Design and validation of an artificial intelligence system to detect the quality of colon cleansing before colonoscopy / Diseño y validación de un sistema de inteligencia artificial para detectar la calidad de la limpieza del colon previa a la realización de la colonoscopia

Background and aims Patients’ perception of their bowel cleansing quality may guide rescue cleansing strategies before colonoscopy. The main aim of this study was to train and validate a convolutional neural network (CNN) for classifying rectal effluent during bowel preparation intake as “adequate” or “inadequate” cleansing before colonoscopy.Patients and methodsPatients referred for outpatient colonoscopy were asked to provide images of their rectal effluent during the bowel preparation process. The images were categorized as adequate or inadequate cleansing based on a predefined 4-picture quality scale. A total of 1203 images were collected from 660 patients. The initial dataset (799 images), was split into a training set (80%) and a validation set (20%). The second dataset (404 images) was used to develop a second test of the CNN accuracy. Afterward, CNN prediction was prospectively compared with the Boston Bowel Preparation Scale (BBPS) in 200 additional patients who provided a picture of their last rectal effluent.ResultsOn the initial dataset, a global accuracy of 97.49%, a sensitivity of 98.17% and a specificity of 96.66% were obtained using the CNN model. On the second dataset, an accuracy of 95%, a sensitivity of 99.60% and a specificity of 87.41% were obtained. The results from the CNN model were significantly associated with those from the BBPS (P<0.001), and 77.78% of the patients with poor bowel preparation were correctly classified.ConclusionThe designed CNN is capable of classifying “adequate cleansing” and “inadequate cleansing” images with high accuracy. (AU)

Antecedentes y objetivos La percepción de los pacientes sobre la calidad de su limpieza intestinal puede guiar las estrategias de limpieza de rescate antes de una colonoscopia. El objetivo principal de este estudio fue entrenar y validar una red neuronal convolucional (CNN) para clasificar el efluente rectal durante la preparación intestinal como «adecuado» o «inadecuado».Pacientes y métodosPacientes no seleccionados proporcionaron imágenes del efluente rectal durante el proceso de preparación intestinal. Las imágenes fueron categorizadas como una limpieza adecuada o inadecuada según una escala de calidad de 4 imágenes predefinida. Se recopilaron un total de 1.203 imágenes de 660 pacientes. El conjunto de datos inicial (799 imágenes) se dividió en un conjunto de entrenamiento (80%) y un conjunto de validación (20%). Un segundo conjunto de datos (404 imágenes) se utilizó para evaluar la precisión de la CNN. Posteriormente, la predicción de la CNN se comparó prospectivamente con la escala de preparación colónica de Boston (BBPS) en 200 pacientes que proporcionaron una imagen de su último efluente rectal.ResultadosEn el conjunto de datos inicial, la precisión global fue del 97,49%, la sensibilidad del 98,17% y la especificidad del 96,66%. En el segundo conjunto de datos, se obtuvo una precisión del 95%, una sensibilidad del 99,60% y una especificidad del 87,41%. Los resultados del modelo de CNN se asociaron significativamente con la escala de preparación colónica de Boston (p<0,001), y el 77,78% de los pacientes con una preparación intestinal deficiente fueron clasificados correctamente.ConclusiónLa CNN diseñada es capaz de clasificar imágenes de «limpieza adecuada» y «limpieza inadecuada» con alta precisión. (AU)

Design and validation of an artificial intelligence system to detect the quality of colon cleansing before colonoscopy.

BACKGROUND AND AIMS: Patients' perception of their bowel cleansing quality may guide rescue cleansing strategies before colonoscopy. The main aim of this study was to train and validate a convolutional neural network (CNN) for classifying rectal effluent during bowel preparation intake as "adequate" or "inadequate" cleansing before colonoscopy. PATIENTS AND METHODS: Patients referred for outpatient colonoscopy were asked to provide images of their rectal effluent during the bowel preparation process. The images were categorized as adequate or inadequate cleansing based on a predefined 4-picture quality scale. A total of 1203 images were collected from 660 patients. The initial dataset (799 images), was split into a training set (80%) and a validation set (20%). The second dataset (404 images) was used to develop a second test of the CNN accuracy. Afterward, CNN prediction was prospectively compared with the Boston Bowel Preparation Scale (BBPS) in 200 additional patients who provided a picture of their last rectal effluent. RESULTS: On the initial dataset, a global accuracy of 97.49%, a sensitivity of 98.17% and a specificity of 96.66% were obtained using the CNN model. On the second dataset, an accuracy of 95%, a sensitivity of 99.60% and a specificity of 87.41% were obtained. The results from the CNN model were significantly associated with those from the BBPS (P<0.001), and 77.78% of the patients with poor bowel preparation were correctly classified. CONCLUSION: The designed CNN is capable of classifying "adequate cleansing" and "inadequate cleansing" images with high accuracy.

Exploring the use of hexadecane by Yarrowia lipolytica: Effect of dissolved oxygen and medium supplementation.

This work aimed to evaluate the effect of medium composition and volumetric oxygen transfer coefficient (kLa) on Y. lipolytica growth and production of microbial lipids and enzymes from hexadecane. In the stirred tank bioreactor, increasing kLa from 11 h-1 to 132 h-1 improved the hexadecane assimilation rate, biomass concentration, and lipids synthesis (0.90 g·L-1). A cost-effective hexadecane-based medium supplemented with corn steep liquor and a low amount of ammonium sulfate boosted lipids production up to 2.1 g·L-1, composed of palmitic, palmitoleic, oleic, and linoleic acids. The unsaturated/saturated fraction was dependent on the C/N ratio. Lipids of Y. lipolytica CBS 2075 are promising feedstock for animal feed, food additives, or the biodiesel industry. Simultaneous synthesis of extracellular lipase and protease from hexadecane was observed, which is a new feature that was not previously reported. The highest enzyme activity was obtained at the highest C/N ratio conditions. These results open new perspectives on the application of Y. lipolytica-based cultures for the biotransformation of hexadecane-polluted streams into valuable compounds, fulfilling an interesting strategy towards the circular economy concept.

Post-COVID-19 functional status scale: Cross-cultural adaptation and measurement properties of the Brazilian Portuguese version.

BACKGROUND: The Post-COVID-19 Functional Status (PCFS) scale was created to assess the functional status of patients after hospital discharge due to COVID-19. OBJECTIVE: To perform cross-cultural adaptation of the PCFS Scale and Manual into Brazilian Portuguese and evaluate its measurement properties in patients post-COVID-19. METHODS: For the cross-cultural adaptation, independent translations and back-translations were performed. This was followed by a pre-test, with analysis of the Content Validity Index (CVI), and preparation of the final version, after evaluating the measurement properties. Spearman's correlation between the PCFS and the WHO Disability Classification Scheme (WHODAS 2.0) was used for convergent validity. Weighted Kappa (wκ) was used for test-retest and interobserver reliability for PCFS scores and Kappa (κ) for PCFS items. Internal consistency was assessed using Cronbach's alpha. Only patients with post-discharge COVID-19 were evaluated through video-conferencing platforms. RESULTS: The CVI was 0.75-0.83 for comprehension and 0.83-0.84 for the language of the self-administered questionnaire and the structured interview version. For measurement properties, 63 patients were evaluated, 68% male, 51.50 (12.60) years, 12.28 (7.62) days of hospitalization. For the convergent validity, a strong correlation was found (r = 0.73; p<0.01). The test-retest (wκ=0.54) and interobserver (wκ=0.43) reliability was moderate and the item-by-item analyzes ranged from fair to substantial (κ=0.25-0.66) and weak to substantial (κ=0.07-0.79). Internal consistency was excellent (0.85). CONCLUSION: The final PCFS in Brazilian Portuguese showed adequate content validity, reliability, internal consistency, and convergent validity for the functional assessment of patients after hospital discharge due to COVID-19.

Elevated plasma levels of IL-6 and MCP-1 selectively identify CML patients who better sustain molecular remission after TKI withdrawal.

Treatment-free remission (TFR) in chronic myeloid leukemia (CML) is safe under adequate molecular monitoring, but questions remain regarding which factors may be considered predictive for TFR. Argentina Stop Trial (AST) is a multicenter TFR trial showing that 65% of patients sustain molecular remission, and the prior time in deep molecular response (DMR) was associated with successful TFR. Luminex technology was used to characterize cytokines in plasma samples. Using machine learning algorithms, MCP-1 and IL-6 were identified as novel biomarkers and MCP-1low/IL-6low patients showed eightfold higher risk of relapse. These findings support the feasibility of TFR for patients in DMR and MCP-1/IL-6 plasma levels are strong predictive biomarkers.

Clinical and biochemical short-term effects of hyperbaric oxygen therapy on SARS-Cov-2+ hospitalized patients with hypoxemic respiratory failure.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) has been proposed to address COVID-19- associated respiratory failure. However, its biochemical effects are poorly known. METHOD: 50 patients with hypoxemic COVID-19 pneumonia were divided into C group (standard care) and H group (standard care plus HBOT). Blood was obtained at t = 0 and t = 5 days. Oxygen saturation (O2 Sat) was followed up. White blood cell (WC) count, lymphocytes (L) and platelets (P) and serum analysis (glucose, urea, creatinine, sodium, potassium, ferritin, D dimer, LDH and CRP) were carried out. Plasma levels of sVCAM, sICAM, sPselectin, SAA and MPO, and of cytokines (IL-1ß, IL-1RA, IL-6, TNFα, IFNα, IFNγ, IL-15, VEGF, MIP1α, IL-12p70, IL-2 and IP-10) were measured by multiplex assays. Angiotensin Converting Enzyme 2 (ACE-2) levels were determined by ELISA. RESULTS: The average basal O2 Sat was 85 ± 3%. The days needed to reach O2 Sat >90% were: H: 3 ± 1 and C: 5 ± 1 (P < 0,01). At term, H increased WC, L and P counts (all, H vs C: P < 0,01). Also, H diminished D dimer levels (H vs C, P < 0,001) and LDH concentration (H vs C, P < 0.01]. At term, H showed lower levels of sVCAM, sPselectin and SAA than C with respect to basal values (H vs C: ΔsVCAM: P < 0,01; ΔsPselectin: P < 0,05; ΔSAA: P < 0,01). Similarly, H showed diminished levels of TNFα (ΔTNFα: P < 0,05) and increased levels of IL-1RA and VEGF than C respect to basal values (H vs C: ΔIL-1RA and ΔVEGF: P < 0,05). CONCLUSION: Patients underwent HBOT improved O2 Sat with lower levels of severity markers (WC and platelets count, D dimer, LDH, SAA). Moreover, HBOT reduced proinflammatory agents (sVCAM, sPselectin, TNFα) and increased anti-inflammatory and pro-angiogenic ones (IL-1RA and VEGF).

Bio-oil production for biodiesel industry by Yarrowia lipolytica from volatile fatty acids in two-stage batch culture.

Microbial lipids-derived biodiesel is garnering much attention owing to its potential to substitute diesel fuel. In this study, lipid accumulation by Yarrowia lipolytica from volatile fatty acids (VFAs) was studied in a lab-scale stirred tank bioreactor. In batch cultures, Y. lipolytica NCYC 2904 was able to grow in 18 g·L-1 of VFAs (acetate, propionate, and butyrate), and the addition of a co-substrate (glucose) led to a fivefold improvement in lipid concentration. Furthermore, the two-stage batch culture (growth phase in glucose (1st stage) followed by a lipogenic phase in VFAs (2nd stage)) was the best strategy to obtain the highest lipid content in the cells (37%, w/w), with aeration conditions that kept dissolved oxygen concentration between 40% and 50% of saturation during the lipogenic phase. The estimated fuel properties of biodiesel produced from Y. lipolytica NCYC 2904 lipids are comparable with those of the biodiesel produced from vegetable oils and are in accordance with the international standards (EN 14214 and ASTM D6751). The cultivation strategies herein devised enable a sustainable, eco-friendly, and economical production of microbial lipids, based on feedstocks such as VFAs that can be derived from the acidogenic fermentation of organic wastes. KEY POINTS: • Addition of glucose to VFAs enhances lipids in Y. lipolytica in batch cultures • Two-stage batch culture - growth in glucose followed by VFAs pulse - rises lipids • Dissolved oxygen of 40-50% of saturation is crucial at the lipogenic phase.

Yarrowia lipolytica as a biorefinery platform for effluents and solid wastes valorization - challenges and opportunities.

Due to its physiological and enzymatic features, Yarrowia lipolytica produces several valuable compounds from a wide range of substrates. Appointed by some authors as an industrial workhorse, Y. lipolytica has an extraordinary ability to use unrefined and complex low-cost substrates as carbon and nitrogen sources, aiding to reduce the waste surplus and to produce added-value compounds in a cost-effective way. Dozens of review papers regarding Y. lipolytica have been published till now, proving the interest that this yeast arouses in the scientific community. However, most of them are focused on metabolic pathways involved in substrates assimilation and product formation, or the development of synthetic biology tools in order to obtain engineered strains for biotechnological applications. This paper provides an exhaustive and up-to-date revision on the application of Y. lipolytica to valorize liquid effluents and solid wastes and its role in developing cleaner biotechnological approaches, aiming to boost the circular economy. Firstly, a general overview about Y. lipolytica is introduced, describing its intrinsic features and biotechnological applications. Then, an extensive survey of the literature regarding the assimilation of oily wastes (waste cooking oils, oil cakes and olive mill wastewaters), animal fat wastes, hydrocarbons-rich effluents, crude glycerol and agro-food wastes by Y. lipolytica strains will be discussed. This is the first article that brings together the environmental issue of all such residues and their valorization as feedstock for valuable compounds production by Y. lipolytica. Finally, it will demonstrate the potential of this non-conventional yeast to be used as a biorefinery platform.

Análisis de la capa de células ganglionares con deep learning en el diagnóstico de glaucoma / Ganglion cell layer analysis with deep learning in glaucoma diagnosis

Objetivo Determinar y comparar la precisión diagnóstica en glaucoma de dos modelos de aprendizaje profundo, usando imágenes en infrarrojo del nervio óptico, del fondo de ojo y de la capa de células ganglionares (CCG). Métodos Hemos seleccionado una muestra de pacientes normales y con glaucoma. Se recogieron tres imágenes en infrarrojo con un tomógrafo de coherencia óptica de tipo spectral-domain (SD-OCT). La primera corresponde a la imagen de barrido confocal del fondo de ojo, la segunda es un recorte de la primera centrada en el nervio óptico, y la tercera fue la imagen del corte SD-OCT de la CCG. Nuestros modelos de aprendizaje profundo se desarrollaron en la plataforma MATLAB con las redes neuronales preentrenadas ResNet50 y VGG19. Resultados Se recogieron 498 ojos de 298 pacientes. De los 498 ojos, 312 son glaucomatosos y 186 son normales. En la prueba, la precisión de los modelos fue de 96% (ResNet50) y 96% (VGG19) para las imágenes de la CCG, de 90% (ResNet50) y 90% (VGG19) para las imágenes del nervio óptico y de 82% (ResNet50) y 84% (VGG19) para las de fondo de ojo. El área ROC en la prueba fue de 0,96 (ResNet50) y 0,97 (VGG19) para las imágenes de la CCG, de 0,87 (ResNet50) y 0,88 (VGG19) para las imágenes del nervio óptico, y de 0,79 (ResNet50) y 0,81 (VGG19) para las imágenes de fondo de ojo. Conclusiones Los dos modelos de aprendizaje profundo analizados, aplicados sobre las imágenes de la CCG, ofrecen una alta precisión diagnóstica, sensibilidad y especificidad en el diagnóstico de glaucoma (AU)

Objective To determine and compare the diagnostic precision in glaucoma of two deep learning models using infrared images of the optic nerve, eye fundus, and the ganglion cell layer (GCL). Methods We have selected a sample of normal and glaucoma patients. Three infrared images were registered with a spectral-domain optical coherence tomography (SD-OCT). The first corresponds to the confocal scan image of the fundus, the second is a cut-out of the first centered on the optic nerve, and the third was the SD-OCT image of the GCL. Our deep learning models are developed on the MatLab platform with the ResNet50 and VGG19 pre-trained neural networks. Results 498 eyes of 298 patients were collected. Of the 498 eyes, 312 are glaucoma and 186 are normal. In the test, the precision of the models was 96% (ResNet50) and 96% (VGG19) for the GCL images, 90% (ResNet50) and 90% (VGG19) for the optic nerve images and 82% (ResNet50) and 84% (VGG19) for the fundus images. The ROC area in the test was 0.96 (ResNet50) and 0.97 (VGG19) for the GCL images, 0.87 (ResNet50) and 0.88 (VGG19) for the optic nerve images, and 0.79 (ResNet50) and 0.81 (VGG19) for the fundus images. Conclusions Both deep learning models, applied to the GCL images, achieve high diagnostic precision, sensitivity and specificity in the diagnosis of glaucoma (AU)

Asociación entre interleuquinas inflamatorias y la presencia de trastornos intraventriculares de la conducción en pacientes con serología positiva para enfermedad de Chagas y función ventricular conservada / Association between inflammatory interleukins and intraventricular conduction disturbances in patients with positive serology for Chagas disease and preserved ventricular function

RESUMEN Introducción: Los trastornos intraventriculares de la conducción constituyen una manifestación habitual en los pacientes con enfermedad de Chagas con función ventricular izquierda conservada. Se desconoce si su presencia puede estar asociada a una mayor actividad inflamatoria. Objetivos: Determinar si existe una correlación entre los niveles de interleuquinas y la presencia de trastornos intraventriculares de la conducción en pacientes con serología positiva para enfermedad de Chagas y fracción de eyección ventricular izquierda conservada. Material y métodos: Se evaluó a 22 pacientes con edades comprendidas entre 21 y 80 años, seropositivos para enfermedad de Chagas, de más de 20 años de evolución y fracción de eyección ventricular izquierda mayor del 50%. Se analizó, además, un grupo control de 14 individuos sanos. Se determinaron las concentraciones en plasma de IFN-γ, IL-1β, IL-6, IL-10, IL-12 (p70), IL-15, IL-17A, MCP-1/CCL2, MIP-1 a/CCL3, TNF-a e IL-2. Se consideró trastornos intraventriculares de la conducción a la presencia de bloqueo de rama derecha, hemibloqueo anterior izquierdo o bloqueo de rama izquierda. Resultados: De los 22 pacientes con serología positiva para enfermedad de Chagas, 10 presentaron trastornos de la intraventriculares de la conducción (45,4%). En el grupo con trastornos intraventriculares de la conducción, se observaron niveles elevados de interleuquinas de alto efecto inflamatorio como INF-γ, IL-15, IL-2 (p70), IL-12, MP1-a, en comparación al grupo control, además de presentar altos valores de IL-10 como mecanismo modulador de una respuesta inmunitaria excesiva. Conclusiones: La asociación entre niveles elevados de interleuquinas y la presencia de trastornos intraventriculares de la conducción plantea un posible proceso inflamatorio crónico para su desarrollo en pacientes chagásicos con fracción de eyección ventricular izquierda conservada.

ABSTRACT Background: Intraventricular conduction disturbances are common in patients with Chagas disease and preserved left ventricular ejection fraction, but their association with higher inflammatory activity is unknown. Objectives: The aim of this study was to determine the presence of an association between interleukin levels and intraventricular conduction disturbances in patients with positive serology for Chagas disease and preserved left ventricular function. Methods: Twenty-two patients between 22 and 80 years of age with positive serology test for Chagas disease with more than 20 years progression and left ventricular ejection fraction ≥50% were included in the study and compared with a control group of 14 healthy individuals. Plasma levels of IFN-γ, IL-1β, IL-6, IL-10, IL-12 (p70), IL-15, IL-17A, MCP-1/CCL2, MIP-1 a/CCL3, TNF-a and IL-2 were measured in patients and controls. Right bundle branch block, left anterior hemiblock or left bundle branch block were considered intraventricular conduction disturbances. Results: Among the 22 patients with positive serology for Chagas disease, 10 presented intraventricular conduction disturbances (45.4%). This group had elevated levels of interleukins with high inflammatory effect such as INF-γ, IL-15, IL-2, IL-12, MIP-1 a, compared with the control group, and high levels of IL-10 as a regulatory mechanism of an excessive immune response. Conclusions: The association between elevated levels of inflammatory interleukins and intraventricular conduction disturbances suggests that chronic inflammation may play a role in the development of these abnormalities in patients with positive serology for Chagas disease and preserved left ventricular ejection function.

Factors affecting microbial lipids production by Yarrowia lipolytica strains from volatile fatty acids: Effect of co-substrates, operation mode and oxygen.

Volatile fatty acids (VFAs), which can be generated by acidogenesis of organic wastes, are important building blocks for chemicals production, and are intermediates in many bioprocesses such as microbial lipids production. Important factors affecting the bioconversion of VFAs (acetate, propionate and butyrate) by Yarrowia lipolytica W29 and NCYC 2904 for growth and lipids accumulation were studied. Yarrowia lipolytica grew efficiently in VFAs-based media, but lipids production was enhanced by the addition of co-substrates (glucose or glycerol) in batch cultures. A two-stage batch culture - growth phase on glucose, followed by VFAs addition, improved lipids accumulation. Lipids concentrations of 2.3 g·L-1 and 3.5 g·L-1 were obtained with this mode of operation, with addition of 18 g·L-1 VFAs, for Y. lipolytica W29 and NCYC 2904, respectively. For the first time, it was demonstrated that oxygen mass transfer is a crucial factor for lipids production by Y. lipolytica from VFAs. Intracellular lipids produced by Y. lipolytica strains were mainly composed by oleic and linoleic acids, similar to common vegetable oils, making these lipids suitable for biodiesel production. Moreover, margaric acid, which may improve biodiesel properties, was only detected in propionate medium. The strategies studied herein will contribute to the feasibility of using VFAs as low-cost feedstock for microbial lipids production by Y. lipolytica strains.

High prevalence of prolonged QTc interval among individuals in ambulatory diabetic care in southwestern Uganda.

BACKGROUND: Heart rate-corrected QT (QTc) interval is associated with increased risk for cardiovascular events and mortality among individuals with diabetes mellitus (DM). Little is known about the epidemiology of prolonged QTc among people with DM in resource-limited settings. METHODS: We conducted a cross-sectional study among adults with diabetes in ambulatory care at the Mbarara Regional Referral Hospital, from November 2018 to April 2019. Twelve-lead ECG recordings were performed on all participants. We collected clinical and laboratory data related to diabetes disease status and treatment control. We estimated QTc using Bazett's formula and categorized it according to standardized sex-adjusted thresholds. Linear regression analysis was performed to identify correlates of QTc. RESULTS: We recruited 299 participants with a mean age of 50.1 years (SD±9.8) and mean HbA1c of 9.7 % (SD±2.6), and 69.6% were female. We detected prolonged and borderline QTc in 6.4% (19/299, 95% CI: 3.9-9.7%) and 23.4% (70/299, 95% CI: 18.7-28.6%) of participants, respectively. In multivariate models, factors associated with increasing QTc interval were mean arterial pressure (ß=0.34; 95% CI: 0.07-0.63, p=0.019) and female sex (ß=15.26; 95% CI: 7.58-22.94, p0.001). CONCLUSIONS: The prevalence of abnormal QTc among individuals in routine diabetes care in southwestern Uganda was high. Female sex and mean arterial pressure were correlated with QTc interval. Given these findings, future studies should explore the clinical impact of abnormal QTc in this patient population.

Ganglion cell layer analysis with deep learning in glaucoma diagnosis. / Análisis de la capa de células ganglionares con deep learning en el diagnóstico de glaucoma.

OBJECTIVE: To determine and compare the diagnostic precision in glaucoma of two deep learning models using infrared images of the optic nerve, eye fundus, and the ganglion cell layer (GCL). METHODS: We have selected a sample of normal and glaucoma patients. Three infrared images were registered with a spectral-domain optical coherence tomography (SD-OCT). The first corresponds to the confocal scan image of the fundus, the second is a cut-out of the first centered on the optic nerve, and the third was the SD-OCT image of the GCL. Our deep learning models are developed on the MatLab platform with the ResNet50 and VGG19 pre-trained neural networks. RESULTS: 498 eyes of 298 patients were collected. Of the 498 eyes, 312 are glaucoma and 186 are normal. In the test, the precision of the models was 96% (ResNet50) and 96% (VGG19) for the GCL images, 90% (ResNet50) and 90% (VGG19) for the optic nerve images and 82% (ResNet50) and 84% (VGG19) for the fundus images. The ROC area in the test was 0.96 (ResNet50) and 0.97 (VGG19) for the GCL images, 0.87 (ResNet50) and 0.88 (VGG19) for the optic nerve images, and 0.79 (ResNet50) and 0.81 (VGG19) for the fundus images. CONCLUSIONS: Both deep learning models, applied to the GCL images, achieve high diagnostic precision, sensitivity and specificity in the diagnosis of glaucoma.

Inflammatory conditions promote a switch of oligosaccharyltransferase (OST) catalytic subunit isoform expression.

Oligosaccharyltransferase (OST) complex catalyzes the N-glycosylation of nascent polypeptides in the endoplasmic reticulum. Glycoproteins are critical for normal cell-cell interactions, especially during an immune response. Abnormal glycosylation is an insignia of several inflammatory diseases. However, the mechanisms that regulate the differential N-glycosylation are not fully understood. The OST complex can be assembled with one out of two catalytic subunits, STT3A or STT3B, which have different enzymatic properties. In this work, we investigated the expression of STT3A and STT3B in several mouse models such as a crossbreeding of normal and abortion-prone mice and an intestinal inflammation model. These animals were either exposed or not to acoustic stress (acute or chronic). The expression of the isoforms was analysed by immunohistochemistry and protein immunoblot. Finally, we investigated the gene regulatory elements employing public databases. Results demonstrated that inflammation alters the balance between the expression of both isoforms in the affected tissues. In homoeostatic conditions, STT3A expression predominates over STT3B, especially in epithelial cells. This relation is reversed as a consequence of inflammation. An increase in STT3B activity was associated to the generation of mannose-rich N-glycans. Accordingly, this type of N-glycans were found to decorate diverse inflamed tissues. The STT3A and STT3B genes are differentially regulated, which could account for the differences in the expression levels observed here. Our results support the idea that these isoforms could play different roles in cellular physiology. This study opens the possibility of studying the STT3A/STT3B expression ratio as a biomarker in acute inflammation or chronic diseases.

Prevalence and Correlates of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes in Uganda: A Hospital-Based Cross-sectional Study.

Background: Cardiovascular autonomic neuropathy (CAN) is a common complication in individuals with diabetes mellitus (DM) but often overlooked in clinical practice. The burden and correlates of CAN have not been extensively studied in low-income countries, particularly in sub-Saharan Africa. Objectives: To determine the prevalence and correlates of CAN among adults in ambulatory diabetes care in southwestern Uganda. Method: We conducted a cross-sectional study among adults with diabetes from November 2018 to April 2019. CAN was assessed using the five autonomic function tests: deep breathing, Valsalva maneuver, postural index on standing, change in blood pressure during standing and diastolic blood pressure response to isometric exercise. We estimated the prevalence of CAN and fit regression models to identify its demographic and clinical correlates. Results: We enrolled 299 individuals. The mean age was 50.1 years (SD ± 9.8), mean HbA1c was 9.7 (SD ± 2.6) and 69.6% were female. CAN was detected in 156/299 (52.2%) of the participants on the basis of one or more abnormal cardiovascular autonomic reflex tests. Out of 299 participants, 88 (29.4%) were classified as early CAN while 61/299 (20.4%) and 7/299 (2.3%) were classified as definite and severe (advanced) CAN respectively. In multivariable regression models, age over 50 years (aOR 3.48, 95%CI 1.35 -8.99, p = 0.010), duration of diabetes over 10 years (aOR 4.09, 95%CI 1.78 -9.38, p = 0.001), and presence of diabetic retinopathy (aOR 2.25, 95%CI 1.16 -4.34, p = 0.016) were correlated with CAN. Conclusions: Our findings reveal a high prevalence of CAN among individuals in routine outpatient care for diabetes mellitus in Uganda. Older age, longer duration of diabetes and coexistence of retinopathy are associated with CAN. Future work should explore the clinical significance and long term outcomes associated with CAN in this region.

Network Analysis of Cattle Movement in Mato Grosso Do Sul (Brazil) and Implications for Foot-and-Mouth Disease.

Foot-and mouth disease (FMD) is an animal disease that generates many economic impacts and sanctions on the international market. In 2018, Brazil, the world's largest beef exporter, had the recognition by World Organization for Animal Health (OIE) as a country free of FMD with vaccination and proposed to withdraw FMD vaccination throughout the country, based on a 10-year schedule, beginning in 2019. Therefore, Brazil needs studies to help the decision-making process, particularly regarding the availability of resources for strengthening of official animal health services. The state of Mato Grosso do Sul (MS) was chosen to be analyzed for three reasons: the size of its herd, the economic importance of its livestock and its location-which lies on the border with Paraguay and Bolivia. The current study adopted the Social Network Analysis and performed an exploratory analysis of cattle movement in MS. The most central municipalities in the networks were identified and they can be seen as crucial in strategies to monitor animal movement and to control outbreaks. The cattle movement networks demonstrated to be strongly connected, implying a high-speed potential FMD diffusion, in case of reintroduction. In a second stage, we performed an exploratory analysis of animal movement within the state, assuming distinct points in time for the identification of animal origin. The results of the analysis underlined the need and relevance of investing in animal control, sanitary education for producers and equipment and technologies to assist in the early detection, diagnosis, and eradication of outbreaks in a fast and efficient manner, preventing a possible outbreak from spreading to other regions.

Acoustic stress induces long term severe intestinal inflammation in the mouse.

The influence of noise on the presentation and progression of inflammatory bowel diseases has been poorly analyzed. We designed this study to investigate immediate and late effects of acoustic stress (AS) on small intestine. To this aim, CBA/J, BALB/c and DBA/2 mice were divided into AS and control groups. AS mice were exposed to noise (300Hz-70dB) during 24hs and randomized into: A) Acute effects group: mice were killed after AS; L) Late effects group: mice were killed 3 weeks after AS and O) Over-exposed effects group: mice were submitted to AS once a week during a month and killed. Small intestine sections were histologically examined. The expression of cytokines (IL-17, IL-22, TNF-α, INF-É£ and TGF-ß), CCL-25 and Ki67 was studied by immunohistochemistry and immunofluorescence techniques. "A" group displayed short and fragmented villi, diminished number of lamina propria cells, leucocyte infiltration, higher number of goblet cells and predominance of IL-17 expression. "L" group showed epithelial proliferative foci (CCL25+Ki67+) and increased TNFα/TGF-ß expression. Tissue damage was aggravated in "O" group. In conclusion, AS is able to trigger a severe intestinal inflammatory process in healthy mice, which spontaneously amplifies and perpetuates. Noise might be harmful to humans by aggravating inflammatory bowel diseases.

Analysis of triglyceride synthesis unveils a green algal soluble diacylglycerol acyltransferase and provides clues to potential enzymatic components of the chloroplast pathway.

BACKGROUND: Microalgal triglyceride (TAG) synthesis has attracted considerable attention. Particular emphasis has been put towards characterizing the algal homologs of the canonical rate-limiting enzymes, diacylglycerol acyltransferase (DGAT) and phospholipid:diacylglycerol acyltransferase (PDAT). Less work has been done to analyze homologs from a phylogenetic perspective. In this work, we used HMMER iterative profiling and phylogenetic and functional analyses to determine the number and sequence characteristics of algal DGAT and PDAT, as well as related sequences that constitute their corresponding superfamilies. We included most algae with available genomes, as well as representative eukaryotic and prokaryotic species. RESULTS: Amongst our main findings, we identified a novel clade of DGAT1-like proteins exclusive to red algae and glaucophyta and a previously uncharacterized subclade of DGAT2 proteins with an unusual number of transmembrane segments. Our analysis also revealed the existence of a novel DGAT exclusive to green algae with moderate similarity to plant soluble DGAT3. The DGAT3 clade shares a most recent ancestor with a group of uncharacterized proteins from cyanobacteria. Subcellular targeting prediction suggests that most green algal DGAT3 proteins are imported to the chloroplast, evidencing that the green algal chloroplast might have a soluble pathway for the de novo synthesis of TAGs. Heterologous expression of C. reinhardtii DGAT3 produces an increase in the accumulation of TAG, as evidenced by thin layer chromatography. CONCLUSIONS: Our analysis contributes to advance in the knowledge of complex superfamilies involved in lipid metabolism and provides clues to possible enzymatic players of chloroplast TAG synthesis.

Multiparity upregulates placental plasminogen and urokinase-type plasminogen activator.

PROBLEM: Multiparity increased the number of trophoblast cells in decidua of both low and high fetal loss mouse models. However, they differ in fetal survival rate and maternal thymocyte subpopulations, suggesting that trophoblast invasiveness is not equivalent. Our aim was to explore the involved mechanism. METHOD OF STUDY: We studied placentae from primiparous and multiparous females of low and high fetal loss models. We investigated invasiveness in vitro, expression of plasminogen, and its activators: tissue type (tPA)-urokinase type (uPA), and activity and expression of matrix metalloproteinases (MMP)-2 and MMP-9. RESULTS: Placental invasiveness is upregulated by multiparity, but lesser in the high fetal loss model. Multiparous animals showed elevated expression of plasminogen and uPA. However, the high fetal loss combination showed higher expression of a short and less active fragment of uPA (LMW-uPA). MMP-2, MMP-9, and tPA were unaffected. CONCLUSION: uPA would participate in the increased multiparity-associated placental invasiveness.