Vascular Contributions to Brain Health: Cross-Cutting Themes

As life expectancy grows, brain health is increasingly seen as central to what we mean by successful aging—and vascular brain health as central to overall brain health. Cerebrovascular pathologies are highly prevalent independent contributors to age-related cognitive impairment and at least partly modifiable with available treatments. The current Focused Update addresses vascular brain health from multiple angles, ranging from pathophysiologic mechanisms and neuroimaging features to epidemiologic risk factors, social determinants, and candidate treatments. Here we highlight some of the shared themes that cut across these distinct perspectives: 1) the lifetime course of vascular brain injury pathogenesis and progression; 2) the scientific and ethical imperative to extend vascular brain health research in non-White and non-affluent populations; 3) the need for improved tools to study the cerebral small vessels themselves; 4) the potential role for brain recovery mechanisms in determining vascular brain health and resilience; and 5) the cross-pathway mechanisms by which vascular and neurodegenerative processes may interact. The diverse perspectives featured in this Focused Update offer a sense of the multidisciplinary approaches and collaborations that will be required to launch our populations towards improved brain health and successful aging.

Care Gaps and Recommendations in Vestibular Migraine: An Expert Panel Summit

Vestibular migraine (VM) is an increasingly recognized pathology yet remains as an underdiagnosed cause of vestibular disorders. While current diagnostic criteria are codified in the 2012 Barany Society document and included in the third edition of the international classification of headache disorders, the pathophysiology of this disorder is still elusive. The Association for Migraine Disorders hosted a multidisciplinary, international expert workshop in October 2020 and identified seven current care gaps that the scientific community needs to resolve, including a better understanding of the range of symptoms and phenotypes of VM, the lack of a diagnostic marker, a better understanding of pathophysiologic mechanisms, as well as the lack of clear recommendations for interventions (nonpharmacologic and pharmacologic) and finally, the need for specific outcome measures that will guide clinicians as well as research into the efficacy of interventions. The expert group issued several recommendations to address those areas including establishing a global VM registry, creating an improved diagnostic algorithm using available vestibular tests as well as others that are in development, conducting appropriate trials of high quality to validate current clinically available treatment and fostering collaborative efforts to elucidate the pathophysiologic mechanisms underlying VM, specifically the role of the trigemino-vascular pathways.

OMICS in Chronic Kidney Disease: Focus on Prognosis and Prediction

Chronic kidney disease (CKD) patients are characterized by a high residual risk for cardiovascular (CV) events and CKD progression. This has prompted the implementation of new prognostic and predictive biomarkers with the aim of mitigating this risk. The ‘omics’ techniques, namely genomics, proteomics, metabolomics, and transcriptomics, are excellent candidates to provide a better understanding of pathophysiologic mechanisms of disease in CKD, to improve risk stratification of patients with respect to future cardiovascular events, and to identify CKD patients who are likely to respond to a treatment. Following such a strategy, a reliable risk of future events for a particular patient may be calculated and consequently the patient would also benefit from the best available treatment based on their risk profile. Moreover, a further step forward can be represented by the aggregation of multiple omics information by combining different techniques and/or different biological samples. This has already been shown to yield additional information by revealing with more accuracy the exact individual pathway of disease.

Obstructive Sleep Apnea Syndrome: The Effect of Acute and Chronic Responses of Exercise

Obstructive Sleep Apnea Syndrome (OSAS) is a sleep disorder with high prevalence in general population, but alarmingly low in clinicians' differential diagnosis. We reviewed the literature on PubMed and Scopus from June 1980–2021 in order to describe the altered systematic pathophysiologic mechanisms in OSAS patients as well as to propose an exercise program for these patients. Exercise prevents a dysregulation of both daytime and nighttime cardiovascular autonomic function, reduces body weight, halts the onset and progress of insulin resistance, while it ameliorates excessive daytime sleepiness, cognitive decline, and mood disturbances, contributing to an overall greater sleep quality and quality of life.

Human Adenovirus Species D Interactions with Corneal Stromal Cells

Notable among the many communicable agents known to infect the human cornea is the human adenovirus, with less than ten adenoviruses having corneal tropism out of more than 100 known types. The syndrome of epidemic keratoconjunctivitis (EKC), caused principally by human adenovirus, presents acutely with epithelial keratitis, and later with stromal keratitis that can be chronic and recurrent. In this review, we discuss the current state of knowledge regarding the molecular biology of adenovirus infection of corneal stromal cells, among which the fibroblast-like keratocyte is the most predominant, in order to elucidate basic pathophysiologic mechanisms of stromal keratitis in the human patient with EKC.

Pathophysiologic Mechanisms of Insulin Secretion and Signaling-Related Genes in Etiology of Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women. PCOS is characterized by anovulation, hyperandrogenism, polycystic ovaries, insulin resistance, and obesity. Despite the finding that the genetic origin of PCOS is well demonstrated in previous twin and familial clustering studies, genes and factors that can exactly explain the PCOS pathophysiology are not known. Objective(s). In this review, we attempted to identify genes related to secretion and signaling of insulin aspects of PCOS and their physiological functions in order to explain the pathways that are regulated by these genes which can be a prominent function in PCOS predisposition. Materials and Methods. For this purpose, published articles and reviews dealing with genetic evaluation of PCOS in women from peer-reviewed journals in PubMed and Google Scholar databases were included in this review. Results. The genomic investigations in women of different populations identified many candidate genes and loci that are associated with PCOS. The most important of them are INSR, IRS1-2, MTNR1A, MTNR1B, THADA, PPAR-γ2, ADIPOQ, and CAPN10. These are mainly associated with metabolic aspects of PCOS. Conclusions. In this review, we proposed that each of these genes may interrupt specific physiological pathways by affecting them and contribute to PCOS initiation. It is clear that the role of genes involved in insulin secretion and signaling is more critical than other pathways.

404 Acute coronary syndromes after healing from COVID-19: report of the initial observation

Aims Severe pulmonary complications are well described in the coronavirus disease 2019 (COVID-19) and cardiovascular diseases (CVDs) have been documented as well. Most patients (pts) recover quickly; nevertheless, the potential long-term cardiovascular sequalae of COVID-19 remain currently unknown. The aim was to report cases of acute coronary syndromes (ACS) after healing from COVID-19 and their features at coronary angiography; secondary purpose was to hypothesize the underlying mechanisms. Methods and results A retrospective study was performed by acquiring data from the electronic medical record. From January to June 2021, four hypertensive pts (64 ± 17 years old; three males) with no history of CVDs and previous symptomatic SARS-CoV-2 infection (mean interval from first positive molecular swab 47 ± 32 days; all recovered after 15 days with double negative swab) were admitted to the emergency department for ST-elevation myocardial infarction (3 anterior and one inferior). At admission, the SARS-CoV-2 molecular swab tested negative, left ventricle ejection fraction was 42 ± 12%, troponin T and Nt-proBNP values were 47 ± 24 ng/l and 1180 ± 978 ng/l, respectively. Emergency coronary angiography showed single-vessel acute thrombotic occlusion (in three cases of the anterior descending artery and in one case of the right coronary artery), with no evidence of atherosclerotic disease. Because of the high thrombotic burden, in all cases a mechanical thrombus aspiration system was used, tirofiban infusion started and no balloon angioplasty or drug-eluting stent implantation was necessary (Figures A–D). After 72 h, a second SARS-CoV-2 molecular swab tested also negative. In the following days, the pts gradually recovered and they were discharged home. Conclusions These cases deserve specific considerations both on the pathophysiologic mechanisms of the ACS possibly related to SARS-CoV-2 and on the subsequent long-term sequelae. Among various pathophysiologic mechanisms proposed, the high affinity of the spike protein for the angiotensin converting enzyme two receptor (expressed by both cardiac and endothelial cells) could explain direct cardiac viral infection and vasculitis with possible development of thrombosis. The latter could contribute both to acute and long-term cardiac sequelae, even months after the acute infection, configuring a sort of ‘cardiac post-Covid syndrome’. Whether and how long this status persists, making COVID-19 a risk factor for subsequent CVDs, is still an unresolved question. In this regard, continuous monitoring of these pts and larger future studies will be essential.

Ranolazine: a better understanding of pathophysiology and patient profile to guide treatment of chronic stable angina

Chronic stable angina pectoris, the most prevalent symptomatic manifestation of coronary artery disease, greatly impairs quality of life and is associated with an increased risk for adverse cardiovascular outcomes. Better understanding of the pathophysiologic mechanisms of myocardial ischemia permitted new therapeutic strategies to optimize the management of angina patients. Ideally, antianginal drug treatment should be tailored to individual patient’s profile and chosen according to the pathophysiology, hemodynamic profile, adverse effects, potential drug interactions and comorbidities. In this respect, and because of its peculiar mechanism of action, ranolazine represents an alternative therapeutic approach in patients with chronic stable angina and may be considered the first choice in presence of comorbidities that difficult the use of traditional therapies.