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Introduction . Adherence is a major virulence trait in Candida glabrata that, in many strains, depends on the EPA (epithelial adhesin) genes, which confer the ability to adhere to epithelial and endothelial cells of the host. The EPA genes are generally found at subtelomeric regions, which makes them subject to subtelomeric silencing. In C. glabrata , subtelomeric silencing depends on different protein complexes, such as silent information regulator and yKu complexes, and other proteins, such as Repressor/activator protein 1 (Rap1) and Abf1. At the EPA1 locus, which encodes the main adhesin Epa1, we previously found at least two cis -acting elements, the protosilencer Sil2126 and the negative element, that contribute to the propagation of silencing from the telomere to the subtelomeric region. Hypothesis . Abf1 binds to the regulatory regions of EPA1 and other regions at the telomere E-R, thereby negatively regulating EPA1 transcription. Aim . To determine whether Abf1 and Rap1 silencing proteins bind to previously identified cis- acting elements on the right telomere of chromosome E (E-R subtelomeric region), resulting in negative regulation of EPA1 transcription and infer Abf1 and Rap1 recognition sites in C. glabrata . Methodology . We used chromatin immunoprecipitation (ChIP) followed by quantitative PCR to determine the binding sites for Abf1 and Rap1 in the intergenic regions between EPA1 and EPA2 and HYR1 and EPA1 , and mutants were used to determine the silencing level of the EPA1 promoter region. Results . We found that Abf1 predominantly binds to the EPA1 promoter region, leading to negative regulation of EPA1 expression. Furthermore, the mutant abf1-43 , which lacks the last 43 amino acids at its C-terminal end and is defective for subtelomeric silencing, exhibits hyperadherence to epithelial cells in vitro compared to the parental strain, suggesting that EPA1 is derepressed. We also determined the motif-binding sequences for Abf1 and Rap1 in C. glabrata using data from the ChIP assays. Conclusion . Together these data indicate that Abf1 negatively regulates EPA1 expression, leading to decreased adhesion of C. glabrata to epithelial cells.

Individuals with dementia and neurodegenerative diseases (NDDs) often suffer from cardiovascular diseases (CVDs). Neuroinflammation driven by conditions involved in CVDs is linked to disruptions in the central nervous system triggering immune reactions, perpetuating an "inflammatory-like" environment. The Mediterranean diet (MedDiet), known for its anti-inflammatory and antioxidant properties, has been proposed as a key factor to attenuate these risks. Blood nuclear cell samples were collected from 134 participants of the PREDIMED trial, which randomized participants to three diets: one supplemented with extra-virgin olive oil (MedDiet-EVOO), another with nuts (MedDiet-Nuts), and a low-fat control diet. These samples were analyzed at baseline and 12-month follow-up to assess the impact of these dietary interventions on gene expression markers. We first selected target genes by analyzing intersections between NDD and CVD associations. Significant gene expression changes from baseline to 12 months were observed in the participants allocated to the MedDiet-EVOO, particularly in CDKN2A, IFNG, NLRP3, PIK3CB, and TGFB2. Additionally, TGFB2 expression changed over time in the MedDiet-Nuts group. Comparative analyses showed significant differences in TGFB2 between MedDiet-EVOO and control, and in NAMPT between MedDiet-Nuts and control. Longitudinal models adjusted for different covariates also revealed significant effects for TGFB2 and NAMPT. In conclusion, our results suggest that one year of traditional MedDiet, especially MedDiet-EVOO, modulates gene expression associated with CVD risk and NDDs in older adults at high CV risk.

Introduction: Translation is a fundamental process of life. In eukaryotes, the elongation step of translation is highly conserved and is driven by eukaryotic translation elongation factors (eEF)1A and eEF2. A significant variation of the elongation is the activity of eukaryotic elongation factor (eEF) 3 in Saccharomyces cerevisiae encoded by the gene yeast elongation factor ( YEF3 ) with orthologs in all fungal species, a few algae, and some protists. In S. cerevisiae, YEF3 is an essential gene and eEF3 plays a critical role in translation elongation, as it promotes binding of the ternary complex acylated-Transfer RNA (tRNA)-eEF1A-Guanosine-5'-triphosphate (GTP) to the aminoacyl (A) site of the ribosome, the release of uncharged tRNAs after peptide translocation, and ribosome recycling. Even though YEF3 was discovered more than 40 years ago, eEF3 has been characterized almost exclusively in S. cerevisiae ., Methods: We undertook an in vivo genetic approach to assess the functional conservation of eEF3 across phylogenetically distant fungal species., Results: We found that eEF3 from Zygosaccharomyces rouxii and Candida glabrata (both belonging to phylum Ascomycota), Ustilago maydis ( phylum Basidiomycota), and Gonapodya prolifera ( phylum Monoblepharomycota), but not Aspergillus nidulans ( phylum Ascomycota), supported the growth of S. cerevisiae lacking the endogenous YEF3 gene. We also proved that eEF3 is an essential gene in the ascomycetes C. glabrata and A. nidulans ., Discussion: Given that most existing knowledge on fungal translation has only been obtained from S. cerevisiae , our findings beyond this organism showed variability in the elongation process in Fungi. We also proved that eEF3 is essential in pathogenic fungi, opening the possibility of using eEF3 as a target to fight candidiasis., Competing Interests: The C. glabrata strain ura3Δ::KANMX, eEF3Δ::NATMX is claimed by the patent MX/a/2019/000406, application file MX/E/2019/001890, 10th January of 2019, property of Instituto Nacional de Cancerología, Mexico. GH declared that he was an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. 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 © 2024 Maldonado, García, Herrero, Castaño, Altmann, Fischer and Hernández.)

Introduction: Obesity is a pathological state that involves the dysregulation of different metabolic pathways and adipose tissue cells, constituting a risk factor for the development of other diseases. Bariatric surgery is the most effective treatment. The study of the behavior of pollutants in situations of extreme weight loss can provide biomonitoring information and tools to manage diseases of environmental etiology., Aim: To determine the prevalence of serum persistent and non-persistent pollutants in obese patients subjected to bariatric surgery and analyze the impact of sociodemographic variables on these changes., Methods: GC-MS/MS and UHPLC-MS/MS were utilized to determine the detection rates and concentrations of 353 compounds, including persistent organic pollutants (POPs), pesticides, pharmaceuticals, and rodenticide, in serum samples of 59 obese patients before and after undergoing bariatric surgery., Results: Detection rates of p,p'-DDE, HCB, β-HCH, naphthalene, phenanthrene and PCB congeners 138, 153 and 180 significantly increased due to surgery-induced weight loss. Serum levels of p,p'-DDE, PCB-138, PCB-153 and PCB-180 also increased after surgery. Correlations between naphthalene levels, weight loss, variation of total lipids and time after surgery were found. Additionally, correlations were observed between concentrations of PCB-138 and weight loss, and between phenanthrene levels and reduction of total lipids. No statistically significant differences were observed for other groups of contaminants, pharmaceuticals and other chemicals included in the quantification methods., Conclusions: Increment of POPs was observed after bariatric surgery. Serum concentrations of POPs after surgery were influenced by adiposity-related variables. Although biomonitoring studies show a decreasing tendency of exposure, rapid weight loss leads to an increase of circulating POPs. Further research on the interplay between adipose tissue, POPs and peripheral organs is required., 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 © 2024 Díaz-González, Ramos-Luzardo, Henríquez-Hernández, Serra-Majem, Bautista-Castaño, Acosta-Dacal, Luzardo, Hernández-García, Cornejo-Torre, Hernández-Hernández and Fernández-Valerón.)

Candida glabrata (Nakaseomyces glabrata) is an emergent and opportunistic fungal pathogen that colonizes and persists in different niches within its human host. In this work, we studied five clinical isolates from one patient (P7), that have a clonal origin, and all of which come from blood cultures except one, P7-3, obtained from a urine culture. We found phenotypic variation such as sensitivity to high temperature, oxidative stress, susceptibility to two classes of antifungal agents, and cell wall porosity. Only isolate P7-3 is highly resistant to the echinocandin caspofungin while the other four isolates from P7 are sensitive. However, this same isolate P7-3, is the only one that displays susceptibility to fluconazole (FLC), while the rest of the isolates are resistant to this antifungal. We sequenced the PDR1 gene which encodes a transcription factor required to induce the expression of several genes involved in the resistance to FLC and found that all the isolates encode for the same Pdr1 amino acid sequence except for the last isolate P7-5, which contains a single amino acid change, G1099C in the putative Pdr1 transactivation domain. Consistent with the resistance to FLC, we found that the CDR1 gene, encoding the main drug efflux pump in C. glabrata, is highly overexpressed in the FLC-resistant isolates, but not in the FLC-sensitive P7-3. In addition, the resistance to FLC observed in these isolates is dependent on the PDR1 gene. Additionally, we found that all P7 isolates have a different proportion of cell wall carbohydrates compared to our standard strains CBS138 and BG14. In P7 isolates, mannan is the most abundant cell wall component, whereas β-glucan is the most abundant component in our standard strains. Consistently, all P7 isolates have a relatively low cell wall porosity compared to our standard strains. These data show phenotypic and genotypic variability between clonal isolates from different niches within a single host, suggesting microevolution of C. glabrata during an infection., 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 © 2024. Published by Elsevier Inc.)

Bariatric surgery therapy (BST) is an effective treatment for obesity; however, little is known about its impacts on health-related quality of life (HRQoL) and related factors. This study aimed to evaluate changes in HRQoL and its relationship with weight loss, depression status, physical activity (PA), and nutritional habits after BST. Data were obtained before and 18 months postprocedure from 56 obese patients who underwent BST. We administered four questionnaires: Short Form-36 health survey for HRQoL, 14-item MedDiet adherence questionnaire, Rapid Assessment of PA (RAPA) questionnaire, and Beck's Depression Inventory-II. Multivariable linear regression analysis was used to identify factors associated with improvement in HRQoL. After the surgery, MedDiet adherence and HRQoL improved significantly, especially in the physical component. No changes in PA were found. Patients without previous depression have better mental quality of life, and patients who lost more than 25% of %TBWL have better results in physical and mental quality of life. In the multivariable analysis, we found that %TBWL and initial PCS (inversely) were related to the improvement in PCS and initial MCS (inversely) with the MCS change. In conclusion, BST is an effective intervention for obesity, resulting in significant weight loss and improvements in HRQoL and nutritional habits.

Inflammatory and antimicrobial diseases constitute a major burden for society, and fighting them is a WHO strategic priority. Most of the treatments available to fight inflammatory diseases are anti-inflammatory drugs, such as corticosteroids or immunomodulators that lack cellular specificity and lead to numerous side effects. In addition to suppressing undesired inflammation and reducing disease progression, these drugs lessen the immune system protective functions. Furthermore, treating infectious diseases is more and more challenging due to the rise of microbial resistance to antimicrobial drugs. Thus, controlling the inflammatory process locally without compromising the ability to combat infections is an essential feature in the treatment of inflammatory diseases. We isolated three forms (DRS-DA2N, DRS-DA2NE, and DRS-DA2NEQ) of the same peptide, DRS-DA2, which belongs to the dermaseptin family, from the Mexican tree frog Pachymedusa dacnicolor . Interestingly, DRS-DA2N and DRS-DA2NEQ exhibit a dual activity by inducing the death of leukocytes as well as that of Gram-negative and Gram-positive bacteria, including multiresistant strains, without affecting other cells such as epithelial cells or erythrocytes. We showed that the death of both immune cells and bacteria is induced rapidly by DRS-DA2 and that the membrane is permeabilized, leading to the loss of membrane integrity. We also validated the capacity of DRS-DA2 to regulate the pool of inflammatory cells in vivo in a mouse model of noninfectious peritonitis. After the induction of peritonitis, a local injection of DRS-DA2N could decrease the number of inflammatory cells locally in the peritoneal cavity without inducing a systemic effect, as no changes in the number of inflammatory cells could be detected in blood or in the bone marrow. Collectively, these data suggest that this peptide could be a promising tool in the treatment of inflammatory diseases, such as inflammatory skin diseases, as it could reduce the number of inflammatory cells locally without suppressing the ability to combat infections., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2024 Claire Lacombe et al.)

The aim of this study was to evaluate the biomechanical changes in the cornea after wearing soft contact lenses (CLs) in healthy myopic patients measured with a Corvis ST ® (CST, Oculus Optikgeräte GmbH, Wetzlar, Germany) analyser. This prospective, cross-sectional, single-centre study was performed on twenty-two Caucasian patients aged between 19 and 24 years (20.64 ± 1.21 years) range. Five device-specific biomechanical parameters, the central corneal thickness (CCT), and biomechanically corrected intraocular pressure (bIOP) were measured prior to fitting and one month after CL wear. Differences between the means of the deflection amplitude ratio (DA Ratio) and the standard deviation of the DA Ratio (SD DA Ratio) pre- and post-CL wear were found to be significant ( p value = 0.002 in both cases). Significant differences were found between pre- and post-CL wear values in CCT ( p value = 0.013). For all other biomechanical measures, no significant differences were observed before and after treatment. A significant association was found between changes in bIOP and classification according to changes in Int. Radius ( p value = 0.047) and SSI ( p value = 0.026) standard deviations. The corneal biomechanical indices provided by CST demonstrate that the fitting of soft CLs is a safe optical compensation method for the stability of corneal stiffness. No significant differences were found pre- and post-CL wear in the assessment of bIOP.

Essential oils are known to exhibit diverse antimicrobial properties, showing their value as a natural resource. Our work aimed to investigate the primary mode of action of Cuban Lippia graveolens (Kunth) essential oil (EO) against Salmonella enterica subsp. enterica serovar Typhimurium ( S. enterica ser. Typhimurium). We assessed cell integrity through various assays, including time-kill bacteriolysis, loss of cell material with absorption at 260 and 280 nm, total protein leakage, and transmission electron microscopy (TEM). The impact of L. graveolens EO on membrane depolarization was monitored and levels of intracellular and extracellular ATP were measured by fluorescence intensity. The minimum inhibitory and bactericidal concentrations (MIC and MBC) of L. graveolens EO were 0.4 and 0.8 mg/mL, respectively. This EO exhibited notable bactericidal effects on treated cells within 15 min without lysis or leakage of cellular material. TEM showed distinct alterations in cellular ultrastructure, including membrane shrinkage and cytoplasmic content redistribution. We also observed disruption of the membrane potential along with reduced intracellular and extracellular ATP concentrations. These findings show that L. graveolens EO induces the death of S. enterica ser. Typhimurium, important information that can be used to combat this foodborne disease-causing agent.

Background: Dialysis patients have been maintaining a high rate of cardiovascular morbidity and mortality. For this reason, it is to introduce necessary new technical advances in clinical practice. There is a relation between toxins retention and inflammation, mortality and morbidity. Medium cut-off (MCO) membranes are a new generation of membranes that allow the removal of a greater number of medium-sized molecules compared with high-flux hemodialysis (HF-HD), but retaining albumin. MCO membranes have an increased permeability and the presence of internal filtration. Because of these special properties, MCO generated a new concept of therapy called expanded HD (HDx). Until now, online hemodiafiltration (OL-HDF) has demonstrated its superiority, in terms of survival, compared with HF-HD. However, the comparison between OL-HDF and HDx remains an unsolved question., Methods: The MOTheR HDx study trial (NCT03714386) is an open-label, multicenter, prospective, 1:1 randomized, parallel-group trial designed to evaluate the efficacy and safety of HDx compared with OL-HDF in patients treated for dialysis in Spain for up to 36 months. The main endpoint is to determinate whether HDx is non inferior to OL-HDF at reducing the combined outcome of all-cause death and stroke (ischemic or hemorrhagic), acute coronary syndrome (angina and myocardial infarction), peripheral arterial disease (amputation or revascularization) and ischemic colitis (mesenteric thrombosis)., Results: The trial has already started., Competing Interests: P.d.S. reports honorarium for conferences, consulting fees and advisory boards from Amgen, Astellas, AstraZeneca, Baxter, Braun, Fresenius Medical Care, GlaxoSmithKline, Nipro, Otsuka, Sandoz, Nipro and Vifor-Pharma. She is the present president of the Spanish Society of Nephrology (S.E.N.). R.P.-G. reports honorarium from Nipro. A.V. has received consultancy fees and lecture fees from Baxter, Braun and Astellas. P.M.-M. report honorarium for conferences and consulting fee from Nipro. M.F.-L. reports honorarium for conferences from Nipro. E.C. reports honorarium for conferences from Fresenius, Astellas and AstraZeneca, and studies from Baxter. I.C. reports honorarium for conferences from Braun, Palex and Vifor Pharma. F.M. has received consultancy fees and lecture fees from Baxter, Fresenius Medical Care, Medtronic, Nipro, Toray and Vifor. K.P.d.V., A.L.G.-H., J.G., M.A.G.-R., E.M. and B.G.-C. have no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

C. glabrata, an opportunistic fungal pathogen, can adapt and resist to different stress conditions. It is highly resistant to oxidant stress compared to other Candida spp and to the phylogenetically related but non-pathogen Saccharomyces cerevisiae. In this work, we describe the Trx/Trr system of C. glabrata composed of Trr1 and Trr2 (thioredoxin reductases) and Trx2 (thioredoxin) that are localized in the cytoplasm and Trx3 present in the mitochondrion. The transcriptional induction of TRR2 and TRX2 by oxidants depends on Yap1 and Skn7 and TRR1 and TRX3 have a low expression level. Both TRR2 and TRX2 play an important role in the oxidative stress response. The absence of TRX2 causes auxotrophy of methionine and cysteine. Trr1 and Trr2 are necessary for survival at high temperatures and for the chronological life span of C. glabrata. Furthermore, the Trx/Trr system is needed for survival in the presence of neutrophils. The role of TRR1 and TRX3 is not clear, but in the presence of neutrophils, they have non-overlapping functions with their TRR2 and TRX2 paralogues., 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 Inc. All rights reserved.)

Background: This study aimed to analyse the psychometric properties of the Curiosity and Exploration Inventory-II (CEI-II) to provide evidence of validity for its use in research on health promotion and the quality of life of young Spanish university students., Method: A sample of 807 participants (75.09% female) aged 18-26 years (M = 20.68; SD = 2.13) completed the CEI-II and health and quality of life measures questionnaire., Results: A unidimensional structure was confirmed, but the original two-dimensional structure also showed an adequate fit. The measures obtained from the CEI-II were gender- and age-invariant, which exhibited adequate internal consistency for both the full scale and subscales, and showed a statistically significant relationship with life satisfaction, sense of coherence, and psychological distress., Conclusions: The CEI-II can be used as unidimensional, which is recommended, but also as a two-dimensional measure. Both structures provide reliable, valid, and invariant measures across gender and age of exploratory behaviours in Spanish university students. Furthermore, the results confirm the association between exploratory behaviours and greater health management.

Cancer originates from the uncontrolled growth of healthy cells into a mass. Chromophores, such as hemoglobin and melanin, characterize skin spectral properties, allowing the classification of lesions into different etiologies. Hyperspectral imaging systems gather skin-reflected and transmitted light into several wavelength ranges of the electromagnetic spectrum, enabling potential skin-lesion differentiation through machine learning algorithms. Challenged by data availability and tiny inter and intra-tumoral variability, here we introduce a pipeline based on deep neural networks to diagnose hyperspectral skin cancer images, targeting a handheld device equipped with a low-power graphical processing unit for routine clinical testing. Enhanced by data augmentation, transfer learning, and hyperparameter tuning, the proposed architectures aim to meet and improve the well-known dermatologist-level detection performances concerning both benign-malignant and multiclass classification tasks, being able to diagnose hyperspectral data considering real-time constraints. Experiments show 87% sensitivity and 88% specificity for benign-malignant classification and specificity above 80% for the multiclass scenario. AUC measurements suggest classification performance improvement above 90% with adequate thresholding. Concerning binary segmentation, we measured skin DICE and IOU higher than 90%. We estimated 1.21 s, at most, consuming 5 Watts to segment the epidermal lesions with the U-Net++ architecture, meeting the imposed time limit. Hence, we can diagnose hyperspectral epidermal data assuming real-time constraints.

The prevalence of obesity has risen exponentially, and patients living with obesity suffer from its debilitating consequences. The treatment options for obesity have expanded significantly and include lifestyle changes, pharmacotherapy, endoscopic bariatric therapies (EBTs), and bariatric surgery. Endoscopic bariatric therapies comprise volume-reducing procedures such as endoscopic gastroplasty and gastric space-occupying devices such as intragastric balloons. Because of its minimally invasive nature and ease of delivery, EBTs are increasingly being adopted as a treatment option for obesity in several centers. These procedures mainly achieve weight loss by inducing early satiety and reducing meal volume. While the technical aspects of EBTs have been well explained, the nutritional management surrounding EBTs and the effectiveness of multidisciplinary team for maximizing weight loss is less described. There is considerable variation in post-EBT care between studies and centers. In this paper, we review the existing literature and share our experience on nutrition and the role of multidisciplinary management of obesity following EBT., Competing Interests: Gontrand Lopez Nava is a paid consultant for Apollo Endosurgery and USGI Medical, USA. Ravishankar Asokkumar is a consultant for Apollo Endosurgery, USA. All other authors have no conflict of interest.

Obesity in humans is a growing global problem and is one of the greatest public health challenges we face today. Most researchers agree that, as in humans, the incidence in the companion animal population is also increasing. The aim of this study was to evaluate the risk factors contributing to canine obesity in a region with a high rate of human obesity (Canary Islands, Spain), co-occurrence of obesogenic risk factors, and a canine population with a high percentage of unneutered dogs. We have focused on owner risk factors that promote obesity in humans, such as weight, lifestyle, nutritional habits, and low physical activity, among others. Thus, the human-animal interaction relationship that contributes to human obesity and influences canine obesity has been studied. A multicentre cross-sectional analytical study of 198 pairs of dogs from urban households and their owners was used. A multivariable logistic regression study was completed to analyse owner characteristics variables associated with canine obesity. This transdisciplinary study was conducted with physicians and veterinarians using a "One Health" approach. Our results suggest that, in a region of high obesogenic risk, obese/overweight dogs are primarily female, older than 6 years, and neutered. Being an overweight dog owner was found to be the most important factor in the occurrence of obesity in dogs. Owners of overweight dogs were mainly females, older than 40 years, who did not engage in any physical activity. A strong correlation has been found between dog owners with low levels of education and obesity in their dogs. We suggest that veterinarians should develop and design strategies to encourage pet owners to engage in physical activity with their dogs for the benefit of both.

Background: Endoscopic bariatric therapies can help address widening management gaps in obesity. Their ability to facilitate weight loss is largely tied to influences on appetite through perturbations of gastric emptying and accommodation. As these tools gain traction in obesity therapy, their physiologic underpinnings require exploration, which may enhance efficacy, tolerance, and patient-tailored care., Methods: We prospectively assessed consecutive subjects with fluid-filled intragastric balloons (IGBs) ( n  = 18) placed between October 2016 and June 2017 or underwent endoscopic sleeve gastroplasty (ESG) ( n  = 23) from March 2018 to June 2018. Patients underwent physiologic appraisal at 3 months with 13 C-spirulina-based gastric emptying breath test to determine time to half emptying (T50), as well as maximum tolerated volume (MTV) of a standard nutrient drink test. Changes in T50 and MTV at 3 months were compared with percent total body weight loss (%TBWL) at 3 and 6 months using best-fit linear regression., Results: The change in T50 at 3 months correlated with %TBWL at 3 months for IGB ( P  = 0.01) and ESG ( P  = 0.01) but with greater impact on %TBWL in IGB compared to ESG ( R2  = 0.42 vs . 0.26). Change in T50 at 3 months was predictive of weight loss at 6 months for IGB ( P  = 0.01) but not ESG ( P  = 0.11). ESG was associated with greater decrease in MTV compared to IGB (340.25 ± 297.97 mL vs. 183.00 ± 217.13 mL, P  = 0.08), indicting an enhanced effect on satiation through decreased gastric accommodation. Changes in MTV at 3 months did not correlate with %TBWL for either IGB ( P  = 0.26) or ESG ( P  = 0.49) but trended toward significance for predicting %TBWL at 6 months for ESG ( P  = 0.06) but not IGB ( P  = 0.19)., Conclusion: IGB and ESG both induce weight loss but likely through distinct gastric motor function phenotypes, and gastric emptying may predict future weight loss in patients with IGB., (Copyright © 2022 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

C. glabrata is an opportunistic fungal pathogen and the second most common cause of opportunistic fungal infections in humans, that has evolved virulence factors to become a successful pathogen: strong resistance to oxidative stress, capable to adhere and form biofilms in human epithelial cells as well as to abiotic surfaces and high resistance to xenobiotics. Hst1 (a NAD + -dependent histone deacetylase), Sum1 (putative DNA binding protein) and Rfm1 (connector protein) form a complex (HRS-C) and control the resistance to oxidative stress, to xenobiotics (the antifungal fluconazole), and adherence to epithelial cells. Hst1 is functionally conserved within the Saccharomycetaceae family, Rfm1 shows a close phylogenetic relation within the Saccharomycetaceae family while Sum1 displays a distant phylogenetic relation with members of the family and is not conserved functionally. CDR1 encodes for an ABC transporter (resistance to fluconazole) negatively controlled by HRS-C, for which its binding site is located within 223 bp upstream from the ATG of CDR1. The absence of Hst1 and Sum1 renders the cells hyper-adherent, possibly due to the overexpression of AED1, EPA1, EPA22 and EPA6, all encoding for adhesins. Finally, in a neutrophil survival assay, HST1 and SUM1, are not required for survival. We propose that Sum1 in the HRS-C diverged functionally to control a set of genes implicated in virulence: adherence, resistance to xenobiotics and oxidative stress., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Obesity is an expanding disease responsible for significant deterioration in the Health-Related Quality of Life (HRQL) of those who suffer from it. Bariatric Endoscopy (BE) therapies have proven to be an effective treatment for this pathology. A multidisciplinary approach is essential for the successful therapeutic management of BE. This article addresses the multidisciplinary treatment of BE by considering the possible variables that can influence treatment. In particular, the variables that can facilitate or hinder changes in patients' habits are discussed. These include the neuropsychological, emotional, and social implications that may influence the formation of healthy habits necessary for improvement in a patient's quality of life; the individual and environmental psychological factors that influence the monitoring of nutritional and physical activity indications; and different psychological disorders such as depression, anxiety, or disorders related to eating. The main objective of BE treatment, except in certain special biological situations, must be to establish a long-term sustainable change in habits such that patients, once they reach a healthy weight, do not revert to the lifestyle that caused their obesity, as well as identifying and addressing major problems that may exist prior to, or arise during, treatment.

Chromatin architecture has an enormous impact on gene regulation, DNA replication, repair, and packaging. Chromatin is organized in a complex hierarchical manner in which distant fragments of DNA can interact with each other through DNA loops. DNA loops can interact between themselves to form topologically associated domains (TADs) that are further organized into functional compartments. In the last two decades, Chromatin Conformation Capture (3C technology) and its high-throughput derivatives allowed detailed analysis of the chromatin architecture. The 3C method is based on ligation of distant fragments brought together by DNA looping. The method analyzes a particular genomic region of interest and quantifies the interactions between a defined fragment with all the surrounding fragments of the region. It consists of four steps: (1) The long-distance interacting chromatin fragments are fixed with formaldehyde in whole cells which are then lysed; (2) the fixed chromatin is digested with a carefully chosen restriction enzymes to separate intervening DNA fragments; (3) the fragments brought into proximity by DNA looping are ligated in conditions favoring intramolecular ligation; and (4) the interactions are quantified by quantitative PCR using the TaqMan technology and unidirectional primers. Herein, we describe the use of this methodology to analyze the chromatin conformation at a subtelomeric locus containing three genes encoding adhesins and several cis-regulatory elements, in the pathogenic yeast Candida glabrata., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The most common nosocomial fungal infections are caused by several species of Candida, of which Candida glabrata is the second most frequently isolated species from bloodstream infections. C. glabrata displays relatively high minimal inhibitory concentration values (MIC) to the antifungal fluconazole and is associated with high mortality rates. To decrease mortality rates, the appropriate treatment must be administered promptly. C. glabrata contains in its genome several non-identical copies of species-specific sequences. We designed three pairs of C. glabrata-specific primers for endpoint PCR amplification that align to these species-specific sequences and amplify the different copies in the genome. Using these primers, we developed a fast, sensitive, inexpensive, and highly specific PCR-based method to positively detect C. glabrata DNA in a concentration-dependent manner from mixes of purified genomic DNA of several Candida species, as well as from hemocultures and urine clinical samples. This tool can be used for positive identification of C. glabrata in the clinic., (© 2021. Sociedade Brasileira de Microbiologia.)

Accurate DNA replication and segregation is key to reproduction and cell viability in all organisms. Autonomously replicating sequence-binding factor 1 (Abf1) is a multifunctional protein that has essential roles in replication, transcription, and regional silencing in the model yeast Saccharomyces cerevisiae . In the opportunistic pathogenic fungus Candida glabrata , which is closely related to S. cerevisiae , these processes are important for survival within the host, for example, the regulation of transcription of virulence-related genes like those involved in adherence. Here, we describe that CgABF1 is an essential gene required for cell viability and silencing near the telomeres, where many adhesin-encoding genes reside. Cg Abf1 mediated subtelomeric silencing depends on the 43 C-terminal amino acids. We also found that abnormal expression, depletion, or overexpression of Abf1, results in defects in nuclear morphology, nuclear segregation, and transit through the cell cycle. In the absence of ABF1 , cells are arrested in G2 but start cycling again after 9 h, coinciding with the loss of cell viability and the appearance of cells with higher DNA content. Overexpression of CgABF1 causes defects in nuclear segregation and cell cycle progression. We suggest that these effects could be due to the deregulation of DNA replication.

Background: The POSE-2 procedure shortens and narrows the stomach using multiple full-thickness plications in the gastric body. We studied the efficacy and safety of POSE-2 for obesity at 1 year in a real-world setting., Methods: We reviewed the records of 75 patients who underwent POSE-2 at our unit. The primary outcome was percentage total body weight loss (%TBWL) at 1 year. Secondary outcomes were safety and durability. We used linear mixed model analysis., Results: 46 patients completed 1 year. Mean age and body mass index (BMI) were 49.3 years (standard deviation [SD] 10.2) and 38.2 kg/m 2 (SD 6.6), respectively. Technical success rate was 98.7 % (n = 74). Mean TBWL, %TBWL, and BMI decline at 1 year were 20 kg (SD 12.7), 17.8 % (SD 9.5), 7 kg/m 2 (SD 4.3). Adverse events occurred in four patients. The median length of stay was 1 day. Endoscopy at 1 year in 15 patients showed intact sutures and a reduction in gastric length compared with baseline (26.9 cm [SD 5.3] vs. 35.7 cm [SD 3.5]; P  < 0.001)., Conclusion: POSE-2 induced significant weight loss at 1 year. It appears to be safe, durable, and required only a short hospital stay., Competing Interests: Gontrand Lopez Nava is a paid consultant for Apollo Endosurgery, USGI Medical, USA and Nitinotes. All other authors declare that they have no conflicts of interest., (Thieme. All rights reserved.)

Candida albicans, Candida glabrata , Candida parapsilosis and Candida tropicalis are the four most common human fungal pathogens isolated that can cause superficial and invasive infections. It has been shown that specific metabolites present in the secretomes of these fungal pathogens are important for their virulence. C. glabrata is the second most common isolate world-wide and has an innate resistance to azoles, xenobiotics and oxidative stress that allows this fungal pathogen to evade the immune response and persist within the host. Here, we analyzed and compared the C. glabrata secretome with those of C. albicans, C. parapsilosis, C. tropicalis and the non-pathogenic yeast Saccharomyces cerevisiae . In C. glabrata , we identified a different number of metabolites depending on the growth media: 12 in synthetic complete media (SC), 27 in SC-glutamic acid and 23 in rich media (YPD). C. glabrata specific metabolites are 1-dodecene (0.09 ± 0.11%), 2,5-dimethylundecane (1.01 ± 0.19%), 3,7-dimethyldecane (0.14 ± 0.15%), and octadecane (0.4 ± 0.53%). The metabolites that are shared with C. albicans, C. glabrata , C. parapsilosis, &nbsp; C. tropicalis and S. cerevisiae are phenylethanol, which is synthesized from phenylalanine, and eicosane and nonanoic acid (identified as trimethylsilyl ester), which are synthesized from fatty acid metabolism. Phenylethanol is the most abundant metabolite in all fungi tested: 26.36 ± 17.42% ( C. glabrata ), 46.77 ± 15.58% ( C. albicans ), 49.76 ± 18.43% ( C. tropicalis ), 5.72 ± 0.66% ( C. parapsilosis .) and 44.58 ± 27.91% ( S. cerevisiae ). The analysis of C. glabrata's secretome will allow us to further our understanding of the possible role these metabolites could play in its virulence.

Background: Endoscopic sleeve gastroplasty (ESG) is an effective treatment option for obesity. However, data comparing its efficacy to bariatric surgery are scarce. We aimed to compare the effectiveness and safety of ESG with laparoscopic sleeve gastrectomy (LSG) and laparoscopic greater curve plication (LGCP) at 2 years. METHODS : We reviewed 353 patient records and identified 296 patients who underwent ESG (n = 199), LSG (n = 61), and LGCP (n = 36) at four centers in Spain between 2014 and 2016. We compared their total body weight loss (%TBWL) and safety over 2 years. A linear mixed model (LMM) was used to analyze repeated measures of weight loss outcomes at 6, 12, 18, and 24 months to compare the three procedures. RESULTS : Among the 296 patients, 210 (ESG 135, LSG 43, LGCP 32) completed 1 year of follow-up and 102 (ESG 46, LSG 34, LGCP 22) reached 2 years. Their mean (standard deviation [SD]) body mass index (BMI) was 39.6 (4.8) kg/m 2 . There were no differences in age, sex, or BMI between the groups. In LMM analysis, adjusting for age, sex, and initial BMI, we found ESG had a significantly lower TBWL, %TBWL, and BMI decline compared with LSG and LGCP at all time points ( P  = 0.001). The adjusted mean %TBWL at 2 years for ESG, LSG, and LGCP were 18.5 %, 28.3 %, and 26.9 %, respectively. However, ESG, when compared with LSG and LGCP, had a shorter inpatient stay (1 vs. 3 vs. 3 days; P  < 0.001) and lower complication rate (0.5 % vs. 4.9 % vs. 8.3 %; P  = 0.006). CONCLUSION : All three procedures induced significant weight loss in obese patients. Although the weight loss was lower with ESG compared with other techniques, it displayed a better safety profile and shorter hospital stay., Competing Interests: G. Lopez-Nava is a consultant for Apollo Endosurgery and USGI Medical, USA. E. Espinett Coll is a consultant for Apollo Endosurgery. The remaining authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

This paper shows new contributions in the detection of skin cancer, where we present the use of a customized hyperspectral system that captures images in the spectral range from 450 to 950 nm. By choosing a 7 × 7 sub-image of each channel in the hyperspectral image (HSI) and then taking the mean and standard deviation of these sub-images, we were able to make fits of the resulting curves. These fitted curves had certain characteristics, which then served as a basis of classification. The most distinct fit was for the melanoma pigmented skin lesions (PSLs), which is also the most aggressive malignant cancer. Furthermore, we were able to classify the other PSLs in malignant and benign classes. This gives us a rather complete classification method for PSLs with a novel perspective of the classification procedure by exploiting the variability of each channel in the HSI.

Critically ill patients are physiologically unstable and recent studies indicate that the intestinal microbiota could be involved in the health decline of such patients during ICU stays. This study aims to assess the intestinal microbiota in critically ill patients with and without sepsis and to determine its impact on outcome variables, such as medical complications, ICU stay time, and mortality. A multi-center study was conducted with a total of 250 peri-rectal swabs obtained from 155 patients upon admission and during ICU stays. Intestinal microbiota was assessed by sequencing the V3-V4 hypervariable regions of the 16S rRNA gene. Linear mixed models were used to integrate microbiota data with more than 40 clinical and demographic variables to detect covariates and minimize the effect of confounding factors. We found that the microbiota of ICU patients with sepsis has an increased abundance of microbes tightly associated with inflammation, such as Parabacteroides, Fusobacterium and Bilophila species. Female sex and aging would represent an increased risk for sepsis possibly because of some of their microbiota features. We also evidenced a remarkable loss of microbial diversity, during the ICU stay. Concomitantly, we detected that the abundance of pathogenic species, such as Enterococcus spp., was differentially increased in sepsis patients who died, indicating these species as potential biomarkers for monitoring during ICU stay. We concluded that particular intestinal microbiota signatures could predict sepsis development in ICU patients. We propose potential biomarkers for evaluation in the clinical management of ICU patients.

Objective: To determine the concentration of stool short-chain fatty acids (SCFAs) in critically ill patients with sepsis and to compare the results between the critically ill patient and the control group. Methods: This descriptive, multicenter, observational study was conducted in five health institutions. Over a 6-month study period, critically ill patients with sepsis who were admitted to the intensive care unit (ICU) and met the inclusion criteria were enrolled, and a control, paired by age and sex, was recruited for each patient. A spontaneous stool sample was collected from each participant and a gas chromatograph coupled to a mass spectrometer (Agilent 7890/MSD 5975 C) was used to measure the concentrations SCFAs. Results: The final sample included 44 patients and 45 controls. There were no differences in the age and sex distributions between the groups ( p  > 0.05). According to body mass index (BMI), undernutrition was more prevalent among critically ill patients, and BMI in control subjects was most frequently classified as overweight ( p  = 0.024). Propionic acid, acetic acid, butyric acid, and isobutyric acid concentrations were significantly lower in the critically ill patient group than in the control group ( p  = 0.000). No association with outcome variables (complications, ICU stay, and discharge condition) was found in the patients, and patients diagnosed with infection on ICU admission showed significant decreases in butyric and isobutyric acid concentrations with respect to other diagnostic criteria ( p  < 0.05). Conclusions: The results confirm significantly lower concentrations of stool SCFAs in critically ill patients with sepsis than in control subjects. Due to its role in intestinal integrity, barrier function, and anti-inflammatory effect, maintaining the concentration of SCFAs may be important in the ICU care protocols of the critical patient.

Background: The intragastric balloon (IGB) is commonly used for weight loss. Identifying patients who are most likely to tolerate and benefit from IGB therapy will optimize outcomes. Our aims were to prospectively utilize a gastric emptying study to predict intolerance and treatment response with a single fluid-filled IGB and to develop a physiologic prediction model with a treatment algorithm., Materials and Methods: A total of 32 patients had a gastric emptying study before and 2-3 months after placement of an IGB. Multiple logistic regression analyses were performed to calculate likelihood ratios and to develop a physiologic prediction model., Results: Patients in the higher gastric retention quartile at baseline had a 6.2-time higher likelihood ratio for early balloon removal secondary to intolerance (p = 0.013). Utilizing baseline gastric emptying to predict intolerance to the IGB may have prevented 75% of early removal cases. Decreased gastric emptying at 3 months after balloon placement was significantly correlated with percent total body weight loss (%TWBL) at 6 and 12 months (p = 0.01 and p = 0.014, respectively). At 6 months after IGB, patients with no change in their gastric emptying at 3 months lost significantly less weight compared with those with increased gastric retention (median %TBWL = 9.0% [4.5-14.7] versus 17.3% [12.2-24.4], p = 0.016)., Conclusion: Utilizing gastric emptying as a physiologic predictor of intolerance and response to the single fluid-filled IGB can improve outcomes. This pilot feasibility trial ushers in the era of personalized endoscopic bariatric therapies to maximize patients' tolerance, cost-effectiveness, and meaningful weight loss.

Introduction: ESG reduces gastric lumen similar to LSG and induces significant weight loss. However, the metabolic and physiological alteration after ESG is not fully understood. We aim to study the gastrointestinal hormone changes after ESG and compared it with LSG., Methods: We conducted a prospective pilot study comparing ESG and LSG at two centers in Spain. We administered a standard test meal after an overnight fast, and collected blood samples before and after meal. We measured the levels of ghrelin, GLP-1, peptide-YY, insulin, leptin, and adiponectin. We evaluated the hormone profile and weight changes (%TBWL) at baseline and at 6 months after the procedure., Results: Twenty-four patients were recruited (ESG-12, LSG-12). The baseline age, sex, BMI, and fasting hormone levels were similar between the groups. At 6-month post-ESG, there was a significant decline in the leptin levels. We found a trend towards a decrease in insulin levels and improvement in insulin secretory pattern. We did not observe any change in fasting ghrelin levels, GLP-1, and PYY. At 6 months, LSG induced a significant reduction in the ghrelin, and leptin levels, and increase in peptide-YY, and adiponectin levels, respectively. A trend towards an increase in GLP-1 level was noted. However, no change in insulin was observed. LSG achieved greater %TBWL (24.4 vs. 13.3, p < 0.001) and significantly change in ghrelin, PYY, and adiponectin levels at 6 months compared to ESG., Conclusion: ESG induced gut hormone changes differently as compared to LSG. ESG prevented a compensatory rise in ghrelin and promoted beneficial changes in the insulin secretory pattern with weight loss.

Skin cancer is one of the most common forms of cancer worldwide and its early detection its key to achieve an effective treatment of the lesion. Commonly, skin cancer diagnosis is based on dermatologist expertise and pathological assessment of biopsies. Although there are diagnosis aid systems based on morphological processing algorithms using conventional imaging, currently, these systems have reached their limit and are not able to outperform dermatologists. In this sense, hyperspectral (HS) imaging (HSI) arises as a new non-invasive technology able to facilitate the detection and classification of pigmented skin lesions (PSLs), employing the spectral properties of the captured sample within and beyond the human eye capabilities. This paper presents a research carried out to develop a dermatological acquisition system based on HSI, employing 125 spectral bands captured between 450 and 950 nm. A database composed of 76 HS PSL images from 61 patients was obtained and labeled and classified into benign and malignant classes. A processing framework is proposed for the automatic identification and classification of the PSL based on a combination of unsupervised and supervised algorithms. Sensitivity and specificity results of 87.5% and 100%, respectively, were obtained in the discrimination of malignant and benign PSLs. This preliminary study demonstrates, as a proof-of-concept, the potential of HSI technology to assist dermatologists in the discrimination of benign and malignant PSLs during clinical routine practice using a real-time and non-invasive hand-held device.

Introduction: Endoscopic bariatric therapies (EBT) have demonstrated to induce weight loss and improve comorbidities in obese patients. However, little is known about its impact on health-related quality of life (HRQOL) outcomes and physical activity status. This study aimed to evaluate the change in HRQOL and physical activity following EBT induced weight loss in obese patients., Methods: We approached 181 patients who underwent EBT in a standardized multidisciplinary follow-up program to participate in the study. We provided them two questionnaires-a) Short Form-36 health survey with the physical (PSC) and mental (MSC) summary component scores to capture generic HRQOL, and b) international physical activity questionnaire (IPAQ) for physical activity (PA). We administered the survey at baseline and at 9 months post-procedure. We expressed the procedure outcome as percentage total body weight loss (%TBWL). We expressed continuous variables as mean (SD) or median and categorical variables as percentages. We used non-parametric tests for comparison and performed multivariable linear regression analysis to identify factors associated with improvement in HRQOL., Results: The mean age was 42.2 (11.3) years, and the mean BMI was 38 (5.9)kg/m 2 . A majority of them were female (n-132, 73%). The EBT included intragastric balloons (n-136, 75%) and endoscopic sleeve gastroplasty (n-24, 25%). The mean %TBWL achieved after the intervention was 16.9 (9.7)%. We noticed a significant improvement in the median PSC (77.8 vs. 90.4, p < 0.001) and MSC (67 vs. 80.2, p < 0.001) scores after EBT. Similarly, we observed a significant positive change in physical activity compared to baseline (1606.2 vs. 2749 MET-minutes/week, p = < 0.001). Linear regression analysis showed an increase in %TBWL was associated with significant improvement in PSC (β = 0.193, p = 0.003) and MSC (β = 0.166, p = 0.02) scores of HRQOL, and likewise, increase in PA was independently associated with improvement in MSC (β = 0.192, p = 0.01). We did not find any difference in outcome based on gender or the type of intervention., Conclusion: EBT improves HRQOL in obese patients regardless of the type of intervention. The weight loss induced by EBT and the improvement in PA positively influence the health outcomes and quality of life.

Dietary polyphenol intake is associated with improvement of metabolic disturbances. The aims of the present study are to describe dietary polyphenol intake in a population with metabolic syndrome (MetS) and to examine the association between polyphenol intake and the components of MetS. This cross-sectional analysis involved 6633 men and women included in the PREDIMED (PREvención con DIeta MEDiterranea-Plus) study. The polyphenol content of foods was estimated from the Phenol-Explorer 3.6 database. The mean of total polyphenol intake was 846 ± 318 mg/day. Except for stilbenes, women had higher polyphenol intake than men. Total polyphenol intake was higher in older participants (>70 years of age) compared to their younger counterparts. Participants with body mass index (BMI) >35 kg/m 2 reported lower total polyphenol, flavonoid, and stilbene intake than those with lower BMI. Total polyphenol intake was not associated with a better profile concerning MetS components, except for high-density lipoprotein cholesterol (HDL-c), although stilbenes, lignans, and other polyphenols showed an inverse association with blood pressure, fasting plasma glucose, and triglycerides. A direct association with HDL-c was found for all subclasses except lignans and phenolic acids. To conclude, in participants with MetS, higher intake of several polyphenol subclasses was associated with a better profile of MetS components, especially HDL-c.

Candida glabrata is an opportunistic fungal pathogen that can cause life-threatening infections in immunocompromised patients. To ensure a successful infection, C. glabrata has evolved a variety of strategies to avoid killing within the host. One of these strategies is the resistance to oxidative stress. Here we show that the sulfiredoxin Srx1 and the peroxiredoxins, Tsa1 and Tsa2, are implicated in the oxidative stress response (OSR) and required for virulence. We analyzed null mutations in SRX1, TSA1 and TSA2 and showed that TSA2 and SRX1 are required to respond to oxidative stress. While TSA1 expression is constitutive, SRX1 and TSA2 are induced in the presence of H 2 O 2 in a process dependent on H 2 O 2 concentration and on both transcription factors Yap1 and Skn7. Msn2 and Msn4 are not necessary for the regulation of SRX1, TSA1 and TSA2. Interestingly, TSA1 and TSA2, which are localized in the cytoplasm, are induced in the presence of neutrophils and required for survival in these phagocytic cells., 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 © 2019 Elsevier Inc. All rights reserved.)

Gene therapy has recently come of age with seven viral vector-based therapies gaining regulatory approval in recent years. In tissue engineering, non-viral vectors are preferred over viral vectors, however, lower transfection efficiencies and difficulties with delivery remain major limitations hampering clinical translation. This study describes the development of a novel multi-domain cell-penetrating peptide, GET, designed to enhance cell interaction and intracellular translocation of nucleic acids; combined with a series of porous collagen-based scaffolds with proven regenerative potential for different indications. GET was capable of transfecting cell types from all three germ layers, including stem cells, with an efficiency comparable to Lipofectamine ® 3000, without inducing cytotoxicity. When implanted in vivo, GET gene-activated scaffolds allowed for host cell infiltration, transfection localized to the implantation site and sustained, but transient, changes in gene expression - demonstrating both the efficacy and safety of the approach. Finally, GET carrying osteogenic (pBMP-2) and angiogenic (pVEGF) genes were incorporated into collagen-hydroxyapatite scaffolds and with a single 2 μg dose of therapeutic pDNA, induced complete repair of critical-sized bone defects within 4 weeks. GET represents an exciting development in gene therapy and by combining it with a scaffold-based delivery system offers tissue engineering solutions for a myriad of regenerative indications., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Research examining associations between objectively-measured napping time and type 2 diabetes (T2D) is lacking. This study aimed to evaluate daytime napping in relation to T2D and adiposity measures in elderly individuals from the Mediterranean region. A cross-sectional analysis of baseline data from 2190 elderly participants with overweight/obesity and metabolic syndrome, in the PREDIMED-Plus trial, was carried out. Accelerometer-derived napping was measured. Prevalence ratios (PR) and 95% confidence intervals (CI) for T2D were obtained using multivariable-adjusted Cox regression with constant time. Linear regression models were fitted to examine associations of napping with body mass index (BMI) and waist circumference (WC). Participants napping ≥90 min had a higher prevalence of T2D (PR 1.37 (1.06, 1.78)) compared with those napping 5 to <30 min per day. Significant positive associations with BMI and WC were found in those participants napping ≥30 min as compared to those napping 5 to <30 min per day. The findings of this study suggest that longer daytime napping is associated with higher T2D prevalence and greater adiposity measures in an elderly Spanish population at high cardiovascular risk.

A fundamental question in biology is to understand how appropriate transcriptional regulation and dense packaging of the genetic material within the eukaryotic nucleus are achieved. The exquisite gene expression control and other metabolic processes of DNA require a highly complex, multilayered, three-dimensional architecture of the chromatin and its specific compartmentalization within the nucleus. Some of these architectural and sub-nuclear positioning mechanisms have been extensively co-opted by eukaryotic pathogens to keep fine expression control and expansion of virulence-related gene families in Plasmodium falciparum, Trypanosoma brucei and Candida glabrata. For example non-linear interactions between distant cis-acting regions and the formation of chromatin loops are required for appropriate regulation of the expression of virulence-related multi-gene families encoding cell surface proteins. These gene families are located near the chromosome ends and tethered to the nuclear periphery. Consequently, only one or very few genes of the family are expressed at a time. These genes are involved in antigenic variation in parasites and the generation of subpopulations of cells with diverse antigenic proteins at the surface in some pathogenic fungi, making them highly efficient pathogens.

MicroRNA (miRNA) therapeutics is increasingly being developed to either target bone-related diseases such as osteoporosis and osteoarthritis or as the basis for novel bone tissue engineering strategies. A number of miRNAs have been reported as potential osteo-therapeutics but no consensus has yet been established on the optimal target. miR-16 has been studied extensively in nonosteogenic functions and used as functionality reporter target in the development of nonviral miRNA delivery platforms. This study hypothesized that miR-16 may also play an inhibitory role in osteogenesis due to its ability to directly target Smad5 and AcvR2a. This study thus aimed to assess the potential of miR-16 inhibition to increase osteogenesis in human mesenchymal stem cells (hMSCs) using a previously established miRNA delivery platform composed of nanohydroxyapatite (nHA) particles as nonviral vectors in combination with collagen-nHA scaffolds designed specifically for bone repair. Initial results showed that antagomiR-16 delivery efficiently increased the relative levels of both putative targets and Runx2, the key transcription factor for osteogenesis, while also increasing osteocalcin levels. Furthermore, significant increases in mineral calcium deposition by hMSCs were found in both monolayer and most importantly in scaffold-based osteodifferentiation studies, ultimately demonstrating that miR-16 inhibition further enhances the therapeutic potential of a scaffold with known potential for bone repair applications and thus holds significant therapeutic potential as a novel bone tissue engineering strategy. Furthermore, we suggest that harnessing the additional functions known to miR-16 by incorporating either its enhancers or inhibitors to tissue-specific tailored scaffolds provides exciting opportunities for a diverse range of therapeutic indications.

An important virulence factor for the fungal pathogen Candida glabrata is the ability to adhere to the host cells, which is mediated by the expression of adhesins. Epa1 is responsible for ∼95% of the in vitro adherence to epithelial cells and is the founding member of the Epa family of adhesins. The majority of EPA genes are localized close to different telomeres, which causes transcriptional repression due to subtelomeric silencing. In C. glabrata there are three Sir proteins (Sir2, Sir3 and Sir4) that are essential for subtelomeric silencing. Among a collection of 79 clinical isolates, some display a hyperadherent phenotype to epithelial cells compared to our standard laboratory strain, BG14. These isolates also express several subtelomeric EPA genes simultaneously. We cloned the SIR2, SIR3 and SIR4 genes from the hyperadherent isolates and from the BG14 and the sequenced strain CBS138 in a replicative vector to complement null mutants in each of these genes in the BG14 background. All the SIR2 and SIR4 alleles tested from selected hyper-adherent isolates were functional and efficient to silence a URA3 reporter gene inserted in a subtelomeric region. The SIR3 alleles from these isolates were also functional, except the allele from isolate MC2 (sir3-MC2), which was not functional to silence the reporter and did not complement the hyperadherent phenotype of the BG14 sir3Δ. Consistently, sir3-MC2 allele is recessive to the SIR3 allele from BG14. Sir3 and Sir4 alleles from the hyperadherent isolates contain several polymorphisms and two of them are present in all the hyperadherent isolates analyzed. Instead, the Sir3 and Sir4 alleles from the BG14 and another non-adherent isolate do not display these polymorphisms and are identical to each other. The particular combination of polymorphisms in sir3-MC2 and in SIR4-MC2 could explain in part the hyperadherent phenotype displayed by this isolate., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Adherence, an important virulence factor, is mediated by the EPA (Epithelial Adhesin) genes in the opportunistic pathogen Candida glabrata Expression of adhesin-encoding genes requires tight regulation to respond to harsh environmental conditions within the host. The majority of EPA genes are localized in subtelomeric regions regulated by subtelomeric silencing, which depends mainly on Rap1 and the Sir proteins. In vitro adhesion to epithelial cells is primarily mediated by Epa1. EPA1 forms a cluster with EPA2 and EPA3 in the right telomere of chromosome E (E -R ). This telomere contains a cis -acting regulatory element, the protosilencer Sil2126 between EPA3 and the telomere. Interestingly, Sil2126 is only active in the context of its native telomere. Replacement of the intergenic regions between EPA genes in E -R revealed that cis -acting elements between EPA2 and EPA3 are required for Sil2126 activity when placed 32 kb away from the telomere (Sil@-32kb). Sil2126 contains several putative binding sites for Rap1 and Abf1, and its activity depends on these proteins. Indeed, Sil2126 binds Rap1 and Abf1 at its native position and also when inserted at -32 kb, a silencing-free environment in the parental strain. In addition, we found that Sil@-32kb and Sil2126 at its native position can physically interact with the intergenic regions between EPA1-EPA2 and EPA2-EPA3 respectively, by chromosome conformation capture assays. We speculate that Rap1 and Abf1 bound to Sil2126 can recruit the Silent Information Regulator complex, and together mediate silencing in this region, probably through the formation of a chromatin loop., (Copyright © 2018 by the Genetics Society of America.)

Introduction: many patients that undergo bariatric surgery (Roux-en-Y gastric bypass [RYGB]) may regain some of their weight lost over time. A transoral outlet reduction (TORe) with endoscopic suture could be a valid alternative in these patients., Methods: this was a retrospective initial series of 13 consecutive patients with weight regain after RYGB and a dilated gastro-jejunal anastomosis (> 15 mm). TORe was performed using an endoscopic transmural suture device (OverStitch-Apollo®), which was used to reduce the anastomosis aperture and also to treat the gastric pouch. The initial data of feasibility, safety and weight loss are described with a limited follow-up of six months., Results: there was a mean maximum weight loss of 37.69 kg after RYGB and a subsequent average regain of 21.62 kg. The mean anastomosis diameter was 36 mm (range 20-45) which was reduced to 9 mm (range 5-12) (75% reduction), with an average of 2.5 sutures. The mean pouch size was 7.2 cm (range 2-10), which decreased to 4.7 cm (range 4-5) (34.72% reduction), with an average of 2.7 sutures. The mean weight loss six months after TORe was 12.29 kg, a weight loss of 56.85% of the weight regained after RYGB. No complications related to the procedure were recorded., Conclusions: endoscopic suture reduction of the dilated gastro-jejunal anastomosis and the gastric pouch seems a feasible and safe option in our limited initial experience. With a multidisciplinary approach and a short term follow-up, this seems to be a minimally invasive and effective option to control weight regain after RYGB.

Gene-activated scaffolds have been shown to induce controlled, sustained release of functional transgene both in vitro and in vivo. Bone morphogenetic proteins (BMPs) are potent mediators of osteogenesis however we found that the delivery of plasmid BMP-2 (pBMP-2) alone was not sufficient to enhance bone formation. Therefore, the aim of this study was to assess if the use of a series of modified BMP-2 plasmids could enhance the functionality of a pBMP-2 gene-activated scaffold and ultimately improve bone regeneration when implanted into a critical sized bone defect in vivo. A multi-cistronic plasmid encoding both BMP-2 and BMP-7 (BMP-2/7) was employed as was a BMP-2-Advanced plasmid containing a highly truncated intron sequence. With both plasmids, the highly efficient cytomegalovirus (CMV) promoter sequence was used. However, as there have been reports that the elongated factor 1-α promoter is more efficient, particularly in stem cells, a BMP-2-Advanced plasmid containing the EF1α promoter was also tested. Chitosan nanoparticles (CS) were used to deliver each plasmid to MSCs and induced transient up-regulation of BMP-2 protein expression, in turn significantly enhancing MSC-mediated osteogenesis when compared to untreated controls (p < 0.001). When incorporated into a bone mimicking collagen-hydroxyapatite scaffold, the BMP-2-Advanced plasmid, under the control of the CMV promotor, induced MSCs to produce approximately 2500 μg of calcium per scaffold, significantly higher (p < 0.001) than all other groups. Just 4 weeks post-implantation in vivo, this cell-free gene-activated scaffold induced significantly more bone tissue formation compared to a pBMP-2 gene-activated scaffold (p < 0.001) as indicated by microCT and histomorphometry. Immunohistochemistry revealed that the BMP-2-Advanced plasmid accelerated differentiation of osteoprogenitor cells to mature osteoblasts, thus causing rapid healing of the bone defects. This study confirms that optimising the plasmid construct can enhance the functionality of gene-activated scaffolds and translate to accelerated bone formation in a critical sized defect., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Candida glabrata is the second most common cause of candidemia, and its ability to adhere to different host cell types, to microorganisms, and to medical devices are important virulence factors. Here, we consider three characteristics that confer extraordinary advantages to C. glabrata within the host. (1) C. glabrata has a large number of genes encoding for adhesins most of which are localized at subtelomeric regions. The number and sequence of these genes varies substantially depending on the strain, indicating that C. glabrata can tolerate high genomic plasticity; (2) The largest family of CWPs (cell wall proteins) is the EPA (epithelial adhesin) family of adhesins. Epa1 is the major adhesin and mediates adherence to epithelial, endothelial and immune cells. Several layers of regulation like subtelomeric silencing, cis- acting regulatory regions, activators, nutritional signaling, and stress conditions tightly regulate the expression of many adhesin-encoding genes in C. glabrata , while many others are not expressed. Importantly, there is a connection between acquired resistance to xenobiotics and increased adherence; (3) Other subfamilies of adhesins mediate adherence to Candida albicans , allowing C. glabrata to efficiently invade the oral epithelium and form robust biofilms. It is noteworthy that every C. glabrata strain analyzed presents a unique pattern of CWPs at the cell surface.

The human fungal pathogen Candida glabrata is causing more and more problems in hospitals, as this species shows an intrinsic antifungal drug resistance or rapidly becomes resistant when challenged with antifungals. C. glabrata only grows in the yeast form, so it is lacking a yeast-to-hyphae switch, which is one of the main virulence factors of C. albicans . An important virulence factor of C. glabrata is its capacity to strongly adhere to many different substrates. To achieve this, C. glabrata expresses a large number of adhesin-encoding genes and genome comparisons with closely related species, including the non-pathogenic S. cerevisiae , which revealed a correlation between the number of adhesin-encoding genes and pathogenicity. The adhesins are involved in the first steps during an infection; they are the first point of contact with the host. For several of these adhesins, their importance in adherence to different substrates and subsequent biofilm formation was demonstrated in vitro or in vivo. In this review, we provide an overview of the role of C. glabrata adhesins during adhesion and biofilm formation both, under in vitro and in vivo conditions.