Global Antimicrobial Susceptibility Patterns of Staphylococcus aureus in Atopic Dermatitis: A Systematic Review and Meta-Analysis.

Importance: Individuals with atopic dermatitis are frequently colonized and infected with Staphylococcus aureus. Empirical antibiotic therapy for individuals with atopic dermatitis is common, but data about the antimicrobial susceptibility profiles of S aureus strains isolated from these individuals are scarce for those living in particular geographic areas. Objective: To determine the antimicrobial susceptibility of S aureus from individuals with atopic dermatitis and analyze differences according to the income level of the country of origin and the data collection period. Data Sources: A meta-analysis of the literature was performed from the inception of the included databases (MEDLINE, Embase, Web of Science, Scopus, and Cochrane) to June 20, 2023, using predetermined Medical Subject Headings. Study Selection: Studies were included if they reported antibiotic susceptibility profiles of 1 or more S aureus cutaneous isolates from individuals with atopic dermatitis. Articles written in English, Spanish, French, or German were included. Data Extraction and Synthesis: Working in pairs, 6 of the authors conducted the data extraction. The guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) were followed. Main Outcomes and Measures: The outcome of interest was antimicrobial susceptibility. Results: A total of 61 studies reported 4091 S aureus isolates from individuals with atopic dermatitis. For 4 of the 11 commonly used antibiotics (36.4%), antimicrobial susceptibility was 85% or less, including for methicillin (binomial proportion, 0.85 [95% CI, 0.76-0.91]), erythromycin (binomial proportion, 0.73 [95% CI, 0.61-0.83]), fusidic acid (binomial proportion, 0.80 [95% CI, 0.62-0.91]), and clindamycin (binomial proportion, 0.79 [95% CI, 0.65-0.89]). Most studies (46; 75.4%) were conducted in high-income countries. Antimicrobial susceptibility to erythromycin, methicillin, and trimethoprim and sulfamethoxazole was significantly lower in lower middle-income countries and upper middle-income countries. Regarding the temporal trends, 33 studies (54.1%) reported data collected from 1998 to 2010. Antimicrobial susceptibility patterns have not changed over time. Conclusions and Relevance: In this systematic review and meta-analysis, antimicrobial susceptibility of S aureus to ß-lactams, erythromycin, clindamycin, and fusidic acid may be suboptimal for empirical use in individuals with atopic dermatitis. Significant differences in antimicrobial susceptibility patterns were found in high-income countries and in lower middle-income countries and upper middle-income countries for some antibiotics.

Immunometabolic Regulation of Vaccine-Induced Antibody Responses in Aging Mice.

Immune cells undergo metabolic reprogramming to meet the demands associated with immune responses. The effects of aging on these pathways and on the metabolic phenotype of the immune cells participating in antibody responses to vaccines are still largely unknown. Here we used a vaccine for SARS-CoV-2 that utilizes the cellular heat shock chaperone glycoprotein 96 (gp96), engineered to co-express SARS-CoV-2 Spike (spike) protein (gp96-Ig-S). Results show that this vaccine induces comparable B cell primary responses in young and old mice at later time points, but a significantly lesser secondary response in old as compared to young mice, with the antibodies generated in the secondary response being also of lower avidity. This occurs because aging changes the B cell metabolic phenotype and induces hyper-metabolic B cells that are associated with higher intrinsic inflammation and decreased protective antibody responses. However, the gp96-Ig-S vaccine was found to be effective in significantly reducing the metabolic/inflammatory status of B cells from old mice, suggesting the possibility that targeting metabolic pathways may improve immune function in old mice that do not respond adequately to the vaccine.

Vascular malformations in pediatric patients: 10-year experience of a vascular anomalies clinic.

BACKGROUND: Vascular malformations (VaMs) are caused by errors in vascular morphogenesis. Diagnosis and treatment can be complex. Few specialized centers care for these patients, and limited literature exists regarding their characteristics and clinical course. The vascular anomalies clinic (VAC) at the Instituto Nacional de Pediatría (National Institute for Pediatrics) is a multidisciplinary team and has been a reference center for patients with VaMs since 2012. We sought to describe the characteristics of patients cared for at the VAC, types of VaMs, treatments used, and clinical course. METHODS: This was a descriptive, observational, retrospective, and cross-sectional study conducted from 2012 to 2022. RESULTS: We included 435 patients with VaMs; the median age of presentation was 1 month. The most frequent signs and symptoms were increased volume (97.2%), superficial color change (65.5%), and pain (43.3%). The most common VaMs were lymphatic (36.7%) and venolymphatic (18.3%). Sclerotherapy was the most frequent treatment (73.4%), followed by medical treatment with sirolimus (18.5%); response to both was excellent/good in > 85% of cases. CONCLUSION: In this retrospective study of children with VaMs, we found that low-flow malformations were the most common, and sclerotherapy and sirolimus were the most frequently used treatments. The therapeutic response was excellent/good in most cases.

INTRODUCCIÓN: Las malformaciones vasculares (MaV) son secundarias a errores en la morfogénesis vascular. El diagnóstico y tratamiento puede ser complejo. Existen pocos centros especializados en su atención y escasa literatura respecto a características y evolución clínica. La Clínica de Anomalías Vasculares (CAV) del Instituto Nacional de Pediatría es un equipo multidisciplinario y centro de referencia para estos pacientes desde 2012. Buscamos describir las características de los pacientes atendidos en la CAV, tipo de MaV, tratamiento y evolución clínica. MÉTODOS: Estudio descriptivo, observacional, retrospectivo y transversal del periodo 2012 al 2022. RESULTADOS: Se incluyeron 435 pacientes con MaV, con edad mediana de presentación de 1 mes de vida. Los síntomas y signos más reportados fueron aumento de volumen (97.2%), cambio en coloración de la piel (65.5%) y dolor (43.3%). Las MaV más comunes fueron linfáticas (36.7%), siguiéndoles las venolinfáticas (18.3%). La escleroterapia fue el tratamiento más frecuente (73.4%) y el tratamiento médico más utilizado fue sirolimus (18.5%), ambos con excelente/buena respuesta en > 85% de los pacientes. CONCLUSIONES: En este estudio retrospectivo de niños con MaV encontramos que las más frecuentes son de bajo flujo y el tratamiento más usado escleroterapia y sirolimus. La respuesta terapéutica de la mayoría fue excelente/buena.

Clinical course in older patients diagnosed with syncope treated in Spanish emergency departments: results from the Emergency Department and Elder Needs-17 study. / Evolución clínica de los pacientes mayores diagnosticados de síncope en servicios de urgencias en España: resultados del estudio EDEN-17.

OBJECTIVE: To study factors associated with hospitalization in an unselected population of patients aged 65 years or older treated for syncope in Spanish hospital emergency departments (EDs). To determine the prevalence of adverse events at 30 days in patients discharged home and the factors associated with such events. METHODS: We included all patients aged 65 years or older who were diagnosed with syncope during a single week in 52 Spanish EDs, recording patient clinical and ED case management data. We compared the findings between hospitalized patients and those discharged home, following the latter for 30 days. In discharged patients, we explored predictors of a composite adverse-event outcome (occurrence of any of the following: ED revisits, hospitalization related to the index visit, or any-cause death). RESULTS: A total of 477 patients with syncope were identified; 67 (14%) were admitted, and 5 (7.5%) died. The median (interquartile range) length of hospital stay was 6 days (3-11 days). Comorbidity increased the probability of hospitalization (odds ratio, 2.172; 95% CI, 1.013-4.655). Among the 410 patients (86%) discharged home from the ED, 9.2% experienced an adverse event within 30 days (ED revisits, 8.,1%; hospitalization, 2.2%; death, 1.5%). No factors were associated with the 30-day composite outcome. CONCLUSIONS: The majority of patients aged 65 years or older are discharged home from EDs, and 30-day adverse events, while infrequent, are difficult to predict. Hospitalization was related to comorbidity and an absence of cognitive decline.

OBJETIVO: Investigar en una muestra no seleccionada de población mayor (65 o más años) atendida en servicios de urgencias hospitalarios (SUH) españoles por síncope los factores que se asociaron con la hospitalización, prevalencia de eventos adversos (EA) a 30 días y los factores asociados a estos entre los pacientes dados de alta desde urgencias. METODO: Se incluyeron todos pacientes con 65 o más años diagnosticados de síncope durante una semana en 52 SUH españoles. Se recogieron datos de la situación clínica y el manejo en urgencias, que se compararon entre los pacientes hospitalizados y los dados de alta directamente desde urgencias. Estos últimos fueron seguidos durante 30 días y se identificaron aquellos que presentaron un EA combinado (reconsulta en urgencias u hospitalización relacionada con el evento índice y muerte por cualquier causa), y se investigaron los factores que predecían dicho EA combinado. RESULTADOS: Se identificaron 477 pacientes con síncope. Hospitalizaron 67 (14%), de los que fallecieron 5 (7,5%) y la estancia mediana fue de 6 días (RIC 3-11). La comorbilidad incrementó la probabilidad de ingreso (OR: 2,172, IC 95%: 1,013-4,655). Entre los 410 pacientes dados de alta de urgencias (86%), el 9,2% tuvo un EA durante los 30 días siguientes (reconsulta a urgencias: 8,1%; hospitalización: 2,2%; muerte: 1,5%). Ningún factor se asoció con el riesgo de EA combinado a 30 días. CONCLUSIONES: La mayoría de los pacientes con 65 años o más atendidos en los SUH por síncope son dados de alta directamente desde urgencias, y los EA a los 30 días fueron poco frecuentes, pero difíciles de predecir. La hospitalización se relacionó con presencia de comorbilidad y ausencia de deterioro cognitivo.

Retrospective study on the outcomes and satisfaction with endometrial ablation by bipolar energy (NovaSure®) for the treatment of heavy menstrual bleeding.

PURPOSE: To determine the effectiveness, safety, and participant satisfaction with endometrial ablation by bipolar energy (NovaSure®) in the treatment of heavy menstrual bleeding (HMB), and to investigate factors associated with poorer outcomes. METHODS: Multicenter retrospective observational study based on medical record review of the outcomes related to endometrial ablation by the bipolar-energy technique procedure to treat HMB in the setting of three university teaching hospitals in Spain. RESULTS: A total of 333 women were included in the study. Most bipolar-energy ablations were successful (85.12%; n = 269 out of 316), with amenorrhea the most frequent outcome (39.6%, n = 131 out of 316). The majority of participants had no complications (95.5%; n = 317 out of 332), and of those who did, only 2.1% were related to the technique. No further treatment was required for HMB in 82.8% of women (n = 274 out of 331), and surgery was avoided in 91.8%; only 5.9% of women underwent ablation-related hysterectomy. In women with previous transverse cesarean sections (CS), 91.0% avoided subsequent surgical treatment. Eighty-six percent of women (n = 221 out of 257) were satisfied with the procedure. CONCLUSION: Bipolar-energy ablation is very effective and safe for the treatment of HMB and yielded a high rate of participant satisfaction in our setting. The presence of comorbidities or previous CS may slightly reduce the effectiveness of the method, while performing concomitant surgery (mainly curettage) increases the rate of complications. Notably, despite the known increased risk of hysterectomy, most participants with previous CSs who underwent ablation avoided major surgery.

Time-of-Day Adrenal Modulation of Corticosterone Synthesis is Affected by Sex and Diet but Not by Proanthocyanidins in Rat.

SCOPE: The aim of this study is to investigate the effect of time-of-day on serum hormones and gene expression in adrenal glands, studying the impact of sex, obesogenic diet, and timing of proanthocyanidins administration, with a focus on glucocorticoids synthesis by this gland. METHODS AND RESULTS: Female and male rats, assigned to a standard chow or a cafeteria diet-fed group, receive a daily oral dose of a grape seed proanthocyanidin extract (GSPE), or a vehicle (when light is turned on, or when light is turned off). Corticosterone, estradiol, and testosterone serum levels, and the expression analysis of clock genes and genes related to corticosterone synthesis pathway, are assessed. Serum hormone levels exhibited a marked time-of-day effect also see in the expression of scavenger receptor class B member 1 (Scarb1) and cyp11b genes. The correlation between these two genes and period circadian regulator 2 (Per2) is also extended to other clock genes, although to a lesser extent: cryptochrome (Cry) and nuclear receptor subfamily 1 group D member 1 (Rev-erba). CONCLUSION: The strong correlations found suggest an important role of local Per2 (but also of Cry and Rev-erbA) in regulating the expression of the enzymes involved in the corticosterone synthesis pathway. The expression of clock genes in adrenals is influenced by sex and diet but not by GSPE.

Monte Carlo QM/MM simulation studies of the Cannizzaro reaction in ionic liquids for improved biofuel production.

The conversion of biomass to 5-hydroxymethylfurfural (HMF) holds substantial promise as a renewable energy source. Notably, HMF can be transformed into 2,5-bis(hydroxymethyl)furan (BHMF), a crucial reactant in biofuel production, but requires harsh operating conditions, H2, and precious metal catalysts. A recently reported Cannizzaro reaction of HMF to BHMF, characterized by its efficiency, mild conditions, and eco-friendliness, instead employed ionic liquids (ILs) to achieve high yields. In this study, combined quantum mechanical and molecular mechanical (QM/MM) simulations in conjunction with Metropolis Monte Carlo statistical mechanics and free-energy perturbation theory utilized M06-2X/6-31+G(d), PDDG/PM3, and the OPLS-VSIL force field to uncover important solute-solvent interactions present in the HMF to BHMF reaction pathway. The Cannizzaro reaction was examined in water and in five ILs composed of the 1-butyl-3-methylimidazolium [BMIM] cation coupled to hexafluorophosphate, tetrafluoroborate, thiocyanate, chloride, and bromide. Energetic and structural analysis of the rate-determining hydride transfer between HMF and the hydride-donor anion HMFOH- attributed the enhanced reactivity to highly organized solvent interactions featuring (1) hydrogen bonding between the ring protons of [BMIM] and the negatively charged carbonyl oxygen atoms on the transition structure, (2) favorable electrostatic interactions between the IL anions and solute hydroxyl groups, and (3) beneficial π-π stacking interactions between [BMIM] and the two aromatic rings present in HMF and HMFOH-.

Evolution of a bistable genetic system in fluctuating and nonfluctuating environments.

Epigenetic mechanisms can generate bacterial lineages capable of spontaneously switching between distinct phenotypes. Currently, mathematical models and simulations propose epigenetic switches as a mechanism of adaptation to deal with fluctuating environments. However, bacterial evolution experiments for testing these predictions are lacking. Here, we exploit an epigenetic switch in Salmonella enterica, the opvAB operon, to show clear evidence that OpvAB bistability persists in changing environments but not in stable conditions. Epigenetic control of transcription in the opvAB operon produces OpvABOFF (phage-sensitive) and OpvABON (phage-resistant) cells in a reversible manner and may be interpreted as an example of bet-hedging to preadapt Salmonella populations to the encounter with phages. Our experimental observations and computational simulations illustrate the adaptive value of epigenetic variation as an evolutionary strategy for mutation avoidance in fluctuating environments. In addition, our study provides experimental support to game theory models predicting that phenotypic heterogeneity is advantageous in changing and unpredictable environments.

Alignment of Patient Information Leaflets with the Health Literacy Skills of Future End-Users: Are We on the Same Page?

Effective health communication will not be possible if the messages directed to patients do not adapt to their health literacy skills. In this sense, if the Patient Information Leaflets (PILs) are not understood properly, they will not fulfill their purpose. Secondary education aims to develop students' fundamental skills, including reading comprehension, which should align with future patients. This study assesses reading comprehension of commonly used PILs among secondary education students. An observational cross-sectional study involved 590 Spanish secondary school students from March to June 2022. They read 3 original PILs and completed a questionnaire about medication use information. The European health literacy survey questionnaire (short version) and sociodemographic data were collected. The average correct answer rate was only 51%, with just 14.58% understanding when to take ibuprofen, results that fell significantly below the minimum 80% threshold required by the European Union. Age, gender, and cultural background didn't significantly impact comprehension. In conclusion, health literacy skills acquired in secondary education are insufficient for understanding current PILs. Educational reform is necessary to improve students' ability to comprehend medication instructions and enhance PILs for effective communication. At the same time, our work highlights that current PILs need to be redesigned to reduce the cognitive burden imposed on patients.

Immunometabolic effects of lactate on humoral immunity in healthy individuals of different ages.

Aging is characterized by chronic systemic inflammation and metabolic changes. We compare the metabolic status of B cells from young and elderly donors and found that aging is associated with higher oxygen consumption rates, and especially higher extracellular acidification rates, measures of oxidative phosphorylation and of anaerobic glycolysis, respectively. Importantly, this higher metabolic status, which reflects age-associated expansion of pro-inflammatory B cells, is found associated with higher secretion of lactate and autoimmune antibodies after in vitro stimulation. B cells from elderly individuals induce in vitro polarization of CD4+ T cells from young individuals into pro-inflammatory CD4+ T cells through metabolic pathways mediated by lactate, which can be inhibited by targeting lactate enzymes and transporters, as well as signaling pathways supporting anaerobic glycolysis. Lactate also induces immunosenescent B cells that are glycolytic, express transcripts for multiple pro-inflammatory molecules, and are characterized by a higher metabolic status. These results altogether may have relevant clinical implications and suggest alternative targets for therapeutic interventions in the elderly and patients with inflammatory conditions and diseases.

Improving functional and nutritional profiles of barley flours with diverse starch types through pearling.

A comparative analysis of chemical, functional, and digestive parameters was conducted on five new barley genotypes designed for food purposes, differing in starch type, ß-glucans, and arabinoxylan content. Both whole and pearled grain flours were examined. Amylose exhibited positive correlations with least gelation capacity (r = 0.60), gelation temperature (r = 0.90), and resistant starch (r = 0.80). Waxy varieties showed greater water-holding capacity, viscosity, and rapid digestibility compared to normal and high-amylose varieties. Pearling (10%) decreased arabinoxylans by 48% and proteins by 7%, while increasing ß-glucans by 8% and starch by 13%. Additionally, pearling improved viscosity and hydration parameters across varieties. This allowed normal and high-amylose genotypes to enhance their functional properties and nutritional value through increased ß-glucan and resistant starch content. This exploration advances the understanding of barley's functional attributes for food industry and underscores the potential of pearling to augment consumer nutritional value and health-promoting properties.

Livedo-like acute cutaneous graft-versus-host disease in two children.

We present two pediatric patients who exhibited an unusual clinical presentation of cutaneous acute graft-versus-host disease (GVHD), characterized by livedo-like appearance. Such manifestations of cutaneous acute GVHD have not been previously documented.

Mechanisms of Medial Wall Thinning in Chronic Total Occlusion.

BACKGROUND: The success rate of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is lower and the risk for complications higher compared with other non-CTO PCI. Although interventionalists focus on intimal plaque characteristics, the coronary media is an important (especially for techniques involving antegrade dissection and re-entry) but poorly understood structure in CTO PCI. OBJECTIVES: The aim of the present study was to investigate coronary medial wall thinning in CTO lesions and determine how this thinning might affect CTO PCI. METHODS: A total of 2,586 sections were investigated, from arteries with evidence of CTO from 54 subjects (1,383 sections) and arteries without evidence of CTO from 54 subjects with non-coronary-related deaths (1,203 sections) after matching for age, gender, body weight, and body height. RESULTS: The medial thickness in subjects with CTO was lower than that in those with non-coronary-related death (P < 0.001). In subjects with CTO, CTO lesions had thinner medial walls compared with those with lower luminal narrowing (P < 0.001). At the CTO distal segments, the 6- to 12-mm distal segment from the distal end of the CTO had significantly less luminal narrowing (P < 0.001), and similar medial thickness, compared with the distal end of the CTO. Immunohistochemical analysis revealed that short-duration CTO had more cleaved caspase-3-positive cells in media and had significantly more CD3+, CD4+, CD8+, and CD4+CD28null T cells compared with long-duration CTO. CONCLUSIONS: CTO lesions demonstrated coronary medial thinning compared with non-CTO lesions. Further investigation of the cause-and-effect relationship among inflammation, apoptosis, and coronary medial wall thinning is warranted in future mechanistic studies.

Bacteriophage Removal from Infected Salmonella Cultures.

Bacteriophages, or simply phages, play a vital role in microbial environments, impacting bacterial populations and shaping their evolution and interactions. These organisms are viruses that infect and replicate within bacterial hosts. Phages are ubiquitous on Earth, highly diverse, and very abundant. While bacteriophages have valuable roles in different environments and are a key area of research in microbiology and ecology, their presence can be undesirable in certain industrial processes or products. Considering the abundance and ubiquity of bacteriophages on Earth, the design of procedures for the removal of bacteriophages from bacterial cultures is crucial in diverse laboratory and industrial applications to preserve the integrity of the cultures and ensure accurate experimental results or product quality. Here, we have fine-tuned a protocol to eliminate the bacteriophages from infected Salmonella enterica cultures, using a strategy based on the use of lipopolysaccharides (LPS) located in the outer membrane of Gram-negative bacteria. Bacterial LPS plays an important role in host recognition by phages, and we make use of this property to design an effective procedure for the removal of phages, which use LPS as a receptor, in Salmonella bacterial cultures.

Another Round: Influence of Alcohol-Related Conditions and Other Drug Use-Related Disorders in Emergency Department Frequent Use - A Single-Site Matched Case-Control Study in Spain.

INTRODUCTION: Patients who make 5 or more visits per year to hospital emergency departments (EDs) are usually considered ED frequent users (FUs). This study aims to better characterize the influence of alcohol and other drug use-related disorders in this phenomenon in a European Mediterranean country with public, universal, tax-financed healthcare system. METHODS: Matched case-control study. Cases were adults between 18 and 65 years old who consulted 5 or more times the ED of a tertiary hospital in Spain between December 2018 and November 2019. Each case was assigned a control of the same age and gender, who appeared to the ED on the same day, but who made 4 visits or less to the service during the study period. The electronic record of the first ED visit during this period was used to extract the variables of interest: emergency care received, clinical and social characteristics. Predictors of frequent ED use were identified with conditional logistic regression. RESULTS: 609 case-control pairs (total n = 1,218) were selected. History of alcohol-related conditions (adjusted odds ratio [AOR] = 1.82 [95% CI: 1.26-2.64] p = 0.001) and also other drug use-related disorders (AOR = 1.50 [95% CI: 1.11-2.03] p = 0.009) significantly increased the probability of frequent use of emergency services. DISCUSSION/CONCLUSION: Alcohol-related conditions and other drug use-related disorders must be evaluated in all ED FUs. Specific action protocols to concurrently address repeated attendance and addictions in the emergency room could be a good tool to reduce frequent ED use.

Influence of serum uric acid on bone and fracture risk in postmenopausal women.

AIMS: Uric acid has been associated with several metabolic conditions, including bone diseases. Our objective here was to consider the relationship between serum uric acid levels and various bone parameters (bone mineral density, ultrasonographic parameters, vitamin D, PTH and serum calcium), as well as the prevalence and risk of fragility fracture. METHODS: An observational and cross-sectional study carried out on 679 postmenopausal women, classified into 3 groups according to their serum uric acid levels, in whom bone densitometry, calcaneus ultrasounds, PTH, vitamin D and serum calcium analysis were done. Bone fractures were collected through the clinical history and lateral spinal X-ray. RESULTS: Higher uric acid levels were found in women with older age, high BMI, diabetes, and high blood pressure. Higher levels of PTH and serum calcium were also observed, but did not effect on vitamin D. Serum uric acid was positively related to densitometric and ultrasonic parameters and negatively associated with vertebral fractures. CONCLUSIONS: In the population of postmenopausal women studied, sUA levels were correlated with BMD, BUA, and QUI-Stiffness, and this correlation was independent of age and BMI. In addition, sUA was associated with a decrease in vertebral fractures. These results imply a beneficial influence of sUA on bone metabolism, with both a quantitative and qualitative positive effect, reflected in the lower prevalence of vertebral fractures.

The Expression of Genes Related to Reverse Cholesterol Transport and Leptin Receptor Pathways in Peripheral Blood Mononuclear Cells Are Decreased in Morbid Obesity and Related to Liver Function.

Obesity is frequently accompanied by non-alcoholic fatty liver disease (NAFLD). These two diseases are associated with altered lipid metabolism, in which reverse cholesterol transport (LXRα/ABCA1/ABCG1) and leptin response (leptin receptor (Ob-Rb)/Sam68) are involved. The two pathways were evaluated in peripheral blood mononuclear cells (PBMCs) from 86 patients with morbid obesity (MO) before and six months after Roux-en-Y gastric bypass (RYGB) and 38 non-obese subjects. In the LXRα pathway, LXRα, ABCA1, and ABCG1 mRNA expressions were decreased in MO compared to non-obese subjects (p < 0.001, respectively). Ob-Rb was decreased (p < 0.001), whereas Sam68 was increased (p < 0.001) in MO. RYGB did not change mRNA gene expressions. In the MO group, the LXRα pathway (LXRα/ABCA1/ABCG1) negatively correlated with obesity-related variables (weight, body mass index, and hip), inflammation (C-reactive protein), and liver function (alanine-aminotransferase, alkaline phosphatase, and fatty liver index), and positively with serum albumin. In the Ob-R pathway, Ob-Rb and Sam68 negatively correlated with alanine-aminotransferase and positively with albumin. The alteration of LXRα and Ob-R pathways may play an important role in NAFLD development in MO. It is possible that MO patients may require more than 6 months following RYBGB to normalize gene expression related to reverse cholesterol transport or leptin responsiveness.

HELIX Syndrome, a Claudinopathy with Relevant Dermatological Manifestations: Report of Two New Cases.

HELIX syndrome (Hypohidrosis-Electrolyte disturbances-hypoLacrimia-Ichthyosis-Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin 10 b protein, secondary to pathogenic CLDN10 variants. So far, only ten families have been described. We aim to describe the phenotype in the first Spanish family identified, highlight the skin anomalies as an important clue, and expand the genotypic spectrum. Two adult brothers from consanguineous parents with suspected ectodermal dysplasia (ED) since early childhood were re-evaluated. A comprehensive phenotypic exam and an aCGH + SNP4 × 180 K microarray followed by Sanger sequencing of the CLDN10 gene were performed. They presented hypohidrosis, xerosis, mild ichthyosis, plantar keratosis, palm hyperlinearity, alacrima, and xerostomia. In adulthood, they also developed a salt-losing nephropathy with hypokalemia and hypermagnesemia. The molecular study in both patients revealed a novel pathogenic homozygous deletion of 8 nucleotides in exon 2 of the CLDN10 gene [CLDN10 (NM_0006984.4): c.322_329delGGCTCCGA, p.Gly108fs*] leading to a premature truncation of the protein. Both parents were heterozygous carriers. Hypohidrosis, ichthyosis, and plantar keratosis associated with alacrima and xerostomia should raise suspicion for HELIX syndrome, which also includes nephropathy and electrolyte disturbances in adults. Given the potential for ED misdiagnosis in infancy, it is important to include the CLDN10 gene in a specific genodermatosis next-generation sequencing (NGS) panel to provide early diagnosis, accurate management, and genetic counseling.

The Crucial Role of Inflammation and the Immune System in Colorectal Cancer Carcinogenesis: A Comprehensive Perspective.

Chronic inflammation drives the growth of colorectal cancer through the dysregulation of molecular pathways within the immune system. Infiltration of immune cells, such as macrophages, into tumoral regions results in the release of proinflammatory cytokines (IL-6; IL-17; TNF-α), fostering tumor proliferation, survival, and invasion. Tumors employ various mechanisms to evade immune surveillance, effectively 'cloaking' themselves from detection and subsequent attack. A comprehensive understanding of these intricate molecular interactions is paramount for advancing novel strategies aimed at modulating the immune response against cancer.