Spontaneous generation of functional osteoclasts from synovial fluid mononuclear cells as a model of inflammatory osteoclastogenesis

In osteoimmunology, osteoclastogenesis is understood in the context of the immune system. Today, the in vitro model for osteoclastogenesis necessitates the addition of recombinant human receptor activator of nuclear factor kappa‐B ligand (RANKL) and macrophage colony‐stimulating factor (M‐CSF). The peripheral joints of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) are characterized by an immune‐mediated inflammation that can lead to bone destruction. Here, we evaluate spontaneous in vitro osteoclastogenesis in cultures of synovial fluid mononuclear cells (SFMCs) activated only in vivo. SFMCs were isolated and cultured for 21 days at 0.5–1.0 × 10⁶ cells/mL in culture medium. SFMCs and healthy control peripheral blood monocytes were cultured with RANKL and M‐CSF as controls. Tartrate‐resistant acid phosphatase (TRAP) positive multinucleated cells were found in the SFMC cultures after 21 days. These cells expressed the osteoclast genes calcitonin receptor, cathepsin K, and integrin β3, formed lacunae on dentin plates and secreted matrix metalloproteinase 9 (MMP9) and TRAP. Adding RANKL and M‐CSF potentiated this secretion. In conclusion, we show that SFMCs from inflamed peripheral joints can spontaneously develop into functionally active osteoclasts ex vivo. Our study provides a simple in vitro model for studying inflammatory osteoclastogenesis.     

International survey of peritoneal dialysis training programs.

OBJECTIVE: To survey nurses around the world about current practices for peritoneal dialysis (PD) home training programs. DESIGN: Random sampling of nurses to complete a written survey from the International Society for Peritoneal Dialysis Nursing Liaison Committee. Settings: United States, Canada, South America (Brazil, Columbia), The Netherlands, Hong Kong. METHODS: Surveys and responses were sent by fax whenever possible, or by regular mail, or hand carried, or conducted by telephone. Results were stratified by geographic areas as well as by cumulative responses and were expressed as medians with ranges. Kruskal-Wallis was used to evaluate differences in responses. Associations between variables were tested with Pearson correlation. Univariate regression analysis was used to evaluate the impact of variables on peritonitis rates. Variables with p < 0.10 were included in a multivariate analysis. RESULTS: A total of 317 nurses responded: 88 in the United States, 46 in Canada, 58 in South America, 58 in Hong Kong, and 67 in The Netherlands. This represented 37% of all surveys distributed. Respondents had a median of 12 years' experience in nephrology (range 1-35 years), but only 31% had a formal background in adult education. Nearly half received their guidance to patient training from a nurse colleague, 11% were guided by a corporate colleague, and 8% were simply self-taught. Clinics responding had a median of 30 PD patients (range 1-400) and reported they trained a median of 8 patients per year (range 0-86). Reported peritonitis rates were a median 0.46 per year or 1 episode every 26 months. Peritonitis rates, however, were not known by 53% of respondents. Total training time per patient had a very wide range of hours, from 6 to 96. There was no correlation between training time and peritonitis rates among the study respondents (p = 0.38), nor with any other variables. CONCLUSIONS: There is wide variation in practices for PD patient training programs within countries and around the world. Training time did not appear to be related to peritonitis rates. Randomized trials of training practices are needed to determine which approaches produce the best outcomes for patients.     

Knee arthroscopy and arthrotomy under local anesthesia

We report our experience with knee arthroscopy in local anesthesia in 64 patients with subsequent arthrotomy in 14 of these. The effectiveness of the anesthetic method was evaluated by both the patient and the anesthetic personnel. There was no difference in pain assessment between arthroscopy alone and arthroscopy followed by arthrotomy. Half of the patients had no pain and only one regarded the procedure as very painful. Supplementary analgesia with 0.05 mg fentanyl was given to half of the patients not undergoing arthrotomy and to two thirds of those who had arthrotomy. It was not necessary to abandon any arthroscopic or surgical procedure because of pain. We conclude that local anesthesia is a safe and practical method for diagnostic arthroscopy, arthroscopic surgery, and minor arthrotomy.     

Moment-to-moment dynamics of ADHD behaviour in South African children

Background  

The behaviour of children with Attention-Deficit/Hyperactivity Disorder is characterized by low predictability of responding. Low behavioural predictability is one way of operationalizing intra-individual ADHD-related variability. ADHD-related variability may be caused by inefficient behavioural selection mechanisms linked to reinforcement and extinction, as suggested by the recently published dynamic developmental theory (DDT) of ADHD. DDT argues that ADHD is a basic neurobehavioural disorder, caused by dysfunctioning dopamine systems. For establishing ADHD as a neurobehavioural disorder, findings from studies conducted in Western countries should be replicated in other cultural populations. The present study replicated the study conducted in Norway, with children from the Limpopo province in the Republic of South Africa.     

Altered cAMP Response after Isoprenaline Stimulation of Mononuclear Leucocytes from Insulin-Dependent Diabetic Patients with Hypoglycaemia Unawareness

Abstract: Loss of adrenergic hypoglycaemic symptoms is the most distinctive feature in insulin-dependent diabetes mellitus (IDDM) patients with hypoglycaemia unawareness. Previous reports from in vivo studies show reduced heart rate responsiveness both to adrenergic agonists and antagonists in these patients. This study was carried out to investigate whether the reduced adrenergic sensitivity in IDDM patients with hypoglycaemia unawareness (IDDM-unaware) also could be demonstrated as reduced increase in cAMP production in mononuclear leucocytes induced by isoprenaline stimulation, or reduced inhibition by ICI-118551 (a selective β₂-adrenergic receptor blocker) of isoprenaline induced cAMP production. We found that the slope of the concentration-response curves of isoprenaline/cAMP and the maximal cAMP concentrations obtained after isoprenaline stimulation were reduced in IDDM-unaware compared to control and IDDM patients with normal hypoglycaemia awareness (IDDM-aware). We did not find any significant differences in the response to ICI-118551 between control, IDDM-aware and IDDM-unaware. This study supports the reports of reduced sensitivity of adrenergic agonists as a part of the pathophysiological changes in hypoglycaemia unawareness, but we have not been able to confirm the reports of an association between hypoglycaemia unawareness and reduced effect of adrenergic antagonists.     

The diffusion of cardiovascular disease in the Norwegian farming community: a combination of morbidity and mortality data

This article analyses an observed increase in cardiovascular morbidity among male farmers in Norway during the last decade in the light of the traditionally low mortality in farmers. Three hypotheses to explain the increases in CVD morbidity are tested, of which one, stating that there is a time lag in the spread of risk factors, proves to be most fruitful. Mortality data for agricultural communities show no increase in overall CVD rates, but when age-specific rates are analysed, an increase in the younger age groups emerges, especially for ischaemic heart disease. If this process continues, farmers and farming areas may change from low to high mortality, relatively speaking. It is argued that this change is due to a time lag in two waves, first an increase in risk factors such as smoking, more fatty diets and less physically demanding work, then improved lifestyles due to a better perception of risk factors. Both waves may be affecting rural areas later than the urban centres. Knowledge of such geographical and socio-economic diffusion processes is important in the planning and implementation of prevention programmes.     

Functional activities and immunoglobulin variable regions of human and murine monoclonal antibodies specific for the P1.7 PorA protein loop of Neisseria meningitidis

The meningococcal PorA protein is considered a promising vaccine candidate. Although much is understood regarding the structure of PorA proteins, little is known about the structure-function relationships of PorA antibodies. The aim of this study was to compare the functional and molecular characteristics of a human monoclonal antibody (MAb) and three murine MAbs specific for the PorA P1.7 serosubtype. Murine MAbs 207,B-4 (immunoglobulin G2a [IgG2a]) and MN14C11.6 (IgG2a) were both bactericidal and opsonophagocytic for P1.7-expressing meningococci, whereas human MAb SS269 (IgG3) and murine MAb 208,D-5 (IgA) initiated neither effector function. Epitope mapping with synthetic peptides revealed that MAbs 207,B-4 and 208,D-5 recognized the sequence ASGQ, which is the same specificity motif that a previous study had established for SS269 and MN14C11.6. Nucleotide and amino acid sequence analyses of the variable regions of the four MAbs showed that the SS269 V(H) region belonged to the VH3 family and was approximately 70% homologous to those of the murine MAbs which were all from the 7183 family, whereas the SS269 V(L) region belonged to the Vlambda1-b family and was less than 40% homologous to those of the murine MAbs which were all members of the Vkappa1 family. The Fab fragment of SS269 was cloned and expressed in Escherichia coli and was shown by enzyme-linked immunosorbent assay analyses to bind as well as intact SS269 MAb to P1.7,16 serosubtype group B strain 44/76. We conclude that distinct differences exist in the effector function activities and variable region gene sequences of human and murine P1.7-specific MAbs despite their recognition of similar epitopes.     

How to stay motivated: A focus group study of Norwegian caregivers' experiences with community healthcare services to their parents with dementia

Motivation to provide care is a significant predictor of informal caregiving among family caregivers of persons with dementia. Adequate support is an important source of help and relief to caregivers, but fragmentation of dementia care services is common and better ways of supporting these caregivers are needed. Knowledge of adult-child caregivers' motivation and how this motivation is influenced by community healthcare services is lacking. The aim of this study is therefore to describe and explore adult children's experiences with community healthcare services for their home-dwelling parent with dementia and how these influence their caregiver motivation. The study applied a qualitative design based on three focus group interviews with 15 of these caregivers (40–69 years) in Norway in 2017. The study results indicate three categories supporting adult children's sustained motivation as caregivers: (a) caregivers prioritize their parent's need for healthcare services over their own need for support; (b) caregivers need acknowledgement through respect and involvement; and (c) caregivers need timely information and competence as the dementia progresses. To stimulate collaboration among adult-child caregivers, their parents with dementia, and community healthcare services, we claim that a relationship-centred care framework could be emphasised as a way of supporting sustained motivation among caregivers to parents with dementia as part of community healthcare services.     

The capacity of particles to increase allergic sensitization is predicted by particle number and surface area, not by particle mass.

Particle exposure has traditionally been monitored as mass concentration of PM10 (particles with an aerodynamic diameter less than 10 microm), more recently also as PM2.5. The mass concentration is strongly influenced by the large particles. Therefore, particle mass is a poor measure for characterizing the amount of the small, possibly more biologically potent particles. We used polystyrene particles (PSP) ranging in diameter from 0.0588 to 11.14 microm, carbon black (CB), and diesel exhaust particles (DEP), to study the adjuvant effect of particles on the immune response to the allergen ovalbumin (OVA) after sc injection into the footpad of BALB/cA mice. At a given mass dose, the small particles (0.0588 and 0.202 microm PSP, CB, and DEP) increased the allergen-specific IgE serum levels to a substantially higher degree than the larger particles (1.053, 4.64, and 11.14 microm PSP). Further, in the draining lymph node during the primary response, the fine particles (0.202 microm) with OVA increased cell numbers, expression of surface markers (CD19, MHC class II, CD86, and CD23) and ex vivo production of IL-4 and IL-10, whereas the largest (11.14 microm) particles did not. Linear regression analyses indicated that the IgE response was not predicted by particle mass (R2 = 0.06), but was predicted by the total particle surface area (R2 = 0.64), number of particles (R2 = 0.62), and particle diameter (R2 = 0.58). In conclusion, we found that fine particles exerted stronger adjuvant effects on allergic responses than larger particles at equal mass doses. Consequently, the dose described as total particle surface area or particle number predicts the adjuvant effect of particles better than the currently used particle mass.