Teaching homophones in grades one, two and three

Thesis (Ed.M.)--Boston Universit

Developing a clinical pathway for the identification and management of anxiety and depression in adult cancer patients: an online Delphi consensus process

Purpose: People with cancer and their families experience high levels of psychological morbidity. However many cancer services do not routinely screen patients for anxiety and depression and there are no standardized clinical referral pathways. This study aimed to establish consensus on elements of a draft clinical pathway tailored to the Australian context. Methods: A two-round Delphi study was conducted to gain consensus among Australian oncology and psycho-oncology clinicians about the validity of 39 items that form the basis of a clinical pathway that includes screening, assessment, referral and stepped-care management of anxiety and depression in the context of cancer. The expert panel comprised 87 multidisciplinary clinician members of the Australian Psycho-oncology Cooperative Research Group (PoCoG). Respondents rated their level of agreement with each statement on a 5-point likert scale. Consensus was defined as >80% of respondents scoring within 2 points on the likert scale. Results: Consensus was reached for 21 of 39 items, and a further 15 items approached consensus except for specific contextual factors, after 2 Delphi rounds. Formal screening for anxiety and depression, a stepped care model of management and recommendations for inclusion of length of treatment and time to review were endorsed. Consensus was not reached on items related to roles and responsibilities, particularly those not applicable across cancer settings. Conclusions: This study identified a core set of evidence- and consensus-based principles considered essential to a stepped care model of care incorporating identification, referral and management of anxiety and depression in adult cancer patients.This study was funded by Sydney Catalyst Translational Cancer Research Centr

A microfluidic “baby machine” for cell synchronization

Common techniques used to synchronize eukaryotic cells in the cell cycle often impose metabolic stress on the cells or physically select for size rather than age. To address these deficiencies, a minimally perturbing method known as the “baby machine” was developed previously. In the technique, suspension cells are attached to a membrane, and as the cells divide, the newborn cells are eluted to produce a synchronous population of cells in the G1 phase of the cell cycle. However, the existing “baby machine” is only suitable for cells which can be chemically attached to a surface. Here, we present a microfluidic “baby machine” in which cells are held onto a surface by pressure differences rather than chemical attachment. As a result, our method can in principle be used to synchronize a variety of cell types, including cells which may have weak or unknown surface attachment chemistries. We validate our microfluidic “baby machine” by using it to produce a synchronous population of newborn L1210 mouse lymphocytic leukemia cells in G1 phase.National Cancer Institute (U.S.). Physical Sciences-Oncology Center (U54CA143874)National Institute of General Medical Sciences (U.S.) (EUREKA R01GM085457

Isoform-specific expression of the Coxsackie and adenovirus receptor (CAR) in neuromuscular junction and cardiac intercalated discs

BACKGROUND: The Coxsackie and adenovirus receptor (CAR) has a restricted expression pattern in the adult. In skeletal muscle, although CAR is expressed in immature fibers, its transcript levels are barely detectable in mature muscle. This is in contrast to the robust expression observed in the heart. However, both heart and skeletal muscle are susceptible to infection with the Coxsackie B virus which utilizes primarily CAR for cellular internalization. The specific point of viral entry in skeletal and heart muscle remains unknown. RESULTS: Using antibodies directed against the extracellular and the cytoplasmic domains of CAR, we show CAR in normal human and mouse skeletal muscle to be a novel component of the neuromuscular junction. In cardiac muscle, CAR immunoreactivity is observed at the level of intercalated discs. We demonstrate a single isoform of CAR to be expressed exclusively at the human neuromuscular junction whereas both predominant CAR isoforms are expressed at the intercalated discs of non-diseased human heart. CONCLUSION: The localization of CAR to these important junctional complexes suggests that CAR may play both a structural and a regulatory role in skeletal and cardiac muscle, and that these complexes may serve as a point of entry for Coxsackie B virus

Clinical pathway for the screening, assessment and management of anxiety and depression in adult cancer patients: Australian guidelines.

Purpose A clinical pathway for anxiety and depression in adult cancer patients was developed to guide best practice in Australia. Methods The pathway was based on a rapid review of existing guidelines, systematic reviews and meta-analyses, stakeholder interviews, a Delphi process with 87 multi-disciplinary stakeholders and input from a multidisciplinary advisory panel. Results The pathway recommends formalised routine screening for anxiety and depression in patients with cancer at key points in the patient’s journey. The Edmonton Symptom Assessment System (ESAS) or Distress Thermometer (DT) with problem checklist are recommended as brief screening tools, combined with a more detailed tool, such as the Hospital Anxiety and Depression Scale (HADS), to identify possible cases. A structured clinical interview will be required to confirm diagnosis. When anxiety or depression is identified it is recommended one person in a treating team takes responsibility for co-ordinating appropriate assessment, referral and follow-up (not necessarily carrying these out themselves). A stepped care model of intervention is proposed, beginning with the least intensive available that is still likely to provide significant health gain. The exact intervention, treatment length and follow up timelines as well as professionals involved, are provided as a guide only. Each service should identify their own referral network based on local resources and current service structure, as well as patient preference. Discussion This clinical pathway will assist cancer services to design their own systems to detect and manage anxiety and depression in their patients, to improve the quality of care

Deformability of Tumor Cells versus Blood Cells

The potential for circulating tumor cells (CTCs) to elucidate the process of cancer metastasis and inform clinical decision-making has made their isolation of great importance. However, CTCs are rare in the blood, and universal properties with which to identify them remain elusive. As technological advancements have made single-cell deformability measurements increasingly routine, the assessment of physical distinctions between tumor cells and blood cells may provide insight into the feasibility of deformability-based methods for identifying CTCs in patient blood. To this end, we present an initial study assessing deformability differences between tumor cells and blood cells, indicated by the length of time required for them to pass through a microfluidic constriction. Here, we demonstrate that deformability changes in tumor cells that have undergone phenotypic shifts are small compared to differences between tumor cell lines and blood cells. Additionally, in a syngeneic mouse tumor model, cells that are able to exit a tumor and enter circulation are not required to be more deformable than the cells that were first injected into the mouse. However, a limited study of metastatic prostate cancer patients provides evidence that some CTCs may be more mechanically similar to blood cells than to typical tumor cell lines.Janssen Pharmaceutical Ltd.National Cancer Institute (U.S.). Physical Sciences Oncology Center (U54CA143874)MIT-Harvard Center of Cancer Nanotechnology Excellence (Grant 26697290-47281-A)Stand Up To CancerNational Institutes of Health (U.S.). P41 Biotechnology Resource CenterNational Cancer Institute (U.S.) (Koch Institute Support Grant P30-CA14051

Relationship between susceptibility of Blackface sheep to Teladorsagia circumcincta infection and an inflammatory mucosal T cell response

<p>Abstract</p> <p><it>Teladorsagia circumcincta</it> is the most economically important gastrointestinal (abomasal) nematode parasite of sheep in cool temperate regions, to which sheep show genetically-varying resistance to infection. Lambs, from parents with genetic variation for resistance<it>,</it> were trickle infected with L3 larvae over 12 weeks. 45 lambs were identified with a range of susceptibilities as assessed by: adult worm count at post mortem, faecal egg count (FEC) and IgA antibody levels. This project investigated the correlation of T cell cytokine expression and resistance to infection at the mature stage of response, when the resistant lambs had excluded all parasites.</p> <p>Histopathology showed only minor changes in resistant animals with a low level lymphocyte infiltration; but in susceptible lambs, major pathological changes were associated with extensive infiltration of lymphocytes, eosinophils and neutrophils.</p> <p>Absolute quantitative RT-qPCR assays on the abomasal lymph node (ALN) revealed a significant positive correlation between IL6, IL21 and IL23A transcript levels with adult worm count and FEC. IL23A was also negatively correlated with IgA antibody levels. Significantly positive correlation of TGFB1 levels with adult worm count and FEC were also seen in the abomasal mucosa. These data are consistent with the hypothesis that the inability to control L3 larval colonization, adult worm infection and egg production is due to the activation of the inflammatory Th17 T cell subset.</p

Targeted mitochondrial therapy using MitoQ shows equivalent renoprotection to angiotensin converting enzyme inhibition but no combined synergy in diabetes.

Mitochondrial dysfunction is a pathological mediator of diabetic kidney disease (DKD). Our objective was to test the mitochondrially targeted agent, MitoQ, alone and in combination with first line therapy for DKD. Intervention therapies (i) vehicle (D); (ii) MitoQ (DMitoQ;0.6 mg/kg/day); (iii) Ramipril (DRam;3 mg/kg/day) or (iv) combination (DCoAd) were administered to male diabetic db/db mice for 12 weeks (n = 11-13/group). Non-diabetic (C) db/m mice were followed concurrently. No therapy altered glycaemic control or body weight. By the study end, both monotherapies improved renal function, decreasing glomerular hyperfiltration and albuminuria. All therapies prevented tubulointerstitial collagen deposition, but glomerular mesangial expansion was unaffected. Renal cortical concentrations of ATP, ADP, AMP, cAMP, creatinine phosphate and ATP:AMP ratio were increased by diabetes and mostly decreased with therapy. A higher creatine phosphate:ATP ratio in diabetic kidney cortices, suggested a decrease in ATP consumption. Diabetes elevated glucose 6-phosphate, fructose 6-phosphate and oxidised (NAD+ and NADP+) and reduced (NADH) nicotinamide dinucleotides, which therapy decreased generally. Diabetes increased mitochondrial oxygen consumption (OCR) at complex II-IV. MitoQ further increased OCR but decreased ATP, suggesting mitochondrial uncoupling as its mechanism of action. MitoQ showed renoprotection equivalent to ramipril but no synergistic benefits of combining these agents were shown