Integrated transcriptomics contrasts fatty acid metabolism with hypoxia response in ß-cell subpopulations associated with glycemic control.

BACKGROUND: Understanding how heterogeneous ß-cell function impacts diabetes is imperative for therapy development. Standard single-cell RNA sequencing analysis illuminates some factors driving heterogeneity, but new strategies are required to enhance information capture. RESULTS: We integrate pancreatic islet single-cell and bulk RNA sequencing data to identify ß-cell subpopulations based on gene expression and characterize genetic networks associated with ß-cell function in obese SM/J mice. We identify ß-cell subpopulations associated with basal insulin secretion, hypoxia response, cell polarity, and stress response. Network analysis associates fatty acid metabolism and basal insulin secretion with hyperglycemic-obesity, while expression of Pdyn and hypoxia response is associated with normoglycemic-obesity. CONCLUSIONS: By integrating single-cell and bulk islet transcriptomes, our study explores ß-cell heterogeneity and identifies novel subpopulations and genetic pathways associated with ß-cell function in obesity.

Longitudinal Changes in Fecal Calprotectin Levels Among Pregnant Women With and Without Inflammatory Bowel Disease and Their Babies.

BACKGROUND & AIMS: The effect of pregnancy on inflammatory bowel disease (IBD) remains poorly understood. We aimed to monitor intestinal inflammation using fecal calprotectin (FC) in pregnant women and their babies during early life. METHODS: Pregnant women with or without IBD and their infants were prospectively enrolled. FC levels were measured at each trimester of pregnancy and in babies throughout the first 3 years of life. Repeated-measures analysis was applied to investigate changes in FC levels while adjusting for confounders. The FC levels were correlated with the bacterial abundance in both mothers and babies. RESULTS: Six hundred and fourteen fecal samples from 358 mothers (98 with IBD) and 1005 fecal samples from 289 infants (76 born to IBD mothers) were analyzed. Pregnant Patients with IBD maintained higher FC levels through pregnancy compared with controls (P = 7.5 × 10-54). FC gradually increased in controls and declined in Patients with IBD throughout pregnancy (P for interaction = 5.8 × 10-7). Babies born to mothers with IBD presented with significantly higher FC levels than those born to controls up to 3 years of age, after adjusting for sex, delivery mode, feeding behavior, and antibiotics exposure (2 weeks to 3 months of age, P = .015; 12-36 months of age, P = .00003). Subdoligranulum, Roseburia, Fusicatenibacter, and Alistipes negatively correlated, and Streptococcus, Prevotella, Escherichia-Shigella, and Bifidobacterium positively correlated with maternal FC levels at T3. Faecalibacterium, Bifidobacterium, and Alistipes showed negative correlations, and Streptococcus were positively correlated with FC levels within 3 months of birth. CONCLUSIONS: Pregnancy is associated with decreased inflammatory activity in mothers with IBD. Higher FC levels in babies born to mothers with IBD suggest subclinical inflammation in early life, the long-term consequences of which are uncertain.

Pancreatic ß-cell heterogeneity in health and diabetes: classes, sources, and subtypes.

Pancreatic ß-cells perform glucose-stimulated insulin secretion, a process at the center of type 2 diabetes etiology. Efforts to understand how ß-cells behave in healthy and stressful conditions have revealed a wide degree of morphological, functional, and transcriptional heterogeneity. Sources of heterogeneity include ß-cell topography, developmental origin, maturation state, and stress response. Advances in sequencing and imaging technologies have led to the identification of ß-cell subtypes, which play distinct roles in the islet niche. This review examines ß-cell heterogeneity from morphological, functional, and transcriptional perspectives, and considers the relevance of topography, maturation, development, and stress response. It also discusses how these factors have been used to identify ß-cell subtypes, and how heterogeneity is impacted by diabetes. We examine open questions in the field and discuss recent technological innovations that could advance understanding of ß-cell heterogeneity in health and disease.

Prognostic implications of neutrophil-lymphocyte ratio in COVID-19.

BACKGROUND: The clinical presentation of COVID-19 ranges from a mild, self-limiting disease, to multiple organ failure and death. Most severe COVID-19 cases present low lymphocytes counts and high leukocytes counts, and accumulated evidence suggests that in a subgroup of patients presenting severe COVID-19, there may be a hyperinflammatory response driving a severe hypercytokinaemia which may be, at least in part, signalling the presence of an underlying endothelial dysfunction. In this context, available data suggest a prognostic role of neutrophil-lymphocyte ratio (NLR) in various inflammatory diseases and oncological processes. Following this rationale, we hypothesized that NLR, as a marker of endothelial dysfunction, may be useful in identifying patients with a poor prognosis in hospitalized COVID-19 cases. DESIGN: A retrospective observational study performed at Hospital Universitario HM Puerta del Sur, Madrid, Spain, which included 119 patients with COVID-19 from 1 March to 31 March 2020. Patients were categorized according to WHO R&D Expert Group. RESULTS: Forty-five (12.1%) patients experienced severe acute respiratory failure requiring respiratory support. Forty-seven (12.6%) patients died. Those with worse outcomes were older (P = .002) and presented significantly higher NLR at admission (P = .001), greater increase in Peak NLR (P < .001) and higher increasing speed of NLR (P = .003) compared with follow-up patients. In a multivariable logistic regression, age, cardiovascular disease and C-reactive protein at admission and Peak NLR were significantly associated with death. CONCLUSIONS: NLR is an easily measurable, available, cost-effective and reliable parameter, which continuous monitoring could be useful for the diagnosis and treatment of COVID-19.

Liver Fibrosis and Metabolic Alterations in Adults With alpha-1-antitrypsin Deficiency Caused by the Pi*ZZ Mutation.

BACKGROUND & AIMS: Alpha-1 antitrypsin deficiency (AATD) is among the most common genetic disorders. Severe AATD is caused by a homozygous mutation in the SERPINA1 gene that encodes the Glu342Lys substitution (called the Pi*Z mutation, Pi*ZZ genotype). Pi*ZZ carriers may develop lung and liver diseases. Mutation-associated lung disorders have been well studied, but less is known about the effects in liver. We assessed the liver disease burden and associated features in adults with this form of AATD. METHODS: We collected data from 554 Pi*ZZ adults (403 in an exploratory cohort, 151 in a confirmatory cohort), in 9 European countries, with AATD who were homozygous for the Pi*Z mutation, and 234 adults without the Pi*Z mutation (controls), all without pre-existing liver disease. We collected data on demographic parameters, comorbidities, lung- and liver-related health, and blood samples for laboratory analysis. Liver fibrosis was assessed non-invasively via the serum tests Aspartate Aminotransferase to Platelet Ratio Index and HepaScore and via transient elastography. Liver steatosis was determined via transient elastography-based controlled attenuation parameter. We performed histologic analyses of livers from transgenic mice that overexpress the AATD-associated Pi*Z variant. RESULTS: Serum levels of liver enzymes were significantly higher in Pi*ZZ carriers vs controls. Based on non-invasive tests for liver fibrosis, significant fibrosis was suspected in 20%-36% of Pi*ZZ carriers, whereas signs of advanced fibrosis were 9- to 20-fold more common in Pi*ZZ carriers compared to non-carriers. Male sex; age older than 50 years; increased levels of alanine aminotransferase, aspartate aminotransferase, or γ-glutamyl transferase; and low numbers of platelets were associated with higher liver fibrosis burden. We did not find evidence for a relationship between lung function and liver fibrosis. Controlled attenuation parameter ≥280 dB/m, suggesting severe steatosis, was detected in 39% of Pi*ZZ carriers vs 31% of controls. Carriers of Pi*ZZ had lower serum concentrations of triglyceride and low- and very-low-density lipoprotein cholesterol than controls, suggesting impaired hepatic secretion of lipid. Livers from Pi*Z-overexpressing mice had steatosis and down-regulation of genes involved in lipid secretion. CONCLUSIONS: In studies of AATD adults with the Pi*ZZ mutation, and of Pi*Z-overexpressing mice, we found evidence of liver steatosis and impaired lipid secretion. We identified factors associated with significant liver fibrosis in patients, which could facilitate hepatologic assessment and counseling of individuals who carry the Pi*ZZ mutation. ClinicalTrials.gov Number NCT02929940.

Hydroa Vacciniforme-Like T-Cell Lymphoma: A Further Brazilian Case.

Hydroa vacciniforme (HV)-like lymphoma is a rare, usually fatal Epstein-Barr virus-driven lymphoproliferative disease affecting children from Asia, Mexico, and South America. Cutaneous manifestations imitate HV, a benign photodermatosis in which systemic symptoms are not observed, and spontaneous regression occurs later in adolescence or young adulthood. We report a case of HV-like lymphoma in a 12-year-old girl, descendent from an ancient Amazon indigenous tribe that, as far as we know, represents the second Brazilian case ever reported in the medical literature.

MonoSeq Variant Caller Reveals Novel Mononucleotide Run Indel Mutations in Tumors with Defective DNA Mismatch Repair.

Next-generation sequencing has revolutionized cancer genetics, but accurately detecting mutations in repetitive DNA sequences, especially mononucleotide runs, remains a challenge. This is a particular concern for tumors with defective mismatch repair (MMR) that accumulate strand-slippage mutations. We developed MonoSeq to improve indel mutation detection in mononucleotide runs, and used MonoSeq to investigate strand-slippage mutations in endometrial cancers, a tumor type that has frequent loss of MMR. We performed extensive Sanger sequencing to validate both clonal and subclonal MonoSeq mutation calls. Eighty-one regions containing mononucleotide runs were sequenced in 540 primary endometrial cancers (223 with defective MMR). Our analyses revealed that the overall mutation rate in MMR-deficient tumors was 20-30-fold higher than in MMR-normal tumors. MonoSeq analysis identified several previously unreported mutations, including a novel hotspot in an A7 run in the terminal exon of ARID5B.The ARID5B indel mutations were seen in both MMR-deficient and MMR-normal tumors, suggesting biologic selection. The analysis of tumor mRNAs revealed the presence of mutant transcripts that could result in translation of neopeptides. Improved detection of mononucleotide run strand-slippage mutations has clear implications for comprehensive mutation detection in tumors with defective MMR. Indel frameshift mutations and the resultant antigenic peptides could help guide immunotherapy strategies.

Determination of the ratio of fluorophore/nanoparticle for fluorescence-labelled nanoparticles.

Optical analysis based on fluorescence labeling has been extensively used for the selective tagging of a wide range of biomedical important targets or for sensing purposes. Fluorescent nanoparticles (NPs) offer interesting properties as labels, as they can be also used as active labels that change their properties upon changes in the environment, such as pH- or distance-dependent fluorescence. In case NPs are not intrinsically fluorescent, they can be made fluorescent by attaching fluorophores to their volume and/or surface. Dye-labelled NPs can produce a highly amplified optical signal compared to a single dye molecule, as there are many dye molecule attached to each NP, providing a great improvement in analytical sensitivity. However, an appropriate control to quantify the fluorophore/NP ratio is required to succeed in the preparation of quantitative platforms matching the required application. Here a methodology to determine such parameter, the fluorophore/NP ratio, is presented. The methodology combines data obtained from UV/Vis absorption spectroscopy for determination of the dye concentration and inductively coupled plasma-mass spectrometry (ICP-MS) analysis for determination of the NP concentration. To validate the approach, it has been applied to the analysis of different sets of fluorophore-NP conjugates prepared using diverse fluorescent dyes (i.e. fluorophores with different structures and emissions) and several types of NPs (i.e. PbS QDs, Au NPs and FePt NPs). The fluorophore-NP conjugates hereby were designed to incorporate the dye directly into an amphiphilic polymer coating. The developed methodology allows for quantification of fluorophore-NP coupling, and therefore, opens up the possibility of selecting controlled conjugates.

Clear Cell Papulosis: Report of a Case With Unique Clinical and Histologic Findings.

Clear cell papulosis is a rare, self-limited, benign disease of early childhood, characterized by white macules and flat papules over the milk line. Histopathologically, it is characterized by scattered clear cells throughout the basal and/or suprabasal epidermal layers, which-as clear cells of Toker of the nipple do-typically express cytokeratin 7. They also exhibit other markers expected for adenoid differentiation, such as low-molecular weight cytokeratins, carcinoembryonic antigen, epithelial membrane antigen, and mucin. The age of onset, distribution of lesions, histopathology, and its benign behavior nature help to exclude clinically similar conditions, either benign or malignant. The authors report a case of clear cell papulosis in a 7-year-old Brazilian girl in whom lesions were observed on the legs and histologically formed by solid and adenoid aggregates of clear cells, in a similar fashion than clear fetal cells of Toker.

Polymer-Matrix Composites: Characterising the Impact of Environmental Factors on Their Lifetime.

Polymer-matrix composites are widely used in engineering applications. Yet, environmental factors impact their macroscale fatigue and creep performances significantly, owing to several mechanisms acting at the microstructure level. Herein, we analyse the effects of water uptake that are responsible for swelling and, over time and in enough quantity, for hydrolysis. Seawater, due to a combination of high salinity and pressures, low temperature and biotic media present, also contributes to the acceleration of fatigue and creep damage. Similarly, other liquid corrosive agents penetrate into cracks induced by cyclic loading and cause dissolution of the resin and breakage of interfacial bonds. UV radiation either increases the crosslinking density or scissions chains, embrittling the surface layer of a given matrix. Temperature cycles close to the glass transition damage the fibre-matrix interface, promoting microcracking and hindering fatigue and creep performance. The microbial and enzymatic degradation of biopolymers is also studied, with the former responsible for metabolising specific matrices and changing their microstructure and/or chemical composition. The impact of these environmental factors is detailed for epoxy, vinyl ester and polyester (thermoset); polypropylene, polyamide and poly etheretherketone (thermoplastic); and for poly lactic acid, thermoplastic starch and polyhydroxyalkanoates (biopolymers). Overall, the environmental factors mentioned hamper the fatigue and creep performances, altering the mechanical properties of the composite or causing stress concentrations through microcracks, promoting earlier failure. Future studies should focus on other matrices beyond epoxy as well as on the development of standardised testing methods.

Colloidal Silver Nanoparticles Obtained via Radiolysis: Synthesis Optimization and Antibacterial Properties.

Silver nanoparticles (AgNPs) with broad-spectrum antimicrobial properties are gaining increasing interest in fighting multidrug-resistant bacteria. Herein, we describe the synthesis of AgNPs, stabilized by polyvinyl alcohol (PVA), with high purity and homogeneous sizes, using radiolysis. Solvated electrons and reducing radicals are induced from solvent radiolysis and no other chemical reducing agents are needed to reduce the metal ions. Another advantage of this method is that it leads to sterile colloidal suspensions, which can be directly used for medical applications. We systematically investigated the effect of the silver salt precursor on the optical properties, particle size, and morphology of the resulting colloidal AgNPs. With Ag2SO4 precursor, the AgNPs displayed a narrow size distribution (20 ± 2 nm). In contrast, AgNO3 and AgClO4 precursors lead to inhomogeneous AgNPs of various shapes. Moreover, the optimized AgNPs synthesized from Ag2SO4 were stable upon storage in water and phosphate-buffered saline (PBS) and were very effective in inhibiting the growth of Staphylococcus aureus (S. aureus) at a concentration of 0.6 µg·mL-1 while completely eradicating it at a concentration of 5.6 µg·mL-1. When compared with other AgNPs prepared by other strategies, the remarkable bactericidal ability against S. aureus of the AgNPs produced here opens up new perspectives for further applications in medicine, cosmetics, the food industry, or in elaborating antibacterial surfaces and other devices.

Effects of Cow's Milk Processing on MicroRNA Levels.

MicroRNAs (miRNAs) regulate gene expression and might resist adverse physicochemical conditions, which makes them potential biomarkers. They are being investigated as biomarkers of dairy production systems, based on the variations in their levels in raw milk depending on animal diet and management. Whether miRNA levels can serve as biomarkers for dairy products remains unclear, since technological or culinary treatments, such as fermentation, may alter their levels. Here, 10 cow dairy farms were sampled in Asturias (north-west Spain) and milk samples were subjected to microwave heating or used to produce yogurt or cheese. Total RNA was isolated from raw milk and three derived products, and levels of seven miRNAs, selected based on previous studies as possible milk production system biomarkers, were assessed by RT-qPCR. The treatments decreased levels of all miRNAs to some extent. These results also imply that cheesemaking increases the concentration of miRNAs in this product; raw milk and cheese supposedly may provide similar concentrations of miRNAs, higher than those of yogurt and microwaved milk. They also indicate that the content of certain miRNAs in raw milk cannot necessarily be extrapolated to other dairy products.

Industrial impact on sustainable dairy farms: Essential elements, hazardous metals and polycyclic aromatic hydrocarbons in forage and cow's milk.

Sustainable dairy farms are characterised by the self-production of forage for animal feed. These farms are sometimes located near industrial areas, entailing a risk of food chain contamination with hazardous metals and polycyclic aromatic hydrocarbons (PAHs). Accordingly, evaluating the impact of pollution on forage and milk is of great interest. In this study, the effects of industrial factors on sustainable forage from 43 dairy farms and possible correlations between inorganic elements and PAHs were studied. Spearman's correlation and principal component analysis (PCA) were performed for the forage and milk. Most of the inorganic elements in the forage were below the maximum residual limits for cadmium (Cd) and lead (Pb), established in EU 2013/1275 and EU 2019/1869, respectively. However, arsenic (As) and mercury (Hg) levels were above their respective limits in the forage (EU 2019/1869). No milk samples exceeded the maximum residual limits for Pb (EU 488/2014) or Cd (EU 1881/2006) in dairy products. Heavy-weight PAHs (HW-PAHs, four or more aromatic rings) were detected in forage but not in milk. In the forage samples, HW-PAHs were positively correlated with Zn and Cd. In addition, some hazardous metals (chromium (Cr), iron (Fe), As, Hg, and Pb) also were positively correlated with Zn and Cd. Interestingly, no correlations were found between forage pollutants and milk, suggesting that these pollutants have a low transfer rate to milk. The PCA results highlighted the predominant contribution of PAHs to the global variance in forage samples collected at different distances from industrial areas. In milk, the contributions of hazardous metals and PAHs were more balanced than in forages. Finally, when distances to potential pollution sources were included in the PCA of forage samples, a negative correlation was observed between the former and the concentrations of HW-PAHs, Cd, and Zn, suggesting that thermal power plants and steel factory emissions were the main sources of polluting forage in this area.

Impact of Potentially Toxic Compounds in Cow Milk: How Industrial Activities Affect Animal Primary Productions.

Potentially toxic elements (PTEs) and polycyclic aromatic hydrocarbons (PAHs) frequently coexist in soils near industrial areas and sometimes in environmental compartments directly linked to feed (forage) and food (milk) production. However, the distribution of these pollutants along the dairy farm production chain is unclear. Here, we analyzed soil, forage, and milk samples from 16 livestock farms in Spain: several PTEs and PAHs were quantified. Farms were compared in terms of whether they were close to (<5 km) or far away from (>5 km) industrial areas. The results showed that PTEs and PAHs were enriched in the soils and forages from farms close to industrial areas, but not in the milk. In the soil, the maximum concentrations of PTEs reached 141, 46.1, 3.67, 6.11, and 138 mg kg-1 for chromium, arsenic, cadmium, mercury, and lead, respectively, while fluoranthene (172.8 µg kg-1) and benzo(b)fluoranthene (177.4 µg kg-1) were the most abundant PAHs. Principal component analysis of the soil PTEs suggested common pollution sources for iron, arsenic, and lead. In the forage, the maximum contents of chromium, arsenic, cadmium, mercury, and lead were 32.8, 7.87, 1.31, 0.47, and 7.85 mg kg-1, respectively. The PAH found in the highest concentration in the feed forage was pyrene (120 µg kg-1). In the milk, the maximum PTE levels were much lower than in the soil or the feed forages: 74.1, 16.1, 0.12, 0.28, and 2.7 µg kg-1 for chromium, arsenic, cadmium, mercury, and lead, respectively. Neither of the two milk samples exceeded the 20 µg kg-1 limit for lead set in EU 1881/2006. Pyrene was the most abundant PAH found in the milk (39.4 µg kg-1), while high molecular weight PAHs were not detected. For PTEs, the results showed that soil-forage transfer factors were higher than forage-milk ratios. Our results suggest that soils and forages around farms near industries, as well as the milk produced from those farms, have generally low levels of PTE and PAH contaminants.

Radiotherapy for Brain Metastases Near the End of Life: Characterizing Patients and Tumor Features.

PURPOSE: Patients with brain metastases are often referred for brain radiotherapy (BrRT) when exclusive palliative management would be more appropriate. To assess the indication of BrRT during end-of-life (EOL) care and evaluate the characteristics of the patients who underwent the treatment. METHODS: This retrospective study comprised patients from four independent oncology centers who had undergone BrRT for metastases. The variables included were Karnofsky performance status (KPS), primary tumor site, metastatic status, neurologic symptomatic status, the number and size of metastases, posterior fossa or meningeal involvement, type of BrRT, having undergone brain metastasectomy, and the availability of systemic therapies after BrRT. Patients were allocated into three subgroups with ≤30, 31-60, and 61-90 days of survival, and a control group of patients who survived >90 days. RESULTS: A total of 546 patients were included in the study. A KPS of <70 (P = .021), the number of brain metastases (P = .001), the lack of brain metastasectomy (P = .006), and the lack of systemic therapies after BrRT (P = .047) were significantly associated with the EOL subgroups. Multivariate analysis showed that a KPS of <70 (P < .001), the lack of brain metastasectomy (P = .015), and the lack of systemic therapies after BrRT (P = .027) were significantly associated with worse survival. In all, 241 (44.1%) patients died within 90 days-120 (22.0%) within 30 days, 75 (13.7%) within 31-60 days, and 46 (8.4%) within 61-90 days of BrRT. Patients with colorectal cancer were significantly more likely to die within 90 days of BrRT than >90 days. CONCLUSION: Considering patients' performance status and whether they are candidates for brain metastasectomy or systemic therapies after BrRT is critical to improving BrRT benefits in scenarios of EOL.

LipoParticles: a lipid membrane coating onto polymer particles to enhance the internalization in osteoblast cells.

LipoParticles, core-shell assemblies consisting of a polymer core coated by a lipid membrane, are promising carriers for drug delivery applications with intracellular targets. This is of great interest since it is actually challenging to treat infections involving intracellular bacteria such as bone and joint infections where the bacteria are hidden in osteoblast cells. The present work reports for the first time to the best of our knowledge the proof of enhanced internalization of particles in osteoblast cells thanks to a lipid coating of particles (= LipoParticles). The ca. 300 nm-sized assemblies were elaborated by reorganization of liposomes (composed of DPPC/DPTAP 10/90 mol/mol) onto the surface of poly(lactic-co-glycolic acid) (PLGA) particles, and were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and zetametry. Optimization of these assemblies was also performed by adding poly(ethylene glycol) (PEG) chains on their surface (corresponding to a final formulation of DPPC/DPTAP/DPPE-PEG5000 8/90/2 mol/mol/mol). Interestingly, this provided them colloidal stability after their 20-fold dilution in PBS or cell culture medium, and made possible their freeze-drying without forming aggregates after their re-hydration. Their non-cytotoxicity towards a human osteoblast cell line (MG63) was also demonstrated. The enhanced internalization of LipoParticles in this MG63 cell line, in comparison with PLGA particles, was proven by observations with a confocal laser scanning microscope, as well as by flow cytometry assays. Finally, this efficient internalization of LipoParticles in MG63 cells was confirmed by TEM on ultrathin sections, which also revealed localization close to intracellular Staphylococcus aureus.

Parent-of-origin effects propagate through networks to shape metabolic traits.

Parent-of-origin effects are unexpectedly common in complex traits, including metabolic and neurological traits. Parent-of-origin effects can be modified by the environment, but the architecture of these gene-by-environmental effects on phenotypes remains to be unraveled. Previously, quantitative trait loci (QTL) showing context-specific parent-of-origin effects on metabolic traits were mapped in the F16 generation of an advanced intercross between LG/J and SM/J inbred mice. However, these QTL were not enriched for known imprinted genes, suggesting another mechanism is needed to explain these parent-of-origin effects phenomena. We propose that non-imprinted genes can generate complex parent-of-origin effects on metabolic traits through interactions with imprinted genes. Here, we employ data from mouse populations at different levels of intercrossing (F0, F1, F2, F16) of the LG/J and SM/J inbred mouse lines to test this hypothesis. Using multiple populations and incorporating genetic, genomic, and physiological data, we leverage orthogonal evidence to identify networks of genes through which parent-of-origin effects propagate. We identify a network comprised of three imprinted and six non-imprinted genes that show parent-of-origin effects. This epistatic network forms a nutritional responsive pathway and the genes comprising it jointly serve cellular functions associated with growth. We focus on two genes, Nnat and F2r, whose interaction associates with serum glucose levels across generations in high-fat-fed females. Single-cell RNAseq reveals that Nnat expression increases and F2r expression decreases in pre-adipocytes along an adipogenic trajectory, a result that is consistent with our observations in bulk white adipose tissue.

Prevalence and Progression of Incidental Terminal Ileitis on Non-diagnostic Colonoscopy: A Systematic Review and Meta-analysis.

BACKGROUND: Incidentally diagnosed terminal ileitis [IDTI] has been reported among asymptomatic persons undergoing non-diagnostic colonoscopy. The purpose of our study was to determine the prevalence and long-term outcomes of asymptomatic terminal ileitis. METHODS: We performed a systematic review using three biomedical databases [Medline, Embase, and Web of Science] and relevant scientific meeting abstracts. We identified observational studies that reported the prevalence of IDTI in adults undergoing screening or polyp surveillance colonoscopy and/or the long-term outcomes of such lesions. A random-effects meta-analysis was conducted to determine the pooled prevalence rate of IDTI. The progression of IDTI to overt Crohn's disease [CD] was also described. RESULTS: Of 2388 eligible studies, 1784 were screened after excluding duplicates, 84 were reviewed in full text, and 14 studies were eligible for inclusion. Seven studies reported the prevalence of IDTI in 44 398 persons undergoing non-diagnostic colonoscopy, six studies reported follow-up data, and one study reported both types of data. The pooled prevalence rate of IDTI was 1.6% (95% confidence interval [CI] 0.1-21.8%) with significant heterogeneity [I2 = 99.7]. Among patients who had undergone non-diagnostic colonoscopy and had follow-up data [range 13-84 months reported in five studies], progression to overt CD was rare. CONCLUSIONS: IDTI is not uncommon on non-diagnostic colonoscopies. Based on limited data, the rate of its progression to overt CD seems low, and watchful waiting is likely a reasonable strategy. Further long-term follow-up studies are needed to inform the natural history of incidental terminal ileitis, factors that predict progression to CD, and therapeutic implications.

Computational and experimental analysis of a Glaucoma flat drainage device.

This paper presents a computational and experimental analysis of a glaucoma flat drainage device (FDD). The FDD consists of a metallic microplate placed into the eye sclerocorneal limbus, which creates a virtual path between the anterior chamber and its exterior, allowing the intraocular pressure (IOP) to be kept in a normal range. It also uses the surrounding tissue as a flow regulator in order to provide close values of IOP for a wide range of aqueous humor (AH) flow rates. The Neo Hookean hyperelastic model is used for the solid part, while the Reynolds thin film fluid model is used for the fluid part. On the other hand, a gravitational-driven flow test is implemented in order to validate the simulation process. An in vitro experiment evaluated the flow characteristics of the device implanted in fourteen extirpated pig eyes, giving as a result the best-fit for the Young modulus of the tissue surrounding the device. Finally, according to the resulting computational model, for a range of 1.4-3.1 µL/min, the device presents a pressure variation range of 6-7.5 mmHg.

Lymphoma presented as dysphagia: a diagnosis hard to swallow.

An 18-year-old woman presented with progressive oesophageal dysphagia, weight loss and night sweats over a 6-month period. Oesophagogastroduodenoscopy revealed a diffuse luminal narrowing with normal mucosa, whose biopsies were inconclusive. A cervical and thoracic CT scan showed a thickening of the upper oesophagus, densification of the mediastinal fat, several adenopathies and a 4.3×2.4 cm mass with infiltrative appearance and heterogeneous enhancement in right cervical paravertebral location. Positron emission tomography-CT showed marked increased fluorodeoxyglucose uptake in supradiaphragmatic lymph nodes, pleuropulmonary tissue, paraspinal musculature and bone marrow. Imaging-guided and surgical incisional biopsies of the paravertebral mass were inconclusive. During hospitalisation, she developed right cervicobrachial paraesthesia. Only excisional biopsy of the mass allowed the diagnosis of high-grade B-cell lymphoma not otherwise specified, Ann Arbor stage IV-B. The patient underwent chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone), followed by R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin hydrochloride). Follow-up at 12 months revealed complete response.