Parental poverty and occupation as risk factors for pediatric sleep-disordered breathing.

Previous studies have found associations between pediatric sleep-disordered breathing (SDB) and socioeconomic status (SES), as well as a neighborhood-related disadvantage. This study analyzes the association among familial SES, parental occupation, and SDB in Swedish offspring

An Exploration of the Occupational Therapy Doctoral Capstone: Perspectives from Capstone Coordinators, Graduates, and Site Mentors

Few studies have investigated entry-level doctoral capstone outcomes regarding how the experience and project relate to employment opportunities. This descriptive study reports various stakeholders’ perspectives regarding the entry-level occupational therapy doctoral (OTD) capstone in relation to employment opportunities and awareness of the profession. Authors disseminated a nationwide survey to doctoral capstone coordinators, entry-level OTD graduates, and capstone site mentors. Ten doctoral capstone coordinators, 68 OTD graduates, and 22 capstone site mentors responded to the survey. Collectively, doctoral capstone coordinators reported that 117 OTD graduates obtained employment in a setting related to the focus of their doctoral capstone and gave examples of graduates employed as entrepreneurs, faculty, program specialists, and supervisors. OTD graduates most often completed their doctoral capstones in community-based settings with projects focusing on program development. Sixty-four percent of the OTD graduates were employed at their doctoral capstone site or at a site similar to where they completed their doctoral capstone. Professional background of capstone site mentors varied, and all mentors who were not occupational therapy professionals reported improved awareness of occupational therapy after mentoring an OTD student. Outcomes of the OTD doctoral capstone are needed to support the efficacy of this experience and project. This study begins to provide such outcomes by reporting findings related to employment and awareness of the profession

A Snapshot of How Entry-Level Occupational Therapy Programs Collect and Use Doctoral Capstone Outcomes

Entry-level occupational therapy doctorate (OTD) programs are required to gather program evaluation data regarding the doctoral capstone for accreditation purposes. This study aims to describe the processes used by a sample of OTD programs to gather doctoral capstone outcome data and to determine the type of data collected in order to understand the perspectives regarding doctoral capstone outcomes by doctoral capstone coordinators (DCCs) within the United States. The investigators used purposeful sampling to recruit DCCs at accredited entry-level OTD programs in the United States. The most common outcome data collected included information about the doctoral capstone experience from students, student performance outcomes, employment and scholarship outcomes from alumni and employers, and various outcomes from site/expert/faculty mentors. Results highlight the need to disseminate doctoral capstone outcomes as few participants in this study used the data they were collecting outside of their program. By sharing and reporting outcomes of the doctoral capstone, OTD programs, and the profession can collectively benefit. Development of common outcomes, collected across programs, can help to provide data large enough to draw meaningful conclusions regarding the value of the doctoral capstone in occupational therapy education and in strengthening the knowledge of the profession among the public

Systemic and Intra-Nodal Activation of NK Cells After Rituximab Monotherapy for Follicular Lymphoma

Monotherapy with the anti-CD20 monoclonal antibody rituximab can induce complete responses (CR) in patients with follicular lymphoma (FL). Resting FcRγIII+ (CD16+) natural killer (NK) cells respond strongly to rituximab-coated target cells in vitro. Yet, the contribution of NK cells in the therapeutic effect in vivo remains unknown. Here, we followed the NK cell repertoire dynamics in the lymph node and systemically during rituximab monotherapy in patients with FL. At baseline, NK cells in the tumor lymph node had a naïve phenotype albeit they were more differentiated than NK cells derived from control tonsils as determined by the frequency of CD56dim NK cells and the expression of killer cell immunoglobulin-like receptors (KIR), CD57 and CD16. Rituximab therapy induced a rapid drop in NK cell numbers coinciding with a relative increase in the frequency of Ki67+ NK cells both in the lymph node and peripheral blood. The Ki67+ NK cells had slightly increased expression of CD16, CD57 and higher levels of granzyme A and perforin. The in vivo activation of NK cells was paralleled by a temporary loss of in vitro functionality, primarily manifested as decreased IFNγ production in response to rituximab-coated targets. However, patients with pre-existing NKG2C+ adaptive NK cell subsets showed less Ki67 upregulation and were refractory to the loss of functionality. These data reveal variable imprints of rituximab monotherapy on the NK cell repertoire, which may depend on pre-existing repertoire diversity

Intermittent PI3Kδ inhibition sustains anti-tumour immunity and curbs irAEs

Phosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies1-3. Although studies in mouse models of solid tumours have demonstrated that PI3Kδ inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in humans remains unclear. Here we assessed the effects of the PI3Kδi AMG319 in human patients with head and neck cancer in a neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no. 2014-004388-20). PI3Kδ inhibition decreased the number of tumour-infiltrating regulatory T (Treg) cells and enhanced the cytotoxic potential of tumour-infiltrating T cells. At the tested doses of AMG319, immune-related adverse events (irAEs) required treatment to be discontinued in 12 out of 21 of patients treated with AMG319, suggestive of systemic effects on Treg cells. Accordingly, in mouse models, PI3Kδi decreased the number of Treg cells systemically and caused colitis. Single-cell RNA-sequencing analysis revealed a PI3Kδi-driven loss of tissue-resident colonic ST2 Treg cells, accompanied by expansion of pathogenic T helper 17 (TH17) and type 17 CD8+ T (TC17) cells, which probably contributed to toxicity; this points towards a specific mode of action for the emergence of irAEs. A modified treatment regimen with intermittent dosing of PI3Kδi in mouse models led to a significant decrease in tumour growth without inducing pathogenic T cells in colonic tissue, indicating that alternative dosing regimens might limit toxicity

Nerve lesions in pharynx : an aetiology of obstructive sleep apnoea

"Heavy snorers disease" is defined as the progression from habitual snoring to obstructive sleep apnoea (OSA). Apart from a significant weight gain, the aetiology underlying progression to a collapse of the upper airways during inspiration and sleep remains unclear. Previous studies have shown that nocturnal respiratory disturbances became worse even in some OSA patients who did not gain weight. Chronic vibration of a tissue may cause neuronal damage. Therefore, our hypothesis is that the snoring vibration, may cause a progressive pharyngeal nerve lesion. To study whether uvulopalatopharyngoplasty (UPPP) prevents progression in habitual snorers without OSA, we performed a five-year follow-up in 56 such patients. In the patients' estimation, the postoperative results were good. However, sleep recordings before and five years after surgery in 53 of them showed a slight but significant increase in respiratory disturbances, significantly correlated to weight gain. Six patients developed OSA postoperatively, one of them despite a weight loss of 10 kg. The patency of the upper airways depends on the balance between the negative intrapharyngeal pressure developed during inspiration and its counteraction by dilating muscles. The reflexogenic dilation is probably mediated by afferent nerve endings in the pharyngeal mucosa. To investigate whether there are signs of a local nerve lesion, three methods were used in patients with habitual snoring and various degrees of respiratory disturbances and in non-snoring controls: I) Biopsies of m. palatopharyngeus from 21 patients (10 with OSA) and 10 controls were investigated. The severity of the morphological abnormalities, including signs of efferent nerve lesions (e.g., type-grouping), was significantly greater in patients than in controls. The individual abnormality score correlated significantly to the amount of obstructive breatbing, but not to the oxygen desaturation index. 2) The vascular reaction in the soft palatal mucosa after afferent nerve stimulation was recorded by a laser Doppler perfusion monitoring method in 35 patients (24 with OSA) and in 13 controls Electrical stimulation activates nerve endings of C-fibre type, which release vasoactive agents- e.g., substance P (SP) and calcitonin gene-related peptide (CGRP)- resulting in vasodilation. The snorers and some mild OSA patients showed significantly more vasodilation after stimulation, than did controls, indicating sensitized nerves, e.g., due to sprouting. Patients with moderate-to-severe OSA demonstrated significantly less vasodilation than in controls, indicating degenerated nerves. 3) Biopsies of the soft palatal mucosa from 21 patients (10 with OSA) and 11 controls were immunohistochemically stained with PGP 9.5 (specific nerve-protein), SP and CGRP. All three substances showed an increase in the number of varicose nerve endings, in and below the epithelium in nine of 10 patients with rnild-to-moderate OSA and in four of 11 habitual snorers, compared to controls. This indicates a nerve lesion, e.g., nervous sprouting. CONCLUSIONS: UPPP does not completely prevent the development of OSA, especially if the patients gain weight postoperatively. The histological and physiological methods used indicate a progressive local nerve lesion. This lesion may be an aetiology to the collapse of upper airways in OSA

Pharyngeal disturbances in OSAS patients before and 1 year after UPPP

Conclusions: The results indicate that conservative uvulopalatopharyngoplasty with tonsillectomy (UPPP) did not change the degree of pharyngeal disturbances in patients with obstructive sleep apnea syndrome (OSAS). Objectives: To investigate if the symptom scores of pharyngeal disturbances in OSAS patients were changed 1 year after UPPP, by using a questionnaire pre- and postoperatively, and to compare with healthy non-snoring controls. Methods: Fifty men and eight women, median age 46 years (range 25–75), median body mass index (BMI) 28 kg/m2 (20–38), and median preoperative oxygen desaturation index 16 (7–100) were included as they had all failed non-surgical treatment and wanted pharyngeal surgery. The questionnaire consisted of 10 questions with 4 degrees of disturbances; the maximum score was 30 and was evaluated before and 1 year after surgery. Fifteen age-, gender- and BMI-matched controls responded to the same questionnaire. Results: Responses to the questionnaire were provided pre- and postoperatively by 47 of 58 patients (81%). Their median score was unchanged from 5 (range 0–17) to 5 (0–19), compared with controls 1 (0–3). Analyses of separate questions showed a significant decrease in the score for ‘globus sensation’ and ‘swelling’ postoperatively

Emotional Awareness Correlated With Number of Awakenings From Polysomnography in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome : A Pilot Study

Introduction: Unrefreshing sleep is one of the diagnostic criteria in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which could be explained by sleep disorders, for example obstructive sleep apnea, reported in our previous study with polysomnography. Our previous findings also indicate difficulties in emotional regulation when measuring alexithymia by TAS-20 (Toronto Alexithymia Scale) and level of emotional awareness by LEAS (Level of Emotional Awareness Scale) in ME/CFS patients. However, the reasons for this are unknown. The purpose of this study was to investigate correlations between data from subjective emotional regulation and polysomnography. Methods: Twenty-three ME/CFS patients (5 men and 18 women) of mean age 43, and 30 matched healthy controls (9 males and 21 women) of mean age 45, filled in TAS-20, LEAS, and Hospital Depression and Anxiety Scale (HADS). A polysomnography was performed on patients but not on healthy controls. Thus, values of normal population were used for sleep evaluation in ME/CFS patients. Result: There were significant differences between patients and controls in several aspects of emotional regulation, for example LEAS-self and LEAS-total. Seventy percent of the patients had increased numbers of awakenings (shifts from any sleep stage to awake), 22% had obstructive sleep apneas, and 27% had periodic limb movements. Correlation analysis showed that number of awakenings significantly correlated with LEAS-self and LEAS-total, p < 0.01, respectively. There were no other significant correlations. Conclusion: This pilot study demonstrated significant correlations between reduced emotional awareness and number of awakenings in polysomnography. Future studies with larger cohorts need to be conducted