Sodium and mineralocorticoids in normal pregnancy

For many years clinicians have speculated that abnormal sodium metabolism plays an important role in the pathogenesis of hypertension. This consideration probably has been most evident in obstetrical practices directed toward preventing hypertensive disorders of pregnancy. It was commonly assumed that normal gestation was associated with sodium-retaining tendencies, which were thought to be causally related to the development of preeclampsia. Accordingly, pregnant women customarily were treated as though threatened by excessive sodium retention; dietary salt restriction and diuretics were prescribed routinely as precautionary measures.In view of this concern, it is quite understandable that the discovery of aldosterone and the recognition of its causal relationship to hypertension in Conn's syndrome quickly led early investigators to study the possible pathogenic role of this potent mineralocorticoid in the hypertensive disorders of pregnancy. Initial reports suggesting that aldosterone levels were higher in preeclamptic than in nonpregnant women generated considerable excitement, which quickly was tempered by the observation that aldosterone secretion was increased to an even greater extent in normal gravidas [1]. Since then, results of numerous studies have provided confirmation that aldosterone levels are markedly elevated in normal gravidas compared with nonpregnant women on similar salt intakes [2, 3]. More recently, it has been shown that secretion of another potent mineralocorticoid, desoxycorticosterone, also is increased substantially during normal pregnancy [4, 5]. Nonetheless, normal gravidas do not demonstrate clinical evidence of mineralocorticoid excess, and the blood pressure falls below pregnancy values during the first two trimesters.Although the regulation of aldosterone secretion in pregnancy has been studied extensively, the physiologic significance of the markedly increased secretion of aldosterone remains controversial. There is considerable evidence that normal pregnancy results in a tendency towards a reduced effective blood volume, despite the high levels not only of aldosterone and desoxycorticosterone, but also of estrogens, which have sodium-retaining effects in man. Thus, some propose that the enhanced secretion of aldosterone is a compensatory response required to maintain normal volume homeostasis [6]. Others argue that the augmented extracellular and intravascular fluid volumes measured in normal pregnancy, as well as the accompanying rise in cardiac output and in the GFR, are inconsistent with functional hypovolemia, and suggest that these changes more likely reflect sodium retention induced by aldosterone hypersecretion [7].Questions regarding the role of increased aldosterone in pregnancy, whether it is associated with a tendency to lose or to retain sodium, not only have a bearing upon routine management of pregnant women, but are also of fundamental importance to our understanding of the pathophysiology of the gestational hypertensive disorders. In attempting to resolve these issues, it would seem appropriate to review studies that might help to define the role of increased mineralocorticoids in normal pregnancy

Postoperative complications of combined phacoemulsification and pars plana vitrectomy in diabetic retinopathy patients

PurposeTo compare intra- and postoperative complications in combined phacoemulsification and pars plana vitrectomy surgeries performed in patients with non-proliferative diabetic retinopathy (NPDR) vs. proliferative diabetic retinopathy (PDR). MethodsRetrospective, case series of patients with diabetic retinopathy who underwent combined phacovitrectomy surgery between 2008 and 2017. We compared intraoperative complications including posterior capsular rupture and retinal tear, and postoperative complications including corneal edema, macular edema (ME), epiretinal membrane (ERM), neovascular glaucoma and persistent inflammation. ResultsA total of 104 eyes of 104 patients were included in this study. Twenty-four eyes (23.1%) were categorized as NPDR and 80 eyes (76.9%) as PDR. The most common indications for surgery in the NPDR group were ERM (67%) and rhegmatogenous retinal detachment (12.5%), while in the PDR group, indications were vitreous hemorrhage (56%) and tractional retinal detachment (19%). The most common intraoperative complication was retinal tear (8% in NPDR and 19% in PDR, p = 0.195) and postoperative complication was ME (29% in NPDR and 26% in PDR, p = 0.778). There were no statistically significant differences in intra- and postoperative complication rates between the NPDR and PDR groups, even after adjusting for confounders; patient age at surgery and indication for surgery. ConclusionAfter combined phacovitrectomy in NPDR and PDR patients, new-onset ME was found in about a quarter of eyes in both groups. Intraoperative anti-VEGF or steroid administration, and intense postoperative anti-inflammatory medication and follow-up should be regarded after phacovitrectomy regardless of the DR level.Peer reviewe

Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer\u27s disease: Research outline and call for collaboration.

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer\u27s disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer\u27s Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will be evaluated, in addition to direct microbial culture and metabolomic techniques. The goal is to provide a roadmap for detecting infectious agents in patients with mild cognitive impairment or AD. Positive findings would then prompt tailoring of antimicrobial treatments that might attenuate or remit mounting clinical deficits in a subset of patients

What is an intelligent building? Analysis of recent interpretations from an international perspective

In recent years, the notion of intelligent buildings (IBs) has become increasingly popular due to their potentials for deploying design initiatives and emerging technologies towards maximized occupants’ comfort and well-being with sustainable design. However, various definitions, interpretations, and implications regarding the essence of IBs exist. Various key performance indicators of IBs have been proposed in different contexts. This study explores the notion of IBs and presents an analysis of their main constituents. Through a comparison of these constituents in different contexts, this study aims to extract the common features of IBs leading to an evolved definition which could be useful as a reference framework for design, evaluation, and development of future IBs. Findings also scrutinize the long run benefits of IBs, while demonstrating the constraints and challenges of the current international interpretations

The ARCH Projects: design and rationale (IAASSG 001)

OBJECTIVE A number of factors limit the effectiveness of current aortic arch studies in assessing optimal neuroprotection strategies, including insufficient patient numbers, heterogenous definitions of clinical variables, multiple technical strategies, inadequate reporting of surgical outcomes and a lack of collaborative effort. We have formed an international coalition of centres to provide more robust investigations into this topic. METHODS High-volume aortic arch centres were identified from the literature and contacted for recruitment. A Research Steering Committee of expert arch surgeons was convened to oversee the direction of the research. RESULTS The International Aortic Arch Surgery Study Group has been formed by 41 arch surgeons from 10 countries to better evaluate patient outcomes after aortic arch surgery. Several projects, including the establishment of a multi-institutional retrospective database, randomized controlled trials and a prospectively collected database, are currently underway. CONCLUSIONS Such a collaborative effort will herald a turning point in the surgical management of aortic arch pathologies and will provide better powered analyses to assess the impact of varying surgical techniques on mortality and morbidity, identify predictors for neurological and operative risk, formulate and validate risk predictor models and review long-term survival outcomes and quality-of-life after arch surger

Ethnic differences in DNA methyltransferases expression in patients with systemic lupus erythematosus

Systemic lupus erythematous (SLE) is a systemic autoimmune inflammatory disease with both genetic and epigenetic etiologies. Evidence suggests that deregulation of specific genes through epigenetic mechanisms may be a contributing factor to SLE pathology. There is increasing evidence that DNA methyltransferase activity may be involved. This study demonstrated modulation in expression of DNA methyltransferases (DNMTs) according to ethnicity in patients diagnosed with SLE. Furthermore, differential expression in one of the DNMTs was found in a subset of lupus patients on dehydroepiandrosterone (DHEA) therapy. Real-time PCR analyses of DNMT1, DNMT3A and DNMT3B in peripheral blood mononuclear cells from a cohort of African American and European American lupus and non-lupus women were conducted. Also, global DNA methylation was assessed using the MethylFlash.sup.TM methylated quantification colorimetric assay. These findings suggest that epigenetic changes may play a critical role in the manifestations of the disease observed among ethnic groups, particularly African American women who often have a higher incidence of lupus. DHEA therapy effects on DNMT3A expression in AA women warrant further investigation in a larger population