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Find video protocols related to scientific articles indexed in Pubmed.
Recalcitrant Hypocalcaemia in Autoimmune Enteropathy.
Pediatrics
PUBLISHED: 11-19-2014
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Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome is a monogenic disorder associated with autoimmune destruction of both endocrine and nonendocrine tissues. The classic triad includes candidiasis, hypoparathyroidism, and Addison disease. Up to 25% of patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome also have gastrointestinal manifestations, which can have an impact on the management of other aspects of the disease. The management of the case discussed was challenging because of the complex interplay between the manifestations and treatment of his hypoparathyroidism, Addison disease, and autoimmune enteropathy. Attempts at management of hypocalcemia were largely unsuccessful until the introduction of immunosuppressive therapy for autoimmune enteropathy. This case supports early consideration of immunosuppression in this condition.
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Nutrient-sensing nuclear receptors coordinate autophagy.
Nature
PUBLISHED: 10-13-2014
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Autophagy is an evolutionarily conserved catabolic process that recycles nutrients upon starvation and maintains cellular energy homeostasis. Its acute regulation by nutrient-sensing signalling pathways is well described, but its longer-term transcriptional regulation is not. The nuclear receptors peroxisome proliferator-activated receptor-? (PPAR?) and farnesoid X receptor (FXR) are activated in the fasted and fed liver, respectively. Here we show that both PPAR? and FXR regulate hepatic autophagy in mice. Pharmacological activation of PPAR? reverses the normal suppression of autophagy in the fed state, inducing autophagic lipid degradation, or lipophagy. This response is lost in PPAR? knockout (Ppara(-/-), also known as Nr1c1(-/-)) mice, which are partially defective in the induction of autophagy by fasting. Pharmacological activation of the bile acid receptor FXR strongly suppresses the induction of autophagy in the fasting state, and this response is absent in FXR knockout (Fxr(-/-), also known as Nr1h4(-/-)) mice, which show a partial defect in suppression of hepatic autophagy in the fed state. PPAR? and FXR compete for binding to shared sites in autophagic gene promoters, with opposite transcriptional outputs. These results reveal complementary, interlocking mechanisms for regulation of autophagy by nutrient status.
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The Wide Range Achievement Test-4 Reading subtest "holds" in HIV-infected individuals.
J Clin Exp Neuropsychol
PUBLISHED: 10-06-2014
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Background: In order to detect HIV-associated neurocognitive decline, it is important to accurately estimate individuals' premorbid levels of cognitive functioning. Although previous studies have operated under the assumption that word reading tests are valid and stable indicators of premorbid abilities in HIV infection, studies of other populations have found that this is not always the case. Therefore, it is important to empirically examine the validity of word reading tests as estimates of premorbid functioning specifically within the HIV population. Method: The Wide Range Achievement Test-4 Reading subtest (WRAT-4 Reading) was administered along with comprehensive neurocognitive assessments to 150 HIV seropositive (HIV+) and 76 HIV seronegative (HIV-) age-, education-, and sex-matched participants; a subset of 48 HIV+ individuals completed a second study visit (M = 14.4 months), in which the alternate version of the WRAT-4 was administered. Results: Although HIV+ individuals evidenced worse current neurocognitive functioning than HIV- participants, WRAT-4 Reading performance was comparable between groups. Longitudinally, HIV+ participants evidenced improved disease and neuropsychological functioning, yet WRAT-4 Reading demonstrated strong test-retest reliability and no practice effect, and did not differ between the initial and follow-up assessments. Test-retest differences in reading performance were minor and were not associated with changes in neurocognitive performance or changes in HIV disease. Conclusions: We found no evidence of WRAT-4 Reading performance decline in HIV infection, despite HIV+/HIV- group differences in neurocognitive functioning. Additionally, reading performances among HIV+ individuals demonstrated consistency across study visits. These results begin to support the validity of the WRAT-4 Reading subtest as an indicator of premorbid cognitive functioning in HIV+ individuals.
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The effect of pain and the anticipation of pain on temporal perception: A role for attention and arousal.
Cogn Emot
PUBLISHED: 09-10-2014
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The overestimation of the duration of fear-inducing stimuli relative to neutral stimuli is a robust finding within the temporal perception literature. Whilst this effect is consistently reported with auditory and visual stimuli, there has been little examination of whether it can be replicated using painful stimulation. The aim of the current study was, therefore, to explore how pain and the anticipation of pain affected perceived duration of time. A modified verbal estimation paradigm was developed in which participants estimated the duration of shapes previously conditioned to be associated with pain, compared to those not associated with pain. Duration estimates were significantly longer on trials in which pain was received or anticipated than on control trials. Slope and intercept analysis revealed that the anticipation of pain resulted in steeper slopes and greater intercept values than for control trials. The results suggest that increased arousal and attention, when anticipating and experiencing pain, result in longer perceived durations. The results are discussed in relation to internal clock theory and neurocognitive models of time perception.
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Clinical management of concurrent diabetes and tuberculosis and the implications for patient services.
Lancet Diabetes Endocrinol
PUBLISHED: 09-08-2014
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Diabetes triples the risk for active tuberculosis, thus the increasing burden of type 2 diabetes will help to sustain the present tuberculosis epidemic. Recommendations have been made for bidirectional screening, but evidence is scarce about the performance of specific tuberculosis tests in individuals with diabetes, specific diabetes tests in patients with tuberculosis, and screening and preventive therapy for latent tuberculosis infections in individuals with diabetes. Clinical management of patients with both diseases can be difficult. Tuberculosis patients with diabetes have a lower concentration of tuberculosis drugs and a higher risk of drug toxicity than tuberculosis patients without diabetes. Good glycaemic control, which reduces long-term diabetes complications and could also improve tuberculosis treatment outcomes, is hampered by chronic inflammation, drug-drug interactions, suboptimum adherence to drug treatments, and other factors. Besides drug treatments for tuberculosis and diabetes, other interventions, such as education, intensive monitoring, and lifestyle interventions, might be needed, especially for patients with newly diagnosed diabetes or those who need insulin. From a health systems point of view, delivery of optimum care and integration of services for tuberculosis and diabetes is a huge challenge in many countries. Experience from the combined tuberculosis and HIV/AIDS epidemic could serve as an example, but more studies are needed that include economic assessments of recommended screening and systems to manage concurrent tuberculosis and diabetes.
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Infectious Diseases and Tropical Disease Pathology: SC16-1 rRNA SEQUENCING IN MOLECULAR MICROBIOLOGICAL DIAGNOSIS OF BACTERIAL INFECTIONS IN THE AUTOPSY SETTING.
Pathology
PUBLISHED: 09-05-2014
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Diagnosing the aetiology of infectious diseases at autopsy, such as pneumonia, meningitis, sepsis or SUDI, is complicated due to issues including post mortem contamination, difficulty culturing fastidious organisms and subjective interpretation of polymicrobial cultures. Death of organisms may also occur post mortem, especially if antibiotics were given to the patient, but residual DNA from non-viable organisms, amenable to molecular detection, may remain. The 16S rRNA gene is present in all bacteria with conserved and hyper-variable regions along its length, allowing amplification and sequencing of all bacterial 16S sequences present in a sample. 16S sequencing offers potential advantages over culture-based diagnostics and is increasingly used in clinical practice. It has been used to identify bacteria in formalin fixed paraffin embedded (FFPE) surgical pathology specimens but its use has not been reported in autopsy diagnosis. This talk will summarise a study aimed to assess the utility of 16S sequencing as an adjunctive microbiological test in the autopsy. Our preliminary work has used post mortem lung tissue samples from children dying with pneumonia as part of the Pneumonia Etiology Research for Child Health (PERCH) project. The technique has identified known pathogens in some cases and provided additional diagnostic information in others. The presentation will discuss the technical aspects of 16S sequencing from FFPE and autopsy material, and the issues surrounding its application to diagnosis in comparison with standard culture based diagnostics on surgical/autopsy material.
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Percutaneous absorption of salicylic acid - in vitro and in vivo studies.
Int J Pharm
PUBLISHED: 08-29-2014
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Salicylic acid (SA) has been used in pharmaceutical and cosmetic preparations for many years. Although there are a number of studies which report on the permeation characteristics of this molecule in vitro, to our knowledge the disposition of SA in vivo has not been studied in detail. In the present work we prepared a range of SA formulations with different gelling agents. Permeation of SA from the formulations was studied in vitro using conventional Franz cells and in vivo using confocal Raman spectroscopy (CRS). Selection of the gelling agent clearly influenced the efficacy of SA delivery from all formulations. It was possible to detect SA in vivo using CRS and to depth profile the molecule. A good in vitro-in vivo correlation was also found when the cumulative amounts of SA which permeated in vitro were plotted against the CRS signal in the skin. The findings provide further confidence in the application of CRS for the study of drug disposition in the skin.
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Phosphorylation of activating transcription factor-2 (ATF-2) within the activation domain is a key determinant of sensitivity to tamoxifen in breast cancer.
Breast Cancer Res. Treat.
PUBLISHED: 08-22-2014
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Activating transcription factor-2 (ATF-2) has been implicated as a tumour suppressor in breast cancer (BC). c-JUN N-terminal kinase (JNK) and p38 MAPK phosphorylate ATF-2 within the activation domain (AD), which is required for its transcriptional activity. To date, the role of ATF-2 in determining response to endocrine therapy has not been explored. Effects of ATF-2 loss in the oestrogen receptor (ER)-positive luminal BC cell line MCF7 were explored, as well as its role in response to tamoxifen treatment. Genome-wide chromatin binding patterns of ATF-2 when phosphorylated within the AD in MCF-7 cells were determined using ChIP-seq. The expression of ATF-2 and phosphorylated ATF-2 (pATF-2-Thr71) was determined in a series of 1,650 BC patients and correlated with clinico-pathological features and clinical outcome. Loss of ATF-2 diminished the growth-inhibitory effects of tamoxifen, while tamoxifen treatment induced ATF-2 phosphorylation within the AD, to regulate the expression of a set of 227 genes for proximal phospho-ATF-2 binding, involved in cell development, assembly and survival. Low expression of both ATF-2 and pATF-2-Thr71 was significantly associated with aggressive pathological features. Furthermore, pATF-2 was associated with both p-p38 and pJNK1/2 (< 0.0001). While expression of ATF-2 is not associated with outcome, pATF-2 is associated with longer disease-free (p = 0.002) and BC-specific survival in patients exposed to tamoxifen (p = 0.01). Furthermore, multivariate analysis confirmed pATF-2-Thr71 as an independent prognostic factor. ATF-2 is important for modulating the effect of tamoxifen and phosphorylation of ATF-2 within the AD at Thr71 predicts for improved outcome for ER-positive BC receiving tamoxifen.
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Family-based interventions for substance misuse: a systematic review of systematic reviews--protocol.
Syst Rev
PUBLISHED: 08-15-2014
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Worldwide, there are an estimated 15 million individuals with drug use disorders and over five times as many with alcohol use disorders (WHO 1:2, 2005). Most individuals with substance misuse have families who are affected. Initial scoping searches identified an expanse of broad and disparate studies and reviews on the family interventions for substance misuse. This systematic review of systematic reviews aims to bring together the expanse of research on the effectiveness of family-based interventions in substance misuse.Initial scoping searches identified an expanse of broad and disparate studies and reviews on the family interventions for substance misuse. This systematic review of systematic reviews aims to bring together the expanse of research on the effectiveness of family-based interventions in substance misuse.
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Negative printing by soft lithography.
ACS Appl Mater Interfaces
PUBLISHED: 08-13-2014
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In inkless microcontact printing (I?CP) by soft lithography, the poly(dimethylsiloxane) (PDMS) stamp transfers uncured polymer to a substrate corresponding to its pattern. The spontaneous diffusion of PDMS oligomers to the surface of the stamp that gives rise to this deleterious side effect has been leveraged to fabricate a variety of devices, such as organic thin film transistors, single-electron devices, and biomolecular chips. Here we report an anomalous observation on a partially cured PDMS stamp where the transfer of oligomers onto Au occurred on regions that were not in contact with the stamp, while the surface in contact with the stamp was pristine with no polymer. On the SiO2 surface of the same chip, as expected, the transfer of PDMS occurred exclusively on regions in contact with the stamp. The printing on Au was quantified by a novel method where the submonolayer of PDMS transfer was measured by probing the local electrochemical passivation of the Au. The local transfer of polymer on SiO2 (and also Au) was measured by selective deposition of Au nanoparticle necklaces that exclusively deposited on PDMS at submonolayer sensitivity. It was discovered that the selectivity and sharpness of PDMS deposition on Au for inkless printing (i.e., negative) is significantly better than the traditional (positive) microcontact printing where the stamp is "inked" with low molecular weight PDMS.
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Risk Factors for Invasive Pneumococcal Disease among Children less Than 5 Years of Age in a High HIV-Prevalence Setting, South Africa, 2010 to 2012.
Pediatr. Infect. Dis. J.
PUBLISHED: 07-04-2014
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Invasive pneumococcal disease (IPD) causes significant disease burden, especially in developing countries, even in the era of pneumococcal conjugate vaccine (PCV) and maternal-to-child HIV transmission prevention programs. We evaluated factors that might increase IPD risk in young children in a high HIV prevalence setting.
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ACR appropriateness Criteria® advanced stage endometrial cancer.
Am. J. Clin. Oncol.
PUBLISHED: 07-01-2014
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Patients with advanced stage endometrial carcinoma constitute a heterogeneous group of patients with different stages, tumor histologic types, and involved sites. Hysterectomy, bilateral salpingo-ophorectomy, and surgical staging are the cornerstone of surgical management in these patients. The optimal adjuvant therapy is yet to be established. An expert panel was convened to reach consensus on the most appropriate management options in this group of patients.
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Counterpublic health and the design of drug services for methamphetamine consumers in Melbourne.
Health (London)
PUBLISHED: 06-21-2014
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This article is interested in how notions of the 'public' are conceived, marshalled and enacted in drug-treatment responses to methamphetamine use in Melbourne, Australia. After reviewing qualitative data collected among health-care providers and methamphetamine consumers, we draw on the work of Michael Warner to argue that services for methamphetamine consumers in Melbourne betray ongoing tensions between 'public' and 'counterpublic' constituencies. Our analysis indicates that these tensions manifest in two ways: in the management of 'street business' in the delivery of services and in negotiating the meaning of health and the terms of its restoration or promotion. Reflecting these tensions, while the design of services for methamphetamine consumers is largely modelled on public health principles, the everyday experience of these services may be more accurately characterised in terms of what Kane Race has called 'counterpublic health'. Extending Race's analysis, we conclude that more explicit focus on the idea of counterpublic health may help local services engage with methamphetamine consumers in new ways, providing grounds for novel outreach, harm-reduction and treatment strategies.
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Effectiveness of 7-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in HIV-infected and -uninfected children in south africa: a matched case-control study.
Clin. Infect. Dis.
PUBLISHED: 06-09-2014
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South Africa introduced 7-valent pneumococcal conjugate vaccine (PCV7) in April 2009 using a 2 + 1 schedule (6 and 14 weeks and 9 months). We estimated the effectiveness of ?2 PCV7 doses against invasive pneumococcal disease (IPD) in human immunodeficiency virus (HIV)-infected and -uninfected children.
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Refining a personalized mHealth intervention to promote medication adherence among HIV+ methamphetamine users.
AIDS Care
PUBLISHED: 06-09-2014
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Mobile health (mHealth) interventions to promote antiretroviral therapy (ART) adherence have shown promise; however, among persons living with HIV who abuse methamphetamine (MA), effective tailoring of content to match the expressed needs of this patient population may be necessary. This study aimed (1) to understand patient perspectives of barriers and facilitators of ART adherence among people with HIV who use MA, and (2) to obtain feedback on the thematic content of an mHealth intervention in order to tailor the intervention to this subgroup. Two separate focus groups, each with 10 HIV+/MA+ individuals, were conducted. Transcribed audio recordings were qualitatively analyzed to identify emergent themes. Inter-rater reliability of themes was high (mean Kappa = .97). Adherence barriers included MA use, misguided beliefs about ART adherence, memory and planning difficulties, social barriers and perceived stigma, and mental heath issues. Facilitators of effective ART adherence were cognitive compensatory strategies, promotion of well-being, health-care supports, adherence education, and social support. Additionally, the focus groups generated content for reminder text messages to be used in the medication adherence intervention. This qualitative study demonstrates the feasibility of using focus groups to derive patient-centered intervention content to address the health challenge at hand in targeted populations.
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Anthropometric characteristics, high prevalence of undernutrition and weight loss: impact on outcomes in patients with adolescent idiopathic scoliosis after spinal fusion.
Eur Spine J
PUBLISHED: 05-16-2014
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Abnormal anthropometry including comparably lower weight and body mass index (BMI) in the adolescent idiopathic scoliosis (AIS) population is increasingly recognised, however, no study has examined postoperative weight loss or its clinical relevance in these relatively thin patients. This study aimed to assess perioperative nutritional status as well as clinically severe involuntary weight loss and its impact on outcomes in patients with AIS undergoing posterior spinal fusion (PSF). A further objective was to compare preoperative anthropometric measurements of the current AIS cohort with healthy controls.
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Nuclear receptor LRH-1/NR5A2 is required and targetable for liver endoplasmic reticulum stress resolution.
Elife
PUBLISHED: 04-17-2014
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Chronic endoplasmic reticulum (ER) stress results in toxicity that contributes to multiple human disorders. We report a stress resolution pathway initiated by the nuclear receptor LRH-1 that is independent of known unfolded protein response (UPR) pathways. Like mice lacking primary UPR components, hepatic Lrh-1-null mice cannot resolve ER stress, despite a functional UPR. In response to ER stress, LRH-1 induces expression of the kinase Plk3, which phosphorylates and activates the transcription factor ATF2. Plk3-null mice also cannot resolve ER stress, and restoring Plk3 expression in Lrh-1-null cells rescues ER stress resolution. Reduced or heightened ATF2 activity also sensitizes or desensitizes cells to ER stress, respectively. LRH-1 agonist treatment increases ER stress resistance and decreases cell death. We conclude that LRH-1 initiates a novel pathway of ER stress resolution that is independent of the UPR, yet equivalently required. Targeting LRH-1 may be beneficial in human disorders associated with chronic ER stress. DOI: http://dx.doi.org/10.7554/eLife.01694.001.
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Relationship between disclosure of same-sex sexual activity to providers, HIV diagnosis and sexual health services for men who have sex with men in Vancouver, Canada.
Can J Public Health
PUBLISHED: 04-16-2014
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Men who have sex with men (MSM) report challenges to accessing appropriate health care. We sought to understand the relationship between disclosure of same-sex sexual activity to a health care practitioner (HCP), sexual behaviour and measures of sexual health care.
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Kinetic evidence suggests spinodal phase separation in stratum corneum models by IR spectroscopy.
J Phys Chem B
PUBLISHED: 04-16-2014
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Although lipid structure in models for the stratum corneum (SC), the main barrier to skin permeability, has been extensively studied, only limited data are extant concerning the kinetic mechanism for the formation of domains, lamellar phases, and lipid packing motifs. Such information would be of substantial interest in the characterization of the effects of disease states which disrupt the barrier. Kinetic IR spectroscopy measurements probed the temporal sequence of molecular events producing ordered structures in a three-component SC model of equimolar ceramide[NS] (cer[NS]), perdeuterated stearic acid-d35 (SA-d35), and cholesterol. Samples, heated above Tm, were quenched to 31 °C, and then spectra were recorded at ?15 min intervals for a total of 20-150 h. IR provides unique molecular structure information about headgroup H-bonding, lipid packing, and lipid chain order. The following sequence for phase separation was observed: (1) Formation of ceramide amide H-bonds from disordered forms to ordered structures (0.5-4 h); (2) appearance of ordered ceramide chains with some orthorhombically packed structures (0.5-8 h); and (3) phase separation of large orthorhombic domains of SA-d35 (4-10 h). A spinodal decomposition mechanism, defined by continuous composition changes during the phase separation, suggests a qualitative description for these events.
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Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance.
Brain
PUBLISHED: 04-10-2014
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Despite being a canonical presenting feature of mitochondrial disease, the genetic basis of progressive external ophthalmoplegia remains unknown in a large proportion of patients. Here we show that mutations in SPG7 are a novel cause of progressive external ophthalmoplegia associated with multiple mitochondrial DNA deletions. After excluding known causes, whole exome sequencing, targeted Sanger sequencing and multiplex ligation-dependent probe amplification analysis were used to study 68 adult patients with progressive external ophthalmoplegia either with or without multiple mitochondrial DNA deletions in skeletal muscle. Nine patients (eight probands) were found to carry compound heterozygous SPG7 mutations, including three novel mutations: two missense mutations c.2221G>A; p.(Glu741Lys), c.2224G>A; p.(Asp742Asn), a truncating mutation c.861dupT; p.Asn288*, and seven previously reported mutations. We identified a further six patients with single heterozygous mutations in SPG7, including two further novel mutations: c.184-3C>T (predicted to remove a splice site before exon 2) and c.1067C>T; p.(Thr356Met). The clinical phenotype typically developed in mid-adult life with either progressive external ophthalmoplegia/ptosis and spastic ataxia, or a progressive ataxic disorder. Dysphagia and proximal myopathy were common, but urinary symptoms were rare, despite the spasticity. Functional studies included transcript analysis, proteomics, mitochondrial network analysis, single fibre mitochondrial DNA analysis and deep re-sequencing of mitochondrial DNA. SPG7 mutations caused increased mitochondrial biogenesis in patient muscle, and mitochondrial fusion in patient fibroblasts associated with the clonal expansion of mitochondrial DNA mutations. In conclusion, the SPG7 gene should be screened in patients in whom a disorder of mitochondrial DNA maintenance is suspected when spastic ataxia is prominent. The complex neurological phenotype is likely a result of the clonal expansion of secondary mitochondrial DNA mutations modulating the phenotype, driven by compensatory mitochondrial biogenesis.
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Metabolic activation of the indoloquinazoline alkaloids evodiamine and rutaecarpine by human liver microsomes: dehydrogenation and inactivation of cytochrome P450 3A4.
Drug Metab. Dispos.
PUBLISHED: 04-02-2014
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Evodiamine and rutaecarpine are the main active indoloquinazoline alkaloids of the herbal medicine Evodia rutaecarpa, which is widely used for the treatment of hypertension, abdominal pain, angina pectoris, gastrointestinal disorder, and headache. Immunosuppressive effects and acute toxicity were reported in mice treated with evodiamine and rutaecarpine. Although the mechanism remains unknown, it is proposed that metabolic activation of the indoloquinazoline alkaloids and subsequent covalent binding of reactive metabolites to cellular proteins play a causative role. Liquid chromatography-tandem mass spectrometry analysis of incubations containing evodiamine and NADPH-supplemented microsomes in the presence of glutathione (GSH) revealed formation of a major GSH conjugate which was subsequently indentified as a benzylic thioether adduct on the C-8 position of evodiamine by NMR analysis. Several other GSH conjugates were also detected, including conjugates of oxidized and demethylated metabolites of evodiamine. Similar GSH conjugates were formed in incubations with rutaecarpine. These findings are consistent with a bioactivation sequence involving initial cytochrome P450-catalyzed dehydrogenation of the 3-alkylindole moiety in evodiamine and rutaecarpine to an electrophile 3-methyleneindolenine. Formation of the evodiamine and rutaecarpine GSH conjugates was primarily catalyzed by heterologously expressed recombinant CYP3A4 and, to a lesser extent, CYP1A2 and CYP2D6, respectively. It was found that the 3-methyleneindolenine or another reactive intermediate was a mechanism-based inactivator of CYP3A4, with inactivation parameters KI = 29 µM and kinact = 0.029 minute(-1), respectively. In summary, these findings are of significance in understanding the bioactivation mechanisms of indoloquinazoline alkaloids, and dehydrogenation of evodiamine and rutaecarpine may cause toxicities through formation of electrophilic intermediates and lead to drug-drug interactions mainly via CYP3A4 inactivation.
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Decisions, decisions: the importance of condom use decision making among HIV sero-discordant couples in a prospective cohort study in Uganda.
Sex Transm Infect
PUBLISHED: 04-02-2014
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We examined sexual decision making type among couples in HIV sero-discordant partnerships in Uganda, and investigated how sexual decision making type changed over time and its effect on condom use.
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Cohort Profile: HAART Observational Medical Evaluation and Research (HOMER) cohort.
Int J Epidemiol
PUBLISHED: 03-19-2014
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Since 1986, antiretroviral therapy (ART) has been available free of charge to individuals living with HIV in British Columbia (BC), Canada, through the BC Centre of Excellence in HIV/AIDS (BC-CfE) Drug Treatment Program (DTP). The Highly Active Antiretroviral Therapy (HAART) Observational Medical Evaluation and Research (HOMER) cohort was established in 1996 to maintain a prospective record of clinical measurements and medication profiles of a subset of DTP participants initiating HAART in BC. This unique cohort provides a comprehensive data source to investigate mortality, prognostic factors and treatment response among people living with HIV in BC from the inception of HAART. Currently over 5000 individuals are enrolled in the HOMER cohort. Data captured include socio-demographic characteristics (e.g. sex, age, ethnicity, health authority), clinical variables (e.g. CD4 cell count, plasma HIV viral load, AIDS-defining illness, hepatitis C co-infection, mortality) and treatment variables (e.g. HAART regimens, date of treatment initiation, treatment interruptions, adherence data, resistance testing). Research findings from the HOMER cohort have featured in numerous high-impact peer-reviewed journals. The HOMER cohort collaborates with other HIV cohorts on both national and international scales to answer complex HIV-specific research questions, and welcomes input from external investigators regarding potential research proposals or future collaborations. For further information please contact the principal investigator, Dr Robert Hogg (robert_hogg@sfu.ca).
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Optimisation of an immunohistochemistry method for the determination of androgen receptor expression levels in circulating tumour cells.
BMC Cancer
PUBLISHED: 03-10-2014
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AZD3514 inhibits and down regulates the androgen receptor (AR) and has undergone clinical trials in prostate cancer. To provide proof-of-mechanism (POM) in patients, an immunohistochemistry (IHC) method for determination of AR in circulating tumour cells (CTC) was developed and validated.
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Quantification of skeletal metastases in castrate-resistant prostate cancer predicts progression-free and overall survival.
BJU Int.
PUBLISHED: 03-05-2014
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To report a simplified and effective method for substratification of M1 castrate-resistant prostate cancer (CRPC) by correlating progression-free (PFS) and overall survival (OS) with simple quantification of skeletal metastases.
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Protocol for a systematic review and economic evaluation of the clinical and cost-effectiveness of non-hospital-based non-invasive ventilation (NIV) in patients with stable end-stage COPD with hypercapnic respiratory failure.
Syst Rev
PUBLISHED: 03-03-2014
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Chronic obstructive pulmonary disease (COPD) remains a significant public health burden. Non-invasive ventilation (NIV) is a method of supported breathing used as standard care for acutely unwell patients in hospital with COPD, but there is uncertainty around the potential benefits of using NIV in the treatment of stable patients in a non-hospital setting. This is a protocol for systematic reviews of the clinical and cost-effectiveness of NIV in this context, being undertaken in support of a model based economic evaluation.
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Community mapping and respondent-driven sampling of gay and bisexual men's communities in Vancouver, Canada.
Cult Health Sex
PUBLISHED: 02-12-2014
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Literature suggests formative research is vital for those using respondent-driven sampling (RDS) to study hidden populations of interest. However, few authors have described in detail how different qualitative methodologies can address the objectives of formative research for understanding the social network properties of the study population, selecting seeds and adapting survey logistics to best fit the population. In this paper we describe the use of community mapping exercises as a tool within focus groups to collect data on social and sexual network characteristics of gay and bisexual men in the metropolitan area of Vancouver, Canada. Three key themes emerged from analysing community maps along with other formative research data: (1) connections between physical spaces and social networks of gay and bisexual men, (2) diversity in communities and (3) substance use linked to formation of sub-communities. We discuss how these themes informed the planning and operations of a longitudinal epidemiological cohort study recruited by RDS. We argue that using community mapping within formative research is a valuable qualitative tool for characterising network structures of a diverse and differentiated population of gay and bisexual men in a highly developed urban setting.
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'Hyped up': assemblages of alcohol, excitement and violence for outer-suburban young adults in the inner-city at night.
Int. J. Drug Policy
PUBLISHED: 01-30-2014
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Young adults from across greater Melbourne are drawn to the city centre night time economy (NTE). There is some evidence that young adults who live in outer-suburbs are involved in higher rates of weekend night time assaults than their inner-urban peers, both as perpetrators and as victims. Using the notion of 'assemblages', this article explores outer-suburban people's participation in the affectively charged spaces of inner-city entertainment precincts to show that trouble in the NTE cannot be attributed to alcohol and other drugs alone.
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A delayed and rather unusual presentation of a bladder injury after pelvic trauma: 5 years after a road traffic accident.
Case Rep Orthop
PUBLISHED: 01-21-2014
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Associated injuries frequently occur in patients who sustain fractures of the pelvis. Specifically, high-energy trauma resulting in pelvic fractures places the bladder and urethra at risk for injury, often resulting in significant complications. Timely identification and management of genitourinary injuries minimize associated morbidity. Prompt injury identification depends upon a systematic evaluation with careful consideration of the mechanism of injury. Physical examination is pertinent as well as analysis of the urine and appropriate diagnostic imaging. Despite such increased vigilance genitourinary injuries get missed and delayed presentations in the order of a few weeks have been well documented. To our knowledge, this is the first report of its kind in the literature showing such a particularly delayed (5 years) and rather unusual presentation of a bladder injury after pelvic trauma.
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Sex hormone pathway gene polymorphisms are associated with risk of advanced hepatitis C-related liver disease in males.
Int J Mol Epidemiol Genet
PUBLISHED: 01-01-2014
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Males have excess advanced liver disease and cirrhosis risk including from chronic hepatitis C virus (HCV) infection though the reasons are unclear.
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Carbon dioxide hydrogenation to aromatic hydrocarbons by using an iron/iron oxide nanocatalyst.
Beilstein J Nanotechnol
PUBLISHED: 01-01-2014
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The quest for renewable and cleaner energy sources to meet the rapid population and economic growth is more urgent than ever before. Being the most abundant carbon source in the atmosphere of Earth, CO2 can be used as an inexpensive C1 building block in the synthesis of aromatic fuels for internal combustion engines. We designed a process capable of synthesizing benzene, toluene, xylenes and mesitylene from CO2 and H2 at modest temperatures (T = 380 to 540 °C) employing Fe/Fe3O4 nanoparticles as catalyst. The synthesis of the catalyst and the mechanism of CO2-hydrogenation will be discussed, as well as further applications of Fe/Fe3O4 nanoparticles in catalysis.
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Association between childhood physical abuse, unprotected receptive anal intercourse and HIV infection among young men who have sex with men in Vancouver, Canada.
PLoS ONE
PUBLISHED: 01-01-2014
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The association between childhood sexual abuse and HIV risk among men who have sex with men (MSM) is well established. However, no studies have examined the potential impact of other forms of childhood maltreatment on HIV incidence in this population.
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Temporal association in hospitalizations for tuberculosis, invasive pneumococcal disease and influenza virus illness in South African children.
PLoS ONE
PUBLISHED: 01-01-2014
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The seasonal variability in hospitalization for tuberculosis may in part relate to super-imposed bacterial or predisposing respiratory viral infections. We aimed to study the temporal association between hospitalization for culture-confirmed pulmonary tuberculosis (PTB), invasive pneumococcal disease (IPD) and influenza virus epidemics in South African children.
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Expansion of HAART coverage is associated with sustained decreases in HIV/AIDS morbidity, mortality and HIV transmission: the "HIV Treatment as Prevention" experience in a Canadian setting.
PLoS ONE
PUBLISHED: 01-01-2014
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There has been renewed call for the global expansion of highly active antiretroviral therapy (HAART) under the framework of HIV treatment as prevention (TasP). However, population-level sustainability of this strategy has not been characterized.
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Vitamin D Receptor Activation Down-regulates Small Heterodimer Partner and Increases CYP7A1 to Lower Cholesterol.
Gastroenterology
PUBLISHED: 12-15-2013
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Little is known about effects of the vitamin D receptor (VDR) on hepatic activity of CYP7A1 and cholesterol metabolism. We studied these processes in mice and mouse and human hepatocytes.
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Breast cancer in lesbians and bisexual women: systematic review of incidence, prevalence and risk studies.
BMC Public Health
PUBLISHED: 11-26-2013
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The UK Parliamentary Enquiry and USA Institute of Medicine state that lesbians may be at a higher risk of breast cancer but there is insufficient information. Lesbians and bisexual (LB) women have behavioural risk-factors at higher rates compared to heterosexuals such as increased alcohol intake and higher stress levels. Conversely, breast cancer rates are higher in more affluent women yet income levels in LB women are relatively low. This systematic review investigated all evidence on whether there is, or likely to be, higher rates of breast cancer in LB women.
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Intergenerational Sex as a Risk Factor for HIV Among Young Men Who Have Sex with Men: A Scoping Review.
Curr HIV/AIDS Rep
PUBLISHED: 11-26-2013
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An emerging body of evidence suggests that intergenerational sexual partnerships may increase risk of HIV acquisition among young men who have sex with men (YMSM). However, no studies have comprehensively evaluated literature in this area. We applied a scoping review methodology to explore the relationships between age mixing, HIV risk behavior, and HIV seroconversion among YMSM. This study identified several individual, micro-, and meso-system factors influencing HIV risk among YMSM in the context of intergenerational relationships: childhood maltreatment, coming of age and sexual identity, and substance use (individual-level factors); family and social support, partner characteristics, intimate partner violence, connectedness to gay community (micro-system factors); and race/ethnicity, economic disparity, and use of the Internet (meso-system factors). These thematic groups can be used to frame future research on the role of age-discrepant relationships on HIV risk among YMSM, and to enhance public health HIV education and prevention strategies targeting this vulnerable population.
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Branched oligopeptides form nanocapsules with lipid vesicle characteristics.
Langmuir
PUBLISHED: 11-18-2013
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In a recent article (Gudlur et al. PLOS ONE, 2012, 7 (9) e45374), we described the special properties of a mixed branched peptide assembly in which equimolar bis(FLIVI)-K-KKKK and bis(FLIVIGSII)-K-KKKK self-associate to form bilayer delimited capsules capable of trapping solutes. These polycationic vesicle-like capsules are readily taken up by epithelial cells in culture, escape or evade the endocytic pathway, and accumulate in the perinuclear region where they persist without any apparent degradation. In this report, we examine the lipidlike properties of this system including initial assembly; solute encapsulation and washing; fusion and resizing by membrane extrusion through polycarbonate filters with defined pore sizes. The resized peptide capsules have uniform diameters in nm size ranges. Once resized, the capsules can be maintained at the new size by storing them at 4 °C. Having the ability to prepare stable uniform nanoscale capsules of desired sizes makes them potentially attractive as biocompatible delivery vehicles for various solutes/drugs.
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Role of constitutive androstane receptor in toll-like receptor-mediated regulation of gene expression of hepatic drug-metabolizing enzymes and transporters.
Drug Metab. Dispos.
PUBLISHED: 11-05-2013
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Impairment of drug disposition in the liver during inflammation has been attributed to downregulation of gene expression of drug-metabolizing enzymes (DMEs) and drug transporters. Inflammatory responses in the liver are primarily mediated by Toll-like receptors (TLRs). We have recently shown that activation of TLR2 or TLR4 by lipoteichoic acid (LTA) and lipopolysaccharide (LPS), respectively, leads to the downregulation of gene expression of DMEs/transporters. However, the molecular mechanism underlying this downregulation is not fully understood. The xenobiotic nuclear receptors, pregnane X receptor (PXR) and constitutive androstane receptor (CAR), regulate the expression of DMEs/transporter genes. Downregulation of DMEs/transporters by LTA or LPS was associated with reduced expression of PXR and CAR genes. To determine the role of CAR, we injected CAR(+/+) and CAR(-/-) mice with LTA or LPS, which significantly downregulated (?40%-60%) RNA levels of the DMEs, cytochrome P450 (Cyp)3a11, Cyp2a4, Cyp2b10, uridine diphosphate glucuronosyltransferase 1a1, amine N-sulfotransferase, and the transporter, multidrug resistance-associated protein 2, in CAR(+/+) mice. Suppression of most of these genes was attenuated in LTA-treated CAR(-/-) mice. In contrast, LPS-mediated downregulation of these genes was not attenuated in CAR(-/-) mice. Induction of these genes by mouse CAR activator 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene was sustained in LTA- but not in LPS-treated mice. Similar observations were obtained in humanized CAR mice. We have replicated these results in primary hepatocytes as well. Thus, LPS can downregulate DME/transporter genes in the absence of CAR, whereas the effect of LTA on these genes is attenuated in the absence of CAR, indicating the potential involvement of CAR in LTA-mediated downregulation of DME/transporter genes.
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Focussed ion beam serial sectioning and imaging of monolithic materials for 3D reconstruction and morphological parameter evaluation.
Analyst
PUBLISHED: 10-25-2013
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A new characterisation method, based on the utilisation of focussed ion beam-scanning electron microscopy (FIB-SEM), has been employed for the evaluation of morphological parameters in porous monolithic materials. Sample FIB serial sectioning, SEM imaging and image processing techniques were used to extract the pore boundaries and reconstruct the 3D porous structure of carbon and silica-based monoliths. Since silica is a non-conducting material, a commercial silica monolith modified with activated carbon was employed instead to minimise the charge build-up during FIB sectioning. This work therefore presents a novel methodology that can be successfully employed for 3D reconstruction of porous monolithic materials which are or can be made conductive through surface or bulk modification. Furthermore, the 3D reconstructions were used for calculation of the monolith macroporosity, which was in good agreement with the porosity values obtained by mercury intrusion porosimetry (MIP).
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Dried blood spots for qPCR diagnosis of acute Bartonella bacilliformis infection.
Am. J. Trop. Med. Hyg.
PUBLISHED: 09-16-2013
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Bartonella bacilliformis is the etiological agent of a life-threatening illness. Thin blood smear is the most common diagnostic method for acute infection in endemic areas of Peru but remains of limited value because of low sensitivity. The aim of this study was to adapt a B. bacilliformis-specific real-time polymerase chain reaction (PCR) assay for use with dried blood spots (DBS) as a sampling method and assess its performance and use for the diagnosis and surveillance of acute Bartonella infection. Only two of 65 children (3%) that participated in this study had positive blood smears for B. bacilliformis, whereas 16 (including these two) were positive by PCR performed on DBS samples (24.6%). The use of DBS in combination with B. bacilliformis-specific PCR could be a useful tool for public health in identifying and monitoring outbreaks of infection and designing control programs to reduce the burden of this life-threatening illness.
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MCF-7 cells expressing nuclear associated lysyl oxidase-like 2 (LOXL2) exhibit an epithelial-to-mesenchymal transition (EMT) phenotype and are highly invasive in vitro.
J. Biol. Chem.
PUBLISHED: 09-06-2013
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LOXL2 is a copper- and lysine tyrosylquinone-dependent amine oxidase that has been proposed to function both extracellularly and intracellularly to activate oncogenic signaling pathways leading to EMT and invasion of breast cancer cells. In this study, we selected MCF-7 cells that stably express forms of recombinant LOXL2 differing in their subcellular localizations and catalytic competencies. This enabled us to dissect the molecular functions of intracellular and extracellular LOXL2s and examine their contributions to breast cancer metastasis/invasion. We discovered that secreted LOXL2 (~100-kDa) is N-glycosylated at Asn-455 and Asn-644, whereas intracellular LOXL2 (~75-kDa) is nonglycosylated and N-terminally processed, and is primarily associated with the nucleus. Both forms of LOXL2 can oxidize lysine in solution. However, we found that expression of intracellular LOXL2 is more strongly associated with EMT and invasiveness than secreted LOXL2 in vitro. The results indicate that nuclear associated LOXL2 contributes to the stabilization of Snail1 transcription factor at the protein level to induce EMT and promote invasion in vitro, through repression of E-cadherin, occludin, and estrogen receptor-?, and up-regulation of vimentin, fibronectin, and MT1-MMP.
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Preventing acute hypercapnic respiratory failure in COPD patients.
Nurs Stand
PUBLISHED: 08-31-2013
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Patients with chronic obstructive pulmonary disease (COPD) are at risk of developing acute hypercapnic respiratory failure (AHRF) if given high-concentration uncontrolled oxygen inappropriately. This article analyses a critical incident involving a patient who developed AHRF, and identifies areas for improvement in clinical practice that would improve the standard of care for patients with COPD.
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FXR-induced secretion of FGF15/19 inhibits CYP27 expression in cholangiocytes through p38 kinase pathway.
Pflugers Arch.
PUBLISHED: 08-21-2013
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Cholangiocytes, bile duct lining cells, actively adjust the amount of cholesterol and bile acids in bile through expression of enzymes and channels involved in transportation and metabolism of the cholesterol and bile acids. Herein, we report molecular mechanisms regulating bile acid biosynthesis in cholangiocytes. Among the cytochrome p450 (Cyp) enzymes involved in bile acid biosynthesis, sterol 27-hydroxylase (Cyp27) that is the rate-limiting enzyme for the acidic pathway of bile acid biosynthesis expressed in cholangiocytes. Expression of other Cyp enzymes for the basic bile acid biosynthesis was hardly detected. The Cyp27 expression was negatively regulated by a hydrophobic bile acid through farnesoid X receptor (FXR), a nuclear receptor activated by bile acid ligands. Activated FXR exerted the negative effects by inducing an expression of fibroblast growth factor 15/19 (FGF15/19). Similar to its repressive function against cholesterol 7?-hydroxylase (Cyp7a1) expression in hepatocytes, secreted FGF15/19 triggered Cyp27 repression in cholangiocytes through interaction with its cognate receptor fibroblast growth factor receptor 4 (FGFR4). The involvements of FXR and FGFR4 for the bile acid-induced Cyp27 repression were confirmed in vivo using knockout mouse models. Different from the signaling in hepatocytes, wherein the FGF15/19-induced repression signaling is mediated by c-Jun N-terminal kinase (JNK), FGF15/19-induced Cyp27 repression in cholangiocytes was mediated by p38 kinase. Thus, the results collectively suggest that cholangiocytes may be able to actively regulate bile acid biosynthesis in cholangiocytes and even hepatocyte by secreting FGF15/19. We suggest the presence of cholangiocyte-mediated intrahepatic feedback loop in addition to the enterohepatic feedback loop against bile acid biosynthesis in the liver.
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ACR Appropriateness Criteria® management of locoregionally advanced squamous cell carcinoma of the vulva.
Am. J. Clin. Oncol.
PUBLISHED: 07-23-2013
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Locoregionally advanced vulvar cancer (LRAVC) is a rare disease that presents many challenging medical decisions. An expert panel was convened to reach consensus on the most appropriate pretreatment assessment and therapeutic interventions in LRAVC patients.
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Real-world impact of neurocognitive deficits in acute and early HIV infection.
J. Neurovirol.
PUBLISHED: 07-17-2013
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The acute and early period of HIV-1 infection (AEH) is characterized by neuroinflammatory and immunopathogenic processes that can alter the integrity of neural systems and neurocognitive functions. However, the extent to which central nervous system changes in AEH confer increased risk of real-world functioning (RWF) problems is not known. In the present study, 34 individuals with AEH and 39 seronegative comparison participants completed standardized neuromedical, psychiatric, and neurocognitive research evaluations, alongside a comprehensive assessment of RWF that included cognitive symptoms in daily life, basic and instrumental activities of daily living, clinician-rated global functioning, and employment. Results showed that AEH was associated with a significantly increased risk of dependence in RWF, which was particularly elevated among AEH persons with global neurocognitive impairment (NCI). Among those with AEH, NCI (i.e., deficits in learning and information processing speed), mood disorders (i.e., Bipolar Disorder), and substance dependence (e.g., methamphetamine dependence) were all independently predictive of RWF dependence. Findings suggest that neurocognitively impaired individuals with AEH are at notably elevated risk of clinically significant challenges in normal daily functioning. Screening for neurocognitive, mood, and substance use disorders in AEH may facilitate identification of individuals at high risk of functional dependence who may benefit from psychological and medical strategies to manage their neuropsychiatric conditions.
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Dynamic indices of methamphetamine dependence and HIV infection predict fluctuations in affective distress: a five-year longitudinal analysis.
J Affect Disord
PUBLISHED: 06-29-2013
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Methamphetamine (METH) use and human immunodeficiency virus (HIV) infection are highly comorbid, and both are associated with increased prevalence of affective distress. Delineating the trajectory of affective distress in the context of METH dependence and HIV infection is important given the implications for everyday functional impairment, adverse health behaviors, and increased risk for adverse health outcomes.
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Selflessness is sexy: reported helping behaviour increases desirability of men and women as long-term sexual partners.
BMC Evol. Biol.
PUBLISHED: 06-18-2013
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Despite its short-term costs, behaviour that appears altruistic can increase an individuals inclusive fitness by earning direct (selfish) and/or indirect (kin-selected) benefits. An evolved preference for other-regarding or helping behaviour in potential mates has been proposed as an additional mechanism by which these behaviours can yield direct fitness benefits in humans.
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The prevalence of abnormal preoperative coagulation tests in pediatric patients undergoing spinal surgery for scoliosis.
Spine J
PUBLISHED: 06-16-2013
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Multilevel spinal fusion surgery for deformity correcting spinal surgery in pediatric patients with scoliosis has typically been associated with significant blood loss. The mechanism of bleeding in such patients is not fully understood. Coagulation abnormalities, which may be associated with scoliosis, are thought to play a role.
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Broad-spectrum biosensor capable of detecting and identifying diverse bacterial and Candida species in blood.
J. Clin. Microbiol.
PUBLISHED: 06-12-2013
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We describe an assay which uses broad-spectrum, conserved-site PCR paired with mass spectrometry analysis of amplicons (PCR/electrospray ionization-mass spectrometry [ESI-MS]) to detect and identify diverse bacterial and Candida species in uncultured specimens. The performance of the assay was characterized using whole-blood samples spiked with low titers of 64 bacterial species and 6 Candida species representing the breadth of coverage of the assay. The assay had an average limit of detection of 100 CFU of bacteria or Candida per milliliter of blood, and all species tested yielded limits of detection between 20 and 500 CFU per milliliter. Over 99% of all detections yielded correct identifications, whether they were obtained at concentrations well above the limit of detection or at the lowest detectable concentrations. This study demonstrates the ability of broad-spectrum PCR/ESI-MS assays to detect and identify diverse organisms in complex natural matrices that contain high levels of background DNA.
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Allele-dose association of the C5orf30 rs26232 variant with joint damage in rheumatoid arthritis.
Arthritis Rheum.
PUBLISHED: 06-10-2013
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There is increasing evidence to indicate that genetic factors contribute significantly to radiologic joint damage in rheumatoid arthritis (RA). The aim of the present study was to determine whether genotypes of 10 recently identified RA susceptibility loci are associated with radiologic severity.
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Bile Acids Activate YAP to Promote Liver Carcinogenesis.
Cell Rep
PUBLISHED: 05-30-2013
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Elevated bile acid levels increase hepatocellular carcinoma by unknown mechanisms. Here, we show that mice with a severe defect in bile acid homeostasis due to the loss of the nuclear receptors FXR and SHP have enlarged livers, progenitor cell proliferation, and Yes-associated protein (YAP) activation and develop spontaneous liver tumorigenesis. This phenotype mirrors mice with loss of hippo kinases or overexpression of their downstream target, YAP. Bile acids act as upstream regulators of YAP via a pathway dependent on the induction of the scaffold protein IQGAP1. Patients with diverse biliary dysfunctions exhibit enhanced IQGAP1 and nuclear YAP expression. Our findings reveal an unexpected mechanism for bile acid regulation of liver growth and tumorigenesis via the Hippo pathway. VIDEO ABSTRACT:
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Cardiomyopathy reverses with recovery of liver injury, cholestasis and cholanemia in mouse model of biliary fibrosis.
Liver Int.
PUBLISHED: 05-28-2013
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Triggers and exacerbants of cirrhotic cardiomyopathy (CC) are poorly understood, limiting treatment options in patients with chronic liver diseases. Liver transplantation alone reverses some features of CC, but the physiology behind this effect has never been studied.
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Protocol for a systematic review of prognostic models for the recurrence of venous thromboembolism (VTE) following treatment for a first unprovoked VTE.
Syst Rev
PUBLISHED: 05-24-2013
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Venous thromboembolism (VTE) is a chronic disease, with fatal recurrences occurring in 5% to 9% of patients, yet it is also one of the best examples of preventable disease. Prognostic models that utilise multiple prognostic factors (demographic, clinical and laboratory patient characteristics) in combination to predict individual outcome risk may allow the identification of patients who would benefit from long-term anticoagulation therapy, and conversely those that would benefit from stopping such therapy due to a low risk of recurrence. The study will systematically review the evidence on potential prognostic models for the recurrence of VTE or adverse outcomes following the cessation of therapy, and synthesise and summarise each models prognostic value. The review has been registered with PROSPERO (CRD42013003494).
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Producing the "problem" of addiction in drug treatment.
Qual Health Res
PUBLISHED: 05-03-2013
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In this article, we argue that the "problem" of addiction emerges as an effect of treatment policy and practice as well as a precursor to it. We draw on the work of Marrati to analyze interviews with policy makers and practitioners in Australia. The interviews suggest that the episode-of-care system governing service activity, outcomes, and funding relies on certain notions of addiction and treatment that compel service providers to designate service users as addicts to receive funding. This has a range of effects, not least that in acquiring the label of "addict," service users enter into bureaucratic and epidemiological systems aimed at quantifying addiction. Rather than treating pre-existing addicts, the system produces "addicts" as an effect of policy imperatives. Because addiction comes to be produced by the very system designed to treat it, the scale of the problem appears to be growing rather than shrinking.
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Physical exercise is associated with less neurocognitive impairment among HIV-infected adults.
J. Neurovirol.
PUBLISHED: 05-02-2013
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Neurocognitive impairment (NCI) remains prevalent in HIV infection. Randomized trials have shown that physical exercise improves NCI in non-HIV-infected adults, but data on HIV-infected populations are limited. Community-dwelling HIV-infected participants (n?=?335) completed a comprehensive neurocognitive battery that was utilized to define both global and domain-specific NCI. Participants were divided into "exercise" (n?=?83) and "no exercise" (n?=?252) groups based on whether they self-reported engaging in any activity that increased heart rate in the last 72 h or not. We also measured and evaluated a series of potential confounding factors, including demographics, HIV disease characteristics, substance use and psychiatric comorbidities, and physical functioning. Lower rates of global NCI were observed among the exercise group (15.7 %) as compared to those in the no exercise group (31.0 %; p?
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Cysteine sulfinic acid decarboxylase regulation: A role for farnesoid X receptor and small heterodimer partner in murine hepatic taurine metabolism.
Hepatol. Res.
PUBLISHED: 04-16-2013
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Bile acid synthesis is regulated by nuclear receptors including farnesoid X receptor (FXR) and small heterodimer partner (SHP), and by fibroblast growth factor 15/19 (FGF15/19). We hypothesized that hepatic cysteine sulfinic acid decarboxylase (CSAD) (a key enzyme in taurine synthesis) is regulated by bile acids (BA). The aim of this study was to investigate CSAD regulation by BA dependent regulatory mechanisms.
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"Meth circles" and "pipe pirates": crystal methamphetamine smoking and identity management among a social network of young adults.
Subst Use Misuse
PUBLISHED: 04-12-2013
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This article analyzes crystal methamphetamine smoking among a social network of young Australian adults. Ethnographic data were collected from 2005 to 2007 among 60 individuals, and semistructured in-depth interviews were conducted with a sub-set of 25 individuals. Fieldnotes and interview transcripts were entered into NVivo7 and thematically analyzed. We argue that although drug use may be considered "normal" among some social networks, the management of stigma associated with drug use is more complex and contested than portrayed in the literature. Policy implications are discussed. The study was supported by funds from Australias National Health and Medical Research Council.
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Bmal1 and ?-cell clock are required for adaptation to circadian disruption, and their loss of function leads to oxidative stress-induced ?-cell failure in mice.
Mol. Cell. Biol.
PUBLISHED: 04-01-2013
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Circadian disruption has deleterious effects on metabolism. Global deletion of Bmal1, a core clock gene, results in ?-cell dysfunction and diabetes. However, it is unknown if this is due to loss of cell-autonomous function of Bmal1 in ? cells. To address this, we generated mice with ?-cell clock disruption by deleting Bmal1 in ? cells (?-Bmal1(-/-)). ?-Bmal1(-/-) mice develop diabetes due to loss of glucose-stimulated insulin secretion (GSIS). This loss of GSIS is due to the accumulation of reactive oxygen species (ROS) and consequent mitochondrial uncoupling, as it is fully rescued by scavenging of the ROS or by inhibition of uncoupling protein 2. The expression of the master antioxidant regulatory factor Nrf2 (nuclear factor erythroid 2-related factor 2) and its targets, Sesn2, Prdx3, Gclc, and Gclm, was decreased in ?-Bmal1(-/-) islets, which may contribute to the observed increase in ROS accumulation. In addition, by chromatin immunoprecipitation experiments, we show that Nrf2 is a direct transcriptional target of Bmal1. Interestingly, simulation of shift work-induced circadian misalignment in mice recapitulates many of the defects seen in Bmal1-deficient islets. Thus, the cell-autonomous function of Bmal1 is required for normal ?-cell function by mitigating oxidative stress and serves to preserve ?-cell function in the face of circadian misalignment.
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Preliminary Evidence for Feasibility, Use, and Acceptability of Individualized Texting for Adherence Building for Antiretroviral Adherence and Substance Use Assessment among HIV-Infected Methamphetamine Users.
AIDS Res Treat
PUBLISHED: 03-29-2013
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The feasibility, use, and acceptability of text messages to track methamphetamine use and promote antiretroviral treatment (ART) adherence among HIV-infected methamphetamine users was examined. From an ongoing randomized controlled trial, 30-day text response rates of participants assigned to the intervention (individualized texting for adherence building (iTAB), n = 20) were compared to those in the active comparison condition (n = 9). Both groups received daily texts assessing methamphetamine use, and the iTAB group additionally received personalized daily ART adherence reminder texts. Response rate for methamphetamine use texts was 72.9% with methamphetamine use endorsed 14.7% of the time. Text-derived methamphetamine use data was correlated with data from a structured substance use interview covering the same time period (P < 0.05). The iTAB group responded to 69.0% of adherence reminder texts; among those responses, 81.8% endorsed taking ART medication. Standardized feedback questionnaire responses indicated little difficulty with the texts, satisfaction with the study, and beliefs that future text-based interventions would be helpful. Moreover, most participants believed the intervention reduced methamphetamine use and improved adherence. Qualitative feedback regarding the intervention was positive. Future studies will refine and improve iTAB for optimal acceptability and efficacy. This trial is registered with ClinicalTrials.gov NCT01317277.
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Impact of the antiretroviral treatment program on the burden of hospitalization for culture-confirmed tuberculosis in South African children: a time-series analysis.
Pediatr. Infect. Dis. J.
PUBLISHED: 03-19-2013
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The HIV epidemic increased the burden of tuberculosis (TB) in sub-Saharan Africa. We evaluated the impact that scaling-up of the public-funded antiretroviral treatment (ART) program had on incidence of hospitalization for culture-confirmed and overall-TB in HIV-infected and HIV-uninfected children from 2005 to 2009.
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Enacting multiple methamphetamines: the ontological politics of public discourse and consumer accounts of a drug and its effects.
Int. J. Drug Policy
PUBLISHED: 02-27-2013
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Over the last decade in Australia, methamphetamine has come to be seen as a significant issue for drug research, policy and practice. Concerns have been expressed over its potency, the increasing prevalence of its use and its potential for producing greater levels, and more severe forms, of harm compared to amphetamine or other drugs. In this article, we critically examine some of the ways in which methamphetamine and its effects are produced and reproduced within and through Australian public discourse, focusing in particular on the associations made between methamphetamine and psychosis. We show how public discourse enacts methamphetamine as an anterior, stable, singular and definite object routinely linked to the severe psychological harm of psychosis. We contrast the enactment of methamphetamine within public discourse with how methamphetamine is enacted by consumers of the drug. In their accounts, consumers perform different methamphetamine objects and offer different interpretations of the relationships of these objects to psychological problems and of the ontological nature (i.e. relating to what is real, what is, what exists) of these problems. In examining public discourse and consumer accounts, we challenge conventional ontological understandings of methamphetamine as anterior, singular, stable and definite, and of its psychological effects as indicative of pathology. In line with recent critical social research on drugs, we draw on social studies of science and technology that focus on the performativity of scientific knowledge and material practices. We suggest that recognising the ontological contingency, and therefore the multiplicity, of methamphetamine offers a critical counterpoint to conventional research, policy and practice accounts of methamphetamine and its psychological effects.
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Protocol for a systematic review of the diagnostic and prognostic utility of tests currently available for the detection of aspirin resistance in patients with established cardiovascular or cerebrovascular disease.
Syst Rev
PUBLISHED: 02-18-2013
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The benefits of aspirin as an anti-platelet agent are well established; however, there has been much debate about the lack of uniformity in the efficacy of aspirin to inhibit platelet function. In some patients, aspirin fails to inhibit platelets even where compliance has been verified, a phenomenon which has been termed "aspirin resistance". These patients may in turn be at a higher risk of future vascular events. The proportion of "resistant" patients identified depends on the type of platelet function test. Therefore, the aim of this systematic review is to determine which, if any, platelet function test has utility in terms of identifying patients with a high risk of vascular events. The review has been registered with PROSPERO (CRD42012002151).
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Farnesoid X receptor inhibits gankyrin in mouse livers and prevents development of liver cancer.
Hepatology
PUBLISHED: 02-15-2013
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One of the early events in the development of liver cancer is a neutralization of tumor suppressor proteins Rb, p53, hepatocyte nuclear factor 4? (HNF4?), and CCAAT/enhancer binding protein (C/EBP) ?. The elimination of these proteins is mediated by a small subunit of proteasome, gankyrin, which is activated by cancer. The aim of this study was to determine the mechanisms that repress gankyrin in quiescent livers and mechanisms of activation of gankyrin in liver cancer. We found that farnesoid X receptor (FXR) inhibits expression of gankyrin in quiescent livers by silencing the gankyrin promoter through HDAC1-C/EBP? complexes. C/EBP? is a key transcription factor that delivers HDAC1 to gankyrin promoter and causes epigenetic silencing of the promoter. We show that down-regulation of C/EBP? in mouse hepatoma cells and in mouse livers reduces C/EBP?-HDAC1 complexes and activates the gankyrin promoter. Deletion of FXR signaling in mice leads to de-repression of the gankyrin promoter and to spontaneous development of liver cancer at 12 months of age. Diethylnitrosoamine (DEN)-mediated liver cancer in wild-type mice also involves the reduction of FXR and activation of gankyrin. Examination of liver cancer in old mice and liver cancer in human patients revealed that FXR is reduced, while gankyrin is elevated during spontaneous development of liver cancer. Searching for animal models with altered levels of FXR, we found that long-lived Little mice have high levels of FXR and do not develop liver cancer with age and after DEN injections due to failure to activate gankyrin and eliminate Rb, p53, HNF4? and C/EBP? proteins.
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Pulsed electric field (PEF) as an intensification pretreatment for greener solvent lipid extraction from microalgae.
Biotechnol. Bioeng.
PUBLISHED: 02-04-2013
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Microalgae, with their high lipid content, are a promising feedstock for renewable fuels. Traditionally, human and environmentally toxic solvents have been used to extract these lipids, diminishing the sustainability of this process. Herein, pulsed electric field technology was utilized as a process intensification strategy to enhance lipid extraction from Ankistrodesmus falcatus wet biomass using the green solvent, ethyl acetate. The extraction efficiency for ethyl acetate without PEF was lower (83-88%) than chloroform. In addition, the ethyl acetate exhibited a 2-h induction period, while the chloroform showed no time dependence. Utilizing PEF technology resulted in 90% of the cells being lysed and a significant enhancement in the rate of lipid recovery using ethyl acetate. The increase in lipid recovery was due to the presence of the electric field and not due to temperature effects. The PEF technology uses less energy than other PEF systems reported in the literature.
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Drug-induced hepatotoxicity: incidence of abnormal liver function tests consistent with volatile anaesthetic hepatitis in trauma patients.
Liver Int.
PUBLISHED: 02-01-2013
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Volatile anaesthetic drug-induced liver injury can range from asymptomatic alanine transaminase elevations to fatal hepatic necrosis. There is very limited research regarding hepatotoxicity of modern volatile anaesthetic agents. The aim of this study was to determine how common liver injury consistent with volatile anaesthetic hepatitis is, following exposure to isoflurane, desflurane and sevoflurane; and to propose risk factors for its development.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.