During the last decades, a renewed interest for negative symptoms (NS) was brought about by the increased awareness that they interfere severely with real-life functioning, particularly when they are ...primary and persistent.
In this guidance paper, we provide a systematic review of the evidence and elaborate several recommendations for the conceptualization and assessment of NS in clinical trials and practice.
Expert consensus and systematic reviews have provided guidance for the optimal assessment of primary and persistent negative symptoms; second-generation rating scales, which provide a better assessment of the experiential domains, are available; however, NS are still poorly assessed both in research and clinical settings.This European Psychiatric Association (EPA) guidance recommends the use of persistent negative symptoms (PNS) construct in the context of clinical trials and highlights the need for further efforts to make the definition of PNS consistent across studies in order to exclude as much as possible secondary negative symptoms. We also encourage clinicians to use second-generation scales, at least to complement first-generation ones.The EPA guidance further recommends the evidence-based exclusion of several items included in first-generation scales from any NS summary or factor score to improve NS measurement in research and clinical settings. Self-rated instruments are suggested to further complement observer-rated scales in NS assessment.Several recommendations are provided for the identification of secondary negative symptoms in clinical settings.
The dissemination of this guidance paper may promote the development of national guidelines on negative symptom assessment and ultimately improve the care of people with schizophrenia.
Negative symptoms of schizophrenia remain a major therapeutic challenge. The progress in the conceptualization and assessment is not yet fully reflected by treatment research. Nevertheless, there is ...a growing evidence base regarding the effects of biological and psychosocial interventions on negative symptoms. The importance of the distinction between primary and secondary negative symptoms for treatment selection might seem evident, but the currently available evidence remains limited. Good clinical practice is recommended for the treatment of secondary negative symptoms. Antipsychotic treatment should be optimized to avoid secondary negative symptoms due to side effects and due to positive symptoms. For most available interventions, further evidence is needed to formulate sound recommendations for primary, persistent, or predominant negative symptoms.However, based on currently available evidence recommendations for the treatment of undifferentiated negative symptoms (including both primary and secondary negative symptoms) are provided. Although it has proven difficult to formulate an evidence-based recommendation for the choice of an antipsychotic, a switch to a second-generation antipsychotic should be considered for patients who are treated with a first-generation antipsychotic. Antidepressant add-on to antipsychotic treatment is an option. Social skills training is recommended as well as cognitive remediation for patients who also show cognitive impairment. Exercise interventions also have shown promise. Finally, access to treatment and to psychosocial rehabilitation should be ensured for patients with negative symptoms. Overall, there is definitive progress in the field, but further research is clearly needed to develop specific treatments for negative symptoms.
The Alzheimer's disease (AD) afflicted brain is neuropathologically defined by extracellular amyloid-β (Aβ) plaques and intraneuronal neurofibrillary tangles composed of hyperphosphorylated tau ...protein. However, accumulating evidence suggests that the presynaptic protein α-synuclein (αSyn), mainly associated with synucleinopathies like Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), is involved in the pathophysiology of AD. Lewy-related pathology (LRP), primarily comprised of αSyn, is present in a majority of autopsied AD brains, and higher levels of αSyn in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI) and AD have been linked to cognitive decline. Recent studies also suggest that the asymptomatic accumulation of Aβ plaques is associated with higher CSF αSyn levels in subjects at risk of sporadic AD and in individuals carrying autosomal dominant AD mutations. Experimental evidence has further linked αSyn mainly to tau hyperphosphorylation, but also to the pathological actions of Aβ and the APOEε4 allele, the latter being a major genetic risk factor for both AD and DLB. In this review, we provide a summary of the current evidence proposing an involvement of αSyn either as an active or passive player in the pathophysiological ensemble of AD, and furthermore describe in detail the current knowledge of αSyn structure and inferred function.
Anthelmintic resistance is reported in equine nematodes with increasing frequency in recent years, and no new anthelmintic classes have been introduced during the past 40 years. This manuscript ...reviews published literature describing anthelmintic resistance in cyathostomins, Parascaris spp., and Oxyuris equi with special emphasis on larvicidal efficacy against encysted cyathostomin larvae and strongylid egg reappearance periods (ERP). Resistance to benzimidazoles and pyrimidines is highly prevalent in cyathostomin populations around the world, and macrocyclic lactone resistance has been documented in cyathostomins in recent years as well. Two recent studies have documented resistance to the larvicidal regimen of fenbendazole, whereas the larvicidal efficacy of moxidectin is variable, but with no evidence of a reduction from historic levels. In the 1990s, ERP estimates were 8–10 and 12–16 weeks for ivermectin and moxidectin, respectively, while several studies published after year 2000 found ERPs to be 5 weeks for both compounds. This is a clear change in anthelmintic performance, but it remains unclear if this is due to development of anthelmintic resistance or selection for other biological traits leading to a quicker resumption of strongylid egg shedding following anthelmintic treatment. Macrocyclic lactone resistance is common in Parascaris spp. around the world, but recent reports suggests that resistance to the two other classes should be monitored as well. Finally, O. equi has been reported resistant to ivermectin and moxidectin in countries representing four continents. In conclusion, multi-drug resistance is becoming the norm in managed cyathostomin populations around the world, and a similar pattern may be emerging in Parascaris spp. More work is required to understand the mechanisms behind the shortened ERPs, and researchers and veterinarians around the world are encouraged to routinely monitor anthelmintic efficacy against equine nematodes.
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•Cyathostomins are widely resistant to pyrimidines and benzimidazoles.•Cyathostomins have been reported resistant to macrocyclic lactones in recent years.•The interpretation of shortened egg reappearance periods is not clear.•Parascaris spp. are widely resistant to macrocyclic lactones.•Oxyuris equi has been documented resistant to macrocyclic lactones.
Abstrct
Background
Acute high‐risk abdominal (AHA) surgery carries a very high risk of morbidity and mortality and represents a massive healthcare burden. The aim of the present study was to evaluate ...the effect of a standardized multidisciplinary perioperative protocol in patients undergoing AHA surgery.
Methods
The AHA study was a prospective single‐centre controlled study in consecutive patients undergoing AHA surgery, defined as major abdominal pathology requiring emergency laparotomy or laparoscopy including reoperations after elective gastrointestinal surgery. Consecutive patients were included after initiation of the AHA protocol as standard care. The intervention cohort was compared with a predefined, consecutive historical cohort of patients from the same department. The protocol involved continuous staff education, consultant‐led attention and care, early resuscitation and high‐dose antibiotics, surgery within 6 h, perioperative stroke volume‐guided haemodynamic optimization, intermediate level of care for the first 24 h after surgery, standardized analgesic treatment, early postoperative ambulation and early enteral nutrition. The primary outcome was 30‐day mortality.
Results
Six hundred patients were included in the study and compared with 600 historical controls. The unadjusted 30‐day mortality rate was 21·8 per cent in the control cohort compared with 15·5 per cent in the intervention cohort (P = 0·005). The 180‐day mortality rates were 29·5 and 22·2 per cent respectively (P = 0·004).
Conclusion
The introduction of a multidisciplinary perioperative protocol was associated with a significant reduction in postoperative mortality in patients undergoing AHA surgery. NCT01899885 (http://www.clinicaltrials.gov).
Reduces mortality
Surface polysaccharides are important for bacterial interactions with multicellular organisms, and some are virulence factors in pathogens. In the legume-rhizobium symbiosis, bacterial ...exopolysaccharides (EPS) are essential for the development of infected root nodules. We have identified a gene in Lotus japonicus, Epr3, encoding a receptor-like kinase that controls this infection. We show that epr3 mutants are defective in perception of purified EPS, and that EPR3 binds EPS directly and distinguishes compatible and incompatible EPS in bacterial competition studies. Expression of Epr3 in epidermal cells within the susceptible root zone shows that the protein is involved in bacterial entry, while rhizobial and plant mutant studies suggest that Epr3 regulates bacterial passage through the plant's epidermal cell layer. Finally, we show that Epr3 expression is inducible and dependent on host perception of bacterial nodulation (Nod) factors. Plant-bacterial compatibility and bacterial access to legume roots is thus regulated by a two-stage mechanism involving sequential receptor-mediated recognition of Nod factor and EPS signals.
Usually the dense extracellular structure in fibrotic tissues is described as extracellular matrix (ECM) or simply as collagen. However, fibrosis is not just fibrosis, which is already exemplified by ...the variant morphological characteristics of fibrosis due to viral versus cholestatic, autoimmune or toxic liver injury, with reticular, chicken wire and bridging fibrosis. Importantly, the overall composition of the ECM, especially the relative amounts of the many types of collagens, which represent the most abundant ECM molecules and which centrally modulate cellular functions and physiological processes, changes dramatically during fibrosis progression.
We hypothesize that there are good and bad collagens in fibrosis and that a change of location alone may change the function from good to bad. Whereas basement membrane collagen type IV anchors epithelial and other cells in a polarized manner, the interstitial fibroblast collagens type I and III do not provide directional information. In addition, feedback loops from biologically active degradation products of some collagens are examples of the importance of having the right collagen at the right place and at the right time controlling cell function, proliferation, matrix production and fate. Examples are the interstitial collagen type VI and basement membrane collagen type XVIII. Their carboxyterminal propeptides serve as an adipose tissue hormone, endotrophin, and as a regulator of angiogenesis, endostatin, respectively.
We provide an overview of the 28 known collagen types and propose that the molecular composition of the ECM in fibrosis needs careful attention to assess its impact on organ function and its potential to progress or reverse. Consequently, to adequately assess fibrosis and to design optimal antifibrotic therapies, we need to dissect the molecular entity of fibrosis for the molecular composition and spatial distribution of collagens and the associated ECM.
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Bacteria evolve rapidly not only by mutation and rapid multiplication, but also by transfer of DNA, which can result in strains with beneficial mutations from more than one parent. Transformation ...involves the release of naked DNA followed by uptake and recombination. Homologous recombination and DNA-repair processes normally limit this to DNA from similar bacteria. However, if a gene moves onto a broad-host-range plasmid it might be able to spread without the need for recombination. There are barriers to both these processes but they reduce, rather than prevent, gene acquisition.
Determining diet is a key prerequisite for understanding species interactions, food web structure and ecological dynamics. In recent years, there has been considerable development in both the ...methodology and application of novel and more traditional dietary tracing methods, yet there is no comprehensive synthesis that systematically and quantitatively compares the different approaches.
Here we conceptualise diet tracing in ecology, provide recommendations for method selection, and illustrate the advantages of method integration. We summarise empirical evidence on how different methods quantify diet mixtures, by contrasting estimates of dietary proportions from multiple methods applied to the same consumer‐resource datasets, or from experimental studies with known diet compositions.
Our data synthesis revealed an urgent need for more experiential comparisons among the dietary methods. The comparison of diet quantifications from field observations showed that different techniques aligned well in cases with less than six diet items, but diverged considerably when applied to more complex diet mixtures.
Efforts are ongoing to further advance dietary estimation, including how reliably compound specific stable isotope analyses and fatty acid profiles can quantify more prey items than bulk stable isotope analyses. Similarly, DNA analyses, which can depict trophic interactions at a higher resolution than any other method, are generating new ways to better quantify diets and differentiate among life‐stages of prey. Such efforts, combined with more empirical testing of each dietary method and establishment of open data repositories for dietary data, promise to greatly advance community and ecosystem ecology.
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