Authors response on Schick et al. 2017 \u201cAn experiment of the impact of a neonicotinoid pesticide on honey bees; the value of a formal analysis of the data\u201d. Environ Sci Eur (2017)

Abstract Whilst a formal statistical analysis of any experimental data is always preferable in principle, in the case of Pilling et al. (PLoS ONE 8:e77193, 2013 ), it is hard to see how the results of any formal analysis\u2014including those provided by Schick et al.\u2014could be considered reliable. Regardless of the issue of statistical analysis, there was a wealth of valuable and novel biological and chemical residue data generated under field conditions of use in Pilling et al., which when taken into consideration alongside other relevant available published data and information (i.e. expert judgement) demonstrated a low risk to honeybees from thiamethoxam when used as a seed treatment on oilseed rape. Indeed, similar conclusions have been reported in subsequent published honeybee field studies using thiamethoxam seed-treated oilseed rape, thus supporting the original conclusions of Pilling et al

Comparative transcriptomics of elasmobranchs and teleosts highlight important processes in adaptive immunity and regional endothermy

Abstract Background Comparative genomic and/or transcriptomic analyses involving elasmobranchs remain limited, with genome level comparisons of the elasmobranch immune system to that of higher vertebrates, non-existent. This paper reports a comparative RNA-seq analysis of heart tissue from seven species, including four elasmobranchs and three teleosts, focusing on immunity, but concomitantly seeking to identify genetic similarities shared by the two lamnid sharks and the single billfish in our study, which could be linked to convergent evolution of regional endothermy. Results Across seven species, we identified an average of 10,877 Swiss-Prot annotated genes from an average of 32,474 open reading frames within each species\u2019 heart transcriptome. About half of these genes were shared between all species while the remainder included functional differences between our groups of interest (elasmobranch vs. teleost and endotherms vs. ectotherms) as revealed by Gene Ontology (GO) and selection analyses. A repeatedly represented functional category, in both the uniquely expressed elasmobranch genes (total of 259) and the elasmobranch GO enrichment results, involved antibody-mediated immunity, either in the recruitment of immune cells (Fc receptors) or in antigen presentation, including such terms as \u201cantigen processing and presentation of exogenous peptide antigen via MHC class II\u201d, and such genes as MHC class II, HLA-DPB1 . Molecular adaptation analyses identified three genes in elasmobranchs with a history of positive selection, including legumain ( LGMN ), a gene with roles in both innate and adaptive immunity including producing antigens for presentation by MHC class II. Comparisons between the endothermic and ectothermic species revealed an enrichment of GO terms associated with cardiac muscle contraction in endotherms, with 19 genes expressed solely in endotherms, several of which have significant roles in lipid and fat metabolism. Conclusions This collective comparative evidence provides the first multi-taxa transcriptomic-based perspective on differences between elasmobranchs and teleosts, and suggests various unique features associated with the adaptive immune system of elasmobranchs, pointing in particular to the potential importance of MHC Class II. This in turn suggests that expanded comparative work involving additional tissues, as well as genome sequencing of multiple elasmobranch species would be productive in elucidating the regulatory and genome architectural hallmarks of elasmobranchs

Primary neuroendocrine breast carcinomas are associated with poor local control despite favourable biological profile: a retrospective clinical study

Abstract Background Breast carcinomas with neuroendocrine features (NEBC) are a very rare entity of mammary neoplasms, WHO classification of which has recently been revised. There are very limited data available about the clinical behaviour and treatment options of NEBC. Methods We collected retrospectively patients with NEBC from Oulu and Helsinki University Hospitals in 2007\u20132015. There were 43 NEBC cases during the period. Results The incidence of NEBC from all breast cancers varied from 0.1% in Helsinki to 1.3% in Oulu. The mean tumor size was 2.2\ua0cm and 23 patients (55.8%) had no lymph node metastases when diagnosed. In total, 4 patients (9.3%) had distant metastases at the time of diagnosis. High estrogen receptor (ER) expression was observed in 41 (97.7%) patients. When non-metastatic NEBC were compared to a prospective set of ductal carcinomas (n\u2009=\u2009506), NEBC were more often HER2 negative ( p\u2009= \u20090.046), ER positive ( p\u2009= \u20090.0062) and the NEBC patients were older ( p \u2009<\u20090.0005) than patients with ductal carcinomas. Plasma chromogranin A correlated only to higher age at diagnosis ( p\u2009= \u20090.0028). Relapse-free survival ( p\u2009= \u20090.0013), disease-free survival ( p\u2009= \u20090.024) and overall survival ( p\u2009= \u20090.0028) favoured ductal carcinomas compared to NEBC, while no difference was observed in distant disease-free survival or in breast cancer-specific survival. Conclusions There is remarkable variation in the incidence of NEBC in Finland, which is likely to be explained by differences in the use of neuroendocrine marker immunostainings. Poor local control and worse overall survival may be linked to the more aggressive biology of the disease, despite its association with apparently indolent prognostic factors

A misdiagnosed case of osteoid osteoma of the talus: a case report and literature review

Abstract Background Osteoid osteoma (OO) is a common benign bone tumour that is rarely found in the talus. Its nidus is difficult to detect on early imaging. The atypical symptoms of OO and the presence of concurrent trauma or sports injuries may lead to misdiagnosis and delayed treatment. We herein analyse a case of misdiagnosis of OO of the talus and discuss how to improve the early diagnosis of this rare lesion, thereby permitting rapid treatment. Case presentation A 23-year-old man with a history of left ankle sprains and chronic pain was diagnosed with another ankle sprain and managed conservatively based on normal X-ray findings. After 1\ua0year of recurring pain, he was diagnosed with ankle traumatic arthritis and underwent arthroscopic surgery. His preoperative ankle X-ray findings were still normal, and magnetic resonance imaging at that time demonstrated bone marrow oedema of the left talus. His symptoms reappeared shortly after surgery and progressively worsened. Magnetic resonance imaging performed 3\ua0months after surgery demonstrated widespread bone marrow oedema of the talus. The patient presented to our hospital for pain assessment and was diagnosed with OO of the talus 3\ua0years after his symptoms began. Preoperative computed tomography (CT) demonstrated a typical nidus of OO of the talus. After a second surgery, the patient\u2019s symptoms completely resolved, and pathologic examination confirmed that the lesion was OO. The patient recovered 3\ua0months later and was able to walk normally. Conclusions OO of the ankle joint exhibits a progressive course and is difficult to diagnose at an early stage. Patients with OO of the talus often have atypical imaging findings, no signs of ankle instability, and no anterior talofibular ligament tenderness. CT is valuable for diagnosing OO, although multiple CT scans may be required to detect the nidus. Proper imaging helps doctors to achieve the correct diagnosis early in the disease course, significantly shortening the treatment cycle and improving the patient\u2019s quality of life

Hypolipidemic, antioxidant and anti-atherosclerogenic effect of aqueous extract leaves of Cassia. occidentalis Linn (Caesalpiniaceae) in diet-induced hypercholesterolemic rats

Abstract Background Hyperlipidemia and oxidative stress are major risk factors for atherosclerosis, and all three are among the most important risk factors for cardiovascular diseases. Cassia occidentalis aqueous extract has been used in African traditional medicine for the treatment of hypertension and associated cardiovascular diseases. This study was undertaken to evaluate the hypolipidemic and anti-atherosclerotic properties of the aqueous extract of the leaves of C. occidentalis in rats with hypercholesterolemia (HC). Sixty Normocholesterolemic (NC) male rats were divided into six groups ( n \u2009=\u200910) and fed a high-cholesterol (HC) diet for 30\ua0days (5 groups), or normal rat chow (normal control group). The plant extract was administered to animals at the increasing dose of 240, 320 and 400\ua0mg/kg. After 4\ua0weeks of treatment 5 rats out of 10 were sacrificed, blood samples, aorta, liver, and fresh faecal were collected and processed for biochemical tests. The experiments were conducted under the same conditions with a group of rat treated with Atorvastatin (1\ua0mg/kg), used positive control. The effects of C. occidentalis on weight gain, water and food consumptions, levels of serum lipids and lipoprotein lipid oxidation and stress markers in blood and liver were also examined. Results A significant body weight gain was observed in general in all the group of animals without any treatment after 4\ua0weeks. During the treatment period, the C. occidentalis extract induced a significant increase ( P \u2009<\u20090.01) in water consumption and food intakes. After 4\ua0weeks of treatment with hypercholesterolemia, the body temperature and organ weights including the liver, kidney, heart and the testis did not present any significant change. The administration of C. occidentalis extract significantly ( p \u2009<\u20090.05) prevented the elevation in TC, LDL-C, VLDL-C, hepatic and aortic TG and TC. The atherogenic, triglycerides, and lipid peroxidation (TBARS) index were also decreased in the rats treated with the plant extract. C. occidentalis favoured the performance of faecal cholesterol. It also significantly inhibited the changes and the formation of aortic atherosclerotic plaques. Conclusion This study provides evidence of hypolipidemic and antiatherosclerotic effects of C. occidentalis extract. C. occidenntalis aqueous extract reduced bad cholesterols, triglycerides and increasing good cholesterols in rats subjected to a feeding regime enriched with cholesterol. The results support the traditional use of the extract of this plant in the ..

Maternal intake of dietary virgin coconut oil modifies essential fatty acids and causes low body weight and spiky fur in mice

Abstract Background Coconut oil is commonly used as herbal medicine worldwide. There is limited information regarding its effects on the developing embryo and infant growth. Methods We investigated the effect of virgin coconut oil post-natally and until 6\ua0weeks old in mice (age of maturity). Females were fed with either standard, virgin olive oil or virgin coconut oil diets 1\ua0month prior to copulation, during gestation and continued until weaning of pups. Subsequently, groups of pups borne of the respective diets were continuously fed the same diet as its mother from weaning until 6\ua0weeks old. Profiles of the standard and coconut oil diets were analysed by gas chromatography flame ionization detector (GCFID). Results Analysis of the mean of the total weight gained/ loss over 6\ua0weeks revealed that in the first 3\ua0weeks, pups whose mothers were fed virgin coconut oil and virgin olive oil have a significantly lower body weight than that of standard diet pups. At 6\ua0weeks of age, only virgin coconut oil fed pups exhibited significantly lower body weight. We report that virgin coconut oil modifies the fatty acid profiles of the standard diet by inducing high levels of medium chain fatty acids with low levels of essential fatty acids. Furthermore, pups borne by females fed with virgin coconut oil developed spiky fur. Conclusion Our study has demonstrated that virgin coconut oil could affect infant growth and appearance via maternal intake; we suggest the use of virgin coconut oil as herbal medicine to be treated with caution

Effects of an L-arginine-based multi ingredient product on endothelial function in subjects with mild to moderate hypertension and hyperhomocysteinemia - a randomized, double-blind, placebo-controlled, cross-over trial

Abstract Background Nutrition plays an important role in prevention and management of cardiovascular diseases (CVD) in early stages. Recent research demonstrated beneficial effects of various nutritional ingredients on vascular health. The aim of the current study was to evaluate the effects of an L-arginine-based multi ingredient product (AbMIP) on vascular function. Methods Twenty-five male and female subjects, aged between 45 and 65\ua0years with elevated blood pressure and hyperhomocysteinemia were included in this cross-over trial. Subjects were randomly assigned to one of the two sequence groups (AbMIP -placebo or placebo \u2013 AbMIP). AbMIP and placebo were taken for 4\ua0weeks, each. Endothelial function under fasting conditions, blood pressure, postprandial endothelial function after consumption of a high fat meal, homocysteine, asymmetric dimethyl arginine (ADMA) and Hba1c were determined. Results AbMIP significantly improved fasting endothelial function determined by EndoPAT\u2122 when compared to placebo ( p \u2009=\u20090.047). Similarly, homocysteine levels were significantly decreased after verum supplementation when compared to placebo ( p \u2009<\u20090.0001). Systolic blood pressure decreased significantly under AbMIP ( p \u2009=\u20090.002) and the reduction was more pronounced when compared to placebo. However, due to placebo-effects no significant difference could be found between groups ( p \u2009=\u20090.586). The effects on postprandial endothelial function were stronger for AbMIP when compared with placebo but did not reach significance ( p \u2009=\u20090.201). No significant effects of AbMIP were observed regarding HbA1c, ADMA and diastolic blood pressure. Conclusions Due to improvement on endothelial function, decrease of elevated homocysteine levels and excellent tolerability, AbMIP was demonstrated to be a beneficial option for dietary treatment of endothelial dysfunction and hyperhomocysteinemia in early stages of CVD. Trial registration The clinical trials.gov identifier is NCT02392767 , November 14, 2014

Chlorella sorokiniana induces mitochondrial-mediated apoptosis in human non-small cell lung cancer cells and inhibits xenograft tumor growth in vivo

Abstract Background Lung cancer is one of the leading causes of cancer related deaths worldwide. Marine microalgae are a source of biologically active compounds and are widely consumed as a nutritional supplement in East Asian countries. It has been reported that Chlorella or Chlorella extracts have various beneficial pharmacological compounds that modulate immune responses; however, no studies have investigated the anti-cancer effects of Chlorella sorokiniana (CS) on non-small cell lung cancer (NSCLC). Methods In this study, we evaluated the anti-cancer effects of CS in two human NSCLC cell lines (A549 and CL1-5 human lung adenocarcinoma cells), and its effects on tumor growth in a subcutaneous xenograft tumor model. We also investigated the possible molecular mechanisms governing the pharmacological function of CS. Results Our results showed that exposure of the two cell lines to CS resulted in a concentration-dependent reduction in cell viability. In addition, the percentage of apoptotic cells increased in a dose-dependent manner, suggesting that CS might induce apoptosis in human NSCLC cells. Western blot analysis revealed that exposure to CS resulted in increased protein expression of the cleaved/activated forms of caspase-3, caspase-9, and PARP, except caspase-8. ZDEVD (caspase-3 inhibitor) and Z-LEHD (caspase-9 inhibitor) were sufficient at preventing apoptosis in both A549 and CL1-5 cells, proving that CS induced cell death via the mitochondria-mediated apoptotic pathway. Exposure of A549 and CL1-5 cells to CS for 24\ua0h resulted in decreased expression of Bcl-2 protein and increased expression of Bax protein as well as decreased expression of two IAP family proteins, survivin and XIAP. Conclusions We demonstrated that CS induces mitochondrial-mediated apoptosis in NSCLC cells via downregulation of Bcl-2, XIAP and survivin. In addition, we also found that the tumors growth of subcutaneous xenograft in vivo was markedly inhibited after oral intake of CS

Factors associated with mode of colorectal cancer detection and time to diagnosis: a population level study

Abstract Background Although it is well-known that early detection of colorectal cancer (CRC) is important for optimal patient survival, the relationship of patient and health system factors with delayed diagnosis are unclear. The purpose of this study was to identify the demographic, clinical and healthcare factors related to mode of CRC detection and length of the diagnostic interval. Methods All residents of Alberta, Canada diagnosed with first-ever incident CRC in years 2004\u20132010 were identified from the Alberta Cancer Registry. Population-based administrative health datasets, including hospital discharge abstract, ambulatory care classification system and physician billing data, were used to identify healthcare services related to CRC diagnosis. The time to diagnosis was defined as the time from the first CRC-related healthcare visit to the date of CRC diagnosis. Mode of CRC detection was classified into three groups: urgent, screen-detected and symptomatic. Quantile regression was performed to assess factors associated with time to diagnosis. Results 9626 patients were included in the study; 25% of patients presented as urgent, 32% were screen-detected and 43% were symptomatic. The median time to diagnosis for urgent, screen-detected and symptomatic patients were 6\ua0days (interquartile range (IQR) 2\u201314 days), 74\ua0days (IQR 36\u2013183 days), 84\ua0days (IQR 39\u2013223 days), respectively. Time to diagnosis was greater than 6\ua0months for 27% of non-urgent patients. Healthcare factors had the largest impact on time to diagnosis: 3 or more visits to a GP increased the median by 140\ua0days whereas 2 or more visits to a GI-specialist increased it by 108\ua0days compared to 0\u20131 visits to a GP or GI-specialist, respectively. Conclusion A large proportion of CRC patients required urgent work-up or had to wait more than 6\ua0months for diagnosis. Actions are needed to reduce the frequency of urgent presentation as well as improve the timeliness of diagnosis. Findings suggest a need to improve coordination of care across multiple providers

Systemic nocardiosis in a dog caused by Nocardia cyriacigeorgica

Abstract Background Systemic nocardiosis due to Nocardia cyriacigeorgica has not been reported in dogs. Case presentation Light and electron microscopy, microbiological culture and molecular identification (PCR) were used to diagnose systemic nocardiosis caused by Nocardia cyriacigeorgica in a 3-month-old husky dog. The postmortem changes included multifocal to coalescing, sharply circumscribed pyogranulomatous inflammation and abscess formation in lungs, liver, myocardium, spleen, kidneys, brain, and hilar lymph nodes. The organism was isolated and sequencing of its 16S rRNA allowed its identification and speciation. Examination of the bacterial culture by scanning electron-microscope showed filamentous branching with fragmentation into widely bacillary and cocoid forms of the bacteria. There was no history of immunosupressive drug administration and infection by the immunosuppresive viral pathogens, canine distemper and parvovirus were excluded via PCR. Conclusion N. cyriacigeorgica should be considered potential cause of systemic pyogranulomatous lesions in dogs. It is the first reported case of systemic nocardiosis due to N. cyriacigeorgica in a dog