Iron-catalyzed stereoselective C-H alkylation for simultaneous construction of C-N axial and C-central chirality.

The assembly of chiral molecules with multiple stereogenic elements is challenging, and, despite of indisputable advances, largely limited to toxic, cost-intensive and precious metal catalysts. In sharp contrast, we herein disclose a versatile C-H alkylation using a non-toxic, low-cost iron catalyst for the synthesis of substituted indoles with two chiral elements. The key for achieving excellent diastereo- and enantioselectivity was substitution on a chiral N-heterocyclic carbene ligand providing steric hindrance and extra represented by noncovalent interaction for the concomitant generation of C-N axial chirality and C-stereogenic center. Experimental and computational mechanistic studies have unraveled the origin of the catalytic efficacy and stereoselectivity.

Spirulina (Arthrospira platensis) supplementation: Impact on growth, metabolism, and antioxidant status in zebrafish.

Zebrafish (Danio rerio) is a valuable model for biomedical research because of its mammalian genetic similarities, rapid reproduction, and low maintenance costs. However, further investigation is required regarding their nutritional requirements and standardized laboratory diets. This study evaluated the metabolic and growth responses of zebrafish juveniles fed on diets supplemented with spirulina, Arthrospira platensis (SP) at different levels for 77 days. Six diets with SP inclusion levels of 0%, 2%, 4%, 6%, 8%, and 10% (SP0-SP10) were formulated. A total of 300 zebrafish juveniles with an average initial weight of 0.113 ± 0.10 g (mean ± SD) were randomly distributed across six groups, with five replicates per group, each containing 10 animals. After 77 days, the SP6 group demonstrated significantly enhanced growth performance compared with the other supplementation levels. The condition factor was markedly higher in the SP6 and SP8 groups than in the SP0 group. No significant effects on total cholesterol levels were observed, but the SP4, SP6, and SP10 diets decreased triglyceride levels. Lipase activity was higher in the SP6 and SP8 groups than in the control group, whereas amylase activity showed no significant differences between treatments. Catalase and superoxide dismutase activities were significantly higher in the SP8 and SP10 groups than in the SP0 and SP2 groups. Glutathione S-transferase activity was higher in the SP6, SP8, and SP10 groups than in the SP0 group. In addition, SP inclusion in zebrafish diets improved female gonadal development. In conclusion, this study indicates that SP supplementation has substantial potential as a growth promoter, positively influencing lipid metabolism and antioxidant enzyme activity without affecting zebrafish survival.

Chagas Disease: A Silent Threat for Dogs and Humans.

Chagas disease (CD) is a vector-borne Neglected Zoonotic Disease (NZD) caused by a flagellate protozoan, Trypanosoma cruzi, that affects various mammalian species across America, including humans and domestic animals. However, due to an increase in population movements and new routes of transmission, T. cruzi infection is presently considered a worldwide health concern, no longer restricted to endemic countries. Dogs play a major role in the domestic cycle by acting very efficiently as reservoirs and allowing the perpetuation of parasite transmission in endemic areas. Despite the significant progress made in recent years, still there is no vaccine against human and animal disease, there are few drugs available for the treatment of human CD, and there is no standard protocol for the treatment of canine CD. In this review, we highlight human and canine Chagas Disease in its different dimensions and interconnections. Dogs, which are considered to be the most important peridomestic reservoir and sentinel for the transmission of T. cruzi infection in a community, develop CD that is clinically similar to human CD. Therefore, an integrative approach, based on the One Health concept, bringing together the advances in genomics, immunology, and epidemiology can lead to the effective development of vaccines, new treatments, and innovative control strategies to tackle CD.

Major determinants of primary non function from kidney donation after Maastricht II circulatory death: A single center experience.

PURPOSE: Organ shortage greatly limits treatment of patients with end-stage chronic kidney. Maastricht type 2 donation after circulatory death (DCD) has been shown to have similar results in long term outcomes in kidney transplantation, when compared with brain dead donation. Our main goal was to assess Maastricht type 2 DCD and evaluate factors that impact on early graft function. METHODS: A retrospective study was conducted in an ECMO Referral Centre. All patients who received a kidney transplant from Maastricht type 2 DCD were included in study. Early graft function and short term outcomes were assessed. RESULTS: From October 2017 to December 2022, 47 renal grafts were collected from 24 uDCD donors. Median warm ischemia time was 106 min (94-115), cannulation time was 10 min (8; 20) and duration of extracorporeal reperfusion (ANOR) was 180 min (126-214). Regarding early graft function, 25% had immediate graft function, 63.6% had delayed graft function and 11.4% had primary non-function (PNF). There was a correlation between cannulation time (p = 0.006) and ANOR with PNF (p = 0.016). CONCLUSIONS: Cannulation time and ANOR were the main factors that correlated with PNF. Better understanding of underlying mechanisms should be sought in future studies to reduce the incidence of PNF.

Diet with different concentrations of lychee peel flour modulates oxidative stress parameters and antioxidant activity in zebrafish.

The agri-food industry generates substantial waste, leading to significant environmental impacts. Lychee (Litchi chinensis Sonnerat), which is rich in bioactive compounds in its peel, pulp, and seeds, offers an opportunity for waste use. This study aimed to evaluate the effects of supplementing a high-carbohydrate diet with varying levels of lychee peel flour on lipid metabolism biomarkers and oxidative stress in a zebrafish (Danio rerio) model. A total of 225 zebrafish, approximately four months old, were divided into five groups: control, high-carbohydrate (HC), HC2%, HC4%, and HC6%. The study did not find significant differences in the growth performance of zebrafish in any group. However, the HC6% group exhibited a significant decrease in glucose and triglyceride levels compared with the HC group. Furthermore, this group showed enhanced activities of the antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD), along with reduced levels of malondialdehyde (MDA). Increased antioxidant activity was also evidenced by DPPH-, ABTS+, and ß-carotene/Linoleic acid assays in the HC6% group. A positive correlation was identified between SOD/CAT activity and in vitro antioxidant assays. These findings suggest that dietary supplementation with 6% lychee peel flour can significantly modulate glucose homeostasis, lipid metabolism, and antioxidant activity in zebrafish.

Kidney failure secondary to hereditary xanthinuria due to a homozygous deletion of the XDH gene, in the absence of overt kidney stone disease.

Hereditary xanthinuria (HXAN) is a rare metabolic disorder that results from mutations in either the xanthine dehydrogenase (XDH) or the molybdenum cofactor sulfurase genes (MOCOS), respectively defining HXAN type I and type II. Hypouricemia, hypouricosuria, and abnormally high plasma and urine levels of xanthine, causing susceptibility to xanthine nephrolithiasis and deposition of xanthine crystals in tissues, are the metabolic hallmarks of HXAN. Several pathogenic variants in the XDH gene have so far been identified in patients with HXAN type I, but the clinical phenotype associated with the whole deletion of the human XDH gene is unknown. Herein, we report the case of a woman diagnosed with HXAN, whose molecular genetic testing revealed a homozygous microdeletion involving the XDH gene. Distinctive features of her medical history were the diagnosis of arterial hypertension and microalbuminuria at 22 years of age; a single pregnancy, at the age of 25, complicated by proteinuria and transient kidney function deterioration in the third trimester; unexplained severe hypouricaemia incidentally discovered during pregnancy; inability to breastfeed her newborn daughter due to primary agalactia; chronic kidney disease (CKD) stage 3 diagnosed at age 35; and progression to end-stage kidney disease over the next 12 years. Protocol non-invasive laboratory and imaging investigation was not informative as to the cause of CKD. This is the first description of the clinical phenotype associated with a natural knockout of the human XDH gene. Despite the lack of kidney histopathology data, the striking similarities with the phenotypes exhibited by comparable murine models validates the latter as useful sources of mechanistic insights for the pathogenesis of the human disease, supporting the hypothesis that the absence of xanthine dehydrogenase activity might represent a susceptibility factor for chronic tubulointerstitial nephritis, even in patients without kidney stones.

Sleep deprivation increases the regularity of isometric torque fluctuations.

The regularity of the fluctuations present in torque signals represent the adaptability of the motor control. While previous research showed how it is affected by neuromuscular fatigue and ageing, the underlying mechanisms remain unclear. It is currently under debate whether these changes are explained by central or peripheral neuromuscular mechanisms. Here, we experimentally manipulated the sleep of thirteen young adults through a supervised 24 h-sleep deprivation protocol. This study aimed to investigate the effect of sleep deprivation on the regularity of torque fluctuations, and other standard torque-related outcomes (Peak Torque - PT - and Rate of Torque Development - RTD). The participants were asked to perform knee extension maximal voluntary contractions (MVC) and submaximal knee extensions at 40% of MVC for 30 s. PT and RTD were calculated from the MVC and the regularity of the torque fluctuations was determined on the submaximal task through Sample Entropy (SampEn). In addition, rate of perceived effort (RPE) was collected. We found no significant changes in PT and RTD. The regularity of torque fluctuations significantly increased (i.e., a decrease in SampEn) after 24 h-sleep deprivation (PRE = 1.76 ± 0.268, POS24 = 1.71 ± 0.306; p = 0.044). Importantly, we found a negative correlation between RPE and SampEn relative changes after sleep deprivation. This study brings new insights towards the understanding of the underlying mechanisms that explain changes in torque fluctuations, demonstrating that these changes are not limited to neuromuscular processes but are also likely to be affected by other domains, such as psychological profile, which can indirectly affect the neural drive to the muscles.

The Ketone Bridge Between the Heart and the Bladder: How Fast Should We Go?

Metabolic syndrome (MS) is associated with both cardiovascular and bladder dysfunction. Insulin resistance (IR) and central obesity, in particular, are the main risk factors. In these patients, vicious pathological cycles exacerbate abnormal carbohydrate metabolism and sustain an inflammatory state, with serious implications for both the heart and bladder. Ketone bodies serve as an alternative energy source in this context. They are considered a "super-fuel" because they generate adenosine triphosphate with less oxygen consumption per molecule, thus enhancing metabolic efficiency. Ketone bodies have a positive impact on all components of MS. They aid in weight loss and glycemic control, lower blood pressure, improve lipid profiles, and enhance endothelial function. Additionally, they possess direct anti-inflammatory, antioxidant, and vasodilatory properties. A shared key player in dysfunction of both the heart and bladder dysfunction is the formation of the NLRP3 inflammasome, which ketone bodies inhibit. Interventions that elevate ketone body levels-such as fasting, a ketogenic diet, ketone supplements, and sodium-glucose cotransporter 2 inhibitors-have been shown to directly affect cardiovascular outcomes and improve lower urinary tract symptoms derived from MS. This review explores the pathophysiological basis of the benefits of ketone bodies in cardiac and bladder dysfunction.

Effects of interprofessional practice on nursing workload in hospitals: A systematic review.

OBJECTIVE: To synthesise scientific evidence on interprofessional practice in hospital care and the effects on nursing workload. METHODS: Systematic mixed method review, registered in PROSPERO (CRD42021225627) and conducted in the following databases: CINAHL, Medline, Web of Science and Scopus, with no restrictions on the publication period of the studies. Primary studies were recruited on nurses' interprofessional practice (actions and interactions with other professional categories) in hospitals and the effects on one or more dimensions of nursing workload (quantitative, qualitative, physical, cognitive, emotional, time and variation). Scientific articles available in open access, in English, Spanish or Portuguese, were included. The searches were carried out in January 2021. The studies were evaluated by pairs of independent researchers to verify methodological quality, through the Mixed Method Appraisal Tool, and data extraction. To summarise the studies, thematic analysis was adopted. RESULTS: A total of 1774 publications were assessed for eligibility and 17 studies were included. Of these, two were mixed methods, four were qualitative, and 11 were quantitative, published between 2011 and 2020. The main scenarios investigated were Intensive Care Units and/or Inpatient Units. During data analysis, three thematic categories emerged: Interprofessional practice in coping with emotional overload; Time dedicated by nurses to professional communication; and Working conditions and patient care. The third category consisted of three subthemes: Conflict and flexibility in the context of practice; Working conditions and interprofessional practice; and Effects on patient care. CONCLUSIONS: The evidence points to the emotional overload of nurses in the face of uncooperative practices. Interprofessional actions, especially communicative ones, demand nurses' time and impact the care provided. The results contribute to political decisions and health work management.

High-throughput phenotyping using VIS/NIR spectroscopy in the classification of soybean genotypes for grain yield and industrial traits.

Employing visible and near infrared sensors in high-throughput phenotyping provides insight into the relationship between the spectral characteristics of the leaf and the content of grain properties, helping soybean breeders to direct their program towards improving grain traits according to researchers' interests. Our research hypothesis is that the leaf reflectance of soybean genotypes can be directly related to industrial grain traits such as protein and fiber contents. Thus, the objectives of the study were: (i) to classify soybean genotypes according to the grain yield and industrial traits; (ii) to identify the algorithm(s) with the highest accuracy for classifying genotypes using leaf reflectance as model input; (iii) to identify the best input data for the algorithms to improve their performance. A field experiment was carried out in randomized block design with three replications and 32 soybean genotypes. At 60 days after emergence, spectral analysis was carried out on three leaf samples from each plot. A hyperspectral sensor was used to capture reflectance between the wavelengths from 450 to 824 nm. Representative spectral bands were selected and grouped into means. After harvest, grain yield was assessed and laboratory analyses of industrial traits were carried out. Spectral, industrial traits and yield data were subjected to statistical analysis. Data were analyzed by the following machine learning algorithms: J48 (J48) and REPTree (DT) decision trees, Random Forest (RF), Artificial Neural Networks (ANN), Support Vector Machine (SVM), and conventional Logistic Regression (LR) analysis. The clusters formed were used as the output of the models, while two groups of input data were used for the input of the models: the spectral variables (WL) noise-free obtained by the sensor (450-828 nm) and the spectral means of the selected bands (SB) (450.0-720.6 nm). Soybean genotypes were grouped according to their grain yield and industrial traits, in which the SVM and J48 algorithms performed better at classifying them. Using the spectral bands selected in the study improved the classification accuracy of the algorithms.

Integrity and filtration efficiency of decontaminated N95/PFF2 masks to protect health care professionals against COVID-19: A systematic literature review and meta-analysis.

BACKGROUND: To evaluate the evidence related to maintaining the integrity and filtration efficiency of N95 and/or PFF2 respirators after decontamination in health care professionals' protection against COVID-19. METHODS: Systematic review, developed based on the guidelines from Joanna Briggs Institute for syntheses focusing on effectiveness evidence. The protocol was registered on the International Prospective Register of Ongoing Systematic Reviews platform, under the number CRD42022354256. This study report was developed in accordance with the guidelines recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Publications between January 2020 and August 2022 were selected of Embase, Medline, CINAHL, Web of Science, Cochrane, SciELO and Virtual Health Library databases. Joanna Briggs critical appraisal tool for nonrandomized experimental tests was used to evaluate the evidence quality. RESULTS: Seven articles were included in the data extraction and critical evaluation, and 3 in the meta-analysis. Four studies evaluated the integrity by visual inspection and 2 by electron microscopy. There was no association between the number of cycles increase and the reduction in filtration in up to 10 cycles. None study was considered of high methodological quality. CONCLUSIONS: There is some evidence that integrity and filtration capacity were maintained after decontamination of N95/PFF2 respirators to prevent COVID-19.

Evaluation of the Anti-Inflammatory and Antioxidant Potential of Cymbopogon citratus Essential Oil in Zebrafish.

This study explored the protective capacity of the essential oil (EO) of Cymbopogon citratus against oxidative stress induced by hydrogen peroxide (H2O2) and the inflammatory potential in zebrafish. Using five concentrations of EO (0.39, 0.78, 1.56, 3.12, and 6.25 µg/mL) in the presence of 7.5 mM H2O2, we analyzed the effects on neutrophil migration, caudal fin regeneration, cellular apoptosis, production of reactive oxygen species (ROS), and activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) after 96 h of exposure. A significant decrease in neutrophil migration was observed in all EO treatments compared to the control. Higher concentrations of EO (3.12 and 6.25 µg/mL) resulted in a significant decrease in caudal fin regeneration compared to the control. SOD activity was reduced at all EO concentrations, CAT activity significantly decreased at 3.12 µg/mL, and GST activity increased at 0.78 µg/mL and 1.56 µg/mL, compared to the control group. No significant changes in ROS production were detected. A reduction in cellular apoptosis was evident at all EO concentrations, suggesting that C. citratus EO exhibits anti-inflammatory properties, influences regenerative processes, and protects against oxidative stress and apoptosis.

Clinical guidelines for posterior restorations based on Coverage, Adhesion, Resistance, Esthetics, and Subgingival management. The CARES concept: Part III ­ subgingival margins, "ferrule" design, and posts in severely compromised teeth

Despite the clear advances regarding the restoration of posterior teeth, especially with the minimally invasive approach, there are still several topics where the available scientific evidence does not provide clear answers in terms of clinical decisions. The indications, differences, and clinical protocols for partial adhesive restorations (onlays, overlays, and endocrowns) and resistance form restorations (full-contour resistive crowns) were presented in Parts I and II of the present article series based on Coverage of susceptible cusps, Adhesion advantages and limitations, Resistance forms to be implemented, Esthetic concerns, and Subgingival management - the CARES concept. Now, in Part III, the focus is on different approaches of managing subgingival areas, gaining "ferrule" design, and the role of posts on the restorability strategies of severely compromised teeth.

Evaluation of the Influence of Geodimensional and Histological Parameters on the Need for Margin Widening in Breast Lesions Marked With Magnetic Seeds.

Objective: Breast cancer is an important topic worldwide, posing morbidity and mortality to women. Considerable efforts have been put in the early recognition of malignancy through different screening methods, such as mammography and ultrasound. The precise localization of infraclinical malignant lesions is key in surgical management and magnetic seeds gather particular interest for this purpose. As with other systems, a need for reintervention may be needed to obtain adequate surgical margins. This work evaluated the relation between the need for surgical reintervention in order to obtain negative margins and geodimensional and histological parameters. The main objective was the identification of parameters significantly associated with reintervention for margin widening. Materials and Methods: A retrospective analysis of 198 patients from a single centre was performed. The association between pre-defined geodimensional and histological parameters and the need for margin widening in infraclinical lesions marked with magnetic seed was evaluated. Results: Results showed that reintervention to widen margins was significantly higher in patients with ductal carcinoma in situ (DCIS) in the pre-operative biopsy when compared with invasive carcinoma (p = 0.03) in the bivariate analysis. No statistically significant differences were observed between the need for reintervention and lesion size (p = 0.197), breast quadrant location (p = 0.626) and distance of skin to lesion (p = 0.356). Conclusion: This work suggests that a more invasive margin clearance in lesions with a pre-operative DCIS diagnosis might obviate the need for reintervention to obtain negative margins. On the other hand, it is not necessary to be surgically more invasive in larger lesions, deeply located or that are present in a certain quadrant, since there are no significant differences regarding the need for reintervention.

Potential Effects of Essential Oil from Plinia cauliflora (Mart.) Kausel on Leishmania: In Vivo, In Vitro, and In Silico Approaches.

In the search for new chemotherapeutic alternatives for cutaneous leishmaniasis (CL), essential oils are promising due to their diverse biological potential. In this study, we aimed to investigate the chemical composition and leishmanicidal and anti-inflammatory potential of the essential oil isolated from the leaves of Plinia cauliflora (PCEO). The chemical composition of PCEO showed ß-cis-Caryophyllene (24.4%), epi-γ-Eudesmol (8%), 2-Naphthalenemethanol[decahydro-alpha] (8%), and trans-Calamenene (6.6%) as its major constituents. Our results showed that the PCEO has moderate cytotoxicity (CC50) of 137.4 and 143.7 µg/mL on mice peritoneal exudate cells (mPEC) and Vero cells, respectively. The PCEO was able to significantly decrease mPEC infection by Leishmania amazonensis and Leishmania braziliensis. The value of the inhibitory concentration (IC50) on amastigote forms was about 7.3 µg/mL (L. amazonensis) and 7.2 µg/mL (L. braziliensis). We showed that PCEO induced drastic ultrastructural changes in both species of Leishmania and had a high selectivity index (SI) > 18. The in silico ADMET analysis pointed out that PCEO can be used for the development of oral and/or topical formulation in the treatment of CL. In addition, we also demonstrated the in vivo anti-inflammatory effect, with a 95% reduction in paw edema and a decrease by at least 21.4% in migration immune cells in animals treated with 50 mg/kg of PCEO. Taken together, our results demonstrate that PCEO is a promising topical therapeutic agent against CL.

Cerebral Tuberculosis After Therapy With Adalimumab for Hidradenitis Suppurativa: A Rare Case.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with limited therapeutic options. Adalimumab, an anti-tumor necrosis factor-alpha (TNF-α) monoclonal antibody, was the first biological agent approved for the treatment of moderate to severe HS. Tuberculosis (TB) is a highly prevalent global public health problem, affecting individuals worldwide. Continuous immunosuppression from TNF-α treatment increases the risk of TB development. Isolated neurotuberculosis, in the absence of other symptoms, emerges as a rarely observed infection pattern in such patients. We present a case of a 23-year-old woman with severe HS undergoing treatment with adalimumab. After two years, she developed a pronounced occipital tension headache, constant nausea, and persistent fever. The patient's latent TB status was unknown without annual screening. Subsequent magnetic resonance imaging revealed a lesion in the cerebellar vermis. Immunosuppressive therapy was suspended and an etiological study was conducted; the only positive result was the interferon-gamma release assay. Empirically, antituberculosis treatment and prednisolone were initiated, leading to clinical and neurological improvement. After one year of treatment, symptoms resolved without neurological sequelae. This case highlights the importance of vigilant monitoring before, during, and after immunosuppressive treatment. Early recognition, discontinuation of anti-tumor necrosis factor medications, and appropriate management of TB are crucial to prevent complications.

The complexity of decisions in genetics: annotation of three novel variants in the PKD1 and PKD2 genes.

As nephrology practice is evolving towards precision medicine, and genetic tests are becoming widely available, basic genetic literacy is increasingly required for clinical nephrologists. Yet, decisions based on results of genetic tests are seldom straightforward. We report a 37-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) who was referred for medically assisted reproduction with monogenic preimplantation genetic testing (PGT-M). The PKD1 and PKD2 genes were screened for pathogenic variants. Sequencing analysis revealed the presence of three novel missense single nucleotide variants, two in the PKD1 gene - c.349T>G, p.(Leu117Val) and c.1736C>T, p.(Pro579Leu); and the third in the PKD2 gene - c.1124A>G, p.(Asn375Ser). Bioinformatic predictions of the functional effects of those three missense variants were inconsistent across different software tools. The family segregation analysis, which was mandatory to identify the relevant variant(s) for PGT-M, strongly supported that the disease-causing variant was PKD1 c.349T>G p.(Leu117Val), while the other two were non-pathogenic or, at most, phenotypic modulators. Proving the pathogenicity of novel variants is often complex, but is critical to guide genetic counselling and screening, particularly when discussing reproductive alternatives for primary prevention in the progeny of at-risk couples. The family reported herein illustrates those challenges in the setting of ADPKD, and the invaluable importance of a detailed family history and segregation analysis for proper clinical annotation of novel variants. Basic genetic knowledge and proper clinical annotation of novel allelic variants in genes associated with hereditary kidney disorders are increasingly necessary for the contemporary practice of clinical nephrology.

Filarial disease in the Brazilian Amazon and emerging opportunities for treatment and control.

Following the successful eradication of Wuchereria bancrofti, there are now just three species of conventional microfilaremic human filarial parasites endemic to the Brazilian Amazon region: Mansonella ozzardi, Mansonella perstans and Onchocerca volvulus. The zoonotic filarial parasite Dirofilaria immitis is also found in the Amazon region as are several sylvatic filarial parasites, some of which have been recorded causing zoonoses and some of which have never been recorded outside the region. Onchocerca volvulus is only found in the Amazonia onchocerciasis focus in the Brazilian state of Roraima where it affects the people of the Yanomami tribe living around the densely forested Venezuela border region. Mansonella ozzardi is by far the most common filarial parasite in Brazil and has a broad but patchy distribution throughout the western Amazon region. Recorded in the Brazilian states of Acre, Roraima, Matto Grosso, and within almost every municipality of Amazonas state, it is believed that pollution of the urban stream and river systems prevents the development of the simuliid vectors of M. ozzardi and explains the parasite's reduced distribution within urban areas and an absence of recent reports from the state capital Manaus. Decades of WHO-led periodic ivermectin treatment of Yanomami tribe's people have resulted in the partial suppression of O. volvulus transmission in this focus and has also probably affected the transmission of M. ozzardi in the region. Mansonella perstans, O. volvulus and very probably M. ozzardi infections can all be treated and most likely cured with a 4-6-week treatment course of doxycycline. The Brazilian Ministry of Health does not, however, presently recommend any treatment for mansonellosis infections and thus parasitic infections outside the Amazonia focus are typically left untreated. While the long treatment courses required for doxycycline-based mansonellosis therapies preclude their use in control programmes, new fast-acting filarial drug treatments are likely to soon become available for the treatment of both onchocerciasis and mansonellosis in the Amazon region. Filarial disease management in the Brazilian Amazon is thus likely to become dramatically more viable at a time when the public health importance of these diseases is increasingly being recognized.

Development of an automated estimation of foot process width using deep learning in kidney biopsies from patients with Fabry, minimal change, and diabetic kidney diseases.

Podocyte injury plays a key role in pathogenesis of many kidney diseases with increased podocyte foot process width (FPW), an important measure of podocyte injury. Unfortunately, there is no consensus on the best way to estimate FPW and unbiased stereology, the current gold standard, is time consuming and not widely available. To address this, we developed an automated FPW estimation technique using deep learning. A U-Net architecture variant model was trained to semantically segment the podocyte-glomerular basement membrane interface and filtration slits. Additionally, we employed a post-processing computer vision approach to accurately estimate FPW. A custom segmentation utility was also created to manually classify these structures on digital electron microscopy (EM) images and to prepare a training dataset. The model was applied to EM images of kidney biopsies from 56 patients with Fabry disease, 15 with type 2 diabetes, 10 with minimal change disease, and 17 normal individuals. The results were compared with unbiased stereology measurements performed by expert technicians unaware of the clinical information. FPW measured by deep learning and by the expert technicians were highly correlated and not statistically different in any of the studied groups. A Bland-Altman plot confirmed interchangeability of the methods. FPW measurement time per biopsy was substantially reduced by deep learning. Thus, we have developed a novel validated deep learning model for FPW measurement on EM images. The model is accessible through a cloud-based application making calculation of this important biomarker more widely accessible for research and clinical applications.