Carer-supported home-based exercises designed to target physical activity levels and functional mobility after stroke: a scoping review.

PURPOSE: To explore the literature on carer-supported home-based exercise programs for people after stroke, as a form of physical activity. The review focus was to examine the training carers receive, the content of programs, and investigate the physical activity levels and functional mobility of people after stroke. MATERIALS AND METHODS: A scoping review was undertaken, guided by Joanna Briggs Institute methodology. The concept of home-based carer-supported exercise, in people after stroke, was searched across five databases. Outcomes of interest were physical activity levels and functional mobility. RESULTS: We screened 2285 references and included 10 studies: one systematic review, five randomised controlled trials, one trial with non-equivalent control, and four uncontrolled studies. Carer training ranged from one to twelve sessions. Exercise interventions commonly including walking, other whole body functional exercises and balance activities. In eight studies interventions were in addition to standard care. Five studies reported significant between-group differences for functional mobility, favouring the intervention. One study reported physical activity levels. CONCLUSION: There was large variation in the volume and content of training provided to carers. Physical activity levels were infrequently objectively reported. Future studies should include greater details on their protocols to allow for replication and implementation into clinical practice.

Carer-supported home-based exercises may improve functional mobility once home after a stroke.The optimal length, content, and model of delivery of carer training, so carers can provide better targeted home-based exercise support to people after stroke, is not known.Better monitoring of participation in home-based exercise and reporting of short and long-term physical activity is needed.

Pushing through the Barriers: Peer Advice to Increase Physical Activity and Reduce Dementia Risk from Participants in a Massive Open Online Alzheimer's Focused Course.

BACKGROUND: Engagement in physical activity is associated with reduced dementia risk but insufficient physical activity is a global trend. OBJECTIVES: We aimed to explore what advice might be offered to others to increase physical activity and to identify enablers and barriers to physical activity for adults interested in dementia prevention and participating in a massive open online course. PARTICIPANTS: Two thousand, one hundred and thirty-two participants contributed to an online discussion forum. DESIGN: Analysis was conducted using Topic modelling analysis followed by thematic analysis. RESULTS: The themes generated from the discussion posts included time constraints, poor health and lack of motivation as barriers to physical activity, and social interaction, incidental activities, and dog ownership as enablers. Peer advice was frequently suggested around scheduling physical activity into the day and joining a friend or organised activity. CONCLUSION: This online discussion forum uniquely captured ideas from a large, diverse group of participants. Future research may benefit from further examining the role of discussion forums and peer advice in dementia risk reduction initiatives.

Osimertinib and anti-HER3 combination therapy engages immune dependent tumor toxicity via STING activation in trans.

Over the past decade, immunotherapy delivered novel treatments for many cancer types. However, lung cancer still leads cancer mortality, and non-small-cell lung carcinoma patients with mutant EGFR cannot benefit from checkpoint inhibitors due to toxicity, relying only on palliative chemotherapy and the third-generation tyrosine kinase inhibitor (TKI) osimertinib. This new drug extends lifespan by 9-months vs. second-generation TKIs, but unfortunately, cancers relapse due to resistance mechanisms and the lack of antitumor immune responses. Here we explored the combination of osimertinib with anti-HER3 monoclonal antibodies and observed that the immune system contributed to eliminate tumor cells in mice and co-culture experiments using bone marrow-derived macrophages and human PBMCs. Osimertinib led to apoptosis of tumors but simultaneously, it triggered inositol-requiring-enzyme (IRE1α)-dependent HER3 upregulation, increased macrophage infiltration, and activated cGAS in cancer cells to produce cGAMP (detected by a lentivirally transduced STING activity biosensor), transactivating STING in macrophages. We sought to target osimertinib-induced HER3 upregulation with monoclonal antibodies, which engaged Fc receptor-dependent tumor elimination by macrophages, and STING agonists enhanced macrophage-mediated tumor elimination further. Thus, by engaging a tumor non-autonomous mechanism involving cGAS-STING and innate immunity, the combination of osimertinib and anti-HER3 antibodies could improve the limited therapeutic and stratification options for advanced stage lung cancer patients with mutant EGFR.

Unraveling the mystery of "tech red" - a volatile technetium oxide.

We show that a Tc2O5 molecular species is the likely identity of an unknown volatile oxide which has remained uncharacterized for 50+ years. Exploration of this molecule's absorption spectra and intermolecular self-interactions provides a close match to experimental data and an explanation for volatility and resistance to crystallization.

Validity and reliability of eye healthcare professionals in the assessment of glaucoma - a systematic review.

OBJECTIVE(S): To explore the validity and reliability of eye healthcare professionals with different levels of training in diagnosing and/or identifying glaucomatous progression. CLINICAL RELEVANCE: Substantial pressure is being placed on our current eye healthcare workforce by chronic diseases such as glaucoma. Shared care schemes and role expansion of professionals other than ophthalmologists are being proposed to alleviate this pressure. A sound evidence base is imperative to determine whether other allied health professionals are skilled and clinically competent, when it comes to taking on these new roles in glaucoma management. METHODS: A systematic review of research articles identified in MEDLINE, CINAHL, Embase, Scopus and Cochrane Library was performed. Studies which investigated rater reliability of various health professionals in diagnosing and/or identifying glaucoma progression against a reference standard were included. RESULTS: Of the 4088 publications identified by the initial database search, 32 met the inclusion criteria. The majority of studies demonstrated positive results, with most finding moderate to substantial agreement for inter- and intra-rater reliability across all testing modalities. The eye health professionals with ophthalmology training consistently attained the greatest agreement. When allied health professionals with different levels of training were compared, those who had completed residency training were significantly better than those who had not. CONCLUSION: The studies included in this review show promising results, including those raters without ophthalmology training. A lack of power calculations, unequal sample sizes in some studies and the diversity of the testing procedures used make it difficult to make sound inferences.

The use of molecular imaging combined with genomic techniques to understand the heterogeneity in cancer metastasis.

Tumour heterogeneity has, in recent times, come to play a vital role in how we understand and treat cancers; however, the clinical translation of this has lagged behind advances in research. Although significant advancements in oncological management have been made, personalized care remains an elusive goal. Inter- and intratumour heterogeneity, particularly in the clinical setting, has been difficult to quantify and therefore to treat. The histological quantification of heterogeneity of tumours can be a logistical and clinical challenge. The ability to examine not just the whole tumour but also all the molecular variations of metastatic disease in a patient is obviously difficult with current histological techniques. Advances in imaging techniques and novel applications, alongside our understanding of tumour heterogeneity, have opened up a plethora of non-invasive biomarker potential to examine tumours, their heterogeneity and the clinical translation. This review will focus on how various imaging methods that allow for quantification of metastatic tumour heterogeneity, along with the potential of developing imaging, integrated with other in vitro diagnostic approaches such as genomics and exosome analyses, have the potential role as a non-invasive biomarker for guiding the treatment algorithm.

The challenges of integrating molecular imaging into the optimization of cancer therapy.

We review novel, in vivo and tissue-based imaging technologies that monitor and optimize cancer therapeutics. Recent advances in cancer treatment centre around the development of targeted therapies and personalisation of treatment regimes to individual tumour characteristics. However, clinical outcomes have not improved as expected. Further development of the use of molecular imaging to predict or assess treatment response must address spatial heterogeneity of cancer within the body. A combination of different imaging modalities should be used to relate the effect of the drug to dosing regimen or effective drug concentration at the local site of action. Molecular imaging provides a functional and dynamic read-out of cancer therapeutics, from nanometre to whole body scale. At the whole body scale, an increase in the sensitivity and specificity of the imaging probe is required to localise (micro)metastatic foci and/or residual disease that are currently below the limit of detection. The use of image-guided endoscopic biopsy can produce tumour cells or tissues for nanoscopic analysis in a relatively patient-compliant manner, thereby linking clinical imaging to a more precise assessment of molecular mechanisms. This multimodality imaging approach (in combination with genetics/genomic information) could be used to bridge the gap between our knowledge of mechanisms underlying the processes of metastasis, tumour dormancy and routine clinical practice. Treatment regimes could therefore be individually tailored both at diagnosis and throughout treatment, through monitoring of drug pharmacodynamics providing an early read-out of response or resistance.

Caudate blood flow and volume are reduced in HIV+ neurocognitively impaired patients.

OBJECTIVE: To evaluate the effects of HIV-associated neurocognitive impairment on caudate blood flow and volume. METHODS: The authors performed continuous arterial spin labeled MRI on 42 HIV+ patients (23 subsyndromic and 19 HIV neurosymptomatic) on highly active antiretroviral therapy and 17 seronegative controls. They compared caudate blood flow and volume among groups. RESULTS: A stepwise decrease in both caudate blood flow and volume was observed with increasing HIV-associated neurocognitive impairment. Compared with seronegative controls, baseline caudate blood flow was reduced in HIV+ neurosymptomatic patients (p = 0.001) with a similar decreasing trend for subsyndromic HIV+ patients (p = 0.070). Differences in caudate volume were observed only for neurosymptomatic HIV+ patients compared with controls (p = 0.010). A Jonckheere-Terpstra test for trends was significant for both caudate blood flow and volume for each of the three subgroups. Pearson product moment correlation coefficients were not significant between caudate blood flow and volume for each group. CONCLUSIONS: Decreasing trends in caudate blood flow and volume were associated with significantly increasing HIV-associated neurocognitive impairment (HNCI), with the greatest decreases observed for more severely impaired patients. However, reductions in caudate blood flow and volume were poorly correlated. Changes in residual caudate blood flow may act as a surrogate biomarker for classifying the degree of HNCI.

Stress and illness in low-income women: the roles of hardiness, John Henryism, and race.

This study examines the stress-illness relationship in a biracial group (African-American and Caucasian-American) of low-income women. Two personality constructs, hardiness and John Henryism, were studied for their possible moderating influences on the stress-illness relationship. One hundred women, with family incomes below the poverty line, completed questionnaires of stress, illness, hardiness, and John Henryism. Hierarchical regression models indicated that hardiness moderated the stress-illness relationship, with high stress, low hardy women having higher levels of illness. In addition, race also moderated the effect of stress, with high stress, Caucasian women having higher levels of illness. However, John Henryism had no effect on stress-related illness in these low-income women. Analyses of additional stress measures indicated that hardy women perceive their external environments as less stressful, although high and low hardy women have similar levels of network stress. Correlational analyses indicated that life-event stress, network stress and low-income concerns were all associated with illness scores. Thus, a range of stress measures are linked to physical illness in low-income women; furthermore, hardiness and being African-American both buffered the effects of stress on illness.

Psychophysiological correlates of individual differences in patterns of hemodynamic reactivity.

The present study delineates a method for the quantification of six hemodynamic reactivity patterns, in response to a laboratory stressor, and examines the psychophysiological correlates of individual differences in these patterns. One hundred and ninety-four young adult men and women participated in rest periods and two laboratory stressors, mental arithmetic and an anger recall interview. Measures were taken of blood pressure, heart rate, and cardiac output, from which total peripheral resistance was derived, as well as state reports of feelings during the tasks. Six hemodynamic reactor patterns were identified: Non-reactors, Mild Myocardials, Mild Vasculars, Myocardials, Vasculars, and Dual Reactors, each associated with a unique profile of cardiac output and total peripheral resistance change. Myocardial reactors to the interview had the highest resting levels of blood pressure and total peripheral resistance. Dual reactors had the largest increases in diastolic reactivity; Dual and Myocardial reactors had the largest increases in systolic reactivity. The extreme reactor groups (Dual, Myocardial, Vascular) all reported greater task invigoration than the Non-reactors, who reported greater efforts to relax. Reactor groups were similar on anger-related trait affect. Based on both resting blood pressure and magnitude of task-induced reactivity, Myocardial and Dual reactors may be at the greatest risk for subsequent hypertension.

How audit can improve provision of in-patient pain services.

Clinical governance makes it necessary for the cycle of clinical audit to be refined, encouraging a continuous process of quality improvement. This is achieved through the monitoring of practice and benchmarking, and supported by continuing practice development. Reliable information is essential if pain services are to be improved in line with patients' needs.

Hostility and the cardiovascular reactivity of women during interpersonal confrontation.

In order to explore the association between hostility and women's health, this study examined the relationship of hostility to cardiovascular reactivity during stressful, interpersonal confrontations. Prior to the task, each participant's level of hostility, methods of coping with stress, and perceived social support were evaluated. Blood pressure and heart rate were monitored in ninety females during two discussions with a disagreeing confederate. In one discussion, participants were given positive feedback concerning their performance, while in a second discussion, participants were given non-positive feedback concerning their effectiveness in expressing their viewpoint. The results indicate that low hostile women displayed greater systolic blood pressure and heart rate increases than high hostile women during the discussions. In addition, participants exhibited greater systolic blood pressure and diastolic blood pressure reactivity during the positive feedback condition than during the non-positive feedback condition. However, for diastolic blood pressure, these results were qualified by an interaction, such that low hostile women displayed greater reactivity during the positive feedback condition than during the non-positive feedback condition, while high hostile women were equally reactive in both feedback conditions. State assessment of coping styles indicated that high hostile women may be less reactive due to withdrawal and lack of engagement during the task, while low hostile women may show greater engagement, especially when encouraged by positive feedback.

Medication use among children with asthma in East Harlem.

PURPOSE: To examine daily use of antiinflammatory medication among children with asthma in East Harlem, where hospitalization rates for asthma are among the highest in the United States. METHODS: We analyzed parent/guardian reports of medications used by children with current asthma (defined as physician diagnosis and wheezing during the previous 12 months) identified from a cross-sectional survey conducted in 2 elementary schools. RESULTS: From an overall sample of 1319 children, 298 with current asthma were included in this analysis. Most of those with asthma were Puerto Rican (136 [46%]) or black (98 [33%]), 168 (57%) were boys, and the median age was 8 years old. Overall, 65 (22%) were using antiinflammatory medication on a daily basis. A subgroup of 107 children with asthma had been hospitalized during the previous 12 months or had used beta(2)-agonist on a daily basis, suggesting persistent or severe asthma. Of these 107 children, 42 (39%) were taking antiinflammatory medication on a daily basis. Multivariate analysis of these 107 children revealed that daily use of antiinflammatory medication was associated with using a spacer tube (adjusted odds ratio [AOR]: 3. 08; 95% confidence interval [CI]: 1.27,7.47) and having seen a physician in the past 6 months (AOR: 3.46; CI: 1.01,11.9). Compared with Puerto Ricans, blacks (AOR:.32; CI:.12,.89) or children of other races/ethnicities (AOR:.27; CI:.09,.85) were less likely to use antiinflammatory medication on a daily basis. CONCLUSION: Daily use of antiinflammatory medication for children with persistent or severe asthma in East Harlem was underused. Differences in access to care may explain some findings; however, reasons for ethnic differences in use remain unclear. Both community interventions and additional provider education are needed.

An alternative approach for achieving cardiovascular baseline: viewing an aquatic video.

Due to the importance of baseline and recovery levels in the computation of reactivity, two studies were conducted to determine an alternative method to traditional rest for achieving baseline and recovery levels of cardiovascular measurements. Watching a relaxing, aquatic video was compared with a traditional resting baseline to determine the better method for achieving low baseline levels. In addition, watching the video was compared with traditional rest during 5-min post-task recovery periods. Systolic (SBP) and diastolic blood pressure (DBP) decreased more during the baseline period when subjects viewed the video than when subjects rested quietly. Similarly, subjects displayed greater recovery following the mental tasks when they watched a video than when they merely sat quietly. It is recommended that researchers standardize baseline procedures by showing a relaxing video before administering tasks for the assessment of cardiovascular reactivity.

Identification, purification, and subcellular localization of prostate-specific membrane antigen PSM' protein in the LNCaP prostatic carcinoma cell line.

An alternatively spliced variant of prostate-specific membrane antigen (PSMA) designated PSM' was originally described following identification of its mRNA in normal prostate. We have purified the PSM' protein from LNCaP cells using two immunoaffinity columns in tandem. The first column contained a monoclonal antibody (7E11) that was reactive with the NH2 terminus of PSMA, which specifically depleted the LNCaP lysate of full-length PSMA. The nonbinding fraction was then passed over a second column composed of a monoclonal antibody (PEQ226.5), the epitope of which was located within the 134-437 domain of PSMA and shared with PSM'. The protein eluted from the second immunoaffinity column produced a Mr 95,000 band on SDS-PAGE, which was slightly lower than the full-length PSMA at Mr 100,000. The band was NH2-terminally sequenced through 15 residues, and the assigned sequence coincided with the predicted sequence for PSM' protein minus the first two NH2 terminus amino acids. The PSM' protein, therefore, began with residue 60 of PSMA (alanine). LNCaP cells were fractionated, and PSM' was localized to the cytoplasm.