Swine as reservoirs of zoonotic borderline oxacillin-resistant Staphylococcus aureus ST398.

Methicillin resistance mediated by the mecA gene in Staphylococcus aureus, also known as "true MRSA", is typically associated with high oxacillin MIC values (≥8 mg/L). Because non-mecA-mediated oxacillin resistant S. aureus phenotypes can also cause hard-to-treat diseases in humans, their misidentification as methicillin-susceptible S. aureus strains (MSSA) can compromise the efficiency of the antimicrobial therapy. These strains have been refereed as Borderline Oxacillin-Resistant S. aureus (BORSA) but their characterization and role in clinical microbiology have been neglected. Considering the increasing importance of livestock-associated methicillin-resistant S. aureus ST398 (LA-MRSA) as an emerging zoonotic pathogen worldwide, this study aimed to report the genomic context of oxacillin resistance in porcine S. aureus ST398 strains. S. aureus isolates were recovered from asymptomatic pigs from three herds. Oxacillin MIC values ranged from 4 to 32 mg/L. MALDI-TOF-confirmed isolates were screened for mecA and mecC by PCR and genotyped by means of PFGE and Rep-PCR. Seven isolates were whole genome sequenced. None of the isolates harbored the mecA gene or its variants. Although all seven sequenced isolates belonged to one sequence type (ST398), two different spa types (t571 and t1471) were identified. All isolates harbored conserved blaZ gene operon and no mutations on genes encoding for penicillin-binding-proteins were detected. Genes conferring resistance against other drugs such as aminoglycosides, chloramphenicol, macrolide, lincosamide and streptogramin (MLS), tetracycline and trimethoprim were also detected. Isolates also harbored virulence genes encoding for adhesins (icaA; icaB; icaC; icaD; icaR), toxins (hlgA; hlgB; hlgC; luk-PV) and protease (aur). Pigs can serve as reservoirs of non-mecA-mediated oxacillin-resistant ST398 strains potentially pathogenic to humans. Considering that mecA has been the main target to screen methicillin-resistant staphylococci, the occurrence of BORSA phenotypes is probably underestimated in livestock.

Differentiation of hematopoietic stem cell and myeloid populations by ATP is modulated by cytokines.

Extracellular nucleotides are emerging as important regulators of inflammation, cell proliferation and differentiation in a variety of tissues, including the hematopoietic system. In this study, the role of ATP was investigated during murine hematopoiesis. ATP was able to reduce the percentage of hematopoietic stem cells (HSCs), common myeloid progenitors and granulocyte-macrophage progenitors (GMPs), whereas differentiation into megakaryocyte-erythroid progenitors was not affected. In addition, in vivo administration of ATP to mice reduced the number of GMPs, but increased the number of Gr-1(+)Mac-1(+) myeloid cells. ATP also induced an increased proliferation rate and reduced Notch expression in HSCs and impaired HSC-mediated bone marrow reconstitution in sublethally irradiated mice. Moreover, the effects elicited by ATP were inhibited by suramin, a P2 receptor antagonist, and BAPTA, an intracellular Ca(2+) chelator. We further investigated whether the presence of cytokines might modulate the observed ATP-induced differentiation. Treatment of cells with cytokines (stem cell factor, interleukin-3 and granulocyte-monocyte colony stimulator factor) before ATP stimulation led to reduced ATP-dependent differentiation in long-term bone marrow cultures, thereby restoring the ability of HSCs to reconstitute hematopoiesis. Thus, our data suggest that ATP induces the differentiation of murine HSCs into the myeloid lineage and that this effect can be modulated by cytokines.

Spray freeze drying with polyvinylpyrrolidone and sodium caprate for improved dissolution and oral bioavailability of oleanolic acid, a BCS Class IV compound.

Spray-freeze-drying (SFD) of oleanolic acid (OA), a BCS Class IV compound, with polyvinylpyrrolidone-40 (PVP-40) as stabilizer and sodium caprate (SC) as wetting agent and penetration enhancer produced kinetically stable, amorphous solid dispersion systems with superior in vitro dissolution performance, and better and more uniform absorption in comparison with commercial OA tablet. Relative to the SC-free formulation, the presence of SC in the formulation resulted in a significant increase in the in vivo absorption rate of OA while exerting no apparent impact on the extent of OA absorption. The SFD-processed OA formulations and commercial OA tablet generally exhibited large inter-animal variability in oral bioavailability, consistent with the absorption characteristics of BCS Class IV compounds. Inclusion of SC coupled with the replacement of OA with its sodium salt (OA-Na) in the formulation was shown to substantially decrease the observed absorption variability. Above results suggested that increases in both dissolution rate and intestinal permeability of BCS Class IV compounds, as exemplified by the SFD-processed dispersion system containing both OA-Na and SC, are critical to reducing the large inter-individual absorption variability commonly observed with this class of drugs.

Association of patients' perception of health status and exercise electrocardiogram, myocardial perfusion imaging, and ventricular function measures.

BACKGROUND: Patients' viewpoint of their health status is increasingly used as an important outcome measure of the success of treatments. Because clinicians rarely formally measure patients' health-related quality of life, the question arises whether noninvasive testing for ischemia can provide similar information regarding physical functioning and general health perception. METHODS: We measured physical functioning and general health status with the Medical Outcomes Study Short Form (SF-36) survey in 195 consecutive patients (68% male, mean age 55.6 +/- 11.1 years) referred for exercise testing with myocardial perfusion imaging. The survey was completed immediately before the exercise test. RESULTS: In the multivariate analysis, the strongest predictor of physical functioning and general health perception was metabolic equivalents. However, the best model, including demographic, clinical, and test variables, predicted only 14% of the variation in physical functioning and 10% of the variability in general health perception. CONCLUSIONS: The variation in physical functioning and general health perception, as measured by the SF-36, among patients referred for exercise testing is not predicted well by the results of the test. As expected, several test results are significantly associated with physical functioning and general health perception; however, there was substantial overlap among individual patients, suggesting that the parameters are poor surrogates for the actual assessment of the domains. If these domains are deemed important to tracking patient outcomes, then they should supplement the current assessments of these patients.

Population based study of social and productive activities as predictors of survival among elderly Americans.

OBJECTIVES: To examine any association between social, productive, and physical activity and 13 year survival in older people. DESIGN: Prospective cohort study with annual mortality follow up. Activity and other measures were assessed by structured interviews at baseline in the participants' homes. Proportional hazards models were used to model survival from time of initial interview. SETTING: City of New Haven, Connecticut, United States. PARTICIPANTS: 2761 men and women from a random population sample of 2812 people aged 65 and older. MAIN OUTCOME MEASURE: Mortality from all causes during 13 years of follow up. RESULTS: All three types of activity were independently associated with survival after age, sex, race/ethnicity, marital status, income, body mass index, smoking, functional disability, and history of cancer, diabetes, stroke, and myocardial infarction were controlled for. CONCLUSIONS: Social and productive activities that involve little or no enhancement of fitness lower the risk of all cause mortality as much as fitness activities do. This suggests that in addition to increased cardiopulmonary fitness, activity may confer survival benefits through psychosocial pathways. Social and productive activities that require less physical exertion may complement exercise programmes and may constitute alternative interventions for frail elderly people.

Referrals to a rheumatology unit: an evaluation of the views of patients, general practitioners, and consultants.

One hundred and twelve randomly selected patients referred to a rheumatology unit were studied, using structured questionnaires, to gain the views of patients, general practitioners (GPs), and the consultants. There were differences in perception between these respondents on the reason for referral. Major diagnostic changes were made in less than 10% of cases. Nearly all patients claimed that some aspect of their disease had been improved as a result of the appointment. Satisfaction with the communication aspects of the appointment contributed more to patients' overall satisfaction than did improvement in pain or disability. General practitioners' objectives were also met if communication with patients was satisfactory. In the management of chronic disease communication is important and should be recognised as such.