bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of pvdE Pyoverdine Synthesis in Pseudomonas aeruginosa Keratitis
Authors: Suzuki Takashi , Okamoto Sayuri , Oka Naoko , Hayashi Naoki , Gotoh Naomasa , Shiraishi Atsushi
Published: September 2018

Purpose:

Pseudomonas aeruginosa produces pyoverdine, encoded by the pvdE gene, for high-affinity iron uptake from transferrin and lactoferrin. This study investigated the contribution of pyoverdine to P. aeruginosa keratitis pathogenesis using in vitro and in vivo models.

Methods:

The P. aeruginosa strains examined were parental strain PAO1 and isogenic mutant strain pvdE (ΔpvdE) defective in pyoverdine. Bacterial growth in vitro was determined by PAO1 and ΔpvdE optical densities in Luria–Bertani (LB) broth. PAO1 or ΔpvdE (108 colony-forming units/mL) was inoculated onto cultured human corneal epithelial cells (HCECs) for 1 hour. The monolayers were examined for bacterial adhesion and invasion. In addition, the corneas of C57BL/6 mice were infected with PAO1 or ΔpvdE. Corneal virulence was evaluated by determining clinical scores and bacterial counts during infection.

Results:

The growth of PAO1 and ΔpvdE in LB broth was similar. Although adhesion of ΔpvdE onto HCECs was significantly increased compared with PAO1, the invasive capacity of ΔpvdE was significantly decreased. Clinical scores and bacterial numbers were significantly lower in ΔpvdE-infected eyes compared with PAO1-infected eyes at 6, 24, and 48 hours (P < 0.001). ΔpvdE was not detected in mouse corneas and did not induce corneal opacity at 6, 24, or 48 hours.

Conclusions:

ΔpvdE lost invasive ability toward HCECs. Moreover, ΔpvdE did not cause keratitis in vivo. Thus, pvdE pyoverdine synthesis has critical roles in proliferation and invasion on ocular surfaces and could be a target for prevention of P. aeruginosa keratitis.
Fuchs Endothelial Corneal Dystrophy and Mitochondria
Authors: Miyai Takashi
Published: September 2018

Fuchs endothelial corneal dystrophy (FECD) is a bilateral progressive corneal endothelial disease characterized by guttae, which present as partial Descemet membrane thickening, inducing corneal edema at the final stage. Oxidative stress has been reported to play an important role in the pathogenesis of FECD. The electron transport chain and oxidative phosphorylation (oxphos) system in mitochondria are the main sources of endogenous oxidative stress, arising from superoxide generation through premature electron leakage to oxygen. In FECD, corneal endothelial cells have altered mitochondria with mitochondrial DNA damage, decreased oxphos proteins, and lower mitochondrial membrane potential. Mitochondrial dynamics and mitophagy comprise the organelle-level mitochondrial quality control system. Mitochondrial dynamics includes fusion and fission processes. When mitochondria are severely damaged, fission becomes the dominant process to remove damaged mitochondria. Mitophagy is a selective autophagy pathway that removes damaged mitochondria, and is triggered by mitochondrial membrane potential depolarization. In the FECD corneal endothelium, mitochondria have a fission-dominant morphology and low density through mitophagy upregulation because of quality control processes against altered mitochondria.
Congenital Corneal Opacities Associated With Trisomy 8 Mosaicism Syndrome
Authors: Welsh Christopher , Khalili Sina , Hazrati Lili-Naz , Mireskandari Kamiar
Published: September 2018

Purpose:

To describe the clinical, anterior segment optical coherence tomography (OCT) and histopathological features of 2 infants with congenital corneal opacities (CCOs) and undiagnosed trisomy 8 mosaicism syndrome (T8mS).

Methods:

This is a retrospective case report documenting ocular and systemic findings, imaging, pathology and management of 2 patients with T8mS.

Results:

An 11-month-old white male infant and a 4-week-old Asian female were initially seen for unilateral and bilateral CCOs, respectively. Corneal examination revealed para-axial anterior stromal opacities with blood vessels. Superficial irregular opacities were seen on OCT, and specular microscopy revealed normal endothelial cell morphology. One eye required superficial keratectomy to clear the visual axis and developed steroid-induced glaucoma in the early postoperative period, successfully treated with goniotomy. Both patients had hyperopia, anisometropia, and amblyopia, which was managed with glasses and patching. Cytogenetic testing (through microarray and fluorescence in situ hybridization) later diagnosed T8mS in both cases.

Conclusions:

T8mS should be considered in the differential diagnosis for superficial CCOs with blood vessels. Anterior segment OCT can guide management and cytogenetics performed to confirm diagnosis. Systemic associations and, in particular, risk of acute myeloid leukemia and myelodysplastic syndromes warrant prompt diagnosis of this condition.
Exploring the transcriptome of resident spinal microglia after collagen antibody–induced arthritis
Authors: Fernandez-Zafra Teresa , Gao Tianle , Jurczak Alexandra , Sandor Katalin , Hore Zoe , Agalave Nilesh M. , Su Jie , Estelius Johanna , Lampa Jon , Hokfelt Tomas , Wiesenfeld-Hallin Zsuzsanna , Xu Xiaojun , Denk Franziska , Svensson Camilla I.
Published: September 2018

Recent studies have suggested a sexually dimorphic role of spinal glial cells in the maintenance of mechanical hypersensitivity in rodent models of chronic pain. We have used the collagen antibody–induced arthritis (CAIA) mouse model to examine differences between males and females in the context of spinal regulation of arthritis-induced pain. We have focused on the late phase of this model when joint inflammation has resolved, but mechanical hypersensitivity persists. Although the intensity of substance P, calcitonin gene–related peptide, and galanin immunoreactivity in the spinal cord was not different from controls, the intensity of microglia (Iba-1) and astrocyte (glial fibrillary acidic protein) markers was elevated in both males and females. Intrathecal administration of the glial inhibitors minocycline and pentoxifylline reversed mechanical thresholds in male, but not in female mice. We isolated resident microglia from the lumbar dorsal horns and observed a significantly lower number of microglial cells in females by flow cytometry analysis. However, although genome-wide RNA sequencing results pointed to several transcriptional differences between male and female microglia, no convincing differences were identified between control and CAIA groups. Taken together, these findings suggest that there are subtle sex differences in microglial expression profiles independent of arthritis. Our experiments failed to identify the underlying mRNA correlates of microglial actions in the late phase of the CAIA model. It is likely that transcriptional changes are either subtle and highly localised and therefore difficult to identify with bulk isolation techniques or that other factors, such as changes in protein expression or epigenetic modifications, are at play.
Targeting the Nav1.8 ion channel engenders sex-specific responses in lysophosphatidic acid–induced joint neuropathy
Authors: O'Brien Melissa S. , Philpott Holly T.A. , McDougall Jason J.
Published: September 2018

Joint neuropathic pain occurs in a subset of arthritis patients, and lysophosphatidic acid (LPA) has been implicated as a mediator of joint neuropathy. The mechanism by which LPA promotes neuropathic pain is unknown but may be related to altered signalling of the voltage-gated sodium channel Nav1.8 located on nociceptors. Because arthritis and neuropathic pain are more prevalent in females, this study aimed to explore potential sex differences in the development of LPA-induced joint neuropathy and whether Nav1.8 played a role in the associated neuropathic pain. Joint neuropathy was induced in male and female Wistar rats (179-284 g) by intra-articular injection of 50-µg LPA. Pain behaviour was assessed over 21 days using von Frey hair algesiometry. On day 21, electrophysiological recordings of joint primary afferents were conducted to measure peripheral sensitisation. Saphenous nerve morphology and expression of the nerve-damage marker ATF3 and Nav1.8 in ipsilateral dorsal root ganglions were compared on the basis of sex. The analgesic properties of the selective Nav1.8 antagonist A-803467 was determined in pain behaviour and electrophysiology experiments. Females developed more severe mechanical allodynia than males after LPA treatment. Lysophosphatidic acid caused more pronounced demyelination of the saphenous nerve in females, but no sex differences were observed in the expression of ATF3 or Nav1.8 in dorsal root ganglion neurones. Blockade of Nav1.8 channels with A-803467 resulted in a decrease in joint mechanosensitivity and secondary allodynia with females exhibiting a greater response. These findings suggest that LPA has sex-specific effects on joint neuropathy and Nav1.8 gating, which should be considered when treating neuropathic arthritis patients.
Contribution of dorsal root ganglion octamer transcription factor 1 to neuropathic pain after peripheral nerve injury
Authors: Yuan Jingjing , Wen Jing , Wu Shaogen , Mao Yuanyuan , Mo Kai , Li Zhisong , Su Songxue , Gu Hanwen , Ai Yanqiu , Bekker Alex , Zhang Wei , Tao Yuan-Xiang
Published: September 2018

Neuropathic pain genesis is related to gene alterations in the dorsal root ganglion (DRG) after peripheral nerve injury. Transcription factors control gene expression. In this study, we investigated whether octamer transcription factor 1 (OCT1), a transcription factor, contributed to neuropathic pain caused by chronic constriction injury (CCI) of the sciatic nerve. Chronic constriction injury produced a time-dependent increase in the level of OCT1 protein in the ipsilateral L4/5 DRG, but not in the spinal cord. Blocking this increase through microinjection of OCT1 siRNA into the ipsilateral L4/5 DRG attenuated the initiation and maintenance of CCI-induced mechanical allodynia, heat hyperalgesia, and cold allodynia and improved morphine analgesia after CCI, without affecting basal responses to acute mechanical, heat, and cold stimuli as well as locomotor functions. Mimicking this increase through microinjection of recombinant adeno-associated virus 5 harboring full-length OCT1 into the unilateral L4/5 DRG led to marked mechanical allodynia, heat hyperalgesia, and cold allodynia in naive rats. Mechanistically, OCT1 participated in CCI-induced increases in Dnmt3a mRNA and its protein and DNMT3a-mediated decreases in Oprm1 and Kcna2 mRNAs and their proteins in the injured DRG. These findings indicate that OCT1 may participate in neuropathic pain at least in part by transcriptionally activating Dnmt3a and subsequently epigenetic silencing of Oprm1 and Kcan2 in the DRG. OCT1 may serve as a potential target for therapeutic treatments against neuropathic pain.
Psychosocial Predictors of Adjustment to Disability Among Patients With Breast Cancer: A Cross-Sectional Descriptive Study
Authors: ZHANG Qingyue , XIAO Shan , YAN Ling , SUN Liyuan , WANG Yan , HUANG Mengqiu
Published: September 2018

Background:

Acceptance of disability relates to the process of adaptation, which reflects how the values of a patient change over time to accept herself or himself as an intrinsically worthy person. Acceptance of disability (AOD) plays an important role in the adjustment of persons with physical disability to their environment. However, no studies on the level of AOD in patients with breast cancer are available in the literature.

Purpose:

The aim of this study was to explore the significant factors that influence disability acceptance in Chinese women with breast cancer.

Methods:

A cross-sectional study was conducted on 292 patients with breast cancer between January and April 2017. Participants were assessed using the Acceptance of Disability Scale-Revised, Medical Coping Modes Questionnaire, Sense of Coherence Scale, Social Relational Quality Scale, and general information questionnaire. Multiple regression analysis was used to determine the factors associated with the level of disability acceptance.

Results:

The mean score for AOD was 79.14 and ranged from 32 to 128. Multiple regression analysis indicated that family intimacy, friendships, confrontation, manageability, family commitment, marital status, surgery, and acceptance–resignation significantly affected disability acceptance, explaining 49.1% of the total variance in disability acceptance.

Conclusions/Implications for Practice:

The participants had a moderate level of disability acceptance. Disability acceptance is an important factor in the psychosocial adaptation to cancer. Healthcare staff should pay special attention to low scores for this factor and explore the potential of psychological interventions to effectively reduce the posttraumatic stress response, encourage the adoption of positive coping strategies, and hasten disability acceptance and return to society.
Using the Dietary Supplement Label Database to Identify Potentially Harmful Dietary Supplement Ingredients
Authors: Scott Jonathan M. , Lindsey Andrea T. , Costello Rebecca B. , Deuster Patricia A.
Published: September 2018

More than half of young adults, athletes, and Military Service members self-report using at least 1 dietary supplement (DS) 1 or more times per week. Dietary supplement may be consumed because users beige that they improve health, provide more energy, increase muscle strength, and/or enhance performance. The US Food and Drug Administration has raised concerns regarding adulteration, safety, and adverse events associated with DSs marketed for brain health and body building. Some DS products may compromise health as well as lead to a serious adverse event. The National Institutes of Health Dietary Supplement Label Database (DSLD), available at https://dsld.nlm.nih.gov/, can be freely accessed and used by researchers, providers, and consumers alike to screen for potentially harmful DSs. It was developed to serve the research community and as a resource for healthcare providers and the public. Herein, we provide 2 examples of how the database can be used to identify DS ingredients of concern in products marketed for brain health and body building. The search for DSs marketed for brain health returned 49 unique DSs, and the search for DSs marketed for body building returned 18 unique DSs. Search results were cross-referenced with the Operation Supplement Safety High-Risk Supplement List, the US Food and Drug Administration Tainted Products Marketed as Dietary Supplements list, the Natural Medicines database, and the National Institutes of Health Office of Dietary Supplements Fact Sheets. Three ingredients found in DSs marketed for brain health and 2 ingredients in DSs marketed for body building were identified as “of concern.” Educational tools, including the Dietary Supplement Label Database, can help consumers and providers make informed decisions regarding DSs.
What Is the Evidence Base for a Potassium Requirement?
Authors: Weaver Connie M. , Stone Michael S. , Lobene Andrea J. , Cladis Dennis P. , Hodges Joanna K.
Published: September 2018

Increased intake of potassium should be promoted to reduce the risk of cardiovascular disease and stroke and to protect against bone loss, but confidence in recommended intakes depends on the strength of the evidence. All public health recommendations are considerably higher than current average intakes. Evidence on which current potassium intake recommendations for the United States, Europe, and globally have limitations. More recent evidence reviewed by the Agency for Healthcare Research and Quality affirms that more evidence is needed to define specific values for optimal potassium intakes. Potassium requirements undoubtedly vary with a number of factors including energy needs, race, and intake of sodium.
Unique Circulating MicroRNA Profiles in HIV Infection
Authors: Narla Venkata , Bhakta Nirav , Freedman Jane E. , Tanriverdi Kahraman , Maka Kristinalisa , Deeks Steven G. , Ganz Peter , Hsue Priscilla
Published: September 2018

Objective:

MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression. We aimed to determine the association between extracellular miRNAs and HIV infection.

Design:

Single-center, cross-sectional study.

Methods:

We analyzed the expression of 192 plasma-derived miRNAs in 69 HIV-infected individuals and 24 uninfected controls using TaqMan miRNA assays and a high-throughput Real-Time PCR instrument (Fluidigm). False discovery rate (FDR) was applied.

Results:

HIV-infected individuals and controls were similar in age, sex, and traditional risk factors. Among those with HIV, 72.5% were on antiretroviral therapy (ARVs) and 64% had an undetectable viral load. Twenty-nine miRNAs were differentially expressed in the plasma of HIV-infected individuals compared with controls (P < 0.05, FDR < 0.15). Nineteen miRNAs were differentially expressed among HIV+ subjects on ARVs, HIV+ subjects not on ARVs, and HIV− subjects (P < 0.05 and FDR < 0.15). Thirty-four miRNAs were differentially expressed between HIV− subjects and elite controllers (ie, suppressed viral loads despite the absence of ARVs; P < 0.05 and FDR < 0.15). These 34 miRNAs included miRs-29c, 146b, 223, and 382, which were previously reported to have intracellular roles in HIV latency, as well as miRs-126, 145, and let-7, which were previously shown to be differentially expressed in coronary artery disease among uninfected individuals.

Conclusions:

We demonstrate a unique expression profile of 29 miRNAs in HIV+ subjects and 34 miRNAs in elite controllers as compared to HIV− subjects. These miRNA signatures may be useful in further elucidating mechanisms of viral and immunological control and may have diagnostic or prognostic value in HIV-associated coronary artery disease.
Brief Report: Hyperbilirubinemia Is Associated With a Decreased Risk of Carotid Atherosclerosis in HIV-Infected Patients on Virological Suppression
Authors: Muccini Camilla , Galli Laura , Poli Andrea , Carbone Alessia , Maillard Myriam , Giusti Maria Cristina , Spagnuolo Vincenzo , Bigoloni Alba , Guffanti Monica , Gianotti Nicola , Lazzarin Adriano , Castagna Antonella
Published: September 2018

Objective:

To investigate the association between total, direct, and indirect bilirubin and the presence of carotid lesions in a large sample of HIV-1–infected patients on virological suppression.

Design:

Retrospective study on adult HIV-1–infected patients, with a carotid ultrasound (CUS) examination performed between January 2008 and August 2016, with HIV-RNA <50 copies per milliliter at CUS and without previous cardiovascular events.

Methods:

Intima media thickness was measured in 4 segments: carotid common artery and bifurcation on the left and right sides. Carotid lesion was defined as an intima media thickness ≥1.5 mm in ≥1 region at CUS. Patients were classified as: normal if all bilirubin values before CUS were below the upper normal limit and with hyperbilirubinemia if ≥1 bilirubin value above upper normal limit before CUS was recorded. Multivariate logistic regression was used to determine whether hyperbilirubinemia showed association with the presence of ≥1 carotid lesion, after adjusting for confounding factors.

Results:

Overall, 903 patients were evaluated, 511 with ≥1 and 392 without carotid lesions. At multivariate analysis, total [adjusted odds ratio (95% confidence interval) 0.57 (0.36 to 0.90), P = 0.016] and indirect hyperbilirubinemia before CUS [adjusted odds ratio (95% confidence interval) 0.62 (0.40 to 0.97), P = 0.036] were associated with a lower risk of carotid lesions in addition to younger age, negative hepatitis C virus antibodies, higher nadir CD4+, lower low-density lipoprotein cholesterol, higher high-density lipoprotein cholesterol, lower triglycerides, and no use of statin; no effect of atazanavir treatment on carotid lesions was detected.

Conclusions:

In HIV-1–treated patients, total or indirect hyperbilirubinemia was likely associated with the absence of carotid lesions.
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

Innate 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

Background

Indirect 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.

Results

All 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.

Conclusions

Our 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.
Coexistence and cooperation in structured habitats
Authors: Geyrhofer Lukas , Brenner Naama
Published: September 2018

Many natural habitats are structured, which imposes certain environmental conditions on extant populations. Which conditions are important for coexistence of diverse communities, and how social traits in such populations stabilize, have been important ecological and evolutionary questions. We investigate a minimal ecological model of microbial population dynamics, that exhibits crucial features to show coexistence: Populations are repeatedly separated into compartmentalized habitats on a timescale typically longer than growth. In this framework, we consider several scenarios for possible interactions between different strains and their environments, which includes sharing a common nutrient source or expression of public goods that potentially increase population size. Examples for these public good dynamics are collective resistance against antibiotics, and enhanced iron-availability due to pyoverdine. We show that the two features of a long mixing timescale and spatial compartmentalization are already enough to enable coexisting strains. In the case of public goods, stable coexistence immediately entails cooperation.
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

Flavonoids 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

During 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 Statement

During 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

Supplementing 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

Introduction

Disrespect 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.

Objective

To assess the occurrence of women’s disrespect and abuse during childbirth in public health facilities in Arba Minch town, south Ethiopia.

Methods

Institution 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.

Results

A 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 recommendations

The 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.
Interrelationships among key Reproductive Health indicators in Sub-Saharan Africa
Authors: Woldegiorgis Mulu Abraha , Meyer Denny , Hiller Janet E. , Mekonnen Wubegzier , Bhowmik Jahar
Published: September 2018

Introduction

Indicators of reproductive health (RH) services, outputs, outcomes and impacts are expected to be related with each other and with key social determinants. As the provision of RH services is usually integrated, the effort expended to improve one component is also expected to affect the other components. There is a lack of evidence-based models demonstrating the interrelationships among these indicators and between RH indicators and social determinants.

Objective

To examine interrelationships among key RH indicators and their relationship with key social determinants in Sub-Saharan Africa (SSA).

Method

This study used data from the most recent demographic and health survey conducted during the period from 2010 to 2016 in 391 provinces of 29 SSA countries. We focused on seven RH indicator — antenatal care, skilled birth attendance, postnatal care, contraceptive prevalence rate (CPR), ideal number of children, birth interval and total fertility rate (TFR), along with selected socio-demographic indicators. The unit of analysis was sub-national, at provincial level. Structural equation modelling was used to examine the strength of interrelationships among the indicators based on the total standardized effect sizes. Significance tests and 95% confidence intervals for the total effects were presented using a bias-corrected bootstrap method.

Results

Women’s literacy rate, at the centre of the model, has direct connections with all the RH indicators included in the final model. The strongest relationship was observed between women’s literacy rate and CPR with a total standardized (std.) effect size of 0.79 (95% CI: 0.74, 0.83). RH indicators are interrelated directly and/or indirectly. A strong direct effect was also observed in the relationship between CPR and birth interval (β=0.63, 95%: 0.50, 0.77) and the model suggests that the reported ideal number of children is a key predictor of birth interval (Std. effect size=-0.58, 95% CI: -0.69, -0.48) and TFR (Std. effect size=0.52, 95% CI: 0.38, 0.62).

Conclusion

RH indicators are strongly interrelated and are all associated with women’s literacy. The model of interrelationships developed in this study may guide the design, implementation and evaluation of RH policies and programs.