Designing Nutritionally Adequate and Climate-Friendly Diets for Omnivorous,Pescatarian, Vegetarian and Vegan Adolescents in Sweden Using Linear Optimization

Low-carbon diets can counteract climate change and promote health if they are nutritionally adequate, affordable and culturally acceptable. This study aimed at developing sustainable diets and to compare these with the EAT-Lancet diet. The Swedish national dietary survey Riksmaten Adolescents 2016–2017 was used as the baseline. Diets were optimized using linear programming for four dietary patterns: omnivores, pescatarians, vegetarians and vegans. The deviation from the baseline Riksmaten diet was minimized for all optimized diets while fulfilling nutrient and climate footprint constraints. Constraining the diet-related carbon dioxide equivalents of omnivores to 1.57 kg/day resulted in a diet associated with a reduction of meat, dairy products, and processed foods and an increase in potatoes, pulses, eggs and seafood. Climate-friendly, nutritionally adequate diets for pescatarians, vegetarians and vegans contained fewer foods and included considerable amounts of fortified dairy and meat substitutes. The optimized diets did not align very well with the food-group pattern of the EAT-Lancet diet. These findings suggest how to design future diets that are climate-friendly, nutritionally adequate, affordable, and culturally acceptable for Swedish adolescents with different dietary patterns. The discrepancies with the EAT diet indicate that the cultural dietary context is likely to play an important role in characterizing sustainable diets for specific populations.     

Main partitioning criteria for the characterization of the health status in the freshwater mussel Anodonta cygnea from spontaneously polluted area in Western Ukraine

The aim of this study was to appreciate the consequences of spontaneous human activity for freshwater mollusks in the generally ecologically sustainable area in Western Ukraine. For this, bivalve mollusk, Anodonta cygnea, at three sites, with mixed agricultural and municipal activities (A), close to a municipal water inlet (F) and the cooling pond of a nuclear power plant (N), were studied in spring, summer, and autumn. The set of parameters included the characteristics of oxidative stress (activity of catalase (CAT), levels of protein carbonyls (PC)), levels of reduced and oxidized glutathione (GSH, GSSG, respectively), activities of lactate dehydrogenase (LD), cholinesterase (ChE), ethoxyresorufin‐O‐deethylase (EROD), glutathione S‐transferase (GST) in the digestive gland, and concentrations of vitellogenin‐like proteins (Vtg‐LP) in gonads and also morphological indices. Although the discriminant functional analysis confirmed the general seasonal regularities for studied groups, it allowed to discriminate between sites (P < 0.05). At site A, oxidative stress; high levels of LD, EROD, and GST; and low levels of ChE and condition factor were reflected. This demonstrated the sensitivity of mussels to constant effect of mixed pollution. At site N, oxidative injury was shown that might be explained by the constantly high temperature. At site F, abrupt elevations of Vtg‐LP and EROD levels in autumn were probably related to an emergency situation on the nearby dump. So, both chronic and temporal environmental effects were reflected by a set of markers in mollusk. The classification and regression tree (CART) algorithm selected GSH and PC in the digestive gland and Vtg‐LP as partitioning criteria for the characterization of mussel health status. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.     

B7-H3 silencing increases paclitaxel sensitivity by abrogating Jak2/Stat3 phosphorylation

In many types of cancer, the expression of the immunoregulatory protein B7-H3 has been associated with poor prognosis. Previously, we observed a link between B7-H3 and tumor cell migration and invasion, and in present study, we have investigated the role of B7-H3 in chemoresistance in breast cancer. We observed that silencing of B7-H3, via stable short hairpin RNA or transient short interfering RNA transfection, increased the sensitivity of multiple human breast cancer cell lines to paclitaxel as a result of enhanced drug-induced apoptosis. Overexpression of B7-H3 made the cancer cells more resistant to the drug. Next, we investigated the mechanisms behind B7-H3-mediated paclitaxel resistance and found that the level of Stat3 Tyr705 phosphorylation was decreased in B7-H3 knockdown cells along with the expression of its direct downstream targets Mcl-1 and survivin. The phosphorylation of Janus kinase 2 (Jak2), an upstream molecule of Stat3, was also significantly decreased. In contrast, reexpression of B7-H3 in B7-H3 knockdown and low B7-H3 expressing cells increased the phosphorylation of Jak2 and Stat3. In vivo animal experiments showed that B7-H3 knockdown tumors displayed a slower growth rate than the control xenografts. Importantly, paclitaxel treatment showed a strong antitumor activity in the mice with B7-H3 knockdown tumors, but only a marginal effect in the control group. Taken together, our data show that in breast cancer cells, B7-H3 induces paclitaxel resistance, at least partially by interfering with Jak2/Stat3 pathway. These results provide novel insight into the function of B7-H3 and encourage the design and testing of approaches targeting this protein and its partners.     

Magnetic resonance imaging and computed tomography developments in imaging of venous thromboembolism

Venous thromboembolism (VTE) is a disease that causes high morbidity and mortality in the population. At present the first-line imaging test for a suspected pulmonary embolism (PE) is computed tomography (CT) pulmonary angiography, and ultrasonography is widely used for the diagnosis of deep-vein thrombosis (DVT). Although these modalities are proven to be safe and accurate, unresolved issues remain, such as whether CT scanning in patients with a suspected PE should be extended to the legs. Another issue is the diagnosis of recurrent DVT. Magnetic resonance imaging (MRI) offers a number of advantages in the imaging of VTE. Recent developments of scanning protocols with shorter acquisition times, sometimes complemented by navigator gating or making use of endogenous contrast, offer new perspectives for the use of MRI. This review provides an overview of state of the art MRI techniques for the diagnosis of PE and DVT. Furthermore, the use of new contrast agents such as fibrin labeling to detect thrombi are addressed.     

Value of bilateral breast cancer for identification of rare recessive at-risk alleles: evidence for the role of homozygous GEN1 c.2515_2519delAAGTT mutation

Virtually all known tumor predisposing genes have been identified via the analysis of familial cancer cases. Here we argue that this approach is likely to miss recessively acting cancer genes and suggest the analysis of family history-negative patients with multiple primary malignancies for identifying homozygous at-risk genotypes. We performed calculations showing that the homozygous carriers of rare recessive cancer predisposing alleles are unlikely to report a family history of the disease. We further revealed that the c.2515_2519delAAGTT homozygous mutation in a Holliday junction resolvase, GEN1, was overrepresented in women with bilateral breast cancer (BC) as compared to healthy controls [11/360 (3.1 %) vs. 18/1305 (1.4 %); odds ratio (OR) = 2.25 (1.02–4.75); p = 0.031], although this trend was not maintained in unilateral BC patients [23/1851 (1.2 %)]. Noticeably, presence of biallelic c.2515_2519delAAGTT mutation was associated with the absence of BC in mother both in bilateral and unilateral BC cases [7/239 (3.0 %) vs. 0/41 (0 %) and 21/1,558 (1.3 %) vs. 0/215 (0 %), respectively; Mantel–Haenszel p = 0.041]. Thus, this study suggests that identification of dominant and recessive cancer predisposing genes may require distinct study groups.     

MicroRNA-182 promotes leptomeningeal spread of non-sonic hedgehog-medulloblastoma

The contribution of microRNAs to the initiation, progression, and metastasis of medulloblastoma (MB) remains poorly understood. Metastatic dissemination at diagnosis is present in about 30% of MB patients, and is associated with a dismal prognosis. Using microRNA expression profiling, we demonstrate that the retinal miR-183-96-182 cluster on chromosome 7q32 is highly overexpressed in non-sonic hedgehog MBs (non-SHH-MBs). Expression of miR-182 and miR-183 is associated with cerebellar midline localization, and miR-182 is significantly overexpressed in metastatic MB as compared to non-metastatic tumors. Overexpression of miR-182 in non-SHH-MB increases and knockdown of miR-182 decreases cell migration in vitro. Xenografts overexpressing miR-182 invaded adjacent normal tissue and spread to the leptomeninges, phenotypically reminiscent of clinically highly aggressive large cell anaplastic MB. Hence, our study provides strong in vitro and in vivo evidence that miR-182 contributes to leptomeningeal metastatic dissemination in non-SHH-MB. We therefore reason that targeted inhibition of miR-182 may prevent leptomeningeal spread in patients with non-SHH-MB.     

Novel synthetic analogue of ACTH 4–10 (Semax) but not glycine prevents the enhanced nitric oxide generation in cerebral cortex of rats with incomplete global ischemia

This work investigates whether nitric oxide production and lipid peroxidation contribute to the pathophysiology of ischemia and whether glycine and a novel Russian compound, Semax are neuroprotective via a mechanism involving the regulation nitric oxide (NO) and lipid peroxidation. In brief, nitric oxide and indices of lipid peroxidation were elevated following global ischemia. While glycine proved ineffective in reducing NO levels or ameliorating the neurological deficits following global ischemia, Semax proved to be highly effective in abating the rise in nitric oxide and restoring neurologic functioning.     

Coding polymorphisms in Casp5, Casp8 and DR4 genes may play a role in predisposition to lung cancer

Apoptosis plays a role in the elimination of DNA-damaged cells thus protecting the host from cancer development. Some data indicate that normal variations within the sequence of apoptotic genes may lead to suboptimal apoptotic capacity and therefore increased cancer risk. We tested 19 coding apoptotic gene SNPs in 2-stage molecular epidemiological study. For the preliminary sorting of SNP candidates, we employed a “comparison of extremes” approach, where 111 patients with highly pronounced LC susceptibility (non-smokers or young-onset light smokers) were analyzed against 110 subjects with the evidence for LC tolerance (elderly tumor-free heavy smokers). Three genotypes demonstrated possible association with LC risk (Leu/Leu-homozygotes for Casp5 Val318Leu versus other genotypes: OR = 2.47 (95% CI: 1.07–5.69), p = 0.03; His-carriers for Casp8 His302Asp: OR = 2.26 (95% CI: 1.18–4.31), p = 0.02; Arg-carriers for DR4 Lys441Arg: OR = 1.89 (95% CI: 1.05–3.40), p = 0.03), and therefore were selected for the validation. The extended study included 2 case-control series, namely subjects from Russia (351 LC cases and 538 controls) and Moldova (296 LC cases and 295 controls). Interestingly, all three candidate genotypes consistently demonstrated OR above 1 both in Russian and in Moldovian groups. Although the combined Mantel–Haenszel analysis yet failed to reach statistical significance (OR = 1.22 (95% CI: 0.90–1.65), p = 0.21; OR = 1.17 (95% CI: 0.92–1.50), p = 0.21; OR = 1.19 (95% CI: 0.95–1.51), p = 0.14, respectively), the obtained data indicate that Casp5, Casp8 and DR4 gene polymorphisms may deserve consideration in large-scale case-control studies of LC risk modifiers.