Does response selection contribute to inhibition of return?

Inhibition of return (IOR) means delayed responses for targets at a cued compared to targets at an uncued location. It is assumed to reflect delayed reallocation of attention toward a previously attended location. Besides an attentional mechanism, IOR could also be due to a cue‐evoked inhibition to respond toward a cued target. In the present study, IOR with simple, compatible, and incompatible choice responses was compared and tracked by means of event‐related EEG activity. IOR was amplified with simple responses but did not differ between compatible and incompatible responses. Attention‐related ERP correlates were constant across cue target onset asynchronies as were, in part, behavioral effects. Early, rather sensory ERP components varied with time, reflecting sensory or attentional interaction of cue and target processing. None of these effects varied with response requirements, indicating that response selection does not contribute to IOR in manual choice response tasks.     

Does resistance to pyrazinamide accurately indicate the presence of Mycobacterium bovis?

Mycobacterium bovis is best identified by screening those isolates of the Mycobacterium tuberculosis complex that have any pyrazinamide (PZA) resistance, using a confirmatory test such as spoligotyping, biochemical testing, or genomic deletion analysis. The sensitivity for detection of M. bovis is lowered to 82% when only PZA-monoresistant isolates are screened.     

What is the evidence base of used aggregated antibiotic resistance percentages to change empirical antibiotic treatment? A scoping review

ObjectivesAntibiotic resistance requires continuous monitoring by experts to decide whether empirical antibiotic therapies (EATs) should be replaced by alternative antibiotics. The exact moment and criteria for this change are unclear and generally based on consensus between experts. This scoping review aims to identify from the literature the resistance thresholds used for a change in EAT and the criteria on which they are based.MethodsScoping review for which a comprehensive structured literature search was conducted. Rayyan, software for systematic reviews, was used for the screening of abstracts and titles. Data sources were Pubmed and a hand-search of reference lists and grey literature. Papers were eligible if they concerned any type of bacterial infectious disease and mentioned or defined antibiotic resistance thresholds for decision-making purposes for EAT. The inclusion and analysis of articles was done by two researchers; any conflicts were resolved through discussion or by consulting a third reviewer.ResultsWe identified 3146 unique papers. Following title/abstract screening, 125 papers were comprehensively read, and 16 papers were included. The included papers gave thresholds for urinary tract infections, respiratory tract infections, meningitis, skin and soft tissue infections, gonorrhoea, and bone and joint infections. Six criteria were found that were commonly used to base the thresholds on. These were: disease severity, efficacy of treatment, adverse drug events, risk of Clostridioides difficile infection, costs, and increased resistance. The number of criteria used to define each threshold varied from one to six between papers.ConclusionsThe thresholds used for EATs are few, commonly based on expert opinion estimates, and can therefore have broad ranges. Used criteria underlying reported thresholds are heterogenous and require standardization. Considering the rising trend in resistance, there is a clear need for rigid tools to determine thresholds in order to support guideline development with the best and timely evidence.     

Does insulin resistance cause atherosclerosis in the post-prandial period?

Insulin resistance would appear to be a causal factor for the development of early occlusive atherosclerosis. This paper proposes that post-prandial insulin resistance, in association with raised levels of cortisol and catecholamines, plays the major role, and may even be the primary causative factor. Therefore, factors that lead to insulin resistance in the post-prandial period, specifically stress, will accelerate the development of CHD. This may explain the low rate of CHD in France, as their eating habits (in common with many other Mediterranean countries) are more relaxed than those in Northern Europe.     

Does antimicrobial use increase the rate of antimicrobial resistance? A one year experience

Antimicrobial resistance has been a challenge in all countries. The aim of this study is to ascertain the risk factors that predispose patients to infections with extended spectrum beta lactamase (ESBL)-producing gram-negative bacteria and methicillin-resistant Staphylococcus aureus (MRSA). Patients who were treated in the secondary care hospital due to infections in 2009 and their isolates were evaluated retrospectively. In total, 174 patients and their 189 isolates, which contained 36 ESBL-producing gram-negative bacteria, 112 non-ESBL-producing gram-negative bacteria, and 41 gram-positive bacteria were evaluated retrospectively. Hospitalisation in the previous 3 months, comorbidity, and usage of amoxicillin-clavulanate in the previous 3 months were determined to be the risk factors associated with infections by the ESBL-producing gram-negative bacteria. Hospitalisation was found to be a risk factor for infection with MRSA. Hospitalisation and underlying conditions increase the colonisation with resistant bacteria and resistance rates in the patients, hospitals and communities. An infection control programme should be contemplated not only for hospitals, but also for the greater community.     

Does the mechanism responsible for TNF-mediated insulin resistance involve the proteasome?

Recent studies have demonstrated that in many pathological states there is an overproduction of tumour necrosis factor-alpha (TNF). Interestingly, TNF also seems to be responsible for the insulin resistance associated with these pathological states, since decreases the tyrosine kinase activity of the insulin receptor. Our group has demonstrated that TNF is able to activate the proteasome-mediated ubiquitin-dependent proteolysis. Since this proteolytic system is involved in the control of receptor-associated tyrosine kinase activity (i.e. insulin receptor), it is postulated here that the mechanism of TNF-induced insulin resistance is mediated by the activation of the proteasomic, ubiquitin-dependent proteolysis.     

Economic burden of antibiotic resistance: how much do we really know?

The declining effectiveness of antibiotics imposes potentially large health and economic burdens on societies. Quantifying the economic outcomes of antibiotic resistance effectively can help policy-makers and healthcare professionals to set priorities, but determining the actual effect of antibiotic resistance on clinical outcomes is a necessary first step. In this article, we review and discuss the contributions and limitations of studies that estimate the disease burden attributable to antibiotic resistance and studies that estimate the economic burden of resistance. We also consider other factors that are important in a comprehensive approach to evaluating the economic burden of antibiotic resistance.     

Are prions related to the emergence of early life?

DNA and RNA are the modern cellular molecules related to the storage and processing of the genetic information. However, in the Earth primeval environment conditions, these two molecules are far from being the best option for this function due to their great complexity and sensibility to heat. Experiments have been showing that proteins are very stable and reliable molecules even in very extreme conditions and, under certain circumstances, could be related to the transmission of certain phenotypes that are inherited in a non-Mendelian manner. Prions, infective proteins that are associated to several neurological diseases among mammals by replacing their dominant native state of prion protein by a misfolded one, are remarkably resistant to even the most extreme environments. Furthermore, prions are also associated to the transmission of certain fungal traits in an epigenetical model. These two characteristics support the hypothesis that prions are a possible relic of early stage peptide evolution and may represent the reminiscence of a very ancient analogical code of biological transmission of information rather than the digital one represented by modern nucleic acids.     

Does pay-for-performance influence the quality of care?

PURPOSE OF REVIEW: To summarize studies of pay-for-performance programmes designed to address clinical quality of care markers in ambulatory settings at the level of the physician group or individual physician. RECENT FINDINGS: Seven randomized controlled trials and 15 nonrandomized studies were reviewed. Less than half of the randomized controlled trials showed positive results, whereas all but one of the nonrandomized studies showed positive or mixed results. Characteristics of the quality measures, incentives, providers, patients, and concurrent interventions probably influenced the results. Study methodology problems such as small sample sizes, selection bias, and inadequate control for confounders were common. Asthma quality of care markers were included in three nonrandomized studies, two of which showed positive results and one of which was negative. SUMMARY: The data reviewed in this article suggest that pay-for-performance programmes can improve markers of quality, though not always. Even when studies suggest positive effects, the designs often do not permit assurance that the effects are due to the incentives as compared with other factors. More and better-designed studies are needed to determine the actual effectiveness of incentives themselves isolated from other factors, circumstances that promote effectiveness, effectiveness relative to other strategies, and cost-effectiveness.     

Mutant ftsI genes in the emergence of penicillin-binding proteinmediated β-lactam resistance in Haemophilus influenzae in Norway

The most important mechanism for β-lactam resistance in β-lactamase-negative ampicillin-resistant (BLNAR) isolates of Haemophilus influenzae is the alteration of penicillin-binding protein 3 (PBP3) as a result of ftsI gene mutations. The present study aimed to map PBP3 alterations and to determine the correlation to β-lactam resistance in respiratory tract isolates of H. influenzae in Norway, as well as assess the contribution of clonal spread to the emergence of PBP3-mediated resistance. Twenty-three β-lactamase negative respiratory tract isolates with resistance to penicillins and 23 susceptible control isolates were examined by determination of β-lactam MICs, ftsI sequencing and molecular typing by pulsed-field gel electrophoresis (PFGE). Ampicillin MIC ranges in the resistant group and the control group were 1–2 mg/L and 0.125–0.5 mg/L, respectively. All isolates in the resistant group had the PBP3 substitution Asn526 → Lys and were thus categorized as group II low-BLNAR. No control isolate met the genetic BLNAR (gBLNAR) criteria. The PBP3 substitution patterns corresponded well to those observed in previous European studies. Eighty-three percent (19/23) of the resistant isolates belonged to two clones, demonstrating the capability of low-BLNAR strains of clonal dissemination. Combined analysis of ftsI DNA sequences and PFGE patterns revealed distinctly different ftsI alleles in genetically indistinguishable isolates and identical copies of the same ftsI allele in unrelated isolates. A possible explanation of this observation is the recombinational exchange of ftsI alleles. This phenomenon, as well as the possibility of endemic European gBLNAR strains, should be further investigated.     

Rapid emergence of daptomycin resistance in clinical isolates of Corynebacterium striatum… a cautionary tale

The objective of this study was to investigate the observation of daptomycin resistance in Corynebacterium striatum, both in vivo and in vitro. We describe a case of C. striatum bacteremia in a patient with a left ventricular assist device (LVAD); the initial isolate recovered was daptomycin susceptible with a minimum inhibitory concentration (MIC) of 0.125 μg/ml. Two months later, and after daptomycin therapy, the individual became bacteremic with an isolate of C. striatum with a daptomycin MIC of >256 μg/ml. To study the prevalence of daptomycin resistance in C. striatum, clinical isolates of C. striatum were grown in broth culture containing daptomycin to investigate the emergence of resistance to this antimicrobial. Molecular typing was used to evaluate serial isolates from the index patient and the clinical isolates of C. striatum we assayed. In vitro analysis of isolates from the index patient and 7 of 11 additional C. striatum isolates exhibited the emergence of high-level daptomycin resistance, despite initially demonstrating low MICs to this antimicrobial agent. This phenotype was persistent even after serial subculture in the absence of daptomycin. Together, these data demonstrate that caution should be taken when using daptomycin to treat high-inoculum infections and/or infections of indwelling medical devices with C. striatum. To our knowledge, this is the first report characterizing the emergence of daptomycin resistance in C. striatum.     

Does estrogen enhance the antidepressant effects of fluoxetine?

BACKGROUND: While hormone replacement therapy (HRT) has not been shown to be an effective treatment for major depression, preliminary studies suggest that estrogen may potentiate the effect of selective serotonin reuptake inhibitors. METHOD: In an ongoing study, perimenopausal women diagnosed with major depression were randomly assigned to one of three treatment conditions: (1) fluoxetine 10-20 mg alone, (2) estradiol patch 0.1-0.2 mg alone or (3) the combination of fluoxetine 10-20 mg and estradiol patch 0.1-0.2 mg. RESULTS: In the five cases presented here, the combination of fluoxetine and estradiol was most effective, followed by fluoxetine alone and then estradiol alone. LIMITATIONS: These are selected cases from an ongoing study and do not represent statistically significant data. CONCLUSIONS: These preliminary cases suggest that estrogen can enhance the efficacy of antidepressant medication in menopausal women and this adjunctive treatment strategy may be superior to antidepressant or estrogen alone. Further research is needed in elucidating the mechanisms by which estrogen may enhance antidepressant action in perimenopausal women.