Supervised exercise-based rehabilitation for people with intermittent claudication-Study protocol for a Danish implementation process (StRiDE).

Introduction: Intermittent claudication is a peripheral artery disease caused by arteriosclerosis. People with intermittent claudication experience leg cramping during walking, with relief of symptoms during rest. Evidence shows that by participating in supervised exercise therapy and smoking cessation programs, people with intermittent claudication can reduce those symptoms and improve health-related quality of life and maximal walking distance while minimizing the need for an operation.

Visual body size estimation in adolescent anorexia nervosa: Behavioural and neurophysiological data suggest intact visual perception and biased emotional attention.

Body image disturbance is a key symptom of anorexia nervosa (AN). AN patients report body dissatisfaction and overestimate their own body size in several tasks. This study aimed to clarify whether this overestimation arises from deficits in visual perception.

["BodyExperience" - I - You -We and Anorexia Nervosa in Adolescence].

Adolescence can be understood as a physical "awakening", but keeping a childlike mind.The term "awakening" implies movement, straightening, purposeful progress and change as physical occurrences. The development of a sexual identity differentiates in the change of female/male body parts and reaches its peak.

Influence of Identity Development on Weight Gain in Adolescent Anorexia Nervosa.

Background: Anorexia Nervosa (AN) typically begins during early adolescence, an important phase of personality development. A substantial proportion of adolescent AN patients shows impaired personality functioning, which might be a relevant but understudied aspect of illness severity. The developmental status of identity as key element of personality is suggested to influence inpatient treatment outcome in adolescents with AN.

Selective toxicity of antibacterial agents-still a valid concept or do we miss chances and ignore risks?

Background: Selective toxicity antibacteribiotics is considered to be due to interactions with targets either being unique to bacteria or being characterized by a dichotomy between pro- and eukaryotic pathways with high affinities of agents to bacterial- rather than eukaryotic targets. However, the theory of selective toxicity oversimplifies the complex modes of action of antibiotics in pro- and eukaryotes.

Methods And Objective: This review summarizes data describing multiple modes of action of antibiotics in eukaryotes.

Are antibacterial effects of non-antibiotic drugs random or purposeful because of a common evolutionary origin of bacterial and mammalian targets?

Purpose: Advances in structural biology, genetics, bioinformatics, etc. resulted in the availability of an enormous pool of information enabling the analysis of the ancestry of pro- and eukaryotic genes and proteins.

Methods: This review summarizes findings of structural and/or functional homologies of pro- and eukaryotic enzymes catalysing analogous biological reactions because of their highly conserved active centres so that non-antibiotics interacted with bacterial targets.

Perceptive Body Image Distortion in Adolescent Anorexia Nervosa: Changes After Treatment.

One key symptom of anorexia nervosa (AN) is body image distortion (BID). For example, AN patients who are asked to perform body size estimation tasks tend to overestimate their body size; this is thought to indicate a distortion of the perceptive component of body image. Although BID is an important treatment objective, only few treatment approaches explicitly target body image, and even fewer target the perceptive component.

Comparative evaluation of eight in vitro pharmacodynamic models of infection: Activity of moxifloxacin against Escherichia coli and Streptococcus pneumoniae as an exemplary example.

Use of pharmacodynamic in vitro models provides more clinically relevant information about the activities of antibiotics than static endpoints. Several models are used to simulate pharmacokinetics by dilution of the medium. It is discussed whether this procedure would result in a washout of bacteria, particularly if profiles with a short half-life are simulated.

Explorative Randomized Phase II Clinical Study of the Efficacy and Safety of Finafloxacin versus Ciprofloxacin for Treatment of Complicated Urinary Tract Infections.

The broad-spectrum C-8-cyano-fluoroquinolone finafloxacin displays enhanced activity under acidic conditions. This phase II clinical study compared the efficacies and safeties of finafloxacin and ciprofloxacin in patients with complicated urinary tract infection and/or pyelonephritis. A 5-day regimen with 800 mg finafloxacin once a day (q.

Population Pharmacokinetics of Finafloxacin in Healthy Volunteers and Patients with Complicated Urinary Tract Infections.

Finafloxacin is a novel fluoroquinolone with increased antibacterial activity at acidic pH and reduced susceptibility to several resistance mechanisms. A phase II study revealed a good efficacy/safety profile in patients with complicated urinary tract infections (cUTIs), while the pharmacokinetics was characterized by highly variable concentration-versus-time profiles, suggesting the need for an elaborated pharmacokinetic model. Data from three clinical trials were evaluated: 127 healthy volunteers were dosed orally ( = 77) or intravenously ( = 50), and 139 patients with cUTI received finafloxacin intravenously.

Early Clinical Assessment of the Antimicrobial Activity of Finafloxacin Compared to Ciprofloxacin in Subsets of Microbiologically Characterized Isolates.

Two phase II studies were performed with patients with uncomplicated urinary tract infections (uUTIs) and complicated urinary tract infections (cUTIs) or acute pyelonephritis (PN) to compare finafloxacin (300 mg twice a day [b.i.d.

Seventy-Five Years of Research on Protein Binding.

This review summarizes evidence that the impact of protein binding of the activity of antibiotics is multifaceted and more complex than indicated by the numerical value of protein binding alone. A plethora of studies has proven that protein binding of antibiotics matters, as the free fraction only is antibacterially active and governs pharmacokinetics. Several studies have indicated that independent from protein binding of immunoglobulin G, albumin, α-acid-glycoprotein, and pulmonary surfactant acted synergistically with antibacterial agents, thus suggesting that some intrinsic properties of serum proteins may have mediated serum-antibiotic synergisms.

Does the use of antifungal agents in agriculture and food foster polyene resistance development? A reason for concern.

Environmental fungicides are used in agriculture to reduce fungal spoilage of crops to a minimum, and the polyene macrolide natamycin is used as a food preservative. The use of natamycin in yoghurt has recently been authorised in the USA and some other countries. However, resistance development is a serious risk associated with the use of antimicrobials as food additives and environmental fungicides.

Pharmacokinetics of Intravenous Finafloxacin in Healthy Volunteers.

Finafloxacin is a novel fluoroquinolone exhibiting enhanced activity under acidic conditions and a broad-spectrum antibacterial profile. The present study assessed the pharmacokinetic properties and the safety and tolerability of finafloxacin following intravenous infusions. In this mixed-parallel-group, crossover study, healthy male and female volunteers received single ascending doses (18 volunteers, 200 to 1,000 mg) or multiple ascending doses (40 volunteers, 600 to 1,000 mg) of finafloxacin or placebo.

Pharmacodynamics of Finafloxacin, Ciprofloxacin, and Levofloxacin in Serum and Urine against TEM- and SHV-Type Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae Isolates from Patients with Urinary Tract Infections.

The pharmacodynamics of finafloxacin, ciprofloxacin, and levofloxacin against extended-spectrum-β-lactamase (ESBL)-producing isolates were compared. Since quinolones lose activity in acidic media, and particularly in urine, their activities were tested in parallel under conventional conditions and in acidic artificial urine. For this purpose, TEM- and SHV-type ESBL-producing and strains and their wild-type counterparts were exposed in a modified Grasso model to simulated concentrations of drugs in serum and urine following oral doses of either finafloxacin at 800 mg once a day (q.

Analysis of effects of MCB3681, the antibacterially active substance of prodrug MCB3837, on human resident microflora as proof of principle.

The water-soluble prodrug MCB3837 is rapidly converted to MCB3681, active against Gram-positive bacterial species, after intravenous infusion. The aim of this study was to prove the principle that MCB3681 is efficacious in vivo by demonstrating its effect on the resident microflora or colonizers of the human skin, nose, oropharynx and intestine. MCB3837 was infused at a daily dose of 6 mg/kg for 5 days.

Does use of the polyene natamycin as a food preservative jeopardise the clinical efficacy of amphotericin B? A word of concern.

Natamycin is a poorly soluble, polyene macrolide antifungal agent used in the food industry for the surface treatment of cheese and sausages. This use is not of safety concern. However, highly soluble natamycin-cyclodextrin inclusion complexes have been developed for the protection of beverages.

Antiviral, antifungal, and antiparasitic activities of fluoroquinolones optimized for treatment of bacterial infections: a puzzling paradox or a logical consequence of their mode of action?

This review summarizes evidence that commercially available fluoroquinolones used for the treatment of bacterial infections are active against other non-bacterial infectious agents as well. Any of these fluoroquinolones exerts, in parallel to its antibacterial action, antiviral, antifungal, and antiparasitic actions at clinically achievable concentrations. This broad range of anti-infective activities is due to one common mode of action, i.

Pharmacokinetics and pharmacodynamics of aerosolized antibacterial agents in chronically infected cystic fibrosis patients.

Bacteria adapt to growth in lungs of patients with cystic fibrosis (CF) by selection of heterogeneously resistant variants that are not detected by conventional susceptibility testing but are selected for rapidly during antibacterial treatment. Therefore, total bacterial counts and antibiotic susceptibilities are misleading indicators of infection and are not helpful as guides for therapy decisions or efficacy endpoints. High drug concentrations delivered by aerosol may maximize efficacy, as decreased drug susceptibilities of the pathogens are compensated for by high target site concentrations.

Young children's agent-neutral representations of action roles.

Recent developmental research has shown that young children coordinate complementary action roles with others. But what do they understand about the logical structure of such roles? Do they have an agent-neutral conception of complementary action roles, grasping that such roles can be variably filled by any two agents or even by one agent over time? Accordingly, can they make use of such representations for planning both their own and others' actions? To address these questions, 3- and 4-year-olds were introduced to an activity comprising two action roles, A and B, by seeing either two agents performing A and B collaboratively or one agent performing A and B individually. Children's flexible inferences from these demonstrations were then tested by asking them later on to plan ahead for the fulfillment of one of the roles either by themselves or by someone else.

In vitro activity of MCB3681 against Clostridium difficile strains.

One hundred fourteen Clostridium difficile strains were collected from 67 patients and analyzed for the presence of C. difficile toxin B by the cell cytotoxoicity neutralization assay, genes for toxin A, toxin B, binary toxin and TcdC deletion by PCR. All strains were also PCR-ribotyped.

Ecological impact of MCB3837 on the normal human microbiota.

MCB3837 is a novel, water-soluble, injectable prodrug that is rapidly converted to the active substance MCB3681 in vivo following intravenous (i.v.) administration.

Alternative strategies for proof-of-principle studies of antibacterial agents.

The proof that a new antibacterial agent is not only active in vitro but also effective in vivo under clinically relevant conditions is currently provided (i) by using appropriate nonclinical models of infection and pharmacokinetic-pharmacodynamic (PK-PD) analysis providing evidence of the likelihood of clinical efficacy and (ii) by examining the study drug in exploratory clinical trials, as well as dose and schedule finding during phase II of clinical development. This approach is both time-consuming and costly. Furthermore, PK-PD targets for any novel antibacterial agent cannot be derived from studies with experimental animals.