bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Low- and High-Mineral Content Water on the Relative Bioavailability of a Coformulated Abacavir/Dolutegravir/Lamivudine Dispersible Tablet in Healthy Adults
Authors: Singh Rajendra P. , Shaik Jafar S. B. , Skoura Nancy , Joshi Shashidhar , Shreeves Trevor , Casillas Linda , Buchanan Ann M. 
Published: September 2018

Background:
The fixed-dose combination (FDC) tablet formulation of abacavir/dolutegravir/lamivudine is indicated for the treatment of HIV-1 infection in adults and pediatric patients weighing ≥40 kg. Alternative formulations with acceptable palatability and convenient dosing are needed for children who require smaller doses and have difficulty swallowing tablets.

Setting:
A phase 1, open-label, randomized study was conducted in healthy adults to evaluate the relative bioavailability of a novel dispersible FDC tablet of abacavir 150 mg/dolutegravir 10 mg/lamivudine 75 mg administered under 4 different dosing conditions compared with dolutegravir plus abacavir/lamivudine nondispersible, film-coated tablets.

Methods:
The test treatments were 4 dispersible FDC tablets reconstituted in water with high- or zero-mineral content and administered either immediately or after a 30-minute delay. The reference treatment was 4 nondispersible dolutegravir 10-mg tablets plus 1 nondispersible abacavir 600-mg/lamivudine 300-mg tablet administered with zero-mineral content water. The primary endpoints were area under the concentration–time curve from time 0 extrapolated to infinity and the maximum observed plasma concentration.

Results:
Following administration of dispersible abacavir/dolutegravir/lamivudine, the relative bioavailability of dolutegravir was approximately 50% higher. Abacavir and lamivudine demonstrated bioequivalence when administered as the dispersible FDC tablet compared with coadministration of dolutegravir plus abacavir/lamivudine nondispersible, film-coated tablets. Neither the mineral content of the water nor dosing times affected the pharmacokinetics of individual components. The dispersible tablet was safe and well tolerated, and the palatability was acceptable.

Conclusions:
These pharmacokinetic results support further development of a dispersible FDC tablet of abacavir/dolutegravir/lamivudine for future use in pediatric patients.
Stimulant Use and Viral Suppression in the Era of Universal Antiretroviral Therapy
Authors: Carrico Adam W. , Hunt Peter W. , Neilands Torsten B. , Dilworth Samantha E. , Martin Jeffrey N. , Deeks Steven G. , Riley Elise D. 
Published: September 2018

Background:
HIV-positive persons who use stimulants such as methamphetamine experience difficulties navigating the HIV care continuum that undermine the benefits of antiretroviral therapy (ART). However, few studies have examined the association of stimulant use with viral suppression in the era of universal ART.

Setting:
Zuckerberg San Francisco General Hospital.

Methods:
HIV-positive persons participating in a clinical cohort study and taking ART completed assessments every 4–6 months. The exposure was the cumulative, time-varying proportion of assessments with any self-reported stimulant use. The time-varying outcome, HIV viral suppression (ie, <200 copies/mL), was measured at assessments or extracted from the clinical record.

Results:
In total, 1635 HIV-positive participants on ART contributed 17,610 person-visits over a median of 2.3 [interquartile range (IQR) = 1.0–5.3] years of follow-up. Participants were middle-aged (median = 45.0; IQR = 38.0–52.0), predominantly white (57%), sexual minority men (78%), with a median CD4+ T-cell count of 409 (IQR = 225–640) cells/mm3 at enrollment. Significant increases in odds of viral suppression over time were less pronounced among stimulant users compared with nonusers, particularly before the advent of universal ART. Increasing odds of viral suppression were paralleled by declining stimulant use over time. In the universal ART era, increasing odds of viral suppression were observed at lower levels of stimulant use, but not when participants reported using stimulants at every visit.

Conclusions:
Although ART benefits are still not achieved as rapidly in stimulant users, this disparity is not as large in the era of universal ART.
Internal Working Models of Attachment Relationships and HIV Outcomes Among Women Living With HIV
Authors: Turan Bulent , Crockett Kaylee B. , Kempf Mirjam-Colette , Konkle-Parker Deborah , Wilson Tracey E. , Tien Phyllis C. , Wingood Gina , Neilands Torsten B. , Johnson Mallory O. , Weiser Sheri D. , Turan Janet M. 
Published: September 2018

Background:
Treatment adherence and viral suppression remain suboptimal in the United States. Attachment insecurity may be one understudied factor affecting adherence. According to attachment theory, people develop generalized internal working models of interpersonal relationships, which shape their perceptions of the availability of others at times of stress and how they handle stressors as an individual. Two dimensions of attachment insecurity are attachment-related avoidance (avoidance of intimacy with others and avoidance of negative emotions) and attachment-related anxiety (feeling unable to deal with stressors without others' help). For people living with chronic stressful health conditions that require life-long self-management, attachment-related avoidance and attachment-related anxiety may diminish the ability to cope with stressors as an individual leading to negative health outcomes.

Methods:
We examined cross-sectional associations of the 2 attachment-related insecurity dimensions with antiretroviral treatment (ART) adherence, HIV visit adherence, CD4 cell counts, and viral suppression. Survey and clinical data from 453 women living with HIV in 4 US cities were analyzed controlling for age, education, income, time on ART, illicit drug use, and race.

Results:
Attachment-related avoidance was the only unique predictor of suboptimal ART adherence, viral failure, and low CD4 count, and attachment-related anxiety was the only unique predictor of missed HIV care visits. These effects were over and above the effects of all covariates. ART adherence mediated the association of attachment-related avoidance with both viral failure and low CD4 counts.

Conclusions:
Interventions may need to focus on the vulnerable subpopulation with high attachment insecurity and incorporate existing strategies that address insecure attachment models.
The Association of Unmet Needs With Subsequent Retention in Care and HIV Suppression Among Hospitalized Patients With HIV Who Are Out of Care
Authors: Dandachi Dima , May Sarah B. , Davila Jessica A. , Cully Jeffrey , Amico K. Rivet , Kallen Michael A. , Giordano Thomas P. 
Published: September 2018

Background:
Unmet needs among hospitalized patients with HIV may prevent engagement in HIV care leading to worse clinical outcomes. Our aim was to examine the role of unmet subsistence needs (eg, housing, transportation, and food) and medical needs (eg, mental health and substance abuse treatment) as barriers for retention in HIV care and viral load (VL) suppression.

Methods:
We used data from the Mentor Approach for Promoting Patients' Self-Care intervention study, the enrolled hospitalized HIV patients at a large publicly funded hospital between 2010 and 2013, who were out-of-care. We examined the effect of unmet needs on retention in HIV care (attended HIV appointments within 0–30 days and 30–180 days) and VL suppression, 6 months after discharge.

Results:
Four hundred seventeen participants were enrolled, 78% reported having ≥1 unmet need at baseline, most commonly dental care (55%), financial (43%), or housing needs (34%). Participants with unmet needs at baseline, compared to those with no needs, were more likely to be African American, have an existing HIV diagnosis and be insured. An unmet need for transportation was associated with lower odds of retention in care [odds ratio (OR): 0.5; 95% confidence interval (CI): 0.34 to 0.94, P = 0.03], even after adjusting for other factors. Compared to participants with no need, those who reported ≥3 unmet subsistence needs were less likely to demonstrate VL improvement (OR: 0.51; 95% CI: 0.28 to 0.92; P = 0.03) and to be retained in care (OR: 0.52; 95% CI: 0.28 to 0.95; P = 0.03).

Conclusion:
Broader access to programs that can assist in meeting subsistence needs among hospitalized patients could have significant individual and public health benefits.
Levator Morphology and Strength After Obstetric Avulsion of the Levator Ani Muscle
Authors: Handa Victoria L. , Blomquist Joan L. , Roem Jennifer , Muñoz Alvaro , Dietz Hans Peter 
Published: September 2018

Objectives
Obstetric levator avulsion may be an important risk factor for prolapse. This study compares the size of the levator hiatus, the width of the genital hiatus, and pelvic muscle strength between vaginally parous women with or without levator avulsion, 5 to 15 years after delivery.

Methods
Parous women were assessed for levator ani avulsion, using 3-dimensional transperineal ultrasound. Women with and without levator ani avulsion were compared with respect to levator hiatus areas (measured on ultrasound), genital hiatus (measured on examination), and pelvic muscle strength (measured with perineometry). Further analysis also considered the association of forceps-assisted birth.

Results
At a median interval of 11 years from first delivery, levator avulsion was identified in 15% (66/453). A history of forceps-assisted delivery was strongly associated with levator avulsion (45% vs 8%; P < 0.001). Levator avulsion was also associated with a larger levator hiatus area (+7.3 cm2; 95% confidence interval [CI], 4.1–10.4, with Valsalva), wider genital hiatus (+0.6 cm; 95% CI, 0.3–0.9, with Valsalva), and poorer muscle strength (−14.5 cm H2O; 95% CI, −20.4 to −8.7, peak pressure). Among those with levator avulsion, forceps-assisted birth was associated with a marginal increase in levator hiatus size but not genital hiatus size or muscle strength.

Conclusions
Obstetric levator avulsion is associated with a larger levator hiatus, wider genital hiatus, and poorer pelvic muscle strength. Forceps-assisted birth is an important marker for levator avulsion but may not be an independent risk factor for the development of pelvic muscle weakness or changes in hiatus size in the absence of levator avulsion.
The Selective RNA Polymerase I Inhibitor CX-5461 Mitigates Neointimal Remodeling in a Modified Model of Rat Aortic Transplantation
Authors: Dai Chaochao , Sun Mengyao , Wang Fengjiao , Zhu Jiankang , Wei Yaping , Guo Xiaotong , Ma Siqin , Dong Bo , Wang Gejin , Jiang Fan , Wang Jianli 
Published: September 2018

Background
Transplant vasculopathy is a major cause of chronic rejection of transplanted organs. In the present study, we examined the effects of CX-5461, a novel selective inhibitor of RNA polymerase I, on development of transplant vasculopathy using a modified model of rat aortic transplantation.

Methods
The thoracic aortas from Fischer rats were transplanted into the abdominal cavity of Lewis rats. CX-5461 was mixed in pluronic gel and administered via perivascular release.

Results
Treatment with CX-5461 mitigated the development of neointimal hyperplasia and vascular inflammation. This effect was likely to be attributable in part to inhibition of macrophage-dependent innate immunity reactions. Specifically, CX-5461 exhibited potent inhibitory effects on macrophage migration and lipopolysaccharide-induced activation. Treatment with CX-5461 also prevented macrophage differentiation and maturation from primary bone marrow cells. In macrophages, CX-5461 did not alter the total amount of p53 protein, but significantly increased p53 phosphorylation, which was involved in regulating cytokine-stimulated macrophage proliferation.

Conclusions
In conclusion, our results suggest that pharmacological inhibition of RNA polymerase I may be a novel strategy to treat transplantation-induced arterial remodeling.
The N-end rule E3 ligase UBR2 activates Nlrp1b inflammasomes
Authors: Xu Hao , Shi Jianjin , Yang Zhenxiao , Shao Feng , Dong Na 
Published: September 2018

AbstractInnate immunity relies on the formation of different inflammasomes to initiate immune responses. The recognition of diverse infection and other danger signals by innate immune receptors trigger caspase-1 activation that induces pyroptosis. Anthrax lethal factor (LF) is a secreted bacterial protease that known to potently activate Nlrp1b inflammasomes in mouse macrophages, but the molecular mechanism underlying LF-induced Nlrp1b activation remains unknown. We here carried out both a mouse genome-wide siRNA screen and a CRISPR/Cas9 knockout screen seeking to identify genes that participate in Nlrp1b activation triggered by LF treatment. We found that the N-end rule pathway E3 ligase UBR2 is required for Nlrp1b activation and a ubiquitin conjugating E2 enzyme E2O is also involved in this process via its physically interaction with UBR2. We show that LF triggers activation of Nlrp1b by initiating the degradation of the N-terminal fragment of Nlrp1b itself that produced via an auto-cleavage process. This study deepens our understanding of innate immunity defense against bacterial infection by elucidating the functional role of UBR2-mediated N-end rule pathway in LF-induced Nlrp1b activation.
Fatiguing Effects of Indirect Vibration Stimulation in Upper Limb Muscles- pre, post and during Isometric Contractions Superimposed on Upper Limb Vibration
Authors: Pujari Amit N. , Neilson Richard D. , Cardinale Marco 
Published: September 2018

AbstractBackgroundIndirect vibration stimulation i.e. whole body vibration and upper limb vibration (ULV), are gaining popularity as exercise intervention for sports and rehabilitation applications. However, the fatiguing effects of indirect vibration stimulation are not yet fully understood. In addition, current vibration stimulation devices have a series of limitations. For this scope, we investigated the effects of ULV superimposed on fatiguing graded isometric contractions using a newly, purpose developed upper limb stimulation device. Twelve healthy volunteers were exposed to both ULV superimposed to fatiguing isometric contractions, at 80% of the maximum voluntary contractions (V) and just isometric contractions performed on a custom designed arm curl/flexion device- Control (C). The stimulation used consisted of 30Hz frequency of 0.4mm amplitude. Surface electromyographic (EMG) activity of the Biceps Brachii (BB), Triceps Brachii (TB), and Flexor Carpi Radialis (Forearm- FCR) were measured during both V and C conditions. EMG amplitude (EMGrms) and mean frequency (MEF) were computed to quantify muscle activity and fatigue levels respectively.ResultsAll three muscles BB, TB and FCR displayed significantly higher reduction in MEFs and corresponding significant increase in EMGrms with the V than the C, during fatiguing contractions (P < 0.05). Post vibration treatment, all muscles showed higher levels of MEFs after recovery compared to the control.ConclusionsOur results show that near maximal (80% of MVC) isometric fatiguing contractions superimposed on vibration stimulation lead to a higher rate of fatigue development compared to the isometric contraction alone in the upper limb muscles. Results also show, higher manifestation of mechanical fatigue post treatment with vibration compared to the control. Vibration superimposed on isometric contraction not only seems to alter the neuromuscular function during fatiguing efforts by inducing higher neuromuscular load but also post vibration treatment, potentially through the augmentation of stretch reflex and/or higher central motor command excitability.
Mechanistic basis for the evolution of chalcone synthase catalytic cysteine reactivity in land plants
Authors: Liou Geoffrey , Chiang Ying-Chih , Wang Yi , Weng Jing-Ke 
Published: September 2018

AbstractFlavonoids are important polyphenolic natural products, ubiquitous in land plants, that play diverse functions in plants’ survival in their ecological niches, including UV protection, pigmentation for attracting pollinators, symbiotic nitrogen fixation, and defense against herbivores. Chalcone synthase (CHS) catalyzes the first committed step in plant flavonoid biosynthesis and is highly conserved in all land plants. In several previously reported crystal structures of flowering plant CHSs, the catalytic cysteine is oxidized to sulfinic acid, indicating enhanced nucleophilicity in this residue associated with its increased susceptibility to oxidation. In this study, we report a set of new crystal structures of CHSs representing all five major lineages of land plants. We reveal that the structures of CHS from a lycophyte and a moss species preserve the catalytic cysteine in a reduced state, in contrast to the cysteine sulfinic acid seen in all euphyllophyte CHS structures. In vivo complementation, in vitro biochemical and mutagenesis analyses, as well as molecular dynamics simulations identify a set of residues that differ between basal-plant and euphyllophyte CHSs and modulate catalytic cysteine reactivity. We propose that the CHS active-site environment has evolved in euphyllophytes to further enhance the nucleophilicity of the catalytic cysteine since the divergence of euphyllophytes from other vascular plant lineages 400 million years ago. These changes in CHS could have contributed to the diversification of flavonoid biosynthesis in euphyllophytes, which in turn contributed to their dominance in terrestrial ecosystems.
MET-2, a SETDB1 family methyltransferase, coordinates embryo events through distinct histone H3 methylation states
Authors: Mutlu Beste , Chen Huei-Mei , Hall David H. , Mango Susan E. 
Published: September 2018

AbstractDuring the first hours of embryogenesis, formation of higher-order heterochromatin coincides with the loss of developmental potential. Here we examine the relationship between these two processes, and we probe the determinants that contribute to their onset. Mutations that disrupt histone H3 lysine 9 (H3K9) methyltransferases reveal that the methyltransferase MET-2 helps terminate developmental plasticity, likely through mono- and di- methylation of H3K9 (me1/me2), and promotes heterochromatin formation, likely through H3K9me3. We examine how MET-2 is regulated and find that methylated H3K9 appears gradually and depends on the accumulated time of embryogenesis. H3K9me is independent of zygotic genome activation or cell counting. These data reveal how central events are synchronized during embryogenesis and distinguish distinct roles for different H3K9 methylation states.Summary StatementDuring early embryogenesis, heterochromatin formation and loss of developmental plasticity are coordinately regulated by distinct Histone H3 Lysine 9 (H3K9) methylation states, by the methyltransferase MET-2.
Metabolomic analyses of plasma and liver of mice fed with immature Citrus tumida peel
Authors: Toyoda Atsushi , Sato Mizuho , Muto Masaki , Goto Tatsuhiko , Miyaguchi Yuji , Inoue Eiichi 
Published: September 2018

AbstractSupplementing food with functional small molecules has been shown to prevent diseases and improve the quality of life, especially in elderly people. Citrus fruits and citrus fruit-products are popular food supplements across the world. In this study, we focused on a Japanese citrus fruit, Citrus tumida hort. ex Tanaka (C. tumida), and elucidated the effects of supplementation of the peels of immature C. tumida (PIC) on food intake, body and fat tissue weights, and metabolic profiles of plasma and liver in mice. Supplementation with 5% (w/w) PIC for 4 weeks significantly suppressed body weight gain and decreased adipose tissue weight, including that of the epididymal, perirenal, and subcutaneous fats. Metabolome analyses using capillary electrophoresis time-of-flight mass spectrometry showed that the level of 2-hydroxyvaleric acid was reduced in the blood plasma of mice fed with PIC. Supplementation with PIC significantly elevated the levels of dipeptides (Thr-Asp, Ser-Glu, and Ala-Ala), glucuronic acid (and/or galacturonic acid-2), and S-methylglutathione, and significantly reduced the levels of betaine aldehyde in the liver. In conclusion, PIC supplementation affects the metabolism of fatty acids, pectin, glutathione, and choline. Our study demonstrates the potential beneficial effects of PIC, especially in metabolic syndrome and obesity. PIC may be developed as a functional food and used in the treatment of these diseases. Nutritional and metabolome studies are effective in studying the effects of specific dietary supplements and will contribute to the development of functional foods.
Disrespect and abuse of women during childbirth in public health facilities in Arba Minch town, South Ethiopia – a cross-sectional study
Authors: Ukke Gebresilasea Gendisha , Gurara Mekdes Kondale , Boynito Wanzahun Godana 
Published: September 2018

AbstractIntroductionDisrespect and abuse during childbirth is the main deterring factor to skilled birth utilization as compared to other more commonly known factors such as financial and physical inaccessibility.ObjectiveTo assess the occurrence of women’s disrespect and abuse during childbirth in public health facilities in Arba Minch town, south Ethiopia.MethodsInstitution based cross-sectional study design was employed at all public health institutions in Arba Minch town, south Ethiopia. Systematic sampling method was used to include 281 women who had given birth at public health institutions between January 01 and February 28, 2017. Data were collected by face to face interview by four midwife tutors and supervised by the principal investigator on daily bases. Semi-structured pretested questionnaire was used to collect data. Epi info version 7.1.2.0 and SPSS version 24 were used to enter and analyze the data respectively.ResultsA total of 281 women were participated in this study. The overall prevalence of non-respectful care was 98.9%. The women’s right to information and informed consent was the most frequently violated right with a prevalence of 92.5% (95% CI: 90.9, 94.1) followed by non-dignified care (36.7, 95% CI: 34.9, 38.5), physical abuse (29.5%, 95% CI: 24.2, 34.8), discrimination (18.1%, 95% CI: 13.6, 22.6), non-confidential care (17.1%,95% CI: 12.7, 21.5) and abandonment of care (4.3%, 95% CI: 3.1, 5.5). However, there is no woman who had been kept in detention in the health facilities. Being rural resident, giving birth in hospital, having no or low educational status and giving birth by cesarean route were factors which were significantly associated with specific women’s rights violations.Conclusions and recommendationsThe status of non-respectful and abusive care in the health care facilities in this study area is unacceptably high and needs serious attention by the health managers to tackle the problem.