Micronutrient fortification of food and its impact on woman and child health: A systematic review

Background: Vitamins and minerals are essential for growth and metabolism. The World Health Organization estimates that more than 2 billion people are deficient in key vitamins and minerals. Groups most vulnerable to these micronutrient deficiencies are pregnant and lactating women and young children, given their increased demands. Food fortification is one of the strategies that has been used safely and effectively to prevent vitamin and mineral deficiencies.Methods: A comprehensive search was done to identify all available evidence for the impact of fortification interventions. Studies were included if food was fortified with a single, dual or multiple micronutrients and impact of fortification was analyzed on the health outcomes and relevant biochemical indicators of women and children. We performed a meta-analysis of outcomes using Review Manager Software version 5.1.Results: Our systematic review identified 201 studies that we reviewed for outcomes of relevance. Fortification for children showed significant impacts on increasing serum micronutrient concentrations. Hematologic markers also improved, including hemoglobin concentrations, which showed a significant rise when food was fortified with vitamin A, iron and multiple micronutrients. Fortification with zinc had no significant adverse impact on hemoglobin levels. Multiple micronutrient fortification showed non-significant impacts on height for age, weight for age and weight for height Z-scores, although they showed positive trends. The results for fortification in women showed that calcium and vitamin D fortification had significant impacts in the post-menopausal age group. Iron fortification led to a significant increase in serum ferritin and hemoglobin levels in women of reproductive age and pregnant women. Folate fortification significantly reduced the incidence of congenital abnormalities like neural tube defects without increasing the incidence of twinning. The number of studies pooled for zinc and multiple micronutrients for women were few, though the evidence suggested benefit. There was a dearth of evidence for the impact of fortification strategies on morbidity and mortality outcomes in women and children.Conclusion: Fortification is potentially an effective strategy but evidence from the developing world is scarce. Programs need to assess the direct impact of fortification on morbidity and mortality

Deep learning-based segmentation and quantification in experimental kidney histopathology

Background Nephropathologic analyses provide important outcomes-related data in experiments with the animal models that are essential for understanding kidney disease pathophysiology. Precision medicine increases the demand for quantitative, unbiased, reproducible, and efficient histopathologic analyses, which will require novel high-throughput tools. A deep learning technique, the convolutional neural network, is increasingly applied in pathology because of its high performance in tasks like histology segmentation. Methods We investigated use of a convolutional neural network architecture for accurate segmentation of periodic acid-Schiff-stained kidney tissue from healthy mice and five murine disease models and from other species used in preclinical research. We trained the convolutional neural network to segment six major renal structures: glomerular tuft, glomerulus including Bowman’s capsule, tubules, arteries, arterial lumina, and veins. To achieve high accuracy, we performed a large number of expert-based annotations, 72,722 in total. Results Multiclass segmentation performance was very high in all disease models. The convolutional neural network allowed high-throughput and large-scale, quantitative and comparative analyses of various models. In disease models, computational feature extraction revealed interstitial expansion, tubular dilation and atrophy, and glomerular size variability. Validation showed a high correlation of findings with current standard morphometric analysis. The convolutional neural network also showed high performance in other species used in research—including rats, pigs, bears, and marmosets—as well as in humans, providing a translational bridge between preclinical and clinical studies. Conclusions We developed a deep learning algorithm for accurate multiclass segmentation of digital whole-slide images of periodic acid-Schiff-stained kidneys from various species and renal disease models. This enables reproducible quantitative histopathologic analyses in preclinical models that also might be applicable to clinical studies

Next-Generation Morphometry for pathomics-data mining in histopathology

Pathology diagnostics relies on the assessment of morphology by trained experts, which remains subjective and qualitative. Here we developed a framework for large-scale histomorphometry (FLASH) performing deep learning-based semantic segmentation and subsequent large-scale extraction of interpretable, quantitative, morphometric features in non-tumour kidney histology. We use two internal and three external, multi-centre cohorts to analyse over 1000 kidney biopsies and nephrectomies. By associating morphometric features with clinical parameters, we confirm previous concepts and reveal unexpected relations. We show that the extracted features are independent predictors of long-term clinical outcomes in IgA-nephropathy. We introduce single-structure morphometric analysis by applying techniques from single-cell transcriptomics, identifying distinct glomerular populations and morphometric phenotypes along a trajectory of disease progression. Our study provides a concept for Next-generation Morphometry (NGM), enabling comprehensive quantitative pathology data mining, i.e., pathomics

Radioterapia: lesões inflamatórias e funcionais de órgãos pélvicos Radiotherapy: inflammatory and functional lesions of pelvic organs

A radioterapia pélvica tem sido cada vez mais indicada, em doses crescentes,como coadjuvante no tratamento das neoplasias pélvicas, com resultados cada vez melhores, mas com efeitos colaterais significativos. O advento da radioterapia tridimensional conformal estabelece um método que permite a mais precisa seleção de direção e de intensidade de raios emitidos para alvos pontuais, objetivando quase que exclusivamente o tumor, com a conseqüente preservação dos tecidos vizinhos, portanto com maior efetividade e com o mínimo de efeitos colaterais crônicos e insolúveis. Essas são as possibilidades teóricas que precisam ser comprovadas na prática.Elas envolvem um campo de observação cujos resultados reais tem sido subestimados, principalmente quando referidos a efeitos adversos. Esses não se limitam exclusivamente às mucosites, mas, também, a aspectos funcionais envolvendo incapacidades que vão, quando se trata do reto, além do que sempre foi atribuído à suposta síndrome da ressecção anterior 58, para abranger danos diretos da radiação sobre os complexos esfincterianos e os nervos dos plexos lombo-sacrais 21,22,59-63. Por enquanto, seja para o câncer de reto, para o câncer ginecológico e para o câncer de próstata, somos conclamados a investir no modelo mais preventivo do que curativo, ainda que o preventivo signifique apenas a mais precoce ação, pois para essas doenças de altas incidências e mortalidades "prevenir" no sentido de ação mais precoce é, sem dúvida, bem melhor que remediar, principalmente quando se faz uso das terapias neo-adjuvantes que poderiam ser dispensadas, em casos selecionados, para não somar ao desconforto emocional do portador do câncer todas as impossibilidades das iatrogenias inerentes ao tratamento que objetiva a cura. Assim, precisamos encontrar os fatores preditivos que nos permitam escolher os pacientes com probabilidade de cura apenas com o tratamento cirúrgico, para que eles fiquem livres da radioterapia e, por outro lado, buscar o aperfeiçoamento da técnica de radiação para os casos cujas necessidades excedam a abrangência do tratamento cirúrgico, exclusivo.<br>Radiotherapy reducing local failure rates and improving overall survival has a favorable impact on the primary treatment of rectal cancer. However, radiation as an adjuvant therapy for that purpose and other pelvic malignances has been shown to increase long-term morbidity causing severe rectal or vesical mucositis, sometimes stenosis, undistensibler rectum with reduced capacity and/or anorectal dysfunction due lombosacralneuropathy with physiologic changes whose interaction remains poorly understood 60,63. Those iatrogenic outcomes stress the need for finding predictive factors for local recurrence to exclude patients with very high probability for cure with surgery alone and to use optimized radiation techniques22,64