Effects of 8 weeks of continuous positive airway pressure on abdominal adiposity in obstructive sleep apnoea

The aim of the present study was to investigate the effect of continuous positive airway pressure (CPAP) treatment on regional adipose tissue distribution in patients with moderate or severe obstructive sleep apnoea. Patients received both therapeutic and sham CPAP in a random order for 2 months each with an intervening 1-month washout. Abdominal subcutaneous, visceral and liver fat were quantified using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Liver enzymes and plasma glucose were also determined. Measurements were obtained at baseline and at the end of both treatment arms. 38 eligible patients were randomly assigned to a treatment order, with 27 patients having complete MRI/MRS data. No significant difference was observed in subcutaneous (-28.6 cm(3); p=0.49) or visceral (-16.8 cm(3); p=0.59) adipose tissue, intrahepatic lipid (-0.2%; p=0.21), or fasting glucose measurements (-0.1 mmol·L(-1); p=0.46) between treatment modalities. Alkaline phosphatase decreased (-3.1 U·L(-1); p=0.02) while on therapeutic CPAP compared with sham CPAP but other liver enzymes, including aspartate aminotransferase (0.3 U·L(-1); p=0.82), alanine aminotransferase (1.34 U·L(-1); p=0.59) and γ-glutamyltransferase (-2.3 U·L(-1); p=0.33), remained unchanged. In this first randomised, sham-controlled trial, there was no change in adipose tissue distribution after 8 weeks of therapeutic CPAP compared with 8 weeks of sham CPAP. Longer duration of CPAP use may be necessary to demonstrate a difference.     

Altered thermogenesis and impaired bone remodeling in Misty mice

Fat mass may be modulated by the number of brown‐like adipocytes in white adipose tissue (WAT) in humans and rodents. Bone remodeling is dependent on systemic energy metabolism and, with age, bone remodeling becomes uncoupled and brown adipose tissue (BAT) function declines. To test the interaction between BAT and bone, we employed Misty (m/m) mice, which were reported be deficient in BAT. We found that Misty mice have accelerated age‐related trabecular bone loss and impaired brown fat function (including reduced temperature, lower expression of Pgc1a, and less sympathetic innervation compared to wild‐type (+/ +)). Despite reduced BAT function, Misty mice had normal core body temperature, suggesting heat is produced from other sources. Indeed, upon acute cold exposure (4°C for 6 hours), inguinal WAT from Misty mice compensated for BAT dysfunction by increasing expression of Acadl, Pgc1a, Dio2, and other thermogenic genes. Interestingly, acute cold exposure also decreased Runx2 and increased Rankl expression in Misty bone, but only Runx2 was decreased in wild‐type. Browning of WAT is under the control of the sympathetic nervous system (SNS) and, if present at room temperature, could impact bone metabolism. To test whether SNS activity could be responsible for accelerated trabecular bone loss, we treated wild‐type and Misty mice with the β‐blocker, propranolol. As predicted, propranolol slowed trabecular bone volume/total volume (BV/TV) loss in the distal femur of Misty mice without affecting wild‐type. Finally, the Misty mutation (a truncation of DOCK7) also has a significant cell‐autonomous role. We found DOCK7 expression in whole bone and osteoblasts. Primary osteoblast differentiation from Misty calvaria was impaired, demonstrating a novel role for DOCK7 in bone remodeling. Despite the multifaceted effects of the Misty mutation, we have shown that impaired brown fat function leads to altered SNS activity and bone loss, and for the first time that cold exposure negatively affects bone remodeling.     

A combination of genetic,molecular and haemodynamic risk factors contributes to the formation,enlargement and rupture of brain aneurysms

Many people carry cerebral aneurysms but are generally unaware of their presence until they rupture, resulting in high morbidity or mortality. The pathogenesis and aetiology of aneurysms are largely unknown; however, a greater understanding, by analysing the genetic, molecular and haemodynamic risk factors involved in the initiation, enlargement, and rupture of aneurysms, could lead to effective prevention, early diagnosis and more effective treatment. The risk of aneurysm is increased by a family history of aneurysms, and amongst certain populations, namely in Japan and Finland. Several other risk factors are documented, including hypertension, smoking, alcohol consumption, and female sex. Studies indicate a higher occurrence of cerebral aneurysms in females compared to males. Oestrogen protects several components within the artery wall, and inhibits some of the inflammatory molecules that could cause aneurysms. At menopause, the oestrogen level decreases and the incidence of aneurysm increases. Haemodynamic stresses have been shown to be involved in the formation, growth and rupture of aneurysms. This is often associated with hypertension, which also increases the risk of aneurysm rupture. When an unruptured aneurysm is detected the decision to treat can be complicated, since only 1–2% of aneurysms eventually rupture. Haemodynamic simulation software offers an effective tool for the consideration of treatment options for patients who carry unruptured aneurysms. The assessment must consider the risks of interventional treatments versus non-interventional management options, such as controlling blood pressure.     

Pigmented villonodular synovitis: a crowdsourcing study of two hundred and seventy two patients

Purpose

We aimed to ascertain the feasibility of crowdsourcing via Facebook for medical research purposes; by investigating surgical, oncological and functional outcome and quality-of-life (QOL) in patients with pigmented villonodular synovitis (PVNS) enrolled in a Facebook community (1112 members).

Methods

Patients completed online open surveys on demographics, surgery and clinical outcomes (group 1); and patient-reported outcome measures (PROMs) including knee-injury osteoarthritis outcome score (KOOS), hip-disability osteoarthritis outcome score (HOOS), Toronto extremity salvage score (TESS) and SF-36 (group 2). Mean follow-up was 70 months (12–374). Consistency checks were performed with Cohen’s kappa statistic for intra-rater agreement.

Results

The first survey was completed by 272 patients (group 1) and 72 patients completed the second (group 2). In group 1, recurrence-rate was 58 % (69/118) after arthroscopic, 36 % (35/97) after open and 50 % (5/10) after combined synovectomy (p?=?0.003). In group 2, recurrence-rate was 67 % (26/39) after arthroscopic and 51 % (17/33) after open synovectomy (p?=?0.19). Recurrence-risk was increased for diffuse disease (OR?=?16; 95%CI?=?3.2–85; p?<?0.001). Mean function and QOL did not differ after arthroscopic or open synovectomy: KOOS 49 vs. 58 (p?=?0.24), HOOS 62 vs. 53 (p?=?0.56), TESS 78 vs. 82 (p?=?0.86), SF-36 61 vs. 66 (p?=?0.41). Cohen’s kappa statistic for intra-rater agreement was good to outstanding (κ?=?0.68–0.95; p?<?0.001).

Conclusion

Local recurrence-risk was higher for diffuse-type disease and arthroscopic synovectomy. Functional outcome and QOL were comparable for both types of surgery. Gathering data via crowdsourcing seems a promising and innovative way of evaluating rare diseases including PVNS.

     

Partial urethral obstruction of rabbit urinary bladder: stereological evidence that the increase in muscle content is mostly driven by changes in number, rather than size, of smooth muscle cells

The effects of partial urethral obstruction on the detrusor muscle of rabbit urinary bladder were investigated using stereological sampling and estimation tools. Twelve female Norfolk rabbits (2.5-3.0 kg body weight) were divided into four groups: 3, 7 and 12 weeks after surgical intervention to produce a standard partial obstruction and unobstructed controls. Following removal, bladder axes (craniocaudal, dorsoventral and laterolateral) and organ weights were recorded. Bladders were prepared for light microscopy by multistage random sampling procedures. Stereological methods were used to estimate the volume of muscle and the packing density and total number of myocyte nuclei in each bladder. We also estimated mean myocyte volume and the mean cross-sectional area and length of myocytes. Group comparisons were made by one-way analysis of variance. Changes in bladder axes were mainly laterolateral and craniocaudal. Mean bladder weight increased roughly six-fold by 3 weeks and 17-fold by 12 weeks and was accompanied, on average, by 12- and 33-fold increases in total muscle volume. These variables did not differ at 3 and 7 weeks post-obstruction. Increases in muscle content were not accompanied by changes in packing densities but were associated with increases in the total numbers of myocyte nuclei (13-fold by 3 weeks, 28-fold by 12 weeks). Mean myocyte volume did not vary significantly between groups but cells in obstructed groups were shorter and wider. These findings support the notion that partial outflow obstruction leads to an increase in the number, but not mean volume, of myocytes. If due solely to myocyte mitosis, the total of 43 x 10(8) cells found at 12 weeks could be generated by the original complement of 15 x 10(7) cells if an average of only 2.1 x 10(6) new cells was produced every hour. In reality, even this modest proliferation rate is unlikely to be achieved because myocyte proliferation rates are very low and it is possible that new myocytes can arise by differentiation of mesenchymal or other precursor cells.     

New tick defensin isoform and antimicrobial gene expression in response to Rickettsia montanensis challenge

Recent studies aimed at elucidating the rickettsia-tick interaction have discovered that the spotted fever group rickettsia Rickettsia montanensis, a relative of R. rickettsii, the etiologic agent of Rocky Mountain spotted fever, induces differential gene expression patterns in the ovaries of the hard tick Dermacentor variabilis. Here we describe a new defensin isoform, defensin-2, and the expression patterns of genes for three antimicrobials, defensin-1 (vsnA1), defensin-2, and lysozyme, in the midguts and fat bodies of D. variabilis ticks that were challenged with R. montanensis. Bioinformatic and phylogenetic analyses of the primary structure of defensin-2 support its role as an antimicrobial. The tissue distributions of the three antimicrobials, especially the two D. variabilis defensin isoforms, are markedly different, illustrating the immunocompetence of the many tissues that R. montanensis presumably invades once acquired by the tick. Antimicrobial gene expression patterns in R. montanensis-challenged ticks suggest that antimicrobial genes play a role during the acquisition-invasion stages in the tick.