Concomitant melanoma and keratoma affecting the equine digit: clinical, pathological, and long-term follow-up findings.

BACKGROUND: This case report details a long-term follow-up of a hoof melanoma with dermo-epidermal activity (resembling Spreading Superficial Melanoma (SSM)) in a bay horse with a history of a right front hoof keratoma. Melanomas involving the horse's foot are seldom reported and usually diagnosed as anaplastic melanomas based on signalment and post-mortem examination. The clinical-pathological characteristics of the foot melanoma in this bay horse are consistent with SSM-like described in humans, which is considered an intermediate malignant tumour attending their biological behaviour. However, a definitive diagnosis is limited by the single case and the lack of references in horses. CASE PRESENTATION: A 12-year-old bay Andalusian gelding underwent keratoma removal on the lateral aspect of the hoof wall. A partial resection of the hoof wall was performed for this purpose. Additionally, a plaque-like, hyperkeratotic pigmented lesion, 2 × 2X0,4 cm in size, was observed at the lateral aspect of the coronary band and was also resected for histopathological examination. Microscopically, a melanocytic tumour, characterised by small nests of large polygonal or epithelioid cells infiltrating the basal and suprabasal epidermis, the dermo - epidermal junction, and the superficial dermis, was observed. The neoplastic cells exhibited large euchromatic nuclei, prominent nucleoli, moderate pleomorphism and 4 mitotic figures per 2,37mm2; variable amounts of dark granules (melanin) were present in the cytoplasm, as well as in numerous peritumoral macrophages. The immunophenotype of the tumour cells was PNL2 + + + , S100 + + , AE1/AE3-. A diagnosis of melanoma with dermo-epidermal junction and marked intraepidermal activity (consistent with superficial spreading melanoma) was made. A magnetic resonance imaging (MRI) performed, revealed no further invasion into surrounding structures. Treatment was based on surgical resection and multiple local chemotherapy sessions with cisplatin were applied. The biopsies obtained after treatment showed partial regression of the tumour and different stages of healing. After 26 months of follow-up, there was no signs of malignant spreading into surrounding structures including the pedal bone and distal metastasis but a dark - coloured area persists over the lateral aspect of the coronary band. CONCLUSIONS: This case presents a concomitant keratoma and melanoma with dermo - epidermal activity, resembling a spreading superficial melanoma. After a follow - up of 26 months the horse remains healthy and sound providing new information for clinicians and pathologists. Despite the poor prognosis associated with foot malignant melanocytic tumours, it is important that an early and accurate diagnosis is reached through different diagnostic modalities such as advanced imaging techniques and histopathology. Additionally, these findings demonstrate that the current classification and prognosis for equine foot melanomas are insufficient.

Expression of tryptophan hydroxylase in rat adrenal glands: Upregulation of TPH2 by chronic stress.

It has been shown that chronic restraint stress (CRS) increases adrenal 5-HT levels and turnover through a mechanism that appears unrelated to tryptophan hydroxylase (TPH). In the present study we re-analyzed the effects of CRS (20 min/day) for 14 days relative to control (CTRL) conditions on TPH expression, distribution, and activity in rat adrenal glands. On day 15, adrenal glands were collected for TPH1 and TPH2 immunohistochemistry, Western blot, and RT-PCR; TPH activity was estimated by quantification of 5-hydroxytryptophan (5-HTP) and, indirectly, through measurement of 5-HT and 5-hydroxindolacetic acid (5-HIAA) levels and turnover (5-HIAA/5-HT ratio) by HPLC. TPH expression and activity in the dorsal raphe nucleus (DRN) were also determined for comparison. TPH1 and TPH2 immunostaining was observed in the adrenal medulla, and measurable levels of TPH1 and TPH2 protein and mRNA were detected in rat adrenal glands from CTRL animals. CRS exposure noticeably increased TPH2- but not THP1-immunostaining in the medulla and the outer adrenocortical areas of left (LAG) but not of right adrenal glands (RAG). In addition, CRS exposure increased TPH2 protein and mRNA levels in LAG; however, both measures decreased in DRN. Finally, CRS treatment produced an increase and a decrease of TPH activity and 5-HT turnover in LAG and DRN, respectively. Results indicate that TPH is indeed expressed in rat adrenal glands. Exposure to CRS upregulates TPH2 in LAG, while inducing downregulation of it in the DRN. Then, the increased levels of 5-HT in LAG from CRS-exposed animals likely results from TPH2-mediated synthesis.

Nutritional Strategies for Optimizing Health, Sports Performance, and Recovery for Female Athletes and Other Physically Active Women: A Systematic Review.

CONTEXT: Despite the progress toward gender equality in events like the Olympic Games and other institutionalized competitions, and the rising number of women engaging in physical exercise programs, scientific studies focused on establishing specific nutritional recommendations for female athletes and other physically active women are scarce. OBJECTIVE: This systematic review aimed to compile the scientific evidence available for addressing the question "What dietary strategies, including dietary and supplementation approaches, can improve sports performance, recovery, and health status in female athletes and other physically active women?" DATA SOURCES: The Pubmed, Web of Science, and Scopus databases were searched. DATA EXTRACTION: The review process involved a comprehensive search strategy using keywords connected by Boolean connectors. Data extracted from the selected studies included information on the number of participants and their characteristics related to sport practice, age, and menstrual function. DATA ANALYSIS: A total of 71 studies were included in this review: 17 focused on the analysis of dietary manipulation, and 54 focused on the effects of dietary supplementation. The total sample size was 1654 participants (32.5% categorized as competitive athletes, 30.7% as highly/moderately trained, and 37.2% as physically active/recreational athletes). The risk of bias was considered moderate, mainly for reasons such as a lack of access to the study protocol, insufficient description of how the hormonal phase during the menstrual cycle was controlled for, inadequate dietary control during the intervention, or a lack of blinding of the researchers. CONCLUSION: Diets with high carbohydrate (CHO) content enhance performance in activities that induce muscle glycogen depletion. In addition, pre-exercise meals with a high glycemic index or rich in CHOs increase CHO metabolism. Ingestion of 5-6 protein meals interspersed throughout the day, with each intake exceeding 25 g of protein favors anabolism of muscle proteins. Dietary supplements taken to enhance performance, such as caffeine, nitric oxide precursors, ß-alanine, and certain sport foods supplements (such as CHOs, proteins, or their combination, and micronutrients in cases of nutritional deficiencies), may positively influence sports performance and/or the health status of female athletes and other physically active women. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD480674.

The Similarity Degree of the Anthropometric and Body Composition Variables of Brazilian and Mozambican Schoolchildren: A New Approach Using the Smoothed Jaccard Index Surface.

BACKGROUND/OBJECTIVES: Brazil and Mozambique face similar socioeconomic challenges, including common indicators of undernutrition and overnutrition among children. This study evaluated the similarity degree of the anthropometric and body composition variables of Brazilian and Mozambican children by using the Jaccard index. METHODS: A total of 1831 children of both genders aged 7-10 years from three Brazilian cities (Recife, Vitoria de Santo Antao, and Lagoa do Carro) and three Mozambican cities (Maputo, Boane, and Inhambane) participated in this study. Anthropometric (height, body mass, and waist circumference) and body composition (body fat percentage [%BF], lean mass, and fat mass) variables were measured and the Smoothed Jaccard Index Surface (SJIS) was used to evaluate the similarity degree. RESULTS: Brazilian children were taller and heavier and had a higher %BF and fat mass than Mozambican children. Children living in urban areas were taller than those living in rural zones in both countries. Brazilian and Mozambican children showed high similarity only between %BF and lean mass. Children from Recife and Maputo had high similarities among waist circumference, body mass, fat mass, height, and %BF. Finally, a high SJIS degree was observed among height and %BF for schoolchildren from rural and urban zones. CONCLUSION: Brazilian and Mozambican children exhibit differences in growth characteristics but a high degree of similarity when children from rural and urban zones are compared.

Kelp forest food webs as hot spots for the accumulation of microplastic and polybrominated diphenyl ether pollutants.

Kelp forests (KFs) are one of the most significant marine ecosystems in the planet. They serve as a refuge for a wide variety of marine species of ecological and economic importance. Additionally, they aid with carbon sequestration, safeguard the coastline, and maintain water quality. Microplastic (MP) and polybrominated diphenyl ethers (PBDEs) concentrations were analyzed across trophic levels in KFs around Todos Santos Bay. Spatial variation patterns were compared at three sites in 2021 and temporal change at Todos Santos Island (TSI) in 2021 and 2022. We analyzed these MPs and PBDEs in water, primary producers (Macrocystis pyrifera), grazers (Strongylocentrotus purpuratus), predators (Semicossyphus pulcher), and kelp detritus. MPs were identified in all samples (11 synthetic and 1 semisynthetic polymer) and confirmed using Fourier-transform infrared microspectroscopy-attenuated total reflectance (µ-FTIR-ATR). The most abundant type of MP is polyester fibers. Statistically significant variations in MP concentration were found only in kelps, with the greatest average concentrations in medium-depth kelps from TSI in 2022 (0.73 ± 0.58 MP g-1 ww) and in the kelp detritus from TSI in 2021 (0.96 ± 0.64 MP g-1 ww). Similarly, PBDEs were found in all samples, with the largest concentration found in sea urchins from Punta San Miguel (0.93 ± 0.24 ng g-1 ww). The similarity of the polymers can indicate a trophic transfer of MPs. This study shows the extensive presence of MP and PBDE subtropical trophic web of a KF, but correlating these compounds in environmental samples is highly complex, influenced by numerous factors that could affect their presence and behavior. However, this suggests that there is a potential risk to the systems and the services that KFs offer.

Differing contributions of the gut microbiota to the blood pressure lowering effects induced by first-line antihypertensive drugs.

BACKGROUND AND PURPOSE: This study analyses whether first-line antihypertensive drugs ameliorate the dysbiosis state in hypertension, and to test if this modification contributes to their blood pressure (BP) lowering properties in a genetic model of neurogenic hypertension. EXPERIMENTAL APPROACH: Twenty-week-old male Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were untreated or treated with captopril, amlodipine or hydrochlorothiazide. A faecal microbiota transplantation (FMT) experiment was also performed by gavage of faecal content from donor SHR-treated groups to SHR recipients for 3 weeks. KEY RESULTS: Faeces from SHR showed gut dysbiosis, characterized by lower acetate- and higher lactate-producing bacteria and lower strict anaerobic bacteria. All three drugs increased the anaerobic bacteria proportion, captopril and amlodipine restored the proportion of acetate-producing bacterial populations to WKY levels, whereas hydrochlorothiazide decreased butyrate-producing bacteria. Captopril and amlodipine decreased gut pathology and permeability and attenuated sympathetic drive in the gut. Both drugs decreased neuroinflammation and oxidative stress in the hypothalamic paraventricular nuclei. Hydrochlorothiazide was unable to reduce neuroinflammation, gut sympathetic tone and gut integrity. FMT from SHR-amlodipine to SHR decreased BP, ameliorated aortic endothelium-dependent relaxation to acetylcholine, lowered NADPH oxidase activity, aortic Th17 infiltration and reduced neuroinflammation, whereas FMT from SHR-hydrochlorothiazide did not have these effects. CONCLUSIONS AND IMPLICATIONS: First-line antihypertensive drugs induced different modifications of gut integrity and gut dysbiosis in SHR, which result in no contribution of microbiota in the BP lowering effects of hydrochlorothiazide, whereas the vasculo-protective effect induced by amlodipine involves gut microbiota reshaping and gut-immune system communication.

Fermentation of Orange Peels by Lactic Acid Bacteria: Impact on Phenolic Composition and Antioxidant Activity.

Orange processing generates peel by-products rich in phenolic compounds, particularly flavanones like hesperidin and narirutin, offering potential health benefits. Utilizing these by-products is of significant interest in supporting Spain's circular bioeconomy. Therefore, the aim of this study was to investigate the fermentation of orange peels by different lactic acid bacteria (LAB) strains and its impact on phenolic composition and antioxidant activity. Three different LAB strains, two Lactiplantibacillus plantarum, and one Levilactobacillus brevis were utilized. The phenolic compounds were measured by HPLC-ESI-TOF-MS, and antioxidant activity was assessed using DPPH and ABTS methods. The growth of the LAB strains varied, showing initial increases followed by gradual declines, with strain-specific patterns observed. Medium acidification occurred during fermentation. A phenolic analysis revealed an 11% increase in phenolic acids in peels fermented by La. plantarum CECT 9567-C4 after 24 h, attributed to glycosylation by LAB enzymes. The flavonoid content exhibited diverse trends, with Le. brevis showing an 8% increase. The antioxidant assays demonstrated strain- and time-dependent variations. Positive correlations were found between antioxidant activity and total phenolic compounds. The results underscore the importance of bacterial selection and fermentation time for tailored phenolic composition and antioxidant activity in orange peel extracts. LAB fermentation, particularly with La. plantarum CECT 9567 and Le. brevis, holds promise for enhancing the recovery of phenolic compounds and augmenting antioxidant activity in orange peels, suggesting potential applications in food and beverage processing.

Acquired Perforating Dermatosis and Dermatology Life Quality Index in Patients Receiving hemodialysis.

INTRODUCTION: Acquired perforating dermatosis (APD) is a frequent disorder in hemodialysis patients and the effect on the quality of life is poorly described. We investigated the prevalence of APD in hemodialysis patients, measured and compared APD-associated quality of life. METHODS: We developed a prospective, observational, and descriptive study. We invited patients over the age of 18 in hemodialysis. Data was obtained from their electronic file and a dermatological examination was performed. The Dermatology Life Quality Index (DLQI) was applied. Descriptive analysis of demographic variables, clinical features, and dermoscopy findings, as well as comparison of DLQI scores, was made. RESULTS: The sample consisted of 46 patients, with a prevalence of APD of 11%. Patients with APD were leaner and younger compared to patients without APD. The time on hemodialysis was longer in patients with APD compared to those without APD, with a median of 90 versus 32 months (p = 0.015). The impact on quality of life was greater in patients with APD compared to those without APD, with some effect in all patients with APD and 33% in patients without APD (p = 0.001). Patients with APD had more frequent pruritus compared to those without APD (p = 0.007). CONCLUSIONS: Age, time on hemodialysis and BMI are associated with the presence of APD. Patients with APD had a higher prevalence of pruritus and a greater impact on quality of life in dermatology compared to patients without APD.

Impact of Technological Processes on the Formation of Furosine, Acrylamide and Furan in Traditional Venezuelan Cocoa.

The present study was conducted to determine and analyse the content of furosine, acrylamide and furan in fermented cocoa beans from the Chuao ("criollo variety") and Barlovento ("trinitario variety") regions of Venezuela, after roasting (in the shell at 110-180 °C for 15-60 min) and alkalisation (with sodium bicarbonate or potassium carbonate, at concentrations of 10-25 g/kg in order to evaluate the impact of these operations. The highest furosine contents (up to 249 mg/100 g of protein) were found in fermented, sun-dried samples, and were higher in the nibs than in the shells. The acrylamide content increased in line with the temperature, to 160 °C in the shells, and to 180 °C in the nibs. At temperatures of up to 140 °C, the acrylamide content was higher in the shells than in the nibs. The furan content increased in line with the temperature and in this case too, was greater in the shells. The content of both furosine and furan decreased with alkalisation, while the presence of acrylamide was irregular and determined by the roasting temperature and the alkalising agent employed. Although the furosine, acrylamide and furan contents varied between the beans from the two regions and the varieties considered (Chuao and Barlovento), these three compounds were correlated to a statistically significant degree.

Changes in the expression of genes encoding xanthophyl acyltransferases during the postharvest ripening of avocado (Persea americana) fruit.

BACKGROUND: Avocado fruit is rich in xanthophylls, which have been related to positive effects on human health. Xanthophyl acetyltransferases (XATs) are enzymes catalyzing the esterification of carboxylic acids to the hydroxyl group of the xanthophyll molecule. This esterification is thought to increase the lipophilic nature of the xanthophyll and its stability in a lipophilic environment. Studies on XATs in fruits are very scarce, and no studies had been carried out in avocado fruit during postharvest. The objective of this work was to investigate the changes in the expression of genes encoding XAT, during avocado fruit ripening. RESULTS: Avocado fruits were obtained from a local market and stored at 15 °C for 8 days. The fruit respiration rate, ethylene production, and fruit peel's color space parameters (L*, a*, b*) were measured during storage. Fruit mesocarp samples were taken after 1, 3, 5, and 7 days of storage and frozen with liquid nitrogen. Total RNA was extracted from fruit mesocarp, and the quantification of the two genes designated as COGE_ID: 936743791 and COGE_ID: 936800185 encoding XATs was performed with real-time quantitative reverse transcription polymerase chain reaction using actin as a reference gene. The presence of a climacteric peak and large changes in color were recorded during postharvest. The two genes studied showed a large expression after 3 days of fruit storage. CONCLUSIONS: We conclude that during the last stages of ripening in avocado fruit there was an active esterification of xanthophylls with carboxylic acids, which suggests the presence of esterified xanthophylls in the fruit mesocarp. © 2024 Society of Chemical Industry.

Identification and Structural Characterization of Twisted Atomically Thin Bilayer Materials by Deep Learning.

Two-dimensional materials are expected to play an important role in next-generation electronics and optoelectronic devices. Recently, twisted bilayer graphene and transition metal dichalcogenides have attracted significant attention due to their unique physical properties and potential applications. In this study, we describe the use of optical microscopy to collect the color space of chemical vapor deposition (CVD) of molybdenum disulfide (MoS2) and the application of a semantic segmentation convolutional neural network (CNN) to accurately and rapidly identify thicknesses of MoS2 flakes. A second CNN model is trained to provide precise predictions on the twist angle of CVD-grown bilayer flakes. This model harnessed a data set comprising over 10,000 synthetic images, encompassing geometries spanning from hexagonal to triangular shapes. Subsequent validation of the deep learning predictions on twist angles was executed through the second harmonic generation and Raman spectroscopy. Our results introduce a scalable methodology for automated inspection of twisted atomically thin CVD-grown bilayers.

Enhancing the stability and efficiency of carbon-based perovskite solar cell performance with ZrO2-decorated rGO nanosheets in a mesoporous TiO2 electron-transport layer.

Improving the role of electron-transport layers (ETLs) in carbon-based perovskite solar cells (CPSCs) is a promising method to increase their photovoltaic efficiency. Herein, we employed rGO sheets decorated with ZrO2 nanoparticles to increase the electron transport capability of mesoporous TiO2 ETLs. We found that the rGO/ZrO2 dopant enhanced the conductivity of the ETL, reducing the charge-transfer resistance at the ETL/perovskite interface and reducing charge recombination in the corresponding CPSCs. Notably, this dopant did not effectively change the transparency of ETLs, while increasing the light-harvesting ability of their own top perovskite layer by improving the crystallinity of the perovskite layer. The rGO/ZrO2-containing ETLs produced a champion efficiency of 15.21%, while devices with a net ETL recorded a maximum efficiency of 11.88%. In addition, the modified devices showed a higher stability behavior against ambient air than the net devices, which was linked to the passivated grain boundaries of the modified perovskite layers along with the improved hydrophobicity.

Sensory and behavioral modulation of thalamic head-direction cells.

Head-direction (HD) neurons are thought to exclusively encode directional heading. In awake mice, we found that sensory stimuli evoked robust short-latency responses in thalamic HD cells, but not in non-HD neurons. The activity of HD cells, but not that of non-HD neurons, was tightly correlated to brain-state fluctuations and dynamically modulated during social interactions. These data point to a new role for the thalamic compass in relaying sensory and behavioral-state information.

Agreement between the perception of colon cleansing reported by patients and colon cleansing assessed by a validated colon cleansing scale.

AIMS: Patients' perception of their cleansing quality can guide strategies to improve cleansing during colonoscopy. There are no studies assessing the agreement between the quality of cleansing perceived by patients and cleansing quality assessed during colonoscopy using validated bowel preparation scales. The main aim of this study was to compare the cleansing quality reported by patients with the quality during colonoscopy using the Boston Bowel Preparation Scale (BBPS). PATIENTS AND METHODS: Consecutive patients referred to an outpatient colonoscopy were included. Four drawings representing different degrees of cleansing were designed. Patients chose the drawing that most resembled the last stool. The predictive ability of the patient's perception and agreement between the patient's perception and the BBPS were calculated. A BBPS score of <2 points in any segment was considered inadequate. RESULTS: Six hundred and thirty-three patients were included (age: 62.8±13.7 years, male: 53.4%). Overall, 107 patients (16.9%) had inadequate cleansing during colonoscopy, and in 12.2% of cases, the patient's perception was poor. The patient's perception compared to the quality of cleanliness during colonoscopy presented a positive and negative predictive value of 54.6% and 88.3%, respectively. The agreement between patient perception and the BBPS was significant (P<0.001), although fair (k=0.37). The results were similar in a validation cohort of 378 patients (k=0.41). CONCLUSIONS: The cleanliness perceived by the patient and the quality of cleanliness using a validated scale were correlated, although fair. However, this measure satisfactorily identified patients with adequate preparation. Cleansing rescue strategies may target patients who self-report improper cleaning. Registration number of the trial: NCT03830489.

Síndrome metabólico y su relación con la microbiota intestinal / Metabolic syndrome and its relationship with gut microbiota

Introducción: el síndrome metabólico es uno de los problemas de salud pública más importantes en la actualidad, considerado como una epidemia mundial. Es producto de la interacción entre los procesos de inflamación y la resistencia a la insulina. Objetivo: actualizar los conocimientos concernientes al papel de la microbiota en el desarrollo del síndrome metabólico Método: se realizó una búsqueda bibliográfica no sistemática en las bases de datos PubMed, SciELO, Science Direct, EMBASE, LILACS y Redalyc. Los criterios de inclusión fueron publicaciones en inglés, portugués y español, en las que el título y palabras clave, incluyeran información pertinente con el objetivo planteado, con una periodicidad de 10 años, obteniendo 50 artículos de los cuales fueron seleccionados 30. Resultados: los 30 artículos presentaban correspondencia continua con el tema planteado en esta revisión, entre ellos 1 consenso de expertos, 25 revisiones narrativas y documentales, 1 investigación original, 2 libros uno de ellos actualizado y 1 estudio prospectivo. Discusión: la microbiota intestinal tiene un rol importante en la conservación de la homeostasis intestinal, proporcionando energía y nutrientes, así como protección contra la colonización de patógenos. La alteración de la composición y la actividad de la microbiota intestinal. La alteración de la composición y actividad de la microbiota intestinal se conoce como disbiosis y está implicada en la etiopatogenia de múltiples enfermedades crónicas, incrementando el riesgo cardiovascular en el contexto del síndrome metabólico. Conclusiones: entre las estrategias para la prevención y tratamiento del síndrome metabólico, sobresale la modificación de los patrones de alimentación de manera individualizada, se recomienda además una dieta rica en vegetales, fibra, granos integrales y baja en grasas. El uso de los prebióticos y probióticos ejercen un efecto beneficioso sobre la salud del hospedador, mediante la modulación de la microbiota intestinal.

Observation and Measurement of Ice Morphology in Foods: A Review.

Freezing is an effective technology with which to maintain food quality. However, the formation of ice crystals during this process can cause damage to the cellular structure, leading to food deterioration. A good understanding of the relationship between food microstructure and ice morphology, as well as the ability to effectively measure and control ice crystals, is very useful to achieve high-quality frozen foods. Hence, a brief discussion is presented on the fundamentals/principles of optical microscopic techniques (light microscopy), electronic microscopic techniques (transmission electron microscopy (TEM) and scanning electron microscopy (SEM)), as well as other non-invasive techniques (X-rays, spectroscopy, and magnetic resonance) and their application to measuring ice formation rates and characterizing ice crystals, providing insight into the freezing mechanisms as well as direct monitoring of the entire process. And, in addition, this review compares (the negative and positive aspects of) the use of simple and cheap but destructive technologies (optical microscopy) with detailed microscopic technologies at the micro/nanometer scale but with pretreatments that alter the original sample (SEM and TEM), and non-destructive technologies that do not require sample preparation but which have high acquisition and operational costs. Also included are images and examples which demonstrate how useful an analysis using these techniques can be.

Protective effect of microbiota-derived short chain fatty acids on vascular dysfunction in mice with systemic lupus erythematosus induced by toll like receptor 7 activation.

Our objective was to investigate whether short-chain fatty acids (SCFAs), specifically acetate and butyrate, could prevent vascular dysfunction and elevated blood pressure (BP) in mice with systemic lupus erythematosus (SLE) induced by TLR7 activation using imiquimod (IMQ). Treatment with both SCFAs and dietary fibers rich in resistant starch (RS) or inulin-type fructans (ITF) effectively prevented the development of hypertension and cardiac hypertrophy. Additionally, these treatments improved aortic relaxation induced by acetylcholine and mitigated vascular oxidative stress. Acetate and butyrate treatments also contributed to the maintenance of colonic integrity, reduced endotoxemia, and decreased the proportion of helper T (Th)17 cells in mesenteric lymph nodes (MLNs), blood, and aorta in TLR7-induced SLE mice. The observed changes in MLNs were correlated with increased levels of GPR43 mRNA in mice treated with acetate and increased GPR41 levels along with decreased histone deacetylase (HDAC)- 3 levels in mice treated with butyrate. Notably, the effects attributed to acetate, but not butyrate, were nullified when co-administered with the GPR43 antagonist GLPG-0974. T cell priming and differentiation into Th17 cells in MLNs, as well as increased Th17 cell infiltration, were linked to aortic endothelial dysfunction and hypertension subsequent to the transfer of faecal microbiota from IMQ-treated mice to germ-free (GF) mice. These effects were counteracted in GF mice through treatment with either acetate or butyrate. To conclude, these findings underscore the potential of SCFA consumption in averting hypertension by restoring balance to the interplay between the gut, immune system, and vascular wall in SLE induced by TLR7 activation.

Comprehensive Single-Cell Immune Profiling Defines the Patient Multiple Myeloma Microenvironment Following Oncolytic Virus Therapy in a Phase Ib Trial.

PURPOSE: Our preclinical studies showed that the oncolytic reovirus formulation pelareorep (PELA) has significant immunomodulatory anti-myeloma activity. We conducted an investigator-initiated clinical trial to evaluate PELA in combination with dexamethasone (Dex) and bortezomib (BZ) and define the tumor immune microenvironment (TiME) in patients with multiple myeloma treated with this regimen. PATIENTS AND METHODS: Patients with relapsed/refractory multiple myeloma (n = 14) were enrolled in a phase Ib clinical trial (ClinicalTrials.gov: NCT02514382) of three escalating PELA doses administered on Days 1, 2, 8, 9, 15, and 16. Patients received 40 mg Dex and 1.5 mg/m2 BZ on Days 1, 8, and 15. Cycles were repeated every 28 days. Pre- and posttreatment bone marrow specimens (IHC, n = 9; imaging mass cytometry, n = 6) and peripheral blood samples were collected for analysis (flow cytometry, n = 5; T-cell receptor clonality, n = 7; cytokine assay, n = 7). RESULTS: PELA/BZ/Dex was well-tolerated in all patients. Treatment-emergent toxicities were transient, and no dose-limiting toxicities occurred. Six (55%) of 11 response-evaluable patients showed decreased paraprotein. Treatment increased T and natural killer cell activation, inflammatory cytokine release, and programmed death-ligand 1 expression in bone marrow. Compared with nonresponders, responders had higher reovirus protein levels, increased cytotoxic T-cell infiltration posttreatment, cytotoxic T cells in significantly closer proximity to multiple myeloma cells, and larger populations of a novel immune-primed multiple myeloma phenotype (CD138+ IDO1+HLA-ABCHigh), indicating immunomodulation. CONCLUSIONS: PELA/BZ/Dex is well-tolerated and associated with anti-multiple myeloma activity in a subset of responding patients, characterized by immune reprogramming and TiME changes, warranting further investigation of PELA as an immunomodulator.

The coexistence of diabetic retinopathy and diabetic nephropathy is associated with worse kidney outcomes.

Background: Up to 50-60% of patients with diabetes have non-diabetic kidney disease (NDKD) on kidney biopsy. Diabetic retinopathy (DR) is a microvascular complication of diabetes frequently associated with diabetic nephropathy (DN). The objective of the current study was to investigate the kidney outcomes and survival in patients with biopsy diagnoses of DN and NDKD according to the presence of DR. Methods: We conducted an observational, multicentre and retrospective study of the pathological findings of renal biopsies from 832 consecutive patients with diabetes from 2002 to 2014 from 18 nephrology departments. The association of DR with kidney replacement therapy (KRT) or survival was assessed by Kaplan-Meier and Cox regression analyses. Results: Of 832 patients with diabetes and renal biopsy, 768 had a retinal examination and 221/768 (22.6%) had DR. During a follow-up of 10 years, 288/760 (37.9%) patients with follow-up data needed KRT and 157/760 (20.7%) died. The incidence of KRT was higher among patients with DN (alone or with NDKD) and DR [103/175 (58.9%)] than among patients without DR [88/216 (40.7%), P < .0001]. The incidence of KRT was also higher among patients with only NDKD and DR than among those without DR [18/46 (39.1%) versus 79/331 (23.9%), P < .0001]. In multivariate analysis, DR or DN were independent risk factors for KRT {hazard ratio [HR] 2.48 [confidence interval (CI) 1.85-3.31], P < .001}. DN (with or without DR) was also identified as an independent risk factor for mortality [HR 1.81 (CI 1.26-2.62), P = .001]. Conclusions: DR is associated with a higher risk of progression to kidney failure in patients with histological DN and in patients with NDKD.

Three-Dimensional Volume Rendering in Computed Tomography for Evaluation of the Temporomandibular Joint in Dogs.

Based on computed tomography (CT) images, volume rendering was used to obtain a three-dimensional representation of data (3DVR). The aims of this study included: describing the bone anatomy of the temporomandibular joint (TMJ) of dogs; comparing the TMJs of each dog by skull type and age; comparing 3DVR images with three-standard-plane CTs; assessing soft tissues adjacent to the TMJ and assessing pathological cases. Multidetector computed tomography scans of bilateral TMJs of 410 dogs were observed. From a ventral view, slight displacements in the positions of the skulls were seen, whereas from a caudal view, differences in amplitude of the articular space were observed. Dolichocephalic and mesaticephalic dogs showed more similar TMJ features than brachycephalic dogs. The shape of the TMJ bones were irregular in dogs under 1 year old. The 3DVR images related to the three-standard-plane CT improved the overall comprehension of the changes in the articular space amplitude and condylar process morphology. The fovea pterygoidea, mandibular fossa and retroarticular process were perfectly shown. A better spatial situation of adjacent soft tissues was obtained. The 3DVR represents an ancillary method to the standard-plane CT that could help in the understanding of the anatomy and diagnoses of different pathologies of the TMJ in dogs.