Generation of normal human red cell volume, hemoglobin content, and membrane area distributions by "birth" or regulation?

Using flow cytometry and osmotic lysis measurements, we document here the means and coefficients of variation of the following red cell (RBC) properties: hemoglobin (Hb) content, volume, Hb concentration, and relative lytic tonicity distributions in populations of normal human RBCs, before and after density fractionation. The distributions showed a pattern characterized by much larger coefficients of variation of the Hb content and volume distributions than of the Hb concentration and relative lytic tonicity distributions. From analysis of the factors that determine those RBC properties, the patterns were interpreted as reflecting previously unrecognized statistical proportionalities between cell osmolyte content, Hb content, and membrane area. The possible origin of these statistical links was analyzed by considering alternative models with and without the participation of regulatory processes during cell maturation. A model was shown to be feasible in which mature RBC variability with proportional volume, area, and Hb content arises solely from cell size variability at the last erythroid cell division.     

Administration of pegylated recombinant human megakaryocyte growth and development factor to humans stimulates the production of functional platelets that show no evidence of in vivo activation

This report describes the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and platelet function in humans. Subjects with advanced solid tumors received PEG-rHuMGDF daily for up to 10 days. There was no increase in circulating platelet count at doses of 0.03 or 0.1 microgram/kg/d by day 12 of study. At doses of 0.3 and 1.0 microgram/kg/d there was a threefold median increase (maximum 10-fold) in platelet count by day 16. The platelets produced in vivo in response to PEG-rHuMGDF showed unchanged aggregation and adenosine triphosphate (ATP)-release responses in in vitro assays. Tests included aggregation and release of ATP in response to adenosine diphosphate (ADP) (10, 5, 2.5, and 1.25 mumol/L), collagen (2 micrograms/mL), thrombin-receptor agonist peptide (TRAP, 10 mumol/L) and ristocetin (1.5 mg/mL). Administration of aspirin to an individual with platelet count of 1,771 x 10(3)/L resulted in the typical aspirin-induced ablation of the normal aggregation and ATP-release response to stimulation with arachidonic acid (0.5 mg/mL), collagen, and ADP (2.5 and 1.25 mumol/L). There was no change in the expression of the platelet-surface activation marker CD62P (P-selectin) nor induction of the fibrinogen binding site on glycoprotein IIb/IIIa as reported by the monoclonal antibody, D3GP3. An elevation of reticulated platelets was evident after 3 days of treatment with PEG-rHuMGDF and preceded the increase in circulating platelet count by 5 to 8 days; this reflected the production of new platelets in response to PEG-rHuMGDF. At later time points, the mean platelet volume (MPV) decreased in a manner inversely proportional to the platelet count. Levels of plasma glycocalicin, a measure of platelet turnover, rose 3 days after the initial increase in the peripheral platelet count. The level of plasma glycocalicin was proportional to the total platelet mass, suggesting that platelets generated in response to PEG-rHuMGDF were not more actively destroyed. Thus, the administration of PEG-rHuMGDF, to humans, increased the circulating platelet count and resulted in fully functional platelets, which showed no detectable increase in reactivity nor alteration in activation status.     

What matters to users of services? An explorative study to promote shared decision making in health care

Background Involving service users and carers in decisions about their health care is a key feature of health‐care practice. Professional health and social care students need to develop skills and attributes to best enable this to happen. Aims The aims were to explore service user and carer perceptions of behaviours, attributes and context required to enable shared decision making; to compare these perceptions to those of students and academic staff with a view to utilizing the findings to inform the development of student assessment tools. Methods A mixed methods approach was used including action learning groups (ALG) and an iterative process alongside a modified Delphi survey. Participants The ALGs were from an existing service user and carer network. The survey was sent to sixty students, sixty academics and 30 service users from 16 different professional disciplines, spanning four Universities in England. Results The collaborative enquiry process and survey identified general agreement that being open and honest, listening, showing respect, giving time and being up to date were important. The qualitative findings identified that individual interpretation was a key factor. An unexpected result was an insight into possible insecurities of students. Conclusions The findings indicate that distilling rich qualitative information into a format for student assessment tools could be problematic as the individual context could be lost, it is therefore proposed that the information could be better used as a learning rather than assessment tool. Several of those involved identified how they valued the process and found it beneficial.     

Attention‐network specific alterations of structural connectivity in the undamaged white matter in acute neglect

Visual neglect results from dysfunction within the spatial attention network. The structural connectivity in undamaged brain tissue in neglect has barely been investigated until now. In the present study, we explored the microstructural white matter characteristics of the contralesional hemisphere in relation to neglect severity and recovery in acute stroke patients. We compared age‐matched healthy subjects and three groups of acute stroke patients (9 ± 0.5 days after stroke): (i) patients with nonrecovered neglect (n = 12); (ii) patients with rapid recovery from initial neglect (within the first week post‐stroke, n = 7), (iii) stroke patients without neglect (n = 17). We analyzed the differences between groups in grey and white matter density and fractional anisotropy (FA) and used fiber tracking to identify the affected fibers. Patients with nonrecovered neglect differed from those with rapid recovery by FA‐reduction in the left inferior parietal lobe. Fibers passing through this region connect the left‐hemispheric analogues of the ventral attention system. Compared with healthy subjects, neglect patients with persisting neglect had FA‐reduction in the left superior parietal lobe, optic radiation, and left corpus callosum/cingulum. Fibers passing through these regions connect centers of the left dorsal attention system. FA‐reduction in the identified regions correlated with neglect severity. The study shows for the first time white matter changes within the spatial attention system remote from the lesion and correlating with the extent and persistence of neglect. The data support the concept of neglect as disintegration within the whole attention system and illustrate the dynamics of structural‐functional correlates in acute stroke. Hum Brain Mapp 35:4678–4692, 2014. © 2014 Wiley Periodicals, Inc .     

The contribution of primary care practitioners to interventions reducing loneliness and social isolation in older people—An integrative review

Background

Social connection is a fundamental human need. Its absence can lead to loneliness and social isolation, adversely impacting health and well-being. Given their regular contact and trusted relationships with older people, practitioners delivering community-based primary care are well-positioned to address this issue. However, their contribution to addressing loneliness and social isolation is unclear.

Aim

This integrative review explores the contribution of the primary care workforce to interventions aimed at reducing loneliness and social isolation in community-dwelling older people.

Method

Using an integrative review method, Scopus, Web of Science, CINAHL and PubMed were searched for original research published between 2000 and 2022. Fourteen papers reporting 13 primary studies were appraised for methodological quality and included in the review. Data were extracted into a summary table and analysed using thematic analysis.

Results

Included studies came from over six countries. Internationally, primary care services have diverse structures, funding and workforces influencing their response to loneliness and social isolation. All but one intervention was multi-component, with ten studies including a group-based activity and three providing primarily individual-level activities. Only six studies reported reductions in loneliness following the intervention. Three themes were identified: characteristics of interventions; implementation context, barriers and facilitators; and differing contributions of primary care practitioners in addressing loneliness and social isolation of older people.

Conclusion

There is increasing demand and scope for primary care practitioners to assist lonely and socially isolated older people. It is important to understand how to equip and incentivise these practitioners to routinely identify, assess and respond to lonely and socially isolated older people despite varying implementation contexts. There is a need for further research that explores how the primary care team can be better utilised to deliver effective interventions that reduce the health impacts of loneliness and social isolation.