bluuebunny/crossref_metadata_2025 huggingface dataset:
X-linked inhibitor of apoptosis protein inhibition induces apoptosis and enhances chemotherapy sensitivity in human prostate cancer cells
Authors: Amantana Adams , London Carla A. , Iversen Patrick L. , Devi Gayathri R.
Published: June 2022

Androgen-insensitive prostate cancer cells are highly resistant to several chemotherapeutic drugs and are characterized by the appearance of apoptosis-resistant cells. In this study, we identified the critical role of X-linked inhibitor of apoptosis protein (XIAP), a potent antiapoptotic factor, in conferring chemotherapy resistance in an androgen-insensitive DU145 human prostate cancer cell line. Results reveal that DU145 cells were highly resistant to cisplatin, but this resistance was overridden when the cells were treated for a prolonged time (>96 hours) with cisplatin (IC50 = 27.5 to 35.5 μmol/L). A decrease in levels of XIAP and Akt/phospho-Akt and an increase in caspase-3 activity were identified to be key factors in cisplatin sensitivity (40% to 55% decrease in cell viability) at later time points. In contrast, tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) treatment caused a 40% to 50% decrease in cell viability within 6 hours (IC50 = 135 to 145 ng/mL). However, increasing concentrations or prolonged treatment with TRAIL did not change drug potency. A significant increase in caspase-3 activity was observed with TRAIL treatment with no apparent change in XIAP levels. Specific inhibition of XIAP expression using an antisense XIAP phosphorodiamidate morpholino oligomer induced apoptosis and increased caspase-3 activity. Combination of cisplatin with XIAP antisense potentiated cisplatin sensitivity by decreasing the IC50 from >200 μmol/L with cisplatin alone to 9 to 20 μmol/L and decreasing incubation time required for activity from 96 to 24 hours. Similarly, TRAIL in combination with XIAP antisense phosphorodiamidate morpholino oligomer enhanced TRAIL potency by 12- to 13-fold. In conclusion, abrogation of XIAP expression is essential for therapeutic apoptosis and enhanced chemotherapy sensitization in androgen-refractory prostate cancer cells.
Epigallocatechin-3-gallate induces apoptosis in estrogen receptor–negative human breast carcinoma cells via modulation in protein expression of p53 and Bax and caspase-3 activation
Authors: Roy Anshu M. , Baliga Manjeshwar S. , Katiyar Santosh K.
Published: June 2022

Epigallocatechin-3-gallate (EGCG) has been shown to have anticarcinogenic effects in in vitro and in vivo models, and this effect is mediated at least in part by its ability to induce apoptosis in cancer cells without affecting normal cells. It has been recognized that estrogen receptor (ER)–dependent breast cancers generally have a better prognosis and are often responsive to antiestrogen therapy; however, ER-independent breast cancers are more aggressive and unresponsive to antiestrogens. Using the MDA-MB-468 human breast cancer cell line as an in vitro model of ER-negative breast cancers, we found that treatment of EGCG resulted in dose-dependent (5-80 μg/mL) and time-dependent (24-72 hours) inhibition of cellular proliferation (15-100%) and cell viability (3-78%) in MDA-MB-468 cells. Decrease in cell viability was associated with the induction of apoptosis (18-66%) which was analyzed by DNA ladder assay, fluorescence staining, and flow cytometry. Induction of apoptosis by EGCG could be corroborated to the increased expression of tumor suppressor protein p53 and its phosphorylation at Ser 15 residue. EGCG decreased the expression of antiapoptotic protein Bcl-2 but increased proapoptotic protein Bax in these cells. The increased ratio of Bax/Bcl-2 proteins after EGCG treatment may have resulted in increased release of cytochrome c from mitochondria into cytosols, increased expression of Apaf-1, and activation of caspase-3 and poly(ADP-ribose) polymerase, which may lead to apoptosis in MDA-MB-468 cells. Together, the results of this study provide evidence that EGCG possesses anticarcinogenic effect against ER-negative breast cancer cells and thus provide the molecular basis for the future development of EGCG as a novel and pharmacologically safe chemopreventive agent for breast cancer prevention.
Inhibition of ABCB1 (MDR1) and ABCB4 (MDR3) expression by small interfering RNA and reversal of paclitaxel resistance in human ovarian cancer cells
Authors: Duan Zhenfeng , Brakora Katherine A. , Seiden Michael V.
Published: June 2022

Ovarian cancer is currently the most lethal gynecologic malignancy in developed countries, and paclitaxel is a cornerstone in the treatment of this malignancy. Unfortunately, the efficacy of paclitaxel is limited by the development of drug resistance. Clinical paclitaxel resistance is often associated with ABCB1 (MDR1) overexpression, and in vitro paclitaxel resistance typically demonstrates overexpression of the ABCB1 gene. In this study, we demonstrate that paclitaxel-resistant cell lines overexpress both ABCB1 and ABCB4 (MDR3). To evaluate the role of these transporters in paclitaxel-resistant ovarian cancer cells, small interference RNAs (siRNAs) were used to target ABCB1 and ABCB4 RNA in the paclitaxel-resistant SKOV-3TR and OVCAR8TR ovarian cancer cell lines. Treatment of these lines with either chemically synthesized siRNAs or transfection with specific vectors that express targeted siRNAs demonstrated decreased mRNA and protein levels of ABCB1 or ABCB4. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays of siRNA-treated cells demonstrated 7- to 12.4-fold reduction of paclitaxel resistance in the lines treated with the synthesized siRNA of ABCB1 and 4.7- to 7.3-fold reduction of paclitaxel resistance in the cell lines transfected with siRNA of ABCB1 expressing vectors. ABCB4 siRNA-treated cell lines showed minor reduction in paclitaxel resistance. These results indicate that siRNA targeted to ABCB1 can sensitize paclitaxel-resistant ovarian cancer cells in vitro and suggest that siRNA treatment may represent a new approach for the treatment of ABCB1-mediated drug resistance.
Quantitative analysis of p53-targeted gene expression and visualization of p53 transcriptional activity following intratumoral administration of adenoviral p53 in vivo
Authors: Ohtani Shoichiro , Kagawa Shunsuke , Tango Yasuhisa , Umeoka Tatsuo , Tokunaga Naoyuki , Tsunemitsu Yousuke , Roth Jack A. , Taya Yoichi , Tanaka Noriaki , Fujiwara Toshiyoshi
Published: June 2022

To analyze the mechanism of the antitumor effect of an adenoviral vector expressing the p53 tumor suppressor (Ad-p53) in vivo, we quantitatively assessed p53-targeted gene expression and visualized transcriptional activity of p53 in tumors in nude mice treated with Ad-p53. Human lung cancer (H1299) xenografts established in nude mice were treated by intratumoral administration of Ad-p53. The levels of expression of exogenous p53 and p53-targeted genes p21, MDM2, Noxa, and p53AIP1 were quantified by real-time reverse transcription-PCR (RT-PCR) and induction of apoptosis was observed histochemically on days 1–3, 7, and 14 after treatment. Expression of mRNA of exogenous p53 and p53-targeted genes (except p53AIP1) was at its maximum 1 day after Ad-p53 treatment and then decreased rapidly; apoptosis was evident in situ 2–3 days after treatment. We developed a noninvasive and simple method for monitoring the transcriptional activity of exogenous p53 following intratumoral administration of Ad-p53 in nude mice. We established H1299 cells that express the green fluorescent protein (GFP) reporter gene under the control of p53-responsive p21 promoter (i.e., the p53R-GFP reporter system). Xenografts of these cells in nude mice were treated by intratumoral administration of Ad-p53, and the transcriptional activity of exogenous p53 could be visualized as intratumoral GFP expression in real time by 3-CCD camera. Expression of GFP was maximal 3 days after treatment and decreased remarkably by 7 days after treatment. We demonstrated that Ad-p53 treatment rapidly induced p53-targeted genes and apoptosis in tumors and succeeded in visualizing p53 transcriptional activity in vivo. We also found that Ad-p53 infection induced phosphorylation of p53 at Ser46 in p53-sensitive H1299 cells in vitro but not in p53-resistant H226Br cells, suggesting that phosphorylation of Ser46 is involved in p53-dependent apoptosis. Our data indicate that quantitative analysis of p53-targeted gene expression by real-time quantitative RT-PCR and visualization of p53 transcriptional activity in fresh xenografts by using the p53R-GFP reporter system may be useful in assessing the mechanisms of the antitumor effects of Ad-p53 and novel therapeutic approaches.
Abstract A04: Geographic and socioeconomic disparities in exposure to carcinogenic air toxics in St. Louis, Missouri
Authors: Ekenga Christine , Yeung Cheuk Yui , Oka Masayoshi
Published: June 2022

Background: Residential segregation has been associated with exposure to hazardous air pollutants in the United States. However, few studies have utilized spatial approaches for measuring segregation at the neighborhood level. We used spatial epidemiologic methods to examine associations between neighborhood characteristics and exposure to carcinogenic air toxics in St. Louis, Missouri.

Methods: We obtained cancer risk data from the United States Environmental Protection Agency’s 2011 National Air Toxics Assessment and used a geographic information system to identify air toxic hotspots in the St. Louis region. Census tract-level data from 2010 to 2014 from the American Community Survey were used to develop isolation measures that capture spatial patterns of residential segregation within the St. Louis region. In the current analysis, we developed a black isolation measure and a poverty isolation measure as indicators of spatial separation from other racial/ethnic populations and from nonpoverty populations, respectively. Relative risks were used to evaluate relationships between neighborhood characteristics and air toxic hotspots.

Results: The distribution of carcinogenic air toxics varied throughout the St. Louis region and clustered near interstate highways. Neighborhood-level measures of the racial and economic isolation were associated with air toxic hotspots. Census tracts in the highest quartile of black isolation were eight times more likely to be located in an air toxic hotspot than tracts in the lowest quartile (RR = 8.1, 95% Confidence Interval = 5.9-12.1). Census tracts in the highest quartile of economic isolation were five times more likely to be located in an air toxic hotspot than tracts in the lowest quartile (RR = 5.0 95% Confidence Interval = 3.3-9.4).

Conclusions: There are geographic and socioeconomic disparities in exposure to carcinogenic air toxics in the St. Louis region. The identification of local air toxic hotspots can inform public health efforts to eliminate disparities in exposure to air toxics.

Citation Format: Christine Ekenga, Cheuk Yui Yeung, Masayoshi Oka. Geographic and socioeconomic disparities in exposure to carcinogenic air toxics in St. Louis, Missouri [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A04.
Abstract IA06: Mutational signatures of environmental carcinogens in mouse and human cancers
Authors: Balmain Allan
Published: June 2022

Mouse models of cancer have been instrumental in the development of our understanding of the processes that drive multistage carcinogenesis from the initiation stage to metastasis. Tumors induced in mice by exposure to carcinogenic chemicals replicate many of the biologic and genetic features of multistage cancer in human populations. Skin and lung tumors initiated by chemical mutagens generally have carcinogen-specific mutations in Hras and Kras, respectively. However, these mutation patterns are seen not only in the target Ras genes, but also can be detected genome-wide as “mutational signatures” that are diagnostic for each carcinogen. We have extended this concept to search for new mutation signatures in tumors induced in mice by a wide range of physical (high- and low-energy radiation) and chemical carcinogens to which humans are exposed. In collaboration with the National Toxicology Program and the Sanger Institute (UK), we have carried out whole-genome and/or -exome sequencing of several hundred mouse tumors induced by a wide range of known or suspected human carcinogens. Our data identify highly variable tumor genomic imprints of carcinogen exposure as reflected in the relative numbers and types of structural variants (copy number changes, translocations, complex rearrangements) and point mutational signatures found in tumors induced by different agents. Analysis of these mutation patterns may illuminate the specific mechanisms by which these agents act to initiate or promote cancer development and provide novel information for use in risk assessment.

Citation Format: Allan Balmain. Mutational signatures of environmental carcinogens in mouse and human cancers [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr IA06.
Abstract PR07: Latent class analysis of multipollutant exposure
Authors: Larsen Alexandra , Kolpacoff Viktoria , McCormack Kara , Hyslop Terry
Published: June 2022

Recent work suggests that air pollutants, toxic chemicals, and other environmental exposures negatively impact health in a synergistic way. In order to measure and understand this impact, we propose a latent class mixture model of multipollutant exposure. Our model incorporates the joint behavior of individual pollutants that inform overall exposure levels and provides clear measures of multipollutant exposure. We identify low, medium, and high levels of joint exposure to volatile organic compounds (VOC), particulate matter (PM), and heavy metals (HM), and present estimated class-membership for each census tract in the US (>76,000). We use publicly available data from the EPA, including the National Air Toxics Assessment (NATA), measured at the census tract level. Model results indicate that mixtures of 5 levels of VOC, 2 levels of PM, and 4 levels of HM best fit data at the national level. Twelve percent of U.S. census tracts are in the highest levels of all 3 categories of pollutants. While frequently observed in metropolitan areas, rural areas are sometimes detected at the highest levels, as well. Our next focus is to incorporate spatial correlations as well as linkages to our earlier latent model work on socioeconomic status (SES). Taken together, these extensions can then be incorporated into a holistic, exposome modeling framework for estimating disparities in cancer survival.

This abstract is also being presented as Poster A31.

Citation Format: Alexandra Larsen, Viktoria Kolpacoff, Kara McCormack, Terry Hyslop. Latent class analysis of multipollutant exposure [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr PR07.
Specific IgE to Total IgE Ratio Does Not Improve Peanut Diagnostic Accuracy in Adults
Authors: Mustillo Ariana , Paradis Louis , Des Roches Anne , Dubé Normand , Masse Marie-Soleil , Bégin Philippe , Paradis Jean , Graham François
Published: June 2022

Background: Peanut specific IgE (sIgE) can lead to false-positive results. Objective: We aimed to assess whether peanut sIgE to total IgE (tIgE) ratio improves accuracy in predicting clinical reactivity to peanut compared to peanut sIgE alone, which has not been explored in the adult population so far. Method: A retrospective chart review was performed for adults who underwent peanut oral food challenge (OFC) and/or oral immunotherapy (OIT) at the Centre Hospitalier de l’Université de Montréal’s allergy clinic between January 2017 and July 2021. Patients with positive peanut OFC and/or undergoing OIT were considered peanut-allergic. Patients with negative OFC were considered peanut-tolerant. Peanut sIgE to tIgE ratios were calculated and performance characteristics of the sIgE to tIgE ratio were compared to sIgE alone by using receiver operator characteristics curves. Results: Forty-two patients were included (52% male) with a median age of 26 years (range 14–54). Forty-five percent had atopic dermatitis. Median sIgE levels were 2.64 kUA/L (range 0.1–100), median tIgE levels were 154 kUA/L (range 19–3,400), and median sIgE to tIgE ratio was 0.66% (range 0.04–38.3). Twenty-four patients (57%) were classified as peanut-allergic and 18 (43%) as peanut tolerant. The area under the curve for peanut sIgE was 0.921 compared to 0.926 for peanut sIgE/tIgE (p not statistically significant). Conclusions: We found that there was no significant benefit in using peanut sIgE to tIgE ratio over sIgE alone to predict peanut reactivity in an adult population. Larger prospective studies are needed to further confirm these findings.
Twenty-Four-Hour Pulsatile Hemodynamics Predict Brachial Blood Pressure Response to Renal Denervation in the SPYRAL HTN-OFF MED Trial
Authors: Weber Thomas , Wassertheurer Siegfried , Mayer Christopher C. , Hametner Bernhard , Danninger Kathrin , Townsend Raymond R. , Mahfoud Felix , Kario Kazuomi , Fahy Martin , DeBruin Vanessa , Peterson Nicole , Negoita Manuela , Weber Michael A. , Kandzari David E. , Schmieder Roland E. , Tsioufis Konstantinos P. , Binder Ronald K. , Böhm Michael
Published: June 2022

Background:

Renal denervation (RDN) lowers blood pressure (BP), but BP response is variable in individual patients. We investigated whether measures of pulsatile hemodynamics, obtained during 24-hour ambulatory BP monitoring, predict BP drop following RDN.

Methods:

From the randomized, sham-controlled SPYRAL HTN-OFF MED Pivotal trial, we performed a post hoc analysis of BP waveforms from 111 RDN patients and 111 sham controls, obtained with a brachial cuff-based sphygmomanometer. Waveforms were acquired during ambulatory BP monitoring at diastolic BP level and processed with validated ARCSolver algorithms to derive hemodynamic parameters (augmentation index; augmentation pressure; backward and forward wave amplitude; estimated aortic pulse wave velocity). We investigated the relationship between averaged 24-hour values at baseline and the change in 24-hour BP at 3 months in RDN patients, corrected for observed trends in the sham group.

Results:

There was a consistent inverse relationship between baseline augmentation index/augmentation pressure/backward wave amplitude/forward wave amplitude/estimated aortic pulse wave velocity and BP response to RDN: the decrease in 24-hour systolic BP/diastolic BP was 7.8/5.9 (augmentation index), 8.0/6.3 (augmentation pressure), 6.7/5.4 (backward wave amplitude), 5.7/4.7 (forward wave amplitude), and 7.8/5.2 (estimated aortic pulse wave velocity) mm Hg greater for patients below versus above the respective median value (
P
<0.001 for all comparisons, respectively). Taking augmentation index/augmentation pressure/backward wave amplitude/forward wave amplitude/estimated aortic pulse wave velocity into account, a favorable BP response following RDN, defined as a drop in 24-hour systolic blood pressure of ≥5 mm Hg, could be predicted with an area under the curve of 0.70/0.74/0.70/0.65/0.62 (
P
<0.001 for all, respectively).

Conclusions:

These results suggest that pulsatile hemodynamics, obtained during 24-hour ambulatory BP monitoring, may predict BP response to RDN.
The Immune System in Hypertension: a Lost Shaker of Salt 2021 Lewis K. Dahl Memorial Lecture
Authors: Lu Xiaohan , Crowley Steven D.
Published: June 2022

The seminal observations of Dr Lewis Dahl regarding renal mechanisms of hypertension remain highly relevant in light of more recent experiments showing that immune system dysfunction contributes to hypertension pathogenesis. Dr Dahl established that inappropriate salt retention in the kidney plays a central role via Ohm’s Law in permitting blood pressure elevation. Nevertheless, inflammatory cytokines whose expression is induced in the early stages of hypertension can alter renal blood flow and sodium transporter expression and activity to foster renal sodium retention. By elaborating these cytokines and reactive oxygen species, myeloid cells and T lymphocytes can connect systemic inflammatory signals to aberrant kidney functions that allow sustained hypertension. By activating T lymphocytes, antigen-presenting cells such as dendritic cells represent an afferent sensing mechanism triggering T cell activation, cytokine generation, and renal salt and water reabsorption. Manipulating these inflammatory signals to attenuate hypertension without causing prohibitive systemic immunosuppression will pose a challenge, but disrupting actions of inflammatory mediators locally within the kidney may offer a path through which to target immune-mediated mechanisms of hypertension while capitalizing on Dr Dahl’s key recognition of the kidney’s importance in blood pressure regulation.
Effect of Renin-Angiotensin-Aldosterone System Inhibitors on the Rupture Risk Among Hypertensive Patients With Intracranial Aneurysms
Authors: Zhong Ping , Lu Zhiwen , Li Zhangyu , Li Tianxiao , Lan Qing , Liu Jianmin , Wang Zhanxiang , Chen Sifang , Huang Qinghai
Published: June 2022

Background:

Mounting experimental evidence supports the concept that the RAAS (renin-angiotensin-aldosterone system) is involved in the pathogenesis of intracranial aneurysm rupture. However, whether RAAS inhibitors could reduce the rupture risk of intracranial aneurysms remains unclear.

Methods:

We performed a chart review of a multicenter, prospectively maintained database of 3044 hypertensive patients with intracranial aneurysms from 20 medical centers in China. The patients were separated into ruptured and unruptured groups. Univariable and multivariable logistical regression analyses were performed to determine the association between the use of RAAS inhibitors and the rupture risk. Sensitivity analyses and subgroup analyses were performed to verify the robustness of the results.

Results:

In multivariable analyses, female sex, passive smoking, uncontrolled, or unmonitored hypertension, use of over 2 antihypertensive medications, RAAS inhibitors use, antihyperglycemic agents use, hyperlipidemia, ischemic stroke, and aneurysmal location were independently associated with the rupture risk. The use of RAAS inhibitors was significantly associated with a reduced rupture risk compared with the use of non-RAAS inhibitors (odds ratio, 0.490 [95% CI, 0.402–0.597];
P
=0.000). Compared with the use of non-RAAS inhibitors, the use of ACE (angiotensin-converting enzyme) inhibitors (odds ratio, 0.559 [95% CI, 0.442–0.709];
P
=0.000) and use of ARBs (angiotensin receptor blockers; odds ratio, 0.414 [95% CI, 0.315–0.542];
P
=0.000) were both significantly associated with a reduced rupture risk. The negative association of the rupture risk with RAAS inhibitors was consistent across 3 analyzed data and the predefined subgroups (including controlled hypertension).

Conclusions:

The use of RAAS inhibitors was significantly associated with a decreased rupture risk independent of blood pressure control among hypertensive patients with intracranial aneurysms.
Mineralocorticoid Receptor Antagonists Cause Natriuresis in the Absence of Aldosterone
Authors: Maeoka Yujiro , Su Xiao-Tong , Wang Wen-Hui , Duan Xin-Peng , Sharma Avika , Li Na , Staub Olivier , McCormick James A. , Ellison David H.
Published: June 2022

Background:

MR (mineralocorticoid receptor) antagonists are recommended for patients with resistant hypertension even when circulating aldosterone levels are not high. Although aldosterone activates MR to increase epithelial sodium channel (ENaC) activity, glucocorticoids also activate MR but are metabolized by 11βHSD2 (11β-hydroxysteroid dehydrogenase type 2). 11βHSD2 is expressed at increasing levels from distal convoluted tubule (DCT) through collecting duct. Here, we hypothesized that MR maintains ENaC activity in the DCT2 and early connecting tubule in the absence of aldosterone.

Methods:

We studied AS (aldosterone synthase)-deficient (AS
−/−
) mice, which were backcrossed onto the same C57BL6/J strain as kidney-specific MR knockout (KS-MR
−/−
) mice. KS-MR
−/−
mice were used to compare MR expression and ENaC localization and cleavage with AS
−/−
mice.

Results:

MR was highly expressed along DCT2 through the cortical collecting duct (CCD), whereas no 11βHSD2 expression was observed along DCT2. MR signal and apical ENaC localization were clearly reduced along both DCT2 and CCD in KS-MR
−/−
mice but were fully preserved along DCT2 and were partially reduced along CCD in AS
−/−
mice. Apical ENaC localization and ENaC currents were fully preserved along DCT2 in AS
−/−
mice and were not increased along CCD after low salt. AS
−/−
mice exhibited transient Na
+
wasting under low-salt diet, but administration of the MR antagonist eplerenone to AS
−/−
mice led to hyperkalemia and decreased body weight with higher Na
+
excretion, mimicking the phenotype of MR
−/−
mice.

Conclusions:

Our results provide evidence that MR is activated in the absence of aldosterone along DCT2 and partially CCD, suggesting glucocorticoid binding to MR preserves sodium homeostasis along DCT2 in AS
−/−
mice.
Differences in Regulation of Cortisol Secretion Contribute to Left Ventricular Abnormalities in Patients With Essential Hypertension
Authors: Brosolo Gabriele , Catena Cristiana , Da Porto Andrea , Bulfone Luca , Vacca Antonio , Verheyen Nicolas D. , Sechi Leonardo A.
Published: June 2022

Background:

Left ventricular (LV) abnormalities were reported in patients with overt and subclinical Cushing syndrome. The aim of this study was to investigate the relationships of daily plasma cortisol profile and cortisol response to an overnight suppression test with cardiac changes in patients with hypertension.

Methods:

In a cross-sectional study, we included 136 nondiabetic, patients with essential hypertension who were free of cardiovascular and renal complications. Plasma cortisol was measured at 8
am
, 3
pm
, and 12
am
and at 8
am
after overnight suppression with 1 mg dexamethasone (dexamethasone suppression test [DST]). Echocardiography was performed with standard B-mode and tissue-Doppler imaging.

Results:

LV hypertrophy was present in 30% and LV diastolic dysfunction in 51% of patients who were older and had significantly higher body mass index, systolic blood pressure, duration of hypertension, and 12
am
and DST cortisol. LV mass index and relative wall thickness increased progressively across tertiles of DST cortisol, together with progressive worsening of diastolic function. LV mass index was directly related to age, systolic blood pressure, duration of hypertension, and 12
am
and DST cortisol, and inversely to creatinine clearance. Multivariate regression analysis showed independent correlation of LV mass index with body mass index, systolic blood pressure, and 12
am
and DST cortisol. Logistic regression showed that DST cortisol independently predicted LV hypertrophy.

Conclusions:

Midnight and DST plasma cortisol levels are independent determinants of LV mass and geometry in patients with essential hypertension suggesting that even minor changes in regulation of cortisol secretion could contribute to cardiac abnormalities in these patients.
Intraarterial Nimodipine Versus Induced Hypertension for Delayed Cerebral Ischemia: A Modified Treatment Protocol
Authors: Weiss Miriam , Albanna Walid , Conzen-Dilger Catharina , Kastenholz Nick , Seyfried Katharina , Ridwan Hani , Wiesmann Martin , Veldeman Michael , Schmidt Tobias Philip , Megjhani Murad , Schulze-Steinen Henna , Clusmann Hans , Aries Marinus Johannes Hermanus , Park Soojin , Schubert Gerrit Alexander
Published: June 2022

Background:

Rescue treatment for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage can include induced hypertension (iHTN) and, in refractory cases, endovascular approaches, of which selective, continuous intraarterial nimodipine (IAN) is one variant. The combination of iHTN and IAN can dramatically increase vasopressor demand. In case of unsustainable doses, iHTN is often prioritized over IAN. However, evidence in this regard is largely lacking. We investigated the effects of a classical (iHTN+IAN) and modified (IAN
only
) treatment protocol for refractory DCI in an observational study.

Methods:

Rescue treatment for DCI was initiated with iHTN (target >180 mm Hg systolic) and escalated to IAN in refractory cases. Until July 2018, both iHTN and IAN were offered in cases refractory to iHTN alone. After protocol modification, iHTN target was preemptively lowered to >120 mm Hg when IAN was initiated (IAN
only
). Primary outcome was noradrenaline demand. Secondary outcomes included noradrenaline-associated complications, brain tissue oxygenation, DCI-related infarction and favorable 6-month outcome (Glasgow Outcome Scale 4–5).

Results:

N=29 and n=20 patients were treated according to the classical and modified protocol, respectively. Protocol modification resulted in a significant reduction of noradrenaline demand (iHTN+IAN 0.70±0.54 µg/kg per minute and IAN
only
0.26±0.20 µg/kg per minute,
P
<0.0001) and minor complications (15.0% versus 48.3%, unadjusted odds ratio, 0.19 [95% CI, 0.05–0.79];
P
<0.05) with comparable rates of major complications (20.0% versus 20.7%, odds ratio, 0.96 [0.23–3.95];
P
=0.95). Incidence of DCI-related infarction (45.0% versus 41.1%, odds ratio, 1.16 [0.37–3.66];
P
=0.80) and favorable clinical outcome (55.6% versus 40.0%, odds ratio, 1.88 [0.55–6.39];
P
=0.32) were similar. Brain tissue oxygenation was significantly higher with IANonly (26.6±12.8, 39.6±15.4 mm Hg;
P
<0.01).

Conclusions:

Assuming the potential of iHTN to be exhausted in case of refractory hypoperfusion, additional IAN may serve as a last-resort measure to bridge hypoperfusion in the DCI phase. With close monitoring, preemptive lowering of pressure target after induction of IAN may be a safe alternative to alleviate total noradrenaline load and potentially reduce complication rate.
Petalidium sesfonteinense (Acanthaceae), a new species from the Kaokoveld, Namibia
Authors: SWANEPOEL WESSEL , MANZITTO-TRIPP ERIN A.
Published: June 2022

Petalidium sesfonteinense, previously most commonly confused with the widespread P. variabile, is here described as a new species. It is only known from the Sesfontein area in the Kaokoveld Centre of Endemism, northwestern Namibia, where it grows on hillsides and along ephemeral riverbeds. Diagnostic characters for P. sesfonteinense include the short, stout trunk on older plants, white bark that peels on the younger branches in long, narrow strips, dendritic trichomes on vegetative parts, flowers in short dichasia with acute oblanceolate bracts, flowers with externally glabrous corollas, corolla lobes that are pink, magenta, apricot or cream and with the two upper lobes connate towards the base and the lower lobe with two yellow spots near the base. A comparison of some of the more prominent morphological features to differentiate Petalidium sesfonteinense from close relatives is provided. Based on IUCN Red List categories and criteria, a conservation assessment of Least Concern (LC) is recommended for the new species.
Taxonomic update and first record of Aphelandra martiusii (Acanthaceae) in Peru
Authors: VILLANUEVA-ESPINOZA ROSA , AZEVEDO IGOR H.F. , TORRES MONTENEGRO LUIS
Published: June 2022

A taxonomic update is provided for Aphelandra martiusii (Acanthaceae), a poorly known species from the Amazon Forest. The species was previously known from Brazil and Colombia and it is recorded for the first time in the Department of Loreto, Peru. The name A. martiusii is lectotypified by a specimen housed at Staatliche Naturwissenschaftliche Sammlungen Bayerns (M). A detailed morphological description, photographs, a line drawing, a distribution map, and a discussion on the taxonomy, geographic distribution, and conservation status of this species are provided.
Phylogenetic relationships of southern Wallacean ranid frogs (Anura: Ranidae: Hylarana)
Authors: REILLY SEAN B. , ARIFIN UMILAELA , STUBBS ALEXANDER L. , KARIN BENJAMIN R. , KAISER HINRICH , FREDERICK JEFFREY H. , ARIDA EVY , ISKANDAR DJOKO T. , MCGUIRE JIMMY A.
Published: June 2022

Frogs in the family Ranidae are diverse in Asia and are thought to have dispersed to the Sahul Shelf approximately 10 million years ago, where they radiated into more than a dozen species. Ranid species in the intervening oceanic islands of Wallacea, such as Hylarana florensis and H. elberti from the Lesser Sundas and H. moluccana from eastern Wallacea, are assumed to belong to the subgenus Papurana, yet this has not been confirmed with molecular data. We analyzed mitochondrial DNA of Hylarana species from five islands spanning the reported ranges of H. florensis and H. elberti and compared them to confirmed Papurana species and closely related subgenera within Hylarana. We find that the Lesser Sunda H. florensis and H. elberti form a clade that is sister to the rest of the Australo-Papuan Papurana assemblage. Species delimitation analyses and divergence time estimates suggest that populations of H. florensis on Lombok may be distinct from those on Flores at the species level. Likewise, populations of H. elberti on Sumba and Timor may be distinct from each other and from those on Wetar, tshe type locality of H. elberti. Samples from Babar Island thought to be members of H. elberti in fact belong to the wide-ranging H. daemeli, which occurs in northern Australia, across New Guinea, and on the neighboring island of Tanimbar. These results suggest that the Lesser Sundas may have served as a stepping-stone for colonization of the Sahul Shelf and that species diversity of Papurana frogs is underestimated in the Lesser Sundas.
A Brief History of Exposure Notification During the COVID-19 Pandemic in the United States, 2020-2021
Authors: Bair Henry , Wanger Jenny D. , Shah Nirav R.
Published: June 2022

The swift global spread of COVID-19 prompted public health authorities to explore digital technologies to aid in contact tracing for infection control. Exposure notification, a mobile device–based technology that notifies individuals of potential exposure to COVID-19 without requiring personally identifiable information, has been broadly favored because of its relative ease of use, scalability, and protection of personal privacy. Although several exposure notification protocols were developed, a partnership between Google and Apple led to the development of the most widely implemented exposure notification protocol in the world, including in the United States. In this article, we first describe the development of the Google Apple Exposure Notification (GAEN) protocol, noting the value of the discourse among software developers and public health authorities concerning the protocol’s design and features. We track states’ deployment of GAEN mobile applications (apps) and population-level adoption rates, finding the nationwide rollout of GAEN apps to be more fragmented than anticipated. We then discuss how the limited data collected from these apps make assessments of their effectiveness challenging. Finally, we consider the importance of the federal government playing a greater role in GAEN’s early development, emphasize the power of public–private partnerships, and highlight the overriding importance of public messaging over technological details.
Analysis of polymer jet motion in the non-isothermal melt-blown process
Authors: Zou Fangdong , Meng Lin , Li Yifei , Sun Xiaoxia , Li Zhimin , Chen Changjie , Han Wanli , Wang Xinhou
Published: June 2022

The motion characteristic of the polymer jet in a non-isothermal airflow field during melt blowing plays a crucial role in the process of fiber formation and has always been difficult to measure in situ. Many numerical models have been established to simulate the motion of the polymer jet during melt blowing. However, the complex interplay between the airflow field and the polymer jet in these models was usually missed. Here, a coupled air–polymer two-phase flow model in the non-isothermal airflow field was developed by the level-set method, and the temperature dependence of viscosity and density for the polymer jet were also taken into account in our model. Based on the model, the motion of the polymer jet in the melt-blowing process was simulated considering the coupled effect between the air and the polymer jet. The velocities of the polymer jet along x-direction ([Formula: see text]) and y-direction ([Formula: see text]), the whipping amplitude of the polymer jet motion, and the final diameter were discussed and verified. In addition, the effects of critical parameters, such as the inlet airflow velocity, inlet polymer flow velocity, inlet air temperature, and polymer viscosity, on the motion characteristics and temperature of the polymer jet were analyzed numerically.
Does Knowing Other Workers’ Wage Level Promote Employees’ Pay Fairness Perception? Evidence From a Randomized Survey Experiment
Authors: Bae Kwang Bin , Sohn Hosung , Cho Il Hyeong , Han Dongsook
Published: June 2022

Pay fairness perception is considered a significant determinant of employee turnover. This study analyzes whether public-sector employees’ pay fairness perception is promoted when workers are notified of the wage level of similar employees working in other sectors (i.e., relative wage). A randomized survey experiment was conducted to test the hypothesis that relative wages matter for pay fairness perception. The results show that informing employees of other workers’ wage levels enhances pay fairness perception. The subgroup analysis shows that the effect is more pronounced for employees who are relatively early in their career. The results imply that providing information on relative wage can be an effective way of promoting pay fairness perception, thereby reducing worker turnover and contributing potentially to productivity gains in public-sector organizations where turnover rate is salient.
Gender Disparities in Healthy Aging: A Cross-National Comparative Study in the United States and South Korea from 2006 to 2016
Authors: Chu Lanlan , Lor Anjelynt , Moisan Mary-Genevieve , Phi Kieu My
Published: June 2022

Using the 2006–2016 wave of Health and Retirement Study and Korean Longitudinal Study of Aging, this study explores the gender disparities in the health of older adults in the United States and South Korea. A logit model is adopted to explore the differences in the likelihood of aging healthily by gender in two countries. Results indicate that older females in the United States have a significantly higher probability of healthy aging than their male counterparts. However, the opposite finding is demonstrated among the older population in South Korea. These results are verified using various robustness check methods. The heterogeneities in the gender disparities in healthy aging across age groups and income levels are further explored. The gender effect in each healthy aging domain is investigated to understand the underlying causes of gender disparities. These findings can provide cross-national insights for policymakers to establish targeted aging policies with a gender perspective.
Local Prohibitions on Marijuana: Factors Associated With Bans on Medical and Recreational Businesses
Authors: Yaskewich David M.
Published: June 2022

Marijuana legalization in U.S. states has introduced new regulatory processes, which allow for some degree of local authority. A common provision in state laws has provided a local option, which enables municipalities to prohibit commercial cannabis facilities within their borders. This paper examined potential determinants of prohibition decisions, with an emphasis on community and local government characteristics. Using a multivariate logistic regression model, determinants of local decisions to prohibit cannabis businesses in Michigan were analyzed. A unique feature of Michigan’s approach to legalization included separate local options to opt into medical marijuana and opt out of recreational marijuana. The results found that both community and local government characteristics explain variation in prohibitions on marijuana businesses. In general, local governments were more tolerant of marijuana businesses in areas with lower densities of senior citizens and higher densities of Black residents. However, the effects of some determinants varied based on whether the decision was to allow medical or recreational marijuana. Higher income areas were more likely to opt out of recreational marijuana, but they were no different from other areas on the likelihood of opting into medical marijuana. Prohibition decisions also were affected by local government characteristics, such as the number of members on city council, female representation, and having a council-manager form of government.
Playing Offense: How Athletes are Impacting a Changing Administrative State
Authors: Thomas Michael Blair , Daniel Jamie Levine
Published: June 2022

The start of the 2020s presents a broken American administrative system plagued by state ineptitude in a time of turmoil and government distrust. In their protests, marginalized citizens have seen their voices amplified by integral parts of their communities for whom they have cheered: Athletes. This Perspective draws attention to the idea of super citizens and their ability to influence policy. We argue that Black athlete activism that centers their social reality and legitimizes Black Lives Matter for broader populations is one example of a punctuated equilibrium that work to achieve administrative state change.
Fault-tolerant adaptive PID switched control of robot manipulator based on average dwell time
Authors: Wang Juan , Wei Qiang , Sun Liangliang , Li Zhigang
Published: June 2022

The multi-mode tracking control of robot manipulators with unknown dynamics is investigated in this paper. In view of varying loads, robot manipulators are modeled as multi-mode switched systems. Adaptive PID (proportion–integration–differentiation)–like switched controllers are designed via the error transformation and multiple Lyapunov function method, which can make the error system practical stability within prescribed time under a class of switching signals satisfying average dwell time. Furthermore, two cases under the healthy actuator and faulty actuator are discussed. For the case of the partial failure of the actuator, the fault-tolerant adaptive PID-like controller is presented, which consists of two parts. Finally, a simulation example is given to demonstrate the effectiveness of the proposed method.
‘It’s Nothing Serious I Suppose’ Family Help-Seeking for Adolescent Social Anxiety
Authors: Mc Donagh Cal , Hennessy Eilis
Published: June 2022

This article investigates how families seek professional supports for adolescent social anxiety. Many adolescents meet diagnostic criteria for social anxiety disorder but do not access professional mental health supports. Access to timely interventions is important because social anxiety has a range of developmental implications and typically persists into adulthood when untreated. Twelve adolescents (aged 14 to 18) who had attended mental health services for support with social anxiety and 13 mothers of such adolescents participated in semi-structured interviews which were analysed thematically. Findings indicated that mothers play an important role in noticing difficulties and initiating help-seeking for their children, although adolescents and their mothers can initially view anxiety as ‘just shyness’ and often seek help for a range of difficulties, including unhappiness, rather than anxiety specifically. Furthermore, many adolescents described experiencing help-seeking as embarrassing or shameful. Implications for facilitating families to access professional supports for adolescents are discussed.
Examining the source of island effects in native speakers and second language learners of English
Authors: Aldosari Saad , Covey Lauren , Gabriele Alison
Published: June 2022

We investigate sensitivity to island constraints in English native speakers and Najdi Arabic learners of English, examining (1) whether second language (L2) learners whose native language (L1) does not instantiate overt wh-movement are sensitive to island constraints and (2) the source of island effects. Under a grammatical account of islands, these effects arise due to violations of syntactic constraints. Under the resource-limitation account, island effects arise due to processing difficulty. The source of island effects is interesting to examine in L2 learners because it is possible that reduced processing abilities in the L2 may lead to the low acceptance of sentences with island violations simply due to the complexity of the sentences themselves as opposed to an adherence to grammatical constraints. To tease apart these accounts, we followed Sprouse et al. in focusing on individual differences in working memory (WM). We used an acceptability judgment task (AJT) to quantify island sensitivity and an automated operation span task to measure WM. Building on Sprouse et al., the AJT tested four island types, but we made several modifications to the task design to address concerns raised by Hofmeister et al.: the stimuli included a ‘context’ sentence to improve the naturalness of the complex wh-sentences. The stimuli also included complex wh-fillers (e.g. which worker) as opposed to bare fillers ( who), as semantically rich wh-phrases have been found to be easier to process. Our results showed that learners, like natives, exhibited island sensitivity, and there was no evidence that individual differences in WM modulated island sensitivity for either natives or learners. Our results are compatible with the grammatical view of island effects and suggest that wh-dependencies in both L1 and L2 grammars are similarly constrained by syntax.
Oxygen extraction efficiency and white matter lesion burden in older adults exhibiting radiological evidence of capillary shunting
Authors: Juttukonda Meher R , Stephens Kimberly A , Yen Yi-Fen , Howard Casey M , Polimeni Jonathan R , Rosen Bruce R , Salat David H
Published: June 2022

White matter lesions (WML) have been linked to cognitive decline in aging as well as in Alzheimer’s disease. While hypoperfusion is frequently considered a cause of WMLs due to the resulting reduction in oxygen availability to brain tissue, such reductions could also be caused by impaired oxygen exchange. Here, we tested the hypothesis that venous hyperintense signal (VHS) in arterial spin labeling (ASL) magnetic resonance imaging (MRI) may represent a marker of impaired oxygen extraction in aging older adults. In participants aged 60–80 years (n = 30), we measured cerebral blood flow and VHS with arterial spin labeling, maximum oxygen extraction fraction (OEFmax) with dynamic susceptibility contrast, and WML volume with T1-weighted MRI. We found a significant interaction between OEFmax and VHS presence on WML volume ( p = 0.02), where lower OEFmax was associated with higher WML volume in participants with VHS, and higher OEFmax was associated with higher WML volume in participants without VHS. These results indicate that VHS in perfusion-weighted ASL data may represent a distinct cerebrovascular aging pattern involving oxygen extraction inefficiency as well as hypoperfusion.