Gabriela Constantinescu

Granzyme B-Induced Apoptosis Requires Both Direct Caspase Activation and Relief of Caspase Inhibition

Cytotoxic lymphocytes employ Granzyme B as a potent initiator of apoptosis to cleave and activate effector caspases. Unexpectedly, cells transfected with Bcl-2 were resistant to granzyme B-induced killing, suggesting that a mitochondrial pathway was critical. Utilizing cells expressing a dominant-negative caspase 9, the current study demonstrated that caspase activation via the apoptosome was not required. Indeed, cleavage of caspase 3 to p20 still occurred in Bcl-2-transfectants but processing to p17 was blocked. This blockade was recapitulated by the Inhibitor-of-Apoptosis-Protein XIAP and relieved by Smac/DIABLO. Thus granzyme B mediates direct cleavage of caspase 3 and also activates mitochondrial disruption, resulting in the release of proapoptotic proteins that suppress caspase inhibition. Engagement of both pathways is critical for granzyme-induced killing.

Epidermal electronics for electromyography: An application to swallowing therapy ✩

Head and neck cancer treatment alters the anatomy and physiology of patients. Resulting swallowing difficulties can lead to serious health concerns. Surface electromyography (sEMG) is used as an adjuvant to swallowing therapy exercises. sEMG signal collected from the area under the chin provides visual biofeedback from muscle contractions and is used to help patients perform exercises correctly. However, conventional sEMG adhesive pads are relatively thick and difficult to effectively adhere to a patients altered chin anatomy, potentially leading to poor signal acquisition in this population. Here, the emerging technology of epidermal electronics is introduced, where ultra-thin geometry allows for close contouring of the chin. The two objectives of this study were to (1) assess the potential of epidermal electronics technology for use with swallowing therapy and (2) assess the significance of the reference electrode placement. This study showed comparative signals between the new epidermal sEMG patch and the conventional adhesive patches used by clinicians. Furthermore, an integrated reference yielded optimal signal for clinical use; this configuration was more robust to head movements than when an external reference was used. Improvements for future iterations of epidermal sEMG patches specific to day-to-day clinical use are suggested.

Patient Perception of Speech Outcomes: The Relationship Between Clinical Measures and Self-Perception of Speech Function Following Surgical Treatment for Oral Cancer

Purpose Treatment for oral cancer can result in speech impairments that can have varying impacts on patient quality of life. This study explored the relationship between clinical measures of speech impairment and the perception that patients had of this change in the early stage of recovery. Method This was a quasi-experimental 1-group pre-post study design carried out on 10 patients with surgical intervention for oral cancer. Two clinical measures (word intelligibility and consonant phoneme error) and 2 patient-perception measures (Speech Handicap Index total score and Speech Handicap Index patient criteria score) were collected at preoperative and 1-month postoperative appointments. Results Qualitative analysis revealed discordance between clinical and patient-perceived measures in 4 of 10 patients. Change in consonant phoneme error and change in word intelligibility were significantly correlated (r = .827). Furthermore, on average, statistically significant relationships were not found between clinical and patient-perceived measures or between the 2 patient-perception measures. Conclusions Discordance between clinical and patient-perceived measures was observed in almost half of the sample, indicating that clinical tests did not fully explain the extent of impairment perceived by patients. Speech outcomes should focus on both types of measures, and patient perception outcomes should be carefully considered when recommending speech therapy.

Flow and Grit by Design: Exploring Gamification in Facilitating Adherence to Swallowing Therapy

Purpose Delivery of swallowing therapy is faced with challenges regarding access to in-clinic services and adherence to prescribed home programs. Mobile health (mHealth) technologies are being developed at a rapid pace to address these difficulties. Whereas some benefits to using these modern tools for therapy are obvious (e.g., electronic reminders), other advantages are not as well understood. One example is the potential for mHealth devices and apps to enhance adherence to treatment regimens. Method This article introduces a number of psychological concepts that relate to adherence and that can be leveraged by mHealth. Elements that contribute to flow (optimal experience) during an activity and those that reinforce grit (perseverance to achieve a long-term goal) can be used to engage patients in their own rehabilitation. Results The experience of flow can be targeted by presenting the rehabilitation exercise as an optimally challenging game, one that offers a match between challenge and ability. Grit can be supported by reinforcing routine and by varying the therapy experience using different games. Conclusions A combination of hardware and software design approaches have the potential to transform uninteresting and repetitive activities, such as those that make up swallowing therapy regimens, into engaging ones. The field of gamification, however, is still developing, and gamified mHealth apps will need to withstand scientific testing of their claims and demonstrate effectiveness in all phases of outcome research.

Usability testing of an mHealth device for swallowing therapy in head and neck cancer survivors

The objective of this study was to conduct the first patient usability testing of a mobile health (mHealth) system for in-home swallowing therapy. Five participants with a history of head and neck cancer evaluated the mHealth system. After completing an in-application (app) tutorial with the clinician, participants were asked to independently complete five tasks: pair the device to the smartphone, place the device correctly, exercise, interpret progress displays, and close the system. Quantitative and qualitative methods were used to evaluate the effectiveness, efficiency, and satisfaction with the system. Critical changes to the app were found in three of the tasks, resulting in recommendations for the next iteration. These issues were related to ease of Bluetooth pairing, placement of device, and interpretation of statistics. Usability testing with patients identified issues that were essential to address prior to implementing the mHealth system in subsequent clinical trials. Of the usability methods used, video observation (synced screen capture with videoed gestures) revealed the most information.

Mobili-T: A Mobile Swallowing-Therapy Device: An Interdisciplinary Solution for Patients with Chronic Dysphagia

Swallowing impairments, or dysphagia, can lead to serious health problems and psychosocial concerns. Effective treatment can be enhanced with the use of adjuvant visual biofeedback from surface electromyography (sEMG) to monitor muscle movement during intensive swallowing exercises. However, access to this therapy is currently possible only in a clinical setting, and is therefore restricted due to limited clinical capacity and technology costs. In this paper, we describe the concept for a new hardware-and-software mobile system for swallowing therapy: Mobili-T. The system, designed by an interdisciplinary team of biomedical engineers, clinicians, and industrial designers, will help patients with dysphagia go through their rehabilitation regimens at home.