Contracting skeletal muscle can overcome sympathetic vasoconstrictor activity (functional sympatholysis), which allows for a blood supply that matches the metabolic demand. This ability is thought to ...be mediated by locally released substances that modulate the effect of noradrenaline (NA) on the α‐receptor. Tyramine induces local NA release and can be used in humans to investigate the underlying mechanisms and physiological importance of functional sympatholysis in the muscles of healthy and diseased individuals as well as the impact of the active muscles’ training status. In sedentary elderly men, functional sympatholysis and muscle blood flow are impaired compared to young men, but regular physical activity can prevent these age related impairments. In young subjects, two weeks of leg immobilization causes a reduced ability for functional sympatholysis, whereas the trained leg maintained this function. Patients with essential hypertension have impaired functional sympatholysis in the forearm, and reduced exercise hyperaemia in the leg, but this can be normalized by aerobic exercise training. The effect of physical activity on the local mechanisms that modulate sympathetic vasoconstriction is clear, but it remains uncertain which locally released substance(s) block the effect of NA and how this is accomplished. NO and ATP have been proposed as important inhibitors of NA mediated vasoconstriction and presently an inhibitory effect of ATP on NA signalling via P2 receptors appears most likely.
Esophageal cancer is the eighth most common cancer globally and has the sixth worst prognosis because of its aggressiveness and poor survival. Data regarding cancer treatment in older patients is ...limited because the elderly have been under-represented in clinical trials. Therefore, we reviewed the existing literature regarding treatment results for elderly patients (70+ years). Areas covered: We used pubmed to analyze the actual literature according to elderly esophageal cancer patients with subheading of incidence, esophagectomy, chemoradiation or chemotherapy. The main points of interest were treatment options for patients with Barrett's esophagus or early carcinoma, advanced tumor stages, and inoperable cancer. Expert opinion: The incidence of esophageal cancer has been increasing over the past thirty years, with a rapid increase of esophageal adenocarcinoma in Western industrialized nations. Patients aged over 60 years have been particularly affected. In this review, we have shown that elderly patients with esophageal cancer have various alternatives for adequate treatment. Clinical evaluation of comorbidity is necessary to make treatment decisions. Therapeutic options for early carcinomas are endoscopic or surgical resection. For elderly patients with advanced carcinomas, preoperative chemoradiation or chemotherapy should be discussed.
This study presents concentrations of perfluorinated compounds in food and the dietary intake of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in The Netherlands. The concentrations ...of perfluorinated compounds in food were analyzed in pooled samples of foodstuffs randomly purchased in several Dutch retail store chains with nation-wide coverage. The concentrations analyzed for PFOS and PFOA were used to assess the exposure to these compounds in The Netherlands. As concentrations in drinking water in The Netherlands were missing for these compounds, conservative default concentrations of 7 pg/g for PFOS and 9 pg/g for PFOA, as reported by European Food Safety Authority, were used in the exposure assessment. In food, 6 out of 14 analyzed perfluorinated compounds could be quantified in the majority of the food categories (perfluoroheptanoic acid (PFHpA), PFOA, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoro-1-hexanesulfonate (PFHxS), and PFOS). The highest concentration of the sum of these six compounds was found in crustaceans (825 pg/g product, PFOS: 582 pg/g product) and in lean fish (481 pg/g product, PFOS: 308 pg/g product). Lower concentrations were found in beef, fatty fish, flour, butter, eggs, and cheese (concentrations between 20 and 100 pg/g product; PFOS, 29–82 pg/g product) and milk, pork, bakery products, chicken, vegetable, and industrial oils (concentration lower than 10 pg/g product; PFOS not detected). The median long-term intake for PFOS was 0.3 ng/kg bw/day and for PFOA 0.2 ng/kg bw/day. The corresponding high level intakes (99th percentile) were 0.6 and 0.5 ng/kg bw/day, respectively. These intakes were well below the tolerable daily intake values of both compounds (PFOS, 150 ng/kg bw/day; PFOA, 1500 ng/kg bw/day). The intake calculations quantified the contribution of drinking water to the PFOS and PFOA intake in The Netherlands. Important contributors of PFOA intake were vegetables/fruit and flour. Milk, beef, and lean fish were important contributors of PFOS intake.
Infections caused by carbapenemase-producing, multidrug-resistant (MDR), or extensively drug-resistant (XDR) Gram-negative bacteria constitute a major therapeutic challenge. Whether combination ...antibiotic therapy is superior to monotherapy remains unknown. In this systematic review and meta-analysis OVID MEDLINE, EMBASE, PubMed, The Cochrane Library, and Scopus databases were searched for randomized controlled trials (RCTs) and observational studies published by December 2016 comparing mono- with combination antibiotic therapy for infections with carbapenemase-producing, MDR, or XDR Gram-negative bacteria. Mortality and clinical cure rates served as primary and secondary outcome measures, respectively. Of 8847 initially identified studies, 53 studies - covering pneumonia (n = 10 studies), blood stream (n = 15), osteoarticular (n = 1), and mixed infections (n = 27) - were included. 41% (n = 1848) of patients underwent monotherapy, and 59% (n = 2666) combination therapy. In case series/cohort studies (n = 45) mortality was lower with combination- vs. monotherapy (RR 0.83, CI 0.73-0.93, p = 0.002, I
= 24%). Subgroup analysis revealed lower mortality with combination therapy with at least two in-vitro active antibiotics, in blood stream infections, and carbapenemase-producing Enterobacteriaceae. No mortality difference was seen in case-control studies (n = 6) and RCTs (n = 2). Cure rates did not differ regardless of study type. The two included RCTs had a high and unknown risk of bias, respectively. 16.7% (1/6) of case-control studies and 37.8% (17/45) of cases series/cohort studies were of good quality, whereas quality was poor in the remaining studies. In conclusion, combination antimicrobial therapy of multidrug-resistant Gram-negative bacteria appears to be superior to monotherapy with regard to mortality.
Studying the behavioral and life history transitions from a cooperative, eusocial life history to exploitative social parasitism allows for deciphering the conditions under which changes in behavior ...and social organization lead to diversification. The Holarctic ant genus
is ideally suited for studying the evolution of social parasitism because half of its 172 species are confirmed or suspected social parasites, which includes all three major classes of social parasitism known in ants. However, the life history transitions associated with the evolution of social parasitism in this genus are largely unexplored. To test competing hypotheses regarding the origins and evolution of social parasitism, we reconstructed a global phylogeny of
ants. The genus originated in the Old World ∼30 Ma ago and dispersed multiple times to the New World and back. Within
, obligate dependent colony-founding behavior arose once from a facultatively polygynous common ancestor practicing independent and facultative dependent colony foundation. Temporary social parasitism likely preceded or arose concurrently with obligate dependent colony founding, and dulotic social parasitism evolved once within the obligate dependent colony-founding clade. Permanent social parasitism evolved twice from temporary social parasitic ancestors that rarely practiced colony budding, demonstrating that obligate social parasitism can originate from a facultative parasitic background in socially polymorphic organisms. In contrast to permanently socially parasitic ants in other genera, the high parasite diversity in
likely originated via allopatric speciation, highlighting the diversity of convergent evolutionary trajectories resulting in nearly identical parasitic life history syndromes.
The availability of purely semiconducting single-walled carbon nanotube (s-SWCNT) dispersions has prompted their widespread application in solution-processed thin-film transistors with excellent ...device performance but has also raised the question of how their precise composition influences charge transport properties in random networks. Here, we compare hole and electron transport in three different polymer-sorted s-SWCNT networks from nearly monochiral (6,5) nanotubes (diameter 0.76 nm) to mixed networks of s-SWCNTs with medium (0.8–1.3 nm) and large (1.2–1.6 nm) diameters. Temperature-dependent field-effect mobilities are extracted from gated four-point probe measurements that exclude any contributions by contact resistance and indicate thermally activated transport. The mobility data can be fitted to the fluctuation-induced tunneling model, although with significant differences between the network compositions. The network with the broadest diameter and thus bandgap range results in the strongest temperature dependence in agreement with numerical simulations based on a random resistor model of nanotube junctions. However, the experimental data for mixed networks of large diameter nanotubes and their deviation from the simple junction model implies a significant contribution of intra-nanotube transport with its specific diameter and temperature dependence to the overall charge transport properties of the network.
We experimentally investigate behavior and reasoning in various competitive resource allocation games with large strategy spaces. In the experiment, a team of two players plays as one entity against ...other teams. Team members communicate with one another before choosing a strategy. We analyze their messages using three different classification approaches and find that the vast majority of players think in terms of dimensions or characteristics of strategies rather than in terms of individual elements of the strategy space. Furthermore, the dimensions’ metric allows linking the reasoning across the different games. Thus, we suggest that multi-dimensional reasoning is a frequently used decision procedure that connects the behavior observed in various resource allocation games.
Campylobacter spp. are a leading cause of bacterial enteritis worldwide, including countries in Africa, and have been identified by the World Health Organisation (WHO) as one of the high priority ...antimicrobial resistant pathogens. However, at present there is little knowledge on the prevalence, molecular epidemiology or antimicrobial susceptibility of Campylobacter spp. isolates in Botswana, both in patients and in the zoonotic context. Some data indicate that ~14% of diarrhoeal disease cases in a paediatric setting can be ascribed to Campylobacter spp., urging the need for the magnitude of Campylobacter-associated diarrhoea to be established. In this survey, we have characterised the genomic diversity of Campylobacter spp. circulating in Botswana isolated from cases of diarrhoeal disease in humans (n = 20) and from those that colonised commercial broiler (n = 35) and free-range (n = 35) chickens. Phylogeny showed that the Campylobacter spp. isolated from the different poultry and human sources were highly related, suggesting that zoonotic transmission has likely occurred. We found that for Campylobacter spp. isolated from humans, broilers and free-range chickens, 52% was positive for tetO, 47% for gyrA-T86I, 72% for blaOXA-61, with 27% carrying all three resistance determinants. No 23S mutations conferring macrolide resistance were detected in this survey. In summary, our study provides insight into Campylobacter spp. in poultry reservoirs and in diarrhoeal patients, and the relevance for treatment regimens in Botswana.
Due to their unique surfactant properties, poly- and perfluorinated compounds (PFCs) have been extensively used and can be found all over the environment. Concern about their environmental fate and ...toxicological properties has initiated several research projects. In the present study, we investigated if PFCs can compete with thyroxine (T4, i.e., the transport form of thyroid hormone) for binding to the human thyroid hormone transport protein transthyretin (TTR). Such competitive capacity may lead to decreased thyroid hormone levels as previously reported for animals exposed to PFCs. Twenty-four PFCs, together with 6 structurally similar natural fatty acids, were tested for binding capacity in a radioligand-binding assay. The binding potency decreased in the order: perfluorohexane sulfonate > perfluorooctane sulfonate/perfluorooctanoic acid > perfluoroheptanoic acid > sodium perfluoro-1-octanesulfinate > perfluorononanoic acid, with TTR binding potencies 12.5–50 times lower than the natural ligand T4. Some lower molecular weight compounds with structural similarity to these PFCs were > 100 times less potent than T4. Simple descriptors based on the two-dimensional molecular structures of the compounds were used to visualize the chemical variation and to model the structure-activity relationship for the competitive potencies of the TTR-binding compounds. The models indicated the dependence on molecular size and functional groups but demanded a more detailed description of the chemical properties and data for validation and further quantitative structure-activity relationship (QSAR) development. Competitive binding of PFCs to TTR, as observed for human TTR in the present study, may explain altered thyroid hormone levels described for PFC-exposed rats and monkeys. Median human blood levels of the most potent TTR-binding PFCs are one to two orders of magnitude lower than concentration at 50% inhibition (IC50) values determined in the present study. In addition, this study contributes to the understanding of the bioaccumulation of PFCs in man and possibly in other wildlife species.
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