Fitness cost associated with resistance to fluoroquinolones is diverse across clones of Klebsiella pneumoniae and may select for CTX-M-15 type extended-spectrum β-lactamase

Lowered fitness cost associated with resistance to fluoroquinolones was recently demonstrated to influence the clonal dynamics of methicillin-resistant Staphylococcus aureus (MRSA) in the health care setting. We investigated whether or not a similar mechanism impacts Klebsiella pneumoniae. The fitness of K. pneumoniae isolates from major international hospital clones (ST11, ST15, ST147) already showing high-level resistance to fluoroquinolones and of strains from three minor clones (ST25, ST274, ST1028) in which fluoroquinolone resistance was induced in vitro was tested in a propagation assay. Strains from major clones showed significantly less fitness cost than three of four fluoroquinolone-resistant derivatives of minor clone isolates. In addition, plasmids with CTX-M-15 type extended-spectrum β-lactamase (ESBL) genes were all retained in both major and minor clone isolates, irrespective of the strains’ level of fluoroquinolone resistance, while each plasmid harboring SHV-type ESBLs had been lost during the induction of resistance. Major clone K. pneumoniae strains harbored more amino acid substitutions in the quinolone resistance determining regions (QRDRs) of the gyrA and parC genes than minor clone isolates. The presence of an active efflux system could be demonstrated in all fluoroquinolone-resistant derivatives of originally SHV-producing minor clone isolates but not in any CTX-M-15-producing strain. Further investigations are needed to expand and confirm our findings on a larger sample. In addition, a long-term observation of our ciprofloxacin-resistant minor clone isolates is required in order to elucidate whether or not they are capable of restoring their fitness while concomitantly retaining high minimum inhibitory concentration (MIC) values.     

El consumo de alcohol en la población joven (12-17 años). El punto de vista de los profesionales de la salud

ObjectiveTo find out the opinions of health professionals on adolescent alcohol drinking and their evaluation of the existing legal regulation measures.MethodologyDesign: Qualitative and exploratory study, based on semi-structured interviews.Setting: Four cities representing four different regions in Spain: Palma de Mallorca, Granada, Barcelona and Pamplona.Participants: A total of 36 physicians and nurses from four Spanish regions, working in Primary Care and Emergency Care, selected by intentiones samples.Measurements: A total of 36 deep interviews, analysed using the software Nudist Vivo 4.0.ResultsHealth professionals accept their important role in preventing and intervening in adolescent alcohol drinking. Generally, they consider it as a public health problem. Prevention is associated with Primary Care, while the Emergency Departments act in specific situations of alohol abuse. Adolescents infrequently visit Primary Care, thus prevention must centre on education system and constant coordination between health professional and parents. Health personnel do not have sufficient knowledge on legal regulations. They consider educational measures as more efficient than sanctions.ConclusionsSpecific professional training is required in order to guarantee the coordination between the health and education systems and the family.     

A novel percutaneous technique for accessing the normal pericardium: a single-center successful experience of 53 porcine procedures

Recently, the pericardial space has been under consideration as an ideal site for prevention and treatment of coronary artery and heart disease. Historically, safe percutaneous entry has not been possible to sample or remove pericardial fluids for diagnostic purposes or to employ therapeutic agents in the absence of a sizable pericardial effusion. A non-surgical percutaneous approach to permit rapid access to the normal or minimally effused pericardial space holds high potential for considerable diagnostic and therapeutic utility. This study examines the utility of the PerDUCER pericardial access device, a simplistic approach to permit percutaneous access to the normal, minimal or diseased pericardial space, in a large series of animals (swine). The PerDUCER , inserted through the introducer sheath in a sub-xiphoid position, allowed capture and delivery of the intrapericardial guidewire into the pericardial space in all animals. The procedure was well tolerated by all animals and exhibited no signs of significant adverse hemodynamic effects. Twelve animals were sacrificed immediately after the experiment, while 41 animals were sacrificed 28 days after the procedure. Histologic examination showed no occurrence of epicardial vessel or myocardial damage. In addition, no late complications were found related to pericardial access with the PerDUCER . This initial experiment demonstrates that the PerDUCER provides an efficient, safe and effective technique to gain pericardial access in the normal or minimal pericardial space to obtain diagnostic sampling of the pericardial fluids and renders local intrapericardial delivery of therapeutic agents a possibility.     

Intraparental Inconsistency: The Influence of Parenting Behaviors on Aggression and Depression in Children

The authors examined several different predictive and mediation models of longitudinal parental inconsistency over a 3‐year time span. They hypothesized that parental behavior (communication/affection, kindness, and positive control) mediated the relationship between parental inconsistency (mother or father) and two emotional problems in children: (a) aggression and (b) depression. Data were obtained from a 3‐wave study (2007, 2008, and 2009) of 523 Spanish families with children ranging from 9–15 years of age at the beginning of Wave 1 (41.3% boys). Structural equation models revealed that multiple dimensions of parenting (mother or father) fully or partially mediated the relationship between longitudinal parental inconsistency and the child's adjustment. Communication/affection and kindness are the main processes through which parental inconsistency affects a child's aggression and depression. These results represent an important contribution to the improvement of parenting models of relationships between parental inconsistency and child adjustment.     

What are the costs to society and the potential benefits from the effective management of early rheumatoid arthritis?

Rheumatoid arthritis is a chronic disabling condition associated with a significant long-term loss of function and a significant socio-economic impact on individual sufferers and their families, as well as on society as a whole. There is a suggestion that the incidence and severity of the disease may be abating slightly, which has been attributed to the trend to 'invert the pyramid' and to diagnose and treat rheumatoid disease earlier and more aggressively. Studies have confirmed that the erosions, which lead to subsequent joint damage, occur early in the course of the disease. Ongoing disease activity, both clinically and serologically, has now been linked to increasing morbidity, loss of function and mortality. New agents have been developed and, together with combinations of old and new agents, have been shown to be more effective if used earlier in the course of the disease. The better the early control of the disease, the better the long-term outcome. Early and more vigorous treatment, particularly of those patients with a high joint count, early loss of function and an elevated titre of inflammatory markers, has potential to reduce the twofold increase in mortality seen among rheumatoid arthritis patients. The scene is set to have a greater impact on the long-term disability and associated cost to the individual and society by treating early and treating often. Combination therapy and the new 'biologicals' are, however, far more expensive than the previously available agents, and the direct medical costs associated with medication, as well as the monitoring costs for rheumatoid arthritis, are increasing. It is difficult to value the long-term prevention of pain and suffering, and the maintenance of productivity. However, if the disease were effectively controlled early, there would be long-term benefits to be offset against the higher treatment cost. It behooves the rheumatological community to use the new agents wisely to gain the greatest advantage for all patients as well as to monitor the long-term benefits and drawbacks so that cost-effectiveness can be comprehensively evaluated.     

Cigarette smoke-induced airway hyperresponsiveness is not dependent on elevated immunoglobulin and eosinophilic inflammation in a mouse model of allergic airway disease

Epidemiologic studies suggest that children raised in homes of cigarette smokers have a higher incidence of asthma than children who are raised in homes of nonsmokers. We sought to develop an experimental model to understand the mechanisms involved. Female BALB/c mice were paired with male DO11.10 ovalbumin (OVA)-T cell receptor hemizygous (+/-) mice such that the offspring were either transgene positive (+/-) or negative (-/-). Mice were exposed to either air or mainstream cigarette smoke (100 mg/m(3) total particulate matter, 6 hours/day, 7 days/week) during pregnancy. Immediately after birth, newborn mice were exposed for 4 weeks to either air or sidestream cigarette smoke (SS; 5 mg/m(3) total particulate matter, 6 hours/day, 5 days/week) and then exposed for the following 6 weeks to either air, SS, OVA (5 mg/m(3), 6 hours/day, 5 days/week) or a combination of OVA-SS. DO11.10 +/- offspring exposed to OVA had increased airway hyperresponsiveness (AHR) to methacholine challenge, total IgE, OVA-specific IgE and IgG(1), lymphocytes, and neutrophils in bronchoalveolar lavage and perivascular and peribronchiolar inflammation. Exposure to SS alone caused a significant increase in AHR in both +/- and -/- mice. Transgene -/- mice did not exhibit AHR after OVA exposure unless it was delivered in combination with SS. When compared with OVA-only exposure, OVA-SS exposure decreased total IgE, OVA-specific IgE, and IgG(1) amounts in +/- mice. These results indicate that exposure to SS after birth enhanced AHR in offspring that are both predisposed (+/-) and nonpredisposed (-/-) to develop an allergic response to OVA, but this AHR was not associated with elevated lung eosinophilia or OVA-specific Ig amounts.