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Grape pomace (GP) and pecan shell (PS) are two by-products rich in phenolic compounds (PC), and dietary fiber (DF) that may be considered for the development of functional baked foods. In this study, four formulations with different GP:PS ratios (F1(8%:5%), F2(5%:5%), F3(5%:2%), F4(0%:5%), and control bread (CB)) were elaborated and characterized (physiochemical and phytochemical content). Also, their inner structure (SEM), changes in their FTIR functional group's vibrations, and the bioaccessibility of PC and sugars, including an in vitro glycemic index, were analyzed. Results showed that all GP:PS formulations had higher mineral, protein, DF (total, soluble, and insoluble), and PC content than CB. Additionally, PC and non-starch polysaccharides affected gluten and starch absorbance and pores distribution. In vitro digestion model showed a reduction in the glycemic index for all formulations, compared to CB. These findings highlight the possible health benefits of by-products and their interactions in baked goods.

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OBJECTIVES: Patients with systemic sclerosis present with severe gastroesophageal reflux disease, often refractory to proton-pump inhibitors (PPI) treatment. The aim of the present study was to identify factors associated with PPI-refractory esophagitis. METHODS: We performed a cross-sectional study in a single-center cohort of patients diagnosed with systemic sclerosis. We included patients who underwent an esophagogastroduodenoscopy while on PPI treatment. Patients with PPI-refractory erosive esophagitis were compared with those with endoscopically normal esophageal mucosa. RESULTS: A total of 69 patients were included, from these, 23 patients (33%) had PPI-refractory esophagitis (Grade A, n = 11; Grade B, n = 7; Grade C, n = 2; Grade D, n = 3) and 46 (67%) had an endoscopically normal esophageal mucosa. On univariate analysis, patients with PPI-refractory esophagitis were more frequently diffuse SSc subset (43% vs 17%; p= 0.041). Evaluating gastrointestinal motility tests, neither absent esophageal contractility (39% vs 25%, p= 0.292) nor hypotensive lower esophageal sphincter (47% vs 44%, p= 0.980) were significantly associated with PPI-refractory esophagitis. Gastrointestinal dysmotility, defined as abnormal gastric emptying and/or small bowel dilated loops, was significantly associated with PPI-refractory esophagitis (66 vs 8%, p = <0.001). On a multivariate regression model to evaluate the association between motility test results adjusted for the diffuse subset, gastrointestinal dysmotility (ß = 0.751, p= 0.010) was independently associated with PPI-refractory esophagitis, while absent esophageal contractility (ß = 0.044, p= 0.886) or a hypotensive LES were not (ß=-0.131, p= 0.663). CONCLUSIONS: Our findings suggest that gastric and small intestinal motor dysfunction may be an important contributor to the development of PPI-refractory esophagitis in patients with systemic sclerosis.

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Toxoplasmosis is a worldwide parasitosis that is usually asymptomatic; cell-mediated immunity, particularly T cells, is a crucial mediator of the immune response against this parasite. Membrane protein expression has been studied for a long time in T lymphocytes, providing vital information to determine functional checkpoints. However, less is known about the role of post-translational modifications in T cell function. Glycosylation plays essential roles during maturation and function; particularly, sialic acid modulation is determinant for accurate T cell regulation of processes like adhesion, cell-cell communication, and apoptosis induction. Despite its importance, the role of T cell sialylation during infection remains unclear. Herein, we aimed to evaluate whether different membrane sialylation motifs are modified in T cells during acute Toxoplasma gondii infection using different lectins. To this end, BALB/c Foxp3EGFP mice were infected with T. gondii, and on days 3, 7, and 10 post-infection, splenocytes were obtained to analyze conventional (Foxp3-) CD4+ and CD8+ populations by flow cytometry. Among the different lectins used for analysis, only Sambucus nigra lectin, which detects sialic acid α2,6 linkages, revealed two distinctive populations (SNBright and SN-/Dim) after infection. Further characterization of CD4+ and CD8+ SN-/Dim lymphocytes showed that these are highly activated cells, with a TEf/EM or TCM phenotype that produce high IFN-γ levels, a previously undescribed cell state. This work demonstrates that glycan membrane analysis in T cells reveals previously overlooked functional states by evaluating only protein expression.

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Doyne honeycomb retinal dystrophy (DHRD), also termed malattia leventinese (MLVT), is a dominantly inherited ocular disease characterized by the progressive accumulation of macular and peripapillary drusenoid material beneath the retinal pigment epithelium in the Bruch membrane. In all affected individuals genetically characterized to date, DHRD/MLVT is caused by a single heterozygous p.Arg345Trp missense variant in the EGF-containing fibulin-like extracellular matrix protein 1, EFEMP1. Recently, pathogenic variants in the EFEMP1 gene have also been demonstrated in several families with juvenile or adult-onset hereditary isolated glaucoma. Here, we describe a family featuring a unique phenotype of juvenile glaucoma and DHRD/MLVT caused by a novel EFEMP1 variant. Our results expand both the ocular phenotype associated with EFEMP1 variants and the molecular spectrum causing DHRD by describing the first non-p.Arg345Trp EFEMP1 pathogenic allele.

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SARS-CoV-2 infects via the respiratory tract, but COVID-19 includes an array of non-respiratory symptoms, among them gastrointestinal (GI) manifestations such as vomiting and diarrhea. Here we investigated the GI pathology of SARS-CoV-2 infections in rhesus macaques and humans. Macaques experienced mild infection with USA-WA1/2020 and shed viral RNA in the respiratory tract and stool, including subgenomic RNA indicative of replication in the GI tract. Intestinal immune cell populations were disturbed, with significantly fewer proliferating (Ki67+) jejunal B cells in SARS-CoV-2-infected macaques than uninfected ones. Modest translocation of bacteria/bacterial antigen was observed across the colonic epithelium, with a corresponding significant increase in plasma soluble CD14 (sCD14) that may be induced by LPS. Human plasma demonstrated significant decreases in interleukin (IL)-6 and sCD14 upon recovery from COVID-19, suggesting resolution of inflammation and response to translocated bacteria. sCD14 significantly positively correlated with zonulin, an indicator of gut barrier integrity, and IL-6. These results demonstrate that GI perturbations such as microbial translocation can occur in even mild SARS-CoV-2 infections and may contribute to the COVID-19 inflammatory state.IMPORTANCEThis study investigates gastrointestinal (GI) barrier disruption in SARS-CoV-2 infections and how it may contribute to disease. We observed bacteria or bacterial products crossing from the colon interior (the lumen) to the lamina propria during SARS-CoV-2 infection in macaques. Bacteria/bacterial products are tolerated in the lumen but may induce immune responses if they translocate to the lamina propria. We also observed a significant increase in soluble CD14, which is associated with an immune response to bacterial products. In addition, we observed that humans recovering from COVID-19 experienced a significant decrease in soluble CD14, as well as the inflammatory marker interleukin (IL)-6. IL-6 and sCD14 correlated significantly across macaque and human samples. These findings suggest that SARS-CoV-2 infection results in GI barrier disruption that permits microbial translocation and a corresponding immune response. These findings could aid in developing interventions to improve COVID-19 patient outcomes.

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Herbivorous insects and their host plants comprise most known species on Earth. Illuminating how herbivory repeatedly evolved in insects from non-herbivorous lineages is critical to understanding how this biodiversity is created and maintained. We characterized the trophic niche of Scaptomyza flava, a representative of a lineage nested within the Drosophila that transitioned to herbivory ~10-15 million years ago. We used natural history studies to determine if S. flava is a true herbivore or a cryptic microbe-feeder, given that the ancestral character state for the family Drosophilidae is likely microbe-feeding. Specifically, we quantified oviposition substrate choice and larval viability across food-types, trophic-related morphological traits, and nitrogen isotope and sterol profiles across putatively herbivorous and non-herbivorous drosophilids. The results of these studies show that S. flava is an obligate herbivore of living plants. Paired with its genetic model host, Arabidopsis thaliana, S. flava is a novel and powerful system for exploring mechanisms underlying the evolution of herbivory, a complex trait that enabled the exceptional diversification of insects.

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CONTEXT: Heavy menstrual bleeding (HMB) is common and debilitating, but the precise endometrial mechanisms causing increased menstrual blood loss (MBL) remain undefined. We have previously identified a role for hypoxia in endometrial repair following progesterone withdrawal. OBJECTIVE: As hypoxia inducible factor 2 alpha (HIF2A) is known to alter vascular function in other tissues, we hypothesised that endometrial HIF2A is involved in pre-menstrual optimisation of endometrial function during the secretory phase to limit MBL. RESULTS: Women with objective HMB had higher endometrial HIF2A during the mid-secretory phase when compared to those with normal MBL (p=0.0269). In a mouse model of simulated menses, genetic or pharmacological manipulation of HIF2A did not significantly affect endometrial breakdown/repair, volume of MBL or endometrial hypoxia. However, 88% of Hif2a heterozygote mice reached early-full repair by 24h versus only 65% of wild-type mice. Mean MBL was 0.39 µl (±0.67) in Hif2a heterozygote mice versus 0.98 µl (±0.79) in wild-type mice. Conversely, when we increased HIF2A pre-menstrually, 11% reached early repair at by 8h versus 30% of vehicle-treated mice. Mean MBL was 2.61 µl (±1.10) in mice with HIF2A stabilisation and 2.24 µl (±1.14) in vehicle-treated mice. These non-significant but consistent trends indicate that increased endometrial HIF2A may contribute to delayed endometrial repair and HMB. CONCLUSIONS: Increased HIF2A in the secretory endometrium is unlikely to be sufficient to account for the phenotype of HMB, but limitation of HIF2 levels may optimise endometrial function at menstruation.

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BACKGROUND: Potential differences in organ preservation between total neoadjuvant therapy (TNT) regimens integrating long-course chemoradiotherapy (LCCRT) and short-course radiotherapy (SCRT) in rectal cancer remain undefined. PATIENTS AND METHODS: This natural experiment arose from a policy change in response to the COVID-19 pandemic during which our institution switched from uniformly treating patients with LCCRT to mandating that all patients be treated with SCRT. Our study includes 323 locally advanced rectal adenocarcinoma patients treated with LCCRT-based or SCRT-based TNT from January 2018 to January 2021. Patients who achieved clinical complete response were offered organ preservation with watch-and-wait (WW) management. The primary outcome was 2-year organ preservation. Additional outcomes included local regrowth, distant recurrence, disease-free survival (DFS), and overall survival (OS). RESULTS: Patient and tumor characteristics were similar between LCCRT (n = 247) and SCRT (n = 76) cohorts. Median follow-up was 31 months. Similar clinical complete response rates were observed following LCCRT and SCRT (44.5% versus 43.4%). Two-year organ preservation was 40% [95% confidence interval (CI) 34% to 46%] and 31% (95% CI 22% to 44%) among all patients treated with LCCRT and SCRT, respectively. In patients managed with WW, LCCRT resulted in higher 2-year organ preservation (89% LCCRT, 95% CI 83% to 95% versus 70% SCRT, 95% CI 55% to 90%; P = 0.005) and lower 2-year local regrowth (19% LCCRT, 95% CI 11% to 26% versus 36% SCRT, 95% CI 16% to 52%; P = 0.072) compared with SCRT. The 2-year distant recurrence (10% versus 6%), DFS (90% versus 90%), and OS (99% versus 100%) were similar between WW patients treated with LCCRT and SCRT, respectively. CONCLUSIONS: While WW eligibility was similar between cohorts, WW patients treated with LCCRT had higher 2-year organ preservation and lower local regrowth than those treated with SCRT, yet similar DFS and OS. These data support induction LCCRT followed by consolidation chemotherapy as the preferred TNT regimen for patients with locally advanced rectal cancer pursuing organ preservation.

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The blubber is the characteristic fatty tissue of most marine mammals; it comprises adipocytes, blood vessels, lymphatics, and abundant collagen and elastic fibers. Containing the reserve of excess and accumulated energy from feeding. Previous studies found that the adipocyte area may change according to the amount of accumulated and expended energy during migration, reproduction, lactation and breeding. This cellular characteristic reflects the energetic status of an individual (i.e., the balance between intake and total energy investment), which can be interpreted as reproductive success and general health. In the present study, we measured the adipocyte area of the gray whales wintering in Laguna San Ignacio, Baja California Sur, Mexico, to evaluate body condition. Adipose tissue was sampled from 116 individuals (31 calves, 22 mothers, and 63 solitary individuals) over a study period of 62 days. Each whale was assigned a priori body condition (good, fair, poor). Histological preparations stained with hematoxylin-eosin were microphotographs used to measure the adipocyte area with the software Adiposoft as a plugin to ImageJ. The adipocyte area of the calves was significantly lower than that of the adults and showed an increase during the study period. The three body condition categories found no differences in the adipocyte area. The adipocyte area analysis applied in the present study appears to be a useful tool in assessing body condition in calves, although it appears to be limited to adults. According to the OneHealth paradigm, environmental health is closely related to the health of the gray whale, which in turn is related to public health and the socioeconomic well-being of local communities that use this species as a resource.

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The current diagnostic criteria for the autism spectrum disorder (ASD) include the possibility to specify concomitant language difficulties. Purpose: Our main aim was to explore whether children with ASD-Level 1 (ASD-L1) present difficulties in the acquisition of structural language, as little work has been done in this regard so far. As a secondary aim we evaluated the degree to which the potential language impairment in ASD is directly associated with their social communication deficits or it represents a distinct deficit. Methods: To further clarify the nature and characteristics of putative language difficulties in ASD-L1, we evaluated language skills in 89 children and preadolescents diagnosed with ASD-L1, and a group of typically developing participants (TD). All of them were between 8 and 13 years old and had similar socioeconomic backgrounds. Results: Children with ASD-L1 obtained lower scores than those in TD group in repeating sentences, in finding the semantic relationships between words, and in applying word structure rules (morphology). Congruently, the core language standard score was lower in the ASD-L1 group, and the proportion of language delay was significantly higher in the ASD-L1 group than in the control group. Conclusion: Language scores were associated with autistic traits; thus, language performance in ASD-L1 is closely related to autistic symptoms. These results are discussed according to the literature on linguistic deficits in ASD-L1 and their relations with phonological working memory.

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INTRODUCTION: pigmented villonodular synovitis (PVNS) is a benign condition that affects the knee, leading to abnormal proliferation of the synovial membrane and the accumulation of hemosiderin in the joint cavity. Although it can be surgically treated, PVNS tends to have a high recurrence rate, potentially resulting in chronic joint damage. CASE REPORT: we present the case of a young woman who experienced localized pain in her right knee due to a recurrence of PVNS. Magnetic resonance imaging revealed multiple multilobulated cystic lesions affecting the entire joint, including the ligaments. The patient underwent open surgical resection with a favorable clinical outcome. Histopathological examinations confirmed the absence of malignancy. CONCLUSION: while arthroscopy is typically the preferred treatment for PVNS, this case highlights the tendency for recurrence associated with this approach. Open surgical resection, supported by benign histopathological findings in this case, suggests a favorable long-term prognosis.

INTRODUCCIÓN: la sinovitis villonodular pigmentada (SVNP) es una enfermedad benigna que afecta la articulación de la rodilla, que causa una proliferación anormal de la membrana sinovial y la acumulación de hemosiderina en la cavidad articular. A pesar de que es posible tratarla mediante cirugía, la SVNP tiende a tener una alta tasa de recurrencia, lo que puede resultar en daño articular crónico. REPORTE DEL CASO: se presenta el caso de una mujer joven que experimentó dolor localizado en la rodilla derecha debido a una recurrencia de SVNP. La resonancia magnética reveló múltiples lesiones quísticas multilobuladas que afectaban a toda la articulación, incluyendo los ligamentos. La paciente fue sometida a una resección quirúrgica abierta, con una evolución clínica favorable. Los exámenes histopatológicos confirmaron la ausencia de malignidad. CONCLUSIÓN: aunque la artroscopía se considera el tratamiento de elección para la SVNP, este caso ilustra la tendencia a la recurrencia asociada con este enfoque. La resección quirúrgica abierta, respaldada por los hallazgos histopatológicos benignos en este caso, sugiere un pronóstico favorable a largo plazo.

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Background: Adipose tissue excess is associated with adverse health outcomes, including type 2 diabetes. Body mass index (BMI) is used to evaluate obesity but is inaccurate as it does not account for muscle mass, bone density, and fat distribution. Accurate measurement of adipose tissue through dual-energy X-ray absorptiometry (DXA) and computed axial tomography (CT) is crucial for managing and monitoring adiposity-related diseases. Still, these are not easily accessible in most hospitals in Mexico. Bioelectrical impedance analysis (BIA) is non-invasive and low-cost but may not be reliable in conditions affecting the body's hydration status, like diabetes. Objectives: To assess fat mass concordance between BIA and DXA in Hispanic-American adults with type 2 diabetes mellitus (T2DM). Methods: Cross-sectional study of a non-probabilistic sample of subjects over 18 years with type 2 diabetes. We used DXA as the reference method. Results: We evaluated the accuracy of FM estimation through BIA and DXA in 309 subjects with type 2 diabetes. Results showed a trend of overestimating the diagnosis of obesity using BIA, especially in individuals with a higher fat mass index (FMI). At the group level, we found BIA accurate; however, at the individual level, it is not. The bias between the 2 methods showed a statistically significant overestimation of body fat by BIA (P ⩽ .01) in both sexes. BIA demonstrated high precision in estimating fat mass. We were able to provide a correction factor of 0.55 kg in men. Conclusion: BIA is inaccurate compared to DXA for body composition assessment in patients with diabetes. Inaccurate measurements can result in misclassification. However, BIA is precise for body composition assessment in patients with diabetes, so it is reliable for tracking patient progress over time.

Agreement between bioelectrical impedance analysis and dual-energy X-ray absorptiometry to estimate fat mass in adults with type 2 Diabetes Mellitus This study compares 2 methods for measuring body composition in patients with diabetes in Mexico. The first method is Bioelectrical Impedance Analysis (BIA), which is non-invasive, low-cost, and easy to use but may not be reliable in conditions that affect the body's hydration status, like diabetes. The second method is Dual-energy X-ray Absorptiometry (DXA), which is more accurate but less easily accessible. The study was a cross-sectional evaluation of 309 participants over 18 years with type 2 diabetes mellitus (T2DM) by HbA1C levels. The present study found BIA to be precise for body composition assessment but not accurate compared to DXA as the reference method. The study showed a trend of overestimating the diagnosis of obesity using BIA, especially in individuals with a higher fat mass index. This study found BIA is accurate at the group level but not at the individual level. The bias between the 2 methods showed a statistically significant overestimation of body fat by BIA. We provided a correction factor of 0.55 kg in men but not women. BIA is not ideal for diagnosing obesity but is reliable for tracking patient progress over time.

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Knowledge of differential life-history strategies in arbuscular mycorrhizal (AM) fungi is relevant for understanding the ecology of this group and its potential role in sustainable agriculture and carbon sequestration. At present, AM fungal life-history theories often focus on differential investment into intra- vs extraradical structures among AM fungal taxa, and its implications for plant benefits. With this Viewpoint we aim to expand these theories by integrating a mycocentric economics- and resource-based life-history framework. As in plants, AM fungal carbon and nutrient demands are stoichiometrically coupled, though uptake of these elements is spatially decoupled. Consequently, investment in morphological structures for carbon vs nutrient uptake is not in competition. We argue that understanding the ecology and evolution of AM fungal life-history trade-offs requires increased focus on variation among structures foraging for the same element, that is within intra- or extraradical structures (in our view a 'horizontal' axis), not just between them ('vertical' axis). Here, we elaborate on this argument and propose a range of plausible life-history trade-offs that could lead to the evolution of strategies in AM fungi, providing testable hypotheses and creating opportunities to explain AM fungal co-existence, and the context-dependent effects of AM fungi on plant growth and soil carbon dynamics.

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AIMS: This study aimed to assess the effects of AEO in an in vitro model of cell lines derived from cervical cancer-namely, HeLa and SiHa-by screening for AEO's cytotoxic properties and examining its influence on the modulation of gene expression. BACKGROUND: Cervical cancer stands as a prevalent global health concern, affecting millions of women worldwide. The current treatment modalities encompass surgery, radiation, and chemotherapy, but significant limitations and adverse effects constrain their effectiveness. Therefore, exploring novel treatments that offer enhanced efficacy and reduced side effects is imperative. Arborvitae essential oil, extracted from Thuja Plicata, has garnered attention for its antimicrobial, anti-inflammatory, immunomodulatory, and tissue-remodeling properties; however, its potential in treating cervical cancer remains uncharted. OBJECTIVE: The objective of this study was to delve into the molecular mechanisms induced by arborvitae essential oil in order to learn about its anticancer effects on cervical cancer cell lines. METHODS: The methods used in this study were assessments of cell viability using WST-1 and annexin V- propidium iodide, mRNA sequencing, and subsequent bioinformatics analysis. RESULTS: The findings unveiled a dose-dependent cytotoxic effect of arborvitae essential oil on both HeLa and SiHa cell lines. Minor effects were observed only at very low doses in the HaCaT non-tumorigenic human keratinocyte cells. RNA-Seq bioinformatics analysis revealed the regulatory impact of arborvitae essential oil on genes enriched in the following pathways: proteasome, adherens junctions, nucleocytoplasmic transport, cell cycle, proteoglycans in cancer, protein processing in the endoplasmic reticulum, ribosome, spliceosome, mitophagy, cellular senescence, and viral carcinogenesis, among others, in both cell lines. It is worth noting that the ribosome and spliceosome KEGG pathways are the most significantly enriched pathways in HeLa and SiHa cells. CONCLUSION: Arborvitae essential oil shows potential as a cytotoxic and antiproliferative agent against cervical cancer cells, exerting its cytotoxic properties by regulating many KEGG pathways.

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Chronic hepatitis B virus (HBV) infection affects 257-291 million people worldwide. The World Health Organization reported 890,000 HBV-related deaths in 2019, higher than reported previously. There are 10 HBV genotypes (A-J) subdivided into several subgenotypes that differ considerably by geography. Various virologic factors, including genotype and subgenotype, impact the odds of acquiring a chronic HBV infection, the type of treatment prescribed, and the risk of developing hepatocarcinoma. Information on the HBV genotypes and subgenotypes that circulate in Ecuador remains low. To address this gap, the current study took a preliminary look at HBV-infected human samples from this region to identify the most common genotypes and subgenotypes. Samples from 44 patients in the Andean, Coastal, and Amazon regions of Ecuador were amplified and two major genotypes were identified, genotype F (42/44; 95.5%) and genotype E (2 patients; 4.5%). The genotype F subgenotypes were F3 (35/42; 83.33%), F4 (6/42; 14.28%), and F1b (1/42, 2.39%). This is the first epidemiological study to assess the distribution of HBV genotypes in Ecuador. The findings can inform antiviral drug effectivity studies specific to HBV genotypes prevalent in South America.

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A series of polyimides (PIs) was synthesized from 6FDA and two o-OH substituted diamines having bulky pendant phenyl, Ph, and trifluoromethyl, CF3, groups as precursors for thermally rearranged polybenzoxazole, TR-PBO, membranes. One diamine had two pendant Ph substituents; in the other, the substituents were Ph and CF3. Applying azeotropic and chemical cyclizations allowed the obtention of four o-hydroxy (o-OH) or/and o-acetoxy (o-OAc) substituted PIs depending on the imidization method. The PIs were labeled as 3Ph-OH, 4Ph-OH, or 3Ph-OAc and 4PH-OAc, respectively. Thermal rearrangements of all four precursors were investigated in the interval from 350 to 450 °C. The conversions to TR-PBO increased with temperature, and almost quantitative conversions were obtained at temperatures close to 450 °C, although o-OH substituted PIs reached conversions slightly higher than those of o-OAc PIs at a given temperature. The TR-polymers' fractional free volume (FFV) also increased with conversion but was higher for the o-OAc substituted precursors. Despite the high TR-PBO conversions, self-supported uniform TR membranes with reasonable mechanical properties were obtained, except for 4Ph-OH. Gas separation behavior of the membranes significantly improved after the thermal treatment, and the final CO2/CH4 permselectivities lay between the 1991 and 2008 Robeson upper bounds. Particularly, TR-membranes derived from o-OAc precursors and with pendant CF3 group demonstrated better gas transport properties with values of P (CO2) = 1121 barrer and αCO2/CH4 = 29 for 3Ph-OAc derived membrane, which positioned it beyond the 2008 upper limit.