Plasma Carotenoid Concentrations of Incubating American Kestrels (\u3cem\u3eFalco sparverius\u3c/em\u3e) Show Annual, Seasonal, and Individual Variation and Explain Reproductive Outcome

In wild birds, the proximate and ultimate factors that affect circulating carotenoid concentrations remain poorly understood. We studied variation in plasma carotenoid concentrations across several scales: annual, seasonal, pair, territory and individual, and evaluated whether plasma carotenoid concentrations explained reproductive outcome of wild American kestrels (Falco sparverius). We sampled plasma carotenoid concentrations of 99 female and 80 male incubating kestrels from April to June in 2008 to 2012. Plasma carotenoid concentrations were explained by an interaction between year and sex, date, and random effects for pair and individual identity. In general, plasma carotenoid concentrations of males were significantly higher than females, but this depended on year. Within a breeding season, earlier nesting kestrels had higher carotenoid concentrations than later nesting kestrels, a pattern that is coincident with seasonal trends in local fitness. Pair and individual identity explained variation in carotenoid concentrations suggesting that carotenoid concentrations of mated birds were correlated, and some individuals consistently maintained higher carotenoid levels than others. Male carotenoid concentrations were positively associated with number of young fledged per pair. These results are consistent with the hypothesis that higher quality individuals have higher carotenoid levels compared to lower quality individuals, despite annual variations in carotenoid availability

Ursodeoxycholic acid as a novel disease-modifying treatment for Parkinson’s disease: protocol for a two-centre, randomised, double-blind, placebo-controlled trial, The 'UP' study

Introduction There are no disease-modifying treatments for Parkinson’s disease (PD). We undertook the first drug screen in PD patient tissue and idntified ursodeoxycholic acid (UDCA) as a promising mitochondrial rescue agent. The aims of this trial are to determine safety and tolerability of UDCA in PD at 30 mg/kg, confirm the target engagement of UDCA, apply a novel motion sensor-based approach to quantify disease progression objectively, and estimate the mean effect size and its variance on the change in motor severity. Methods and analysis This is a phase II, two-centre, double-blind, randomised, placebo-controlled trial of UDCA at a dose of 30 mg/kg in 30 participants with early PD. Treatment duration is 48 weeks, followed by an 8-week washout phase. Randomisation is 2:1, drug to placebo. Assessments are performed at baseline, week 12, 24, 36, 48 and 56. The primary outcome is safety and tolerability. Secondary outcomes will compare the change between baseline and week 48 using the following three approaches: the Movement Disorders Society Unified Parkinson’s Disease Rating Scale Part 3 in the practically defined ‘OFF’ medication state; confirmation of target engagement, applying 31Phosphorus MR Spectroscopy to assess the levels of ATP and relevant metabolites in the brain; and objective quantification of motor impairment, using a validated, motion sensor-based approach. The primary outcome will be reported using descriptive statistics and comparisons between treatment groups. For each secondary outcome, the change from baseline will be summarised within treatment groups using summary statistics and appropriate statistical tests assessing for significant differences. All outcomes will use an intention-to-treat analysis population. Ethics and dissemination This trial has been approved by the East of England – Cambridgeshire and Hertfordshire Research Ethics committee. Results will be disseminated in peer-reviewed journals, presentations at scientific meetings and to patients in a lay-summary format. Trial registration number NCT03840005

A Double-Blind, Randomized, Placebo-Controlled Trial of Ursodeoxycholic Acid (UDCA) in Parkinson's Disease

BACKGROUND: Rescue of mitochondrial function is a promising neuroprotective strategy for Parkinson's disease (PD). Ursodeoxycholic acid (UDCA) has shown considerable promise as a mitochondrial rescue agent across a range of preclinical in vitro and in vivo models of PD. OBJECTIVES: To investigate the safety and tolerability of high-dose UDCA in PD and determine midbrain target engagement. METHODS: The UP (UDCA in PD) study was a phase II, randomized, double-blind, placebo-controlled trial of UDCA (30 mg/kg daily, 2:1 randomization UDCA vs. placebo) in 30 participants with PD for 48 weeks. The primary outcome was safety and tolerability. Secondary outcomes included 31-phosphorus magnetic resonance spectroscopy (31 P-MRS) to explore target engagement of UDCA in PD midbrain and assessment of motor progression, applying both the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) and objective, motion sensor-based quantification of gait impairment. RESULTS: UDCA was safe and well tolerated, and only mild transient gastrointestinal adverse events were more frequent in the UDCA treatment group. Midbrain 31 P-MRS demonstrated an increase in both Gibbs free energy and inorganic phosphate levels in the UDCA treatment group compared to placebo, reflecting improved ATP hydrolysis. Sensor-based gait analysis indicated a possible improvement of cadence (steps per minute) and other gait parameters in the UDCA group compared to placebo. In contrast, subjective assessment applying the MDS-UPDRS-III failed to detect a difference between treatment groups. CONCLUSIONS: High-dose UDCA is safe and well tolerated in early PD. Larger trials are needed to further evaluate the disease-modifying effect of UDCA in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

A review of ECG-based diagnosis support systems for obstructive sleep apnea

Humans need sleep. It is important for physical and psychological recreation. During sleep our consciousness is suspended or least altered. Hence, our ability to avoid or react to disturbances is reduced. These disturbances can come from external sources or from disorders within the body. Obstructive Sleep Apnea (OSA) is such a disorder. It is caused by obstruction of the upper airways which causes periods where the breathing ceases. In many cases, periods of reduced breathing, known as hypopnea, precede OSA events. The medical background of OSA is well understood, but the traditional diagnosis is expensive, as it requires sophisticated measurements and human interpretation of potentially large amounts of physiological data. Electrocardiogram (ECG) measurements have the potential to reduce the cost of OSA diagnosis by simplifying the measurement process. On the down side, detecting OSA events based on ECG data is a complex task which requires highly skilled practitioners. Computer algorithms can help to detect the subtle signal changes which indicate the presence of a disorder. That approach has the following advantages: computers never tire, processing resources are economical and progress, in the form of better algorithms, can be easily disseminated as updates over the internet. Furthermore, Computer-Aided Diagnosis (CAD) reduces intra- and inter-observer variability. In this review, we adopt and support the position that computer based ECG signal interpretation is able to diagnose OSA with a high degree of accuracy

Sleep Disorders and Demand for Medical Services: Evidence from a Population-Based Longitudinal Study

Background: The aim of this study was to investigate whether insomnia and obstructive sleep apnea (OSA) were predictors of hospitalizations or emergency department visits during two years following the Sao Paulo Epidemiologic Sleep Study (EPISONO) sample. Methods and Findings: All participants (n = 1,101) who underwent a baseline evaluation between July and December 2007 were contacted in December 2009 and asked to fill out a questionnaire about body weight changes, number of hospitalizations and visits to the emergency department. Participants lost during the follow-up period represented 3.2 % (n = 35) and 7 subjects had died. Hospitalizations were reported by 116 volunteers (10.5%) and emergency department visits were reported by 136 participants (12.4%). The average body mass index (BMI) did not vary significantly between the first and the second assessment [26.7(95%CI:26.3–27.1) vs. 26.9(26.5–27.4) kg/m2]. After adjusting for confounders, a multiple logistic regression model revealed that female gender [1.4(1.0–1.9)], age $40 years, insomnia diagnosed according to the DSM-IV criteria [1.6(1.0–2.6)], and apneahypopnea index$15 [1.5(1.0–2.2)] were predictors of hospitalizations and/or demand for emergency services. Conclusion: Our study of a probabilistic sample of the Sao Paulo inhabitants shows that over a period of two years, insomnia and OSA were both associated with health impairment. Considering the high prevalence and public health burden of slee

Multimodal assessment of mitochondrial function in Parkinson's disease

The heterogenous aetiology of Parkinson's disease is increasingly recognized; both mitochondrial and lysosomal dysfunction have been implicated. Powerful, clinically applicable tools are required to enable mechanistic stratification for future precision medicine approaches. The aim of this study was to characterize bioenergetic dysfunction in Parkinson's disease by applying a multimodal approach, combining standardized clinical assessment with midbrain and putaminal 31-phosphorus magnetic resonance spectroscopy (31P-MRS) and deep phenotyping of mitochondrial and lysosomal function in peripheral tissue in patients with recent-onset Parkinson's disease and control subjects. Sixty participants (35 patients with Parkinson's disease and 25 healthy controls) underwent 31P-MRS for quantification of energy-rich metabolites [ATP, inorganic phosphate (Pi) and phosphocreatine] in putamen and midbrain. In parallel, skin biopsies were obtained from all research participants to establish fibroblast cell lines for subsequent quantification of total intracellular ATP and mitochondrial membrane potential (MMP) as well as mitochondrial and lysosomal morphology, using high content live cell imaging. Lower MMP correlated with higher intracellular ATP (r = −0.55, P = 0.0016), higher mitochondrial counts (r = −0.72, P < 0.0001) and higher lysosomal counts (r = −0.62, P = 0.0002) in Parkinson's disease patient-derived fibroblasts only, consistent with impaired mitophagy and mitochondrial uncoupling. 31P-MRS-derived posterior putaminal Pi/ATP ratio variance was considerably greater in Parkinson's disease than in healthy controls (F-tests, P = 0.0036). Furthermore, elevated 31P-MRS-derived putaminal, but not midbrain Pi/ATP ratios (indicative of impaired oxidative phosphorylation) correlated with both greater mitochondrial (r = 0.37, P = 0.0319) and lysosomal counts (r = 0.48, P = 0.0044) as well as lower MMP in both short (r = −0.52, P = 0.0016) and long (r = −0.47, P = 0.0052) mitochondria in Parkinson's disease. Higher 31P-MRS midbrain phosphocreatine correlated with greater risk of rapid disease progression (r = 0.47, P = 0.0384). Our data suggest that impaired oxidative phosphorylation in the striatal dopaminergic nerve terminals exceeds mitochondrial dysfunction in the midbrain of patients with early Parkinson's disease. Our data further support the hypothesis of a prominent link between impaired mitophagy and impaired striatal energy homeostasis as a key event in early Parkinson's disease

Observational study on efficacy of negative expiratory pressure test proposed as screening for obstructive sleep apnea syndrome among commercial interstate bus drivers - protocol study

<p>Abstract</p> <p>Background</p> <p>Obstructive sleep apnea (OSA) is a respiratory disease characterized by the collapse of the extrathoracic airway and has important social implications related to accidents and cardiovascular risk. The main objective of the present study was to investigate whether the drop in expiratory flow and the volume expired in 0.2 s during the application of negative expiratory pressure (NEP) are associated with the presence and severity of OSA in a population of professional interstate bus drivers who travel medium and long distances.</p> <p>Methods/Design</p> <p>An observational, analytic study will be carried out involving adult male subjects of an interstate bus company. Those who agree to participate will undergo a detailed patient history, physical examination involving determination of blood pressure, anthropometric data, circumference measurements (hips, waist and neck), tonsils and Mallampati index. Moreover, specific questionnaires addressing sleep apnea and excessive daytime sleepiness will be administered. Data acquisition will be completely anonymous. Following the medical examination, the participants will perform a spirometry, NEP test and standard overnight polysomnography. The NEP test is performed through the administration of negative pressure at the mouth during expiration. This is a practical test performed while awake and requires little cooperation from the subject. In the absence of expiratory flow limitation, the increase in the pressure gradient between the alveoli and open upper airway caused by NEP results in an increase in expiratory flow.</p> <p>Discussion</p> <p>Despite the abundance of scientific evidence, OSA is still underdiagnosed in the general population. In addition, diagnostic procedures are expensive, and predictive criteria are still unsatisfactory. Because increased upper airway collapsibility is one of the main determinants of OSA, the response to the application of NEP could be a predictor of this disorder. With the enrollment of this study protocol, the expectation is to encounter predictive NEP values for different degrees of OSA in order to contribute toward an early diagnosis of this condition and reduce its impact and complications among commercial interstate bus drivers.</p> <p>Trial registration</p> <p><it>Registro Brasileiro de Ensaios Clinicos </it>(local acronym RBEC) [Internet]: Rio de Janeiro (RJ): <it>Instituto de Informaçao Cientifica e Tecnologica em Saude </it>(Brazil); 2010 - Identifier RBR-7dq5xx. Cross-sectional study on efficacy of negative expiratory pressure test proposed as screening for obstructive sleep apnea syndrome among commercial interstate bus drivers; 2011 May 31 [7 pages]. Available from <url>http://www.ensaiosclinicos.gov.br/rg/RBR-7dq5xx/</url>.</p

Traumatic retinal detachment caused by a Nerf gun shot in a pediatric patient

PURPOSE: To present a case of retinal detachment caused by a Nerf-gun shot in a pediatric patient. METHODS: Single case report. RESULTS: A 16-year-old white man presented with a nasal visual field deficit and floaters in his left eye for 1 month after being shot with a foam-ball Nerf gun by a friend. Fundus examination revealed a midperipheral retinal dialysis extending from 1 to 4:30 clock hours with a macula-on retinal detachment and superficial proliferative vitreoretinopathy. He underwent successful 25-gauge pars plana vitrectomy with membrane peel, retinectomy, injection of perfluoron, endolaser, and use of 1,000 centistoke silicone oil for tamponade. CONCLUSION: This is the first reported case of traumatic retinal detachment secondary to a Nerf-gun shot