by users. However, they present limited versatility. Poly-articulated hands afford a wide range of grasp and manipulation types, but require enough residual muscle activation for dexterous control. Several factors, e.g. level of limb loss, personal preferences, cost, current occupation, and hobbies can influence the preference for one option over the other, and is always a result of the trade-off between system performance and users' needs. METHODS: The SoftHand Pro (SHP) is an artificial hand platform that has 19 independent joints (degrees-of-freedom), but is controlled by a single input. The design of this prosthesis is inspired by the concept of postural synergies in motor control and implemented with soft-robotic technologies. Their combination provides increased robustness, safe interaction and the execution of diverse grasps. The potential of the SHP is fully unleashed when users learn how to exploit its features and create an intimate relationship between the technical aspects of the prosthesis design and its control by the user. RESULTS: The great versatility of the SoftHand Pro (a reasearch protpotype) permitted its adaptation to the user requirements. This was experienced by the SoftHand Pro Team during the preparation for different CYBATHLON events (from 2016 to 2020). The mixed power and dexterous hand operations required by each task of the race is inspired by everyday tasks. Our prosthesis was driven by different pilots, with different habits and backgrounds. Consequently, the hand control modality was customized according to the user's preferences. Furthermore, the CYBATHLON tasks had some variations in this period, promoting the continuous development of our technology with a user-centered approach. In this paper, we describe the participation and preparation of the SoftHand Pro Team from 2016 to 2020 with three pilots and two different activation modalities, hybrid body-controlled and myoelectric control. CONCLUSIONS: We introduced our pilots, the implementation of the two control modalities, and describe the successful participation in all CYBATHLON events. This work proves the versatility of the system towards the user's preferences and the changes in the race requirements. Finally, we discussed how the CYBATHLON experience and the training in the real-world scenario have driven the evolution of our system and gave us remarkable insights for future perspectives.

A Review of Foods of Plant Origin as Sources of Vitamins with Proven Activity in Oxidative Stress Prevention according to EFSA Scientific Evidence.

Beyond their nutritional benefits, vitamins could decrease the risk of chronic diseases due to their potent antioxidant capacity. The present work is aimed at reviewing the state of the art regarding (1) the vitamins involved in oxidative stress prevention in accordance with the requirements established by the European Food Safety Authority (EFSA) and (2) the foods of plant origin that are sources of those vitamins and have potential benefits against oxidative stress in humans. According to the European regulations based on EFSA scientific evidence, riboflavin, vitamin C, and vitamin E are those vitamins subjected to the approved health claim "contribute to the protection of cells from oxidative stress". Scientific studies conducted in humans with some natural food sources of riboflavin (almonds, wheat germ, mushrooms, oat bran), vitamin C (guava, kale, black currant, Brussels sprouts, broccoli, orange), and vitamin E (hazelnuts, almonds, peanuts, pistachio nuts, extra virgin olive oil, dates, rye) have been performed and published in the literature. However, no food of plant origin has obtained a favorable EFSA opinion to substantiate the approval of health claims related to its potential properties related to oxidative stress prevention. Further studies (concretely, well-controlled human intervention studies) must be carried out in accordance with EFSA requirements to provide the highest level of scientific evidence that could demonstrate the potential relationship between foods of plant origin and antioxidant capacity. This review could be useful for the scientific community to study the application of health claims referring to the antioxidant capacity potentially exerted by foods of plant origin.

Wild Vitex agnus-castus L.: Phytochemical Characterization, Acute Toxicity, and Bioactive Properties.

Wild Vitex agnus-castus (VAC) is a Mediterranean plant that is rich in bioactive metabolites. This study aimed to validate, for the first time, the beneficial use of VAC fruits and fruit decoctions (VFDs) through in vitro and in vivo trials. Forty-one volatile components were detected in VAC fruits, with 1,8-cineole (30.3%) comprising the majority. The antioxidant activity of VFD was measured by using different in vitro methods (EC50 of 0.16 mg/mL by ß-carotene bleaching inhibition assay) and by measuring the DNA protection power. Using the disc diffusion assay, the antimicrobial activity of VFD was evaluated, and it exhibited a noticeable anticandidal activity. VFD did not cause any toxicity or mortality in rats treated with doses > 200 mg/kg. Using the acetic acid writhing test, the antinociceptive activity of VFD was measured. Our results showed that VFD at 200 mg/kg exhibited a higher analgesic activity (81.68%) than acetylsalicylic acid used as a positive control (74.35%). Its gastroprotective ability was assessed by HCl/ethanol-induced gastric lesions, which were remarkably inhibited (84.62%) by intraperitoneal administration of VFD. This work helps to validate the popular use of VAC to treat nociceptive, inflammatory, and gastric disorders and encourages researchers to further investigate the identification of pharmacological compounds from this species.

IL-34 and protein-tyrosine phosphatase receptor type-zeta-dependent mechanisms limit arthritis in mice.

Myeloid cell mediated mechanisms regulate synovial joint inflammation. IL-34, a macrophage (Mø) growth and differentiation molecule, is markedly expressed in neutrophil and Mø-rich arthritic synovium. IL-34 engages a newly identified independent receptor, protein-tyrosine phosphatase, receptor-type, zeta (PTPRZ), that we find is expressed by Mø. As IL-34 is prominent in rheumatoid arthritis, we probed for the IL-34 and PTPRZ-dependent myeloid cell mediated mechanisms central to arthritis using genetic deficient mice in K/BxN serum-transfer arthritis. Unanticipatedly, we now report that IL-34 and PTPRZ limited arthritis as intra-synovial pathology and bone erosion were more severe in IL-34 and PTPRZ KO mice during induced arthritis. We found that IL-34 and PTPRZ: (i) were elevated, bind, and induce downstream signaling within the synovium in arthritic mice and (ii) were upregulated in the serum and track with disease activity in rheumatoid arthritis patients. Mechanistically, IL-34 and PTPRZ skewed Mø toward a reparative phenotype, and enhanced Mø clearance of apoptotic neutrophils, thereby decreasing neutrophil recruitment and intra-synovial neutrophil extracellular traps. With fewer neutrophils and neutrophil extracellular traps in the synovium, destructive inflammation was restricted, and joint pathology and bone erosion diminished. These novel findings suggest that IL-34 and PTPRZ-dependent mechanisms in the inflamed synovium limit, rather than promote, inflammatory arthritis.

Therapeutic success of sodium thiosulfate in treating cutaneous calciphylaxis in a patient with hyperphosphataemic familial tumoral calcinosis.

Calciphylaxis is a potencially disorder in patients with hyperphosphatemic familial tumoral calcinosis (HFTC). Patients commonly present livedo racemosa and retiform purpura, which may progress to necrosis and very painful ulcers. Treatment with sodium thiosulfate provides good results; however, intralesional and intravenous treatment can be limited by its adverse effects. Topical sodium thiosulfate has been successfully reported for cutaneous calcification associated with connective tissue diseases and calciphylaxis in patients with chronic kidney disease. We provide a case report of a patient with HFTC and calciphylaxis who was treated with topical sodium thiosulfate with a rapid and complete response with no side effects.

Extrusion Cooking Effect on Carbohydrate Fraction in Novel Gluten-Free Flours Based on Chickpea and Rice.

Extrusion cooking allows the development of value-added products from pulses, such as gluten-free snacks with added functional properties. The main objective of this study was to evaluate the changes induced by the extrusion process on the carbohydrate fraction (total carbohydrates, soluble sugars and oligosaccharides, dietary fiber, and arabinoxylans) of novel flour formulations based on chickpeas and rice enriched with different dietary fiber sources. Moreover, the influence of the addition of fiber-rich ingredients, such as Fibersol® and passion fruit, on the analyzed compounds was also evaluated. Sucrose was the main soluble sugar found in analyzed formulations, and raffinose was the prevalent oligosaccharide, followed by stachyose. The content of total α-galactosides tended to be higher after extrusion cooking. As a consequence of the extrusion treatment, the content of total and soluble dietary fiber was statistically increased in most of the analyzed samples. In general, no significant changes were observed in total arabinoxylan content as a consequence of the extrusion process, while the content of water-soluble arabinoxylans was significantly increased in extruded formulations. It was observed that the content of total available carbohydrates, stachyose, and water-soluble arabinoxylans were significantly influenced by the addition of passion fruit, Fibersol®, and both. The incorporation of these ingredients in gluten-free formulations based on chickpeas and rice allows one to obtain suitable functional formulations for the development of innovative, gluten-free, extruded snack-type products, which could be an interesting alternative for people with celiac disease.

Chemical Composition, Nutritional Value, and Biological Evaluation of Tunisian Okra Pods (Abelmoschus esculentus L. Moench).

The aim of this work was to perform an unprecedented in-depth study on the bioactive phytochemicals of Abelmoschus esculentus L. Moench Tunisian landrace (Marsaouia). For this purpose, its nutritional, aroma volatile, and phenolic profiles were characterized, and sundry biological activities were assessed in vitro. The approximate composition revealed that total dietary fiber as the most abundant macronutrient, mainly insoluble dietary fiber, followed by total carbohydrates and proteins. In addition, okra pods were rich in K, Ca, Mg, organic acids, tocopherols, and chlorophylls. Gas Chromatography-Electron Impact Mass Spectrometry (GC-EIMS) analysis showed that oxygenated monoterpenes, sesquiterpene hydrocarbons, and phenylpropanoids were the predominant essential volatile components in A. esculentus pods. A total of eight flavonols were detected by High-Performance Liquid Chromatography coupled to a DAD detector and mass spectrometry by electrospray ionization (HPLC-DAD-MS/ESI); with quercetin-3-O-glucoside being the majority phenolic component, followed by quercetin-O-pentosyl-hexoside and quercetin-dihexoside. This pioneering study, evidences that Tunisian okra display promising antioxidant and cytotoxic actions, in addition to relevant inhibitory effects against α-amylase and α-glucosidase enzymes, and interesting analgesic activity.

Health Education for preschool children in daycare centers.

BACKGROUND: The promotion of health is carried out in preventive services of medical units, in educational programs and textbooks from the general perspective of the population. OBJECTIVE: To determine baseline characteristics of health education for pre-school children, their parents and teachers, by means of specialist doctors. METHOD: Cross-sectional study of an educational program for preschool children. Life skills and health competencies were evaluated. RESULTS: The preschoolers developed resilience (84.12%), empathy (92.23%), assertive communication (93.5%), interpersonal relationships (91.0%), correct decision making (92.56%), problem solving (81.05%), creative thinking (98%), critical thinking (86.08%), emotion management (80.76%), physical activation (97.94%), self-knowledge (98.96%), hygienic habits (94.90%) and co-responsibility (86.25%); 95.59% liked the workshop and 95.75% chose the correct option in the problems described. 63.04% of parents generated changes in their habits and those of their children. CONCLUSION: The educational program implemented can promote empowerment in health from childhood.

[Educación para la salud en preescolares de guarderías].

BACKGROUND: The promotion of health is carried out in preventive services of medical units, in educational programs and textbooks from the general perspective of the population. OBJECTIVE: To determine baseline characteristics of health education for pre-school children, their parents and teachers, by means of specialist doctors. METHOD: Cross-sectional study of an educational program for preschool children. Life skills and health competencies were evaluated. RESULTS: The preschoolers developed resilience (84.12%), empathy (92.23%), assertive communication (93.5%), interpersonal relationships (91.0%), correct decision making (92.56%), problem solving (81.05%), creative thinking (98%), critical thinking (86.08%), emotion management (80.76%), physical activation (97.94%), self-knowledge (98.96%), hygienic habits (94.90%) and co-responsibility (86.25%); 95.59% liked the workshop and 95.75% chose the correct option in the problems described. 63.04% of parents generated changes in their habits and those of their children. CONCLUSION: The educational program implemented can promote empowerment in health from childhood.

ANTECEDENTES: La promoción de la salud se realiza en servicios preventivos de unidades médicas, en programas educativos y libros de texto desde la perspectiva general de la población. OBJETIVO: Determinar características basales de educación en salud a preescolares, sus padres y maestros, mediante médicos especialistas. MÉTODO: Estudio transversal de un programa educativo para preescolares en estancias infantiles. Se evaluaron habilidades para la vida y competencias para la salud. RESULTADOS: Los preescolares desarrollaron resiliencia (84.12%), empatía (92.23%), comunicación asertiva (93.5%), relaciones interpersonales (91.0%), toma correcta de decisiones correctas (92.56%), solución de problemas (81.05%), pensamiento creativo (98%), pensamiento crítico (86.08%), manejo de emociones (80.76%), activación física (97.94%), autoconocimiento (98.96%), hábitos higiénicos (94.90%) y corresponsabilidad (86.25%); al 95.59% les agradó el taller y el 95.75% eligió la opción correcta en los problemas descritos. El 63.04% de los padres generaron cambios en sus hábitos y en los de sus hijos. CONCLUSIÓN: El programa educativo implementado puede favorecer el empoderamiento en salud desde la infancia.

Leccinum molle (Bon) Bon and Leccinum vulpinum Watling: The First Study of Their Nutritional and Antioxidant Potential.

This work presents the chemical profile of two edible species of mushrooms from the genus Leccinum: Leccinum molle (Bon) Bon and Leccinum vulpinum Watling, both harvested on the outskirts of Bragança (Northeastern Portugal). Both species were prepared and characterized regarding their content in nutrients (i.e., free sugars, fatty acids and vitamins), non-nutrients (i.e., phenolic and other organic acids) and antioxidant activity. To the best of our knowledge, no previous studies on the chemical characterization and bioactivity of these species have been undertaken. Accordingly, this study intends to increase the available information concerning edible mushroom species, as well as to highlight another important factor regarding the conservation of the mycological resources--their potential as sources of nutraceutical/pharmaceutical compounds. Overall, both species revealed similar nutrient profiles, with low fat levels, fructose, mannitol and trehalose as the foremost free sugars, and high percentages of mono- and polyunsaturated fatty acids. They also revealed the presence of bioactive compounds, namely phenolic (e.g., gallic acid, protocatechuic acid and p-hydroxybenzoic acid) and organic acids (e.g., citric and fumaric acids) and presented antioxidant properties.

Methanolic Extract of Ganoderma lucidum Induces Autophagy of AGS Human Gastric Tumor Cells.

Ganoderma lucidum is one of the most widely studied mushroom species, particularly in what concerns its medicinal properties. Previous studies (including those from some of us) have shown some evidence that the methanolic extract of G. lucidum affects cellular autophagy. However, it was not known if it induces autophagy or decreases the autophagic flux. The treatment of a gastric adenocarcinoma cell line (AGS) with the mushroom extract increased the formation of autophagosomes (vacuoles typical from autophagy). Moreover, the cellular levels of LC3-II were also increased, and the cellular levels of p62 decreased, confirming that the extract affects cellular autophagy. Treating the cells with the extract together with lysossomal protease inhibitors, the cellular levels of LC3-II and p62 increased. The results obtained proved that, in AGS cells, the methanolic extract of G. lucidum causes an induction of autophagy, rather than a reduction in the autophagic flux. To our knowledge, this is the first study proving that statement.

Adding Molecules to Food, Pros and Cons: A Review on Synthetic and Natural Food Additives.

The pressing issue to feed the increasing world population has created a demand to enhance food production, which has to be cheaper, but at the same time must meet high quality standards. Taste, appearance, texture, and microbiological safety are required to be preserved within a foodstuff for the longest period of time. Although considerable improvements have been achieved in terms of food additives, some are still enveloped in controversy. The lack of uniformity in worldwide laws regarding additives, along with conflicting results of many studies help foster this controversy. In this report, the most important preservatives, nutritional additives, coloring, flavoring, texturizing, and miscellaneous agents are analyzed in terms of safety and toxicity. Natural additives and extracts, which are gaining interest due to changes in consumer habits are also evaluated in terms of their benefits to health and combined effects. Technologies, like edible coatings and films, which have helped overcome some drawbacks of additives, but still pose some disadvantages, are briefly addressed. Future trends like nanoencapsulation and the development of "smart" additives and packages, specific vaccines for intolerance to additives, use of fungi to produce additives, and DNA recombinant technologies are summarized.

Role of PIGM and PIGX in glycosylphosphatidylinositol biosynthesis and human health (Review).

Glycosylphosphatidylinositol-glycan (GPI) is an anchor to specific cell surface proteins known as GPI-anchored proteins (APs) that are localized in lipid rafts and may act as cell co-receptors, enzymes and adhesion molecules. The present review investigated the significance of GPI biosynthesis class phosphatidylinositol-glycan (PIG)M and PIGX in GPI synthesis and their implications in human health conditions. PIGM encodes GPI-mannosyltransferase I (MT-I) enzyme that adds the first mannose to the GPI core structure. PIGX encodes the regulatory subunit of GPI-MT-I. The present review summarizes characteristics of the coding sequences of PIGM and PIGX, and their expression in humans, as well as the relevance of GPI-MT-I and the regulatory subunit in maintaining the presence of GPI-APs on the cell surface and their secretion. In addition, the association of PIGM mutations with paroxysmal nocturnal hemoglobinuria and certain types of GPI-deficiency disease and the altered expression of PIGM and PIGX in cancer were also reviewed. In addition, their interaction with other proteins was described, suggesting a complex role in cell biology. PIGM and PIGX are critical genes for GPI synthesis. Understanding gene and protein regulation may provide valuable insights into the role of GPI-APs in cellular processes.

Ion-bombardment-driven surface modification of porous magnesium scaffolds: Enhancing biocompatibility and osteoimmunomodulation.

Porous Mg scaffolds are promising for bone repair but are limited by high corrosion rates and challenges in preserving coating integrity. We used Directed Plasma Nanosynthesis (DPNS) at 400 eV and a fluence of 1 × 1018 cm-2 to augment the bioactivity and corrosion resistance of porous Mg scaffolds, maintaining their overall material integrity. DPNS creates nanostructures that increase surface area, promote apatite nucleation, and enhance osseointegration, improving the bioactivity and corrosion resistance of porous Mg scaffolds without compromising their structure. Our findings indicate a decrease in surface roughness, with pre-irradiated samples having Rq = 60.4 ± 5.3 nm andRa = 48.2 ± 3.1 nm, and post-DPNS samples showing Rq = 36.9 ± 0.3 nm andRa = 28.6 ± 0.8 nm. This suggests changes in topography and wettability, corroborated by the increased water contact angles (CA) of 129.2 ± 3.2 degrees. The complexity of the solution influences the CA: DMEM results in a CA of 120.4 ± 0.1 degrees, while DMEM + SBF decreases it to 103.6 ± 0.5 degrees, in contrast to the complete spreading observed in non-irradiated samples. DPNS-treated scaffolds exhibit significantly reduced corrosion rates at 5.7 × 10-3 ± 3.8 × 10-4 mg/cm²/day, compared to the control's 2.3 × 10-2 ± 3.2 × 10-4 mg/cm²/day over 14 days (P < 0.01). The treatment encourages the formation of a Ca-phosphate-rich phase, which facilitates cell spreading and the development of focal adhesion points in hBM-MSCs on the scaffolds. Additionally, J774A.1 murine macrophages show an enhanced immune response with diminished TNF-α cytokine expression. These results offer insights into nanoscale modifications of Mg-based biomaterials and their promise for bone substitutes or tissue engineering scaffolds.

Changes in health-related quality of life in common variable immunodeficiency: an eight-year journey, including the COVID-19 pandemic.

BACKGROUND: Personalized medicine requires the assessment of the impact of health care interventions on Health-Related Quality of Life. RESEARCH DESIGN AND METHODS: We run an observational study of HRQoL in 140 CVID patients with biannual assessments over 8 years using a disease-specific tool, the CVID_QoL, and the GHQ questionnaires. Factors influencing changes in HRQoL scores were identified using multiple linear regression models with a stepwise procedure. RESULTS: Infections frequency, female gender, and chronic enteropathy were associated with worse global CVID_QoL scores. The presence of permanent organ damage and older age contributed to the perception of being at risk of health deterioration, while chronic enteropathy was associated with fatigue. The presence of permanent organ damage was also associated with perceived difficulties in usual activities. The frequency of infections was the main risk factor for difficulties in long-term planning and perceptions of vulnerability. Before COVID-19, improved HRQoL scores were associated with reduced respiratory infections and changes in immunoglobulin replacement route and setting. The COVID-19 pandemic caused a sudden deterioration in all HRQoL dimensions, and a further deterioration in the emotional dimension was observed during the pandemic period. Patients who died during the study had worse CVID_QoL scores at all time points, confirming that HRQoL performance is strongly related to patient outcome. CONCLUSIONS: Periodic HRQoL assessments are needed to capture relevant issues that change over time in patients affected by long-term chronic conditions such CVID, possibly identifying areas of intervention.