Isoform-specific C-terminal phosphorylation drives autoinhibition of Casein Kinase 1.

Casein kinase 1 δ (CK1δ) controls essential biological processes including circadian rhythms and Wnt signaling, but how its activity is regulated is not well understood. CK1δ is inhibited by autophosphorylation of its intrinsically disordered C-terminal tail. Two CK1 splice variants, δ 1 and δ 2 , are known to have very different effects on circadian rhythms. These variants differ only in the last 16 residues of the tail, referred to as the extreme C-termini (XCT), but with marked changes in potential phosphorylation sites. Here we test if the XCT of these variants have different effects in autoinhibition of the kinase. Using NMR and HDX-MS, we show that the δ 1 XCT is preferentially phosphorylated by the kinase and the δ 1 tail makes more extensive interactions across the kinase domain. Mutation of δ1 -specific XCT phosphorylation sites increases kinase activity both in vitro and in cells and leads to changes in circadian period, similar to what is reported in vivo. Mechanistically, loss of the phosphorylation sites in XCT disrupts tail interaction with the kinase domain. δ1 autoinhibition relies on conserved anion binding sites around the CK1 active site, demonstrating a common mode of product inhibition of CK1δ . These findings demonstrate how a phosphorylation cycle controls the activity of this essential kinase.

Evaluating the associations between dysautonomia, gastrointestinal transit, and clinical phenotype in patients with systemic sclerosis.

OBJECTIVE: Our objective was to identify systemic sclerosis (SSc) patients with a high burden of autonomic symptoms and to determine whether they have a distinct clinical phenotype, gastrointestinal (GI) transit or extraintestinal features. METHODS: In a prospective cohort of SSc patients with GI disease, clinical data were systematically obtained at routine visits. Dysautonomia was identified by the Composite Autonomic Symptom Score (COMPASS)-31questionnaire. GI transit was measured by whole-gut scintigraphy. Associations between total COMPASS-31 scores and clinical features, GI symptoms, and transit were evaluated. Comparisons between patients with global autonomic dysfunction [(GAD); ≥5 positive COMPASS-31 subdomains] and those with limited autonomic dysfunction [(LAD); <5 positive subdomains] were also studied. RESULTS: 91 patients with SSc and GI involvement were included [mean age 57, 90% female, 74% limited cutaneous disease, 83% significant GI disease (Medsger score ≥2)]. The mean COMPASS-31 score in SSc was higher than controls (38.8 vs. 7.2). 33% had GAD, 67% had LAD. Patients with GAD were more likely to have limited SSc (93% vs. 65%; p<0.01) and have sicca symptoms (100% vs. 77%; p=0.01). Gastric and colonic transit were faster in patients with GAD (p<0.05). Upper GI involvement (Medsger GI score of 1 or 2) was associated with higher total COMPASS-31 scores (p=0.02). CONCLUSION: Symptoms of global dysautonomia are seen in up to one-third of patients with SSc and GI involvement. Identifying specific clinical characteristics associated with GAD in SSc will help to identify a population that may benefit from therapies that modulate the autonomic nervous system.

Development of a dispersive solid phase microextraction method based on the application of MgAl, NiAl, and CoAl-layered double hydroxides for the efficient removal of α- and ß-naphthol isomers from water samples by capillary electrophoresis.

The present work describes a quick, simple, and efficient method based on the use of layered double hydroxides (LDH) coupled to dispersive solid phase micro-extraction (DSPME) to remove α-naphthol (α-NAP) and ß-naphthol (ß-NAP) isomers from water samples. Three different LDHs (MgAl-LDH, NiAl-LDH, and CoAl-LDH) were used to study how the interlayer anion and molar ratio affected the removal performance. The critical factors in the DSPME procedure (pH, LDH amount, contact time) were optimized by the univariate method under the optimal conditions: pH, 4-8; LDH amount, 5 mg; and contact time, 2.5 min. The method can be successfully applied in real sample waters, removing NAP isomers even in ultra-trace concentrations. The large volume sample stacking (LVSS-CE) technique provides limits of detections (LODs) of 5.52 µg/L and 6.36 µg/L for α-naphthol and ß-naphthol, respectively. The methodology's precision was evaluated on intra- and inter-day repeatability, with %RSD less than 10% in all cases. The MgAl/Cl--LDH selectivity was tested in the presence of phenol and bisphenol A, with a removal rate of >92.80%. The elution tests suggest that the LDH MgAl/Cl--LDH could be suitable for pre-concentration of α-naphthol and ß-naphthol in future works.

Psoriatic arthritis subtypes are phenocopied in humanized mice.

Psoriatic arthritis (PsA) is a complex inflammatory disease that challenges diagnosis and complicates the rational selection of effective therapies. Although T cells are considered active effectors in psoriasis and PsA, the role of CD8+ T cells in pathogenesis is not well understood. We selected the humanized mouse model NSG-SGM3 transgenic strain to examine psoriasis and PsA endotypes. Injection of PBMCs and sera from patients with psoriasis and PsA generated parallel skin and joint phenotypes in the recipient mouse. The transfer of human circulating memory T cells was followed by migration and accumulation in the skin and synovia of these immunodeficient mice. Unexpectedly, immunoglobulins were required for recapitulation of the clinical phenotype of psoriasiform lesions and PsA domains (dactylitis, enthesitis, bone erosion). Human CD8+ T cells expressing T-bet, IL-32 and CXCL14 were detected by spatial transcriptomics in murine synovia and by immunofluorescence in the human PsA synovia. Importantly, depletion of human CD8+ T cells prevented skin and synovial inflammation in mice humanized with PsA peripheral blood cells. The humanized model of psoriasis and PsA represents a valid platform for accelerating the understanding of disease pathogenesis, improving the design of personalized therapies, and revealing psoriatic disease targets.

CT strain metrics allow for earlier diagnosis of bronchiolitis obliterans syndrome after hematopoietic cell transplant.

Bronchiolitis obliterans syndrome (BOS) after hematopoietic cell transplantation (HCT) is associated with substantial morbidity and mortality. Quantitative CT (qCT) can help diagnose advanced BOS meeting National Institutes of Health (NIH) criteria (NIH-BOS) but has not been used to diagnose early, often asymptomatic BOS (early BOS), limiting the potential for early intervention and improved outcomes. Using Pulmonary Function Tests (PFT) to define NIH-BOS, early BOS, and mixed BOS (NIH-BOS with restrictive lung disease) in patients from two large cancer centers, we applied qCT to identify early BOS and distinguish between types of BOS. Patients with transient impairment or healthy lungs were included for comparison. PFT were done at month 0, 6, and 12. Analysis was performed with association statistics, principal component analysis, conditional inference trees (CIT), and machine learning (ML) classifier models. Our cohort included 84 allogeneic HCT recipients -- 66 BOS (NIH-defined, early, or mixed) and 18 without BOS. All qCT metrics had moderate correlation with Forced Expiratory Volume in 1 second, and each qCT metric differentiated BOS from those without BOS (non-BOS) (P < 0.0001). CIT's distinguished 94% of participants with BOS versus non-BOS, 85% early BOS versus non-BOS, 92% early BOS versus NIH-BOS. ML models diagnosed BOS with area under the curve (AUC) 0.84 (95% confidence interval [CI] 0.74-0.94) and early BOS with AUC 0.84 (95% CI 0.69 - 0.97). Quantitative CT metrics can identify individuals with early BOS, paving the way for closer monitoring and earlier treatment in this vulnerable population.

Single-cell RNA sequencing reveals placental response under environmental stress.

The placenta is crucial for fetal development, yet the impact of environmental stressors such as arsenic exposure remains poorly understood. We apply single-cell RNA sequencing to analyze the response of the mouse placenta to arsenic, revealing cell-type-specific gene expression, function, and pathological changes. Notably, the Prap1 gene, which encodes proline-rich acidic protein 1 (PRAP1), is significantly upregulated in 26 placental cell types including various trophoblast cells. Our study shows a female-biased increase in PRAP1 in response to arsenic and localizes it in the placenta. In vitro and ex vivo experiments confirm PRAP1 upregulation following arsenic treatment and demonstrate that recombinant PRAP1 protein reduces arsenic-induced cytotoxicity and downregulates cell cycle pathways in human trophoblast cells. Moreover, PRAP1 knockdown differentially affects cell cycle processes, proliferation, and cell death depending on the presence of arsenic. Our findings provide insights into the placental response to environmental stress, offering potential preventative and therapeutic approaches for environment-related adverse outcomes in mothers and children.

Incident Infarcts in Patients With Stroke and Cerebral Small Vessel Disease: Frequency and Relation to Clinical Outcomes.

BACKGROUND AND OBJECTIVES: Factors associated with cerebral small vessel disease (SVD) progression, including incident infarcts, are unclear. We aimed to determine the frequency of incident infarcts over 1 year after minor stroke and their relation to baseline SVD burden, vascular risks, and recurrent stroke and cognitive outcomes. METHODS: We recruited patients with lacunar or nondisabling cortical stroke. After diagnostic imaging, we repeated structural MRI at 3-6 monthly intervals for 12 months, visually assessing incident infarcts on diffusion-weighted imaging or FLAIR. We used logistic regression to determine associations of baseline vascular risks, SVD score, and index stroke subtype with subsequent incident infarcts. We assessed cognitive and functional outcomes at 1 year using Montreal Cognitive Assessment (MoCA) and modified Rankin scale (mRS), adjusting for baseline age, mRS, MoCA, premorbid intelligence, and SVD score. RESULTS: We recruited 229 participants, mean age 65.9 (SD 11.1). Over half of all participants, 131 of 229 (57.2%) had had an index lacunar stroke. From baseline to 1-year MRI, we detected 117 incident infarcts in n = 57/229 (24.8%) participants. Incident infarcts were mainly of the small subcortical (86/117 [73.5%] in n = 38/57 [66.7%]) vs cortical infarct subtype (n = 19/57 [33.3%]). N = 39/57 participants had incident infarcts at 1 visit; 18 of 57 at 2 or more visits; and 19 of 57 participants had multiple infarcts at a single visit. Only 7 of 117 incident infarcts corresponded temporally to clinical stroke syndromes. The baseline SVD score was the strongest predictor of incident infarcts (adjusted odds ratio [OR] 1.87, 95% CI 1.39-2.58), while mean arterial pressure was not associated. All participants with incident infarcts were prescribed an antiplatelet or anticoagulant. Lower 1-year MoCA was associated with lower baseline MoCA (ß 0.47, 95% CI 0.33-0.61), lower premorbid intelligence, and older age. Higher 1-year mRS was associated with higher baseline mRS only (OR 5.57 [3.52-9.10]). Neither outcome was associated with incident infarcts. DISCUSSION: In the year after stroke in a population enriched for lacunar stroke, incident infarcts occurred in one-quarter and were associated with worse baseline SVD. Most incident infarcts detected on imaging did not correspond to clinical stroke/transient ischemic attack. Worse 1-year cognition and function were not associated with incident infarcts.

The Scavenging Activity of Coenzyme Q10 Plus a Nutritional Complex on Human Retinal Pigment Epithelial Cells.

Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are common retinal diseases responsible for most blindness in working-age and elderly populations. Oxidative stress and mitochondrial dysfunction play roles in these pathogenesis, and new therapies counteracting these contributors could be of great interest. Some molecules, like coenzyme Q10 (CoQ10), are considered beneficial to maintain mitochondrial homeostasis and contribute to the prevention of cellular apoptosis. We investigated the impact of adding CoQ10 (Q) to a nutritional antioxidant complex (Nutrof Total®; N) on the mitochondrial status and apoptosis in an in vitro hydrogen peroxide (H2O2)-induced oxidative stress model in human retinal pigment epithelium (RPE) cells. H2O2 significantly increased 8-OHdG levels (p < 0.05), caspase-3 (p < 0.0001) and TUNEL intensity (p < 0.01), and RANTES (p < 0.05), caspase-1 (p < 0.05), superoxide (p < 0.05), and DRP-1 (p < 0.05) levels, and also decreased IL1ß, SOD2, and CAT gene expression (p < 0.05) vs. control. Remarkably, Q showed a significant recovery in IL1ß gene expression, TUNEL, TNFα, caspase-1, and JC-1 (p < 0.05) vs. H2O2, and NQ showed a synergist effect in caspase-3 (p < 0.01), TUNEL (p < 0.0001), mtDNA, and DRP-1 (p < 0.05). Our results showed that CoQ10 supplementation is effective in restoring/preventing apoptosis and mitochondrial stress-related damage, suggesting that it could be a valid strategy in degenerative processes such as AMD or DR.

Gender inequalities in secondary prevention of cardiovascular disease: a scoping review.

BACKGROUND: Despite significant progress in cardiovascular disease (CVD) management, it remains a public health priority and a global challenge. Within the disease process, health care after a cardiovascular event (secondary prevention) is essential to prevent recurrences. Nonetheless, evidence has suggested the existence of gender disparities in CVD management, leaving women in a vulnerable situation. The objective of this study is to identify all available evidence on the existence of gender differences in health care attention after a major adverse cardiovascular event. METHODS: A scoping review following the structure of PRISMA-ScR was conducted. To define the inclusion criteria, we used Joanna Briggs Institute (JBI) population, concept, context framework for scoping reviews. A systematic search was performed in MEDLINE (PubMed), EMBASE and Cochrane. The methods of this review are registered in the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) (INPLASY202350084). RESULTS: The initial search retrieved 3,322 studies. 26 articles were identified manually. After the reviewing process, 93 articles were finally included. The main intervention studied was the pharmacological treatment received (n = 61, 66%), distantly followed by guideline-recommended care (n = 26, 28%) and cardiac rehabilitation (CR) referral (n = 16)". Literature described gender differences in care and management of secondary prevention of CVD. Women were less frequently treated with guideline-recommended medications and seem more likely to be non-adherent. When analysing guideline recommendations, women were more likely to make dietary changes, however, men were more likely to increase physical activity. Studies also showed that women had lower rates of risk factor testing and cholesterol goals attainment. Female sex was associated with lower rates of cardiac rehabilitation referral and participation. CONCLUSIONS: This review allowed us to compile knowledge on the existence of gender inequalities on the secondary prevention of CVD. Additional research is required to delve into various factors influencing therapeutic disparities, referral and non-participation in CR programs, among other aspects, in order to improve existing knowledge about the management and treatment of CVD in men and women. This approach is crucial to ensure the most equitable and effective attention to this issue.

A Remotely Delivered, Personalized Music Therapy Pilot Intervention for Lonely Older Adults During the Covid-19 Pandemic.

Introduction: This study investigated a remotely delivered, therapist-facilitated, personalized music listening intervention for community-dwelling older adults experiencing loneliness during the Covid-19 pandemic. We assessed its feasibility and individuals' experiences of social connection and emotional well-being during the intervention. Methods: Ten cognitively unimpaired older adults who endorsed loneliness completed eight weekly sessions with a board-certified music therapist via Zoom. Participants were guided in developing two online personalized music playlists and were asked to listen to playlists for at least one hour daily. Feasibility metrics were attendance, accessibility, and compliance rates. Post-study interview responses were analyzed using a rapid qualitative methodology. Exploratory pre- and post-study measures of loneliness and other aspects of psychological well-being were obtained using validated questionnaires. Results: Ten participants (mean age 75.38 [65 to 85] years, 80% women) were enrolled from March to August 2021. Attendance and compliance rates were 100% and the accessibility rate was 90%. Most participants associated music with positive memories before the program and many reported that the intervention prompted them to reconnect with music or listen to music with greater intention. They cited increased connection from interacting with the music therapist and the music itself, as well as specific positive emotional impacts from integrating music into their daily lives. Median pre- to post-questionnaire measures of psychological function all changed in an improved direction. Discussion: Remotely delivered music therapy may be a promising intervention to promote regular music listening and socioemotional well-being in lonely older adults.

[Effects of D-tagatose, Stevia and Sucrose on pH and oral bacterial activity in dentistry students. A randomized controlled trial]. / Efectos de D-tagatosa, estevia y sacarosa sobre el pH y la actividad bacteriana oral en estudiantes de odontología. Ensayo controlado y aleatorizado.

BACKGROUND: stevia and D-tagatose have shown a reduction in total calorie and carbohydrate intake as a substitute for sucrose, demonstrating a stabilizing effect on pH and bacterial proliferation. OBJECTIVE: to evaluate the effect of D-tagatose, stevia and sucrose on salivary pH and bacterial activity in odontology students. METHODOLOGY: a controlled study of parallel and randomized groups with a single blind, whose sample considered three groups subjected to a mouthwash of D-tagatose (n = 10), stevia (n = 10) and sucrose (n = 10). These solutions were administered over 1 minute in a single 6.4 % concentrated dose. Data collection and analysis considered the recording of salivary pH 5 min before exposure to the sweetener, immediately after expulsion of the mouthwash and 15 min later, 30 min, 45 min and 48 hours. The counting of the final number of colony-forming units per mL (CFU/mL) was counted using the salivary samples obtained immediately after exposure of the sweetener together with the sample obtained 30 minutes later, with the cultures performed on agar plates. RESULTS: D-tagatose, stevia and sucrose presented significant differences in total CFU/mL at 30 minutes (p < 0.001), while salivary pH showed significant differences at 48 hours after administration (p < 0.001). CONCLUSION: D-tagatose, stevia and sucrose present significant differences in total CFU/mL and salivary pH, these findings being a possible indication of a partial inhibitory effect on bacterial metabolism.

First-line PARP inhibitor maintenance treatment in ovarian carcinoma for older adult women: a review of the current literature.

Ovarian cancer (OC) is the leading cause of death in women with gynecological cancers. Its diagnosis is more likely in advanced ages, with the older population being the most seen in consultations. Poly(ADP-ribose) inhibitors (PARPi) have changed OC clinical practice and evolution, showing great benefit. However, there is a lack of evidence of PARPi in elderly population that can impact the therapeutic decision and the safety/efficacy. It is necessary to avoid age as limiting factor in PARPis prescription. We conducted a review of the most relevant randomized phase III trials of maintenance PARPi after first-line treatment of advanced OC. We observed the lack of a single criterion for considering older patients, varying among trials. There is a benefit of PARPis in different populations. However, PARPi effect on quality of life is not reported, something of great relevance considering their vulnerability. Measures are needed to benefit older patients to better adapt PARPi treatment.

Management of Pediatric Mild Traumatic Brain Injury Patients: S100b, Glial Fibrillary Acidic Protein, and Heart Fatty-Acid-Binding Protein Promising Biomarkers.

Children are highly vulnerable to mild traumatic brain injury (mTBI). Blood biomarkers can help in their management. This study evaluated the performances of biomarkers, in discriminating between children with mTBI who had intracranial injuries (ICIs) on computed tomography (CT+) and (1) patients without ICI (CT-) or (2) both CT- and in-hospital-observation without CT patients. The aim was to rule out the need of unnecessary CT scans and decrease the length of stay in observation in the emergency department (ED). Newborns to teenagers (≤16 years old) with mTBI (Glasgow Coma Scale > 13) were included. S100b, glial fibrillary acidic protein (GFAP), and heart fatty-acid-binding protein (HFABP) performances to identify patients without ICI were evaluated through receiver operating characteristic curves, where sensitivity was set at 100%. A total of 222 mTBI children sampled within 6 h since their trauma were reported. Nineteen percent (n = 43/222) underwent CT scan examination, whereas the others (n = 179/222) were kept in observation at the ED. Sixteen percent (n = 7/43) of the children who underwent a CT scan had ICI, corresponding to 3% of all mTBI-included patients. When sensibility (SE) was set at 100% to exclude all patients with ICI, GFAP yielded 39% specificity (SP), HFABP 37%, and S100b 34% to rule out the need of CT scans. These biomarkers were even more performant: 52% SP for GFAP, 41% for HFABP, and 39% for S100b, when discriminating CT+ versus both in-hospital-observation and CT- patients. These markers can significantly help in the management of patients in the ED, avoiding unnecessary CT scans, and reducing length of stay for children and their families.

Clinical Characteristics of Ocular Mucous Membrane Pemphigoid: A Systematic Review and Meta-Analysis.

PURPOSE: To synthesize the evidence and generate a combined weighted measure on the frequency of ocular manifestations of mucous membrane pemphigoid (OMMP). METHODS: Systematic literature review and meta-analysis, searching PubMed, Embase, VHL, and Google Scholar. Articles reporting patients with mucous membrane pemphigoid and ocular involvement were included. At least, two reviewers independently and in parallel participated in all the following phases; preliminary screening, full-text review, risk of bias assessment by validated tools, and data extraction. Qualitative analysis and meta-analysis were conducted. This study was previously registered in PROSPERO (CRD42023451844). RESULTS: Thirty-five studies met the inclusion criteria, comprising 1,439 patients and 1,040 eyes summarized in qualitative analysis. Twenty-eight studies were included in the meta-analysis. Ages included ranged from 60.4 to 75 years. Women were reported with more frequency. The mean time for diagnosis was 55.1 months, usually with bilateral ocular disease in 90% (95% CI 78%; 96%). Trichiasis and entropion were the most frequent manifestations in up to 92%, followed by symblepharon and punctate keratitis. Ankyloblepharon, persistent epithelial defects, and visual impairment were less frequent complications. Direct immunofluorescence positivity in conjunctival biopsies was 54% (95% CI 43%; 64%). Extraocular involvement was highly frequent, being oral and skin involvement the most frequently reported. CONCLUSIONS: Our systematic review and meta-analysis evidenced that patients around 60 years of age are the most affected population with a female preponderance, usually with bilateral ocular involvement. Trichiasis and entropion were the most frequent findings; although visual impairment and persistent epithelial defects were less reported, they should not be overlooked in suspected OMMP.

Impact of an Intervention Program on Clostridioides difficile Infections: Comparison of 2 Hospital Cohorts.

Background: Clostridioides difficile infection (CDI) occurs in various contexts and care settings and is managed by multiple specialists who are not experts in its management. While there are many initiatives to improve the diagnosis and avoid overdiagnosis, there is less focus on the overall management of the infection. Methods: We studied a cohort of patients with a positive test result for toxigenic C difficile in 2 hospitals. Hospital A has a program that provides advice from an infectious disease specialist (IDS) and promotes continuity of care by providing a phone number to contact the IDS. Hospital B does not have any specific CDI program. The evaluation assessed the proportion of patients not treated (carriers or self-limited disease), adherence to Infectious Diseases Society of America guidelines, access to novel therapies, recurrence and mortality rates, and readmission and emergency department visits due to CDI. We assessed the program's effectiveness through a logistic regression model adjusted for covariates chosen by clinical criteria. Results: Hospital A avoided more unnecessary treatments (19.3% vs 11.5%), provided access to novel therapies more frequently (35.3% vs 13%), and adhered more closely to current guidelines (95.8% vs 71.3%). Although the mortality and recurrence rates did not differ, the absence of an intervention program was associated with greater odds of admission due to recurrence (odds ratio, 4.19; P = .037) and more visits to the emergency department due to CDI (odds ratio, 8.74; P = .001). Conclusions: Implementation of a CDI intervention program based on recommendations from IDSs and improved access to specialized care during the follow-up is associated with enhanced quality of CDI management and potential reductions in hospital resource utilization.

May Measurement Month 2021: an analysis of blood pressure screening results from Venezuela.

Cardiovascular diseases continue to be the main cause of death in Venezuela, and hypertension is the principal risk factor. The May Measurement Month (MMM) campaign is a global initiative aimed to raising awareness of hypertension, which has been conducted in Venezuela since 2017. May Measurement Month 2021 included 46 732 participants with a mean age of 56.4 years (SD 14.4), 57.9% of whom were female. The percentage with hypertension was 60.3% (57.9% of females and 63.7% of males), 82.3% (84.8% of females and 79.2% of males) were aware, and 80.2% were taking antihypertensive medication. Of those on antihypertensive medication, 44.2% (41.2% of females and 48.2% of males) were not controlled [blood pressure (BP) ≥ 140/≥90 mmHg], with 61.3% receiving one drug, 30.0% two drugs, and 8.7% three or more drugs. 87.5% of those on treatment reported taking it regularly. Conditions associated with higher BP levels include fewer years of education, having a previous diagnosis of hypertension, and women who were hypertensive during a previous pregnancy. Physical activity and pregnancy were conditions associated with lower BP levels. A previous positive COVID-19 test was reported in 11.1%, and one or more COVID-19 vaccinations reported in 22.7% of participants. Of those on antihypertensive medication, 78.8% reported their treatment was not affected by COVID-19. Results are consistent with previous MMM campaigns and indicate that the screening campaign is feasible and useful to identify hypertension even in exceptional conditions such as the COVID-19 pandemic.

Diagnostic and therapeutic approach to spondylodiscitis in Spanish children through the RIOPed network: evaluation before and after the publication of the national consensus document.

OBJECTIVE: Pediatric spondylodiscitis (PSD) is an uncommon condition, for which there are no specific international clinical guidelines. Factors related to complications have not been stablished. Our aim was to describe clinical and epidemiological characteristics of PSD, to analyze factors associated with complications and to evaluate adherence to the recommendations of the Spanish National Consensus Document (NCD) for the diagnostic and therapeutic approach to acute osteoarticular infections. MATERIAL AND METHODS: Ambispective, multicenter, national study of two PSD cohorts: historical (2008-2012) and prospective (2015-2020, after publication of NCD). Patients with diagnosis of PSD were included. Demographic, clinical, microbiological and radiological data were recorded. Factors related to the development of complications were analized by logistic regression. Comparisons between both cohorts were performed. RESULTS: Ninety-eight PSD were included. In 84.7%, diagnosis was confirmed by magnetic resonance imaging. Microbiological isolation was obtained in 6.1%, with methicillin-sensitive S. aureus as the main etiologic agent. Complications occurred in 18.9%, the most frequent being soft tissue abscess. Of the 8.6% of patients with sequelae, persistent pain was the most common. Comparing cohorts, there was better adherence to NCD treatment recommendations in the prospective one (57.6% vs. 12.9%, p < 0.01), including a reduction in the length of intravenous antibiotic therapy (10 vs. 14 days, p < 0.01). CONCLUSIONS: The evolution of PSD in our series was favorable, with low frequency of complications and sequelae. The adherence to the recommendations of the NCD was high. Studies with larger sample size are needed to establish new recommendations to optimize the approach to these infections.

Comparison of Ten Surrogate Insulin Resistance and Obesity Markers to Identify Metabolic Syndrome in Mexican Adults.

Metabolic syndrome (MetS) is a group of clinical traits directly linked to type 2 diabetes mellitus and cardiovascular diseases, whose prevalence has been rising nationally and internationally. We aimed to evaluate ten known and novel surrogate markers of insulin resistance and obesity to identify MetS in Mexican adults. The present cross-sectional study analyzed 10575 participants from ENSANUT-2018. The diagnosis of MetS was based on the Adult Treatment Panel III (ATP III) criteria and International Diabetes Federation (IDF) criteria, stratified by sex and age group. According to ATP III, the best biomarker was the metabolic score for insulin resistance (METS-IR) in men aged 20-39 and 40-59 years and lipid accumulation product (LAP) in those aged ≥60 years. The best biomarker was LAP in women aged 20-39 and triglyceride-glucose index (TyG) in those aged 40-59 and ≥60 years. Using the IDF criteria, the best biomarker was LAP in men of all ages. TyG gave the best results in women of all ages. The best biomarker for diagnosis of MetS in Mexican adults depends on the criteria, including sex and age group. LAP and TyG are easy to obtain, inexpensive, and especially useful at the primary care level.

Intelligent Recommendation Systems Powered by Consensus Neural Networks: The Ultimate Solution for Finding Suitable Chiral Chromatographic Systems?

The selection of suitable combinations of chiral stationary phases (CSPs) and mobile phases (MPs) for the enantioresolution of chiral compounds is a complex issue that often requires considerable experimental effort and can lead to significant waste. Linking the structure of a chiral compound to a CSP/MP system suitable for its enantioseparation can be an effective solution to this problem. In this study, we evaluate algorithmic tools for this purpose. Our proposed consensus model, which uses multiple optimized artificial neural networks (ANNs), shows potential as an intelligent recommendation system (IRS) for ranking chromatographic systems suitable for the enantioresolution of chiral compounds with different molecular structures. To evaluate the IRS potential in a proof-of-concept stage, 56 structural descriptors for 56 structurally unrelated chiral compounds across 14 different families are considered. Chromatographic systems under study comprise 7 cellulose and amylose derivative CSPs and acetonitrile or methanol aqueous MPs (14 chromatographic systems in all). The ANNs are optimized using a fit-for-purpose version of the chaotic neural network algorithm with competitive learning (CCLNNA), a novel approach not previously applied in the chemical domain. CCLNNA is adapted to define the inner ANN complexity and perform feature selection of the structural descriptors. A customized target function evaluates the correctness of recommending the appropriate CSP/MP system. The ANN-consensus model exhibits no advisory failures and requires only an experimental attempt to verify the IRS recommendation for complete enantioresolution. This outstanding performance highlights its potential to effectively resolve this problem.