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Allergen-specific sublingual immunotherapy (SLIT) is a potentially effective disease-modification treatment for patients with allergic asthma. Because CD44 signaling enhances regulatory T (Treg) cell-induction, administering CD44 ligands such as hyaluronan (HA) with allergen-specific SLIT may enhance the therapeutic effects. We evaluated the role of CD44 in Treg cell-induction in T helper type 2 (Th2)-mediated chronic airway inflammation using CD44-/- mice and the efficacy of HA on SLIT in a Dermatophagoides farinae (Df)-induced murine model of chronic asthma. Th2 responses and Treg cell induction were evaluated in CD44-/- mice. We devised a new SLIT model of Df-induced chronic asthma utilizing HA as an adjuvant. The effects of HA added to the new SLIT model were evaluated by the early asthmatic response (EAR) and airway hyperresponsiveness (AHR), eosinophilic airway inflammation, and serum Df-specific IgE levels. Th2-mediated chronic eosinophilic airway inflammation was worse in CD44-/- mice compared with Df-sensitized wild-type (WT) mice. HA enhanced the effect of Df-induced Treg cells in a CD44-dependent manner. Sublingual Df treatment in combination with HA, but not alone, normalized EAR and AHR, and significantly reduced the serum IgE levels and the bronchoalveolar lavage fluid (BALF) eosinophil number. HA also induced Treg cells in a Df-sensitized spleen cell culture in a CD44-dependent manner. The treatment-enhancing effects of HA in this SLIT model were diminished in CD44-/- mice. CD44 is a key contributor to Treg cell induction and critical for the enhancing effects of HA in a Df-induced murine model of chronic asthma., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: The individual prevalence of sleep-disordered breathing (SDB), short sleep duration, and obesity is high and increasing. The study aimed to investigate potential associations between SDB, objective sleep duration, obesity, diabetes and hypertension across genders, and the effect of pre- or post-menopausal status., Methods: A cross-sectional study evaluated 7051 community participants with wrist actigraphy for a week, and nocturnal oximetry ≥ 2 nights. SDB was assessed by 3 per cent oxygen desaturation index (ODI) corrected for sleep duration obtained from wrist actigraphy. Moderate-to-severe SDB was defined as ODI3% levels ≥ 15 per hour., Results: Both logODI3% and body mass index showed independent negative associations with sleep duration (β = -0.16, p < 0.001 and β = -0.07, p < 0.001, respectively). Moderate-to-severe SDB (men/premenopausal women/postmenopausal women; 23.7/1.5/9.5%, respectively) was associated with a higher risk of diabetes in premenopausal women (OR 28.1; 95%CI 6.35-124.6; p < 0.001) and postmenopausal women (OR 3.25; 95%CI 1.94-5.46; p < 0.001), but not in men (OR 1.47; 95%CI 0.90-2.40; p = 0.119). Moderate-to-severe SDB was associated with a higher risk of hypertension in men (OR 3.11; 95%CI 2.23-4.33; p < 0.001), premenopausal women (OR 3.88; 95%CI 1.42-10.6; p = 0.008), and postmenopausal women (OR 1.96; 95%CI 1.46-2.63; p < 0.001). Short sleep duration was not associated with diabetes or hypertension. The associations of obesity with diabetes or hypertension were indirectly mediated by SDB (24.0% and 21.5%, respectively), with possible sex differences emerging (men/women; 15.3/27.8% and 27.0/16.9%, respectively)., Conclusions: Notwithstanding the cross-sectional design, SDB and obesity, but not short sleep duration, were independently associated with diabetes and hypertension, with gender and menopausal status-related differences in risk emerging.

Objectives: The lung allocation score (LAS) system has been implemented to reduce waiting list time and mortality in the USA, but it remains uncertain how the LAS would reflect the impairment in health-related quality of life (HRQOL), which is another lung transplantation treatment goal to be improved in addition to survival. We thus investigated the relationships of the LAS with mortality and HRQOL in Japanese lung transplantation candidates., Methods: One hundred and two candidates for lung transplantation at Kyoto University Hospital between 2009 and 2013 were consecutively recruited to participate in this study. Their physiological measurements of pulmonary function and 6-min walking distance, as well as patient-reported measurements of HRQOL, dyspnoea and psychological status, were assessed., Results: Among these 102 patients, 22 died during a mean follow-up of 11.6 months. The LAS was significantly correlated to mortality (P = 0.0026), although other physiological measurements were not. However, regarding its relationship with HRQOL, correlation coefficients between the LAS, Medical Outcomes Study 36-item short form and St George's Respiratory Questionnaire (SGRQ) were relatively low, with the highest at 0.31. Multivariate analyses showed that the LAS was less significantly related to the SGRQ total score than dyspnoea, and psychological status., Conclusions: The LAS was significantly related to mortality in lung transplant candidates in Japan, while, despite its multidimensional scoring, its relationship with health-related quality of life was only weak. Their severity assessment system may be more focused on patients' health and symptoms., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Study Objectives: There are no clinical data comparing adherence and quality of life between auto-adjusting positive airway pressure (APAP) and two different flex positive airway pressure (PAP) devices (A-Flex, C-Flex) in patients with obstructive sleep apnea (OSA)., Design and Setting: Ninety-three patients in whom OSA was newly diagnosed were randomly assigned to receive 3 mo of APAP (n = 31), APAP with C-Flex (n = 31), or APAP with A-Flex (n = 31). Objective adherence was determined after 3 mo of CPAP treatment, and the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Calgary Sleep Apnea Quality of Life Index (SAQLI) were examined at baseline and after 3 mo. After 3 mo, patients in the APAP with A-Flex group and those in the APAP with C-Flex group were crossed over and those in the APAP group were switched to A-Flex for an additional 3 mo., Measurements and Results: The groups were similar demographically. Treatment adherence during the first 3 mo was significantly greater in the APAP with C-Flex group (APAP with C-Flex: 5.19 ± 1.84 h/night versus APAP: 3.96 ± 1.66 h/night versus APAP with A-Flex: 4.27 ± 2.12 h/night, P = 0.04). There was a significant improvement in two of four of the SAQLI domain scores and in the ESS and PSQI in the APAP with C-Flex group. Adherence significantly improved among the poor compliers (< 4 h/night of use) in the APAP group after change to APAP with A-Flex (P = 0.01)., Conclusions: Of these three modes of PAP delivery, adherence was greatest with APAP with C-Flex., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00873977.

Neocortical pyramidal cells are characterized by markedly different structure among cortical areas in the mature brain. In the ventral visual pathway of adult primates, pyramidal cells become increasingly more branched and more spinous with anterior progression through the primary (V1), second (V2), and fourth (V4) visual areas and cytoarchitectonic areas TEO and TE. It is not known how these regional specializations in neuron structure develop. Here, we report that the basal dendritic trees of layer III pyramidal cells in V1, V2, V4, TEO, and TE were characterized by unique growth profiles. Different numbers of spines were grown in the dendritic trees of cells among these cortical areas and then subsequently pruned. In V1, V2, and V4, more spines were pruned than grew resulting in a net decrease in the number of spines in the dendritic trees following the onset of visual experience. In TEO and TE, neurons grew more spines than they pruned from visual onset to adulthood. These data suggest that visual experience may influence neuronal maturation in different ways in different cortical areas.

Background: Severe obstructive sleep apnea (OSA), metabolic syndrome (Mets) and short sleep duration are all risk factors for cardiovascular events. There has been no report which has investigated this relationship in an age- and BMI-matched population-based study. The prevalence of OSA in Mets subjects has not been established, although the converse (i.e., the prevalence of Mets in OSA subjects) has been investigated several times., Methods: This home cardiorespiratory (type 3) sleep study, using an actigraph, was conducted in 275 males working for an urban company. Retrospective measurements of fasting blood parameters were obtained from the company's periodical inspection data. The mean duration between the sleep study and the measurement of blood parameters was 213 days., Results: Although there was a significant relationship between OSA severity and the prevalence of Mets (P < 0.001), the association between severity and Mets was not significant after adjustments were made for age and BMI. Severe OSA was 7.8 times as likely to be present in subjects with Mets (16.2% of all 68 Mets subjects) as those without (2.4% of 207 non-Mets) (P < 0.001). Subject with severe OSA had a significantly short sleep duration (P < 0.05). Sleep duration in Mets subjects was also significantly shorter than in those without (P < 0.05)., Conclusions: Although increased BMI and age both had a significant effect on the prevalence of OSA in patients with Mets, one of 6 subjects with Mets, but only one of 40 without Mets had severe OSA in an urban male population in Japan. Physicians should take into account this high prevalence of severe OSA in patients with Mets. Sleep duration should be taken into consideration as an important factor in studies investigating the prevalence of severe OSA and Mets.

Although it is hypothesized that there is abnormal motor inhibition in patients with dystonia, the question remains as to whether the mechanism related to motor inhibition is specifically impaired. The objective of the present study was to clarify the possible abnormalities of the mechanisms underlying voluntary muscle relaxation during motor preparation and execution in patients with writer's cramp, using event-related functional MRI. Eight patients with writer's cramp and 12 age-matched control subjects participated in the study. Two motor tasks were employed as an experimental paradigm. In the relaxation task, subjects were asked to hold their right wrist in the horizontal plane by maintaining moderate contraction of wrist extensor muscles in the premotor phase; they relaxed those muscles voluntarily just once during each fMRI scanning session. In the contraction task, subjects extended the right wrist voluntarily from the same premotor state as for the relaxation task. Five axial images covering the primary sensorimotor cortex (SMC) and supplementary motor area (SMA) were obtained once every second. Activated volumes in the left SMC and the SMA were significantly reduced in patients for both muscle relaxation and contraction tasks. These data suggest that there is impaired activation in both SMC and SMA in voluntary muscle relaxation and contraction in patients with writer's cramp. This implies that abnormalities of both inhibitory and excitatory mechanisms in motor cortices might play a role in the pathophysiology of focal dystonia.