Deciphering interplay between Salmonella invasion effectors

Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction

Elbow medial collateral ligament injuries

Elbow medial collateral ligament sprain occurs when the elbow is subjected to a valgus force exceeding the tensile properties of the medial collateral ligament (MCL). This is an injury seen more often in throwing athletes. Understanding the differential diagnosis of medial elbow pain is paramount to diagnose MCL injury as well as addressing other medial elbow pathology. A natural evolution regarding MCL injury has occurred over the past 20 years, with modifications of the original surgical procedure, specificity and sensitivity analysis of imaging modalities, and physical exam maneuvers to diagnose MCL pathology. In order for the MCL literature to advance further, more biomechanical and long-term clinical outcome data for the respective surgical modifications are needed. This review describes MCL injury pathophysiology, patient evaluation, reconstruction indications/contraindications, and current and evolving surgical techniques

Intradialytic Massage for Leg Cramps Among Hemodialysis Patients: a Pilot Randomized Controlled Trial

Background: Patients on hemodialysis often experience muscle cramps that result in discomfort, shortened treatment times, and inadequate dialysis dose. Cramps have been associated with adversely affecting sleep and health-related quality of life, depression and anxiety. There is limited evidence available about massage in dialysis; however, massage in cancer patients has demonstrated decreases in pain, inflammation, and feelings of anxiety. These correlations indicate massage may be an effective treatment modality for hemodialysis-related lower extremity cramping.Purpose: To determine the effectiveness of intradialytic massage on the frequency of cramping among hemodialysis patients prone to lower extremity cramping.Participants: 26 maintenance hemodialysis patients with frequent lower extremity cramps.Setting: three outpatient hemodialysis centers in Northeast Ohio.Research Design: randomized controlled trial.Intervention: The intervention group received a 20-minute massage of the lower extremities during each treatment (three times per week) for two weeks. The control group received usual care by dialysis center staff.Main Outcome Measure: change in frequency of lower leg cramping.Results: Patient reported cramping at home decreased by 1.3 episodes per week in the intervention group compared to 0.2 episodes per week in the control group (p=.005). Patient reported cramping during dialysis decreased by 0.8 episodesin the intervention group compared to 0.4 episodes in the control group (p=0.44).Conclusion: Intradialytic massage appears to be an effective way to address muscle cramping. Larger studies with longer duration should be conducted to further examine this approach

Long-term exposure to air pollution and hospital admissions for ischemic stroke. A register-based case-control study using modelled NOx as exposure proxy

Background: Long-term exposure to air pollution is a hypothesized risk factor for ischemic stroke. In a large case-control study with a complete study base, we investigated whether hospital admissions for ischemic stroke were associated with residential concentrations of outdoor NOx, as a proxy for exposure to air pollution, in the region of Scania, Southern Sweden. Methods: We used a two-phase case-control study design, including as first-phase controls all individuals born between 1923 and 1965 and residing in Scania in 2002 (N=556 912). We defined first-phase cases as first-time ischemic stroke patients residing in Scania and registered in the Swedish stroke register between 2001 and 2005 (N=4 904) and second-phase cases as cases for whom we had information on smoking status, diabetes, and medication for hypertension (N=4 375). For the controls, information on these covariables was collected from a public health survey, resulting in 4 716 second-phase controls. With a geographical information system and an emission database, individual residential outdoor annual mean NOx concentration was modelled. The data were analyzed with logistic regression. Results: We found no evident association between NOx and ischemic stroke. For example, the odds ratio for ischemic stroke associated with the NOx category 20-30 mu g/m(3) compared to the reference category of <10 mu g/m(3) was 0.95 (95% CI 0.86-1.06). Conclusion: In this study area, with generally low levels of air pollution, using a complete study base, high-quality ascertainment of cases, and individually modelled exposure, we did not observe any clear association between NOx and ischemic stroke hospital admissions

Study protocol: healthy urban living and ageing in place (HULAP): an international, mixed methods study examining the associations between physical activity, built and social environments for older adults the UK and Brazil

Abstract Background The ability to ‘age in place’ is dependent on a range of inter-personal, social and built environment attributes, with the latter being a key area for potential intervention. There is an emerging body of evidence that indicates the type of built environment features that may best support age friendly communities, but there is a need to expand and consolidate this, while generating a better understanding of how on how research findings can be most effectively be translated in to policy and practice. Methods The study is based on two case study cities, Curtiba (Brazil) and Belfast (UK), which have highly contrasting physical, social and policy environments. The study deploys a mix methods approach, mirrored in each city. This includes the recruitment of 300 participants in each city to wear GPS and accelerometers, a survey capturing physical functioning and other personal attributes, as well as their perception of their local environment using NEWS-A. The study will also measure the built environments of the cities using GIS and develop a tool for auditing the routes used by participants around their neighbourhoods. The study seeks to comparatively map the policy actors and resources involved in healthy ageing in the two cities through interviews, focus groups and discourse analysis. Finally, the study has a significant knowledge exchange component, including the development of a tool to assess the capacities of both researchers and research users to maximise the impact of the research findings. Discussion The HULAP study has been designed and implemented by a multi-disciplinary team and integrates differing methodologies to purposefully impact on policy and practice on healthy ageing in high and low-middle income countries. It has particular strengths in its combination of objective and self-reported measures using validated tools and the integration of GPS, accelerometer and GIS data to provide a robust assessment of ‘spatial energetics’. The strong knowledge exchange strand means that the study is expected to also contribute to our understanding of how to maximise research impact in this field and create effective evidence for linking older adult’s physical activity with the social, built and policy environments

Rapid isolation and characterization of microsatellites in the critically endangered mountain bongo (Tragelaphus eurycerus isaaci)

High-throughput sequencing tools promise to revolutionize many aspects of genetic research, e.g. by allowing the identification of functional adaptive genetic variation. However, the expense and expertise required to apply these tools to basic conservation questions is a challenge for applications outside academia, resulting in a so-called ‘conservation genomics gap’ (Shafer et al.2015). The conservation genetics paradigm is that, basic information about inbreeding and gene flow are often critical to inform conservation management of small populations (Ouborg et al.2010). This information is often needed quickly and ideally should be accessible to workers without special expertise in genomics (DeSalle and Amato 2004). While the inferential power of high-throughput sequencing to interrogate the genome is profound, the cost for population analysis is higher (though decreasing) than for traditional neutral markers. Thus, the use of neutral markers is still relevant in conservation applications. However, this assumes that neutral markers have been discovered and characterized for a given species of conservation concern, which is often untrue for nonmodel organisms. Here, we use a fast, cost-efficient, high-throughput sequencing method (Illumina MiSeq) to rapidly identify and characterize microsatellites in the mountain bongo (Tragelaphus eurycerus isaaci), which has a clear and timely conservation imperative but lacks any described neutral markers