Characterization of the human CD4+ T‐cell repertoire specific for major histocompatibility class I‐restricted antigens

While CD4⁺ T lymphocytes usually recognize antigens in the context of major histocompatibility (MHC) class II alleles, occurrence of MHC class‐I restricted CD4⁺ T cells has been reported sporadically. Taking advantage of a highly sensitive MHC tetramer‐based enrichment approach allowing detection and isolation of scarce Ag‐specific T cells, we performed a systematic comparative analysis of HLA‐A*0201‐restricted CD4⁺ and CD8⁺ T‐cell lines directed against several immunodominant viral or tumoral antigens. CD4⁺ T cells directed against every peptide‐MHC class I complexes tested were detected in all donors. These cells yielded strong cytotoxic and T helper 1 cytokine responses when incubated with HLA‐A2⁺ target cells carrying the relevant epitopes. HLA‐A2‐restricted CD4⁺ T cells were seldom expanded in immune HLA‐A2⁺ donors, suggesting that they are not usually engaged in in vivo immune responses against the corresponding peptide‐MHC class I complexes. However, these T cells expressed TCR of very high affinity and were expanded following ex vivo stimulation by relevant tumor cells. Therefore, we describe a versatile and efficient strategy for generation of MHC class‐I restricted T helper cells and high affinity TCR that could be used for adoptive T‐cell transfer‐ or TCR gene transfer‐based immunotherapies.     

Differing effects of prosaccades and antisaccades on postural stability

The goal of the study was to examine the effect of different types of eye movements on postural stability. Ten healthy young adults (25 ± 3 years) participated in the study. Postural control was measured by the TechnoConcept© platform and recorded in Standard Romberg and Tandem Romberg conditions while participants performed five oculomotor tasks: two fixation tasks (central fixation cross, without and with distractors), two prosaccade tasks toward peripheral targets displayed 4° to the left or to the right of the fixation cross (reactive saccades induced by a gap 0 ms paradigm and voluntary saccades induced by an overlap 600 ms paradigm) and one antisaccade task (voluntary saccade made in the opposite direction of the visual target). The surface, the length, and the mean speed of the center of pressure were analyzed. We found that saccadic eye movements improved postural stability with respect to the fixation tasks. Furthermore, antisaccades were found to decrease postural stability compared to prosaccades (reactive as well as voluntary saccades). This result is in line with the U-shaped nonlinear model described by Lacour et al. (Neurophysiol Clin 38:411–421, 2008), showing that a secondary task performed during a postural task could increase (prosaccade task) or decrease (antisacade task) postural stability depending on its complexity. We suggest that the different degree of attentional resources needed for performing prosaccade or antisaccade tasks are, most likely, responsible for the different effect on postural control.     

Prognostic relevance of clinical and molecular risk factors in children with high-risk medulloblastoma treated in the phase II trial PNET HR+5

BackgroundHigh-risk medulloblastoma is defined by the presence of metastatic disease and/or incomplete resection and/or unfavorable histopathology and/or tumors with MYC amplification. We aimed to assess the 3-year progression-free survival (PFS) and define the molecular characteristics associated with PFS in patients aged 5–19 years with newly diagnosed high-risk medulloblastoma treated according to the phase II trial PNET HR+5.MethodsAll children received postoperative induction chemotherapy (etoposide and carboplatin), followed by 2 high-dose thiotepa courses (600 mg/m²) with hematological stem cell support. At the latest 45 days after the last stem cell rescue, patients received risk-adapted craniospinal radiation therapy. Maintenance treatment with temozolomide was planned to start between 1–3 months after the end of radiotherapy. The primary endpoint was PFS. Outcome and safety analyses were per protocol (all patients who received at least one dose of induction chemotherapy).ResultsFifty-one patients (median age, 8 y; range, 5–19) were enrolled. The median follow-up was 7.1 years (range: 3.4–9.0). The 3 and 5-year PFS with their 95% confidence intervals (95% CI) were 78% (65–88) and 76% (63–86), and the 3 and 5-year OS were 84% (72–92) and 76% (63–86), respectively. Medulloblastoma subtype was a statistically significant prognostic factor (P-value = 0.039) with large-cell/anaplastic being of worse prognosis, as well as a molecular subgroup (P-value = 0.012) with sonic hedgehog (SHH) and group 3 being of worse prognosis than wingless (WNT) and group 4. Therapy was well tolerated.ConclusionsThis treatment based on high-dose chemotherapy and conventional radiotherapy resulted in a high survival rate in children with newly diagnosed high-risk medulloblastoma.     

A Lot of Action,But Not in the Right Direction: Systematic Review and Content Analysis of Smartphone Applications for the Prevention,Detection, and Management of Cancer

Background

Mobile phones have become nearly ubiquitous, offering a promising means to deliver health interventions. However, little is known about smartphone applications (apps) for cancer.

Objective

The purpose of this study was to characterize the purpose and content of cancer-focused smartphone apps available for use by the general public and the evidence on their utility or effectiveness.

Methods

We conducted a systematic review of the official application stores for the four major smartphone platforms: iPhone, Android, Nokia, and BlackBerry. Apps were included in the review if they were focused on cancer and available for use by the general public. This was complemented by a systematic review of literature from MEDLINE, Embase, and the Cochrane Library to identify evaluations of cancer-related smartphone apps.

Results

A total of 295 apps from the smartphone app stores met the inclusion criteria. The majority of apps targeted breast cancer (46.8%, 138/295) or cancer in general (28.5%, 84/295). The reported app purpose was predominantly to raise awareness about cancer (32.2%, 95/295) or to provide educational information about cancer (26.4%, 78/295), followed by apps to support fundraising efforts (12.9%, 38/295), assist in early detection (11.5%, 34/295), promote a charitable organization (10.2%, 30/295), support disease management (3.7%, 11/295), cancer prevention (2.0%, 6/295), or social support (1.0%, 3/295). The majority of the apps did not describe their organizational affiliation (64.1%, 189/295). Apps affiliated with non-profit organizations were more likely to be free of cost (χ² ₁=16.3, P<.001) and have a fundraising or awareness purpose (χ² ₂=13.3, P=.001). The review of the health literature yielded 594 articles, none of which reported an evaluation of a cancer-focused smartphone application.

Conclusions

There are hundreds of cancer-focused apps with the potential to enhance efforts to promote behavior change, to monitor a host of symptoms and physiological indicators of disease, and to provide real-time supportive interventions, conveniently and at low cost. However, there is a lack of evidence on their utility, effectiveness, and safety. Future efforts should focus on improving and consolidating the evidence base into a whitelist for public consumption.     

Rhodium effects on Pt anode materials in a direct alkaline ethanol fuel cell

The development of efficient catalysts for ethanol oxidation in alkaline medium requires a synthetic approach that may prevent the surfactant molecules from being adsorbed at the catalytic sites and decreasing the electrochemical performance of the final direct ethanol fuel cell. Toward this goal, the recently reported surfactant-less Bromide Anion Exchange (BAE) method, appears as a promising route to conveniently aim at preparing PtRh alloys dispersed on carbon substrates. The catalysts prepared herein by the BAE method were characterized physicochemically to obtain structural information on the PtRh/C nanomaterials, their morphology (size and shape), and their chemical and surface composition. Electrochemical behavior and properties of these electrodes were then investigated in a half-cell before the implementation of a direct ethanol fuel cell (DEFC) in a home-made anion exchange membrane Teflon cell. The analysis of the electrolytic solution in the anodic compartment by chromatography revealed that acetate was the major reaction product and the carbonate amount increased with the Rh content in the bimetallic composition. With 2.8–3.6 nm particle sizes, the Pt₅₀Rh₅₀/C catalyst exhibited the highest activity towards the ethanol electrooxidation.

The development of efficient catalysts for ethanol oxidation in alkaline medium requires an approach that avoids surfactant molecules from being adsorbed at active sites and decreasing the electrochemical performance of the direct ethanol fuel cell.     

Immune Reconstitution Inflammatory Syndrome Secondary to Mycobacterium kansasii Infection in a Kidney Transplant Recipient

Nontuberculous mycobacteria (NTM) infection is a challenging diagnosis for clinicians in solid organ transplantation. Immune reconstitution inflammatory syndrome (IRIS) is so far unreported in this context. We report here the case of a renal transplant recipient who developed Mycobacterium kansasii–associated lymphadenitis complicated by IRIS while undergoing reduction of his immunosuppressive therapy. For IRIS, the patient required low‐dose steroids and an increase in global immunosuppression, in association with NTM antibiotherapy.     

Pharmacy ethical reasoning: a comparison of Australian pharmacists and interns

International Journal of Clinical Pharmacy - Background Ethical reasoning informs decision making and professional judgement, is guided by codes of ethics and conduct, and requires navigation...     

CD81-Receptor Associations — Impact for Hepatitis C Virus Entry and Antiviral Therapies

Tetraspanins are integral transmembrane proteins organized in microdomains displaying specific and direct interactions with other tetraspanins and molecular partners. Among them, CD81 has been implicated in a variety of physiological and pathological processes. CD81 also plays a crucial role in pathogen entry into host cells, including hepatitis C virus (HCV) entry into hepatocytes. HCV is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV entry into hepatocytes is a complex process that requires the coordinated interaction of viral and host factors for the initiation of infection, including CD81, scavenger receptor BI, claudin-1, occludin, membrane-bound host cell kinases, Niemann-Pick C1 Like 1, Harvey rat sarcoma viral oncogene homolog (HRas), CD63 and transferrin receptor 1. Furthermore, recent data in HCV model systems have demonstrated that targeting critical components of tetraspanins and associated cell membrane proteins open new avenues to prevent and treat viral infection.