bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Nox2 inhibition Unloading‐induced Changes in Morphology and nNOSμ Translocation in the Rat Soleus
Authors: Lawler John M , Hord Jeffrey M , Rodriquez Dinah A , Lee Yang , Guzzoni Vinicius , Garcia‐Villatoro Erika E , Garcia Marcela , Kuczmarski James M , Lawler Matthew S 
Published: July 2022

Removal of mechanical loading (spaceflight, bedrest, casting) causes rapid atrophy of affected skeletal muscles. Recently, we identified that translocation of the mu‐splice variant of neuronal nitric oxide synthase (nNOSμ) and downstream activation of FoxO3a were redox‐sensitive phenomena. Prospective sources or reactive oxygen species (ROS) include mitochondria and NADPH oxidase‐2 (Nox2). We tested the causal role of Nox2 in unloading induced atrophy using a peptidyl inhibitor (gp91ds‐tat) with the following groups: ambulatory controls (CON), hindlimb unloaded for 7 days with scrambled sequence (HUScr), and unloading for 7 days + 5 mg/kg/day gp91dsTAT (HUG). Nox2 inhibition provided significant against HU‐induced reduction of plantarflexor muscle mass and soleus muscle fiber cross‐sectional area (CSA), measured using ImageJ and SMASH programs. There was a trend towards protection against a partial shift in fiber‐type shift from slow to fast twitch. Loss of sarcolemmal nNOSμ activity with HU, visualized using NADPH diaphorase and confirmed with immunofluorescence were also mitigated by gp91dsTAT. Gp91dsTAT also attenuated membrane localization of the Nox2 subunit p67phox. We conclude that Nox2 inhibition protects against muscle fiber atrophy and translocation of nNOSμ.Support or Funding InformationSupported by NASA (NNX13AE45G), NSBRI, NIH (AR054084), ACSM, Huffines Institute.
Psychostimulants differentially alter performance on the rodent psychomotor vigilance test following radiation exposure
Authors: Gupta Sneha R. , Hienz Robert D. , Davis Catherine M. 
Published: July 2022

To investigate radiation‐induced cognitive deficits, the present report describes performance data obtained with the rPVT (rat Psychomotor Vigilance Test), an animal analog of the human PVT test currently employed in a variety of operational settings. The human PVT was developed as a highly sensitive and standardized assay capable of quantifying temporally dynamic changes in sustained attention, and requires responding to a light stimulus as soon as it appears. In the current study, rats were trained to perform the rPVT to baseline performance levels (≥75% correct and ≤25% premature responses) and were then irradiated with head‐only protons (150 MeV/n) at 25 or 100 cGy or sham‐irradiation. Following radiation exposure, rats were returned to Hopkins and continued daily rPVT assessments. At approximately 6 months post‐radiation exposure, rats were then characterized as radiation sensitive—i.e., those rats displaying radiation‐induced rPVT deficits, or radiation insensitive—i.e., irradiated rats performing the rPVT at sham‐irradiated control levels. Several different drugs were then assessed as countermeasures for these deficits in radiation sensitive rats, and were also assessed in radiation insensitive rats to determine if any performance disruptions would occur. d‐Amphetamine dose‐dependently improved performance in radiation sensitive rats, whereas it impaired rPVT performance in radiation insensitive rats at the two highest doses tested. Amphetamine's effects were decreased by the D1 antagonist, SCH 39166, but not the D2 antagonist, L‐741, 626. Atomoxetine and methylphenidate were also tested, but did not produce these differential effects. This data further supports the role of the dopamine neurotransmitter system in mediating individual differences in radiation‐induced deficits in neurobehavioral performance as assessed by the rPVT.Support or Funding InformationSupported by the NSBRI through NASA cooperative agreement NCC 9‐58, grants NBPF01604, NBPF02802, NBPF04201, and EO00010, and NASA NNX15AC71G
Lower Body Negative Pressure Treadmill Exercise Attenuates Simulated Space Flight‐Induced Reductions of Balance Abilities in Males but not Females
Authors: Macaulay Timothy Ryan , Macias Brandon , Lee Stuart M.C. , Boda Wanda , Watenpaugh Donald E. , Hargens Alan 
Published: July 2022

Spaceflight causes sensorimotor adaptations that result in balance deficiencies upon return to a gravitational environment. Lower Body Negative Pressure (LBNP) treadmill exercise has been shown to protect against deconditioning in various other physiological systems during simulated spaceflight. Therefore, we hypothesized that LBNP treadmill exercise prevents balance losses in both male and female identical twins during 30 days of 6° head‐down‐tilt (HDT) bed rest. Fifteen (8M and 7F) identical twin sets participated in 30 days of bed rest. Within each twin pair, one twin was randomly assigned to an exercise group that performed 40 min of supine LBNP treadmill exercise set to generate 1.0–1.2 body weight, followed by 5 min of static LBNP, 6 days/wk. Their identical sibling was assigned to a non‐exercise control group. Before and immediately after bed rest, subjects completed standing and walking rail balance tests with eyes open and eyes closed. In control subjects, standing rail balance times (men: −42%, women: −40%), rail walk distances (men: −44%, women: −32%), and rail walk times (men: −34%, women: −31%) significantly decreased after bed rest. Compared to controls, subjects in the LBNP treadmill exercise group showed significantly attenuated losses of standing rail balance time, with prevention of 63% of the loss in men, but without a significant prevention in women (41%). In addition, LBNP treadmill exercise mitigated decreases in rail walk time in men, but not in women. Therefore, treadmill exercise within LBNP during spaceflight may maintain balance control; yet this protective effect may, to some extent, depend on gender.Support or Funding InformationThis study was funded by NASA grants NAG 9‐1425, NCC2‐1133, NNX10AM18G, and NNX13AJ12G, NIH grant to the UCSD GCRC M01 RR00827. BRM was supported by National Space Biomedical Research Institute through NCC 9‐58. We thank our outstanding twins and staff at the UCSD General Clinical Research Center, as well as the UCSD Faculty Mentorship Program and the 2015 Julia Brown Research Scholarship.
Expanding Structure Activity Relationships for the preQ1 Riboswitch: Functional Group Requirements and Metal Dependence in Pathogenic Aptamer Domains
Authors: Doan My‐Anh , Pahl Mallory N. , Neilson Ben K. , Suydam Ian T. 
Published: July 2022

Many bacterial species regulate the production of queuosine modified tRNAs by employing riboswitches selective for 7‐aminomethyl‐7‐deazaguanine (preQ1), an essential precursor in the biosynthesis of queuosine. Analogous to other riboswitch systems, the preQ1 riboswitch mediates a feedback mechanism between a target mRNA and a recognized small molecule metabolite. For class‐I preQ1 riboswitches this regulatory mechanism is initiated by the specific binding of preQ1 to an aptamer domain in the 5′‐untranslated of the mRNA, driving the formation of an alternative RNA fold, and leading to a down regulation of protein production at the transcriptional level. The molecular details of this binding event have been well described for the Bacillus subtilis riboswitch aptamer, but the current model fails to explain the high binding affinities observed for several preQ1 analogs, particularly those introducing carbonyl functional groups at the 7‐aminomethyl position. To investigate the origin of these favorable metabolite/RNA contacts we have designed a series of carbonyl containing analogs and have adapted a rapid fluorescence‐based binding assay to measure their affinities as a function of magnesium concentration. Binding data for these analogs will be presented for the Bacillus subtilis aptamer and several pathogenic sequences of variable loop‐I length, including Staphylococcus aureus. These results directly test a binding model requiring inner sphere magnesium coordination between the carbonyl oxygen of these analogs and a phosphodiester oxygen in loop‐I.Support or Funding InformationThis work was supported by the Murdock Trust, the National Aeronautics and Space Administration, the College of Science and Engineering of Seattle University and the Department of Bioengineering of the University of Washington.
Comparison of Anterior Tibial Bone Microvascular Flow, with Macrovascular Flow during Body Tilt
Authors: Becker Rachel Lauren , Siamwala Jamila , Macias Brandon , Hargens Alan R. 
Published: July 2022

PurposeThis study determined whether bone blood flow in the tibia is linearly proportional to blood flow of the feeding anterior tibial artery (ATA) during various positions of body tilt. We hypothesize bone microvascular flow is linearly proportional to input blood flow in the feeding ATA.MethodsThe IRB of UC San Diego approved the study of 18 healthy subjects, 10 females and 8 males, aged 26 ± 7 years. All subjects assumed sitting, supine, 6° head‐down tilt (HDT), 15° HDT, 6° head‐up tilt (HUT), and 15° HUT positions for 5min using an inversion table. All positions were randomized except the sitting position, which was the first position to be used as the baseline. An Ultrasound Device noninvasively measured peak systolic velocity of the right ATA with subsequent calculation of blood flow. A customized photoplethysmography (PPG) device non‐invasively measured the right leg's tibial bone microvascular flow. Blood pressure (BP) and heart rate (HR) were recorded during the third minute of each position.ResultsATA marcovascular blood flow increased significantly from the sitting to the 15°HDT (p=0.041). Tibial bone microvascular flow increased significantly in supine compared to sitting position (p=0.013). Tibial bone microvascular flow also increased significantly in both 6°HDT and 15°HDT compared to sitting positions (p=0.011, p=0.010). Furthermore, when comparing tibial microvascular bone blood flow to ATA macrovascular blood flow, the normalized slope for microvascular flow increases more than the normalized slope for macrovascular flow (p<0.001) (Figure 1, one way ANOVA) (Figure 1).ConclusionOur results document that the tibial bone microvasculature is more variable and widely regulated than the feeding arterial vasculature, probably due to precapillary vasoreactivity. The findings of this study are novel and may aid the understanding of various skeletal processes such as bone healing and bone homeostasis.Support or Funding InformationThis study was supported by NASA grant number NNX13AJ12G.
Antibiotic use and bacterial resistance in patients with acne vulgaris
Authors: Bowman Shelby , Sadowski Catherine K. 
Published: July 2022

ABSTRACT
Acne vulgaris is a prevalent chronic skin disease caused by obstruction and/or inflammation of pilosebaceous follicles. Each year, about 50 million people in the United States are affected. The use of topical and oral antibiotics to manage acne has been associated with the development of bacterial resistance. This article reviews concerns about antimicrobial use, current treatment recommendations, and emerging research in unconventional treatments.
Effectiveness of Continuous Cuff Pressure Control in Preventing Ventilator-Associated Pneumonia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials*
Authors: Maertens Bert , Lin Frances , Chen Yingyan , Rello Jordi , Lathyris Dimitrios , Blot Stijn 
Published: July 2022

OBJECTIVES:
Microaspiration of subglottic secretions is the main pathogenic mechanism for ventilator-associated pneumonia (VAP). Adequate inflation of the endotracheal cuff is pivotal to providing an optimal seal of the extraluminal airway. However, cuff pressure substantially fluctuates due to patient or tube movements, which can induce microaspiration. Therefore, devices for continuous cuff pressure control (CCPC) have been developed in recent years. The purpose of this systematic review and meta-analysis is to assess the effectiveness of CCPC in VAP prevention.

DATA SOURCES:
A systematic search of Embase, the Cochrane Central Register of Controlled Trials, and the International Clinical Trials Registry Platform was conducted up to February 2022.

STUDY SELECTION:
Eligible studies were randomized controlled trials (RCTs) and quasi-RCTs comparing the impact of CCPC versus intermittent cuff pressure control on the occurrence of VAP.

DATA EXTRACTION:
Random-effects meta-analysis was used to calculate odds ratio (OR) and 95% CI for VAP incidence between groups. Secondary outcome measures included mortality and duration of mechanical ventilation (MV) and ICU stay. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach.

DATA SYNTHESIS:
Eleven RCTs with 2,092 adult intubated patients were included. The use of CCPC was associated with a reduced risk of VAP (OR, 0.51). Meta-analyses of secondary endpoints showed no significant difference in mortality but significant differences in durations of MV (mean difference, –1.07 d) and ICU stay (mean difference, –3.41 d) in favor of CCPC. However, the risk of both reporting and individual study bias was considered important. The main issues were the lack of blinding, potential commercial conflicts of interest of study authors and high heterogeneity due to methodological differences between studies, differences in devices used for CCPC and in applied baseline preventive measures. Certainty of the evidence was considered “very low.”

CONCLUSIONS:
The use of CCPC was associated with a reduction in VAP incidence; however, this was based on very low certainty of evidence due to concerns related to risk of bias and inconsistency.
Recombinant human chorionic gonadotropin induces signaling pathways towards cancer prevention in the breast of BRCA1/2 mutation carriers
Authors: Su Yanrong , Dang Nhi M. , Depypere Herman , Santucci-Pereira Julia , Gutiérrez-Díez Pedro J. , Kanefsky Joice , Janssens Jaak Ph. , Russo Jose 
Published: July 2022

Background
Strategies for breast cancer prevention in women with germline BRCA1/2 mutations are limited. We previously showed that recombinant human chorionic gonadotropin (r-hCG) induces mammary gland differentiation and inhibits mammary tumorigenesis in rats. The present study investigated hCG-induced signaling pathways in the breast of young nulliparous women carrying germline BRCA1/2
mutations.

Methods
We performed RNA-sequencing on breast tissues from 25 BRCA1/2 mutation carriers who received r-hCG treatment for 3 months in a phase II clinical trial, we analyzed the biological processes, reactome pathways, canonical pathways, and upstream regulators associated with genes differentially expressed after r-hCG treatment, and validated genes of interest.

Results
We observed that r-hCG induces remarkable transcriptomic changes in the breast of BRCA1/2 carriers, especially in genes related to cell development, cell differentiation, cell cycle, apoptosis, DNA repair, chromatin remodeling, and G protein-coupled receptor signaling. We revealed that r-hCG inhibits Wnt/β-catenin signaling, MYC, HMGA1, and HOTAIR, whereas activates TGFB/TGFBR-SMAD2/3/4, BRCA1, TP53, and upregulates BRCA1 protein.

Conclusion
Our data suggest that the use of r-hCG at young age may reduce the risk of breast cancer in BRCA1/2 carriers by inhibiting pathways associated with stem/progenitor cell maintenance and neoplastic transformation, whereas activating genes crucial for breast epithelial differentiation and lineage commitment, and DNA repair.
Ethoxyquin is a Competent Radical-Trapping Antioxidant for Preventing Ferroptosis in Doxorubicin Cardiotoxicity
Authors: Tadokoro Tomonori , Ikeda Masataka , Abe Ko , Ide Tomomi , Miyamoto Hiroko Deguchi , Furusawa Shun , Ishimaru Kosei , Watanabe Masatsugu , Ishikita Akihito , Matsushima Shouji , Koumura Tomoko , Yamada Ken-ichi , Imai Hirotaka , Tsutsui Hiroyuki 
Published: July 2022

Abstract
Doxorubicin (DOX) is an effective anti-cancer agent for various malignancies. Nevertheless, it has a side effect of cardiotoxicity, referred to as doxorubicin-induced cardiomyopathy (DIC), that is associated with a poorer prognosis. This cardiotoxicity limits the clinical use of DOX as a therapeutic agent for malignancies. Recently, ferroptosis, a form of regulated cell death induced by the accumulation of lipid peroxides, has been recognized as a major pathophysiology of DIC. Ethoxyquin is a lipophilic antioxidant widely used for food preservation and thus may be a potential therapeutic drug for preventing DIC. However, the efficacy of ethoxyquin against ferroptosis and DIC remains to be fully elucidated. Here, we investigated the inhibitory action of ethoxyquin against GPx4-deficient ferroptosis and its therapeutic efficacy against DOX-induced cell death in cultured cardiomyocytes and cardiotoxicity in a murine model of DIC. In cultured cardiomyocytes, ethoxyquin treatment effectively prevented GPx4-deficient ferroptosis. Ethoxyquin also prevented DOX-induced cell death, accompanied by the suppression of malondialdehyde (MDA) and mitochondrial lipid peroxides, which were induced by DOX. Furthermore, ethoxyquin significantly prevented DOX-induced cell death without any suppression of caspase cleavages representing apoptosis. In DIC mice, ethoxyquin treatment ameliorated cardiac impairments, such as contractile dysfunction and myocardial atrophy, and lung congestion. Ethoxyquin also suppressed serum lactate dehydrogenase and creatine kinase activities, decreased the levels of lipid peroxides such as MDA and acrolein, inhibited cardiac fibrosis, and reduced TUNEL-positive cells in the hearts of DIC mice. Collectively, ethoxyquin is a competent antioxidant for preventing ferroptosis in DIC and can be its prospective therapeutic drug.
Results of a pilot study of a cooling mattress pad to reduce vasomotor symptoms and improve sleep
Authors: Avis Nancy E. , Levine Beverly J. , Coeytaux Remy 
Published: July 2022

Abstract

Objective
This single-arm pilot study was designed to generate pilot data on the use of a cooling mattress pad system on vasomotor symptoms (VMS; hot flashes and/or night sweats), self-assessed sleep, and daily hot flash interference among perimenopausal and postmenopausal women.

Methods
A total of 15 perimenopausal and postmenopausal women aged 45 to 59 years experiencing four or more VMS per day were recruited from the community. After completion of baseline questionnaires and a 2-week daily diary to confirm VMS eligibility, all women received a cooling mattress pad system to use at night for 8 weeks, during which time they continued to complete their daily diaries to record VMS frequency and severity. The primary study outcome was change from baseline in VMS frequency. Secondary outcomes were sleep quality, measured by the Pittsburgh Sleep Quality Index, and hot flash interference with daily life, assessed by the Hot Flash Related Daily Interference Scale, where higher sores indicate worse sleep quality and higher interference, respectively. We used repeated-measures methods (analysis of covariance, paired t tests, and McNemar test) to evaluate outcomes.

Results
VMS frequency significantly declined by 52% at 8 weeks (P < 0.0001). Mean total Pittsburgh Sleep Quality Index score significantly declined 3.27 points from 11.14 at baseline to 7.87 at follow-up (P = 0.011). The total Hot Flash Related Daily Interference Scale score significantly declined from 4.16 at baseline to 1.92 at follow-up (P = 0.011).

Conclusions
Women who used a cooling mattress pad system experienced significant and clinically meaningful reductions in VMS frequency, sleep disturbance, and hot flash interference with daily activities over an 8-week period. These results provide preliminary evidence suggesting that a cooling mattress pad used while sleeping can provide a nonpharmacological option to reduce VMS and sleep disturbance for women experiencing menopausal hot flashes.
Simple predictive score for nocturnal hypertension and masked nocturnal hypertension using home blood pressure monitoring in clinical practice
Authors: Narita Keisuke , Hoshide Satoshi , Ae Ryusuke , Kario Kazuomi 
Published: July 2022

Objective:
The decision whether to measure night-time blood pressure (BP) is challenging as these values cannot be easily evaluated because of problems with measurement devices and related stress. Using the nationwide, practice-based Japan Morning Surge-Home BP Nocturnal BP study data, we developed a simple predictive score that physicians can use to diagnose nocturnal hypertension.

Methods:
We divided 2765 outpatients (mean age 63 years; hypertensive patients 92%) with cardiovascular risks who underwent morning, evening, and night-time home BP (HBP) measurements (0200, 0300, and 0400 h) into a calibration group (n = 2212) and validation group (n = 553). We used logistic-regression models in the calibration group to identify the predictive score for nocturnal hypertension (night-time HBP ≥120/70 mmHg) and then evaluated the score's predictive ability in the validation group.

Results:
In the logistic-regression model, male sex, increased BMI) (≥25 kg/m2), diabetes, elevated urine-albumin creatinine ratio (UACR) (≥30 mg/g Cr), elevated office BP (≥140/90 mmHg) and home (average of morning and evening) BP (≥135/85 mmHg) had positive relationships with nocturnal hypertension. The predictive scores for nocturnal hypertension were 1 point (male, BMI, and UACR); 2 points (diabetes); 3 points (office BP ≥140/90 mmHg); 6 points (home BP ≥135/85 mmHg); total 14 points. Over 75% of the nocturnal hypertension cases in the validation group showed at least 10 points [AUC 0.691, 95% CI (0.647–0.735)]. We also developed a score for masked nocturnal hypertension, that is, nocturnal hypertension despite controlled daytime HBP.

Conclusion:
We developed a simple predictive score for nocturnal hypertension that can be used in clinical settings and for diagnoses.
Antihypertensive drug treatment in white-coat hypertension: data from the Plaque HYpertension Lipid-Lowering Italian Study
Authors: Mancia Giuseppe , Facchetti Rita , Quarti-Trevano Fosca , Grassi Guido 
Published: July 2022

Aim:
Little evidence is available on whether antihypertensive treatment lowers cardiovascular risk in white-coat hypertension (WCH). Protection might be indirectly inferred, however, from the blood pressure (BP) effects of treatment as in trials BP reduction is linearly related to outcome reduction. We analyzed the effect of antihypertensive treatment on office and ambulatory BP in WCH using data from the Plaque HYpertension Lipid-Lowering Italian Study (PHYLLIS).

Methods
: Office and ambulatory blood pressure were measured in 470 hypertensive patients randomized to fosinopril or hydrochlorothiazide alone or combined with a statin before treatment and at 6 month or yearly intervals during 2.6 years of follow-up. Patients were divided into two groups according to whether before randomization to treatment office and 24-h mean BP were elevated (sustained hypertension) or office BP was elevated but 24-h BP values were normal (WCH).

Results
: In both sustained hypertension and WCH antihypertensive treatment was associated with an early marked office BP reduction, which persisted virtually unchanged throughout the treatment period. In contrast, 24-h (and day and night) BP showed a marked and persistent treatment-related fall in sustained hypertension but no change in WCH. The results were similar when data were separately analyzed in patients under fosinopril or diuretic, with or without statin treatment.

Conclusion
: In WCH, antihypertensive treatment can effectively and durably reduce office BP. This reduction is accompanied by the inability to lower ambulatory BP from the normal values characterizing this condition at baseline. This appears to be unrelated to the type of treatment employed.