Tumor genotype dictates radiosensitization after Atm deletion in primary brainstem glioma models

Diffuse intrinsic pontine glioma (DIPG) kills more children than any other type of brain tumor. Despite clinical trials testing many chemotherapeutic agents, palliative radiotherapy remains the standard treatment. Here, we utilized Cre/loxP technology to show that deleting Ataxia telangiectasia mutated (Atm) in primary mouse models of DIPG can enhance tumor radiosensitivity. Genetic deletion of Atm improved survival of mice with p53-deficient but not p53 wild-type gliomas after radiotherapy. Similar to patients with DIPG, mice with p53 wild-type tumors had improved survival after radiotherapy independent of Atm deletion. Primary p53 wild-type tumor cell lines induced proapoptotic genes after radiation and repressed the NRF2 target, NAD(P)H quinone dehydrogenase 1 (Nqo1). Tumors lacking p53 and Ink4a/Arf expressed the highest level of Nqo1 and were most resistant to radiation, but deletion of Atm enhanced the radiation response. These results suggest that tumor genotype may determine whether inhibition of ATM during radiotherapy will be an effective clinical approach to treat DIPGs.     

The aerodynamic impact of a range of prostheses designs when cycling with a trans-tibial amputation

Abstract

Previous studies have proposed that an aerodynamically optimized prosthetic limb could provide performance enhancement for competitive paracyclists. Four different designs of prosthetic limbs were assessed for their impact upon the aerodynamic drag of an elite cyclist with a lower-limb amputation. The pylon area acted as the controlled location for the differences in design between the test prostheses. A validated field test method was used to derive the participant’s total aerodynamic drag when using the prostheses designs. The field test method produced a repeatable experimental process and demonstrated that small changes in form made to the pylon region resulted in measurable differences to the participant’s cycling performance. In addition, statistical significance was obtained between a baseline design and the prostheses prototype with the greatest aspect ratio (p=?<.05). The magnitude of improvements recorded in this study could potentially influence a rider’s finishing time at international sporting events like the Paralympic Games.

• Implications for Rehabilitation

• Small changes in form made to a cycling prostheses design can potentially deliver worthwhile performance enhancement.

• Prosthetists may obtain greater end-user satisfaction by taking a broader approach to sports prostheses design than just fit and biomechanical function alone.

• This study indicates that other regions of the cycling prosthesis could now benefit from aerodynamic optimization with the aim to further improve paracycling performance.

     

Shunting away from transradial arterial access?

Due to its increased safety and decrease in significant vascular complications and bleeding events, the use of the radial artery for percutaneous coronary intervention (PCI) is increasing. Transradial access (TRA), however, is not without consequence. TRA arteries when used for coronary artery bypass grafting (CABG) are associated with decreased graft patency rates. Here we comment on a case report in which a patient developed a clinically significant arteriovenous fistula following TRA treated with surgical ligation. We offer insights on the increased use of the radial artery in both PCI and CABG.     

This is who we are: building community for HIV prevention with young gay and bisexual men in Beirut,Lebanon

Young gay men in Beirut are at significantly elevated risk of HIV infection compared with the general Lebanese population. Despite nascent HIV prevention efforts in the region, there is a need for effective community-level HIV prevention interventions tailored for young gay men. This qualitative study examined internal dynamics within Beirut’s gay community as a basis for developing community-level interventions. Peer ethnographers were trained to collect field notes on conversations between young gay men in public spaces in Beirut, and conducted follow-up focus groups with young gay men. Analyses revealed three major themes: (1) the need for safe spaces in which to socialise, (2) the importance of being able to locate and connect with other young gay men, and (3) ambivalence regarding a gay community that was supportive in some ways but also fragmented and often judgemental. Study findings also confirm the existence of external threats to community such as stigma, cultural and familial norms regarding heterosexuality and criminalisation of refugee status. Understanding such community dynamics and the environmental context is central to designing effective community-based HIV prevention programmes.     

Real-Time Assessments of the Strength of Program Implementation for Community Case Management of Childhood Illness: Validation of a Mobile Phone-Based Method in Malawi

Health surveillance assistants (HSAs) in Malawi have provided community case management (CCM) since 2008; however, program monitoring remains challenging. Mobile technology holds the potential to improve data, but rigorous assessments are few. This study tested the validity of collecting CCM implementation strength indicators through mobile phone interviews with HSAs. This validation study compared mobile phone interviews with information obtained through inspection visits. Sensitivity and specificity were measured to determine validity. Using mobile phones to interview HSAs on CCM implementation strength indicators produces accurate information. For deployment, training, and medicine stocks, the specificity and sensitivity of the results were excellent (> 90%). The sensitivity and specificity of this method for drug stock-outs, supervision, and mentoring were lower but with a few exceptions, still above 80%. This study provided a rigorous assessment of the accuracy of implementation strength data collected through mobile technologies and is an important step forward for evaluation of public health programs.