Search

Background: With the arrival of disease-modifying treatments, it is mandatory to find new cognitive markers that are sensitive to Alzheimer's disease (AD) pathology in preclinical stages., Objective: To determine the utility of a newly developed Learning and Associative Memory face test: LAM test. This study examined the relationship between AD cerebrospinal fluid (CSF) biomarkers and performance on LAM test, and assessed its potential clinical applicability to detect subtle changes in cognitively healthy subjects at risk for AD., Methods: We studied eighty cognitively healthy volunteers from the Valdecilla cohort. 61% were women and the mean age was 67.34 years (±6.416). All participants underwent a lumbar puncture for determination of CSF biomarkers and an extensive neuropsychological assessment, including performance on learning and associative memory indices of the LAM-test after 30 min and after 1 week, and two classic word lists to assess verbal episodic memory: the Rey Auditory Verbal Learning Test (RAVLT) and the Free and Cued Selective Reminding Test (FCSRT). We analyzed cognitive performance according to amyloid status (A+ versus A-) and to ATN model (A-T-N-; A+T-N-; A+T+N-/A+T+N+)., Results: Performance on the LAM-test was significantly correlated with CSF Aβ ratio. A+ participants performed worse on both learning (mean difference = 2.19, p = 0.002) and memory LAM measures than A- (mean difference = 2.19, p = 0.004). A decline in performance was observed along the Alzheimer's continuum, with significant differences between ATN groups., Conclusions: Our findings suggest that LAM test could be a useful tool for the early detection of subjects within the AD continuum, outperforming classical memory tests.

Purpose: The scientific community has established Javal's rule as a model linking refractive (RA) and keratometric (KA) astigmatism since its appearance more than 100 years ago. The aim was to improve the accuracy of this relationship according to subject's age by applying the power vector analysis. Posterior corneal curvature has also been studied., Methods: The IOLMaster 700 optical biometer was used to measure the corneal thickness and the radius of curvature of the anterior and posterior corneal surfaces. Refractive error was determined by a non-cycloplegic subjective refraction process with trial lenses. Linear regression analyses were applied using J 0 and J 45 power vector components. An evaluation was carried out according to the subject's age resulting into eight regression relationships for each astigmatic vector component for each relationship., Results: A total of 2254 right eyes from 2254 healthy subjects were evaluated. A trend towards against-the-rule astigmatism (ATR) was found with aging, both for refractive astigmatism (RA) and keratometric astigmatism (KA), with 95.2% of subjects under 20 years old having with-the-rule (WTR) KA, and only 22.8% above 79 years old. The following regression equations were found between RA and KA: [Formula: see text] = 0.73 × [Formula: see text] - 0.18 (R = 0.78) and [Formula: see text] = 0.70 × [Formula: see text] + 0.04 (R = 0.69) and between RA and total corneal astigmatism (TCA): [Formula: see text] = 0.73 × [Formula: see text] + 0.13 (R=0.78) and [Formula: see text] = 0.70 × [Formula: see text] - 0.06 (R = 0.68) for the whole sample, but with sensible differences among age groups, both in the slope and in the intercept., Conclusion: Ignoring the age of the subject when using Javal's rule could lead to an error in the final cylinder calculation that would increase in high astigmatisms. Applying this new power vector approach based on subject's age could improve the accuracy of the astigmatism prediction., (© 2023. The Author(s).)

Background/objectives: Posterior staphyloma is a hallmark of high myopia and its presence associates to greater degrees of myopic maculopathy. Nonetheless, its development, repercussion on visual function and relationship with maculopathy components, is still unclear. The objective was to analyze the impact of posterior staphyloma on the incidence and severity of myopic maculopathy and its repercussion on visual prognosis., Subjects/methods: Cross-sectional study conducted on 473 consecutive eyes of 259 highly myopic patients examined at Puerta de Hierro-Majadahonda University Hospital (Madrid, Spain). All patients underwent complete ophthalmologic examination including best corrected visual acuity (BCVA), axial length (AL), myopic maculopathy classification according to ATN system (atrophic/traction/neovascularization), determined the presence of posterior staphyloma, pathologic myopia (PM) and severe PM. Multimodal imaging were performed including fundus photography, optical coherence tomography (OCT), OCT-angiography, fundus autofluorescence and/ or fluorescein angiography., Results: Out of the total, 70.65% were female patients (n = 173/259), mean BCVA was 0.41 ± 0.54 logMAR units and mean AL was 29.3 ± 2.6 mm (26-37.6). Posterior staphyloma was present in 69.4% of eyes. Eyes with posterior staphyloma compared to non-staphyloma were older (p < 0.05), had greater AL (p < 0.01), worse BCVA (p < 0.01) and higher stage in ATN components (p < 0.01). Moreover, compound subgroup showed worse BCVA (p < 0.01) and greater stage in each of the ATN components (p < 0.01). Staphylomas with macular involvement presented worse BCVA (p < 0.01), higher AL (p < 0.01), and greater ATN (p < 0.05). The risk of posterior staphyloma presence in eyes with PM and severe PM eyes was 89.8% and 96.7%, respectively. Posterior staphyloma was the best predictor for BCVA in myopic patients (p < 0.01)., Conclusions: Posterior staphyloma's presence determines high risk of myopic maculopathy and therefore worse visual prognosis, especially those with macular involvement. Posterior staphyloma represented the best predictor for BCVA in highly myopic patients., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Objectives: Systemic lupus erythematosus (SLE) patients more commonly have insulin resistance (IR) than control subjects. Recent studies have revealed that the complement (C) system is not only a mediator of the immune system but is also related to the pathogenesis of atherosclerosis in the general population. Given that the C alteration is a characteristic of SLE, in the present work we set out to analyse if there is a relationship between the C system and IR in patients with SLE., Methods: New generation functional assays of the three pathways of the C system were performed in 225 non-diabetic patients with SLE. In addition, the serum levels of inactive (C1q, C2, C3, C4, factor D), activated (C3a) and regulators (C1 inhibitor and factor H) molecules of the C system were evaluated. Insulin and C-peptide serum levels were measured, and insulin resistance and indices of beta cell function were calculated using the homeostatic model assessment (HOMA). Metabolic syndrome criteria fulfillments were applied. Multivariable linear regression analysis was performed to assess the relationship between C system and IR indices and the presence of metabolic syndrome., Results: After adjusting for covariates that included traditional cardiovascular risk factors associated with IR and prednisone, serum C3a and factor H levels were positively related to higher levels of the HOMA2-IR index. Besides, in the multivariable analysis, after adjustment for covariates, serum levels of C1q and C3 associated with a higher odds ratio for the presence of metabolic syndrome., Conclusions: IR and metabolic syndrome are positively and independently related to higher serum levels of some serum C elements in patients with SLE with a predominant role of the alternative pathway elements.

Background: Plasma biomarkers of Alzheimer's disease (AD) constitute a non-invasive tool for diagnosing and classifying subjects. They change even in preclinical stages, but it is necessary to understand their properties so they can be helpful in a clinical context., Objective: With this work we want to study the evolution of p-tau231 plasma levels in the preclinical stages of AD and its relationship with both cognitive and imaging parameters., Methods: We evaluated plasma phosphorylated (p)-tau231 levels in 146 cognitively unimpaired subjects in sequential visits. We performed a Linear Mixed-effects Model to analyze their rate of change. We also correlated their baseline levels with cognitive tests and structural and functional image values. ATN status was defined based on cerebrospinal fluid biomarkers., Results: Plasma p-tau231 showed a significant rate of change over time. It correlated negatively with memory tests only in amyloid-positive subjects. No significant correlations were found with any imaging measures., Conclusions: Increases in plasma p-tau231 can be detected at one-year intervals in cognitively healthy subjects. It could constitute a sensitive marker for detecting early signs of neuronal network impairment by amyloid.

Background: Microglial dysfunction plays a causative role in Alzheimer's disease (AD) pathogenesis. Here we focus on a germline insertion/deletion variant mapping SIRPβ1, a surface receptor that triggers amyloid-β(Aβ) phagocytosis via TYROBP., Objective: To analyze the impact of this copy-number variant in SIRPβ1 expression and how it affects AD molecular etiology., Methods: Copy-number variant proxy rs2209313 was evaluated in GERALD and GR@ACE longitudinal series. Hippocampal specimens of genotyped AD patients were also examined. SIRPβ1 isoform-specific phagocytosis assays were performed in HEK393T cells., Results: The insertion alters the SIRPβ1 protein isoform landscape compromising its ability to bind oligomeric Aβ and its affinity for TYROBP. SIRPβ1 Dup/Dup patients with mild cognitive impairment show an increased cerebrospinal fluid t-Tau/Aβ ratio (p = 0.018) and a higher risk to develop AD (OR = 1.678, p = 0.018). MRIs showed that Dup/Dup patients exhibited a worse initial response to AD. At the moment of diagnosis, all patients showed equivalent Mini-Mental State Examination scores. However, AD patients with the duplication had less hippocampal degeneration (p < 0.001) and fewer white matter hyperintensities. In contrast, longitudinal studies indicate that patients bearing the duplication allele show a slower cognitive decline (p = 0.013). Transcriptional analysis also shows that the SIRPβ1 duplication allele correlates with higher TREM2 expression and an increased microglial activation., Conclusions: The SIRPβ1 internal duplication has opposite effects over MCI-to-Dementia conversion risk and AD progression, affecting microglial response to Aβ. Given the pharmacological approaches focused on the TREM2-TYROBP axis, we believe that SIRPβ1 structural variant might be considered as a potential modulator of this causative pathway.

In this study, we explored the impact of caregiving on quality of life and health perceptions and outlined the profile of grandparent caregivers in Andalusia (Spain) in terms of a range of sociodemographic variables related to the care of their grandchildren. A sample of 171 participants (21.6% men) completed the Health-Related Quality of Life (HRQoL) questionnaire and another ad hoc one providing sociodemographic and caregiving data. We studied the relationships between these variables and HRQoL using ANOVA, chi-square and Multiple Linear Regression. We found a mainly female profile for the care of grandchildren and interesting relationships for the physical and mental components of HRQoL. Some relationships were marked by gender: caregiving for pleasure was more often the motive for men while by imposition was more common among women. We discuss the impact of caregiving on health according to the Self-Determination Theory and suggest practical implications derived from the main findings.

Current mesoscale connectivity atlases provide limited information about the organization of thalamocortical projections in the mouse brain. Labeling the projections of spatially restricted neuron populations in thalamus can provide a functionally relevant level of connectomic analysis, but these need to be integrated within the same common reference space. Here, we present a pipeline for the segmentation, registration, integration and analysis of multiple tract-tracing experiments. The key difference with other workflows is that the data is transformed to fit the reference template. As a test-case, we investigated the axonal projections and intranuclear arrangement of seven neuronal populations of the ventral posteromedial nucleus of the thalamus (VPM), which we labeled with an anterograde tracer. Their soma positions corresponded, from dorsal to ventral, to cortical representations of the whiskers, nose and mouth. They strongly targeted layer 4, with the majority exclusively targeting one cortical area and the ones in ventrolateral VPM branching to multiple somatosensory areas. We found that our experiments were more topographically precise than similar experiments from the Allen Institute and projections to the primary somatosensory area were in agreement with single-neuron morphological reconstructions from publicly available databases. This pilot study sets the basis for a shared virtual connectivity atlas that could be enriched with additional data for studying the topographical organization of different thalamic nuclei. The pipeline is accessible with only minimal programming skills via a Jupyter Notebook, and offers multiple visualization tools such as cortical flatmaps, subcortical plots and 3D renderings and can be used with custom anatomical delineations., (© 2023. The Author(s).)

(1) Background: Hospital malnutrition and sarcopenia are common in inpatients and are associated with worse prognosis. Our objective is to determine the association of the positivity of CIPA (Control of Intakes, Proteins and Anthropometry) nutrition screening tool and sarcopenia and evaluate its prognostic implications (length of stay, readmissions and mortality) as well as different components of body composition. (2) Methodology: Cross-sectional single-center study and prospective six months follow-up for prognostic variables. On admission, CIPA and EWGSOP2 criteria were assessed. (3) Results: Four hundred inpatients, a median of 65.71 years old and 83.6% with high comorbidity, were evaluated. In total, 34.8% had positive CIPA and 19.3% sarcopenia. Positive CIPA and sarcopenia had worse results in body composition (fat mass (FM), fat-free mass (FFM) and appendicular skeletal muscle mass index (ASMI)) and dynamometry. Positive CIPA is significantly associated with worse prognosis (mortality (OR = 1.99), readmissions (OR = 1.86) and length of stay (B = 0.19)). Positive CIPA and sarcopenia combined are associated with a tendency to higher mortality (OR = 2.1, p = 0.088). Low hand grip strength (HGS) is significantly related to a higher length of stay (B = -0.12). (4) Conclusions: In hospitalized patients, malnutrition independently and combined with sarcopenia is associated with a worse prognosis but not body composition. Low HGS is related to a higher length of stay.

Purpose: The purpose of this study was to check the efficacy and safety of a novel tear substitute containing hyaluronic acid and low-dose hydrocortisone in the treatment of moderate dry eye disease. Methods: In this prospective randomized study, 38 patients with moderate dry eye disease were divided into two treatment groups: Group 1 received one drop of 0.2% sodium hyaluronate and 0.001% hydrocortisone four times daily for 3 months, while Group 2 received 0.15% sodium hyaluronate and 3% trehalose at the same dosage. OSDI and SANDE questionnaires, Non-Invasive Break-Up time (NIBUT), Tear Meniscus Height (TMH), meibography, Lipid Layer Thickness (LLT), Tear Break-Up Time (TBUT), Corneal Staining Score (CFS), and Intraocular Pressure (IOP) were evaluated at baseline and after 1, 2, and 3 months of treatment. Results: During the treatment period, Group 1 showed statistically significant improvement in OSDI score ( p = 0.002), SANDE score ( p = 0.01), NIBUT ( p < 0.0001), LLT ( p < 0.0001), TBUT ( p = 0.01), and CFS ( p = 0.02). In Group 2, significant improvement was observed only in the TBUT score ( p < 0.05). Comparison of the two groups showed that NIBUT and LLT were significantly different at the end of treatment ( p = 0.001 for both comparisons), with more favorable results for sodium hyaluronate and hydrocortisone than for sodium hyaluronate and trehalose. No significant variations in intraocular pressure were observed in either group during the treatment period ( p > 0.05). Conclusions : The study confirms that a 3-months treatment with hyaluronic acid 0.2% in combination with low-dose hydrocortisone 0.001% improves the signs and symptoms of moderate DED and that a low-dosage 0.001% hydrocortisone can be helpful in preventing the progression to chronic stages of DED.

Introduction: The large family of PE and PPE proteins accounts for as much as 10% of the genome of Mycobacterium tuberculosis . In this study, we explored the immunogenicity of three proteins from this family, PE18, PE31, and PPE26, in humans and mice., Methods: The investigation involved analyzing the immunoreactivity of the selected proteins using sera from TB patients, IGRA-positive household contacts, and IGRA-negative BCG vaccinated healthy donors from the TB endemic country Mozambique. Antigen-recall responses were examined in PBMC from these groups, including the evaluation of cellular responses in healthy unexposed individuals. Moreover, systemic priming and intranasal boosting with each protein, combined with the Quil-A adjuvant, were conducted in mice., Results: We found that all three proteins are immunoreactive with sera from TB patients, IGRA-positive household contacts, and IGRA-negative BCG vaccinated healthy controls. Likewise, antigen-recall responses were induced in PBMC from all groups, and the proteins stimulated proliferation of peripheral blood mononuclear cells from healthy unexposed individuals. In mice, all three antigens induced IgG antibody responses in sera and predominantly IgG, rather than IgA, responses in bronchoalveolar lavage. Additionally, CD4+ and CD8+ effector memory T cell responses were observed in the spleen, with PE18 demonstrating the ability to induce tissue-resident memory T cells in the lungs., Discussion: Having demonstrated immunogenicity in both humans and mice, the protective capacity of these antigens was evaluated by challenging immunized mice with low-dose aerosol of Mycobacterium tuberculosis H37Rv. The in vitro Mycobacterial Growth Inhibition Assay (MGIA) and assessment of viable bacteria in the lung did not demonstrate any ability of the vaccination protocol to reduce bacterial growth. We therefore concluded that these three specific PE/PPE proteins, while immunogenic in both humans and mice, were unable to confer protective immunity under these conditions., Competing Interests: Authors MG-B and MS were employed by LIONEX GmbH, and author LB was employed by ImmunXperts SA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 García-Bengoa, Vergara, Tran, Bossi, Cooper, Pearl, Mussá, von Köckritz-Blickwede, Singh and Reljic.)

Background: Chronic hepatitis E virus (HEV) in persons with immune impairment has a progressive course leading to a rapid progression to liver cirrhosis. However, prospective data on chronic HEV is scarce. The aim of this study was to determine the prevalence and risk factors for chronic HEV infection in subjects with immune dysfunction and elevated liver enzymes., Patients and Methods: CHES is a multicenter prospective study that included adults with elevated transaminases values for at least 6 months and any of these conditions: transplant recipients, HIV infection, haemodialysis, liver cirrhosis, and immunosuppressant therapy. Anti-HEV IgG/IgM (Wantai ELISA) and HEV-RNA by an automated highly sensitive assay (Roche diagnostics) were performed in all subjects. In addition, all participants answered an epidemiological survey., Results: Three hundred and eighty-one patients were included: 131 transplant recipients, 115 cirrhosis, 51 HIV-infected subjects, 87 on immunosuppressants, 4 hemodialysis. Overall, 210 subjects were on immunosuppressants. Anti-HEV IgG was found in 94 (25.6%) subjects with similar rates regardless of the cause for immune impairment. HEV-RNA was positive in 6 (1.6%), all of them transplant recipients, yielding a rate of chronic HEV of 5.8% among solid-organ recipients. In the transplant population, only therapy with mTOR inhibitors was independently associated with risk of chronic HEV, whereas also ALT values impacted in the general model., Conclusions: Despite previous abnormal transaminases values, chronic HEV was only observed among solid-organ recipients. In this population, the rate of chronic HEV was 5.8% and only therapy with mTOR inhibitors was independently associated with chronic hepatitis E., (Copyright © 2023. Publicado por Elsevier España, S.L.U.)

Objective: Through awareness campaigns, we can change the patient's abilities to detect oral cancer at an early stage and their ability to seek help. To focus these campaigns, we need to know the level of knowledge of the population and its interest in learning about this disease. The aim of this study was to assess the level of oral cancer awareness in Asturias and the interest of the population in learning about this pathology., Methods: A representative community-based survey was carried out online using Google Forms®. Responses were transferred to a Microsoft Excel and analysed using the R-program. The relationship between two qualitative variables was studied using Pearson's Chi-square test or Fisher's test. Univariate and multivariate logistic regression models were used to determine which factors are associated with knowledge of oral cancer., Result: We found that those having over 50 years and being health professionals are more likely to know about the existence of oral cancer. Almost 85.1% of participants mentioned tobacco as a risk factor, only 39.8% identified alcohol. The ulcer was the most frequently recognized alarm sign (70.6%). The primary care physician was chosen as the first option for consultation by the 56.5% of the sample. Only 12.4% of the participants reported knowing how to self-examine their mouth. The number of views of a video of how-to self-inspection oral cavity displayed at the end of the questionnaire increased in a 39.38% during our study period., Conclusion: This survey showed a worrying lack of awareness and knowledge about oral cancer among the population of Asturias, especially among those under 50 years old. The interest shown in increasing their knowledge, give us hope in the success of future awareness campaigns.

Objectives: Osteoarthritis has been the subject of abundant research in the last years with limited translation to the clinical practice, probably due to the disease's high heterogeneity. In this study, we aimed to identify different phenotypes in knee osteoarthritis (KOA) patients with joint effusion based on their metabolic and inflammatory profiles., Methods: A non-supervised strategy based on statistical and machine learning methods was applied to 45 parameters measured on 168 female KOA patients with persistent joint effusion, consecutively recruited at our hospital after a monographic OA outpatient visit. Data comprised anthropometric and metabolic factors and a panel of systemic and local inflammatory markers. The resulting clusters were compared regarding their clinical, radiographic and ultrasound severity at baseline and their radiographic progression at two years., Results: Our analyses identified four KOA inflammatory phenotypes (KOIP): a group characterized by metabolic syndrome, probably driven by body fat and obesity, and by high local and systemic inflammation (KOIP-1); a metabolically healthy phenotype with mild overall inflammation (KOIP-2); a non-metabolic phenotype with high inflammation levels (KOIP-3); and a metabolic phenotype with low inflammation and cardiovascular risk factors not associated with obesity (KOIP-4). Of interest, these groups exhibited differences regarding pain, functional disability and radiographic progression, pointing to a clinical relevance of the uncovered phenotypes., Conclusion: Our results support the existence of different KOA phenotypes with clinical relevance and differing pathways regarding their pathophysiology and disease evolution, which entails implications in patients' stratification, treatment tailoring and the search of novel and personalized therapies., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Foreign body airway obstruction (FBAO) is a relatively common emergency and a potential cause of sudden death both in children and older people; bystander immediate action will determine the victim's outcome. Although many school children's basic life support (BLS) training programs have been implemented in recent years, references to specific training on FBAO are lacking. Therefore, the aim was to assess FBAO-solving knowledge acquisition in 10-13-year-old school children. A quasi-experimental non-controlled simulation study was carried out on 564 ten-to-thirteen-year-old children from 5 schools in Galicia (Spain). Participants received a 60-min training led by their physical education teachers (5 min theory, 15 min demonstration by the teacher, and 30 min hands-on training) on how to help to solve an FBAO event. After the training session, the school children's skills were assessed in a standardized adult's progressive FBAO simulation scenario. The assessment was carried out by proficient researchers utilizing a comprehensive checklist specifically designed to address the variables involved in resolving a FBAO event according with current international guidelines. The assessment of school children's acquired knowledge during the simulated mild FBAO revealed that 62.2% of participants successfully identified the event and promptly encouraged the simulated patient to cough actively. When the obstruction progressed, its severity was recognized by 86.2% and back blows were administered, followed by abdominal thrusts by 90.4%. When the simulated victim became unconscious, 77.1% of children identified the situation and immediately called the emergency medical service and 81.1% initiated chest compressions. No significant differences in performance were detected according to participants' age.  Conclusion: A brief focused training contributes to prepare 10-13-year-old school children to perform the recommended FBAO steps in a standardized simulated patient. We consider that FBAO should be included in BLS training programs for school children. What is Known: • Kids Save Lives strategy states that school children should learn basic life support (BLS) skills because of their potential role as first responders. • This BLS training does not include content for resolving a foreign body airway obstruction (FBAO). What is New: • Following a 60-min theoretical-practical training led by physical education teachers, 10-13-year-old school children are able to solve a simulated FBAO situation. • The inclusion of FBAO content in BLS training in schools should be considered., (© 2023. The Author(s).)

Mycotoxins are secondary metabolites produced by fungi such as Aspergillus, Alternaria, and Penicillium, affecting nearly 80% of global food crops. Tenuazonic acid (TeA) is the major mycotoxin produced by Alternaria alternata, a prevalent pathogen affecting plants, fruits, and vegetables. TeA is notably prevalent in European diets, however, TeA biomarkers of exposure and metabolites remain unknown. This research aims to bridge this knowledge-gap by gaining insights about human TeA exposure and metabolization. Nine subjects were divided into two groups. The first group received a single bolus of TeA at the Threshold of Toxicological Concern (TTC) to investigate the presence of TeA urinary biomarkers, while the second group served as a control. Sixty-nine urinary samples were prepared and analyzed using UPLC-Xevo TQ-XS for TeA quantification and UPLC-Orbitrap Exploris for polar metabolome acquisition. TeA was rapidly excreted during the first 13 h and the fraction extracted was 0.39 ± 0.22. The polar metabolome compounds effectively discriminating the two groups were filtered using Orthogonal Partial Least Squares-Discriminant Analysis and subsequently annotated (n = 122) at confidence level 4. Finally, the urinary metabolome was compared to in silico predicted TeA metabolites. Nine metabolites, including oxidized, N-alkylated, desaturated, glucuronidated, and sulfonated forms of TeA were detected., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Baseline intracellular calcium levels are significantly higher in neuronal and glial cells of rat retinas with retinitis pigmentosa (RP). Although this situation could initiate multiple detrimental pathways that lead to cell death, we considered the possibility of TRPC1 being involved in maintaining calcium homeostasis in the retina by acting as a component of store-operated calcium (SOC) channels with special relevance during photoreceptor degeneration. In this study, we examined by Western blot the expression of TRPC1 in healthy control rat retinas (Sprague-Dawley, SD) and retinas with RP (P23H-1 rats). We also analyzed its specific cellular distribution by immunofluorescence to recognize changes during neurodegeneration and to determine whether its presence is consistent with high basal calcium levels and cellular survival in degenerating retinas. We found that TRPC1 immunostaining was widely distributed across the retina in both rat strains, SD and P23H, and its expression levels significantly increased in the retinas with advanced degeneration compared to the age-control SD rats. In the outer retina, TRPC1 immunoreactivity was distributed in pigment epithelium cells, the photoreceptor inner segments of older animals, and the outer plexiform layer. In the inner retina, TRPC1 labeling was detected in horizontal cells, specific somata of bipolar and amacrine cells, and cellular processes in all the strata of the inner plexiform layer. Somata and processes were also highly immunoreactive in the ganglion cell layer and astrocytes in the nerve fiber layer in all animals. In the P23H rat retinas, the TRPC1 distribution pattern changed according to advancing photoreceptor degeneration and the gliosis reaction, with TRPC1 immunoreactive Müller cells mainly in advanced stages of disease. The cellular TRPC1 immunoreactivity found in this work suggests different mechanisms of activation of these channels depending on the cell type. Furthermore, the results support the idea that photoreceptor loss due to RP is associated with robust TRPC1 protein expression in the rat inner retina and raise the possibility of TRPC1 channels contributing to maintain high basal calcium levels during neurodegeneration and/or maintenance processes of the inner retina., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Iron deficiency anemia (IDA) is a global public health concern affecting 1.6 billion people worldwide. The administration of iron supplements during the treatment of IDA adversely affects the intestinal barrier function and the composition and functionality of the intestinal microbiome, both of which are already altered during IDA. For this reason, it is of great interest to develop nutritional strategies aimed at alleviating these gut alterations associated with IDA and its treatment. In this sense, fermented goat's milk (FGM) was studied due to its nutritional quality. Our findings showed that in anemic animals the consumption of a FGM-based diet, compared to a standard diet, had positive modulatory effects on the intestinal microbiome. FGM-based diet restored intestinal dysbiosis, the intestinal barrier functionality, and bacterial translocation, contributing to a more efficient recovery of IDA. Therefore, FGM is a useful nutritional tool to ease intestinal alterations occurring during IDA and during its treatment.

R-loops, which consist of a DNA-RNA hybrid and a displaced DNA strand, are known to threaten genome integrity. To counteract this, different mechanisms suppress R-loop accumulation by either preventing the hybridization of RNA with the DNA template (RNA biogenesis factors), unwinding the hybrid (DNA-RNA helicases), or degrading the RNA moiety of the R-loop (type H ribonucleases [RNases H]). Thus far, RNases H are the only nucleases known to cleave DNA-RNA hybrids. Now, we show that the RNase DICER also resolves R-loops. Biochemical analysis reveals that DICER acts by specifically cleaving the RNA within R-loops. Importantly, a DICER RNase mutant impaired in R-loop processing causes a strong accumulation of R-loops in cells. Our results thus not only reveal a function of DICER as an R-loop resolvase independent of DROSHA but also provide evidence for the role of multi-functional RNA processing factors in the maintenance of genome integrity in higher eukaryotes., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study is to observe and compare the effects of regular yoga practice on the main inspiratory muscle, the diaphragm, by analyzing its thickness, excursion, velocity and contraction time, using ultrasound., Design: A Cross-Sectional Controlled Study., Participants: 80 healthy subjects (40 habitual yoga practitioners and 40 non-practitioners), without previous respiratory pathology participated in this study. During maximum diaphragmatic breathing, the diaphragmatic thickness (at rest and after maximum inspiration), excursion, velocity and contraction time were measured by ultrasound., Results: in the experimental group, practicing yoga, statistically significant differences (p < 0.001) were observed compared to the control group, not practicing, in the thickness of the diaphragm at rest (0.26 ± 0.02 vs 0.22 ± 0.01 cm); the diaphragmatic thickness in maximum inspiration (0.34 ± 0.03 vs 0.28 ± 0.03 cm); contraction velocity (1.54 ± 0.54 vs 2.23 ± 0.86 cm/s), contraction time (3.28 ± 0.45 vs 2.58 ± 0.49 s) and Borg scale of perceived exertion (1.05 ± 1.6 vs 1.70 ± 1.34), p = 0.05. However, the diaphragmatic excursion was greater in the control group (5.45 ± 1.42 vs 4.87 ± 1.33 cm) with no statistically significant differences (p = 0.06)., Conclusions: the regular practice of yoga improves the parameters of diaphragm thickness, speed and contraction time measured in ultrasound and the sensation of perceived exertion during a maximum inspiration. So it can be considered as another method for training the inspiratory muscles in clinical practice., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Complete blood count-derived ratios have been described as inflammatory biomarkers in several diseases. These hematological scores include the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index ([SIRI]; neutrophils × monocytes/lymphocytes). Our aim was to study how these biomarkers are related to disease expression in a large and well-characterized series of patients with systemic lupus erythematosus (SLE). A total of 284 SLE patients and 181 age- and sex-matched healthy controls were recruited. The NLR, MLR, PLR, and SIRI were calculated, and activity (SLEDAI-2K), severity (Katz), and damage index (SLICC-DI) scores were assessed in patients with SLE. Multivariable linear regression analysis was performed to study whether these scores differ between patients and controls and how they are related to clinical and laboratory features of the disease. Crude cell counts of neutrophils, monocytes, lymphocytes, and platelets were lower in SLE patients compared to controls. Despite this, NLR, MLR, and PRL, but not SIRI, were higher in SLE patients than in controls after multivariable analysis. However, the relationship between the different scores and disease characteristics was limited. Only the Katz severity index revealed a significant positive relationship with SIRI, NLR, and MLR after adjustment for covariates. Similarly, alternative complement cascade activation and low C3 were significantly associated with higher NLR, MLR, and PLR. In conclusion, although cytopenias are a common feature of patients with SLE, hematologic composite scores are independently higher in this population compared to controls. However, the relationship of these scores with the characteristics of the disease is scarce, with the relationship with the complement system being the most consistent.

Background: There is a common interest in finding a common consensus in the approach of athletes suffering from DOMS with the aim of accelerating recovery and thereby enhancing performance. The objective of this study was to observe the effects of a paired-associative transcranial and peripheral electromagnetic stimulation on young athletes suffering from DOMS, induced by 1 h of eccentric and plyometric exercises. Methods: Forty-eight young athletes participated in this randomized control trial: 13 were assigned to the peripheral group (P); 12 were in the control group (Cont); 11 were assigned to the transcranial group (T) and 12 were included in the paired-associative group (Comb). The Visual Analogue Scale (VAS) of pain perception and the mechanical Pressure Pain Threshold (PPT) were the tools used to analyze the symptoms of DOMS. On the other hand, the Half Squat (HS) test evaluated with an accelerometer, and the 30 m sprint velocity (30-mSP) test were used to observe the evolution of the sports performance of the lower limbs. All evaluations were performed before and after the eccentric exercise session that caused DOMS, as well as at 24-48, and 72 h afterward. Results: The AS group improved the symptoms of the induced DOMS, since significant positive differences were observed in the VAS and PPT compared to the other groups ( p < 0.001). In addition, the AS group showed a significant improvement in the HS and the 30-mSP tests ( p < 0.001). Based on the results a treatment with both peripheral and transcranial electromagnetic stimulation improves recovery and performance in athletes at 72 h, although these data would need to be verified in future research with a larger sample size. Conclusion: Paired-associative electromagnetic stimulation improved DOMS symptomatology, velocity, and sports performance in the lower limbs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Keriven, Sánchez Sierra, González de-la-Flor, García-Arrabé, Bravo-Aguilar, de la Plaza San Frutos, Garcia-Perez-de-Sevilla, Tornero-Aguilera, Clemente-Suarez and Domínguez-Balmaseda.)

Research institutes and universities have strengthened the development of biomedicine outreach activities, constituing a non-formal education system of science literacy, although with little commitment from undergraduate students. However, as a Service-Learning methodology, these outreach activities could work as a tool for the acquisition of skills by students of Health Science Degrees. Described here is the development of the workshop entitled "Exploring the human body" at the Biodonostia Health Research Institute and the pilot experience of its implementation as a Service-Learning activity at the University of Málaga. Firstly, 359 secondary education students were mentored by Ph.D. students through a 5-station workshop with experiments and activities related to the physiology of the human body. Then, 301 undergraduate students of Medicine and Nursing Degrees advised 965 secondary education students. Both groups of students assessed the workshop via questionnaires and a debriefing. The data showed an overall score of 4.6 out of 5 for the workshop. Undergraduate students reported a positive impact on their academic background (4.8 out of 5), mainly due to the improvement of oral communication skills (34%). Therefore, this methodology could be a valid and applicable tool to develop the cross-disciplinary competences of undergraduate students., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 García-Durán, Claros, Zamorano-González, González-García, Carrillo-Franco, Ponce-Velasco, Gago, García-Fernández, López-González and Aiastui.)

Introduction: The evidence for remdesivir therapy in immunocompromised patients is scarce. To evaluate remdesivir (RDV) effectiveness and safety in COVID-19 outpatients at high risk for progression in a real-world setting, we compare the outcome in immunocompromised (IC) patients with that in non-immunocompromised patients. Methods: Two hospitals conducted a retrospective study of all adult patients with mild-to-moderate SARS-CoV-2 infection at high risk for disease progression who were treated as outpatients with a 3-day course of RDV (1st January-30th September 2022). The primary effectiveness endpoint was a composite of any cause of hospitalization or death by day 30. A multiple logistic regression model was built to explore the association between immune status and clinical outcome, estimating adjusted odds ratios [aORs (95% CI)]. Results: We have included 211 patients, of which 57% were males, with a median age of 65 years (IQR 53-77), 70.1% were vaccinated (three or four doses), and 61.1% were IC. The median duration of symptoms before RDV treatment was 3 days (IQR 2-5). During follow-up, 14 (6.6%) patients were hospitalized, of which 6 (2.8%) were hospitalized for COVID-19 progression. No patient required mechanical ventilation, and two patients died (non-COVID-19-related). After accounting for potential confounders, only anti-CD20 treatment was associated with the composed outcome [aOR 5.35 (1.02-27.5, 95% CI)], whereas the immunocompetence status was not [aOR 1.94 (0.49-7.81, 95% CI)]. Conclusion: Early COVID-19 outpatient treatment with a 3-day course of remdesivir in vaccinated patients at high risk for disease progression during the Omicron surge had a good safety profile. It was associated with a low rate of all-cause hospitalization or death, regardless of immunocompetence status., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ramos-Rincón, Pinargote-Celorio, Llenas-García, Moreno-Pérez, González-Cuello, Gonzalez-de-la-Aleja, Martínez-López, Reus, García-López, Rodríguez, Boix and Merino.)

Serological antibody profiling of tuberculosis (TB) patients and household contacts with latent TB infection (LTBI) could identify risk indicators of disease progression, and potentially also serve as an easily accessible diagnostic tool to discriminate between these two stages of Mycobacterium tuberculosis ( Mtb ) infection. Yet, despite significant efforts over many decades, neither application has yet fully materialised, and this is at least in part due to inconsistent and varying antibody profiles from different TB endemic regions. In this study, we conducted a retrospective exploratory analysis of serum antibodies in a cohort of active TB patients (ATB) and their interferon-gamma release assay (IGRA) positive household contacts (LTBI), as well as healthy controls (HC) from Mozambique, a country with a high TB burden from the Sub-Saharan region. Using several Mtb antigens as well as crude preparations of culture filtrate proteins (CFP) from Mtb and Bacille Calmette Guérin (BCG), we report that the most discriminatory response for TB and LTBI was observed for serum IgA antibodies to the MPT64 antigen, followed by IgG antibodies to Ag85B and CFP, with ATB patients having significantly higher levels than LTBI or BCG-vaccinated healthy controls. Conversely, sera from LTBI individuals had higher levels of IgG antibodies to the HBHA antigen than ATB. While our sample size ( n  = 21 for ATB, 18 for LTBI and 17 for HC) was too small to fully evaluate the diagnostic potential of these differing serological profiles, our study however preliminarily indicated high level of sensitivity (95%) and specificity (97%) of an ELISA MPT64-IgA test for discriminating TB from LTBI and healthy controls, supporting the notion that it alone, or possibly in combination with other antigens such as Ag85B or CFP could lead to development of an easily accessible diagnostic tool for TB., Competing Interests: MG-B is associated with Lionex GmbH, which provided the recombinant antigens. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Tran, Boariu, García-Bengoa, Kim, Vergara, Mussá and Reljic.)

Six novel click-tambjamines (1-6) bearing an alkyl chain of varying length linked to the imine moiety have been formulated in nanostructured lipid carriers (NLCs) to evaluate their transmembrane anion transport activity both when free ( i.e. , not encapsulated) and nanoformulated. Nanostructured lipid carriers (NLCs) are an example of drug delivery systems (DDSs) that stand out because of their versatility. In this work we show that NLCs can be used to efficiently formulate highly lipophilic anionophores and experiments conducted in model liposomes reveal that these formulations are adequate to deliver anionophores without compromising their transport activity. This result paves the way to facilitate the study of highly lipophilic anionophores and their potential use as future drugs.

In the field of Ophthalmology, the mNGS 16S rRNA sequencing method of studying the microbiota and ocular microbiome is gaining more and more weight in the scientific community. This study aims to characterize the ocular microbiota of patients diagnosed with keratoconus who have not undergone any prior surgical treatment using the mNGS 16S rRNA sequencing method. Samples of naïve keratoconus patients were collected with an eNAT with 1 mL of Liquid Amies Medium (Copan Brescia, Italy), and DNA was extracted and analyzed with 16S NGS. The microbiota analysis showed a relative abundance of microorganisms at the phylum level in each sample collected from 38 patients with KC and 167 healthy controls. A comparison between healthy control and keratoconus samples identified two genera unique to keratoconus, Pelomonas and Ralstonia. Our findings suggest that alterations in the microbiota may play a role in the complex scenario of KC development.

Background: The arrival of new disease-modifying treatments for Alzheimer's disease (AD) requires the identification of subjects at risk in a simple, inexpensive, and non-invasive way. With tools allowing an adequate screening, it would be possible to optimize the use of these treatments. Plasma markers of AD are very promising, but it is necessary to prove that alterations in their levels are related to alterations in gold standard markers such as cerebrospinal fluid or PET imaging. With this research, we want to evaluate the performance of plasma Aβ40, Aβ42, and p-tau181 to detect the pathological changes in CSF using the automated Lumipulse platform., Methods: Both plasma and CSF Aβ40, Aβ42, and p-tau181 have been evaluated in a group of 208 cognitively unimpaired subjects with a 30.3% of ApoE4 carriers. We have correlated plasma and CSF values of each biomarker. Then, we have also assessed the differences in plasma marker values according to amyloid status (A - / +), AD status (considering AD + subjects to those A + plus Tau +), and ATN group defined by CSF. Finally, ROC curves have been performed, and the area under the curve has been measured using amyloid status and AD status as an outcome and different combinations of plasma markers as predictors., Results: Aβ42, amyloid ratio, p-tau181, and p-tau181/Aβ42 ratio correlated significantly between plasma and CSF. For these markers, the levels were significantly different in the A + / - , AD + / - , and ATN groups. Amyloid ratio predicts amyloid and AD pathology in CSF with an AUC of 0.89., Conclusions: Plasma biomarkers of AD using the automated Lumipulse platform show good diagnostic performance in detecting Alzheimer's pathology in cognitively unimpaired subjects., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder associated with high risk of malignant transformation. Currently, there is no treatment available, and restrictive follow-up of patients is crucial for a better prognosis. Oral leukoplakia (OL) shares some clinical and microscopic features with PVL but exhibits different clinical manifestations and a lower rate of malignant transformation. This study aimed to investigate the proteomic profile of PVL in tissue and saliva samples to identify potential diagnostic biomarkers with therapeutic implications. Tissue and saliva samples obtained from patients with PVL were compared with those from patients with oral OL and controls. Label-free liquid chromatography with tandem mass spectrometry was employed, followed by qualitative and quantitative analyses, to identify differentially expressed proteins. Potential biomarkers were identified and further validated using immunohistochemistry. Staining intensity scan analyses were performed on tissue samples from patients with PVL, patients with OL, and controls from Brazil, Spain, and Finland. The study revealed differences in the immune system, cell cycle, DNA regulation, apoptosis pathways, and the whole proteome of PVL samples. In addition, liquid chromatography with tandem mass spectrometry analyses showed that calreticulin (CALR), receptor of activated protein C kinase 1 (RACK1), and 14-3-3 Tau-protein (YWHAQ) were highly expressed in PVL samples. Immunohistochemistry validation confirmed increased CARL expression in PVL compared with OL. Conversely, RACK1 and YWHA were highly expressed in oral potentially malignant disorder compared to the control group. Furthermore, significant differences in CALR and RACK1 expression were observed in the OL group when comparing samples with and without oral epithelial dysplasia, unlike the PVL. This research provides insights into the molecular mechanisms underlying these conditions and highlights potential targets for future diagnostic and therapeutic approaches., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Introduction: The effectiveness of the Enhanced Recovery After Surgery (ERAS) protocols in gastric cancer surgery remains controversial., Methods: Multicentre prospective cohort study of adult patients undergoing surgery for gastric cancer. Adherence with 22 individual components of ERAS pathways were assessed in all patients, regardless of whether they were treated in a self-designed ERAS centre. Each centre had a three-month recruitment period between October 2019 and September 2020. The primary outcome was moderate-to-severe postoperative complications within 30 days after surgery. Secondary outcomes were overall postoperative complications, adherence to the ERAS pathway, 30 day-mortality and hospital length of stay (LOS)., Results: A total of 743 patients in 72 Spanish hospitals were included, 211 of them (28.4 %) from self-declared ERAS centres. A total of 245 patients (33 %) experienced postoperative complications, graded as moderate-to-severe complications in 172 patients (23.1 %). There were no differences in the incidence of moderate-to-severe complications (22.3% vs. 23.5%; OR, 0.92 (95% CI, 0.59 to 1.41); P = 0.068), or overall postoperative complications between the self-declared ERAS and non-ERAS groups (33.6% vs. 32.7%; OR, 1.05 (95 % CI, 0.70 to 1.56); P = 0.825). The overall rate of adherence to the ERAS pathway was 52% [IQR 45 to 60]. There were no differences in postoperative outcomes between higher (Q1, > 60 %) and lower (Q4, ≤ 45 %) ERAS adherence quartiles., Conclusions: Neither the partial application of perioperative ERAS measures nor treatment in self-designated ERAS centres improved postoperative outcomes in patients undergoing gastric surgery for cancer., Trial Registration: ClinicalTrials.gov Identifier NCT03865810., (Copyright © 2023 AEC. Published by Elsevier España, S.L.U. All rights reserved.)

The small intestine is a complex organ with a characteristic architecture and a major site for drug and nutrient absorption. The three-dimensional (3D) topography organized in finger-like protrusions called villi increases surface area remarkably, granting a more efficient absorption process. The intestinal mucosa, where this process occurs, is a multilayered and multicell-type tissue barrier. In vitro intestinal models are routinely used to study different physiological and pathological processes in the gut, including compound absorption. Still, standard models are typically two-dimensional (2D) and represent only the epithelial barrier, lacking the cues offered by the 3D architecture and the stromal components present in vivo, often leading to inaccurate results. In this work, we studied the impact of the 3D architecture of the gut on drug transport using a bioprinted 3D model of the intestinal mucosa containing both the epithelial and the stromal compartments. Human intestinal fibroblasts were embedded in a previously optimized hydrogel bioink, and enterocytes and goblet cells were seeded on top to mimic the intestinal mucosa. The embedded fibroblasts thrived inside the hydrogel, remodeling the surrounding extracellular matrix. The epithelial cells fully covered the hydrogel scaffolds and formed a uniform cell layer with barrier properties close to in vivo. In particular, the villus-like model revealed overall increased permeability compared to a flat counterpart composed by the same hydrogel and cells. In addition, the efflux activity of the P-glycoprotein (P-gp) transporter was significantly reduced in the villus-like scaffold compared to a flat model, and the genetic expression of other drugs transporters was, in general, more relevant in the villus-like model. Globally, this study corroborates that the presence of the 3D architecture promotes a more physiological differentiation of the epithelial barrier, providing more accurate data on drug absorbance measurements., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The intestine is a complex tissue with a characteristic three-dimensional (3D) crypt-villus architecture, which plays a key role in the intestinal function. This function is also regulated by the intestinal stroma that actively supports the intestinal epithelium, maintaining the homeostasis of the tissue. Efforts to account for the 3D complex structure of the intestinal tissue have been focused mainly in mimicking the epithelial barrier, while solutions to include the stromal compartment are scarce and unpractical to be used in routine experiments. Here we demonstrate that by employing an optimized bioink formulation and the suitable printing parameters it is possible to produce fibroblast-laden crypt-villus structures by means of digital light projection stereolithography (DLP-SLA). This process provides excellent cell viability, accurate spatial resolution, and high printing throughput, resulting in a robust biofabrication approach that yields functional gut mucosa tissues compatible with conventional testing techniques., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Children with cerebral palsy (CP) often show executive function (EF) impairments that are key to quality of life. The aim of this study was to assess whether a home-based computerized intervention program improves executive functions (EFs) compared to usual care. Sixty participants (30 females) with CP (8-12 years old) were paired by age, sex, motor ability, and intelligence quotient score and then randomized to intervention and waitlist control groups. The intervention group received a 12-week home-based computerized EF intervention (5 days/week, 30 min/day, total dose 30 h). Core and higher-order EFs were assessed before, immediately after, and 9 months after completing the intervention. The intervention group performed better than the waitlist control group in the three core EFs (immediately and 9 months after the intervention): inhibitory control (F = 7.58, p = 0.13 and F = 7.85, p = 0.12), working memory (F = 8.34, p = 0.14 and F = 7.55, p = 0.13), and cognitive flexibility (F = 4.87, p = 0.09 and F = 4.19, p = 0.08). No differences were found between the groups in higher-order EFs or EF manifestations in daily life., Conclusions: A home-based computerized EF intervention improved core EFs in children with CP, but further research is needed to identify strategies that allow the transfer of these improvements to everyday life., Trial Registration: NCT04025749 retrospectively registered on 19 July 2019., What Is Known: • One in two children with cerebral palsy has an intellectual impairment. Visual perception and executive functions are the most reported specific cognitive deficits. • The majority of interventions for cerebral palsy focus on motor impairments, but only a few randomized controlled trials have explored the effect of interventions on executive functions., What Is New: • A home-based computerized cognitive intervention can improve the core executive functions of children with cerebral palsy. • Short- and long-term effects on core executive functions have been found., (© 2023. The Author(s).)

The aim of this study is to evaluate the results obtained on the optical bench and clinically with an isofocal lens (ISOPure, BVI medical, Belgium) to compare them to a standard monofocal one (MicroPure, BVI medical, Belgium). To do so, we have combined laboratory investigation and a prospective, comparative, and randomized clinical study. First, we have measured the wavefront of the two models studied using a NIMO TR1504 (Lambda-X, Belgium) deflectometer for three nominal powers: +10.00, +20.00 and +30.00 D. In the randomized study with 48 patients, half of them implanted with ISOPure and the other with MicroPure, we have measured visual acuities and contrast sensitivity under photopic and mesopic conditions. The optical bench results show that the isofocal lens presented higher power than the monofocal one, at the lens center, due to the spherical aberration (coefficients Z(4,0), Z(6,0) and Z(8,0)) induced by the greater asphericity of its design. The addition obtained depended on the nominal power, from +1.00 to +1.50 D. The results of the clinical study showed that the ISOPure lens presented better visual outcomes, which were statistically significant, at intermediate distance compared to the MicroPure lens ( p -values of 0.014 and 0.022 for 80 and 60 cm, respectively) without decreasing the contrast sensitivity. Clinical outcomes were not affected by pupillary size. In conclusion, due to the increase in power at the lens center due to its highly aspherical design, the isofocal lens evaluated showed better intermediate vision than the monofocal one.

Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) spatially resolves the chemical composition of tissues. Lipids are of particular interest, as they influence important biological processes in health and disease. However, the identification of lipids in MALDI-MSI remains a challenge due to the lack of chromatographic separation or untargeted tandem mass spectrometry. Recent studies have proposed the use of MALDI in-source fragmentation to infer structural information and aid identification. Here we present rMSIfragment, an open-source R package that exploits known adducts and fragmentation pathways to confidently annotate lipids in MALDI-MSI. The annotations are ranked using a novel score that demonstrates an area under the curve of 0.7 in ROC analyses using HPLC-MS and Target-Decoy validations. rMSIfragment applies to multiple MALDI-MSI sample types and experimental setups. Finally, we demonstrate that overlooking in-source fragments increases the number of incorrect annotations. Annotation workflows should consider in-source fragmentation tools such as rMSIfragment to increase annotation confidence and reduce the number of false positives., (© 2023. Springer Nature Switzerland AG.)

An excessive production of lactate by cancer cells fosters tumor growth and metastasis. Therefore, targeting lactate metabolism and transport offers a new therapeutic strategy against cancer, based on dependency of some cancer cells for lactate as energy fuel or as oncogenic signal. Herein we present a family of anionophores based on the structure of click-tambjamines that have proved to be extremely active lactate carriers across phospholipid membranes. Compound 1, the most potent lactate transmembrane carrier, was studied in HeLa cells. The use of a monocarboxylate transporters (MCTs) inhibitor proved that 1 is an active lactate transporter in living cells, confirming the results obtained in phospholipid vesicles. Moreover, an additive effect of compound 1 with cisplatin was observed in HeLa cells. Identification of active lactate anionophores working in living cells opens up ways to exploit this class of compounds as molecular tools and drugs addressing dysregulated lactate metabolism., Competing Interests: A patent application (P202330370) related to this work has been submitted., (© 2023 The Authors.)

Interleukin-6 (IL-6) is a proinflammatory cytokine that mediates pleiotropic functions in immune responses and inflammatory diseases. The literature lacks studies, with a clinical perspective, on the relationship between IL-6 serum levels and the characteristics of the disease in patients with systemic lupus erythematosus (SLE). In the present work, we aimed to analyze the association between circulating IL-6 and disease manifestations in a well-characterized series of patients with SLE. Serum IL-6 levels and disease activity (SLEDAI-2K), severity (Katz) and damage index (SLICC-DI), complete lipid profile, and subclinical carotid atherosclerosis were evaluated in 284 patients with SLE. In addition, a complete characterization of the complement system was performed in samples from patients with SLE. A multivariate linear regression analysis was carried out to study the relationship between clinical and laboratory characteristics of the disease and IL-6 levels. Age (beta coef. 0.07 [95%CI 0.01-0.1] pg/mL, p = 0.014), C-reactive protein (beta coef. 0.21 [95%CI 0.16-0.25] pg/mL, p < 0.01), and male gender (beta coef. 2 [95%CI 0.3-0.5] pg/mL, p = 0.024), were positively associated with higher IL-6 levels in SLE patients. Most disease characteristics and damage and activity indices did not show significant relationships with IL-6. However, after multivariate analysis, IL-6 was associated with lower serum levels of HDL cholesterol (beta coef. -0.04 [95%CI -0.08-(-0.1)] pg/mL, p = 0.011), and apolipoprotein A1 (beta coef. -0.02 [95%CI -0.04-(-0.001)] pg/mL, p = 0.035). In contrast, the alternative complement cascade, C1inh, and C3a were all positively and independently associated with higher serum levels of IL-6. Moreover, stratification of the Systematic Coronary Risk Assessment 2 (SCORE2) results according to different categories of cardiovascular risk was associated with higher circulating serum IL-6 levels (beta coef. 0.2 [95%CI 0.02-0.4], pg/mL, p = 0.028). In conclusion, in a large series of SLE patients, IL-6 was not associated with disease-related features of SLE, including damage, severity, or activity indices. However, an association was found between serum IL-6 levels and circulating C3a and cardiovascular risk. Our study emphasizes the importance that IL-6 could have in cardiovascular disease and complement system disruption of SLE patients. Therapies targeting IL-6 could have a role in these two clinical manifestations of patients with SLE.

Background: Low back pain is one of the most common disabling pathologies in humanity worldwide. Physical exercises have been used in recent decades to reduce the pain, improve the functionality of the lumbar spine and avoid relapses. The purpose of the study is to analyze the effect of a program based on re-education exercises involving preactivation of the abdominal transverse muscle compared to conventional treatment in adults with chronic nonspecific low back pain., Methods: A two-arm, single-blind randomized control trial with 35 primary care patients with chronic nonspecific low back pain. Both groups received a 4-week intervention. Data were collected at baseline and at the end of the intervention. Sixteen patients participated in the intervention group, and 19 patients in the control group., Results: For the experimental group, the outcomes of disability and activation of the abdominal transverse muscle decreased significantly (MD -2.9; CI 95% -5.6 to -0.35; η2 = 0.14; p = 0.028) and (MD 2.3; CI 95% 0.91 to 3.67; η2 = 0.25; p = 0.002) respectively, with a large effect size, compared to the control group. There were no differences between the groups in pain intensity, thickness, and resistance of the transverse abdominal muscle., Conclusion: A 4-week specific program based on re-education exercises of the preactivation of the abdominal transverse muscle is more effective than conventional treatment for reducing disability and increasing the activation of the abdominal transverse muscle measured by VAS scale and PBU., Trial Registration: Clinicaltrials.gov identifier: NCT03097497. Date of registration: 31/03/2017., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Metabolic syndrome (MetS) is a constellation of risk factors increasingly present in the world's population. People with this syndrome are at an increased risk of cardiovascular disease and type 2 diabetes mellitus. Moreover, evidence has shown that it affects different organs. MetS and its risk factors are independently associated with impaired lung function, which can be quantified through spirometric variables., Objective: This study aims to determine whether a high number of MetS criteria is associated with increased lung function decline., Methods: We conducted a descriptive cross-sectional study with a random sample of 1980 workers. Workers with acute respiratory pathology (eg, influenza), chronic respiratory pathology (eg, chronic bronchitis), or exposure to substances harmful to the lungs (eg, organic and inorganic dust) were not included. MetS was established based on harmonized criteria, and lung function was assessed according to spirometric variables. On the basis of these, classification into restrictive lung disease (RLD), obstructive lung disease, and mixed lung disease (MLD) was performed. In addition, the association between MetS and lung function was established based on analysis of covariance, linear trend analysis, and multiple linear regression., Results: MetS was associated with worse lung function according to all the spirometric parameters analyzed (percentage of predicted forced expiratory volume in 1 second: mean 83, SD 13.8 vs mean 89.2, SD 12.8; P<.001 and percentage of predicted forced vital capacity: mean 85.9, SD 11.6 vs mean 92, SD 11.3; P<.001). Moreover, those diagnosed with MetS had a higher prevalence of lung dysfunction (41% vs 21.9%; P<.001), RLD (23.4% vs 11.2%; P<.001), and MLD (7.3% vs 2.2%; P<.001). Furthermore, an increasing number of MetS criteria was associated with a greater impairment of pulmonary mechanics (P<.001). Similarly, with an increasing number of MetS criteria, there was a significant linear trend (P<.001) in the growth of the prevalence ratio of RLD (0 criteria: 1, 1: 1.46, 2: 1.52, 3: 2.53, 4: 2.97, and 5: 5.34) and MLD (0 criteria: 1, 1: 2.68, 2: 6.18, 3: 9.69, and 4: 11.37). Regression analysis showed that the alteration of all MetS risk factors, adjusted for various explanatory variables, was significantly associated with a worsening of spirometric parameters, except for forced expiratory volume in 1 second/forced vital capacity., Conclusions: The findings have shown that an increase in cardiometabolic risk factors is associated with a more significant worsening of spirometric variables and a higher prevalence of RLD and MLD. As spirometry could be a crucial tool for monitoring patients at risk of developing chronic pathologies, we conclude that this inexpensive and easily accessible test could help detect changes in lung function in patients with cardiometabolic disorders. This highlights the need to consider the importance of cardiometabolic health in lung function when formulating public health policies., (©Rafael Molina-Luque, Guillermo Molina-Recio, Domingo de-Pedro–Jiménez, Carlos Álvarez Fernández, María García–Rodríguez, Manuel Romero-Saldaña. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 05.09.2023.)

Lichen planus (LP) is a chronic, inflammatory mucocutaneous disorder associated with systemic diseases such as hepatitis C (HCV). The objective of this study is to evaluate the association between LP and HCV bidirectionally through a systematic review and meta-analysis. A comprehensive search of studies published was performed in the databases of PubMed, Embase, and Web of Science. Out of 18,491 articles, 192 studies were included. The global prevalence of HCV positive (HCV+) in LP patients registered from 143 studies was 9.42% [95% confidence interval (CI), 7.27-11.58%], and from these, 84 studies showed HCV+ 4-fold more frequent in LP than a control group (OR, 4.48; 95% CI, 3.48-5.77). The global prevalence of LP in patients HCV+ recorded from 49 studies was 7.05% (95% CI, 4.85-9.26%), and from these, 15 registered a 3-fold more LP in HCV (OR, 3.65; 95% CI, 2.14-6.24). HCV+ in LP patients showed great geographic variability (OR, 2.7 to 8.57), and the predominantly cutaneous location was higher (OR, 5.95) than the oral location (OR, 3.49). LP in HCV+ patients was more frequent in the Eastern Mediterranean (OR, 5.51; 95% CI, 1.40-15.57). There is a higher prevalence of HCV+ in LP and vice versa than in the control group, especially in certain geographical areas that should be taken into consideration when doing screening in countries with an upper prevalence of HCV among the general population.

Mass spectrometry imaging (MSI) has become a widespread analytical technique to perform nonlabeled spatial molecular identification. The Achilles' heel of MSI is the annotation and identification of molecular species due to intrinsic limitations of the technique (lack of chromatographic separation and the difficulty to apply tandem MS). Successful strategies to perform annotation and identification combine extra analytical steps, like using orthogonal analytical techniques to identify compounds; with algorithms that integrate the spectral and spatial information. In this review, we discuss different experimental strategies and bioinformatics tools to annotate and identify compounds in MSI experiments. We target strategies and tools for small molecule applications, such as lipidomics and metabolomics. First, we explain how sample preparation and the acquisition process influences annotation and identification, from sample preservation to the use of orthogonal techniques. Then, we review twelve software tools for annotation and identification in MSI. Finally, we offer perspectives on two current needs of the MSI community: the adaptation of guidelines for communicating confidence levels in identifications; and the creation of a standard format to store and exchange annotations and identifications in MSI., (© 2022 The Authors. Mass Spectrometry Reviews published by John Wiley & Sons Ltd.)

Objective: Advances in our understanding of the Alzheimer's disease (AD) continuum through in vivo biomarkers have highlighted the need to develop neuropsychological tests that are more sensitive to subtle cognitive changes in the preclinical stages of the disease. Recent data suggest that the assessment of memory retention over extended delays, to detect so-called accelerated long-term forgetting (ALF), may be a reliable way to discriminate between presymptomatic AD and healthy aging. This review aims to present the scientific evidence published to date on this particular aspect of memory., Method: A comprehensive review of all published articles on ALF in AD to the present day., Results: We present findings relating to ALF in neurological disease, discuss theoretical aspects related to the integration of the concept of ALF in the framework of memory models, explain mechanisms that may be involved in its genesis and present supportive work from research in animal models. We focus particularly on aspects relevant to the assessment of ALF in clinical practice., Conclusions: Despite many advances, further research will be needed to define more precisely what ALF is, what neural structures and mechanisms are involved in its occurrence, whether there are distinct patterns of forgetting according to etiology, and when and how to detect ALF most reliably. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Purpose: To analyze the presence of an artery-vein complex (AVC) underneath myopic choroidal neovascularization (mCNV) and to determine its relationship with neovascular activity., Methods: Retrospective analysis of 681 eyes from 362 patients with high myopia defined by an axial length of >26 mm using optical coherence tomography (OCT) and OCT angiography imaging. Patients with clinical diagnosis of mCNV and good quality OCT angiography images were then selected. An AVC was defined by the identification of both perforating scleral vessels and dilated choroidal veins under or in contact with the mCNV in the same case. Swept source OCT (SS-OCT) and SS-OCT angiography images (TRITON; Topcon Corporation, Tokyo, Japan) were reviewed to detect AVC in the mCNV area., Results: Fifty eyes of 49 highly myopic patients with mCNV were analyzed. Eyes with AVC were statistically older (69.95 ± 13.53 vs. 60.83 ± 10.47 years old; P < 0.01), needed less intravitreal injections/year along the follow-up period (0.80 ± 0.62 vs. 1.92 ± 0.17; P < 0.01), and showed less relapses/year (0.58 ± 0.75 vs. 0.46 ± 0.42; P < 0.05) when compared with eyes without AVC. Moreover, eyes with AVC were less likely to relapse during the first year from mCNV activation (n = 5/14 vs. n = 14/16; P < 0.01; P < 0.01). No significant differences were found regarding either axial length (30.55 ± 2.31 vs. 29.65 ± 2.24, P > 0.05) or best-corrected visual acuity (0.4 ± 0.5 vs. 0.4 ± 0.5 Logarithm of the Minimum Angle of Resolution (logMAR), P > 0.05) between groups., Conclusion: AVC complex has an influence over myopic choroidal neovascularization activity resulting in less aggressive neovascular lesions than those with perforating scleral vessels only., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

To elucidate the spectrum of metastatic solid tumors to the testis and their clinicopathologic features. The databases and files of 26 pathology departments from 9 countries on 3 continents were surveyed to identify metastatic solid tumors to the testis and to characterize their clinicopathologic features in detail. We compiled a series of 157 cases of metastatic solid tumors that secondarily involved the testis. The mean patient age at diagnosis was 64 years (range, 12-93 years). Most patients (127/144; 88%) had clinical manifestation of the disease, with testicular mass/nodule (89/127; 70%) being the most common finding. The main mechanism of testicular involvement was metastasis in 154/157 (98%) cases. Bilateral testicular involvement was present in 12/157 (8%) patients. Concurrent or prior extratesticular metastases were present in 78/101 (77%) patients. The diagnosis was made mainly in orchiectomy specimens (150/157; 95%). Different types of carcinomas (138/157; 87%), most commonly adenocarcinoma (72/157; 46%), were the most common malignancies. The most common primary carcinomas included prostatic (51/149; 34%), renal (29/149; 20%), and colorectal (13/149; 9%). Intratubular growth was identified in 13/124 (11%) cases and paratesticular involvement was found in 73/152 (48%) cases. In patients with available follow-up (110/157; 70%), more than half (58/110; 53%) died of disease. In this largest series compiled to date, we found that most secondary tumors of the testis represent metastases from the genitourinary and gastrointestinal tract carcinomas and typically occur in the setting of disseminated disease., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To determine the diagnostic contribution of the absolute quantification of the myocardial deposit of 99m Tc-DPD in patients with cardiac amyloidosis due to transthyretin deposits (ATTR)., Materials and Methods: SPECT/CT was performed in 41 patients with positive scintigraphic results for ATTR cardiac amyloidosis. The patients were divided into two groups (Perugini grades 2 and 3) and the SUVmax at the level of the bone and both ventricles and the percentage of dose calculated in these areas were calculated. The Student's t-test was used to compare results and the area under the curve (AUC) was calculated to assess differential efficacy and establish discriminatory cut-off points between both groups of patients., Results: Statistically significant differences were observed in all the study variables, with the exception of bone SUV max . The differences with the greatest statistical power were observed in the variables SUV maxRV and the percentage of dose in both ventricles (p < 0.001). The cut-off point obtained for the variable SUVm axLV was 8.620 (sensitivity 87.9% and specificity 100%; AUC 0.966), while that of the variable SUV maxRV was 6.195 (sensitivity 81.8% and specificity 100%; AUC 0.955)., Conclusions: The absolute quantification of myocardial uptake of 99m Tc-DPD in the SPECT/CT images of patients with suspected cardiac amyloidosis due to transthyretin deposits represents a new diagnostic tool that allows adequate classification of patients according to the Perugini visual grading scale., (Copyright © 2023 Sociedad Española de Medicina Nuclear e Imagen Molecular. Published by Elsevier España, S.L.U. All rights reserved.)

This work aims to generate the data needed to set epidemiological cut-off values for minimum inhibitory concentration (MIC) and disc-diffusion zone measurements of Vibrio anguillarum. A total of 261 unique isolates were tested, applying standard methods specifying incubation at 28°C for 24-28 h. Aggregated MIC distributions for a total of 247 isolates were determined in 9 laboratories for 11 agents. Data aggregations of the disc zone for the 10 agents analysed contained between 157 and 218 observations made by 4 to 7 laboratories. Acceptable ranges for quality control (QC) reference strains were available for 7 agents and the related multi-laboratory aggregated data were censored, excluding the data of a laboratory that failed to meet QC requirements. Statistical methods were applied to calculate epidemiological cut-off values. Cut-off values for MIC data were calculated for florfenicol (≤1 µg ml-1), gentamicin (≤4 µg ml-1), oxytetracycline (≤0.25 µg ml-1) and trimethoprim/sulfamethoxazole (≤0.125/2.38 µg ml-1). The cut-off values for disc zone data were calculated for enrofloxacin (≥29 mm), florfenicol (≥27 mm), gentamicin (≥19 mm), oxolinic acid (≥24 mm), oxytetracycline (≥24 mm) and trimethoprim/sulfamethoxazole (≥26 mm). MIC and disc-diffusion zone data for the other agents where not supported by QC, thus yielding only provisional cut-off values (meropenem, ceftazidime). Regardless of whether QC is available, some of the aggregated MIC distributions (enrofloxacin, oxolinic acid), disc zone (sulfamethoxazole), and MIC and disc-diffusion distributions (ampicillin, chloramphenicol) did not meet the statistical requirements. The data produced will be submitted to the Clinical Laboratory Standards Institute for their consideration in setting international consensus epidemiological cut-off values.

Background: The high prevalence of oral pathology in children encourages to gain further understanding on their manifestations and urgent nature, objective of the present study Methodology. Cross-sectional study that included patients aged <14 years of age who attended an emergency department over a one-year period. The relationship between the variables collected and oral pathology was analyzed., Results: Fifty-five patients were included, 45.5% girls, mean age 4.11 years (10 days to 13 years). Overall, mucosal pathology (74.5%) prevailed over dental ones, and lesions of infectious origin (54.6%) over the traumatic ones (14.5%). Dental pathology (50% toothache and 35.7% infections) was significantly associated with being >6 years (66.7 vs 10%), pain (40.7 vs 10.7%) and absence of fever (37.9 vs 11.5%). Mucosal pathology (61% infections: 53.7% viral and 31.7% due to herpangina) was significantly associated with being =6 years (60 vs 6.7%) and having fever (76.9 vs 17.2%). Six traumatic lesions on the mucosa and two on the teeth were observed; significantly more patients attended the emergency room within 24 hours (median =1 hour) than in the case of infection (100 vs 51.7%). Being =6 years was significantly associated with fever, mucosal pathology, mucosal infection, and herpangina, and being >6 years was associated with pain, previous antibiotic treatment and at discharge, and previous NSAID regimen., Conclusions: The analyzed pediatric oral pathologies treated in the emergency department are of mucosal and infectious origin. Dental disease prevail in children >6 years of age and mucosal lesions in those =6 years; no sex differences are observed.