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Endocrine Reviews Oct 2019This review covers the epidemiology, pathophysiology, clinical features, diagnosis, and management of diabetic gastroparesis, and more broadly diabetic... (Review)
Review
This review covers the epidemiology, pathophysiology, clinical features, diagnosis, and management of diabetic gastroparesis, and more broadly diabetic gastroenteropathy, which encompasses all the gastrointestinal manifestations of diabetes mellitus. Up to 50% of patients with type 1 and type 2 DM and suboptimal glycemic control have delayed gastric emptying (GE), which can be documented with scintigraphy, 13C breath tests, or a wireless motility capsule; the remainder have normal or rapid GE. Many patients with delayed GE are asymptomatic; others have dyspepsia (i.e., mild to moderate indigestion, with or without a mild delay in GE) or gastroparesis, which is a syndrome characterized by moderate to severe upper gastrointestinal symptoms and delayed GE that suggest, but are not accompanied by, gastric outlet obstruction. Gastroparesis can markedly impair quality of life, and up to 50% of patients have significant anxiety and/or depression. Often the distinction between dyspepsia and gastroparesis is based on clinical judgement rather than established criteria. Hyperglycemia, autonomic neuropathy, and enteric neuromuscular inflammation and injury are implicated in the pathogenesis of delayed GE. Alternatively, there are limited data to suggest that delayed GE may affect glycemic control. The management of diabetic gastroparesis is guided by the severity of symptoms, the magnitude of delayed GE, and the nutritional status. Initial options include dietary modifications, supplemental oral nutrition, and antiemetic and prokinetic medications. Patients with more severe symptoms may require a venting gastrostomy or jejunostomy and/or gastric electrical stimulation. Promising newer therapeutic approaches include ghrelin receptor agonists and selective 5-hydroxytryptamine receptor agonists.
Topics: Animals; Diabetic Neuropathies; Female; Gastroparesis; Humans; Male
PubMed: 31081877
DOI: 10.1210/er.2018-00161 -
Neurosciences (Riyadh, Saudi Arabia) Apr 2023Although not fully understood, sleep is accepted as a vital and organized sequence of events that follows a regular cyclic program each night to ensure the human body... (Review)
Review
Although not fully understood, sleep is accepted as a vital and organized sequence of events that follows a regular cyclic program each night to ensure the human body can perform at its optimum. A lack of sleep, or sleep deprivation (SD), is a widespread phenomenon that can induce adverse changes in cognitive performance. This review focused on the biological explanation as well as the research investigating the numerous effects that SD can have on cognition. A reduction in sleep does not occur independently of the effects on memory, attention, alertness, judgment, decision-making, and overall cognitive abilities in the brain, resulting in decreased function and impaired cognitive performance.
Topics: Humans; Sleep Deprivation; Psychomotor Performance; Cognition; Attention; Sleep
PubMed: 37045455
DOI: 10.17712/nsj.2023.2.20220108 -
Fertility and Sterility Jul 2023To date, recurrent implantation failure (RIF) has no clear definition and no clearly identified impaired function. Hence, the term RIF is currently used somewhat... (Review)
Review
IMPORTANCE
To date, recurrent implantation failure (RIF) has no clear definition and no clearly identified impaired function. Hence, the term RIF is currently used somewhat haphazardly, on the basis of clinicians' judgment.
OBJECTIVE
International experts in reproductive medicine met on July 1, 2022, in Lugano, Switzerland, to review the different facets of RIF and define the diagnosis and its appropriate management.
EVIDENCE REVIEW
A systematic review without meta-analysis of studies published in English from January 2015 to May 2022.
FINDINGS
Data indicated that RIF has been largely overevaluated, overdiagnosed, and overtreated without sufficient critical assessment of its true nature. Our analyses show that true RIF is extremely uncommon-occurring in <5% of couples with infertility-and that reassurance and continued conventional therapies are warranted in most cases of assisted reproductive technology (ART) failure. Although the true biologic determinants of RIF may exist in a small subset of people with infertility, they elude the currently available tools for assessment. Without identification of the true underlying etiology(ies), it is reasonable not to assign this diagnosis to a patient until she has failed at least 3 euploid blastocyst transfers (or the equivalent number of unscreened embryo transfers, adjusted to the patient's age and corresponding euploidy rate). In addition, other factors should be ruled out that may contribute to her reduced odds of sustained implantation. In such cases, implantation failure should not be the only issue considered in case of ART failure because this may result from multiple other factors that are not necessarily repetitive or persistent. In reality, RIF impacting the probability of further ART success is a very rare occurrence.
CONCLUSION
True RIF is extremely uncommon, occurring in <5% of couples with infertility. Reassurance and continued conventional therapies are warranted in most cases. It would seem reasonable not to assign this diagnosis to a patient until she has failed at least 3 euploid embryo transfers (or the equivalent number of unscreened embryos, adjusted to her age).
RELEVANCE
Given the number of internationally recognized experts in the field present at the Lugano meeting 2022, our publication constitutes a consensus statement.
Topics: Humans; Female; Embryo Implantation; Embryo Transfer; Infertility; Reproductive Techniques, Assisted; Aneuploidy; Retrospective Studies
PubMed: 36822566
DOI: 10.1016/j.fertnstert.2023.02.014 -
Neurobiology of Learning and Memory Dec 2020The selective norepinephrine (NE) α2A-adrenoceptor (α2A-AR) agonist, guanfacine (Intuniv™), is FDA-approved for treating Attention Deficit Hyperactivity Disorder... (Review)
Review
The selective norepinephrine (NE) α2A-adrenoceptor (α2A-AR) agonist, guanfacine (Intuniv™), is FDA-approved for treating Attention Deficit Hyperactivity Disorder (ADHD) based on research in animals, a translational success story. Guanfacine is also widely used off-label in additional mental disorders that involve impaired functioning of the prefrontal cortex (PFC), including stress-related disorders such as substance abuse, schizotypic cognitive deficits, and traumatic brain injury. The PFC subserves high order cognitive and executive functions including working memory, abstract reasoning, insight and judgment, and top-down control of attention, action and emotion. These abilities arise from PFC microcircuits with extensive recurrent excitation through NMDAR synapses. There is powerful modulation of these synapses, where cAMP-PKA opening of nearby potassium (K) channels can rapidly and dynamically alter synaptic strength to coordinate arousal state with cognitive state, e.g. to take PFC "offline" during uncontrollable stress. A variety of evidence shows that guanfacine acts within the PFC via post-synaptic α2A-AR on dendritic spines to inhibit cAMP-PKA-K channel signaling, thus strengthening network connectivity, enhancing PFC neuronal firing, and improving PFC cognitive functions. Although guanfacine's beneficial effects are present in rodent, they are especially evident in primates, where the PFC greatly expands and differentiates. In addition to therapeutic actions in PFC, stress-related disorders may also benefit from additional α2-AR actions, such as weakening plasticity in the amygdala, reducing NE release, and anti-inflammatory actions by deactivating microglia. Altogether, these NE α2-AR actions optimize top-down control by PFC networks, which may explain guanfacine's benefits in a variety of mental disorders.
Topics: Adrenergic alpha-2 Receptor Agonists; Animals; Attention Deficit Disorder with Hyperactivity; Cognition; Cognition Disorders; Guanfacine; Humans; Macaca mulatta; Memory, Short-Term; Mice; Nerve Net; Neurons; Prefrontal Cortex; Rats; Synapses
PubMed: 33075480
DOI: 10.1016/j.nlm.2020.107327 -
The International Journal of Angiology... Dec 2022There is a high prevalence of systemic arterial hypertension in the elderly; 70% of adults >65 years have this disease. A key mechanism in the development of...
There is a high prevalence of systemic arterial hypertension in the elderly; 70% of adults >65 years have this disease. A key mechanism in the development of hypertension in the elderly is increased arterial stiffness. This accounts for the increase in systolic blood pressure and pulse pressure and fall in diastolic blood pressure (isolated systolic hypertension) that are commonly seen in the elderly, compared with younger persons. The diagnosis of hypertension is made on the basis of in-office blood pressure measurements together with ambulatory and home blood pressure recordings. Lifestyle changes are the cornerstone of management of hypertension. Comprehensive guidelines regarding blood pressure threshold at which to start pharmacotherapy as well as target blood pressure levels have been issued by both European and American professional bodies. In recent years, there has been considerable interest in intensive lowering of blood pressure in older patients with hypertension. Several large, randomized controlled trials have suggested that a strategy of aiming for a target systolic blood pressure of <120 mm Hg (intensive treatment) rather than a target of <140 mm Hg (standard treatment) results in significant reduction in the incidence of adverse cardiovascular events and total mortality. A systolic blood pressure treatment of <130 mm Hg should be considered favorably in non-institutionalized, ambulatory, free living older patients. In contrast, in the older patient with a high burden of comorbidities and limited life expectancy, an individualized team-based approach, based on clinical judgment and patient preference should be adopted. An increasing body of evidence for older adults with hypertension suggests that intensive blood pressure lowering may prevent or at least partially prevent cognitive decline.
PubMed: 36588864
DOI: 10.1055/s-0042-1759486