数据之美——聚焦全球器官捐献发展趋势

器官移植术是20世纪出现的针对器官功能衰竭的最有效治疗方法，每年拯救全球超过12万例患者。但供器官短缺的现状，与器官移植技术和辅助药物的发展不匹配，制约了器官移植事业的发展。我国自2015年起已成为全球器官捐献和移植大国之一，2017年公民逝世后器官捐献数量超过5 000例，占全球捐献总量的15%以上。黄洁夫教授总结的器官捐献与移植"中国模式"得到了世界卫生组织、国际移植界的高度重视和充分肯定。本文通过整理全球及各国的器官捐献与移植数据，剖析全球现状与发展趋势，进一步探索我国公民器官捐献的影响因素并提出针对性的应对策略，以期实现我国器官捐献和移植的"自给自足"。     

Computer-Aided Diagnosis of Vertebral Compression Fractures Using Convolutional Neural Networks and Radiomics

Journal of Digital Imaging - Vertebral Compression Fracture (VCF) occurs when the vertebral body partially collapses under the action of compressive forces. Non-traumatic VCFs can be secondary to...     

Pinealectomy interferes with the circadian clock genes expression in white adipose tissue

Melatonin, the main hormone produced by the pineal gland, is secreted in a circadian manner (24‐hr period), and its oscillation influences several circadian biological rhythms, such as the regulation of clock genes expression (chronobiotic effect) and the modulation of several endocrine functions in peripheral tissues. Assuming that the circadian synchronization of clock genes can play a role in the regulation of energy metabolism and it is influenced by melatonin, our study was designed to assess possible alterations as a consequence of melatonin absence on the circadian expression of clock genes in the epididymal adipose tissue of male Wistar rats and the possible metabolic repercussions to this tissue. Our data show that pinealectomy indeed has impacts on molecular events: it abolishes the daily pattern of the expression of Clock, Per2, and Cry1 clock genes and Pparγ expression, significantly increases the amplitude of daily expression of Rev‐erbα, and affects the pattern of and impairs adipokine production, leading to a decrease in leptin levels. However, regarding some metabolic aspects of adipocyte functions, such as its ability to synthesize triacylglycerols from glucose along 24 hr, was not compromised by pinealectomy, although the daily profile of the lipogenic enzymes expression (ATP‐citrate lyase, malic enzyme, fatty acid synthase, and glucose‐6‐phosphate dehydrogenase) was abolished in pinealectomized animals.     

Variation of resting energy expenditure after the first chemotherapy cycle in acute leukemia patients

Changes in resting energy expenditure (REE) of cancer patients vary depending on type of tumor, treatment time point and kind of treatment. Little is known about REE of acute leukemia adult patients after treatment, especially with results related to body weight or fat free mass (FFM). This study aimed to assess changes in REE of acute leukemia adult patients before and after the first remission induction. Evaluation of REE was performed by indirect calorimetry and predicted REE was calculated by Harris-Benedict equation. Weight and height were measured and compared to a control group of healthy individuals. FFM was assessed by bioelectrical impedance for adjusting REE values. We evaluated 18 patients and 26 healthy individuals. At diagnosis, patients presented REE, REE/weight, and REE/FFM higher than the controls. Reductions of REE, REE/weight, and REE/FFM were also observed in patients after the first cycle of chemotherapy. The predicted REE for the patients group showed significant lower value compared with measured REE. Before the first cycle of chemotherapy REE was increased but undergoes a reduction after treatment, reaching values similar to the controls. For predictive Harris-Benedict equation, stress factors should be added to avoid underestimation of REE before and after chemotherapy.     

The use of Trichomonas vaginalis purine nucleoside phosphorylase to activate fludarabine in the treatment of solid tumors

Treatment with fludarabine phosphate (9-β-D-arabinofuranosyl-2-F-adenine 5′-phosphate, F-araAMP) leads to regressions and cures of human tumor xenografts that express Escherichia coli purine nucleoside phosphorylase (EcPNP). This occurs despite the fact that fludarabine (F-araA) is a relatively poor substrate for EcPNP, and is cleaved to liberate 2-fluoroadenine at a rate only 0.3% that of the natural E. coli PNP substrate, adenosine. In this study, we investigated a panel of naturally occurring PNPs to identify more efficient enzymes that may be suitable for metabolizing F-araA as part of experimental cancer therapy. We show that Trichomonas vaginalis PNP (TvPNP) cleaves F-araA with a catalytic efficiency 25-fold greater than the prototypic E. coli enzyme. Cellular extracts from human glioma cells (D54) transduced with lentivirus stably expressing TvPNP (D54/TvPNP) were found to cleave F-araA at a rate similar to extracts from D54 cells expressing EcPNP, although much less enzyme was expressed per cell in the TvPNP transduced condition. As a test of safety and efficacy using TvPNP, human head and neck squamous cell carcinoma (FaDu) xenografts expressing TvPNP were studied in nude mice and shown to exhibit robust tumor regressions, albeit with partial weight loss that resolved post-therapy. F-araAMP was also a very effective treatment for mice bearing D54/TvPNP xenografts in which approximately 10% of tumor cells expressed the enzyme, indicating pronounced ability to kill non-transduced tumor cells (high bystander activity). Moreover, F-araAMP demonstrated activity against D54 tumors injected with an E1, E3 deleted adenoviral vector encoding TvPNP. In that setting, despite higher F-araA cleavage activity using TvPNP, tumor responses were similar to those obtained with EcPNP, indicating factors other than F-Ade production may limit regressions of the D54 murine xenograft model. Our results establish that TvPNP is a favorable enzyme for activating F-araA, and support further studies in combination with F-araAMP for difficult-to-treat human cancers.     

Spatial distribution of intestinal parasitic infections in a Kaingáng indigenous village from Southern Brazil

The spatial distribution of enteroparasitosis in an indigenous village from Paraná was evaluated to identify areas of risk for these infections. A cross-sectional study (from November 2010 to June 2011) was performed using Three Faecal Test^® and Kato &; Katz method and a questionnaire on housing and hygiene conditions was administered. Local geostatistical analyses were performed to determine the spatial distribution of intestinal parasitic infections. The overall prevalence of enteroparasites was 67.2?% (457/680), and the most prevalent taxa were Ascaris lumbricoides (48.8?%) and Trichuris trichiura (44.7?%). The prevalence of heavy infection by soil-transmitted helminths was 3.6?% and the families lived in houses with an average of 5.1 residents and < 2 bedrooms per household. The average number of species per individual present spatial heterogeneity with the highest values (≥0.8) in areas with high clustering of residences. The visualization of the spatial distribution of intestinal parasites in this indigenous village is an important contribution to determining health risk areas and planning decisions and services.