The Interobserver Reliability of Grading of Distal Radius Volar Plate Prominence.

PURPOSE: The 3-category rating of volar plate prominence in relation to the most volar edge of the distal radius (the watershed line) on lateral radiographs was reliable among a small group of surgeons and associated with the probability of flexor tendon irritation and potential rupture. Classifications are often less reliable when tested among a large group of practicing surgeons in different environments. METHODS: In this survey-based experiment, an international group of 115 fracture and upper extremity surgeons viewed 1 of 4 sets of 24 lateral radiographs (96 unique lateral radiographs) of patients with distal radius fractures who underwent volar plating in the practice of a single surgeon using 2 types of plates. Surgeons were asked to rate the following metrics: (1) the grade of plate prominence according to Soong, (2) whether the plate was more prominent than the watershed line, (3) whether the plate was separate from the bone distally, and (4) whether there is more than 5° of dorsal angulation of the distal radius articular surface. RESULTS: The interobserver agreement of the classification was "fair" (κ = 0.32; 95% confidence interval [CI] = 0.27-0.36), and grading was more reliable among surgeons who do not supervise trainees. Volar prominence was less reliable (κ = 0.034; 95% CI = 0.013-0.055) than plate separation from bone (κ = 0.50; 95% CI = 0.42-0.59) and more than 5° of dorsal angulation (κ = 0.42; 95% CI = 0.35-0.48). CONCLUSIONS: Among a large number of international practicing surgeons, the classification of volar plate prominence in 3 categories was fair. CLINICAL RELEVANCE: The diagnosis of plate prominence might develop toward criteria with moderate reliability, such as separation of the plate from the bone and residual angulation of the distal radius.

Differences in the sugar content of fast-food products across three countries.

OBJECTIVE: To compare the sugar content of items at four multinational fast-food chains, across three countries. DESIGN: Total sugar (g)/per serving was extracted from online nutrition information, and sugar/100 g serving was calculated. Foods were categorised as: breakfast sandwiches, burgers, sandwiches, desserts and condiments. Beverages were categorised as fountain, frozen or pre-packaged. Sugar (g) was compared across countries using linear mixed-effects models. Pairwise comparisons were performed with Tukey-Kramer adjustments. SETTING: USA, Germany and Australia. PARTICIPANTS: Burger King™ (Hungry Jack's™), Kentucky Fried Chicken™, McDonald's™ and Subway™. RESULTS: Differences in total sugar/100 g or ml were observed across countries for burgers (n 104), desserts (n 110), sandwiches (n 178), pre-packaged beverages (n 36) and frozen beverages (n 72). Comparing identical items across countries (e.g. BigMacTM from McDonalds in USA, Germany and Australia), burgers (n 10 available in all three countries) had lower sugar content in Australia (3·4 g/100 g) compared with the USA (4·7 g/100 g, P = 0·02) or Germany (4·6 g/100 g, P = 0·04), yet no differences were observed in other food categories. Comparing the same beverages across countries (e.g. chocolate shake from Burger King), frozen beverages (n 4 available in all three countries) had lower sugar content in Australia (14·2 g/100 ml), compared with the USA (20·3 g/100 ml, P = 0·0005) or Germany (17·8 g/100 ml, P = 0·0148), yet no differences were observed in other beverage categories. CONCLUSIONS: Heterogeneity in fast-food sugar content across countries suggests that reductions are possible and should be implemented to reduce health risks associated with excess added sugar intake.

Perspective: Chaos in a Bottle-A Critical Evaluation of Beverage Categorization in Nutrition Research.

Beverage consumption is an important contributor to total daily calorie intake among children and adolescents. While associations between excess calories from beverages and development of obesity are well established, a standardized approach for beverage categorization does not exist. As a result, there is marked heterogeneity in assessment and categorization of beverage intake across studies. The purpose of this article is to critically review beverage categorization in recent (published since 2010) observational studies that evaluated beverage intake in relation to weight/adiposity in US youth, and to put forth an initial proposal for a standardized beverage classification system. Standardized beverage classification is critical to ensure transparency in nutrition science research and facilitate comparison of findings across studies. A systematic literature search identified 37 eligible studies, across which beverage categorization varied considerably. The most heterogeneity was observed for categorization of "sugar-sweetened beverages" and the greatest consistency was observed for categorization of 100% juices. This review provides an evidence-based starting point for urgently needed, collaborative work to determine priorities for beverage categorization and leverage existing standards of identity in order to create and disseminate a standardized beverage classification system. A standardized approach will inform meaningful assessment of beverage consumption in research studies and facilitate impactful translation of research findings into public health nutrition policy.

Consumption of Diet Soda Sweetened with Sucralose and Acesulfame-Potassium Alters Inflammatory Transcriptome Pathways in Females with Overweight and Obesity.

SCOPE: Low-calorie sweetener (LCS) consumption is associated with metabolic disease in observational studies. However, physiologic mechanisms underlying LCS-induced metabolic impairments in humans are unclear. This study is aimed at identifying molecular pathways in adipose impacted by LCSs. METHODS AND RESULTS: Seven females with overweight or obesity, who did not report LCS use, consumed 12 ounces of diet soda containing sucralose and acesulfame-potassium (Ace-K) three times daily for 8 weeks. A subcutaneous adipose biopsy from the left abdomen and a fasting blood sample were collected at baseline and post-intervention. Global gene expression were assessed using RNA-sequencing followed by functional pathway analysis. No differences in circulating metabolic or inflammatory biomarkers were observed. However, ANOVA detected 828 differentially expressed annotated genes after diet soda consumption (p < 0.05), including transcripts for inflammatory cytokines. Fifty-eight of 140 canonical pathways represented in pathway analyses regulated inflammation, and several key upstream regulators of inflammation (e.g., TNF-alpha) were also represented. CONCLUSION: Consumption of diet soda with sucralose and Ace-K alters inflammatory transcriptomic pathways (e.g., NF-κB signaling) in subcutaneous adipose tissue but does not significantly alter circulating biomarkers. Findings highlight the need to examine molecular and metabolic effects of LCS exposure in a larger randomized control trial for a longer duration.

Dihydroxyacetone induced autophagy in African trypanosomes.

Dihydroxyacetone (DHA) was examined to explore its trypanocidal activity. The compound is easily taken up by trypanosomes via its aquaglyceroporins but is not converted to a glycolytic intermediate due to the lack of a respective kinase. Investigating the DHA-induced cell death it became evident that parasites die by autophagy rather than by necrosis or apoptosis. Since autophagy is not well studied in African trypanosomes our work offers a way to investigate the importance of autophagy for trypanosomes not only for stress coping but also for organelle reconstruction during differentiation.

Spermine isolated and identified as the major trypanocidal compound from the snake venom of Eristocophis macmahoni causes autophagy in Trypanosoma brucei.

The snake venom from the leaf-nosed viper Eristocophis macmahoni was analyzed regarding its toxic effects on the bloodstream form of Trypanosoma brucei. A considerable trypanocidal effect was measured with an IC5 value of 186 ng/ml in bloodstream form parasites. Following several high performance liquid chromatography (HPLC) separation steps, the major trypanocidal activity was assigned to a single fraction by in vitro toxicity assays. Analysis by off-line ESI-MS(n) revealed an m/z value of 202.2 for the precursor ion and fragment ions of m/z=129.1 (MS2) and 112.1 (MS3), respectively, clearly corresponding to the molecular mass and the fragmentation pattern of the polyamine spermine. Quantification of spermine within the viper venom using an on-line hydrophilic interaction chromatography (HILIC) ESI-MS method revealed that this compound constituted approximately 1% of the dry venom mass. The polyamine oxidase activity in the fetal calf serum used for cultivation was responsible for a trypanocidal effect of pure spermine in the low micromolar range, whereas the antitrypanosomal activity of crude snake venom was virtually independent from serum, suggesting the oxidation of spermine by intrinsic venom components. Using fetal calf serum, spermine was shown to induce autophagy in the parasites using transmission electron microscopy (TEM).

Stereospecific synthesis of chiral 2,3-dihydro-1,4-benzodithiine and methyl-2,3-dihydro-1,4-benzodithiine derivatives and their toxic effects on Trypanosoma brucei.

Preparation of chiral 2,3-dihydro-1,4-benzodithiine and methyl-2,3-dihydro-1,4-benzodithiine derivatives with known absolute configurations from the easily accessible chiral synthons benzyl 4-O-trifloxy-2,3-anhydro-beta-L-ribopyranoside and benzyl 4-O-trifloxy-2,3-anhydro-alpha-D-ribopyranoside is described. These compounds showed significant in vitro toxicity of the bloodstream form of Trypanosoma brucei with an IC50 of 11 microM. The parasites' energy metabolism and consumption of oxygen were found to be affected during incubation.

Kola acuminata proanthocyanidins: a class of anti-trypanosomal compounds effective against Trypanosoma brucei.

Human African trypanosomiasis is undergoing an alarming rate of recrudescence in many parts of sub-Saharan Africa. Yet, there is no successful chemotherapy for the disease due to a limited number of useful drugs, side effects and drawbacks of the existing medication, as well as the development of drug resistance by the parasite. Here we describe a new lead anti-trypanosomal compound isolated from Kola acuminata (Makasu). We purified a proanthocyanidin by chromatographic procedures and confirmed its homogeneity and structure by Nuclear Magnetic Resonance and Matrix-Assisted Laser Desorption Ionisation Time-of-Flight mass spectrometry, respectively. In vitro, this compound potently induced growth arrest and lysis of bloodstream form trypanosomes in a dose- and time-dependent manner. In a mouse model, it exhibited a trypanostatic effect that extended the life of infected, treated animals up to 8 days post-infection against the 4 days for infected, untreated animals. The proanthocyanidin showed a low cytotoxicity against mammalian cells, whereas treated-BF showed massive enlargement of their flagellar pocket and lysosome-like structures caused by an intense formation of multivesicular bodies and vesicles within these organelles. The observed ultrastructural alterations caused rupture of plasma membranes and the release of cell contents, indicative of a necrotic process rather than a programmed cell death. Interestingly, the proanthocyanidin acted against BF but not procyclic form trypanosomes. This new anti-trypanosomal compound should be further studied to determine its efficacy and suitability as an anti-trypanosomal drug and may be used as a tool to define novel specific drug targets in BF trypanosomes.

Genetic characterization of glucose transporter function in Leishmania mexicana.

Both insect and mammalian life cycle stages of Leishmania mexicana take up glucose and express all three isoforms encoded by the LmGT glucose transporter gene family. To evaluate glucose transporter function in intact parasites, a null mutant line has been created by targeted disruption of the LmGT locus that encompasses the LmGT1, LmGT2, and LmGT3 genes. This deltalmgt null mutant exhibited no detectable glucose transport activity. The growth rate of the deltalmgt knockout in the promastigote stage was reduced to a rate comparable with that of WT cells grown in the absence of glucose. deltalmgt cells also exhibited dramatically reduced infectivity to macrophages, demonstrating that expression of LmGT isoforms is essential for viability of amastigotes. Furthermore, WT L. mexicana were not able to grow as axenic culture form amastigotes if glucose was withdrawn from the medium, implying that glucose is an essential nutrient in this life cycle stage. Expression of either LmGT2 or LmGT3, but not of LmGT1, in deltalmgt null mutants significantly restored growth as promastigotes, but only LmGT3 expression substantially rescued amastigote growth in macrophages. Subcellular localization of the three isoforms was investigated in deltalmgt cells expressing individual LmGT isoforms. Using anti-LmGT antiserum and GFP-tagged LmGT fusion proteins, LmGT2 and LmGT3 were localized to the cell body, whereas LmGT1 was localized specifically to the flagellum. These results establish that each glucose transporter isoform has distinct biological functions in the parasite.