Sperm competition intensity affects sperm precedence patterns in a polyandrous gift-giving spider

Abstract Sperm competition drives traits that enhance fertilization success. The amount of sperm transferred relative to competitors is key for attaining paternity. Female reproductive morphology and male mating order may also influence fertilization, however the outcome for sperm precedence under intense sperm competition remains poorly understood. In the polyandrous spider Pisaura mirabilis, males offer nuptial gifts which prolong copulation and increase sperm transfer, factors proposed to alter sperm precedence patterns under strong sperm competition. First, we assessed the degree of female polyandry by genotyping wild broods. A conservative analysis identified up to four sires, with a mean of two sires per brood, consistent with an optimal mating female rate. Then we asked whether intense sperm competition shifts sperm precedence patterns from first male priority, as expected from female morphology, to last male advantage. We varied sexual selection intensity experimentally and determined competitive fertilization outcome by genotyping broods. In double matings, one male monopolised paternity regardless of mating order. A mating order effect with first male priority was revealed when females were mated to four males, however this effect disappeared when females were mated to six males, probably due to increased sperm mixing. The proportion of males that successfully sired offspring drastically decreased with the number of competitors. Longer copulations translated into higher paternity shares independently of mating order, reinforcing the advantage of traits that prolong copulation duration under intense competition, such as the nuptial gift. Sperm competition intensity enhances the impact of competitive sexual traits and imposes multiple effects on paternity

The diagnostic accuracy and clinical impact of FDG-PET/CT follow-up for patients on adjuvant immunotherapy for high-risk malignant melanoma

Objective: The benefit of FDG-PET/CT in follow-up of patients treated with adjuvant immunotherapy after resection of high-risk malignant melanoma (MM) is debated. This study evaluated the diagnostic accuracy and clinical impact of FDG-PET/CT for diagnosing MM recurrence during the first year after surgery. Methods: We retrospectively included 124 patients with resected high-risk MM, who received adjuvant immunotherapy and follow-up FDG-PET/CT. Clinical information and AJCC-8 stage was obtained from patients’ medical records. Recurrence was verified by biopsy/progression on a subsequent scan leading to change of treatment. Non-recurrence was assumed when no metastases were observed until the subsequent follow-up scan. Incidence of recurrence, sensitivity, specificity, positive and negative predictive values (PPV and NPV) were outcome measures. Results: Incidence rate of MM recurrence was 0.27 [95% CI 0.17–0.37] per person-year during the first-year. Recurrence was detected in 13 patients (10%) at 3-month FDG-PET/CT, in 10 patients (8.1%) at 6 months, 1 patient (0.8%) at 9 months, 3 patients (2.4%) at 12 months. The overall sensitivity, specificity, PPV, and NPV were 97% [86–99], 82% [78–86], 39% [29–50], and 99% [98–99], respectively. The PPV trended towards higher values as disease stage increased. At the 3-month scan, the majority of actions derived from positive findings were surgery or earlier expedition of the subsequent follow-up scan. Conclusion: The high rate of recurrence in patients with high-risk MM treated with adjuvant immunotherapy emphasizes the need for follow-up. The potential harm by a moderately low specificity reflecting a high number of false-positive results must be weighed against the benefit of early detection of recurrence.</p

Hepatic encephalopathy

Hepatic encephalopathy (HE) is a prognostically relevant neuropsychiatric syndrome that occurs in the course of acute or chronic liver disease. Besides ascites and variceal bleeding, it is the most serious complication of decompensated liver cirrhosis. Ammonia and inflammation are major triggers for the appearance of HE, which in patients with liver cirrhosis involves pathophysiologically low-grade cerebral oedema with oxidative/nitrosative stress, inflammation and disturbances of oscillatory networks in the brain. Severity classification and diagnostic approaches regarding mild forms of HE are still a matter of debate. Current medical treatment predominantly involves lactulose and rifaximin following rigorous treatment of so-called known HE precipitating factors. New treatments based on an improved pathophysiological understanding are emerging

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Urea cycle dysregulation in non-alcoholic fatty liver disease

Background: In non-alcoholic steatohepatitis (NASH), function of urea cycle enzymes (UCEs) may be affected and result in hyperammonemia with risk of disease progression. We aimed to determine whether expression and function of UCEs are altered in a NASH animal model and in non-alcoholic fatty liver disease (NAFLD) patients and whether this is reversible. / Methods: Rats were fed a high-fat, high-cholesterol diet for 10 months to induce NASH and then changed to normal chow to recover. In humans, we obtained liver biopsies from 20 patients with steatosis and 15 NASH patients. Primary rat hepatocytes were isolated and cultured with free fatty acids. We measured the gene and protein expression, the activity of ornithine transcarbamylase (OTC) and ammonia concentrations. Moreover, we assessed the promoter methylation status of OTC and carbamoyl phosphate synthetase (CPS1) in rats, humans and in steatotic hepatocytes. / Results: In NASH animals, gene and protein expression of OTC and CPS1 and activity of OTC were reversibly reduced and hypermethylation of OTC promotor genes was observed. Also in NAFLD patients, OTC enzyme concentration and activity were reduced and ammonia concentrations were increased and more so in NASH. Furthermore, OTC and CPS1 promoter regions were hypermethylated. In primary hepatocytes induction of steatosis was associated with OTC promoter hypermethylation, reduction in the gene expression of OTC and CPS1 and an increase in ammonia concentration in the supernatant. / Conclusion: NASH is associated with a reduction in gene and protein expression, and activity of UCEs resulting in hyperammonemia, possibly through hypermethylation of UCE genes and impairment of urea synthesis. Our investigations describe for the first time a link between NASH, function of UCEs and hyperammonemia providing a novel therapeutic target. / Lay summary: In patients with fatty liver disease, the enzymes that convert nitrogen waste into urea may be affected leading to the accumulation of the toxic substance, ammonia. This accumulation of ammonia can lead to development of scar tissue and risk of progression of disease. In this study, we show that fat accumulation in the liver produces a reversible reduction in the function of these enzymes that are involved in detoxification of ammonia. These data provide potential new targets for therapy of fatty liver disease

Liver cirrhosis, other liver diseases, and risk of hospitalisation for intracerebral haemorrhage: A Danish population-based case-control study

<p>Abstract</p> <p>Background</p> <p>Liver diseases are suspected risk factors for intracerebral haemorrhage (ICH). We conducted a population-based case-control study to examine risk of ICH among hospitalised patients with liver cirrhosis and other liver diseases.</p> <p>Methods</p> <p>We used data from the hospital discharge registries (1991–2003) and the Civil Registration System in Denmark, to identify 3,522 cases of first-time hospitalisation for ICH and 35,173 sex- and age-matched population controls. Among cases and controls we identified patients with a discharge diagnosis of liver cirrhosis or other liver diseases before the date of ICH. We computed odds ratios for ICH by conditional logistic regressions, adjusting for a number of confounding factors.</p> <p>Results</p> <p>There was an increased risk of ICH for patients with alcoholic liver cirrhosis (adjusted OR = 4.8, 95% CI: 2.7–8.3), non-alcoholic liver cirrhosis (adjusted OR = 7.7, 95% CI: 2.0–28.9) and non-cirrhotic alcoholic liver disease (adjusted OR = 5.4, 95%CI:3.1–9.5) but not for patients with non-cirrhotic non-alcoholic liver diseases (adjusted OR = 0.9, 95%CI:0.5–1.6). The highest risk was found among women with liver cirrhosis (OR = 8.9, 95%CI:2.9–26.7) and for patients younger than 70 years (OR = 6.1, 95%CI:3.4–10.9). There were no sex- or age-related differences in the association between other liver diseases (alcoholic or non-alcoholic) and hospitalisation with ICH.</p> <p>Conclusion</p> <p>Patients with liver cirrhosis and non-cirrhotic alcoholic liver disease have a clearly increased risk for ICH.</p

Development and evaluation of a quality score for abstracts

BACKGROUND: The evaluation of abstracts for scientific meetings has been shown to suffer from poor inter observer reliability. A measure was developed to assess the formal quality of abstract submissions in a standardized way. METHODS: Item selection was based on scoring systems for full reports, taking into account published guidelines for structured abstracts. Interrater agreement was examined using a random sample of submissions to the American Gastroenterological Association, stratified for research type (n = 100, 1992–1995). For construct validity, the association of formal quality with acceptance for presentation was examined. A questionnaire to expert reviewers evaluated sensibility items, such as ease of use and comprehensiveness. RESULTS: The index comprised 19 items. The summary quality scores showed good interrater agreement (intra class coefficient 0.60 – 0.81). Good abstract quality was associated with abstract acceptance for presentation at the meeting. The instrument was found to be acceptable by expert reviewers. CONCLUSION: A quality index was developed for the evaluation of scientific meeting abstracts which was shown to be reliable, valid and useful

Effects of Hepatocyte CD14 Upregulation during Cholestasis on Endotoxin Sensitivity

Cholestasis is frequently related to endotoxemia and inflammatory response. Our previous investigation revealed a significant increase in plasma endotoxin and CD14 levels during biliary atresia. We therefore propose that lipopolysacharides (LPS) may stimulate CD14 production in liver cells and promote the removal of endotoxins. The aims of this study are to test the hypothesis that CD14 is upregulated by LPS and investigate the pathophysiological role of CD14 production during cholestasis. Using Western blotting, qRT-PCR, and promoter activity assay, we demonstrated that LPS was associated with a significant increase in CD14 and MD2 protein and mRNA expression and CD14 promoter activity in C9 rat hepatocytes but not in the HSC-T6 hepatic stellate cell line in vitro. To correlate CD14 expression and endotoxin sensitivity, in vivo biliary LPS administration was performed on rats two weeks after they were subjected to bile duct ligation (BDL) or a sham operation. CD14 expression and endotoxin levels were found to significantly increase after LPS administration in BDL rats. These returned to basal levels after 24 h. In contrast, although endotoxin levels were increased in sham-operated rats given LPS, no increase in CD14 expression was observed. However, mortality within 24 h was more frequent in the BDL animals than in the sham-operated group. In conclusion, cholestasis and LPS stimulation were here found to upregulate hepatic CD14 expression, which may have led to increased endotoxin sensitivity and host proinflammatory reactions, causing organ failure and death in BDL rats