Thinking Through the Chemo-Fog: Occupational Therapy’s Role in Promoting Participation in Adults with Breast Cancer

Breast cancer is currently the most common type of cancer in women (American Cancer Society, 2012). In 2012, 2,971,610 women in the United States were breast cancer survivors (American Cancer Society, 2012). Chemotherapy is often used to effectively treat breast cancer but can cause chemobrain, or chemotherapy-related cognitive impairments (CRCI), including decreased attention, concentration, memory, and difficulty learning new skills and completing routine tasks (American Cancer Society, 2013). CRCI can persist for years and may impact an individual’s occupational performance in daily activities and occupations. Occupational therapy practitioners currently work with this population in other areas including cancer-related fatigue management, lymphedema, physical limitations post-surgery, and psychosocial distress. However, the increasing number of breast cancer survivors and prevalence of CRCI highlight the importance for expanding and defining occupational therapy’s role with this population. The purpose of this presentation is to present the results of a systematic review on interventions within occupational therapy’s scope of practice that can be used to improve CRCI in adults with breast cancer, and to discuss the implications for clinical practice. A comprehensive literature review was performed to understand the role of occupational therapy in treating individuals with chemobrain. CINAHL, Medline and Cochrane databases were used to conduct the review following inclusion criteria (literature published after 2003, and adults with breast cancer who have received chemotherapy) and exclusion criteria. To minimize bias, all articles were critiqued by a primary and secondary reviewer. Thirteen articles were reviewed. The literature review determined health professionals tend to not acknowledge the presence of CRCI, and there is a need for health care professionals to address the symptoms of CRCI. Current interventions that fit within the scope of occupational therapy are being implemented primarily by other disciplines, such as memory strategies and training, and running support groups. The lack of high quality evidence supporting the role of occupational therapy highlights the need for further research and the development of evidence-based interventions that include using compensatory, remedial, psychosocial, and patient education interventions. References: American Cancer Society. (2012). Cancer treatment and survivorship facts & figures 2012-2013. Retrieved from http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-033876.pdf. American Cancer Society. (2013). Chemo brain. Retrieved from http://www.cancer.org/treatment/treatmentsandsideeffects/physicalsideeffects/chemotherapyeffects/chemo-brai

Artificial Intelligence (AI) Assistant Helpfulness

Since Apple first introduced Siri in 2011, artificial intelligence (AI) powered voice assistants (VA\u27s) have become well-established features of mobile devices (Guzman, 2019). Following Siri, additional prominently used voice assistants include Amazon\u27s Alexa, Google\u27s Google Assistant, and Microsoft\u27s Cortana. Recently, there has been a growth in voice-based technology, and many people are now communicating with voice assistants daily in the same way they would with other humans (Sundar et al., 2017). Additionally, though consumer research has shown that people generally prefer female voices over male ones (Griggs, 2011), the context in which the users experience these voices matters. For instance, female voiced computers created to perform a dominant role, such as giving commands or rating performance, were evaluated more negatively by users than male-voiced computers performing the same role (Nass et al., 2006). Thus, we aimed to investigate two relevant hypotheses tested in the present study: First, we hypothesized that listening to a female AI voice assistant would increase sexism ratings, specifically benevolent sexism, compared to listening to a male AI voice assistant. And secondly, we hypothesized that listening to a female AI voice assistant would increase traditional attitudes towards women compared to listening to a male AI voice assistant. We created an online instrument that allows participants to interact with two versions of a digital AI helper (one male, one female) while completing a quiz, and then rate how helpful and accurate the AI helper was. Data collection in the project is ongoing

Job Club: A program to assist occupational therapy students\u27 transition to practice

Transition to practice can be identified as the change from the role of student to the role of practitioner. This period of transition is a time of intense professional and personal development. Typically, it can take anywhere between six months to two years before an entry-level therapist feels competent in the workplace. A number of factors affect the transition process, including role uncertainty, inadequate supervision, and an overall lack of confidence in clinical skills. This paper discusses a case example of a Job Club, provided by a Western Australian Occupational Therapy university program. The concept was initially set up to support students through the process of seeking and gaining employment. Over time, the club developed a broader scope based on the needs of attendees. This example illustrates the needs of students for greater support in this important transition, and lays the groundwork for formal research in future

Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer’s disease-relevant murine model

Mitochondrial dysfunction is a hallmark of neurodegenerative diseases including Alzheimer’s disease (AD), with morphological and functional abnormalities limiting the electron transport chain and ATP production. A contributing factor of mitochondrial abnormalities is loss of nicotinamide adenine dinucleotide (NAD), an important cofactor in multiple metabolic reactions. Depletion of mitochondrial and consequently cellular NAD(H) levels by activated NAD glycohydrolases then culminates in bioenergetic failure and cell death. De Novo NAD+ synthesis from tryptophan requires a multi-step enzymatic reaction. Thus, an alternative strategy to maintain cellular NAD+ levels is to administer NAD+ precursors facilitating generation via a salvage pathway. We administered nicotinamide mononucleotide (NMN), an NAD+ precursor to APP(swe)/PS1(ΔE9) double transgenic (AD-Tg) mice to assess amelioration of mitochondrial respiratory deficits. In addition to mitochondrial respiratory function, we examined levels of full-length mutant APP, NAD+-dependent substrates (SIRT1 and CD38) in homogenates and fission/fusion proteins (DRP1, OPA1 and MFN2) in mitochondria isolated from brain. To examine changes in mitochondrial morphology, bigenic mice possessing a fluorescent protein targeted to neuronal mitochondria (CaMK2a-mito/eYFP), were administered NMN. Mitochondrial oxygen consumption rates were examined in N2A neuroblastoma cells and non-synaptic brain mitochondria isolated from mice (3 months). Western blotting was utilized to assess APP, SIRT1, CD38, DRP1, OPA1 and MFN2 in brain of transgenic and non-transgenic mice (3–12 months). Mitochondrial morphology was assessed with confocal microscopy. One-way or two-way analysis of variance (ANOVA) and post-hoc Holm-Sidak method were used for statistical analyses of data. Student t-test was used for direct comparison of two groups. We now demonstrate that mitochondrial respiratory function was restored in NMN-treated AD-Tg mice. Levels of SIRT1 and CD38 change with age and NMN treatment. Furthermore, we found a shift in dynamics from fission to fusion proteins in the NMN-treated mice. This is the first study to directly examine amelioration of NAD+ catabolism and changes in mitochondrial morphological dynamics in brain utilizing the immediate precursor NMN as a potential therapeutic compound. This might lead to well-defined physiologic abnormalities that can serve an important role in the validation of promising agents such as NMN that target NAD+ catabolism preserving mitochondrial function.https://doi.org/10.1186/s12883-015-0272-

Structural divergence creates new functional features in alphavirus genomes

Alphaviruses are mosquito-borne pathogens that cause human diseases ranging from debilitating arthritis to lethal encephalitis. Studies with Sindbis virus (SINV), which causes fever, rash, and arthralgia in humans, and Venezuelan equine encephalitis virus (VEEV), which causes encephalitis, have identified RNA structural elements that play key roles in replication and pathogenesis. However, a complete genomic structural profile has not been established for these viruses. We used the structural probing technique SHAPE-MaP to identify structured elements within the SINV and VEEV genomes. Our SHAPE-directed structural models recapitulate known RNA structures, while also identifying novel structural elements, including a new functional element in the nsP1 region of SINV whose disruption causes a defect in infectivity. Although RNA structural elements are important for multiple aspects of alphavirus biology, we found the majority of RNA structures were not conserved between SINV and VEEV. Our data suggest that alphavirus RNA genomes are highly divergent structurally despite similar genomic architecture and sequence conservation; still, RNA structural elements are critical to the viral life cycle. These findings reframe traditional assumptions about RNA structure and evolution: rather than structures being conserved, alphaviruses frequently evolve new structures that may shape interactions with host immune systems or co-evolve with viral proteins

Wastewater Surveillance for SARS-CoV-2 on College Campuses: Initial Efforts, Lessons Learned, and Research Needs

Wastewater surveillance for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging approach to help identify the risk of a coronavirus disease (COVID-19) outbreak. This tool can contribute to public health surveillance at both community (wastewater treatment system) and institutional (e.g., colleges, prisons, and nursing homes) scales. This paper explores the successes, challenges, and lessons learned from initial wastewater surveillance efforts at colleges and university systems to inform future research, development and implementation. We present the experiences of 25 college and university systems in the United States that monitored campus wastewater for SARS-CoV-2 during the fall 2020 academic period. We describe the broad range of approaches, findings, resources, and impacts from these initial efforts. These institutions range in size, social and political geographies, and include both public and private institutions. Our analysis suggests that wastewater monitoring at colleges requires consideration of local information needs, sewage infrastructure, resources for sampling and analysis, college and community dynamics, approaches to interpretation and communication of results, and follow-up actions. Most colleges reported that a learning process of experimentation, evaluation, and adaptation was key to progress. This process requires ongoing collaboration among diverse stakeholders including decision-makers, researchers, faculty, facilities staff, students, and community members

Release of Severe Acute Respiratory Syndrome Coronavirus Nuclear Import Block Enhances Host Transcription in Human Lung Cells

The severe acute respiratory syndrome coronavirus accessory protein ORF6 antagonizes interferon signaling by blocking karyopherin-mediated nuclear import processes. Viral nuclear import antagonists, expressed by several highly pathogenic RNA viruses, likely mediate pleiotropic effects on host gene expression, presumably interfering with transcription factors, cytokines, hormones, and/or signaling cascades that occur in response to infection. By bioinformatic and systems biology approaches, we evaluated the impact of nuclear import antagonism on host expression networks by using human lung epithelial cells infected with either wild-type virus or a mutant that does not express ORF6 protein. Microarray analysis revealed significant changes in differential gene expression, with approximately twice as many upregulated genes in the mutant virus samples by 48 h postinfection, despite identical viral titers. Our data demonstrated that ORF6 protein expression attenuates the activity of numerous karyopherin-dependent host transcription factors (VDR, CREB1, SMAD4, p53, EpasI, and Oct3/4) that are critical for establishing antiviral responses and regulating key host responses during virus infection. Results were confirmed by proteomic and chromatin immunoprecipitation assay analyses and in parallel microarray studies using infected primary human airway epithelial cell cultures. The data strongly support the hypothesis that viral antagonists of nuclear import actively manipulate host responses in specific hierarchical patterns, contributing to the viral pathogenic potential in vivo. Importantly, these studies and modeling approaches not only provide templates for evaluating virus antagonism of nuclear import processes but also can reveal candidate cellular genes and pathways that may significantly influence disease outcomes following severe acute respiratory syndrome coronavirus infection in vivo

Pathogenic Influenza Viruses and Coronaviruses Utilize Similar and Contrasting Approaches To Control Interferon-Stimulated Gene Responses

ABSTRACT The broad range and diversity of interferon-stimulated genes (ISGs) function to induce an antiviral state within the host, impeding viral pathogenesis. While successful respiratory viruses overcome individual ISG effectors, analysis of the global ISG response and subsequent viral antagonism has yet to be examined. Employing models of the human airway, transcriptomics and proteomics datasets were used to compare ISG response patterns following highly pathogenic H5N1 avian influenza (HPAI) A virus, 2009 pandemic H1N1, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome CoV (MERS-CoV) infection. The results illustrated distinct approaches utilized by each virus to antagonize the global ISG response. In addition, the data revealed that highly virulent HPAI virus and MERS-CoV induce repressive histone modifications, which downregulate expression of ISG subsets. Notably, influenza A virus NS1 appears to play a central role in this histone-mediated downregulation in highly pathogenic influenza strains. Together, the work demonstrates the existence of unique and common viral strategies for controlling the global ISG response and provides a novel avenue for viral antagonism via altered histone modifications.IMPORTANCEThis work combines systems biology and experimental validation to identify and confirm strategies used by viruses to control the immune response. Using a novel screening approach, specific comparison between highly pathogenic influenza viruses and coronaviruses revealed similarities and differences in strategies to control the interferon and innate immune response. These findings were subsequently confirmed and explored, revealing both a common pathway of antagonism via type I interferon (IFN) delay as well as a novel avenue for control by altered histone modification. Together, the data highlight how comparative systems biology analysis can be combined with experimental validation to derive novel insights into viral pathogenesis

Delay to celiac disease diagnosis and its implications for health-related quality of life

<p>Abstract</p> <p>Background</p> <p>To determine how the delay in diagnosing celiac disease (CD) has developed during recent decades and how this affects the burden of disease in terms of health-related quality of life (HRQoL), and also to consider differences with respect to sex and age.</p> <p>Methods</p> <p>In collaboration with the Swedish Society for Coeliacs, a questionnaire was sent to 1,560 randomly selected members, divided in equal-sized age- and sex strata, and 1,031 (66%) responded. HRQoL was measured with the EQ-5D descriptive system and was then translated to quality-adjusted life year (QALY) scores. A general population survey was used as comparison.</p> <p>Results</p> <p>The mean delay to diagnosis from the first symptoms was 9.7 years, and from the first doctor visit it was 5.8 years. The delay has been reduced over time for some age groups, but is still quite long. The mean QALY score during the year prior to initiated treatment was 0.66; it improved after diagnosis and treatment to 0.86, and was then better than that of a general population (0.79).</p> <p>Conclusions</p> <p>The delay from first symptoms to CD diagnosis is unacceptably long for many persons. Untreated CD results in poor HRQoL, which improves to the level of the general population if diagnosed and treated. By shortening the diagnostic delay it is possible to reduce this unnecessary burden of disease. Increased awareness of CD as a common health problem is needed, and active case finding should be intensified. Mass screening for CD might be an option in the future.</p