Multi-night measurement for diagnosis and simplified monitoring of obstructive sleep apnoea.

Substantial night-to-night variability in obstructive sleep apnoea (OSA) severity has raised misdiagnosis and misdirected treatment concerns with the current prevailing single-night diagnostic approach. In-home, multi-night sleep monitoring technology may provide a feasible complimentary diagnostic pathway to improve both the speed and accuracy of OSA diagnosis and monitor treatment efficacy. This review describes the latest evidence on night-to-night variability in OSA severity, and its impact on OSA diagnostic misclassification. Emerging evidence for the potential impact of night-to-night variability in OSA severity to influence important health risk outcomes associated with OSA is considered. This review also characterises emerging diagnostic applications of wearable and non-wearable technologies that may provide an alternative, or complimentary, approach to traditional OSA diagnostic pathways. The required evidence to translate these devices into clinical care is also discussed. Appropriately sized randomised controlled trials are needed to determine the most appropriate and effective technologies for OSA diagnosis, as well as the optimal number of nights needed for accurate diagnosis and management. Potential risks versus benefits, patient perspectives, and cost-effectiveness of these novel approaches should be carefully considered in future trials.

Cavitating Lung Disease Associated With Sudden Death.

CASE PRESENTATION: A 16-year-old boy presented with 6 days of left iliac fossa pain. He had a medical history of right subtalar dislocation and appendicitis requiring laparotomy 3 years earlier, complicated by wound dehiscence. His family history was significant for his brother's sudden death 3 weeks prior after a 12-month illness with intermittent epigastric pain, weight loss, and hemoptysis. Travel history was significant for travel to the Philippines 3 years prior, in which he spent time in the hospital for appendicitis.

Chronic cough with dual pathologies of pulmonary ossification.

An 81-year-old man presented with chronic cough, which did not respond to the initiation of combined bronchodilator/inhaled corticosteroid therapy. CT of the chest revealed calcified nodules throughout the trachea sparing the posterior membrane, and tiny peripheral parenchymal nodules with basal interlobular septal thickening and calcification. Flexible bronchoscopy demonstrated endobronchial nodularity from the proximal trachea to the mid-sections of both main bronchi, sparing the posterior membrane. Histopathology revealed submucosal fibrous connective tissue and benign bone, confirming a diagnosis of tracheobronchopathia osteochondroplastica. CT was consistent with a concurrent diagnosis of dendriform pulmonary ossification. These two rare phenomena often present with non-specific symptoms, and the diagnosis can be made with imaging in both conditions. There is a role for bronchoscopy in the diagnosis of tracheobronchopathia osteochondropastica, and the endobronchial appearance could be diagnostic. The concurrence of both phenomena in our case might represent activity of a common cellular pathway of ossification in both sites.

A critical review of the efficacy of non-steroidal anti-inflammatory drugs in depression.

Non-steroidal anti-inflammatory drugs (NSAIDs) require further investigation given mixed results regarding efficacy. We critically and systematically reviewed the literature to determine whether selective COX-2 and non-selective COX inhibitor NSAIDs as adjuncts or monotherapy affect depressive symptoms. Electronic databases including Embase, PsycINFO, Ovid Medline, ScienceDirect, Google Scholar and the Cochrane Central Register of Controlled Trials database were searched up to September 2013. We utilised randomised controlled trials (RCTs), cohort studies and an open label study examining the efficacy of NSAIDs as adjuncts or monotherapy on depressive symptoms in subjects without major comorbidities. There were a total of 6 studies exploring the efficacy of selective COX-2 inhibitor NSAIDs on depressive symptoms with a total of 2706 subjects from 6 RCTs. 4 of the RCTs showed a significant effect of NSAIDs; 2 demonstrated no effect. There were a total of 5 studies exploring the efficacy of non-selective COX inhibitor NSAIDs on depressive symptoms with a total of 7978 subjects. There was 1 RCT, 3 cohort studies and 1 open label pilot study. The RCT failed to show a significant result. 1 of the retrospective cohort studies showed a positive result, with the other 2 showing no effect. The pilot study showed a positive result for NSAIDs. These studies demonstrated significant methodological heterogeneity (i.e. age range, sex, presence of antidepressant use, method of depression measure, severity of depressive symptoms, duration and study design (RCT vs. cohort)). The efficacy of NSAIDs on depressive symptoms appears negligible, however firm conclusions are difficult given the inconsistent findings and substantial methodological heterogeneity. Further high quality research is needed to explore NSAID efficacy in clinical and biological subtypes of depression, as monotherapy and adjunct with various antidepressants, and across various ages.

Notch signaling promotes intestinal crypt fission in the infant rat.

BACKGROUND: Growth of the small intestine in the infant rat is promoted by crypt fission and later by increased crypt cell proliferation. Notch signaling could promote crypt fission. Hes-1 is a Notch target gene. AIM: We assessed the effect of Notch signaling on intestinal crypt fission and on growth of the intestine in the infant rat. METHODS: Hes-1 expression was determined in the small intestine of litters of Hooded Wistar rats aged between 3 and 72 days. Hes-1 RNA expression was measured by quantitative RT-PCR. Four groups of rats (n = 8 or 9) were injected daily, ip, either with vehicle or with the Notch inhibitor DAPT at doses of 3, 10, and 30 mg/kg, from days 9 to 13 of life, and killed on day 14. A microdissection technique was used to measure crypt fission, mitotic count, and apoptotic count. Data were analyzed by ANOVA and by use of Dunnett's F test. RESULTS: Hes-1 expression and crypt fission peaked on day 14. DAPT reduced Hes-1 immunostaining in proportion to dose. DAPT reduced villous area to 72 % (p < 0.01), 53 % (p < 0.001), and 38 % (p < 0.001) of control values for 3, 10 and 30 mg/kg doses, respectively, and reduced crypt fission to 53 % (p < 0.001) and 38 % (p < 0.001) of control values, respectively, for 10 and 30 mg/kg doses. Crypt mitotic count was not affected by any DAPT dose. DAPT at 10 and 30 mg/kg significantly increased apoptosis in crypts, by 6.5 and 4.8-fold, respectively. CONCLUSIONS: We conclude that Notch signaling promotes crypt fission and growth of the intestine by maintaining low apoptosis of crypt cells.

Wnt blockade with dickkopf reduces intestinal crypt fission and intestinal growth in infant rats.

OBJECTIVES: Intestinal crypt fission peaks during infancy. In human and experimental familial polyposis coli, increased crypt fission is due to activation of Wnt/ß-catenin signalling, but the molecular basis of crypt fission during intestinal growth has not been examined. The aim of this project was to investigate whether crypt fission and intestinal growth are affected by experimental blockade of the Wnt/ß-catenin signalling pathway. METHODS: Hooded Wistar rats were given either the Wnt inhibitor, dickkopf (30 and 100 ng), daily or vehicle control intraperitoneally from days 11 to 15 and were killed at day 16. Intestinal morphometry was used to measure villous area, crypt area, percentage of crypt fission, and crypt mitotic count. Intestinal stem cells were assessed by expression of real time-polymerase chain reaction for Lgr5 (a stem cell marker), and the number of ß-catenin-expressing crypts by immunostaining was determined after 100-ng dickkopf treatment. RESULTS: Dickkopf at 30 and 100 ng/day reduced villous area to 71% (P = 0.013) and 29% (P < 0.0001), crypt area to 42% (P = 0.0026) and 30% (P = 0.0067), and crypt fission to 51% (P = 0.006) and 29% (P < 0.0001), respectively, of control values. Mitotic count per crypt did not change. Lgr5 RNA expression and the number of ß-catenin-expressing crypts decreased in dickkopf-treated animals. CONCLUSIONS: We conclude that intestinal crypt fission during infancy is mediated by Wnt signalling. It is possible that local treatment with Wnt agonists could be used to increase intestinal growth.