Members of the tetraspanin family including CD9 contribute to the structural organization and plasticity of the plasma membrane. K41, a CD9-specific monoclonal antibody, inhibits the release of HIV-1 ...and canine distemper virus (CDV)- but not measles virus (MV)-induced cell-cell fusion. We now report that K41, which recognizes a conformational epitope on the large extracellular loop of CD9, induces rapid relocation and clustering of CD9 in net-like structures at cell-cell contact areas. High-resolution analyses revealed that CD9 clustering is accompanied by the formation of microvilli that protrude from either side of adjacent cell surfaces, thus forming structures like microvilli zippers. While the cellular CD9-associated proteins β₁-integrin and EWI-F were co-clustered with CD9 at cell-cell interfaces, viral proteins in infected cells were differentially affected. MV envelope proteins were detected within CD9 clusters, whereas CDV proteins were excluded from CD9 clusters. Thus, the tetraspanin CD9 can regulate cell-cell fusion by controlling the access of the fusion machinery to cell contact areas.
Summary To assess continuous subcutaneous hydrocortisone infusion (CSHI) in patients with adrenocortical insufficiency (AI) and difficulties with oral replacement. Three patients with AI and frequent ...hospital admissions attributed to adrenal crises were treated with CSHI, which was delivered via a continuous subcutaneous infusion. All three patients preferred CSHI and remained on it long term, which permitted prolonged follow-up analysis. All three patients reported symptomatic improvement, and in two cases, reduced hospital admission rates and inpatient stay lengths were observed. The cost of hospital admissions and overall treatment was reduced in all cases. CSHI offers a practical and acceptable alternative to oral replacement in a subset of patients with AI. The cost of initiating and maintaining the pump is offset in the long term by reduced frequency and duration of emergency admissions. CSHI can therefore be considered in a select group of patients who are resistant to treatment with conventional oral glucocorticoids. Learning points Continuous subcutaneous infusion of cortisol is a viable alternative in patients unable to take oral steroids. Patient acceptability was high, with three out of three patients preferring to remain on pump treatment. Hospital admissions were reduced in response to pump therapy, which compensated for the increased treatment cost. The daily dosage of hydrocortisone can be reduced by using pump therapy.
For successful tissue engineering in surgical radiotherapy patients, irradiated endothelial cells (EC) must form new blood vessels to nourish and build connections with the engineered segment. ...Therefore, it is critical to understand neovasculogenesis by irradiated EC. The objective of this study was to determine the effects of ionizing radiation on endothelial cell proliferation and capillary-like structures (CLS) formation. Human Umbilical Vein Endothelial Cells (HUVEC) were irradiated with single or fractionated doses of radiation. Proliferation was determined by counting cells. CLS morphology was analyzed from photomicrographs. A single dose of 8 Gy radiation was highly lethal to HUVEC compared to lower dosage. A single dose had more of an inhibitory effect on cell proliferation compared to the same dose delivered in a fractionated manner. CLS formation began after cells reached confluency. To form a CLS, a single cell expanded, and a number of cells rearranged around its periphery in an oval fashion (mimicking a vessel wall). The central cell later disintegrated leaving a void, mimicking the lumen. Irradiated EC can form CLS, although they are fewer and smaller compared to those by sham cells. By disrupting the peripheral cells, ≥
4 Gy doses significantly reduced the number of CLS. The disruptive affect was seen more with large CLS compared to small CLS. At different doses, the shapes of CLS were not significantly different.
Type 1 diabetes (T1D) is a chronic condition affecting nearly 1.9 million people in the United States. Young adults (YAs) with T1D face unique challenges in managing their condition, experiencing ...poorer health and well-being than other age groups. The current study is evaluating the Resilient, Empowered, Active Living (REAL) intervention, previously shown to improve glucose levels and quality of life among YAs with diabetes, using telehealth delivery (REAL-T) to expand reach and accessibility. This paper reports on the methodology and baseline participant characteristics of the REAL-T study.
REAL-T is a two-arm randomized controlled trial that recruited 18-30 year olds with T1D via clinics and social media advertising. Data collection, which was adapted to be fully remote due to COVID-19, occurs every three months for one year. Participants receive either usual care or a 6-month telehealth occupational therapy intervention. The primary outcome is glycated hemoglobin (A1c); secondary outcomes include diabetes distress, quality of life, and continuous glucose monitor-derived measures.
The study enrolled a diverse sample of 209 YAs with T1D. Analysis of baseline data indicates equivalence between the intervention and control groups. Study participants have notably higher diabetes distress and poorer mental well-being than similar populations.
The REAL-T study successfully adapted to remote implementation during the COVID-19 pandemic. By examining long-term outcomes, mediating pathways, and cost-effectiveness, the study will contribute knowledge of the impact of tailored interventions for YAs with T1D, designed to reduce disparities and improve health and well-being in this population.
Fabry disease is an X‐linked disorder caused by a deficiency of lysosomal α‐galactosidase A resulting in accumulation of α‐D‐galatosyl conjugated glycosphingolipids. Clinical manifestations include a ...small‐fiber neuropathy associated with debilitating pain and hypohidrosis. We report the effect of a 3‐year open‐label extension of a previously reported 6‐month placebo‐controlled enzyme replacement therapy (ERT) trial in which 26 hemizygous patients with Fabry disease received 0.2 mg/kg of α‐galactosidase A every 2 weeks. The effect of ERT on neuropathic pain scores while off pain medications, quantitative sensory testing, quantitative sudomotor axon reflex test (QSART), and thermoregulatory sweat test (TST) is reported. In the patients who crossed‐over from placebo to ERT (n = 10), mean pain‐at‐its‐worst scores on a 0–10 scale decreased (from 6.9 to 4.5). There was a significant reduction in the threshold for cold and warm sensation in the foot. At the 3‐year time‐point, pre‐ERT sweat excretion in 17 Fabry patients was 0.24 ± 0.33 μl/mm2 vs. 1.05 ± 0.81 in concurrent controls (n = 38). Sweat function improved 24–72 h post‐enzyme infusion (0.57 ± 0.71 μl/mm2) and normalized in four anhidrotic patients. TST confirmed the QSART results. We conclude that prolonged ERT in Fabry disease leads to a modest but significant improvement in the clinical manifestations of the small‐fiber neuropathy associated with this disorder. QSART may be useful to further optimize the dose and frequency of ERT. Muscle Nerve 28: 703–710, 2003
The present study determined whether a repeated mild restraint stress exposure would differentially alter neuronal activity in male and female rats to gain insights into neurobiological substrates ...involved in sex differences in stress‐induced behavioural responses. In our first set of experiments, we used Western blot analysis to determine whether alterations in several synaptic proteins were elicited by the repeated stress treatment. We found bidirectional changes in synaptophysin levels in female cerebral cortex and hippocampus that diverged between intact and ovariectomised females. There were persistent elevations in spinophilin levels in the male, but not female, hippocampus following the repeated mild restraint stress exposure. By contrast, levels of the NMDA receptor scaffolding protein, PSD‐95, were altered only in intact female cerebral cortex and ovariectomised female hippocampus. We next used immunohistochemical evaluation of Fos expression as a marker for neuronal activation. We found significant increases in Fos immunoreactivity in all sex conditions across multiple brain regions in response to the repeated mild stress. Fos protein induction was greatest in the frontal cortex, piriform cortex and amygdala, with the degree of induction varying by sex condition. Fos induction was dramatically higher in amygdala and piriform cortex only in intact females following repeated stress compared to a single restraint stress exposure, suggestive of sensitisation rather than habituation. By contrast, the frontal cortex of intact and ovariectomised females showed habituation to the repeated stressor. Males displayed modest sensitisation in both the frontal cortex and dentate gyrus with no changes in other brain areas. Taken together, these findings show that exposure to a mild repeated stress results in sex differences in synaptic adaptations and patterns of brain activation that likely contribute to observed sex differences in stress‐induced behaviours. This approach provides valuable insights into interactions between the hormonal milieu and responses to a repeated mild stress, and further supports the importance of considering hormonal status in treatment of stress‐related disorders.
Objective
Little is known about how best to target cardiovascular health promotion messages to minorities. This study describes key lessons that emerged from a community and culture-centered approach ...to developing a multimedia, coronary heart disease (CHD) patient education program (PEP) for medically underserved South Asian immigrants.
Methods
The prototype PEP integrated the surface structures (e.g. language) and deeper structures (e.g. explanatory models (EMs), values) of South Asians' socio-cultural context. Seven focus groups and 13 individual interviews were used to investigate South Asians’ reactions and obtain qualitative feedback after viewing the culturally targeted PEP. Qualitative data were organized into emergent thematic constructs.
Results
Participants (n = 56) mean age was 51 years and 48 % were Hindi speakers. Community members had a strong, negative reaction to some of the targeted messages, "This statement is a bold attack. You are pin-pointing one community." Other important themes emerged from focus groups and interviews about the PEP: 1) it did not capture the community’s heterogeneity; 2) did not sufficiently incorporate South Asians’ EMs of CHD; and 3) did not address economic barriers to CHD prevention. Feedback was used to revise the PEP.
Conclusion
A community and culture-centered approach to developing cardiovascular health promotion messages revealed tensions between the researcher’s vantage point of “cultural targeting” and the community’s perceptions and reactions to these messages. Engaging communities in every phase of message design, incorporating their EMs, recognizing community heterogeneity, and addressing economic and structural barriers, are critical steps to ensuring that health promotion messages reach their intended audience and achieve true cultural appropriateness.
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