A Serious Game for Cognitive Stimulation of Older People With Mild Cognitive Impairment: Design and Pilot Usability Study.

Background: Cognitive stimulation of older people helps prevent, and even treat, age-related diseases, such as mild cognitive impairment. Playing games reduces the probability of experiencing this pathology, which is related to the loss of the ability to carry out some instrumental activities of daily living. Objective: This work describes the design and development of a serious game for the cognitive stimulation of older people, with exercises related to the daily life task of shopping. A pilot study for its preliminary usability validation is also presented. Methods: The designed serious game includes 4 exercises consisting of shopping in a hypermarket, ordering products, making payments, and organizing the purchase, thus dealing with the most frequent cognitive problems of older people associated with episodic declarative memory, naming, calculation, and organization, respectively. Results: A total of 19 older people participated in the pilot study for the usability validation of the serious game. They indicated that they like the aesthetic and interesting topic of the game. They reported that it provides a high level of entertainment and could be useful in daily life for mental stimulation. The participants found the serious game to be intuitive, but the ease of use and readability of the instructions could be improved. Conclusions: This study suggests that the innovative serious game developed could be accepted by older people for their cognitive stimulation to prevent or treat mild cognitive impairment, although a long-term intervention study should be performed as future work. Its ecological validity design, with everyday tasks, adaptable levels of difficulty, and motivational mechanisms, is a differentiating factor compared to similar serious games.

Sequential RAS mutations evaluation in cell-free DNA of patients with tissue RAS wild-type metastatic colorectal cancer: the PERSEIDA (Cohort 2) study.

PURPOSE: RAS (KRAS/NRAS) mutational status on a tumor biopsy is mandatory to guide the best treatment in metastatic colorectal cancer (mCRC). Determining the RAS mutational status by tumor-tissue biopsy is essential in guiding the optimal treatment decision for mCRC. RAS mutations are negative predictive factors for the use of EGFR monoclonal antibodies. Cell-free DNA (cfDNA) analysis enables minimally invasive monitoring of tumor evolution. METHODS/PATIENTS: PERSEIDA was an observational, prospective study assessing cfDNA RAS, BRAF and EGFR mutations (using Idylla™) in first-line mCRC, RAS wild-type (baseline tumor-tissue biopsy) patients (cohort 2). Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression. RESULTS: 117 patients were included (103 received panitumumab + chemotherapy as first-line treatment). At baseline, 7 (6.8%) patients had RAS mutations, 4 (3.9%) BRAF mutations and no EGFR mutations were detected (cfDNA, panitumumab + chemotherapy subpopulation [panitumumab + Ch]). The baseline RAS mutational status concordance between tissue and liquid biopsies was 94.0% (93.2%, panitumumab + Ch). At 20 weeks, only one patient in the study (included in the panitumumab + Ch) had an emerging cfDNA RAS mutation. No emerging BRAF or EGFR mutations were reported. At disease progression, 6 patients had emergent mutations not present at baseline (RAS conversion rate: 13.3% [6/45]; 15.0% [6/40], panitumumab + Ch). CONCLUSIONS: The concordance rate between liquid and solid biopsies at baseline was very high, as previously reported, while our results suggest a considerable emergence of RAS mutations during disease progression. Thus, the dynamics of the genomic landscape in ctDNA may provide relevant information for the management of mCRC patients.

A Computer Vision-Based System to Help Health Professionals to Apply Tests for Fall Risk Assessment.

The increase in life expectancy, and the consequent growth of the elderly population, represents a major challenge to guarantee adequate health and social care. The proposed system aims to provide a tool that automates the evaluation of gait and balance, essential to prevent falls in older people. Through an RGB-D camera, it is possible to capture and digitally represent certain parameters that describe how users carry out certain human motions and poses. Such individual motions and poses are actually related to items included in many well-known gait and balance evaluation tests. According to that information, therapists, who would not need to be present during the execution of the exercises, evaluate the results of such tests and could issue a diagnosis by storing and analyzing the sequences provided by the developed system. The system was validated in a laboratory scenario, and subsequently a trial was carried out in a nursing home with six residents. Results demonstrate the usefulness of the proposed system and the ease of objectively evaluating the main items of clinical tests by using the parameters calculated from information acquired with the RGB-D sensor. In addition, it lays the future foundations for creating a Cloud-based platform for remote fall risk assessment and its integration with a mobile assistant robot, and for designing Artificial Intelligence models that can detect patterns and identify pathologies for enabling therapists to prevent falls in users under risk.

A study protocol of a comparative mixed study of the T-Control catheter.

Background: Foley catheters have been subject to limited development in the last few decades. They fulfil their basic function of draining urine from the bladder but cause other associated problems. T-Control is a new silicone Foley catheter with an integrated fluid control valve whose design aims to reduce the risks associated with bladder catheterization by a multifactorial approach. The general purpose of this study is to determine the effectiveness, comfort, and experience of the patient catheterized with T-Control® compared with patients with a conventional Foley catheter. Study Design: This trial is a mixed-method study comprising a two-arm, pilot comparative study with random allocation to T-Control catheter or traditional Foley catheter in patients with long-term catheterization and a study with qualitative methodology, through discussion groups. Endpoints: The comfort and acceptability of the T-Control® device (qualitative) and the quality of life related to self-perceived health (quantitative) will be analysed as primary endpoints. As secondary endpoints, the following will be analysed: magnitude and rate of infections (symptomatic and asymptomatic); days free of infection; indication of associated antibiotic treatments; determination of biofilm; number of catheter-related adverse events; use of each type of catheterization's healthcare resources; and level of satisfaction and workload of health professionals. Patients and Methods: Eligible patients are male and female adults aged ≥18 years, who require a change of long-term bladder catheter. The estimated sample size is 50 patients. Patient follow-up includes both the time of catheter insertion and its removal or change 4 weeks later, plus the time until the discussion groups take place.

[Initial assessment of immigrant patients in primary care]. / Atención inicial al paciente inmigrante en atención primaria.

The clinical interview of immigrant patients requires cultural competence to ensure good understanding and correct communication, in addition to collecting specific information that differs from that of native patients, such as origin and migratory route or cultural identity. Screening for latent tuberculosis infection is recommended in certain cases and screening for other infections, both cosmopolitan with a higher prevalence in migrants (HIV, syphilis, hepatitis B and C) and imported (Chagas, intestinal parasites, strongyloidiasis, schistosomiasis), depending on origin. It is essential to check the vaccination status and complete the vaccination schedule, adapting it to the current calendar, prioritizing vaccines such as measles, rubella and poliomyelitis. We propose preventive activities to be carried out when traveling to countries of origin, due to their special characteristics and risks: general advice, exploring the risk of malaria, assessing specific vaccinations, advice regarding sexually transmitted infections and special considerations if they have chronic diseases; and addressing, if appropriate, the risks of female genital mutilation.

Effectiveness of the T-Control catheter: A study protocol.

Background: Foley catheters have been subject to limited development in the last few decades. They fulfil their basic function of draining urine from the bladder but cause other associated problems. T-Control is a new silicone Foley catheter with an integrated fluid control valve whose design aims to reduce the risks associated with bladder catheterisation by a multifactorial approach. The general purpose of this study is to evaluate the effectiveness and cost-effectiveness of the T-Control catheter versus the Foley-type catheter in patients with Acute Urine Retention (AUR). Study design: This is a pragmatic, open, multicentre, controlled clinical trial with random allocation to the T-Control catheter or a conventional Foley-type catheter in patients with AUR. Endpoints: The magnitude of infections will be analysed as a primary endpoint. While as secondary endpoint, the following will be analysed: rate of symptomatic and asymptomatic infections; days free of infection; quality of life-related to self-perceived health; indication of associated antibiotic treatments; determination of biofilm; number of catheter-related adverse events; use of each type of catheterisation's healthcare resources; level of satisfaction and workload of health professionals and acceptability of the T-Control device as well as the patient experience. Patients and methods: Eligible patients are male adults aged ≥50 years, with AUR and with an indication of bladder catheterisation for at least 2 weeks. The estimated sample size is 50 patients. Patient follow-up includes both the time of catheter insertion and its removal or change 2 weeks later, plus 2 weeks after this time when the patient will be called for an in-depth interview.

Metastable FeMg particles for controlling degradation rate, mechanical properties, and biocompatibility of Poly(l-lactic) acid (PLLA) for orthopedic applications.

Poly(l-lactic) acid (PLLA) is commonly used in bioabsorbable medical implants, but it suffers from slow degradation rate and rapid decline in mechanical properties for orthopedic applications. To address this drawback, recent research has explored the use of Mg as a filler for PLLA, resulting in composites with improved degradation rate and cytocompatibility compared to neat PLLA. In this study, FeMg powder particles were proposed as fillers for PLLA to investigate the potential of PLLA/FeMg composites for bioabsorbable implants. Cylinder specimens of PLLA, PLLA/Fe, PLLA/Mg and PLLA/FeMg were prepared using solvent casting followed by thermo-molding. The microstructure, thermal behavior, in vitro degradation behavior in simulated body fluid, mechanical properties and cytocompatibility of these composites were examined. The results indicate that the presence of FeMg particles prevents the deterioration of the composite mechanical properties, at least up to 14 days. Once a certain amount of degradation of the composite is reached, the degradation is faster than that of PLLA. Direct cytotoxicity assays revealed that pre-osteoblast MC3T3-E1 cells successfully adhered to and proliferated on the PLLA/FeMg surface. The inclusion of a low percentage of Mg into the Fe lattice not only accelerated the degradation rate of Fe but also improved its cytocompatibility. The enhanced degradation rate, mechanical properties, and osteoconductive properties of this composite make it a promising option for temporary orthopedic biomedical devices.

Bioabsorbable Composites Based on Polymeric Matrix (PLA and PCL) Reinforced with Magnesium (Mg) for Use in Bone Regeneration Therapy: Physicochemical Properties and Biological Evaluation.

Improvements in Tissue Engineering and Regenerative Medicine (TERM)-type technologies have allowed the development of specific materials that, together with a better understanding of bone tissue structure, have provided new pathways to obtain biomaterials for bone tissue regeneration. In this manuscript, bioabsorbable materials are presented as emerging materials in tissue engineering therapies related to bone lesions because of their ability to degrade in physiological environments while the regeneration process is completed. This comprehensive review aims to explore the studies, published since its inception (2010s) to the present, on bioabsorbable composite materials based on PLA and PCL polymeric matrix reinforced with Mg, which is also bioabsorbable and has recognized osteoinductive capacity. The research collected in the literature reveals studies based on different manufacturing and dispersion processes of the reinforcement as well as the physicochemical analysis and corresponding biological evaluation to know the osteoinductive capacity of the proposed PLA/Mg and PCL/Mg composites. In short, this review shows the potential of these composite materials and serves as a guide for those interested in bioabsorbable materials applied in bone tissue engineering.

Factors influencing xerostomia and oral health-related quality of life in polymedicated patients.

OBJECTIVES: To evaluate whether the severity of xerostomia in older polymedicated patients impacts oral health-related quality of life (OHRQoL). BACKGROUND: Medication-associated xerostomia is common in older people. Xerostomia may impair OHRQoL. MATERIALS AND METHODS: This cross-sectional study included older hypertensive patients from two health centres. We assessed the severity of xerostomia and OHRQoL using the Xerostomia Inventory (XI) tool, and the Oral Health Impact Profile-14 (OHIP-14) instrument, respectively. We measured unstimulated (UWS) and stimulated (SWS) salivary flows. Univariate and multiple linear regression analyses evaluated the associations of XI and OHIP-14 and different explanatory variables. RESULTS: Of the 218 patients enrolled, 51.8% had xerostomia, and 38.1% and 27.5% suffered from UWS and SWS hyposalivation, respectively. Patients with xerostomia, UWS, and SWS hyposalivation scored significantly higher on the XI. However, only those with xerostomia or UWS hyposalivation had significantly higher OHIP-14 scores. A moderate correlation was observed between XI and OHIP-14 scores. The multiple regression model showed that factors with the greatest impact on XI were the patient's complaint of xerostomia, UWS flow rate, age and sex. However, only the XI score was significantly associated with the OHIP-14 score. CONCLUSION: Xerostomia has a negative impact on OHRQoL in older polymedicated patients, but this impact is less than in other types of xerostomia. Longitudinal studies are needed to determine whether changes in the detected explanatory variables influence XI and OHIP scores in these patients.

Agarose spot migration assay to measure the chemoattractant potential of extracellular vesicles: applications in regenerative medicine and cancer metastasis.

BACKGROUND: The recruitment of effector cells is one of the novel functions described for extracellular vesicles (EVs) that needs further study. For instance, cell recruitment by mesenchymal stromal cell derived-EVs (MSC-EVs) is one of the features by which MSC-EVs may induce regeneration and ameliorate tissue injury. On the other hand, increasing evidence suggests that cancer EVs play an important role in the preparation of the pre-metastatic niche (PMN) by recruiting their primary tumour cells. Understanding and measuring the potential of MSC-EVs or cancer-EVs to induce cell migration and recruitment is essential for cell-free therapeutic approaches and/or for a better knowledge of cancer metastasis, respectively. In this context, classical in vitro migration assays do not completely mimic the potential situation by which EVs exert their chemotactic capacity. RESULTS: We adapted an agarose spot migration assay as an in vitro system to evaluate the cell recruitment capacity of locally delivered or localized EVs. Cell migration was tracked for 12 h or 48 h, respectively. Thereafter, endpoint migration images and time-lapse videos were analysed to quantify several parameters aiming to determine the migration of cells to either MSC-EV or pro-metastatic EV. The number of cells contained inside the agarose spots, the migration distance, the area occupied by cells, the directionality of the cell movement, and the Euclidean distance were measured. This multi-parametric evaluation revealed the potential of different MSC-EV preparations to recruit endothelial cells and to detect an enhanced recruitment capacity of highly metastatic PC3-derived EVs (PC3-EVs) compared to low-metastatic LNCaP-EVs in a tumour cell-specific manner. CONCLUSIONS: Overall, this agarose spot migration assay may offer a diversity of measurements and migration settings not provided by classical migration assays and reveal its potential use in the EV field in two different contexts with recruitment in common: regeneration and cancer metastasis.

Novel and Accessible Physical Recycling for Expanded Polystyrene Waste with the Use of Acetone as a Solvent and Additive Manufacturing (Direct Ink-Write 3D Printing).

The current high production of plastics has prompted the exploration of alternative pathways to facilitate recycling, aiming for a progressively sustainable society. This paper presents an alternative and affordable technology for treating waste expanded polystyrene (EPS) mixed with acetone in a 100:1 volume ratio to be used as 3D printing ink for Direct Ink Write technology. In order to optimize the printing parameters, a comprehensive study was conducted, evaluating different needle diameters, printing speeds, and bed temperature values to achieve homogenous pieces and a highly repeatable 3D printing process. Results showed that the main optimum printing parameters were using needles with diameters of 14 to 16 G and printing speeds ranging from 2 to 12 mm/s, which were found to yield the most uniform ribbons. Increasing the bed temperature, despite favoring acetone evaporation, led to the generation of more heterogeneous structures due to void growth inside the printed ribbons. Thus, employing room temperature for the bed proved to be the optimal value. Lastly, a comparative study between the starting material and the EPS after the printing process was conducted using FTIR-ATR and GPC analyses, ensuring the preservation of the original polymer's integrity during physical recycling.

Proteomic Serum Profiling of Holstein Friesian Cows with Different Pathological Forms of Bovine Paratuberculosis Reveals Changes in the Acute-Phase Response and Lipid Metabolism.

The lack of sensitive diagnostic methods to detect Mycobacterium avium subsp. paratuberculosis (Map) subclinical infections has hindered the control of paratuberculosis (PTB). The serum proteomic profiles of naturally infected cows presenting focal and diffuse pathological forms of PTB and negative controls (n = 4 per group) were analyzed using TMT-6plex quantitative proteomics. Focal and diffuse are the most frequent pathological forms in subclinical and clinical stages of PTB, respectively. One (focal versus (vs.) control), eight (diffuse vs. control), and four (focal vs. diffuse) differentially abundant (DA) proteins (q-value < 0.05) were identified. Ingenuity pathway analysis of the DA proteins revealed changes in the acute-phase response and lipid metabolism. Six candidate biomarkers were selected for further validation by specific ELISA using serum from animals with focal, multifocal, and diffuse PTB-associated lesions (n = 108) and controls (n = 56). Overall, the trends of the serum expression levels of the selected proteins were consistent with the proteomic results. Alpha-1-acid glycoprotein (ORM1)-based ELISA, insulin-like growth factor-binding protein 2 (IGFBP2)-based ELISA, and the anti-Map ELISA had the best diagnostic performance for detection of animals with focal, multifocal, and diffuse lesions, respectively. Our findings identify potential biomarkers that improve diagnostic sensitivity of PTB and help to elucidate the mechanisms involved in PTB pathogenesis.

Metabolic rewiring induced by ranolazine improves melanoma responses to targeted therapy and immunotherapy.

Resistance of melanoma to targeted therapy and immunotherapy is linked to metabolic rewiring. Here, we show that increased fatty acid oxidation (FAO) during prolonged BRAF inhibitor (BRAFi) treatment contributes to acquired therapy resistance in mice. Targeting FAO using the US Food and Drug Administration-approved and European Medicines Agency-approved anti-anginal drug ranolazine (RANO) delays tumour recurrence with acquired BRAFi resistance. Single-cell RNA-sequencing analysis reveals that RANO diminishes the abundance of the therapy-resistant NGFRhi neural crest stem cell subpopulation. Moreover, by rewiring the methionine salvage pathway, RANO enhances melanoma immunogenicity through increased antigen presentation and interferon signalling. Combination of RANO with anti-PD-L1 antibodies strongly improves survival by increasing antitumour immune responses. Altogether, we show that RANO increases the efficacy of targeted melanoma therapy through its effects on FAO and the methionine salvage pathway. Importantly, our study suggests that RANO could sensitize BRAFi-resistant tumours to immunotherapy. Since RANO has very mild side-effects, it might constitute a therapeutic option to improve the two main strategies currently used to treat metastatic melanoma.

Population-based evaluation of the impact of socioeconomic status on clinical outcomes in patients with heart failure in integrated care settings.

INTRODUCTION AND OBJECTIVES: Low socioeconomic status (SES) is associated with poor outcomes in patients with heart failure (HF). We aimed to examine the influence of SES on health outcomes after a quality of care improvement intervention for the management of HF integrating hospital and primary care resources in a health care area of 209 255 inhabitants. METHODS: We conducted a population-based pragmatic evaluation of the implementation of an integrated HF program by conducting a natural experiment using health care data. We included all individuals consecutively admitted to hospital with at least one ICD-9-CM code for HF as the primary diagnosis and discharged alive in Catalonia between January 1, 2015 and December 31, 2019. We compared outcomes between patients exposed to the new HF program and those in the remaining health care areas, globally and stratified by SES. RESULTS: A total of 77 554 patients were included in the study. Death occurred in 37 469 (48.3%), clinically-related hospitalization in 41 709 (53.8%) and HF readmission in 29 755 (38.4%). On multivariate analysis, low or very low SES was associated with an increased risk of all-cause death and clinically-related hospitalization (all Ps <.05). The multivariate models showed a significant reduction in the risk of all-cause death (HR, 0.812; 95%CI, 0.723-0.912), clinically-related hospitalization (HR, 0.886; 95%CI, 0.805-0.976) and HF hospitalization (HR, 0.838; 95%CI, 0.745-0.944) in patients exposed to the new HF program compared with patients exposed to the remaining health care areas and this effect was independent of SES. CONCLUSIONS: An intensive transitional HF management program improved clinical outcomes, both overall and across SES strata.

Ascaridoid parasites in European sardine throughout the annual cycle: Variability in parasitic load according to host stock features.

In recent years, a drop in the condition of the European sardine has been observed. Although several causes have been attributed to this issue, as overfishing and climate change, little is known about the link between ascaridoid nematode parasitisation and fish status. In this study, sardines were obtained from four fishing grounds along the Mediterranean (Alboran, Northern Spain, Northern Adriatic, and Aegean), and one location in the Atlantic Ocean (Southern Portugal). After analysing individual fish body condition (by direct tissue fat content measurements and condition indices), and reproductive status (by a detailed gonadal examination) throughout the entire annual cycle, ascaridoids were recognised by combining naked eye and UV-press method along flesh, viscera, and gonads. Afterwards, sequence analysis of the rDNA internal transcribed spacers region (ITS) and the mtDNA cox2 gene were used to identify and characterise the different species of ascaridoids from the fish host in the localities throughout the seasons. The main species found along different areas was Hysterothylacium aduncum, present in the Northern Adriatic (prevalence of 7.6%, mean intensity 1.700), the Atlantic (7.5%, 3.889), and the Northern Spain (3.9%, 1.600). Moreover, few individuals of Anisakis simplex (s.s.) and A. pegreffii were observed in the Atlantic (1.7% and 0.8%, respectively), and the latter species was also found in the Adriatic stock (0.8%). All ascaridoid specimens were found in viscera. Obtained results seem to indicate that in stocks with medium sizes, small variations in length are related to parasite intensity. This study highlights the importance of seasonal parasitological analyses at stock level and, especially, in capital breeders, as relationships between condition and reproduction parameters and parasitism are conditioned by seasonality.

Activation of the PP2A-B56α heterocomplex synergizes with venetoclax therapies in AML through BCL2 and MCL1 modulation.

Venetoclax combination therapies are becoming the standard of care in acute myeloid leukemia (AML). However, the therapeutic benefit of these drugs in older/unfit patients is limited to only a few months, highlighting the need for more effective therapies. Protein phosphatase 2A (PP2A) is a tumor suppressor phosphatase with pleiotropic functions that becomes inactivated in ∼70% of AML cases. PP2A promotes cancer cell death by modulating the phosphorylation state in a variety of proteins along the mitochondrial apoptotic pathway. We therefore hypothesized that pharmacological PP2A reactivation could increase BCL2 dependency in AML cells and, thus, potentiate venetoclax-induced cell death. Here, by using 3 structurally distinct PP2A-activating drugs, we show that PP2A reactivation synergistically enhances venetoclax activity in AML cell lines, primary cells, and xenograft models. Through the use of gene editing tools and pharmacological approaches, we demonstrate that the observed therapeutic synergy relies on PP2A complexes containing the B56α regulatory subunit, of which expression dictates response to the combination therapy. Mechanistically, PP2A reactivation enhances venetoclax-driven apoptosis through simultaneous inhibition of antiapoptotic BCL2 and extracellular signal-regulated kinase signaling, with the latter decreasing MCL1 protein stability. Finally, PP2A targeting increases the efficacy of the clinically approved venetoclax and azacitidine combination in vitro, in primary cells, and in an AML patient-derived xenograft model. These preclinical results provide a scientific rationale for testing PP2A-activating drugs with venetoclax combinations in AML.

Influence of the abutment height on marginal bone level changes around two-piece dental implants: Meta-analysis and trial sequential analysis of randomized clinical trials.

BACKGROUND: The focused question was: "In systemically healthy individuals with at least one two-piece dental implant, what is the efficacy of long (≥2 mm; intervention) compared with short (<2 mm; comparison) shoulder height abutments in peri-implant marginal bone level (MBL) changes at <1 year and ≥1 year reported by randomized controlled clinical trials?" MATERIALS AND METHODS: An electronic and hand search was conducted to identify RCTs published up to August 2022. The primary outcome variable was changed in MBL from implant surgery to subsequent follow-ups. Mean values and standard deviations for each study were extracted. Weighted mean differences and 95% confidence intervals were calculated. Meta-analysis for MBL changes was performed through a random-effect restricted maximum-likelihood model at early (<1 year) and late (≥1 year) stages of bone remodeling. Publication bias and sensitivity tests were also applied. Subgroup analysis was performed to further explore possible sources of heterogeneity in the estimated treatment effect. Trial sequential analysis was performed to assess the required information and false-positive results. RESULTS: Six randomized clinical trials fulfilled the inclusion/exclusion criteria and were included in the qualitative and quantitative analysis with a follow-up range from 6 to 36 months after implant surgery. Meta-analysis revealed that long abutments significantly exhibited 0.27 mm (CI 95% -0.60, 0.06) and 0.33 mm (CI 05% -0.50, -0.16) lower MBL changes compared with short ones at <1 year and ≥1 year, respectively. Subgroup meta-analysis revealed that studies with implants placed in a more subcrestal position significantly exhibited less differences in MBL changes between long and short abutments. No meta-analysis was conducted for peri-implant clinical parameters, and soft-tissue changes provided that reported data were scarce. Trial sequential analysis revealed insufficient information size to provide a definitive answer on the effect of abutment height in MBL. CONCLUSIONS: It might be cautiously concluded that two-piece implants with long abutments (≥2 mm) may display a protective role against marginal bone loss when compared with short ones (<2 mm) at <1 year and ≥1 year. A more subcrestal implant position seemed to minimize the effect of the abutment height in terms of MBL.

Risk factors associated with xerostomia and reduced salivary flow in hypertensive patients.

OBJECTIVE: The aim of this study was to evaluate the risk factors associated with xerostomia and hyposalivation in a group of hypertensive patients. SUBJECTS AND METHODS: A cross-sectional study was conducted. Hypertensive patients belonged to two healthcare centers were included. Xerostomia was assessed by asking a question and using the Xerostomia Inventory. Unstimulated salivary flow was collected. Different epidemiological variables were analyzed such as age, sex, habits, diseases, drugs, and blood pressure. RESULTS: 221 individuals were included. Xerostomia was reported in 51.13% of patients. Patients with xerostomia suffered more from osteoarthritis and diaphragmatic hernia. These patients took more anticoagulants (acenocoumarol), antiarrhythmics (amiodarone), analgesics (paracetamol) and epilepsy drugs (pregabalin) and less platelet aggregation inhibitors and angiotensin II receptor blockers (losartan). Unstimulated flow was reduced in 37.56% of patients. Patients suffering hyposalivation presented more diseases such as anxiety, infectious or parasitic diseases, hepatitis C, diaphragmatic hernia, and osteoarthritis. These patients took more repaglinide, thiazides, anti-inflammatories, anti-rheumatics, glucosamine, diazepam, and selective beta-2-adrenoreceptor agonists and less combinations of candesartan and diuretics. CONCLUSIONS: Xerostomia and hyposalivation are frequent in hypertensive patients. It is advisable to take into consideration the comorbidities and the drugs they receive, since they can increase the risk of these salivary disorders.

The Regulators of Peroxisomal Acyl-Carnitine Shuttle CROT and CRAT Promote Metastasis in Melanoma.

Circulating tumor cells are the key link between a primary tumor and distant metastases, but once in the bloodstream, loss of adhesion induces cell death. To identify the mechanisms relevant for melanoma circulating tumor cell survival, we performed RNA sequencing and discovered that detached melanoma cells and isolated melanoma circulating tumor cells rewire lipid metabolism by upregulating fatty acid (FA) transport and FA beta-oxidation‒related genes. In patients with melanoma, high expression of FA transporters and FA beta-oxidation enzymes significantly correlates with reduced progression-free and overall survival. Among the highest expressed regulators in melanoma circulating tumor cells were the carnitine transferases carnitine O-octanoyltransferase and carnitine acetyltransferase, which control the shuttle of peroxisome-derived medium-chain FAs toward mitochondria to fuel mitochondrial FA beta-oxidation. Knockdown of carnitine O-octanoyltransferase or carnitine acetyltransferase and short-term treatment with peroxisomal or mitochondrial FA beta-oxidation inhibitors thioridazine or ranolazine suppressed melanoma metastasis in mice. Carnitine O-octanoyltransferase and carnitine acetyltransferase depletion could be rescued by medium-chain FA supplementation, indicating that the peroxisomal supply of FAs is crucial for the survival of nonadherent melanoma cells. Our study identifies targeting the FA-based cross-talk between peroxisomes and mitochondria as a potential therapeutic opportunity to challenge melanoma progression. Moreover, the discovery of the antimetastatic activity of the Food and Drug Administration‒approved drug ranolazine carries translational potential.

Cross-protection against African swine fever virus upon intranasal vaccination is associated with an adaptive-innate immune crosstalk.

African swine fever virus (ASFV) is causing a worldwide pandemic affecting the porcine industry and leading to important global economic consequences. The virus causes a highly lethal hemorrhagic disease in wild boars and domestic pigs. Lack of effective vaccines hampers the control of virus spread, thus increasing the pressure on the scientific community for urgent solutions. However, knowledge on the immune components associated with protection is very limited. Here we characterized the in vitro recall response induced by immune cells from pigs intranasally vaccinated with the BA71ΔCD2 deletion mutant virus. Vaccination conferred dose-dependent cross-protection associated with both ASFV-specific antibodies and IFNγ-secreting cells. Importantly, bulk and single-cell transcriptomics of blood and lymph node cells from vaccinated pigs revealed a positive feedback from adaptive to innate immunity. Indeed, activation of Th1 and cytotoxic T cells was concomitant with a rapid IFNγ-dependent triggering of an inflammatory response characterized by TNF-producing macrophages, as well as CXCL10-expressing lymphocytes and cross-presenting dendritic cells. Altogether, this study provides a detailed phenotypic characterization of the immune cell subsets involved in cross-protection against ASFV, and highlights key functional immune mechanisms to be considered for the development of an effective ASF vaccine.