First North American case of Hemoglobin Shepherds Bush (ß 74[E18] Gly → Asp) in a central Pennsylvania family.

BACKGROUND: Hemoglobin Shepherds Bush (Human Genome Variation Society name: HBB:c.224G > A) is an unstable hemoglobin variant resulting from a ß 74 GGC to GAC mutation (Gly to Asp) that manifests clinically as hemolytic anemia or gall bladder disease due to chronic subclinical hemolysis. CASE PRESENTATION: We report a Pennsylvania family of English descent with this condition, first noticed in a 6-year-old female. The proband presented with splenomegaly, fatigue, dark urine and an elevated indirect bilirubin. Hemoglobin identification studies and subsequent genetic testing performed according to a systematic algorithm elucidated the diagnosis of Hb Shepherds Bush. CONCLUSIONS: This is the first case of this rare hemoglobin variant identified in North America to our knowledge. It was identified using a systematic algorithm of diagnostic tests that should be followed whenever considering a rare hemoglobinopathy as part of the differential diagnosis.

Obstructive Sleep Apnea as a Risk Factor for COVID-19 Severity-The Gut Microbiome as a Common Player Mediating Systemic Inflammation via Gut Barrier Dysfunction.

The novel corona virus that is now known as (SARS-CoV-2) has killed more than six million people worldwide. The disease presentation varies from mild respiratory symptoms to acute respiratory distress syndrome and ultimately death. Several risk factors have been shown to worsen the severity of COVID-19 outcomes (such as age, hypertension, diabetes mellitus, and obesity). Since many of these risk factors are known to be influenced by obstructive sleep apnea, this raises the possibility that OSA might be an independent risk factor for COVID-19 severity. A shift in the gut microbiota has been proposed to contribute to outcomes in both COVID-19 and OSA. To further evaluate the potential triangular interrelationships between these three elements, we conducted a thorough literature review attempting to elucidate these interactions. From this review, it is concluded that OSA may be a risk factor for worse COVID-19 clinical outcomes, and the shifts in gut microbiota associated with both COVID-19 and OSA may mediate processes leading to bacterial translocation via a defective gut barrier which can then foster systemic inflammation. Thus, targeting biomarkers of intestinal tight junction dysfunction in conjunction with restoring gut dysbiosis may provide novel avenues for both risk detection and adjuvant therapy.

The Hypoglossal Nerve Stimulation as a Novel Therapy for Treating Obstructive Sleep Apnea-A Literature Review.

Obstructive sleep apnea (OSA) is a common sleep disorder that affects all age groups and is associated with many co-morbid diseases (especially cardiovascular diseases). Continuous positive airway pressure (CPAP) is the gold standard for treating OSA. However, adherence to PAP therapy has been a major challenge with an estimated adherence between 20% and 80%. Mandibular advancement devices (MAD) are a good alternative option if used in the appropriate patient. MAD are most effective in mild and moderate OSA but not severe OSA. Surgical options are invasive, not appropriate for severe OSA, and associated with pain and long healing time. Hypoglossal nerve stimulation (HGNS), or upper airway stimulation (UAS), is a novel therapy in treating moderate and severe degrees of OSA in patients who cannot tolerate CPAP therapy. We reviewed the MEDLINE (PubMed) database. The search process yielded 303 articles; 31 met the inclusion and exclusion criteria and were included. We concluded that hypoglossal nerve stimulation is a very effective and novel alternative therapy for moderate and severe OSA in patients who cannot tolerate CPAP therapy. Adherence to HGNS is superior to CPAP. However, more developments are needed to ensure the highest safety profile.

Matrix metalloproteinase-9 as a messenger in the cross talk between obstructive sleep apnea and comorbid systemic hypertension, cardiac remodeling, and ischemic stroke: a literature review.

STUDY OBJECTIVES: OSA is a common sleep disorder. There is a strong link between sleep-related breathing disorders and cardiovascular and cerebrovascular diseases. Matrix metalloproteinase-9 (MMP-9) is a biological marker for extracellular matrix degradation, which plays a significant role in systemic hypertension, myocardial infarction and postmyocardial infarction heart failure, and ischemic stroke. This article reviews MMP-9 as an inflammatory mediator and a potential messenger between OSA and OSA-induced comorbidities. METHODS: We reviewed the MEDLINE database (PubMed) for publications on MMP-9, OSA, and cardiovascular disease, identifying 1,592 studies and including and reviewing 50 articles for this work. RESULTS: There is strong evidence that MMP-9 and tissue inhibitor of metalloproteinase-1 levels are elevated in patients with OSA (mainly MMP-9), systemic hypertension, myocardial infarction, and postmyocardial infarction heart failure. Our study showed variable results that could be related to the sample size or to laboratory methodology. CONCLUSIONS: MMP-9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase-1, are a common denominator in OSA, systemic hypertension, myocardial infarction, and heart failure. This characterization makes MMP-9 a target for developing novel selective inhibitors that can serve as adjuvant therapy in patients with OSA, which may ameliorate the cardiovascular and cerebrovascular mortality associated with OSA.

Differences in sleep timing and related effects between African Americans and non-Hispanic Whites.

STUDY OBJECTIVES: Prior studies have shown a morning chronotype for African Americans compared with non-Hispanic Whites, yet self-reported sleep timing is delayed in African Americans compared with Whites. METHODS: We analyzed data from the Multi-Ethnicity Study of Atherosclerosis, a multisite community-based cohort. Self-reported and actigraphic sleep timing, chronotype measured by the modified Horne-Östberg Morningness-Eveningness Questionnaire, and risk of depression measured by the Center for Epidemiologic Studies Depression scale were examined using nonparametric approaches and linear or logistic regression while comparing between African Americans and Whites and evaluating the effects of delayed sleep phase. RESULTS: In 1,401 participants, there was no difference in chronotype between African Americans and Whites. African Americans were 80% more likely to report a delayed sleep phase (defined as bedtime after midnight) on weekdays and 50% more likely on weekends than were Whites. Actigraphic data showed similar results. Actigraphic midsleep time was delayed 38 minutes on weekdays and 24 minutes on weekends in African Americans compared with Whites. Stratified analysis by chronotype showed that African Americans with a morning or intermediate chronotype had a significantly delayed sleep phase compared with Whites, but there was no difference between African Americans and Whites with an evening chronotype. Delayed sleep phase was associated with depression, but this relationship was only significant in White participants. CONCLUSIONS: African Americans had a delayed sleep phase compared with Whites that was more pronounced in individuals with a morning or intermediate chronotype. Consequences of delayed sleep phase may vary by race and ethnicity.

Effect of wearables on sleep in healthy individuals: a randomized crossover trial and validation study.

STUDY OBJECTIVES: The purpose of this study was to determine whether a wearable sleep-tracker improves perceived sleep quality in healthy participants and to test whether wearables reliably measure sleep quantity and quality compared with polysomnography. METHODS: This study included a single-center randomized crossover trial of community-based participants without medical conditions or sleep disorders. A wearable device (WHOOP, Inc.) was used that provided feedback regarding sleep information to the participant for 1 week and maintained sleep logs versus 1 week of maintained sleep logs alone. Self-reported daily sleep behaviors were documented in sleep logs. Polysomnography was performed on 1 night when wearing the wearable. The Patient-Reported Outcomes Measurement Information System sleep disturbance sleep scale was measured at baseline, day 7 and day 14 of study participation. RESULTS: In 32 participants (21 women; 23.8 ± 5 years), wearables improved nighttime sleep quality (Patient-Reported Outcomes Measurement Information System sleep disturbance: B = -1.69; 95% confidence interval, -3.11 to -0.27; P = .021) after adjusting for age, sex, baseline, and order effect. There was a small increase in self-reported daytime naps when wearing the device (B = 3.2; SE, 1.4; P = .023), but total daily sleep remained unchanged (P = .43). The wearable had low bias (13.8 minutes) and precision (17.8 minutes) errors for measuring sleep duration and measured dream sleep and slow wave sleep accurately (intraclass coefficient, 0.74 ± 0.28 and 0.85 ± 0.15, respectively). Bias and precision error for heart rate (bias, -0.17%; precision, 1.5%) and respiratory rate (bias, 1.8%; precision, 6.7%) were very low compared with that measured by electrocardiogram and inductance plethysmography during polysomnography. CONCLUSIONS: In healthy people, wearables can improve sleep quality and accurately measure sleep and cardiorespiratory variables. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Assessment of Sleep by WHOOP in Ambulatory Subjects; Identifier: NCT03692195.

Renal vasoconstriction is augmented during exercise in patients with peripheral arterial disease.

Peripheral arterial disease (PAD) patients have augmented blood pressure increases during exercise, heightening their cardiovascular risk. However, it is unknown whether patients have exaggerated renal vasoconstriction during exercise and if oxidative stress contributes to this response. Eleven PAD patients and 10 controls (CON) performed 4-min mild, rhythmic, plantar flexion exercise of increasing intensity (0.5-2 kg) with each leg (most and least affected in PAD). Eight patients also exercised with their most affected leg during ascorbic acid (AA) infusion. Renal blood flow velocity (RBFV; Doppler ultrasound), mean arterial blood pressure (MAP; Finometer), and heart rate (HR; electrocardiogram [ECG]) were measured. Renal vascular resistance (RVR), an index of renal vasoconstriction, was calculated as MAP/RBFV. Baseline RVR and MAP were similar while HR was higher in PAD than CON (2.08 ± 0.23 vs. 1.87 ± 0.20 au, 94 ± 3 vs. 93 ± 3 mmHg, and 72 ± 3 vs. 59 ± 3 bpm [P < 0.05] for PAD and CON, respectively). PAD had greater RVR increases during exercise than CON, specifically during the first minute (PAD most: 26 ± 5% and PAD least: 17 ± 5% vs. CON: 3 ± 3%; P < 0.05). AA did not alter baseline RVR, MAP, or HR. AA attenuated the augmented RVR increase in PAD during the first minute of exercise (PAD most: 33 ± 4% vs. PAD most with AA: 21 ± 4%; P < 0.05). In conclusion, these findings suggest that PAD patients have augmented renal vasoconstriction during exercise, with oxidative stress contributing to this response.