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.     

Telemedicine support shortens length of stay after fast-track hip replacement

Background and purpose — Telemedicine could allow patients to be discharged more quickly after surgery and contribute to improve fast-track procedures without compromising quality, patient safety, functionality, anxiety, or other patient-perceived parameters. We investigated whether using telemedicine support (TMS) would permit hospital discharge after 1?day without loss of self-assessed quality of life, loss of functionality, increased anxiety, increased rates of re-admission, or increased rates of complications after hip replacement.

Patients and methods — We performed a randomized controlled trial involving 72 Danish patients in 1 region who were referred for elective fast-track total hip replacement between August 2009 and March 2011 (654 were screened for eligibility). Half of the patients received a telemedicine solution connected to their TV. The patients were followed until 1 year after surgery.

Results — Length of stay was reduced from 2.1 days (95% CI: 2.0–2.3) to 1.1?day (CI: 0.9–1.4; p < 0.001) with the TMS intervention. Health-related quality of life increased in both groups, but there were no statistically significant differences between groups. There were also no statistically significant differences between groups regarding timed up-and-go test and Oxford hip score at 3-month follow-up. At 12-month follow-up, the rates of complications and re-admissions were similar between the groups, but the number of postoperative hospital contacts was lower in the TMS group.

Interpretation — Length of postoperative stay was shortened in patients with the TMS solution, without compromising patient-perceived or clinical parameters in patients undergoing elective fast-track surgery. These results indicate that telemedicine can be of value in fast-track treatment of patients undergoing total hip replacement.     

Antibacterial Activity of Pepducins,Allosterical Modulators of Formyl Peptide Receptor Signaling

Pepducins containing a fatty acid linked to an amino acid sequence derived from cytosolic parts of a G-protein-coupled receptor (GPCR) constitute a new group of lipopeptide tools in GPCR studies. Pepducins corresponding to the third intracellular loop of formyl peptide receptor 2 (FPR2) activate human neutrophils, and we show here that, in addition, these allosteric modulators of receptor activity also kill bacteria. The functional dualism of FPR2 pepducins could potentially be explored as a novel class of antibacterial drugs with immunomodulatory properties.     

Ear measurement of temperature is only useful for screening for fever in an adult emergency department

Background

A new generation of ear thermometers with preheated tips and several measurements points should allow a more precise temperature measurement. The aim of the study was to evaluate if the ear temperature measured by this ear thermometer can be used to screen for fever and whether the thermometer is in agreement with the rectal temperature and if age, use of hearing devices or time after admission influences the temperature measurements.

Methods

Open cross-sectional clinical single site study patients, >?18?years old, who were acutely admitted to the short stay unit at the ED. A sample size of 99 patient per subgroup was recruited as random convenience series. As ear thermometer Braun Thermoscan Pro 4000® and as rectal thermometer Omron Flex Temp Smart ® was used. For different cut off of temperature the AUC was calculated and Bland-Altman analysis for calculation of 95% limits of agreement with rectal temperature, with subgroup analysis concerning age, time span from admission time and use of hearing aid.

Results

Among 599 patients the sensitivity to detect fever with an ear thermometer varied between 68 and 70% with AUC from 0.88–0.97. If the ear temperature was ≥37.5 oC, the sensitivity to detect patients with ≥38.0 oC rectally was 95% which raised to 100% for a rectal temperature of ≥38.3 oC. For the ear thermometer’s ability to determine the exact temperature the 95% limits of agreement were +/??0.8 oC. with no influence from age, duration of hospital stay or hearing aids.

Conclusion

The examined ear thermometer is able to detect fever, defined as ≥38 oC rectally in an adult ED population by using an ear cut-point of 37.5 oC, but not to measure the exact temperature. Used in this way around a fifth of the patients will still be in need of a rectal temperature measurement, but less than 5% with fever ≥38.0 oC will remain undetected and none with fever ≥38.3 oC. Age, admission time and use of hearing aid did not influence the temperature measurements.

Trial registration

Clinical Trials: ID NCT02977481, date 11/18/2016.

     

Thyroid effects of endocrine disrupting chemicals

In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert thyroid effects through a variety of mechanisms of action, and some animal experiments and in vitro studies have focused on elucidating the mode of action of specific chemical compounds. Long-term human studies on effects of environmental chemicals on thyroid related outcomes such as growth and development are still lacking. The human exposure scenario with life long exposure to a vast mixture of chemicals in low doses and the large physiological variation in thyroid hormone levels between individuals render human studies very difficult. However, there is now reasonably firm evidence that PCBs have thyroid-disrupting effects, and there is emerging evidence that also phthalates, bisphenol A, brominated flame retardants and perfluorinated chemicals may have thyroid disrupting properties.     

High nodal FDG uptake increases risk of distant metastasis in patients with oropharyngeal squamous cell carcinoma

European Journal of Nuclear Medicine and Molecular Imaging - The purpose of this study was to investigate if FDG uptake metrics in primary tumor and lymph node metastases in patients with...     

No influence of OPG and its ligands, RANKL and TRAIL, on proliferation and regulation of the calcification process in primary human vascular smooth muscle cells

The aim of this study was to examine the effects of the OPG-RANKL-TRAIL system on proliferation, regulation of calcification-associated genes and calcification of human vascular smooth muscle cells (HVSMCs). Small interfering (si)RNA-mediated knockdown of OPG was followed by treatment of HVSMCs with recombinant RANKL or TRAIL. Regulation of a calcification-associated gene set was assayed by pathway analysis of microarray results. The lack of OPG in HVSMCs or treatment with RANKL or TRAIL did not affect proliferation of HVSMCs. In addition, OPG, RANKL or TRAIL did not modify the regulation of a calcification-associated gene set. Finally, in the long term calcification assay, we found that cells isolated from seven different human donors showed a great variability in the response to RANKL and insulin. However, overall RANKL and/or insulin did not affect the development of calcification of HVSMCs. These studies indicate that OPG knockdown does not alter the calcification process in HVSMCs.     

Environmental chemicals and thyroid function

There is growing evidence that environmental chemicals can disrupt endocrine systems. Most evidence originates from studies on reproductive organs. However, there is also suspicion that thyroid homeostasis may be disrupted. Several groups of chemicals have potential for thyroid disruption. There is substantial evidence that polychlorinated biphenyls, dioxins and furans cause hypothyroidism in exposed animals and that environmentally occurring doses affect human thyroid homeostasis. Similarly, flame retardants reduce peripheral thyroid hormone (TH) levels in rodents, but human studies are scarce. Studies also indicate thyroid-disruptive properties of phthalates, but the effect of certain phthalates seems to be stimulative on TH production, contrary to most other groups of chemicals. Thyroid disruption may be caused by a variety of mechanisms, as different chemicals interfere with the hypothalamic-pituitary-thyroid axis at different levels. Mechanisms of action may involve the sodium-iodide symporter, thyroid peroxidase enzyme, receptors for THs or TSH, transport proteins or cellular uptake mechanisms. The peripheral metabolism of the THs can be affected through effects on iodothyronine deiodinases or hepatic enzymes. Even small changes in thyroid homeostasis may adversely affect human health, and especially fetal neurological development may be vulnerable. It is therefore urgent to clarify whether the animal data showing effects of chemicals on thyroid function can be extended to humans.     

Prevalence of Hypospadias in Danish Boys: A Longitudinal Study, 1977–2005

Background

Hypospadias is a relatively common congenital malformation. Data on temporal trends in prevalence of hypospadias are conflicting. It is unclear whether changes of maternal age distribution over time are associated with changes in hypospadias prevalence.

Objective

To study changes in prevalence of hypospadias in Denmark during a 29-yr period and to investigate whether maternal age was associated with the prevalence of hypospadias.

Design, setting, and participants

Through Denmark's National Patient Registry, covering all Danish hospitals, we identified all boys diagnosed with hypospadias in Denmark. From the Danish Medical Birth Registry, we obtained information on maternal age and on the annual total number of live-born boys from 1977 to 2005.

Measurements

Prevalence of hypospadias at birth.

Results and limitations

Among 921 745 boys born alive from 1977 to 2005, we identified 3490 boys with hypospadias. The prevalence increased from 0.24% in 1977 to 0.52% in 2005, corresponding with an annual increase in prevalence of 2.40% (95% confidence interval: 1.94–2.86). The prevalence of hypospadias did not differ according to maternal age. The mean annual prevalence was 0.38% in sons of mothers aged ≤25 yr, 0.37% in sons of mothers aged 26–30 yr, 0.39% in sons of mothers aged 31–35 yr, and 0.39% in sons of mothers >35 yr.

Conclusions

The hypospadias prevalence was increasing in Denmark from 1977 to 2005. Increased maternal age did not explain this trend.