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Luciana Mascarenhas Fonseca,1,2,* Juliana Janeiro Schmidt,3,* Frank J Snoek,4 Ruth S Weinstock,5 Naomi Chaytor,1 Heather Stuckey,6 Christopher M Ryan,7 Eelco van Duinkerken3,4 1Department of Community and Behavioral Health, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA; 2Programa Terceira Idade (PROTER, Old Age Research Group), Department and Institute of Psychiatry, University of São Paulo School of Medicine, São Paulo, Brazil; 3Post-Graduate Program in Neurology, Universidade Federal Do Estado Do Rio de Janeiro, Rio de Janeiro, Brazil; 4Department of Medical Psychology, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands; 5Department of Medicine, Upstate Medical University, Syracuse, NY, USA; 6Department of Medicine, Penn State University College of Medicine, Hershey, PA, USA; 7Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA*These authors contributed equally to this workCorrespondence: Eelco van Duinkerken, Amsterdam University Medical Centers, Vrije Universiteit, Department of Medical Psychology, De Boelelaan 1117, Amsterdam, 1081 HV, the Netherlands, Email e.vanduinkerken@amsterdamumc.nlAbstract: Over the past decades, life expectancy of people with type 1 diabetes has increased considerably, which brings potential challenges due to the process of aging. Cognitive aging and dementia, as well as reductions in visual acuity, hearing and dexterity, can influence the frequency and quality of daily self-management activities, including medication taking and insulin dosing, glucose self-monitoring, and healthy eating. This can increase the risk for hypo- and hyperglycemic events, which, in turn, may contribute to cognitive decline. Because there is a gap in understanding the barriers and facilitators of self-management in older adults with type 1 diabetes and the relationship to cognitive functioning, the authors 1) review the available literature on cognitive aging and type 1 diabetes, 2) describe what self-management in later adulthood entails and the cognitive functions required for effective self-management behaviors, 3) analyze the interaction between type 1 diabetes, cognition, aging, and self-management behaviors, and 4) describe the barriers and facilitators for self-management throughout the life span and how they may differ for older people. Potential evidence-based practices that could be developed for older adults with type 1 diabetes are discussed. There is need for further studies that clarify the impact of aging on T1D self-management, ultimately to improve diabetes care and quality of life.Keywords: type 1 diabetes, self-management, cognition, aging

Indra Narang,1,2,&ast; Tetyana Kendzerska,3,4,&ast; Austin Heffernan,5 Uzair Malik,6 Carolina G Carvalho,7 Clodagh M Ryan8,9 1Department of Pediatrics, University of Toronto, Toronto, Canada; 2The Hospital for Sick Children, Toronto, Canada; 3Department of Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Canada; 4The Ottawa Hospital Research Institute, Ottawa, Canada; 5UBC, Faculty of Medicine, Vancouver, Canada; 6RCSI University of Medicine and Health Sciences, Dublin, Ireland; 7University Health Network; 8Department of Medicine, University of Toronto, Toronto, Canada; 9Sleep Research laboratory, KITE-UHN&ast;These authors contributed equally to this workCorrespondence: Clodagh M Ryan, 9N-967 Toronto General Hospital, 585 University Ave., Toronto, Ontario, M5G 2N2, Canada, Email clodagh.ryan@uhn.caBackground: There is increasing prevalence of moderate to severe obstructive sleep apnea (OSA) in adolescents, the majority of whom receive treatment with positive airway pressure (PAP). Adherence to PAP is sub-optimal in adolescents with OSA. Moreover, the impact of transition from pediatric to adult healthcare system on PAP adherence is unknown. This is relevant as the transition period is a time of increased stress for youth with chronic illnesses.Research Question: Does PAP adherence decrease during the 1-year transition period from pediatric to adult healthcare system in those with OSA?Study Design and Methods: Youth previously diagnosed with persistent OSA and treated with PAP in a large academic center (Toronto, Canada) between 2017 and 2019 were enrolled on transfer from the pediatric to adult sleep clinic and followed at 12 months. Mixed-effects linear regression models were used to investigate the effect of time since the transfer on objective PAP adherence with adjustment for confounders.Results: Among the 45 enrolled participants, 42.2% were female, the median age was 18 years (interquartile range [IQR]: 17– 18), median BMI was 30.3 (IQR: 24.0– 37.1), and the median apnea-hypopnea index (AHI) was 17.8 events/hour (11.8– 30.7). In univariate analysis, we observed a significant reduction in the 12-month average PAP usage in days used at follow-up compared to PAP use at the time of enrolment: median of 5.0 hours/day (IQR: 1.3– 8.0) vs 2.6 hours/day (0.0– 6.4), p < 0.0001. Following adjustment for age, level of education, employment status and living arrangement, the 12-month average PAP usage in days remained significantly decreased at follow-up compared to at the time of enrolment: change in hours of − 1.14; 95% CI − 2.27 to − 0.01.Interpretation: Among youth with OSA treated with PAP, there is a clinically significant reduction in PAP adherence over the first year during the transition from pediatric to adult health care.Keywords: CPAP adherence, transition care, obstructive sleep apnea, young adults, CPAP compliance

Theresa A Koleck,1,2 Catherine M Bender,1 Beth Z Clark,3,4 Christopher M Ryan,5,6 Puja Ghotkar,1 Adam Brufsky,4,7,8 Priscilla F McAuliffe,4,8,9 Priya Rastogi,4,7 Susan M Sereika,1,10,11 Yvette P Conley,1,12 1School of Nursing, University of Pittsburgh, Pittsburgh, PA, 2School of Nursing, Columbia University, New York, NY, 3Division of Gynecologic Pathology, Magee-Womens Hospital of University of Pittsburgh Medical Center (UPMC), 4School of Medicine, 5Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, 6Department of Psychiatry, University of California San Francisco, San Francisco, CA, 7Division of Hematology/Oncology, Magee-Womens Hospital of UPMC, 8University of Pittsburgh Cancer Institute, 9Division of Breast Surgical Oncology, Magee-Womens Hospital of UPMC, 10Department of Biostatistics, 11Department of Epidemiology, 12Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA Purpose: Inspired by the hypothesis that heterogeneity in the biology of breast cancers at the cellular level may account for cognitive dysfunction symptom variability in survivors, the current study explored relationships between host single-nucleotide polymorphisms (SNPs) in 25 breast cancer-related candidate genes (AURKA, BAG1, BCL2, BIRC5, CCNB1, CD68, CENPA, CMC2, CTSL2, DIAPH3, ERBB2, ESR1, GRB7, GSTM1, MELK, MKI67, MMP11, MYBL2, NDC80, ORC6, PGR, RACGAP1, RFC4, RRM2, and SCUBE2), identified from clinically relevant prognostic multigene-expression profiles for breast cancer, and pretreatment cognitive performance.Patients and methods: The sample (n=220) was comprised of 138 postmenopausal women newly diagnosed with early stage breast cancer and 82 postmenopausal age- and education-matched healthy controls without breast cancer. Cognitive performance was assessed after primary surgery but prior to initiation of adjuvant chemotherapy and/or hormonal therapy using a comprehensive battery of neuropsychological tests encompassing eight cognitive function composite domains: attention, concentration, executive function, mental flexibility, psychomotor speed, verbal memory, visual memory, and visual working memory. In total, 131 SNPs were included in the analysis. Standard and robust multiple linear regression modeling was used to examine relationships between each domain and the presence or absence of one or more minor alleles for each SNP. Genetic risk/protection scores (GRSs) were calculated for each domain to evaluate the collective effect of possession of multiple risk/protective alleles.Results: With the exception of CMC2, MMP11, and RACGAP1, significant (P

Cognitive functioning depends on intact brain networks that can be assessed with functional magnetic resonance imaging (fMRI) techniques. We hypothesized that cognitive decrements in type 1 diabetes mellitus (T1DM) are associated with alterations in resting-state neural connectivity and that these changes vary according to the degree of microangiopathy. T1DM patients with (MA(+): n = 49) and without (MA(-): n = 52) microangiopathy were compared with 48 healthy control subjects. All completed a neuropsychological assessment and resting-state fMRI. Networks were identified using multisubject independent component analysis; specific group differences within each network were analyzed using the dual-regression method, corrected for confounding factors and multiple comparisons. Relative to control subjects, MA(-) patients showed increased connectivity in networks involved in motor and visual processes, whereas MA(+) patients showed decreased connectivity in networks involving attention, working memory, auditory and language processing, and motor and visual processes. Better information-processing speed and general cognitive ability were related to increased degree of connectivity. T1DM is associated with a functional reorganization of neural networks that varies, dependent on the presence or absence of microangiopathy. [ABSTRACT FROM AUTHOR]

Introduction: Fluid displacement into nuchal and peripharyngeal soft tissues while recumbent may contribute to narrowing and increased airflow resistance of the pharynx (Rph), and predispose to pharyngeal collapse in patients at risk for obstructive sleep apnea. OBJECTIVES: To determine whether displacement of fluid from the lower body to the neck will increase both neck circumference and Rph in healthy subjects. METHODS: In 11 healthy, nonobese subjects, studied while awake and supine, leg fluid volume, neck circumference, and Rph were measured at baseline. Subjects were then randomized to a control period or to application of lower body positive pressure (LBPP) of 40 mm Hg via antishock trousers to displace fluid from the legs, after which they crossed over to the other arm. Baseline measurements were repeated at 1 and 5 min during the control and LBPP periods. RESULTS: Compared with the control period, application of LBPP caused a significant reduction in leg fluid volume (p < 0.001) and a significant increase in neck circumference (p = 0.004). Rph remained stable during the control period, but increased significantly from baseline after 1 and 5 min of LBPP (from 0.43 +/- 0.10 to 0.60 +/- 0.11 cm H(2)O/L/s, p = 0.034, and to 0.87 +/- 0.19 cm H(2)O/L/s, p < 0.001, compared with baseline, respectively). CONCLUSIONS: Fluid displacement from the legs by LBPP increases neck circumference and Rph in healthy subjects. These findings suggest the hypothesis that fluid displacement to the upper body during recumbency may predispose to pharyngeal obstruction during sleep, especially in fluid overload states, such as heart and renal failure. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Obstructive sleep apnea is common among patients with heart failure and exposes the left ventricle to trophic mechanical and adrenergic stimuli. We hypothesized that in heart failure patients with nonischemic dilated cardiomyopathy (a condition characterized by eccentric hypertrophy), those with obstructive sleep apnea would have a higher prevalence of left ventricular hypertrophy by wall thickness criteria (> or = 12 mm), and greater septal thickness than those without obstructive sleep apnea. Methods and Results: We performed echocardiography and polysomnography in 47 patients with nonischemic dilated cardiomyopathy. Obstructive sleep apnea was present in 45% of these patients. The prevalence of left ventricular hypertrophy was greater in those with than in those without obstructive sleep apnea (47.6 vs. 15.4%, p = 0.016). Interventricular septal thickness (p < 0.001) and relative wall thickness (p = 0.011) were significantly greater in those with than in those without obstructive sleep apnea. However, there was no significant difference in posterior wall thickness between the groups. The frequency of obstructive apneas and hypopneas during sleep was the only significant independent correlate of septal thickness (p = 0.001). Conclusions: In patients with nonischemic dilated cardiomyopathy, the presence of obstructive sleep apnea is associated with an increased prevalence of left ventricular hypertrophy. The higher relative wall thickness and interventricular septal thickness in patients with obstructive sleep apnea indicate that the left ventricle is relatively less eccentric than in patients without obstructive sleep apnea, and that such remodeling affects mainly the septum. These structural adaptations may reflect unique nocturnal mechanical and adrenergic stimuli associated with obstructive sleep apnea. [ABSTRACT FROM AUTHOR]

Background: Long-standing concern about the effects of type 1 diabetes on cognitive ability has increased with the use of therapies designed to bring glucose levels close to the nondiabetic range and the attendant increased risk of severe hypoglycemia.Methods: A total of 1144 patients with type 1 diabetes enrolled in the Diabetes Control and Complications Trial (DCCT) and its follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study were examined on entry to the DCCT (at mean age 27 years) and a mean of 18 years later with the same comprehensive battery of cognitive tests. Glycated hemoglobin levels were measured and the frequency of severe hypoglycemic events leading to coma or seizures was recorded during the follow-up period. We assessed the effects of original DCCT treatment-group assignment, mean glycated hemoglobin values, and frequency of hypoglycemic events on measures of cognitive ability, with adjustment for age at baseline, sex, years of education, length of follow-up, visual acuity, self-reported sensory loss due to peripheral neuropathy, and (to control for the effects of practice) the number of cognitive tests taken in the interval since the start of the DCCT.Results: Forty percent of the cohort reported having had at least one hypoglycemic coma or seizure. Neither frequency of severe hypoglycemia nor previous treatment-group assignment was associated with decline in any cognitive domain. Higher glycated hemoglobin values were associated with moderate declines in motor speed (P=0.001) and psychomotor efficiency (P<0.001), but no other cognitive domain was affected.Conclusions: No evidence of substantial long-term declines in cognitive function was found in a large group of patients with type 1 diabetes who were carefully followed for an average of 18 years, despite relatively high rates of recurrent severe hypoglycemia. (ClinicalTrials.gov number, NCT00360893.) [ABSTRACT FROM AUTHOR]

Transient lower extremity paralysis has been previously reported following high voltage electrical injury. The following case report describes an unusual presentation of transient acute flaccid lower extremity paralysis following a high voltage electrical injury associated with profound hypokalemia and acid/base abnormalities similar to the periodic paralysis syndrome. The patient's symptoms resolved with correction of severe hypokalemia. Potential mechanisms for a metabolic neuromuscular disorder induced by electrical injury are proposed. [ABSTRACT FROM AUTHOR]