Decreased Striatal RGS2 Expression Is Neuroprotective in Huntington's Disease (HD) and Exemplifies a Compensatory Aspect of HD-Induced Gene Regulation

The molecular phenotype of Huntington's disease (HD) is known to comprise highly reproducible changes in gene expression involving striatal signaling genes. Here we test whether individual changes in striatal gene expression are capable of mitigating HD-related neurotoxicity.We used protein-encoding and shRNA-expressing lentiviral vectors to evaluate the effects of RGS2, RASD2, STEP and NNAT downregulation in HD. Of these four genes, only RGS2 and RASD2 modified mutant htt fragment toxicity in cultured rat primary striatal neurons. In both cases, disease modulation was in the opposite of the predicted direction: whereas decreased expression of RGS2 and RASD2 was associated with the HD condition, restoring expression enhanced degeneration of striatal cells. Conversely, silencing of RGS2 or RASD2 enhanced disease-related changes in gene expression and resulted in significant neuroprotection. These results indicate that RGS2 and RASD2 downregulation comprises a compensatory response that allows neurons to better tolerate huntingtin toxicity. Assessment of the possible mechanism of RGS2-mediated neuroprotection showed that RGS2 downregulation enhanced ERK activation. These results establish a novel link between the inhibition of RGS2 and neuroprotective modulation of ERK activity.Our findings both identify RGS2 downregulation as a novel compensatory response in HD neurons and suggest that RGS2 inhibition might be considered as an innovative target for neuroprotective drug development

Dynamic scene analysis and mosaicing of benthic habitats by FS sonar imaging - Issues and complexities

Photo-mosaics generated automatically from as many as thousands of optical images have proved to be an effective technology to study the ecological patterns and dynamics of underwater ecosystems and benthic environments over spatial scales much larger than a single object or image. Unfortunately, optical systems, while useful in clear waters, are ineffective within environments with sources of turbidity and pollution, including lakes, marine sanctuaries, many ports and harbors. Two-dimensional high-resolution forward-scan imaging systems can serve as a suitable technology for constructing similar visual maps, provided that a range of complex imaging issues can be overcome. This paper investigates some of the complexities in analyzing dynamic events captured by a FS sonar imaging system when used in standard configuration to map the seafloor. Of special interest is the case of imaging targets at shorter ranges to maximize benthic object details. We give mathematical models that describe the dynamics associated with objects and shadows they cast on the seabed, and demonstrate some of these issues through examples from real data obtained in the lake on the University of Miami campus

Positioning and scene analysis from visual motion cues within water column

Over the last dozen or more years, many applications of vision-based positioning and navigation near the sea bottom and surface have been explored. Mid-water operations have primarily relied on traditional positioning systems, namely INS, DVL, gyros, etc. This paper investigates the application of a vision system for mid-water operations by exploiting stationary features within the water column. The unique nature of these environment - namely, the abundance of randomly distributed targets over a wide field of view and range of depth - are ideal for the application of well-known motion vision methods for 3-D motion estimation and scene analysis. We demonstrate through experiments with water tank and ocean data how various visual motion cues may be used for passive navigation, environmental assessment and target/habitat classification based on visual motion behavior

Investigating the benefits and harms of hypodermoclysis of patients in palliative care: A consecutive cohort study

Background: Palliative populations are at risk for dehydration which can cause discomfort, distress and cognitive symptoms. Subcutaneous hydration (‘hypodermoclysis’) has been used as an alternative administration route to the more invasive intravenous route, but research is lacking on its net clinical effects (harms and benefits) for palliative populations, particularly in real world settings. Aim: To quantify prospectively the net clinical effects of hypodermoclysis in palliative patients with advanced disease who required supplementary fluids. Design: Multisite, multinational consecutive cohort study. Setting/participants: Patients receiving hypodermoclysis in an inpatient palliative care setting. Results: Twenty sites contributed data for 99 patients, of which 88 had complete benefits and harms data. The most common primary target symptom for infusion was generalised weakness (18.2%), and the most common non-symptom indication was supplemental hydration (31.8%). Benefits were experienced in 33% of patients in their primary target symptom, and in any symptom in 56.8%. Harms were experienced in 38.7% of patients (42% at Grade 1). Benefits increased with higher performance status, while harms were more frequent in patients with lower performance status (Australia-modified Karnofsky performance status ⩽40). Patients in the terminal phase of their illness experienced the least benefit (15.4% in any indication only) and had more frequent harms (38%). Conclusions: Hypodermoclysis may improve certain symptoms in patients in palliative care but frequency of harms and benefits may differ at certain timepoints in the illness trajectory. Further research is needed to better delineate which patients will derive the most net clinical benefit from hypodermoclysis. </jats:sec

Opportunity is the Greatest Barrier to Providing Palliative Care to Advanced Colorectal Cancer Patients: A Survey of Oncology Clinicians

Palliative care (pc) is part of the recommended standard of care for patients with advanced cancer. Nevertheless, delivery of pc is inconsistent. Patients who could benefit from pc services are often referred late—or not at all. In planning for improvements to oncology pc practice in our health care system, we sought to identify barriers to the provision of earlier pc, as perceived by health care providers managing patients with metastatic colorectal cancer (mcrc). We used the Michie Theoretical Domains Framework (tdf) and Behaviour Change Wheel (bcw), together with knowledge of previously identified barriers, to develop a 31-question survey. The survey was distributed by e-mail to mcrc health care providers, including physicians, nurses, and allied staff. Responses were obtained from 57 providers (40% response rate). The most frequently cited barriers were opportunity-related—specifically, lack of time, of clinic space for consultations, and of access to specialist pc staff or services. Qualitative responses revealed that resource limitations varied by cancer centre location. In urban centres, time and space were key barriers. In rural areas, access to specialist pc was the main limiter. Self-perceived capability to manage pc needs was a barrier for 40% of physicians and 30% of nurses. Motivation was the greatest facilitator, with 89% of clinicians perceiving that patients benefit from pc. Based on the Michie tdf and bcw model, interventions that best address the identified barriers are enablement and environmental restructuring. Those findings are informing the development of an intervention plan to improve oncology pc practices in a publicly funded health care system

sj-pdf-1-pmj-10.1177_02692163221122326 – Supplemental material for Paracentesis for cancer-related ascites in palliative care: An international, prospective cohort study

Supplemental material, sj-pdf-1-pmj-10.1177_02692163221122326 for Paracentesis for cancer-related ascites in palliative care: An international, prospective cohort study by Davinia SE Seah, Andrew Wilcock, Sungwon Chang, Mariana S Sousa, Aynharan Sinnarajah, Cy Oun Teoh, Simon Allan, Richard Chye, Matthew Doogue, Jane Hunt, Meera Agar and David C Currow in Palliative Medicine</p