Investigation of white blood cell characteristics in cerebrospinal fluid samples at pediatric brain tumor diagnosis

Journal of Neuro-Oncology - The role of white blood cells (WBC) in the pediatric central nervous system (CNS) tumor microenvironment is incompletely defined. We hypothesized that the WBC profile in...     

Targeting MYC-driven replication stress in medulloblastoma with AZD1775 and gemcitabine

Journal of Neuro-Oncology - MYC-driven medulloblastomas are highly aggressive childhood tumors with dismal outcomes and a lack of new treatment paradigms. We identified that targeting replication...     

Use of the Fogg Behavior Model to Assess the Impact of a Social Marketing Campaign on Condom Use in Pakistan

The Fogg Behavior Model (FBM) is a new framework which posits that behavior happens when three factors – motivation, ability, and a prompt – occur in the same moment. The FBM categorizes people into four groups based on motivation and ability and posits that those with high motivation and high ability will adopt a behavior when prompted. Two rounds of panel survey data from 617 married men in urban Pakistan were used to test this hypothesis. Multilevel mixed-effects logistic regression was used for the analysis. The results show the relationships between ability, motivation, the prompt and condom use to be as hypothesized by the FBM. After adjustment for a range of variables including fertility desires, education, and household wealth, the odds of condom use among men with high motivation and high ability were 34 times higher than the odds of condom use among men with low motivation and low ability. Moreover, the association between the prompt and condom use operated through increased motivation and ability. The FBM has potential for use in the design and evaluation of behavior change interventions in developing countries.     

Mailed fecal immunochemical test outreach for colorectal cancer screening: Summary of a Centers for Disease Control and Prevention–sponsored Summit

Uptake of colorectal cancer screening remains suboptimal. Mailed fecal immunochemical testing (FIT) offers promise for increasing screening rates, but optimal strategies for implementation have not been well synthesized. In June 2019, the Centers for Disease Control and Prevention convened a meeting of subject matter experts and stakeholders to answer key questions regarding mailed FIT implementation in the United States. Points of agreement included: 1) primers, such as texts, telephone calls, and printed mailings before mailed FIT, appear to contribute to effectiveness; 2) invitation letters should be brief and easy to read, and the signatory should be tailored based on setting; 3) instructions for FIT completion should be simple and address challenges that may lead to failed laboratory processing, such as notation of collection date; 4) reminders delivered to initial noncompleters should be used to increase the FIT return rate; 5) data infrastructure should identify eligible patients and track each step in the outreach process, from primer delivery through abnormal FIT follow-up; 6) protocols and procedures such as navigation should be in place to promote colonoscopy after abnormal FIT; 7) a high-quality, 1-sample FIT should be used; 8) sustainability requires a program champion and organizational support for the work, including sufficient funding and external policies (such as quality reporting requirements) to drive commitment to program investment; and 9) the cost effectiveness of mailed FIT has been established. Participants concluded that mailed FIT is an effective and efficient strategy with great potential for increasing colorectal cancer screening in diverse health care settings if more widely implemented.     

Increased expression of glutamine transporter SNAT2/SLC38A2 promotes glutamine dependence and oxidative stress resistance,and is associated with worse prognosis in triple-negative breast cancer

Background Glutamine (Gln) is an abundant nutrient used by cancer cells. Breast cancers cells and particularly triple-receptor negative breast cancer (TNBC) are reported to be dependent on Gln to produce the energy required for survival and proliferation. Despite intense research on the role of the intracellular Gln pathway, few reports have focussed on Gln transporters in breast cancer and TNBC.Methods The role and localisation of the Gln transporter SLC38A2/SNAT2 in response to Gln deprivation or pharmacological stresses was examined in a panel of breast cancer cell lines. Subsequently, the effect of SLC38A2 knockdown in Gln-sensitive cell lines was analysed. The prognostic value of SLC38A2 in a cohort of breast cancer was determined by immunohistochemistry.Results SLC38A2 was identified as a strongly expressed amino acid transporter in six breast cancer cell lines. We confirmed an autophagic route of degradation for SLC38A2. SLC38A2 knockdown decreased Gln consumption, inhibited cell growth, induced autophagy and led to ROS production in a subgroup of Gln-sensitive cell lines. High expression of SLC38A2 protein was associated with poor breast cancer specific survival in a large cohort of patients (p = 0.004), particularly in TNBC (p = 0.02).Conclusions These results position SLC38A2 as a selective target for inhibiting growth of Gln-dependent breast cancer cell lines.Subject terms: Breast cancer, Cancer metabolism     

Inspiratory muscle training for intensive care patients: A multidisciplinary practical guide for clinicians

ObjectivesTo describe a multidisciplinary approach to inspiratory muscle training (IMT) for patients in the intensive care unit (ICU).BackgroundInspiratory muscle weakness is a known consequence of prolonged mechanical ventilation, and there is emerging evidence that specific IMT can ameliorate this weakness. However, IMT is not yet standard practice in many ICUs, possibly because of the wide variety of methods reported and a lack of published practical guidelines. While the optimal parameters for IMT are yet to be established, we share our detailed methodology which has been shown to be safe in selected ventilator-dependent patients and is the only approach which has been shown to increase quality of life in ICU patients.MethodsPatients who have experienced invasive mechanical ventilation for at least 7 days can commence IMT in either the ventilator-dependent phase or when weaned from mechanical ventilation. Intensity should be prescribed based on maximum inspiratory pressure, which is measurable through the tracheostomy or endotracheal tube via the ventilator or a respiratory pressure meter. Using a removable threshold device, we recommend high-intensity training (5 sets of 6 breaths at a minimum of 50% of maximum inspiratory pressure) performed once per day, supervised by the physiotherapist, with intensity increased daily such that patients can only just complete the 6th breath in each set.ResultsUsing this high-intensity approach, IMT is likely to improve not only inspiratory muscle strength but also quality of life in patients recently weaned from mechanical ventilation of 7 days' duration or longer. Effective IMT requires a multidisciplinary approach to maximise feasibility, with doctors, nurses, and therapists working closely to optimise conditions for successful IMT.ConclusionsThis multidisciplinary approach to implement IMT in ICU patients should assist clinicians in translating best-available evidence into practice, with the potential to enhance patient recovery.     

Melanoma and skin cancers in airline pilots and cabin crew

Ultraviolet radiation (UVR) from the sun is a major cause of skin cancer, including melanoma which is the most deadly form of the disease. As part of their jobs, airline pilots and cabin crews are exposed to cosmic radiation, and airline pilots may receive UVR on the flight deck, potentially resulting in skin cancer. The authors, based in Australia and the U.K, therefore systematically reviewed all relevant studies to find out risk of, and mortality (death) from, melanoma and other skin cancers in airline pilots and cabin crews. The majority of the 12 studies identified were conducted in the 1970s to 1990s in Europe or North America. They found that melanoma and other skin cancers were around twice as common in pilots and cabin crews as in the general community. Melanoma deaths were also doubled in the pilots but not in the aircrew. Ultraviolet B radiation from the sun is the main cause of melanoma and other skin cancer, but ultraviolet B radiation is not detectable or not increased above ground level values in modern airline cabins and flight decks. Also occupational levels of cosmic radiation among pilots and cabin crew are assessed not to be hazardous. However, high recreational sun exposure (i.e. time in the sun when not working) among airline pilots and cabin crews cannot be ruled out, especially in the existing published studies reflecting sun exposure patterns of previous decades. The authors concluded that airline pilots’ and cabin crews’ high risk of melanoma and other skin cancers could not be clearly attributed to occupational (job related) factors. They called for up-to-date studies of the topic.