Persistence of Livestock Associated MRSA CC398 in Humans Is Dependent on Intensity of Animal Contact

INTRODUCTION: The presence of Livestock Associated MRSA (LA-MRSA) in humans is associated with intensity of animal contact. It is unknown whether the presence of LA-MRSA is a result of carriage or retention of MRSA-contaminated dust. We conducted a longitudinal study among 155 veal farmers in which repeated nasal and throat swabs were taken for MRSA detection. Periods with and without animal exposure were covered. METHODS: Randomly, 51 veal calf farms were visited from June-December 2008. Participants were asked to fill in questionnaires (n = 155) to identify potential risk factors for MRSA colonisation. Nasal and throat swabs were repeatedly taken from each participant for approximately 2 months. Swabs were analysed for MRSA and MSSA by selective bacteriological culturing. Spa-types of the isolates were identified and a ST398 specific PCR was performed. Data were analyzed using generalized estimation equations (GEE) to allow for correlated observations within individuals. RESULTS: Mean MRSA prevalence was 38% in farmers and 16% in family members. Presence of MRSA in farmers was strongly related to duration of animal contact and was strongly reduced in periods with absence of animal contact (-58%). Family members, especially children, were more often carriers when the farmer was a carrier (OR = 2,

Permeation Mechanisms in the TMEM16B Calcium-Activated Chloride Channels

TMEM16A and TMEM16B encode for Ca2+-activated Cl- channels (CaCC) and are expressed in many cell types and play a relevant role in many physiological processes. Here, I performed a site-directed mutagenesis study to understand the molecular mechanisms of ion permeation of TMEM16B. I mutated two positive charged residues R573 and K540, respectively located at the entrance and inside the putative channel pore and I measured the properties of wild-type and mutant TMEM16B channels expressed in HEK-293 cells using whole-cell and excised inside-out patch clamp experiments. I found evidence that R573 and K540 control the ion permeability of TMEM16B depending both on which side of the membrane the ion substitution occurs and on the level of channel activation. Moreover, these residues contribute to control blockage or activation by permeant anions. Finally, R573 mutation abolishes the anomalous mole fraction effect observed in the presence of a permeable anion and it alters the apparent Ca2+-sensitivity of the channel. These findings indicate that residues facing the putative channel pore are responsible both for controlling the ion selectivity and the gating of the channel, providing an initial understanding of molecular mechanism of ion permeation in TMEM16B

Does socioeconomic disparity in cancer incidence vary across racial/ethnic groups?

Objective Very few studies have simultaneously examined incidence of the leading cancers in relation to socioeconomic status (SES) and race/ethnicity in populations including Hispanics and Asians. This study aims to describe SES disparity in cancer incidence within each of four major racial/ethnic groups (non-Hispanic white, black, Hispanic, and Asian/Pacific Islander) for five major cancer sites, including female breast cancer, colorectal cancer, cervical cancer, lung cancer, and prostate cancer. Methods Invasive cancers of the five major sites diagnosed from 1998 to 2002 (n = 376,158) in California were included in the study. Composite area-based SES measures were used to quantify SES level and to calculate cancer incidence rates stratified by SES. Relative index of inequality (RII) was generated to measure SES gradient of cancer incidence within each racial/ethnic group. Results Significant variations were detected in SES disparities across the racial/ethnic groups for all five major cancer sites. Female breast cancer and prostate cancer incidence increased with increased SES in all groups, with the trend strongest among Hispanics. Incidence of cervical cancer increased with decreased SES, with the largest gradient among non-Hispanic white women. Lung cancer incidence increased with decreased SES with the exception of Hispanic men and women, for whom SES gradient was in the opposite direction. For colorectal cancer, higher incidence was associated with lower SES in non-Hispanic whites but with higher SES in Hispanics and Asian/Pacific Islander women. Conclusions Examining SES disparity stratified by race/ethnicity enhances our understanding of the complex relationships between cancer incidence, SES, and race/ethnicity

Carpal Tunnel Syndrome: A Review of the Recent Literature

Carpal Tunnel Syndrome (CTS) remains a puzzling and disabling condition present in 3.8% of the general population. CTS is the most well-known and frequent form of median nerve entrapment, and accounts for 90% of all entrapment neuropathies. This review aims to provide an overview of this common condition, with an emphasis on the pathophysiology involved in CTS. The clinical presentation and risk factors associated with CTS are discussed in this paper. Also, the various methods of diagnosis are explored; including nerve conduction studies, ultrasound, and magnetic resonance imaging

Photo-affinity labelling and biochemical analyses identify the target of trypanocidal simplified natural product analogues

This work was supported by the Leverhulme Trust (Grant number RL2012-025). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Current drugs to treat African sleeping sickness are inadequate and new therapies are urgently required. As part of a medicinal chemistry programme based upon the simplification of acetogenin-type ether scaffolds, we previously reported the promising trypanocidal activity of compound 1 , a bis-tetrahydropyran 1,4-triazole (B-THP-T) inhibitor. This study aims to identify the protein target(s) of this class of compound in Trypanosoma brucei to understand its mode of action and aid further structural optimisation. We used compound 3 , a diazirine- and alkyne-containing bi-functional photo-affinity probe analogue of our lead B-THP-T, compound 1 , to identify potential targets of our lead compound in the procyclic form T. brucei. Bi-functional compound 3 was UV cross-linked to its target(s) in vivo and biotin affinity or Cy5.5 reporter tags were subsequently appended by Cu(II)-catalysed azide-alkyne cycloaddition. The biotinylated protein adducts were isolated with streptavidin affinity beads and subsequent LC-MSMS identified the FoF1-ATP synthase (mitochondrial complex V) as a potential target. This target identification was confirmed using various different approaches. We show that (i) compound 1 decreases cellular ATP levels (ii) by inhibiting oxidative phosphorylation (iii) at the FoF1-ATP synthase. Furthermore, the use of GFP-PTP-tagged subunits of the FoF1-ATP synthase, shows that our compounds bind specifically to both the α- and β-subunits of the ATP synthase. The FoF1-ATP synthase is a target of our simplified acetogenin-type analogues. This mitochondrial complex is essential in both procyclic and bloodstream forms of T. brucei and its identification as our target will enable further inhibitor optimisation towards future drug discovery. Furthermore, the photo-affinity labeling technique described here can be readily applied to other drugs of unknown targets to identify their modes of action and facilitate more broadly therapeutic drug design in any pathogen or disease model.Publisher PDFPeer reviewe

Promoting optimal parenting and children’s mental health : a preliminary evaluation of the How-to Parenting Program

Parenting quality is widely accepted as a primary predictor of children’s mental health. The present study examined the effectiveness of a parenting program in fostering optimal parenting and child mental health. The selected program was How to talk so kids will listen & listen so kids will talk (How-to Parenting Program). This program was selected because its content corresponds closely to what the parenting style literature suggests is optimal parenting (i.e., includes structure, affiliation and autonomy support). Eleven groups of six to twelve parents were conducted in 7 local grade schools. The program, offered by two trained leaders, consisted of eight weekly sessions and taught a total of 30 skills. A total of 82 parents completed questionnaires both prior to and after the program. Participants’ children between eight and 12 years old (N = 44) completed questionnaires at school, at both assessment points. Repeated measures ANOVAs using parent reports indicated that structure, affiliation and autonomy support were increased after the program, compared to baseline. The level of child internalizing and externalizing problems also decreased significantly. Importantly, children reports confirmed that parental autonomy support increased from pre to post-test and child-reported well-being improved as well. The preliminary evidence from this pre-test versus post-test repeated measures design suggests that the How-to Parenting Program is effective in improving parenting style and in promoting children’s mental health and that future evaluation research examining the potential of this program is warranted