Uncontrolled and masked uncontrolled blood pressure in treated pregnant women with chronic hypertension and risk for preeclampsia/eclampsia.

To analyze the relationship between the level of BP achieved with treatment and the risk for development of preeclampsia/eclampsia (PE), we conducted a historical cohort study on 149 consecutive pregnant women with treated chronic hypertension, evaluated between January 1, 2016, and November 31, 2022. According to office BP readings and ambulatory blood pressure monitoring (ABPM) performed after 20 weeks of gestation, the cohort was classified in controlled hypertension, white-coat uncontrolled hypertension, masked uncontrolled hypertension and sustained hypertension. Risks for the development of PE were estimated using logistic regression. One hundred and twenty-four pregnant women with a control BP evaluation were included in this analysis. The rates of PE were 19.4%, 27.3%, 44.8% and 47.1% for controlled, white-coat uncontrolled, masked uncontrolled and sustained uncontrolled hypertension, respectively. Compared with women with controlled hypertension, the relative risk for PE increased markedly in women with sustained uncontrolled (OR 3.69, 95% CI, 1.19-11.45) and masked uncontrolled (OR 3.38, 95% CI, 1.30-11.45) hypertension, but not in those with white-coat uncontrolled (OR 1.56 95% CI, 0.36-6.70); adjustment for covariates did not modify the results. Each mmHg higher of systolic and diastolic daytime ABPM increased the relative risk for PE ~4% and ~5%, respectively. Each mmHg higher of systolic and diastolic nocturnal BP increased the risk ~5% and ~6%, respectively. When these risks were adjusted for ABPM values in opposite periods of the day, only nocturnal ABPM remained as a significant predictor. In conclusion, masked uncontrolled hypertension implies a substantial risk for the development of PE, comparable to those of sustained uncontrolled. The presence of nocturnal hypertension seems important.

Hypertension arising after 20 weeks of gestation: gestational hypertension or masked chronic hypertension?

The objectives of this study were 1-to evaluate the prevalence of masked chronic hypertension in pregnant women classified as gestational hypertension 2-to compare the risks of developing preeclampsia in true gestational hypertension vs those women classified as having gestational hypertension but who had had masked hypertension in the first half of pregnancy. We conducted a cohort study in consecutive high-risk pregnancies who were evaluated before 20 weeks of gestation. Women who developed gestational hypertension (normotension in the office before 20 weeks of gestation and office BP ≥ 140/90 mmHg and/or antihypertensive treatment in the second half of gestation) were divided, according to an ABPM performed before 20 weeks of pregnancy, in two subgroups: subgroup 1-if their ABPM was normal, and subgroup 2-if they had masked chronic hypertension. Risks for preeclampsia (PE) were estimated and compared with normotensive women. Before 20 weeks of gestation, 227 women were evaluated (age 32 ± 6 years, median gestation age 15 weeks); 67 had chronic hypertension (29.5%). Of the remaining 160, 39 developed gestational hypertension (16 in subgroup 1 and 23 insubgroup 2. Compared with normotensive pregnant women, subgroup 1 of women with gestational hypertension did not increase the risk of developing PE (OR = 0.76, 95% CI = 0.16-6.65). Conversely, subgroup 2 of gestational hypertension increased the risk of PE more than 4 times (0R = 4.47 CI = 1.16-12.63). Risk estimation did not change substantially after the adjustment for multiple possible confounders. In conclusion, the59% of women initially diagnosed as gestational hypertensive according to current recommendations had masked chronic hypertension and a very high risk of developing PE.

Zinc oxide-induced changes to sunscreen ingredient efficacy and toxicity under UV irradiation.

Sunscreen safety and efficacy is generally evaluated based upon the properties of the individual chemicals in a formulation. However, the photostability of sunscreens has been shown to be highly dependent on the mixture of chemicals present. To better understand how sunscreen formulation influences stability, and to establish a foundation for probing the influence of zinc oxide additives, we formulated five different small-molecule based ultraviolet-filter (UV-filter) mixtures with a Sun Protection Factor (SPF) of 15. These mixtures contained active ingredients approved in either the United States or European Union and were designed to represent formulations of actual products on the market. We evaluated the photostability and toxicity of these mixtures in the absence and presence of zinc oxide after UV exposure for two hours. Changes in UV absorbance were minimal for all five small-molecule-based mixtures without zinc oxide. The presence of either micro- or nano-sized zinc oxide caused significant small-molecule photodegradation and the degraded mixtures exhibited higher levels of toxicity in embryonic zebrafish assays. This study suggests that caution must be taken when formulating sunscreens containing both zinc oxide and small-molecule UV-filters to avoid unintended consequences during use.

Nocturnal hypertension and risk of developing early-onset preeclampsia in high-risk pregnancies.

To test the hypothesis that nocturnal hypertension identifies risk for early-onset preeclampsia/eclampsia (PE), we conducted an historical cohort study of consecutive high-risk pregnancies between 1st January 2016 and 31st March 2020. Office blood pressure (BP) measurements and ambulatory blood pressure monitoring (ABPM) were performed. The cohort was divided into patients without PE or with early- or late-onset PE (<34 and ≥34 weeks of gestation, respectively). The relative risks of office and ABPM hypertension for the development of late- or early-onset PE were estimated with multinomial logistic regression using no PE as a reference category. Four hundred and seventy-seven women (mean age 30 ± 7 years, with 23 ± 7 weeks of gestation at the time of the BP measurements) were analyzed; 113 (23.7%) developed PE, 69 (14.5%) developed late-onset PE, 44 (9.2%) developed early-onset PE. Office and ambulatory BP increased between the groups, and women who developed early-onset PE had significantly higher office and ambulatory BP values than those with late-onset PE or without PE. Hypertension prevalence increased across groups, with the highest values in early-onset PE. Nocturnal hypertension was the most prevalent finding and was highly prevalent in women who developed early-onset PE (88.6%); only 1.6% of women without nocturnal hypertension developed early-onset PE. Additionally, nocturnal hypertension was a stronger predictor for early-onset PE than for late-onset PE (adjusted OR, 5.26 95%CI 1.67-16.60) vs. 2.06, 95%CI 1.26-4.55, respectively). In conclusion, nocturnal hypertension was the most frequent BP abnormality and a significant predictor of early-onset PE in high-risk pregnancies.

Office blood pressure values and the necessity of out-of-office measurements in high-risk pregnancies.

OBJECTIVES: To determine if there is an office blood pressure (BP) value below which out-of-office measurements are unnecessary in high-risk pregnant women. METHODS: We conducted a prospective cohort study in women in the second half of high-risk pregnancies. Office BP measurements and ambulatory blood pressure monitoring (ABPM) was performed. The cohort was divided according to quartiles of office BP and in normotension, white-coat hypertension, masked hypertension and sustained hypertension. The risks for preeclampsia/eclampsia for each category were estimated. RESULTS: Three hundred seventy-three women (30 ±â€Š7 years with 32 ±â€Š4 weeks of gestation) were included; 69 women (18.5%) developed preeclampsia/eclampsia. Risk for preeclampsia/eclampsia increased in a stepwise manner through quartiles of systolic office BP (8.8, 13.4, 19.6 and 32.3%, P < 0.001) and diastolic office BP (6.5, 13.7, 19.6 and 34,4%, P < 0.001). OR increased significantly through quartiles of systolic (P = 0.004) and diastolic (P < 0.001) office BP; the significance becomes evident between the second and third quartile, the cut-off point between these was 125/76 mmHg. Prevalence of white-coat and masked hypertension were 3.8 and 24.7%, respectively. Using ABPM, 14/61 office hypertensive women were reclassified as white-coat hypertension but 92/312 normotensive women as masked hypertension. OR for preeclampsia/eclampsia increased significantly in women with masked hypertension. Absolute risk for preeclampsia/eclampsia in women with office BP less than 125/75 mmHg was similar than that in women with normal ABPM, 7.2 and 7.1%, respectively. CONCLUSION: Masked hypertension was a prevalent and high-risk condition. Office BP at least 125/75 mmHg in the second half of gestation seems appropriate to indicate out-of-office measurements in high-risk pregnancies.

Nocturnal hypertension in high-risk mid-pregnancies predict the development of preeclampsia/eclampsia.

OBJECTIVE: The aim of this study was to test if hypertension detected by ambulatory blood pressure monitoring (ABPM) performed at mid-pregnancy, is a useful predictor for preeclampsia/eclampsia (PEEC). METHODS: The study was performed in women coursing high-risk mid-pregnancies. Office blood pressure (BP) was estimated as the mean of three values, taken by a specialized nurse after a 15-min interview, and office hypertension defined as at least 140/90 mmHg. Immediately after, an ABPM was started. Diurnal hypertension was defined as ABPM at least 135/85 mmHg during daily activities, nocturnal hypertension as ABPM at least 120/70 mmHg during night rest. The adjusted risk of PEEC was estimated using logistic regression. RESULTS: Eighty-seven women (mean age 31 ±â€Š7 years) with 23 ±â€Š2 weeks of pregnancy were included. The prevalence of office and ABPM hypertension was 13.8 and 40.2%, respectively. The concordance between both hypertension diagnosis was low (κ = 0.170, P = 0.044). Nocturnal hypertension (35.6%) was more frequent than diurnal hypertension (26.4%). Nocturnal hypertension markedly increased the relative risk of PEEC (OR 5.32, 95% CI 1.48-19.10). The risk of PEEC attributed to diurnal hypertension did not reach statistical significance; and when both, diurnal and nocturnal hypertension were included in the same model, only the second one was a significant predictor (P = 0.012). The relative risk associated with nocturnal hypertension increased for women not taking acetylsalicylic acid (ASA); (OR 11.40, 95% CI 2.35-55.25). CONCLUSION: Nocturnal hypertension at high-risk mid-pregnancy is a frequent condition and a strong predictor for PEEC; the risk doubled for women not taking ASA.

Tandem malonate-based glucosides (TMGs) for membrane protein structural studies.

High-resolution membrane protein structures are essential for understanding the molecular basis of diverse biological events and important in drug development. Detergents are usually used to extract these bio-macromolecules from the membranes and maintain them in a soluble and stable state in aqueous solutions for downstream characterization. However, many eukaryotic membrane proteins solubilized in conventional detergents tend to undergo structural degradation, necessitating the development of new amphiphilic agents with enhanced properties. In this study, we designed and synthesized a novel class of glucoside amphiphiles, designated tandem malonate-based glucosides (TMGs). A few TMG agents proved effective at both stabilizing a range of membrane proteins and extracting proteins from the membrane environment. These favourable characteristics, along with synthetic convenience, indicate that these agents have potential in membrane protein research.

Resorcinarene-Based Facial Glycosides: Implication of Detergent Flexibility on Membrane-Protein Stability.

As a membrane-mimetic system, detergent micelles are popularly used to extract membrane proteins from lipid environments and to maintain their solubility and stability in an aqueous medium. However, many membrane proteins encapsulated in conventional detergents tend to undergo structural degradation during extraction and purification, thus necessitating the development of new agents with enhanced properties. In the current study, two classes of new amphiphiles are introduced, resorcinarene-based glucoside and maltoside amphiphiles (designated RGAs and RMAs, respectively), for which the alkyl chains are facially segregated from the carbohydrate head groups. Of these facial amphiphiles, two RGAs (RGA-C11 and RGA-C13) conferred markedly enhanced stability to four tested membrane proteins compared to a gold-standard conventional detergent. The relatively high water solubility and micellar stability of the RGAs compared to the RMAs, along with their generally favourable behaviours for membrane protein stabilisation described here, are likely to be, at least in part, a result of the high conformational flexibility of these glucosides. This study suggests that flexibility could be an important factor in determining the suitability of new detergents for membrane protein studies.

Dendronic trimaltoside amphiphiles (DTMs) for membrane protein study.

The critical contribution of membrane proteins in normal cellular function makes their detailed structure and functional analysis essential. Detergents, amphipathic agents with the ability to maintain membrane proteins in a soluble state in aqueous solution, have key roles in membrane protein manipulation. Structural and functional stability is a prerequisite for biophysical characterization. However, many conventional detergents are limited in their ability to stabilize membrane proteins, making development of novel detergents for membrane protein manipulation an important research area. The architecture of a detergent hydrophobic group, that directly interacts with the hydrophobic segment of membrane proteins, is a key factor in dictating their efficacy for both membrane protein solubilization and stabilization. In the current study, we developed two sets of maltoside-based detergents with four alkyl chains by introducing dendronic hydrophobic groups connected to a trimaltoside head group, designated dendronic trimaltosides (DTMs). Representative DTMs conferred enhanced stabilization to multiple membrane proteins compared to the benchmark conventional detergent, DDM. One DTM (i.e., DTM-A6) clearly outperformed DDM in stabilizing human ß2 adrenergic receptor (ß2AR) and its complex with Gs protein. A further evaluation of this DTM led to a clear visualization of ß2AR-Gs complex via electron microscopic analysis. Thus, the current study not only provides novel detergent tools useful for membrane protein study, but also suggests that the dendronic architecture has a role in governing detergent efficacy for membrane protein stabilization.

Significance of masked and nocturnal hypertension in normotensive women coursing a high-risk pregnancy.

OBJECTIVE: The aim was to evaluate the prevalence of nocturnal and masked hypertension and the prognostic values of these blood pressure (BP) abnormalities in normotensive women coursing a high-risk pregnancy. METHODS: The study was performed in pregnant women with 20 or more weeks of gestation coursing a high-risk pregnancy, sent to a specialized hypertension department to perform a prospective defined protocol of BP evaluation. Women with office BP at least 140/90 mmHg were excluded. An ambulatory monitoring of BP was performed to identify masked and nocturnal hypertension (defined according to the current guidelines). The adjusted risk for development of preeclampsia/eclampsia (PEEC) was estimated using logistic regression. The ability of SBP and DBP to identify risk of PEEC was estimated using area under the receiver-operating characteristic curves. RESULTS: Eighty-seven women (29 ±â€Š7 years old, 30 ±â€Š5 weeks of pregnancy) were included in this analysis. The prevalence of masked hypertension was 33.3%. Nocturnal hypertension was found in 42.5% of the women. Remarkably, 27.0% of the women with nocturnal hypertension had normal 24-h values according to ambulatory BP monitoring. Twenty-two patients developed PEEC; adjusted relative risks increased with the presence of nocturnal (odds ratio = 4.72, 95% confidence interval 1.25-19.43, P = 0.023) or masked hypertension (odds ratio = 7.81, 95% confidence interval 2.6-22.86, P = 0.001). Nocturnal SBP and DBP had the highest abilities to predict PEEC (area under the curve = 0.77 and 0.80, respectively). CONCLUSION: Masked and nocturnal hypertension are frequent findings in normotensive women coursing a high-risk pregnancy, and their presence implies an increased risk to develop PEEC.