The association between sleep disturbances and blood pressure variability: a review of the literature.

STUDY OBJECTIVES: Sleep disturbances are an underrecognized public health issue that results in various adverse outcomes and disturbed quality of life. Blood pressure variability (BPV) is an emerging entity in assessing cardiovascular disease risk and accumulating evidence suggests that BPV is closely associated with end-organ damage. This review aims to explore the association between sleep disturbances and BPV. METHODS: A comprehensive systematic literature search was conducted electronically using Web of Science, Ovid MEDLINE, , and SCOPUS. The electronic search was restricted to relevant English-language studies published between 1985 and August 2020. Most studies were prospective cohorts in design. After applying eligibility criteria, 29 articles were included for synthesis. RESULTS: This review shows that sleep disturbances are linked to short-term, midterm, and long-term BPV. Restless legs syndrome, shift work, insomnia, short sleep, long sleep, obstructive sleep apnea, and sleep deprivation were all positively associated with systolic blood pressure or diastolic blood pressure fluctuations. CONCLUSIONS: Given the prognostic implications of BPV and sleep disturbances on cardiovascular mortality, recognizing and treating both disorders is essential. More research is needed to examine the impact of sleep disorder treatment on BPV and cardiovascular mortality. CITATION: Al Haddad N, Costanian C, Zibara V, et al. The association between sleep disturbances and blood pressure variability: a review of the literature. J Clin Sleep Med. 2023;19(8):1533-1544.

Sleep Medicine Knowledge Among Graduating Medical Students in Lebanon During an Economic and Political Crisis: A Preliminary Survey.

Objectives Sleep disorders are prevalent and underrecognized during both economic and political crises. They are a major reason for poor overall health and decreased quality of life. Sleep medicine education is limited at most medical schools, resulting in limited awareness of this important aspect of healthcare. The aim of the study is to assess sleep medicine knowledge of graduating medical students in Lebanon and to assess their readiness to tackle sleep health issues in a country during an unprecedented crisis. Methods Final-year medical students at 7 medical schools in Lebanon were invited to fill a survey between January 2020 and March 2021. The Assessment of Sleep Knowledge in Medical Education survey was used to assess their knowledge in sleep medicine. The curriculum organizers at the medical schools were also surveyed. Student's t -test was used for analysis. Results 158 and 58 students completed the survey during 2020 and 2021, with a mean overall score on sleep knowledge of was 17.5 and 15.9 /30, respectively. There was no difference in mean knowledge scores by gender, age, American versus European medical school systems, and between medical schools that included sleep medicine in their curriculum versus those that did not. Conclusions Presence of sleep medicine education in the curriculum was associated with higher scores on ASKME among graduating Lebanese medical students. Given the low response rate, however, this descriptive pilot data could be used as a launching pad for a larger study, with a more representative sample, for generalizable results.

Case report: Later onset of NRAS-mutant metastatic melanoma in a patient with a partially-excised giant congenital melanocytic nevus.

Despite recent advances in treatment and surveillance, metastatic melanoma still carries a poor prognosis. Large/giant congenital melanocytic nevi (CMNs) constitute a known risk factor for the condition, with the greatest risk for malignant transformation thought to be during childhood (median age at diagnosis of 3 years in a previous cohort). Herein, we present the case of a 30-year-old male who, after undergoing multiple excision/grafting procedures for a giant CMN as a child, was diagnosed with an NRAS-mutant, MDM2-amplified metastatic melanoma more than 20 years later. Response to ipilimumab/nivolumab immunotherapy, cisplatin/vinblastine/temozolomide chemotherapy, and nivolumab/relatlimab immunotherapy was poor. This case highlights the importance of lifetime monitoring with once-yearly dermatological examination (including lymph node palpation) in large/giant CMN patients, as well as the need for further clinical trials evaluating novel therapies for NRAS-mutant melanoma.

Transcatheter tricuspid valve intervention techniques and procedural steps for the treatment of tricuspid regurgitation: a review of the literature.

Severe tricuspid regurgitation (TR) is an undertreated common pathology associated with significant morbidity and mortality. Classically, surgical repair or valve replacement were the only therapeutic options and are associated with up to 10% postprocedural mortality. Transcatheter tricuspid valve interventions are a novel and effective therapeutic option for the treatment of significant TR. Several devices have been developed with different mechanisms of action. They are classified as annuloplasty devices, replacement devices, caval valve implantation and coaptation devices. In this review, we provide a step-by-step description of the procedural steps and techniques of every device along with video support.

Combined anticoagulant and antiplatelet therapy is associated with an improved outcome in hospitalised patients with COVID-19: a propensity matched cohort study.

BACKGROUND: COVID-19 is a respiratory disease that results in a prothrombotic state manifesting as thrombotic, microthrombotic and thromboembolic events. As a result, several antithrombotic modalities have been implicated in the treatment of this disease. This study aimed to identify if therapeutic anticoagulation (TAC) or concurrent use of antiplatelet and anticoagulants was associated with an improved outcome in this patient population. METHODS: A retrospective observational cohort study of adult patients admitted to a single university hospital for COVID-19 infection was performed. The primary outcome was a composite of in-hospital mortality, intensive care unit (ICU) admission or the need for mechanical ventilation. The secondary outcomes were each of the components of the primary outcome, in-hospital mortality, ICU admission, or the need for mechanical ventilation. RESULTS: 242 patients were included in the study and divided into four subgroups: Therapeutic anticoagulation (TAC), prophylactic anticoagulation+antiplatelet (PACAP), TAC+antiplatelet (TACAP) and prophylactic anticoagulation (PAC) which was the reference for comparison. Multivariable Cox regression analysis and propensity matching were done and showed when compared with PAC, TACAP and TAC were associated with less in-hospital all-cause mortality with an adjusted HR (aHR) of 0.113 (95% CI 0.028 to 0.449) and 0.126 (95% CI 0.028 to 0.528), respectively. The number needed to treat in both subgroups was 11. Furthermore, PACAP was associated with a reduced risk of invasive mechanical ventilation with an aHR of 0.07 (95% CI 0.014 to 0.351). However, the was no statistically significant difference in the occurrence of major or minor bleeds, ICU admission or the composite outcome of in-hospital mortality, ICU admission or the need for mechanical ventilation. CONCLUSION: The use of combined anticoagulant and antiplatelet agents or TAC alone in hospitalised patients with COVID-19 was associated with a better outcome in comparison to PAC alone without an increase in the risk of major and minor bleeds. Sufficiently powered randomised controlled trials are needed to further evaluate the safety and efficacy of combining antiplatelet and anticoagulants agents or using TAC in the management of patients with COVID-19 infection.

Epidemiology and management of hypertension among refugees in the Middle East: a review of the literature.

This review aims to explore the burden of hypertension among refugees in the Middle East by reporting its prevalence, risk factors and access to care. A comprehensive literature search was performed using Web of Science, Ovid MEDLINE, PubMed, SCOPUS, CINHAL+, WHO Regional Office for the Eastern Mediterranean (EMRO) and United Nations High Commissioner for Refugees (UNHCR) on articles spanning from 1948 until 2020. Most studies were cross-sectional in design. After applying eligibility criteria 17 articles and 4 reports were included. Findings showed that hypertension represents a major burden among refugees. Hypertension risk factors present among the refugee population included increased salt intake, physical inactivity, and smoking. The majority of hypertensive refugees sought care for their condition at the public health care services. Barriers to seeking care included high cost of healthcare, accessibility to provided services, and lack of knowledge for the need to seek care. Non-adherence to medication among refugees was primarily linked to cost and lack of symptoms. This review highlights the need for further studies to shed light on the importance of targeting hypertension among refugees, to lower morbidity and mortality, in addition to providing adequate healthcare services to this population.

Lactate Mediates the Effects of Exercise on Learning and Memory through SIRT1-Dependent Activation of Hippocampal Brain-Derived Neurotrophic Factor (BDNF).

Exercise promotes learning and memory formation. These effects depend on increases in hippocampal BDNF, a growth factor associated with cognitive improvement and the alleviation of depression symptoms. Identifying molecules that are produced during exercise and that mediate hippocampal Bdnf expression will allow us to harness the therapeutic potential of exercise. Here, we report that an endogenous molecule produced during exercise in male mice induces the Mus musculus Bdnf gene and promotes learning and memory formation. The metabolite lactate, which is released during exercise by the muscles, crosses the blood-brain barrier and induces Bdnf expression and TRKB signaling in the hippocampus. Indeed, we find that lactate-dependent increases in BDNF are associated with improved spatial learning and memory retention. The action of lactate is dependent on the activation of the Sirtuin1 deacetylase. SIRT1 increases the levels of the transcriptional coactivator PGC1a and the secreted molecule FNDC5, known to mediate Bdnf expression. These results reveal an endogenous mechanism to explain how physical exercise leads to the induction of BDNF, and identify lactate as a potential endogenous molecule that may have therapeutic value for CNS diseases in which BDNF signaling is disrupted.SIGNIFICANCE STATEMENT It is established that exercise promotes learning and memory formation and alleviates the symptoms of depression. These effects are mediated through inducing Bdnf expression and signaling in the hippocampus. Understanding how exercise induces Bdnf and identifying the molecules that mediate this induction will allow us to design therapeutic strategies that can mimic the effects of exercise on the brain, especially for patients with CNS disorders characterized by a decrease in Bdnf expression and who cannot exercise because of their conditions. We identify lactate as an endogenous metabolite that is produced during exercise, crosses the blood-brain barrier and promotes hippocampal dependent learning and memory in a BDNF-dependent manner. Our work identifies lactate as a component of the "exercise pill."

Epigenetic changes in diabetes.

The incidence of diabetes is increasing worldwide. Diabetes is quickly becoming one of the leading causes of death. Diabetes is a genetic disease; however, the environment plays critical roles in its development and progression. Epigenetic changes often translate environmental stimuli to changes in gene expression. Changes in epigenetic marks and differential regulation of epigenetic modulators have been observed in different models of diabetes and its associated complications. In this minireview, we will focus DNA methylation, Histone acetylation and methylation and their roles in the pathogenesis of diabetes.