Number 100

No abstract available

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Macrolide-resistant Mycoplasma genitalium infections in Cuban patients: an underestimated health problem

The increasing prevalence of macrolide resistant Mycoplasma genitalium is a major concern worldwide. In Cuba, several cases of clinical treatment failure with 1 g single dose and extended azithromycin regimen hav...

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Adaption and validation of the adherence barriers questionnaire for HIV patients on antiretroviral therapy (ABQ-HIV)

Despite substantial advances in antiretroviral therapy (ART) for human immunodeficiency virus (HIV) in the last decades, non-adherence (NA) continues to be a major challenge in the real-life treatment. To meet...

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A mathematical model of biomedical interventions for HIV prevention among men who have sex with men in China

The new HIV treatment guidelines in China recommend antiretroviral therapy (ART) for all people living with HIV, but significant gaps in implementation still exist. Pre-exposure prophylaxis (PrEP) can effectiv...

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Experimental and theoretical explorations of traveling waves and tonotopic tuning in the bushcricket hearing organ

The ability to detect air-born sound is essential for many animals. Examples from the inner ear of mammals and bushcrickets demonstrate that similar detection strategies evolved in taxonomically distant species. Both mammalian and bushcricket ears possess a narrow strip of sensory tissue that exhibits an anatomical gradient and traveling wave motion responses, used for frequency discrimination. We measured pressure and motion in the bushcricket ear to investigate physical properties, stiffness and mass, which govern the mechanical responses to sound.

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Population Shift Mechanism for Partial Agonism of AMPA Receptor

AMPA ionotropic glutamate receptors mediate fast excitatory neurotransmission in the central nervous system and their dysfunction is associated with neurological diseases. Glutamate binding to ligand-binding domains (LBDs) of AMPA receptors induces channel opening in the transmembrane domains of the receptors. The T686A mutation reduces glutamate efficacy, so that the glutamate behaves as a partial agonist. The crystal structures of wild-type and mutant LBDs are very similar and cannot account for the observed behavior.

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Surface-type chondromyxoid fibroma in an elderly patient: a case report and literature review

Abstract

Chondromyxoid fibroma (CMF) is a rare benign bone neoplasm that typically occurs in young adults. Juxtacortical or surface-type CMF are rarer still and we present the case of a surface-type CMF in a 78-year-old woman, with only one other case described in a patient of a similar age previously. This patient was an otherwise healthy woman who presented for evaluation of a palpable lump in the anterior proximal tibia. Initial radiographs obtained demonstrated a focal soft tissue fullness immediately anterior to the anterior cortex of the proximal tibia, which contained faint chondroid-like matrix internally. There was associated scalloping of the anterior tibial cortex. MRI confirmed the presence of a juxtacortical, enhancing lesion. Subsequent excisional biopsy was performed and histopathology demonstrated features, which was consistent with surface-type CMF. At a 6-month follow-up the patient remained free of recurrence. In a patient of this age, paraosteal chondrosarcoma should be excluded. Surface-type CMF, although rare, has been described in older patients and while it is unlikely to feature in a list of differential considerations on initial imaging, awareness of the entity is important.

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Cytotoxicity of Self-Adhesive Resin Cements on Human Periodontal Ligament Fibroblasts

The aim of this study was to evaluate the potential cytotoxicity of self-adhesive resin cements with or without light irradiation on human periodontal ligament fibroblasts (HPDLFs) in vitro. Three self-adhesive resin cements (RelyX U200, Maxcem Elite and Multilink Speed) were cured with light or not. Cured cements were stored at 37°C for 24 h in water or Dulbecco's modified eagle medium (DMEM) medium. Their chromatographic analysis of water-based extract solution was made and then the DMEM-based extract solution was diluted in complete DMEM 1:5, 1:10, 1:20, 1:40, 1:80 (v/v) for evaluating cell relative growth rate and cell apoptosis/necrosis rate of HPDLFs. The data was analyzed by one-way ANOVA and independent T test. Regardless of light irradiation, cell relative growth rate increased, and the apoptosis/necrosis rate of each resin cement decreased with the increase of gradient dilution. Regardless of gradient dilution, the cell relative growth rate and apoptosis/necrosis rate of RelyX U200 and Maxcem Elite with light irradiation were higher than those without light irradiation. Besides, without light irradiation, Multilink Speed showed higher cell relative growth rate and lower apoptosis/necrosis rate than other cements. Light irradiation and composition difference of self-adhesive resin cements could affect their cytotoxicity on HPDLFs.

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Combination Use of BMP2 and VEGF165 Promotes Osseointegration and Stability of Titanium Implants in Irradiated Bone

Background. Clinical data demonstrated that failure rate of titanium implant in irradiated bone was 2-3 times higher than that in nonirradiated bone and it is difficult to get the ideal results in irradiated bone. Purpose. The aim of the study was to investigate the effects of HBO, BMP2, VEGF165, and combined use of BMP2/VEGF165 on osseointegration and stability of titanium implant in irradiated bone. Materials and Methods. Sixty rabbits were randomly assigned to 5 groups (control group, HBO group, VEGF165 group, BMP2 group, and BMP2/VEGF165 group) after receiving 15 Gy radiation. Implant surgery was performed on tibias eight weeks later. They were sacrificed at two or eight weeks after operation. Implant stability, calcium, and ALP activity in serum, the ratio of bone volume to total volume, the rate of bone growth, and gene expression were assessed. Result. There was no mortality and no implants failed during the experiment. Implant stability was significantly compromised in the control group compared to the other four experimental groups, and the BMP2/VEGF165 group had the highest implant stability. HBO, BMP2, and VEGF165 significantly increased BV/TV and the rate of bone growth, while the BMP2/VEGF165 showed the best effect among groups. The expression of RUNX2 in HBO, BMP2, and VEGF165/BMP2 group was higher than that in the VEGF165 and control groups at two weeks. The expression of OCN in HBO, BMP2, VEGF165, and VEGF165/BMP2 groups was higher than that in the control group, and the gene expression of CD31 was higher in HBO, VEGF165, and BMP2/VEGF165 groups than that in control and BMP2 groups. Conclusion. HBO, BMP2, and VEGF165 could increase bone formation around the implant and improved the implant stability in irradiated bone. The combination use of BMP2 and VEGF165 may be promising in the treatment of implant patients with radiotherapy.

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Does the Current American Society of Anesthesiologists Physical Status Classification Represent the Chronic Disease Burden in Children Undergoing General Anesthesia?

No abstract available

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Pain Management: A Problem-Based Learning Approach

No abstract available

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Speaker Gender Representation at the American Society of Anesthesiology Annual Meeting: 2011–2016

The American Society of Anesthesiologists (ASA) Annual Meeting is the primary venue for anesthesiologists to present research, share innovations, and build networks. Herein, we describe gender representation for physician speakers at the Annual Meeting relative to the specialty overall. Details of ASA Annual Meeting presentations for individuals and panels were abstracted from the ASA archives for 2011–2016. Observed speaker gender composition was compared to expected composition based on the gender distribution of members of the ASA. There were 5167 speaker slots across 2025 presentations and panels. Of the speaker slots, 3874 were assigned to men and 1293 to women. Speaker slot gender composition was relatively consistent between 2011 and 2016 (annual percentage 22.3%–27.7% women, trend test P = .062). ASA membership composition of women increased slightly over the study period (24%–28%). The overall observed number of women in speaker slots over the study period did not differ significantly from what would be expected based on the ASA membership composition (25.0% observed vs 25.9% expected; P = .153). However, the percentage of single speakers who were women was significantly less than would be expected based on the ASA gender distribution (20.2% observed vs 25.9% expected; P

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The Impact of Postoperative Intensive Care Unit Admission on Postoperative Hospital Length of Stay and Costs: A Prespecified Propensity-Matched Cohort Study

BACKGROUND: In this prespecified cohort study, we investigated the influence of postoperative admission to the intensive care unit versus surgical ward on health care utilization among patients undergoing intermediate-risk surgery. METHODS: Of adult surgical patients who underwent general anesthesia without an absolute indication for postoperative intensive care unit admission, 3530 patients admitted postoperatively to an intensive care unit were matched to 3530 patients admitted postoperatively to a surgical ward using a propensity score based on 23 important preoperative and intraoperative predictor variables. Postoperative hospital length of stay and hospital costs were defined as primary and secondary end points, respectively. RESULTS: Among patients with low propensity for postoperative intensive care unit admission, initial triage to an intensive care unit was associated with increased postoperative length of stay (incidence rate ratio, 1.69 [95% CI, 1.59–1.79]; P

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General Anesthesia Alters the Diversity and Composition of the Intestinal Microbiota in Mice

Dysbiosis of the intestinal microbiota has been shown to result in altered immune responses and increased susceptibility to infection; as such, the state of the intestinal microbiome may have profound implications in the perioperative setting. In this first-in-class study, we used 16s ribosomal RNA sequencing and analysis in a mouse model of general anesthesia to investigate the effects of volatile anesthetics on the diversity and composition of the intestinal microbiome. After 4-hour exposure to isoflurane, we observed a decrease in bacterial diversity. Taxonomic alterations included depletion of several commensal bacteria including Clostridiales. These data identify volatile anesthetics as potential contributors to microbial dysbiosis in the postoperative patient. Accepted for publication October 17, 2018. Funding:This work was supported by grants from the National Institutes of Health (R01 GM120519-01). The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Cyrus D. Mintz, MD, PhD, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross Bldg 370, Baltimore, MD 21205. Address e-mail to Cmintz2@jhmi.edu. © 2018 International Anesthesia Research Society

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Remote Surveillance Technologies: Realizing the Aim of Right Patient, Right Data, Right Time

The convergence of multiple recent developments in health care information technology and monitoring devices has made possible the creation of remote patient surveillance systems that increase the timeliness and quality of patient care. More convenient, less invasive monitoring devices, including patches, wearables, and biosensors, now allow for continuous physiological data to be gleaned from patients in a variety of care settings across the perioperative experience. These data can be bound into a single data repository, creating so-called data lakes. The high volume and diversity of data in these repositories must be processed into standard formats that can be queried in real time. These data can then be used by sophisticated prediction algorithms currently under development, enabling the early recognition of patterns of clinical deterioration otherwise undetectable to humans. Improved predictions can reduce alarm fatigue. In addition, data are now automatically queriable on a real-time basis such that they can be fed back to clinicians in a time frame that allows for meaningful intervention. These advancements are key components of successful remote surveillance systems. Anesthesiologists have the opportunity to be at the forefront of remote surveillance in the care they provide in the operating room, postanesthesia care unit, and intensive care unit, while also expanding their scope to include high-risk preoperative and postoperative patients on the general care wards. These systems hold the promise of enabling anesthesiologists to detect and intervene upon changes in the clinical status of the patient before adverse events have occurred. Importantly, however, significant barriers still exist to the effective deployment of these technologies and their study in impacting patient outcomes. Studies demonstrating the impact of remote surveillance on patient outcomes are limited. Critical to the impact of the technology are strategies of implementation, including who should receive and respond to alerts and how they should respond. Moreover, the lack of cost-effectiveness data and the uncertainty of whether clinical activities surrounding these technologies will be financially reimbursed remain significant challenges to future scale and sustainability. This narrative review will discuss the evolving technical components of remote surveillance systems, the clinical use cases relevant to the anesthesiologist's practice, the existing evidence for their impact on patients, the barriers that exist to their effective implementation and study, and important considerations regarding sustainability and cost-effectiveness. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Accepted for publication October 18, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Jeanine P. Wiener-Kronish, MD, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, GRB 4–444, Boston, MA 02114. Address e-mail to jwiener-kronish@partners.org. © 2018 International Anesthesia Research Society

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Optimal Muscle Selection for OnabotulinumtoxinA Injections in Post-stroke Lower-Limb Spasticity: A Randomized Trial

OBJECTIVE To identify optimal muscle selection patterns for onabotulinumtoxinA treatment of post-stroke lower-limb spasticity (PSLLS). DESIGN Adults with PSLLS (ankle Modified Ashworth Scale [MAS] ≥3) were randomized to onabotulinumtoxinA (300 U, mandatory ankle plantar flexors; ≤100 U, optional lower-limb muscles) or placebo. Post hoc analysis assessed the impact of muscle selection patterns on ankle MAS and physician-assessed Clinical Global Impression of Change (CGI) based on change from baseline to average of weeks 4/6 versus placebo. RESULTS Among 468 patients randomized, onabotulinumtoxinA improved ankle MAS (–0.81 vs –0.61; P=0.01) and CGI (0.86 vs 0.65; P=0.012) versus placebo. Injection of mandatory muscles alone was not sufficient in improving ankle MAS (P=0.255) or CGI (P=0.576) versus placebo but was adequate ≤24 months post-stroke (MAS, –1.13 vs –0.62, P=0.019; CGI, 1.24 vs 0.68, P=0.006). Additional injections into toe muscles (flexor digitorum longus, flexor hallucis longus) improved ankle MAS (–0.98 vs –0.52; P=0.002) and CGI (0.80 vs 0.38; P=0.023) versus placebo regardless of time since stroke. OnabotulinumtoxinA was well tolerated, with no new safety findings. CONCLUSIONS Post hoc analyses suggested additional injections of onabotulinumtoxinA into toe flexors improved ankle MAS and CGI scores versus mandatory muscles alone overall and with treatment initiation >24 months post-stroke. Address correspondence to: Alberto Esquenazi, MD, Department of Physical Medicine and Rehabilitation, MossRehab Gait and Motion Analysis Laboratory, 60 Township Line Road, Elkins Park, PA 19027. Phone: 215-663-6676. Fax: 215-663-6686. aesquena@einstein.edu Disclosures: Competing Interests: Alberto Esquenazi, MD: Dr Esquenazi has received research support from and acted as a consultant for Allergan and Ipsen. Theodore H. Wein, MD, FRCPC: Dr Wein has received research funds from Allergan plc, Merz, National Institutes of Health, Accorda, and Boehringer Ingelheim; acted as a consultant for Allergan plc and Ispen; and received honoraria for accredited CME from Bayer and Boehringer Ingelheim. Anthony B. Ward, MD, FRCP: Dr Ward is a speaker and consultant for Allergan plc and Ipsen. Carolyn Geis, MD: Dr Geis has received research support from and is a speaker/consultant for Allergan plc. Chengcheng Liu, PhD, and Rozalina Dimitrova, MD, MPH, are employees of Allergan plc and Rozalina Dimitrova holds stock in the company. Study funding: This study and analysis were sponsored by Allergan plc (Dublin, Ireland). The study sponsor was involved in the study design, data collection, data analysis, data interpretation, and writing of the article. Assistance with medical writing was provided by Complete Healthcare Communications, LLC (West Chester, PA). Details of Previous Presentations: The REFLEX Study subanalysis on muscle selection patterns for onabotulinumtoxinA has been presented at the following conferences: Wein T, Esquenazi A, Ward A, Geis C, Liu C, Dimitrova R. Muscle Selection Patterns for Injection of OnabotulinumtoxinA in Adult Patients With Post-Stroke Lower-Limb Spasticity Influence Outcome: Results From a Double-Blind, Placebo-Controlled Phase 3 Clinical Trial. American Academy of Neurology 2016 - 68th Annual Meeting. 2016. Wein T, Esquenazi A, Ward A, Geis C, Liu C, Dimitrova R. Muscle Selection Patterns for Injection of OnabotulinumtoxinA in Adult Patients With Post-Stroke Lower-Limb Spasticity Influence Outcome: Results From a Double-Blind, Placebo-Controlled Phase 3 Clinical Trial. World Federation for NeuroRehabilitation - 9th World Congress for NeuroRehabilitation. 2016. Wein T, Esquenazi A, Ward A, Geis C, Liu C, Dimitrova R. Muscle Selection Patterns for Injection of OnabotulinumtoxinA in Adult Patients With Post-Stroke Lower-Limb Spasticity Influence Outcome: Results From a Double-Blind, Placebo-Controlled Phase 3 Clinical Trial. Movement Disorder Society - 20th International Congress of Parkinson's Disease and Movement Disorder. 2016. Wein T, Esquenazi A, Ward A, Geis C, Liu C, Dimitrova R. Muscle Selection Patterns for Injection of OnabotulinumtoxinA in Adult Patients With Post-Stroke Lower-Limb Spasticity Influence Outcome: Results From a Double-Blind, Placebo-Controlled Phase 3 Clinical Trial. American Academy of Physical Medicine and Rehabilitation. 2016. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Letter to the Editor Re: Comorbidities and Mobility in Lower Limb Prosthesis Users

No abstract available

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ANALYSIS OF CELL VIABILITY AND GENE EXPRESSION AFTER CONTINUOUS ULTRASOUND THERAPY IN L929 FIBROBLAST CELLS

Objective This study aimed to analyze cell viability and gene expression IL-6 (interleukin-6) and VEGF (vascular endothelial growth factor) after continuous ultrasound therapy of 1 and 3 MHz on L929 fibroblast cells. Design The L929 cells were cultivated in 12-well plates and divided into 5 groups: G1: non-irradiated, G2: 0.2 W/cm2-1 MHz, G3: 0.5 W/cm2-1 MHz, G4: 0.2 W/cm2-3 MHz and G5: 0.5 W/cm2-3 MHz. The cells were irradiated at 24 hours and 48 hours. Cell viability was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. The gene expression analysis was assessed using real-time PCR. Results The G2 and G3 groups showed a decrease in cell viability when compared to the G1 at 48 hours (p

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Enhancement of neuroprotective activity of Sagunja-tang by fermentation with lactobacillus strains

Sagunja-tang (SGT) is widely used in traditional herbal medicine to treat immune system and gastrointestinal disorders and reportedly has protective effects against inflammation, cancer, and osteoporosis. In t...

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Endocrine Therapy for Ductal Carcinoma In Situ (DCIS) of the Breast with Breast Conserving Surgery (BCS) and Radiotherapy (RT): a Meta-Analysis

Abstract

The management of ductal carcinoma in situ (DCIS) with endocrine therapy remains controversial. A meta-analysis was conducted to evaluate the role of endocrine therapy for DCIS with breast conserving surgery (BCS) and radiotherapy (RT). A total of 7 articles with randomized controlled trials were included. Five articles compared the effects of BCS and RT followed by tamoxifen (TAM) or not (BCS + RT + TAM vs BCS + RT) and 2 compared the effects of TAM and anastrozole (ANA). TAM obviously reduced the rates of recurrence of ipsilateral breast cancer (IBCR), recurrence of contralateral breast cancer (CBCR), recurrence of ipsilateral invasive breast cancer (IBCR-INV) and recurrence of contralateral DCIS (CBCR-DCIS), and increased the rate of event-free survival (EFS). While ANA reduced the rates of CBCR and recurrence of contralateral invasive breast cancer (CBCR-INV). Patients with ANA had higher incidence of arthralgia, osteoporosis, hypercholesteremia, headache and vaginal dryness, but lower incidence of deep-vein thrombosis, pulmonary embolism, vasomotor or gynaecological, hot flushes, vaginal haemorrhage, vaginal discharge and vaginal candidiasis than TAM. In conclusion, DCIS patients with positive hormone receptors should be recommended to receive endocrine therapy. Selection of TAM or ANA is based on clinical characteristics and underlying disease of patients, as well as the side-effects of drugs.

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Endometrial Cancer Spheres Show Cancer Stem Cells Phenotype and Preference for Oxidative Metabolism

Abstract

This study aimed to characterize endometrial cancer regarding cancer stem cells (CSC) markers, regulatory and differentiation pathways, tumorigenicity and glucose metabolism. Endometrial cancer cell line ECC1 was submitted to sphere forming protocols. The first spheres generation (ES1) was cultured in adherent conditions (G1). This procedure was repeated and was obtained generations of spheres (ES1, ES2 and ES3) and spheres-derived cells in adherent conditions (G1, G2 and G3). Populations were characterized regarding CD133, CD24, CD44, aldehyde dehydrogenase (ALDH), hormonal receptors, HER2, P53 and β-catenin, fluorine-18 fluorodeoxyglucose ([¹⁸F]FDG) uptake and metabolism by NMR spectroscopy. An heterotopic model evaluated differential tumor growth. The spheres self-renewal was higher in ES3. The putative CSC markers CD133, CD44 and ALDH expression were higher in spheres. The expression of estrogen receptor (ER)α and P53 decreased in spheres, ERβ and progesterone receptor had no significant changes and β-catenin showed a tendency to increase. There was a higher ¹⁸F-FDG uptake in spheres, which also showed a lower lactate production and an oxidative cytosol status. The tumorigenesis in vivo showed an earlier growth of tumours derived from ES3. Endometrial spheres presented self-renewal and differentiation capacity, expressed CSC markers and an undifferentiated phenotype, showing preference for oxidative metabolism.

https://ift.tt/2Av69N5

Exploring variation in how ambulance services address non-conveyance: a qualitative interview study

Objectives

There is considerable variation in non-conveyance rates between ambulance services in England. The aim was to explore variation in how each ambulance service addressed non-conveyance for calls ending in telephone advice and discharge at scene.

Design

A qualitative interview study.

Setting

Ten large regional ambulance services covering 99% of the population in England.

Participants

Between four and seven interviewees from each ambulance service including managers, paramedics and healthcare commissioners, totalling 49 interviews.

Methods

Telephone semistructured interviews.

Results

The way interviewees in each ambulance service discussed non-conveyance within their organisation varied for three broad themes. First, ambulance service senior management appeared to set the culture around non-conveyance within an organisation, viewing it either as an opportunity or as a risky endeavour. Although motivation levels to undertake non-conveyance did not appear to be directly affected by the stability of an ambulance service in terms of continuity of leadership and externally assessed quality, this stability could affect the ability of the organisation to innovate to increase non-conveyance rates. Second, descriptions of workforce configuration differed between ambulance services, as well as how this workforce was used, trained and valued. Third, interviewees in each ambulance service described health and social care in the wider emergency and urgent care system differently in terms of availability of services that could facilitate non-conveyance, the amount of collaborative working between health and social care services and the ambulance service and complexity related to the numbers of services and healthcare commissioners with whom they had to work.

Conclusions

This study suggests that factors within and outside the control of ambulance services may contribute to variation in non-conveyance rates. These findings can be tested in a quantitative analysis of factors affecting variation in non-conveyance rates between ambulance services in England.

https://ift.tt/2AvCeEu

Qualitative study exploring the factors influencing physical therapy management of early knee osteoarthritis in Canada

Objectives

Increasingly, there is emphasis on identifying and initiating treatment of osteoarthritis (OA) in the early phases of the disease. This study aimed to identify the perceived barriers and facilitators to managing clients with early knee OA and the contextual factors affecting implementation of care by physical therapists (PTs).

Design

Qualitative study using in-depth semistructured interviews with 33 PTs. The interviews were audio-recorded, transcribed verbatim and analysed inductively using thematic analysis.

Setting

Canada.

Participants

A purposive sample of PTs who managed clients with knee symptoms and/or diagnosed knee OA in community/outpatient settings in three provinces in Canada (Ontario, Alberta, British Columbia).

Results

Factors that affected physical therapy management of early knee OA were identified at four levels: the community, healthcare system, healthcare provider and client level. Some healthcare provider factors acted primarily as enablers of management, such as PTs' confidence in their ability to manage perceived early knee OA, PTs' beliefs about consequences of OA and the PT scope of practice. However, the study illuminated a range of modifiable factors that can act as barriers to management. These factors included access to services in the community and healthcare system; healthcare provider factors such as time, access to evidence and physician's role in referrals and messaging; and client factors related to client characteristics (eg, general health, socioeconomic status), engagement in management and beliefs about OA.

Conclusion

These findings provide us with a basis to begin to address specific barriers and to optimise care for early knee OA.

https://ift.tt/2FKQFKH

Mental health-related emergency department presentations and hospital admissions in a cohort of urban Aboriginal children and adolescents in New South Wales, Australia: findings from SEARCH

Objectives

The aim of the current study is to quantify mental health-related emergency department (ED) presentations and hospitalisations, and associated child and family characteristics, in children recruited through four Aboriginal Community Controlled Health Organisations.

Setting

Four Aboriginal Community Controlled Health Services that deliver primary care. All services were located in urban or large regional centres in New South Wales, Australia.

Participants

1476 Aboriginal children aged 0–17 years at recruitment to the Study of Environment on Aboriginal Resilience and Child Health.

Primary outcome measures

ED presentations and hospital admissions with a primary mental health diagnosis obtained via linkage to population health datasets.

Results

Over a median of 6-year follow-up, there were 96 ED presentations affecting 62 children (10.7/1000 person-years) and 49 hospitalisations affecting 34 children (5.5/1000 person-years) for mental health conditions. Presentations/admissions increased with age. ED presentation was increased with: living in foster versus parental care (adjusted rate ratio (RR)=3.97, 95% CrI 1.26 to 11.80); high versus low baseline child emotional/behavioural problems (adjusted RR=2.93, 95% CrI 1.50 to 6.10); and caregiver chronic health conditions versus none (adjusted RR=2.81, 95% CrI 1.31 to 6.63). Hospitalisations were significantly increased with caregiver unemployment versus home duties (adjusted RR=4.48, 95% CrI 1.26 to 17.94) and caregiver chronic health problems versus none (adjusted RR=3.83, 95% CrI 1.33 to 12.12).

Conclusions

Tertiary care for mental health issues was relatively common among participating Aboriginal children, with risk elevated for those living in foster care, with prior mental health and behavioural problems and with carers with chronic illness and/or unemployment. While this study suggests high rates of serious mental health events among children from participating communities, the optimum means for reducing these rates, and the need for tertiary care, has not yet been determined. Such information is urgently required to inform policy and programmes to support Aboriginal child and adolescent mental health.

https://ift.tt/2r9iamO

Adverse pregnancy and neonatal outcomes associated with Neisseria gonorrhoeae, Mycoplasma genitalium, M. hominis, Ureaplasma urealyticum and U. parvum: a systematic review and meta-analysis protocol

Introduction

Several bacterial sexually transmitted and genital mycoplasma infections during pregnancy have been associated with poor pregnancy and perinatal outcomes. Comprehensive and systematic information about associations between sexually transmitted infections (STI) and genital infections in pregnancy and adverse perinatal outcomes is needed to improve understanding about the evidence for causal associations between these infections and adverse pregnancy and neonatal outcomes. Our primary objective is to systematically review the literature about associations between: (1) Neisseria gonorrhoeae in pregnancy and preterm birth; (2) Mycoplasma genitalium in pregnancy and preterm birth; (3) M. hominis, Ureaplasma urealyticum and/or U. parvum in pregnancy and preterm birth.

Methods and analysis

We will undertake a systematic search of Medline, Excerpta Medica database and the Cochrane Library and Cumulative Index to Nursing and Allied Health Literature. Following an initial screening of titles by one reviewer, abstracts will be independently assessed by two reviewers before screening of full-text articles. To exclude a manuscript, both reviewers need to agree on the decision. Any discrepancies will be resolved by discussion, or the adjudication of a third reviewer. Studies will be included if they report testing for one or more of N. gonorrhoeae, M. genitalium, M. hominis, U. urealyticum and/or U. parvum during pregnancy and report pregnancy and/or birth outcomes. In this review, the primary outcome is preterm birth. Secondary outcomes are premature rupture of membranes, low birth weight, spontaneous abortion, stillbirth, neonatal mortality and ophthalmia neonatorum. We will use standard definitions, or definitions reported by study authors. We will examine associations between exposure and outcome in forest plots, using the I² statistic to examine between study heterogeneity. Where appropriate, we will use meta-analysis to combine results of individual studies.

Ethics and dissemination

This systematic review of published literature does not require ethical committee approval. Results of this review will be published in a peer reviewed, open access journal.

PROSPERO registration number

CRD42016050962.

https://ift.tt/2FMmWAV

Impact of resilience on health in older adults: a cross-sectional analysis from the International Mobility in Aging Study (IMIAS)

Objectives

Self-rated health (SRH) is a predictor of objective health measures, including mortality and morbidity. The link between resilience and SRH among the elderly is unclear. We aim to examine whether resilience aligns with SRH and, secondarily, whether resilience can override the negative health consequences of adverse childhood experiences (ACE).

Design and setting

We use 2012, 2014 and 2016 data from the International Mobility in Aging Study, a longitudinal cohort study that collects survey and biophysical data from Albania, Brazil, Colombia and Canada. The main independent variables were resilience and ACE (social and economic).

Participants

Community-dwelling 65–74 year olds (in 2012) were recruited through primary care registers. The sample size of the study was 1506.

Primary outcome

The outcome measure was SRH.

Results

We found that sex, site, economic ACE, current income sufficiency, current depressive symptoms, current physical function and current resilience were associated with current SRH. In regression analyses, we showed that the association between ACE and SRH disappeared once factors such as sex, site, income, depression, physical health and resilience were considered.

Conclusions

The association between resilience and health poses a compelling argument for building resilience throughout life.

https://ift.tt/2rcIpsC

Residual pulmonary vascular obstruction and recurrence after acute pulmonary embolism: protocol for a systematic review and meta-analysis of individual participant data

Background

In patients with a first, unprovoked venous thromboembolism (VTE), the optimal duration of anticoagulant therapy (AT) is controversial due to tightly balanced risks and benefits of indefinite anticoagulation. The objective of this study is to assess among patients with a first acute pulmonary embolism (PE) who received ≥3 months of AT and thereafter had a planar lung scan, whether residual pulmonary vascular obstruction (RPVO) is associated with VTE recurrence after discontinuation of AT.

Methods and analysis

We will conduct a systematic review with a meta-analysis of individual participant data of contemporary studies evaluating the prognostic significance of RPVO in patients with a first acute PE. We will search from inception to 24 January 2018, PubMed, Medline, Embase and Cochrane's Central Registry for Randomized Controlled Trials, CENTRAL for randomized controlled trials and prospective cohort studies. Two reviewers will conduct all screening and data collection independently. The methodological quality and risk of bias of eligible studies will be carefully and rigorously assessed using the Risk Of Bias In Non-randomised Studies of Interventions tool. The primary objective will be to assess the relationship between RPVO on ventilation–perfusion scan after completion of at least 3 months of AT after an acute PE event, and the risk of an objectively confirmed symptomatic recurrent VTE (including deep vein thrombosis or PE) or death due to PE. The secondary objectives will include the assessment of the optimal RPVO cut-off and the risk of recurrent VTE, as well as the relationship between the relative change in RPVO between PE diagnosis and at discontinuation of AT (≥3 months) and risk of recurrent VTE.

Ethics and dissemination

This study of secondary data does not require ethics approval. It will be presented internationally and published in the peer-reviewed literature.

PROSPERO registration number

CRD42017081080.

https://ift.tt/2TYD3P9

Improving social inclusion for people with dementia and carers through sharing dance: a qualitative sequential continuum of care pilot study protocol

Introduction

This study examines the potential of dance to improve social inclusion for people living with dementia and carers. Research suggests that arts-based programmes can improve the health of people living with dementia and carers; however, little is known about how these programmes might address barriers to social inclusion. Addressing barriers requires the development and evaluation of accessible, non-stigmatising and affordable programmes that facilitate social inclusion across the continuum of institutional, community and household care settings.

Methods and analysis

The study involves a qualitative sequential pilot study of the innovative Baycrest NBS Sharing Dance Seniors programme underway in non-metropolitan regions of two Canadian provinces. It focuses on the remotely instructed delivery of the programme in care facilities, community centres and households. The study involves five phases of observations, diaries, focus groups and interviews with programme participants (people living with dementia), carers, coordinators, instructors and volunteers as well as critical reflections among research investigators and knowledge users. NVivo-based thematic and narrative analyses of the qualitative data will produce new knowledge about the experiences, effectiveness and challenges of the dance programme that will inform understanding of whether and in what ways it increases social inclusion and quality of life for older people living with dementia and carers. The findings will identify opportunities for programme expansion and support the further development of arts-based approaches.

Ethics and dissemination

The study is approved by the Research Ethics Boards at Trent University and Brandon University, and by participating organisations according to their governance procedures. The perspectives of people living with dementia and carers are incorporated throughout the study (from design to dissemination) and the study adheres to the ethical considerations when including people with dementia. A series of publicly available reports, seminars and symposia will be undertaken in collaboration with knowledge user and collaborating organisation partners.

https://ift.tt/2TXvAzs

Antibiotic use in children with asthma: cohort study in UK and Dutch primary care databases

Objectives

To compare the rate, indications and type of antibiotic prescriptions in children with and without asthma.

Design

A retrospective cohort study.

Setting

Two population-based primary care databases: Integrated Primary Care Information database (IPCI; the Netherlands) and The Health Improvement Network (THIN; the UK).

Participants

Children aged 5–18 years were included from January 2000 to December 2014. A child was categorised as having asthma if there were ≥2 prescriptions of respiratory drugs in the year following a code for asthma. Children were labelled as non-asthmatic if no asthma code was recorded in the patient file.

Main outcome measures

Rate of antibiotic prescriptions, related indications and type of antibiotic drugs.

Results

The cohorts in IPCI and THIN consisted of 946 143 and 7 241 271 person years (PY), respectively. In both cohorts, antibiotic use was significantly higher in asthmatic children (IPCI: 197vs126 users/1000 PY, THIN: 374vs250 users/1000 PY). In children with asthma, part of antibiotic prescriptions were for an asthma exacerbation only (IPCI: 14%, THIN: 4%) and prescriptions were more often due to lower respiratory tract infections then in non-asthmatic children (IPCI: 18%vs13%, THIN: 21%vs12%). Drug type and quality indicators depended more on age, gender and database than on asthma status.

Conclusions

Use of antibiotics was higher in asthmatic children compared with non-asthmatic children. This was mostly due to diseases for which antibiotics are normally not indicated according to guidelines. Further awareness among physicians and patients is needed to minimise antibiotic overuse and limit antibiotic resistance.

https://ift.tt/2TUOuHy

Effectiveness of online interventions in preventing depression: a protocol for systematic review and meta-analysis of randomised controlled trials

Introduction

Although evidence exists for the efficacy of psychosocial interventions in preventing depression, little is known about its prevention through online interventions. The objective of this study is to conduct a systematic review and meta-analysis of randomised controlled trials assessing the effectiveness of online interventions in preventing depression in heterogeneous populations.

Methods and analysis

We will conduct a systematic review and meta-analysis of randomised controlled trials that will be identified through searches of PubMed, PsycINFO, WOS, Scopus, OpenGrey, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and Australia New Zealand Clinical Trials Register . We will also search the reference lists provided in relevant studies and reviews. Experts in the field will be contacted to obtain more references. Two independent reviewers will assess the eligibility criteria of all articles, extract data and determine their risk of bias (Cochrane Collaboration Tool). Baseline depression will be required to have been discarded through standardised interviews or validated self-reports with standard cut-off points. The outcomes will be the incidence of new cases of depression and/or the reduction of depressive symptoms as measured by validated instruments. Pooled standardised mean differences will be calculated using random-effect models. Heterogeneity and publication bias will be estimated. Predefined sensitivity and subgroup analyses will be performed. If heterogeneity is relevant, random-effect meta-regression will be performed.

Ethics and dissemination

The results will be disseminated through peer-reviewed publication and will be presented at a professional conference. Ethical assessment is not required as we will search and assess existing sources of literature.

Trial registration number

CRD42014014804; Results.

https://ift.tt/2Aw6Sxs

The association between insulin therapy and depression in patients with type 2 diabetes mellitus: a meta-analysis

Objectives

Several patients with type 2 diabetes mellitus (T2DM) have depressive disorders. Whether insulin treatment was associated with increased risk of depression remains controversial. We performed a meta-analysis to evaluate the association of insulin therapy and depression.

Design

A meta-analysis.

Methods

We conducted a systematic search of PubMed, PsycINFO, Embase and the Cochrane Library from their inception to April 2016. Epidemiological studies comparing the prevalence of depression between insulin users and non-insulin users were included. A random-effects model was used for meta-analysis. The adjusted and crude data were analysed.

Results

Twenty-eight studies were included. Of these, 12 studies presented with adjusted ORs. Insulin therapy was significantly associated with increased risk of depression (OR=1.41, 95% CI 1.13 to 1.76, p=0.003). Twenty-four studies provided crude data. Insulin therapy was also associated with an odds for developing depression (OR=1.59, 95% CI 1.41 to 1.80, p<0.001). When comparing insulin therapy with oral antidiabetic drugs, significant association was observed for adjusted (OR=1.42, 95% CI 1.08 to 1.86, p=0.008) and crude (OR=1.61, 95% CI 1.35 to 1.93, p<0.001) data.

Conclusions

Our meta-analysis confirmed that patients on insulin therapy were significantly associated with the risk of depressive symptoms.

https://ift.tt/2TWqaoo

Acceptance and commitment therapy (ACT) for adult type 1 diabetes management: study protocol for a randomised controlled trial

Introduction

Integrating diabetes self-management into daily life involves a range of complex challenges for affected individuals. Environmental, social, behavioural and emotional psychological factors influence the lives of those with diabetes. The aim of this study is to evaluate the impact of a stress management group intervention based on acceptance and commitment therapy (ACT) among adults living with poorly controlled type 1 diabetes.

Methods and analysis

This study will use a randomised controlled trial design evaluating treatment as usual (TAU) and ACT versus TAU. The stress management group intervention will be based on ACT and comprises a programme divided into seven 2-hour sessions conducted over 14 weeks. A total of 70 patients who meet inclusion criteria will be recruited over a 2-year period with follow-up after 1, 2 and 5 years.

The primary outcome measure will be HbA_1c. The secondary outcome measures will be the Depression Anxiety Stress Scales, the Swedish version of the Hypoglycemia Fear Survey, the Swedish version of the Problem Areas in Diabetes Scale, The Summary of Self-Care Activities, Acceptance Action Diabetes Questionnaire, Swedish Acceptance and Action Questionnaire and the Manchester Short Assessment of Quality of Life. The questionnaires will be administered via the internet at baseline, after sessions 4 (study week 7) and 7 (study week 14), and 6, 12 and 24 months later, then finally after 5 years. HbA_1c will be measured at the same time points.

Assessment of intervention effect will be performed through the analysis of covariance. An intention-to-treat approach will be used. Mixed-model repeated measures will be applied to explore effect of intervention across all time points.

Ethics and dissemination

The study has received ethical approval (Dnr: 2016/14-31/1). The study findings will be disseminated through peer-reviewed publications, conferences and reports to key stakeholders.

Trial registration number

NCT02914496; Pre-results.

https://ift.tt/2AH04NJ

Do care plans and annual reviews of physical health influence unplanned hospital utilisation for people with serious mental illness? Analysis of linked longitudinal primary and secondary healthcare records in England

Objective

To investigate whether two primary care activities that are framed as indicators of primary care quality (comprehensive care plans and annual reviews of physical health) influence unplanned utilisation of hospital services for people with serious mental illness (SMI).

Design, setting, participants

Retrospective observational cohort study using linked primary care and hospital records (Hospital Episode Statistics) for 5158 patients diagnosed with SMI between April 2006 and March 2014, who attended 213 primary care practices in England that contribute to the Clinical Practice Research Datalink GOLD database.

Outcomes and analysis

Cox survival models were used to estimate the associations between two primary care quality indicators (care plans and annual reviews of physical health) and the hazards of three types of unplanned hospital utilisation: presentation to accident and emergency departments (A&E), admission for SMI and admission for ambulatory care sensitive conditions (ACSC).

Results

Risk of A&E presentation was 13% lower (HR 0.87, 95% CI 0.77 to 0.98) and risk of admission to hospital for ACSC was 23% lower (HR 0.77, 95% CI 0.60 to 0.99) for patients with a care plan documented in the previous year compared with those without a care plan. Risk of A&E presentation was 19% lower for those who had a care plan documented earlier but not updated in the previous year (HR: 0.81, 95% CI 0.67 to 0.97) compared with those without a care plan. Risks of hospital admission for SMI were not associated with care plans, and none of the outcomes were associated with annual reviews.

Conclusions

Care plans documented in primary care for people with SMI are associated with reduced risk of A&E attendance and reduced risk of unplanned admission to hospital for physical health problems, but not with risk of admission for mental health problems. Annual reviews of physical health are not associated with risk of unplanned hospital utilisation.

https://ift.tt/2TVkZ8b

Association of IL-10 and IL-10RA single nucleotide polymorphisms with the responsiveness to HBV vaccination in Chinese infants of HBsAg(+)/HBeAg(-) mothers: a nested case-control study

Objectives

To investigate the association of interleukin (IL)-10 and IL-10 receptor A (IL-10RA) single nucleotide polymorphisms with the responsiveness to hepatitis B virus (HBV) vaccination in newborns whose mothers were hepatitis B surface antigen (HBsAg)(+)/hepatitis B e antigen (HBeAg)(–).

Design

Nested case–control study.

Setting

Changchun, China.

Participants

713 infants from a Han Chinese population whose mothers were HBsAg(+)/HBeAg(–) and participated in the prevention of mother-to-child transmission of HBV at the First Hospital of Jilin University from July 2012 to July 2015 were included. Infants were excluded for HBsAg-positive; unstandardised vaccination process; inadequate blood samples; not Han Chinese and failed genotyping.

Results

Infants with artificial feeding pattern were correlated with low responsiveness to HBV vaccination (p=0.009). The GG genotype of IL-10 rs3021094 was correlated with a higher risk of low responsiveness to HBV vaccination (OR 2.80, 95% CI 1.35 to 5.83). No haplotype was found to be correlated with responsiveness to HBV vaccination. No gene–gene interaction was found between IL-10 and IL-10RA.

Conclusions

Our study found that IL-10 gene variants were significantly associated with the immune response to the HBV vaccine. Identifying these high-risk infants who born to HBsAg(+)/HBeAg(–) mothers and low responses to hepatitis B vaccination will provide evidence for individualised prevention strategies.

https://ift.tt/2AxUFIE

Lay community perceptions and treatment options for hypertension in rural northern Ghana: a qualitative analysis

Objective

Adherence to hypertension treatment is a major public health challenge for low and middle-income countries particularly in sub-Saharan Africa. One potential reason could be the discordance between lay and medical explanatory models of hypertension and its treatment. Understanding community perceptions and practices may contribute to improving hypertension control as they present insights into psychosocial and cultural factors that shape individual behaviour. We explore community perceptions regarding hypertension and its treatment in rural northern Ghana and how they differ from medical understanding.

Design

This was a qualitative study using semi-structured interviews and focus group discussions to collect data, which were analysed using a thematic approach.

Setting

A multisite study conducted in four rural communities in two regions of northern Ghana.

Participants

We conducted 16 semi-structured interviews and eight focus group discussions with community leaders and members, respectively.

Results

Three major themes were identified: community perceptions, treatment options and community support for people with hypertension. Community perceptions about hypertension include hypertension perceived as excess blood in the body and associated with spiritual or witchcraft attacks. Traditional medicine is perceived to cure hypertension completely with concurrent use of biomedical and traditional medicines encouraged in rural communities. Community members did not consider themselves at risk of developing hypertension and reported having inadequate information on how to provide social support for hypertensive community members, which they attributed to low literacy and poverty.

Conclusion

There is a substantial mismatch between communities' perceptions and medical understanding of hypertension and its treatment. These perceptions partly result from structural factors and social norms shaped by collective processes and traditions that shape lay beliefs and influence individual health behaviour. Socioeconomic factors also thwart access to information and contribute to inadequate social support for persons with hypertension. These findings highlight the need for a public health approach to hypertension control targeting families and communities.

https://ift.tt/2TUn8RJ

Posterior Reversible Encephalopathy Syndrome due to Hypomagnesemia: A Case Report and Literature Review

Background. Hypomagnesemia can cause various unspecific neurological complications, which can lead to diagnostic confusion. One of these complications is the posterior reversible encephalopathy syndrome (PRES), which is extremely uncommon and has been reported only twice in the English-language literature. Case presentation. We report the case of a 60-year-old man who presented with PRES involving only the cerebellar hemispheres and associated with hypomagnesemia. After excluding all the other possible etiologies of PRES, we started magnesium replacement therapy, which led to a remarkable but fluctuating clinical and chemical improvement. A full recovery with no need for further supplementation was achieved only after discontinuation of a proton pump inhibitor. Conclusions. This case highlights the role of magnesium in the pathophysiology of PRES; thereby, underlying hypomagnesemia should be considered in every PRES case with unclear etiology.

https://ift.tt/2KEnxUh

To Read More Papers, or to Read Papers Better? A Crucial Point for the Reproducibility Crisis

The overflow of scientific literature stimulates poor reading habits which can aggravate science's reproducibility crisis. Thus, solving the reproducibility crisis demands not only methodological changes, but also changes in our relationship with the scientific literature, especially our reading habits. Importantly, this does not mean reading more, it means reading better.

https://ift.tt/2BFktEs

Proteoglycan 4: From Mere Lubricant to Regulator of Tissue Homeostasis and Inflammation

While Proteoglycan 4 (PRG4) is a well known lubricating molecule, it is hypothesized that it is a potent inflammatory mediator. It is proposed that PRG4 (blue fire) acts to regulate inflammation (red fire). Under pro‐inflammatory conditions, it is suggested that proteases (circular sector shape) generate PRG4 bioactive fragments insufficient to maintain inflammatory homeostasis.

Proteoglycan 4 (PRG4), first identified in synovial fluid, is an extracellular matrix structural protein in the joint implicated in reducing shear at the cartilage surface as well as controlling adhesion‐dependent synovial growth and regulating bulk protein deposition onto the cartilage. However, recent evidence suggests that it can bind to and effect downstream signaling of a number of cell surface receptors implicated in regulating the inflammatory response. Therefore, we pose the hypothesis: Does PRG4 regulate the inflammatory response and maintain tissue homeostasis? Based on these novel findings implicating PRG4 as an inflammatory signaling molecule, we will present and discuss several hypotheses regarding potential mechanisms by which PRG4 may be able to regulate inflammation. If future studies can demonstrate that PRG4 is a potent inflammatory mediator, this will change current paradigms in the musculoskeletal and ophthalmological fields regarding the how the inflammatory microenvironment is regulated in these tissues and potentially others.

https://ift.tt/2KICDbd

Prevalence of autoimmune thyroid diseases among the Turner Syndrome patients: meta-analysis of cross sectional studies

This meta-analysis was done to estimate the prevalence of autoimmune thyroid diseases (ATDs) in Turner Syndrome patients, and to determine the clinical status of thyroid autoimmune diseases that occur frequent...

https://ift.tt/2DQJg9Z

Women’s knowledge and associated factors on preconception care at Public Health Institution in Hawassa City, South Ethiopia

Preconception care is pivotal to improve pregnancy and birth outcome. It is vital for the future health of mother, her child and her family, which is routinely practice. The study aims to assess knowledge of p...

https://ift.tt/2QtsNza

Rapid computation and visualization of data from Kano surveys in R

The Kano model for user satisfaction is a popular survey-based method used by product designers to prioritize the inclusion and implementation of product features based on users' requirements. Despite its over...

https://ift.tt/2DQ50CW

Prevalence of needle-stick and sharp object injuries and its associated factors among staff nurses in Dessie referral hospital Amhara region, Ethiopia, 2018

The aim of this study was to assess the prevalence of needle-stick and sharp object injuries among staff nurses in Dessie referral hospital, Amhara region, Ethiopia, 2018.

https://ift.tt/2Qvtmc4

Effect of enriched environment during adolescence on spatial learning and memory, and voluntary consumption of morphine in maternally separated rats in adulthood

Abstract

This study was designed to examine the effect of environmental enrichment (EE) during adolescence on spatial learning and memory and voluntary morphine consumption in maternally separated (MS) male and female rats in adulthood. Male Wistar rats were allowed to mate with female virgin Wistar rats. Pups were separated from the dams daily for 180 min during postnatal days 2–14. All pups were weaned on day 21. The pups of both sexes were reared in a standard (SE) or enriched (EE) environment during postnatal days 21–50. Then, adulthood rats were tested for spatial learning and memory (Morris Water Maze), and voluntary consumption of morphine using a two‐bottle choice paradigm (TBC). We found that the MS/SE rats showed longer escape latencies to find the platform on the third (the male) and fourth (the female) days of training than No MS/SE rats. Also, exposure to EE shortened the latency to escape in the male and female MS rats as training progressed than MS/SE rats. Moreover, the No MS/EE and MS/EE male rats spent significantly more time in the target zone compared with the SE control groups in the probe test. We also found that voluntary morphine consumption was higher in the male and female MS/SE than No MS/SE rats, while it was lower in the male and female MS/EE rats. The present results have shown that EE treatment may have potential therapeutic application for the prevention of the development of drug addiction and recovery from cognitive deficits following neonatal MS during adulthood.

https://ift.tt/2DS0ILt

Emerging roles of transforming growth factor β signaling in wet age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) is one of the major causes of irreversible blindness among aging populations in developed countries and can be classified as dry or wet according to its progression. Wet AMD, which is characterized by angiogenesis on the choroidal membrane, is uncommonly seen but more severe. Controlling or completely inhibiting the factors that contribute to the progression of events that lead to angiogenesis may be an effective strategy for treating wet AMD. Emerging evidence has shown that transforming growth factor-β (TGF-β) signaling plays a significant role in the progression of wet AMD. In this review, we described the roles of and changes in TGF-β signaling in the development of AMD and discussed the mechanisms of the TGF-β superfamily in choroidal neovascularization (CNV) and wet AMD, including the modulation of angiogenesis-related factors, inflammation, vascular fibrosis, and immune responses, as well as cross-talk with other signaling pathways. These remarkable findings indicate that TGF-β signaling is a potential target for wet AMD treatment.

https://ift.tt/2Rlkjr7

On the statistical convergence of bias in mode-based Kalman filter for switched systems

Many physical and engineered systems (e.g., smart grid, autonomous vehicles, and robotic systems) that are observed and controlled over a communication/cyber infrastructure can be efficiently modeled as stocha...

https://ift.tt/2RnkHoY

Antagonism of glycolysis and reductive carboxylation of glutamine potentiates activity of oncolytic adenoviruses in cancer cells

Tumour cells exhibiting the Warburg effect rely on aerobic glycolysis for ATP production and have a notable addiction to anaplerotic use of glutamine for macromolecular synthesis. This strategy maximises cellular biosynthetic potential while avoiding excessive depletion of NAD+, and provides an attractive anabolic environment for viral infection. Here we evaluate infection of highly permissive and poorly permissive cancer cells with wild type adenoviruses and the oncolytic chimeric adenovirus enadenotucirev (EnAd). All adenoviruses caused an increase in glucose and glutamine uptake along with increased lactic acid secretion. Counterintuitively, restricting glycolysis using 2-deoxyglucose (2DG) or by limiting glucose supply strongly improved virus activity in both cell types. Antagonism of glycolysis also boosted EnAd replication and transgene expression within human tumour biopsies and in xenografted tumours in vivo. In contrast, the virus life cycle was critically dependent on exogenous glutamine. Virus activity in glutamine-free cells was rescued with exogenous membrane-permeable α-ketoglutarate, but not pyruvate or oxaloacetate, suggesting an important role for reductive carboxylation in glutamine usage, perhaps for production of biosynthetic intermediates. This overlap between the metabolic phenotypes of adenovirus infection and transformed tumour cells may provide insight into how oncolytic adenoviruses exploit metabolic transformation to augment their selectivity for cancer cells.

https://ift.tt/2E3r3ag

Functional analysis and fine mapping of the 9p22.2 ovarian cancer susceptibility locus

Genome-wide association studies have identified 40 ovarian cancer risk loci. However, the mechanisms underlying these associations remain elusive. In this study, we conducted a two-pronged approach to identify candidate causal SNPs and assess underlying biological mechanisms at chromosome 9p22.2, the first and most statistically significant associated locus for ovarian cancer susceptibility. Three transcriptional regulatory elements with allele-specific effects and a scaffold/matrix attachment region were characterized and through physical DNA interactions BNC2 was established as the most likely target gene. We determined the consensus binding sequence for BNC2 in vitro, verified its enrichment in BNC2 ChIP-Seq regions and validated a set of its downstream target genes. Fine-mapping by dense regional genotyping in over 15,000 ovarian cancer cases and 30,000 controls identified SNPs in the scaffold/matrix attachment region as among the most likely causal variants. This study reveals a comprehensive regulatory landscape at 9p22.2 and proposes a likely mechanism of susceptibility to ovarian cancer.

https://ift.tt/2SiNZFj

A Gene Expression Classifier from Whole Blood Distinguishes Benign from Malignant Lung Nodules Detected by Low-Dose CT

Low-dose CT (LDCT) is widely accepted as the preferred method for detecting pulmonary nodules. However, the determination of whether a nodule is benign or malignant involves either repeated scans or invasive procedures that sample the lung tissue. Noninvasive methods to assess these nodules are needed to reduce unnecessary invasive tests. In this study, we have developed a pulmonary nodule classifier (PNC) using RNA from whole blood collected in RNA-stabilizing PAXgene tubes that addresses this need. Samples were prospectively collected from high-risk and incidental subjects with a positive lung CT scan. A total of 821 samples from 5 clinical sites were analyzed. Malignant samples were predominantly stage 1 by pathologic diagnosis and 97% of the benign samples were confirmed by 4 years of follow-up. A panel of diagnostic biomarkers was selected from a subset of the samples assayed on Illumina microarrays that achieved a ROC-AUC of 0.847 on independent validation. The microarray data were then used to design a biomarker panel of 559 gene probes to be validated on the clinically tested NanoString nCounter platform. RNA from 583 patients was used to assess and refine the NanoString PNC (nPNC), which was then validated on 158 independent samples (ROC-AUC = 0.825). The nPNC outperformed three clinical algorithms in discriminating malignant from benign pulmonary nodules ranging from 6–20 mm using just 41 diagnostic biomarkers. Overall, this platform provides an accurate, noninvasive method for the diagnosis of pulmonary nodules in patients with non–small cell lung cancer.Significance: These findings describe a minimally invasive and clinically practical pulmonary nodule classifier that has good diagnostic ability at distinguishing benign from malignant pulmonary nodules. Cancer Res; 1–11. ©2018 AACR.

https://ift.tt/2E2zxhO

A Phase I/Ib Trial of the VEGFR-Sparing Multikinase RET Inhibitor RXDX-105 [Research Articles]

RET fusions are oncogenic drivers of various tumors, including non-small cell lung cancers (NSCLCs). The safety and antitumor activity of the multikinase RET inhibitor RXDX-105 were explored in a phase I/Ib trial. A recommended phase 2 dose of 275 mg fed daily was identified. The most common treatment-related adverse events were fatigue (25%), diarrhea (24%), hypophosphatemia (18%), maculopapular rash (18%), and non-maculopapular rash (17%). In the phase 1b cohort of RET inhibitor-naive patients with RET fusion-positive NSCLCs, the objective response rate (ORR) was 19% (95% CI 8%-38%, n=6/31). Interestingly, the ORR varied significantly by the gene fusion partner (p<0.001, Fisher's exact test): 0% (95% CI 0% - 17%, n=0/20) with KIF5B (the most common upstream partner for RET fusion-positive NSCLC), and 67% (95% CI 30% - 93%, n=6/9) with non-KIF5B partners. The median duration of response in all RET fusion-positive NSCLCs was not reached (range 5 to 18+ months).

https://ift.tt/2TRpnW5

FDA Seeks Tighter Restrictions on E-cigarettes [News in Brief]

The agency's plans would restrict youth access to flavored nicotine-containing devices and products.

https://ift.tt/2AAqRv4

A Deep Dive into Immunotherapy Resistance [News in Depth]

Single-cell analyses uncover resistance mechanisms promoted by CD8+ T cells and tumor cells, respectively.

https://ift.tt/2TThJKF

A CK1{alpha} activator penetrates the brain, and shows efficacy against drug-resistant metastatic medulloblastoma

Purpose: Although most children with medulloblastoma (MB) are cured of their disease, SONIC HEDGEHOG (SHH) subgroup MB driven by TRP53 mutations is essentially lethal. Casein Kinase 1α (CK1α) phosphorylates and destabilizes GLI transcription factors, thereby inhibiting the key effectors of SHH signaling. We therefore tested a second-generation CK1α activator against TRP53 mutant, MYCN amplified MB. Experimental Design: The ability of this CK1α activator to block SHH signaling was determined in vitro using GLI reporter cells, granular precursor primary cultures and PATCHED (PTCH1) mutant sphere cultures. While in vivo efficacy was tested using two different MB mouse models: PTCH1 and ND2:SMOA1. Finally, the clinical relevance of CK1α activators was demonstrated using a TRP53 mutant, MYCN amplified patient derived xenograft. Results: SSTC3 inhibited SHH activity in vitro, acting downstream of the vismodegib target SMOOTHENED (SMO), and reduced the viability of sphere cultures derived from SHH MB. SSTC3 accumulated in the brain, inhibited growth of SHH MB tumors, and blocked metastases in a genetically-engineered vismodegib resistant mouse model of SHH MB. Importantly, SSTC3 attenuated growth and metastasis of orthotopic patient-derived TRP53 mutant, MYCN amplified, SHH subgroup MB xenografts, increasing overall survival. Conclusions: A CK1α agonist penetrates into the brain, and shows efficacy against metastatic TRP53 mutant MB, which is resistant to existing therapies including the SMO inhibitors currently being evaluated clinically.

https://ift.tt/2AuyfYJ

Residual Tumor Volume, Cell Volume Fraction and Tumor Cell Kill During Fractionated Chemoradiation Therapy of Human Glioblastoma using Quantitative Sodium MR imaging

Purpose: Spatial and temporal patterns of response of human glioblastoma to fractionated chemoradiation are described by changes in the bioscales of residual tumor volume, tumor cell volume fraction and tumor cell kill, as derived from tissue sodium concentration measured by quantitative sodium magnetic resonance imaging at 3 Tesla. These near real-time patterns during treatment are compared with overall survival. Experimental Design: Bioscales were mapped during fractionated chemoradiation therapy in patients with glioblastomas (n=20) using tissue sodium concentration obtained from serial quantitative sodium magnetic resonance imaging at 3 Tesla and a two-compartment model of tissue sodium distribution. The responses of these parameters in newly diagnosed human glioblastomas undergoing treatment were compared to times to disease progression and survival. Results: Residual tumor volume following tumor resection showed decreased cell volume fraction due to disruption of normal cell packing by edema and infiltrating tumor cells. Cell volume fraction showed either increases back towards normal as infiltrating tumor cells were killed, or decreases as cancer cells continued to infiltrate and extend tumor margins. These highly variable tumor responses showed no correlation with time to progression or overall survival. Conclusions: These bioscales indicate that fractionated chemoradiotherapy of glioblastomas produces variable responses with low cell killing efficiency. These parameters are sensitive to real-time changes within the treatment volume while remaining stable elsewhere, highlighting the potential to individualize therapy earlier in management, should alternative strategies be available.

https://ift.tt/2TSKCqh

Evaluation of Emergent Mutations in Circulating Cell-Free DNA and Clinical Outcomes in Patients With Metastatic Colorectal Cancer Treated With Panitumumab in the ASPECCT Study

Purpose: Mutations in EGFR pathway genes are poor prognostic indicators in patients with metastatic colorectal cancer (mCRC). Plasma analysis of cell-free DNA (cfDNA) is a minimally invasive and highly sensitive method to detect somatic mutations in tumors. Experimental Design: Plasma samples collected from panitumumab-treated patients in the ASPECCT study at baseline and safety follow-up (SFU) were analyzed by a next-generation sequencing-based approach for extended RAS mutant allele frequency as a continuous variable and their association with clinical outcomes and the mutational prevalence of 63 cancer-related genes. The correlation between patient outcome and baseline mutational status of EGFR pathway genes was also examined. Results: Overall, 261 patients in the panitumumab arm had evaluable plasma samples. Patients with a higher RAS mutant allele frequency at baseline had worse clinical outcomes than those with a lower frequency (p < 0.001, Cox PH model); however, RAS mutations did not necessarily preclude patients from deriving benefits. The objective response rate (complete or partial response) was 10.8% for patients with baseline RAS mutations and 21.7% for those with BRAF mutations. The 63-gene panel analysis revealed an increase in tumor mutational burden from baseline to SFU (p < 0.001, Wilcoxon signed rank test). Baseline mutations in EGFR pathway genes, when analyzed both categorically and continuously, were associated with shorter survival. Conclusions: When mutations in EGFR pathway genes were analyzed continuously, higher mutant allele frequency correlated with poorer outcomes. However, extended RAS mutation, by itself, did not preclude clinical responses to panitumumab in a monotherapy setting.

https://ift.tt/2AwA878

BIRC3 expression predicts CLL progression and defines treatment sensitivity via enhanced NF-{kappa}B nuclear translocation

Purpose: Chronic lymphocytic leukemia (CLL) pathophysiology is characterized by a complex crosstalk of tumor cells with the microenvironment. In this regard, NF-kB signaling is considered as important signaling axis, with a variety of key molecules aberrantly expressed or genetically altered in CLL patients. One of these molecules is BIRC3 (cIAP2), a central regulator of non-canonical NF-kB signaling that serves as pathway brake in the absence of microenvironmental signals. However, the contribution of BIRC3 expression to CLL progression and potential therapeutic implications is unknown. Experimental Design: We analyzed the role of BIRC3 mRNA expression in primary CLL samples in correlation to clinical datasets and used ex vivo assays to investigate functional consequences on the level of NK-kB signaling and downstream target gene regulation. For proof of principle experiments, we used genetically modified cell lines. Results: We demonstrate that CLL patients with low BIRC3 expression experience a more rapid disease progression, which coincides with an enhanced activation of canonical NF-kB target genes evidenced by an increased p65/Rel-B nuclear translocation ratio. As a consequence of enhanced canonical NF-kB target gene activation, both anti- and proapoptotic Bcl-2 family members were upregulated in BIRC3^low primary CLL cells, which was associated with higher sensitivity to Venetoclax treatment in vitro. Conclusion: Here we show the impact of BIRC3 expression in CLL disease progression in the absence of BIRC3 mutations and show altered canonical NF-kB target gene activation with therapeutic implications.

https://ift.tt/2TSKBTf

Prognostic role of HPV infection in esophageal squamous cell carcinoma

Abstract

Background

The aims of this study were to evaluate whether HPV infection has a prognostic role in patients with esophageal squamous cell carcinoma who underwent oncological treatment and also to compare the heat shock proteins (Hsp) 90, 27 and 16.2 and growth hormone-releasing hormone receptor (GHRH-R) expression patterns of the pre-treatment tumor biopsies with the HPV status and with the oncological response.

Methods

Pre-treatment tumor biopsies of 74 patients with locally advanced esophageal squamous cell carcinoma were processed retrospectively. The presence of HPV was detected by chromogenic in situ hybridization. Hsp and GHRH-R expressions were determined using immunohistochemistry. Following neoadjuvant or definitive radiochemotherapy, the patients were restaged according to the Response Evaluation Criteria in Solid Tumors. The correlation between the HPV status, response to treatment and Hsp and GHRH-R expressions were evaluated.

Results

Fourteen (19%) patients were HPV-positive. These patients were more likely to respond poorly to multimodal therapy (71.4% were non-responders vs. 28.6% responders) and had shorter survival compared to HPV-negative patients (mean survival of 8 months vs. 11 months), although the difference was not significant. A significantly higher number of HPV-positive patients expressed Hsp 90 and 16.2 at high levels (93 and 79%, respectively) than at low levels (Chi-Square p = 0.019 and p = 0.031). Higher levels of Hsp expressions were associated with poorer response to therapy and worse overall survival. No correlation was found between GHRH-R expression and the HPV status, nor between GHRH-R expression and the treatment response of the examined samples.

Conclusions

We found that HPV infection was associated with poor response to oncological treatment and decreased overall survival, and therefore proved to be a negative prognostic factor in patients with esophageal squamous cell carcinoma. There was a linear correlation between levels of Hsp 90 and 16.2 expression and HPV positivity.

https://ift.tt/2AwAc6S

miR-296-5p suppresses EMT of hepatocellular carcinoma via attenuating NRG1/ERBB2/ERBB3 signaling

Abstract

Background

Accumulation of evidence indicates that miRNAs have crucial roles in the regulation of EMT-associated properties, such as proliferation, migration and invasion. However, the underlying molecular mechanisms are not entirely illustrated. Here, we investigated the role of miR-296-5p in hepatocellular carcinoma (HCC) progression.

Methods

In vitro cell morphology, proliferation, migration and invasion were compared between HCC cell lines with up- or down-regulation of miR-296-5p. Immunofluorescence and Western blot immunofluorescence assays were used to detect the expression of EMT markers. Bioinformatics programs, luciferase reporter assay and rescue experiments were used to validate the downstream targets of miR-296-5p. Xenograft nude mouse models were established to observe tumor growth and metastasis. Immunohistochemical assays were conducted to study the relationships between miR-296-5p expression and Neuregulin-1 (NRG1)/EMT markers in human HCC samples and mice.

Results

miR-296-5p was prominently downregulated in HCC tissues relative to adjacent normal liver tissues and associated with favorable prognosis. Overexpression of miR-296-5p inhibited EMT along with migration and invasion of HCC cells via suppressing NRG1/ERBB2/ERBB3/RAS/MAPK/Fra-2 signaling in vitro. More importantly, miR-296-5p disrupted intrahepatic and pulmonary metastasis in vivo. NRG1, as a direct target of miR-296-5p, mediates downstream biological responses. In HCC tissues from patients and mice, the levels of miR-296-5p and NRG1 also showed an inverse relationship.

Conclusions

miR-296-5p inhibited EMT-related metastasis of HCC through NRG1/ERBB2/ERBB3/RAS/MAPK/Fra-2 signaling.

https://ift.tt/2zyUfSq

Impact of primary tumour location on efficacy of bevacizumab plus chemotherapy in metastatic colorectal cancer

Impact of primary tumour location on efficacy of bevacizumab plus chemotherapy in metastatic colorectal cancer

Impact of primary tumour location on efficacy of bevacizumab plus chemotherapy in metastatic colorectal cancer, Published online: 29 November 2018; doi:10.1038/s41416-018-0304-6

Impact of primary tumour location on efficacy of bevacizumab plus chemotherapy in metastatic colorectal cancer

https://ift.tt/2E1tqKL

A process and mechanism of action evaluation of the effect of early and intensive nutrition care, delivered via telephone or mobile application, on quality of life in people with upper gastrointestinal cancer: a study protocol

Abstract

Background

Cancers of the upper gastrointestinal tract commonly result in malnutrition, which increases morbidity and mortality. Current nutrition best practice lacks a mechanism to provide early and intensive nutrition support to these patients. A 3-arm parallel randomised controlled trial is testing the provision of a tailored, nutritional counselling intervention delivered using a synchronous, telephone-based approach or an asynchronous, mobile application-based approach to address this problem. This protocol outlines the design and methods that will be used to undertake an evaluation of the implementation process, which is imperative for successful replication and dissemination.

Methods

A concurrent triangulation mixed methods comparative analysis will be undertaken. The nutrition intervention will be provided using best practice behaviour change techniques and communicated either via telephone or via mHealth. The implementation outcomes that will be measured are: fidelity to the nutrition intervention protocol and to the delivery approach; engagement; acceptability and contextual factors. Qualitative data from recorded telephone consultations and written messages will be analysed through a coding matrix against the behaviour change techniques outlined in the standard operating procedure, and also thematically to determine barriers and enablers. Negative binomial regression will be used to test for predictive relationships between intervention components with health-related quality of life and nutrition outcomes. Post-intervention interviews with participants and health professionals will be thematically analysed to determine the acceptability of delivery approaches. NVivo 11 Pro software will be used to code for thematic analysis. STATA version 15 will be used to perform quantitative analysis.

Discussion

The findings of this process evaluation will provide evidence of the core active ingredients that enable the implementation of best practice nutrition intervention for people with upper gastrointestinal cancer. Elucidation of the causal pathways of successful implementation and the important relationship to contextual delivery are anticipated. With this information, a strategy for sustained implementation across broader settings will be developed which impact the quality of life and nutritional status of individuals with upper gastrointestinal cancer.

Trial registration

27th January 2017 Australian and New Zealand Clinical Trial Registry (ACTRN12617000152325).

https://ift.tt/2Skbr51

The clinical significance of FAM19A4 methylation in high-risk HPV-positive cervical samples for the detection of cervical (pre)cancer in Chinese women

Abstract

Background

To explore the diagnostic value of FAM19A4 methylation in high-risk human papilloma virus (hrHPV)-positive cervical samples from Chinese women for estimating cervical cancer or its precancerous lesions.

Methods

Cervical samples from 215 women infected with high-risk HPV were collected by smear testing. We purposely chose 61 patients with cervical cancer, 57 with high-grade squamous intraepithelial lesions (HSIL), 31 with low-grade squamous intraepithelial lesions (LSIL), and 66 without cervical intraepithelial neoplasia (CIN) after histological confirmation. Taqman probe-based quantitative PCR (qPCR) was utilized to detect the methylation status of FAM19A4 in the cervical samples and further evaluate the use of this gene in the diagnosis of cervical cancer.

Results

(1) An increasing level of FAM19A4 methylation was detected with increasing progression of cervical lesions, with methylation rates of 10.61%(7/66), 35.48%(11/31), 56.14%(32/57) and 93.44%(57/61) in no CIN, LSIL, HSIL and cervical carcinoma samples respectively. (2) In all hrHPV-positive samples, the levels of FAM19A4 methylation in HPV16/18 groups were higher than that in 12 other hrHPV groups (P < 0.05), but there was no significant difference between two groups after grouping cervical lesions into cervical cancer, HSIL, LSIL and no CIN groups (P>0.05). (3)There were no significant differences of FAM19A4 methylation in different clinicopathological parameters of cervical cancer. (4) Though the sensitivity of FAM19A4 methylation test was inferior to that of cytology and FAM19A4 combining with HPV16/18 genotyping, but showed the best specificity with 81.44% both for detection HSIL alone and ≥ HSIL, with favorable youden index (YI) and area under curve (AUC).

Conclusion

FAM19A4 is a specific biomarker of cancerous lesions of the cervix. FAM19A4 methylation analysis may serve as an auxiliary screening method for diagnosis of cervical (pre)cancer. However, in consideration of the limitations of this retrospective study, prospective population-based studies are necessary for further confirmation of the diagnostic value of FAM19A4 methylation for detection of cervical (pre)cancer in Chinese women.

https://ift.tt/2E3nh0z

Gene Therapy Forms New Polysynaptic Pathways in Parkinson's

WEDNESDAY, Nov. 28, 2018 -- For patients with Parkinson's disease (PD) undergoing gene therapy, new polysynaptic functional pathways develop in the brain, according to a study published in the Nov. 28 issue of Science Translational Medicine. Martin...

https://ift.tt/2AzgA1W

FDA Approves First Biosimilar to Non-Hodgkin's Lymphoma Drug

WEDNESDAY, Nov. 28, 2018 -- Truxima (rituximab-abbs) has been approved by the U.S. Food and Drug Administration as the first biosimilar to the non-Hodgkin's lymphoma drug Rituxan, the agency said today. Truxima, as with Rituxan, is approved to treat...

https://ift.tt/2U0azEC

Lower Mortality Seen for Cardiac Care at Top-Ranked Hospitals

WEDNESDAY, Nov. 28, 2018 -- Compared with nonranked hospitals, top-ranked hospitals have lower 30-day mortality but similar or higher readmission rates for cardiovascular conditions, according to a study published online Nov. 28 in JAMA...

https://ift.tt/2AAlrAe

In-Person Social Contact Tied to Reduced Psychiatric Symptoms

WEDNESDAY, Nov. 28, 2018 -- For military veterans, in-person social interaction, but not social contact on Facebook, is associated with a significantly reduced risk for symptoms of major depression and posttraumatic stress disorder, according to a...

https://ift.tt/2TTboil

ADHD Diagnosis, Treatment Up for August-Born Children

WEDNESDAY, Nov. 28, 2018 -- In states with a Sept. 1 cutoff for kindergarten entry, the rates of attention-deficit/hyperactivity disorder (ADHD) diagnosis and treatment are higher for children born in August than those born in September, according...

https://ift.tt/2AysjOr

Maternal and Neonatal Outcomes after Attempted External Cephalic Version among Women with One Previous Cesarean Delivery

AJP Rep 2018; 08: e349-e354
DOI: 10.1055/s-0038-1676297

Objective This study was aimed to evaluate success rates of (1) external cephalic version (ECV) among women with one prior cesarean delivery (CD) and (2) maternal and neonatal outcomes after ECV among women with prior CD. Study Design Two linked studies using U.S. Natality Database were performed. First we performed a retrospective cohort comparing ECV success rates of women with prior CD and women without prior CD. Then we compared the outcomes of TOLACs (trial of labor after cesarean delivery) that occurred after ECV with those that occurred without ECV. Multivariable logistic regression analysis was used to estimate adverse outcomes. Results A total of 715 women had ECV after 36 weeks with prior CD and 9,976 had ECV without prior scar. ECV success rate with scar was 80.6% and without scar was 86.4% (p < 0.001). Seven hundred and sixteen women underwent TOLAC after ECV attempt and 234,617 underwent TOLAC without a preceding attempt. Women with preceding version had increased risks of maternal transfusion (1 vs. 0.4%, adjusted OR [odds ratio]: 2.48 [95% CI (confidence interval): 1.17–5.23]), unplanned hysterectomy (0.4 vs. 0.06%, adjusted OR: 6.90 [95% CI: 2.19–21.78]), and low 5-minute Apgar's score (2.5 vs. 1.5%, adjusted OR: 1.76 [95% CI: 1.10–2.82]). Conclusion Women with prior CD may have a decrease in the rate of successful ECV. While the absolute risks are low, ECV appears to increase risks of adverse maternal and neonatal outcomes among women undergoing a trial of labor.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

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Maternal and Fetal Outcomes in Pregnancies affected by Bone and Soft Tissue Tumors

AJP Rep 2018; 08: e343-e348
DOI: 10.1055/s-0038-1676289

Objective This study was aimed to describe perinatal outcome of a cohort of pregnant patients with bone and soft tissue tumors and to compare the current series with our group's previously reported experience. Methods Pregnant women diagnosed before and during pregnancy were identified, retrospectively, for the years 2004 to 2014. Relevant maternal and neonatal data were collected. Results Forty-eight patients were identified. Ten cases were diagnosed during pregnancy. Pelvis, abdomen, and extremities were the most common tumor locations. Osteosarcoma, liposarcoma, and Ewing's sarcoma were the most common histological types and comprise more than 50% of the cases. Metastases occurred in nine cases. Most of the cases (60%) were treated surgically during pregnancy and delivery occurred at term. Chemotherapy was delayed until after delivery. There were no perinatal or infant deaths. Patients presented with advanced maternal disease in 18% in previous report (1983–2003) versus 40% in present report (2004–2014). Metastases were present in 40% and maternal death rate was approximately 20% in both cohorts. Conclusion Pregnant women with bone and soft tissue tumors are candidates for standard surgical management during pregnancy. Other treatments, such as chemotherapy and radiotherapy must be evaluated for each woman on a case-by-case basis. Iatrogenic prematurity was common in our findings.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

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Fibroblast growth factor 23 and α-Klotho co-dependent and independent functions

Purpose of review The current review examines what is known about the FGF-23/α-Klotho co-dependent and independent pathophysiological effects, and whether FGF-23 and/or α-Klotho are potential therapeutic targets. Recent findings FGF-23 is a hormone derived mainly from bone, and α-Klotho is a transmembrane protein. Together they form a trimeric signaling complex with FGFRs in target tissues to mediate the physiological functions of FGF-23. Local and systemic factors control FGF-23 release from osteoblast/osteocytes in bone, and circulating FGF-23 activates FGFR/α-Klotho complexes in kidney proximal and distal renal tubules to regulate renal phosphate excretion, 1,25 (OH)2D metabolism, sodium and calcium reabsorption, and ACE2 and α-Klotho expression. The resulting bone–renal–cardiac–immune networks provide a new understanding of bone and mineral homeostasis, as well as identify other biological effects FGF-23. Direct FGF-23 activation of FGFRs in the absence of α-Klotho is proposed to mediate cardiotoxic and adverse innate immune effects of excess FGF-23, particularly in chronic kidney disease, but this FGF-23, α-Klotho-independent signaling is controversial. In addition, circulating soluble Klotho (sKl) released from the distal tubule by ectodomain shedding is proposed to have beneficial health effects independent of FGF-23. Summary Separation of FGF-23 and α-Klotho independent functions has been difficult in mammalian systems and understanding FGF-23/α-Klotho co-dependent and independent effects are incomplete. Antagonism of FGF-23 is important in treatment of hypophosphatemic disorders caused by excess FGF-23, but its role in chronic kidney disease is uncertain. Administration of recombinant sKl is an unproven therapeutic strategy that theoretically could improve the healt span and lifespan of patients with α-Klotho deficiency.

https://ift.tt/2r9fWnJ

Pre, peri and posttransplant diabetes mellitus

Purpose of review The leading cause of death in both chronic kidney disease (CKD) and renal transplant patients is cardiovascular events. Post-transplant diabetes mellitus (PTx-DM), which is a major cardiovascular risk factor, is a metabolic disorder that affects 5.5–60.2% of renal allograft recipients by 1-year posttransplant (PTx). PTx-DM has been associated with a negative impact on patient and graft outcomes and survival. Recent findings Individuals who develop PTx-DM are usually prone to this condition prior to and/or after developing CKD. Genetic factors, obesity, inflammation, medications and CKD all are risk factors for PTx-diabetes mellitus. The path to development of disease continues PTx frequently augmented by the use of diabetogenic maintenance immunosuppressive and some nonimmunosuppressive medications. These risk factors are usually associated with an increase in insulin resistance, a decrease in insulin gene expression and/or β-cell dysfunction and apoptosis. Summary Some new anti-diabetes mellitus medications may help to improve the overall outcome; however, there is a real need for developing a preventive strategy. Identifying and targeting PTx-DM risk factors may help to guide the development of an effective programme. This could include the adoption of nondiabetogenic immunosuppressive protocols for high-risk patients.

https://ift.tt/2FOCqV2

Sex hormones and their influence on chronic kidney disease

Purpose of review The majority of end-stage renal disease including dialysis and kidney transplant patients are men. In contrast, the incidence of chronic kidney disease (CKD) is higher in women compared with men. In this review, we dissect the sex hormone levels and its effects on experimental models and patients with CKD. Recent findings Sex hormones are clearly involved in CKD progression to end-stage renal disease (ESRD). A significant reduction in lipid peroxidation as a mechanism of renoprotection has been observed in kidneys of streptozotocin (STZ)-diabetic ovariectomized rats after estradiol administration. Furthermore, a G-protein-coupled estrogen receptor inhibits podocyte oxidative stress maintaining the integrity of the mitochondrial membrane. Sex hormone depletion has been shown to modulate RAS system and protect against kidney injury in the male STZ-diabetic model. In human primary proximal tubular epithelial cells, a proteomic study showed that dihydrotestosterone dysregulated metabolic, suggesting that the deleterious effect of androgens within the kidney maybe related to altered energy metabolism in renal tubules. Summary Male gender is associated with worse CKD progression and this fact may be ascribed to sex hormone. Although male hormones exert a deleterious effect in terms of increasing oxidative stress, activating RAS system, and worsening fibrosis within the damaged kidney, female hormones exert a renoprotective effect.

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Dilemmas and challenges in apolipoprotein L1 nephropathy research

Purpose of review The purpose of this mini-review is to highlight some unresolved questions and controversies in the evolving story of apolipoprotein L1 (APOL1) nephropathy. Recent findings We highlight studies that introduce complexity in unraveling the mechanisms whereby APOL1 risk variant alleles cause disease. These include studies which support a possible protective role for the APOL1 GO nonrisk ancestral allele, and studies which explore the initiating events that may trigger other downstream pathways mediating APOL1 cellular injury. We also review studies that reconcile the perplexing findings regarding APOL1 anionic or cationic conductance, and pH dependency, and also studies that attempt to characterize the 3-dimensional structure of APOL1 C-terminal in APOL1 variants, as well as that of the serum resistance-associated protein. We also attempt to convey new insights from in-vivo and in-vitro models, including studies that do not support the differential toxicity of APOL1 renal risk variants and recapitulate the clinical variability of individuals at genotypic risk. Summary Along with major progress that had been achieved in the field of APOL1 nephropathy, controversies and enigmatic issues persist. It remains to be determined which of the pathways which have been demonstrated to mediate cell injury by ectopically expressed APOL1 risk variants in cellular and organismal models are relevant to human disease and can pave the way to potential therapy.

https://ift.tt/2FOCoMU

Growth hormone and chronic kidney disease

Purpose of review Elevated circulating levels of growth hormone (GH) and/or increased expression of the GH receptor in the kidney are associated with the development of nephropathy in type1 diabetes and acromegaly. Conditions of GH excess are characterized by hyperfiltration, glomerular hypertrophy, glomerulosclerosis and albuminuria, whereas states of decreased GH secretion or action are protected against glomerulopathy. The direct role of GH's action on glomerular cells, particularly podocytes, has been the focus of recent studies. In this review, the emerging role of GH on the biological function of podocytes and its implications in the pathogenesis of diabetic and chronic kidney disease will be discussed. Recent findings Elevated GH levels impair glomerular permselectivity by altering the expression of podocyte slit-diaphragm proteins. GH stimulates the epithelial–mesenchymal transition of podocytes and decreases podocyte count. GH also induces the expression of prosclerotic molecules transforming growth factor beta, and TGFBIp. Summary Our understanding of the cellular and molecular effects of GH in the pathogenesis of renal complications of diabetes and acromegaly has significantly progressed in recent years. These observations open up new possibilities in the prevention and treatment of diabetic nephropathy.

https://ift.tt/2r6pM9U

Protective association between JC polyoma viruria and kidney disease

Purpose of review The presence of viruses in urine (urine virome) typically reflects infection in the kidneys and urinary tract. The urinary virome is associated with HIV-associated nephropathy and chronic glomerulosclerosis. There are many associations of this microbiome with human diseases that remain to be described. This manuscript reviews emerging data on relationships between kidney disease and urinary tract infection/colonization with JC polyomavirus (JCPyV). Recent findings Approximately 30% of the adult population sheds JCPyV in the urine. Further, urinary tract infection with one polyomavirus strain appears to inhibit secondary infections. The presence of urinary JCPyV and BK polyomavirus (BKPyV) replication were measured with polymerase chain reaction in African Americans to assess relationships with apolipoprotein L1 gene (APOL1)-associated nephropathy. Urinary JCPyV was associated with paradoxically lower rates of nephropathy in those with APOL1 high-risk genotypes. Subsequent studies revealed African Americans with JCPyV viruria had lower rates of nondiabetic nephropathy independent from APOL1. Summary Urinary tract JCPyV replication is common and associates with lower rates of nephropathy. This relationship is observed in diverse settings. Results support a host immune system that fails to eradicate nonnephropathic viruses and is also less likely to manifest renal parenchymal inflammation resulting in glomerulosclerosis.

https://ift.tt/2FWBxtw

Editorial introductions

No abstract available

https://ift.tt/2FKfMgA

Methylglyoxal stress, the glyoxalase system, and diabetic chronic kidney disease

Purpose of review Chronic kidney disease (CKD) remains a serious diabetic complication despite the use of widely employed interventions such as angiotensin-converting enzyme inhibitors and glucose-lowering treatments. Accumulation of methylglyoxal, a highly reactive glucose metabolite and a major precursor in the formation of advanced glycation end products, may link the hemodynamic, inflammatory, metabolic, and structural changes that drive diabetic CKD. Therefore, methylglyoxal may serve as a potential therapeutic target to prevent diabetic CKD. Recent findings Higher plasma methylglyoxal levels were shown to be associated with a decline in the estimated glomerular filtration rate. Furthermore, interventions that lower methylglyoxal levels reduced albuminuria in rodent models of diabetes. In addition, the glyoxalase system, which detoxifies methylglyoxal into D-lactate, has been identified as a key protective enzymatic system against diabetic CKD in both human and rodent studies. Recently, several promising treatments to lower methylglyoxal directly or to boost the glyoxalase system have been identified. Summary The review highlights the mechanisms through which methylglyoxal is formed in diabetes, and how methylglyoxal contributes to the mechanisms that drive CKD in diabetes. Furthermore, we discuss the role of glyoxalase-1 in diabetic CKD. Finally, we discuss recent data about treatments that lower methylglyoxal stress.

https://ift.tt/2r8WNSC