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1.  Terms Used for People Living With HIV in the Democratic Republic of the Congo 
Qualitative health research  2014;24(2):209-216.
For this study we conducted in-depth interviews with 29 youth living with HIV (YLWH) and key informant interviews with 8 HIV care/support providers. We describe terms used to portray people living with HIV (PLWH) in Kinshasa, Democratic Republic of the Congo. Labels commonly used, mostly derogatory, described PLWH as walking corpses, dangers to others, or people deserving to die before others get infected. Blame and other accusations were directed at PLWH through anchoring or objectification. Being labeled sometimes made these youth suffer in silence, afraid to disclose their status, or avoid performing actions in public, preferring to let others do them. YLWH need psychosocial support to mitigate the harmful effects of these labels and strengthen their coping skills, whereas community, institutional, and national efforts are needed for stigma reduction.
doi:10.1177/1049732313519869
PMCID: PMC4326230  PMID: 24463633
adolescents/youth; Africa; Africa; sub-Saharan; HIV/AIDS; stigma; young adults
2.  The Ethics of Globalizing Bioethics 
In the last decade, there have been efforts to globalize the field of bioethics, particularly in developing countries, where biomedical and other research is increasingly taking place. We describe and evaluate some key ethical criticisms directed towards these initiatives, and argue that while they may be marked by ethical, practical, and political tensions and pitfalls, they can nevertheless play an important role in stimulating critical bioethics culture in countries vulnerable to exploitation by foreign agencies and/or their own authorities.
doi:10.1615/EthicsBiologyEngMed.2012004265
PMCID: PMC4306226  PMID: 25632370
bioethics; capacity building; developing countries; research ethics; colonialism; neo-colonialism
3.  Excessive daytime sleepiness among rural residents in Saskatchewan 
Obstructive sleep apnea and its sequelae are emerging public health issues in North America, and symptoms are often under-recognized or under-reported. Although several patient factors have been identified, limited data regarding the prevalence of and predictors for excessive daytime sleepiness in rural or remote populations area available. Accordingly, this study used Epworth Sleepiness Scale scores to evaluate daytime sleepiness in a large rural population participating in the Saskatchewan Rural Health Study.
BACKGROUND:
Obstructive sleep apnea (OSA) is a common diagnosis in clinical practice. Excessive daytime sleepiness may be a warning for possible OSA.
OBJECTIVES:
To assess the prevalence of excessive daytime sleepiness as measured by the Epworth Sleepiness Scale (ESS) in a rural community population; potential risk factors for OSA were also assessed.
METHODS:
In 2010, a baseline respiratory health questionnaire within the Saskatchewan Rural Health Study was mailed to 11,982 households in Saskatchewan. A total of 7597 adults within the 4624 (42%) respondent households completed the ESS questionnaire. Participants were categorized according to normal or high (>10) ESS scores. Data obtained included respiratory symptoms, doctor-diagnosed sleep apnea, snoring, hypertension, smoking and demographics. Body mass index was calculated. Multivariable logistic regression analysis examined associations between high ESS scores and possible risk factors. Generalized estimating equations accounted for the two-tiered sampling procedure of the study design.
RESULTS:
The mean age of respondents was 55.0 years and 49.2% were male. The prevalence of ESS>10 and ‘doctor diagnosed’ OSA were 15.9% and 6.0%, respectively. Approximately 23% of respondents reported loud snoring and 30% had a body mass index >30 kg/m2. Of those with ‘doctor-diagnosed’ OSA, 37.7% reported ESS>10 (P<0.0001) and 47.7% reported loud snoring (P<0.0001). Risk of having an ESS>10 score increased with age, male sex, obesity, lower socioeconomic status, marriage, loud snoring and doctor-diagnosed sinus trouble.
CONCLUSIONS:
High levels of excessive daytime sleepiness in this particular rural population are common and men >55 years of age are at highest risk. Examination of reasons for residual sleepiness and snoring in persons with and without sleep apnea is warranted.
PMCID: PMC4173890  PMID: 24791255
Epworth Sleepiness Scale; Farm; Nonfarm; Obesity; Rural; Sleep apnea; Snoring; Socioeconomic
5.  Treatment of invasive ocular surface squamous neoplasia with proton beam therapy 
Eye  2013;27(10):1223-1224.
doi:10.1038/eye.2013.149
PMCID: PMC3806571  PMID: 23907623
7.  Effects of breakpoint changes on carbapenem susceptibility rates of Enterobacteriaceae: Results from the SENTRY Antimicrobial Surveillance Program, United States, 2008 to 2012 
Antibiotic susceptibility breakpoints are determined at the time of clinical approval for a given drug, but may need to be revised to incorporate additional evidence obtained after approval of the drug. The breakpoints for several common carbapenems were updated between 2010 and 2013. The authors aimed to calculate the change in susceptibility rates for these drugs as a result of the updates to the breakpoints, using susceptibility data of various Enterobacteriaceae species from the North American SENTRY Antimicrobial Surveillance Program.
In the absence of clinical resistance, breakpoints for many antimicrobial agents are often set high. Clinical failures following use of the agents over time requires re-evaluation of breakpoints. This is based on patient response, pharmacokinetic/pharmacodynamic information and in vitro minimal inhibitory concentration data. Data from the SENTRY Antimicrobial Surveillance Program has shown that Clinical and Laboratory Standards Institute breakpoint changes for carbapenems that occurred between 2008 and 2012 in North America have resulted in decreased levels of susceptibility for some species. In particular, reduced susceptibility to imipenem was observed for Proteus mirabilis (35%) and Morganella morganii (80%). Minor decreases in susceptibility were also noted for Enterobacter species with ertapenem (5%) and imipenem (4.3%), and Serratia species with imipenem (6.4%). No significant decreases in susceptibility were observed for meropenem following the breakpoint changes. There were no earlier breakpoints established for doripenem. Very few of these Enterobacteriaceae produce carbapenamase enzymes; therefore, the clinical significance of these changes has not yet been clearly determined. In conclusion, ongoing surveillance studies with in vitro minimum inhibitory concentration data are essential in predicting the need for breakpoint changes and in identifying the impact of such changes on the percent susceptibility of different species.
PMCID: PMC4211354  PMID: 25371693
Carbapenems; Surveillance; Susceptibility breakpoints
8.  Effects of genetic variations on microRNA: target interactions 
Nucleic Acids Research  2014;42(15):9543-9552.
Genetic variations within microRNA (miRNA) binding sites can affect miRNA-mediated gene regulation, which may lead to phenotypes and diseases. We perform a transcriptome-scale analysis of genetic variants and miRNA:target interactions identified by CLASH. This analysis reveals that rare variants tend to reside in CDSs, whereas common variants tend to reside in the 3′ UTRs. miRNA binding sites are more likely to reside within those targets in the transcriptome with lower variant densities, especially target regions in which nucleotides have low mutation frequencies. Furthermore, an overwhelming majority of genetic variants within or near miRNA binding sites can alter not only the potential of miRNA:target hybridization but also the structural accessibility of the binding sites and flanking regions. These suggest an interpretation for certain associations between genetic variants and diseases, i.e. modulation of miRNA-mediated gene regulation by common or rare variants within or near miRNA binding sites, likely through target structure alterations. Our data will be valuable for discovering new associations among miRNAs, genetic variations and human diseases.
doi:10.1093/nar/gku675
PMCID: PMC4150780  PMID: 25081214
9.  Early Postnatal EEG Features of Perinatal Arterial Ischaemic Stroke with Seizures 
PLoS ONE  2014;9(7):e100973.
Background
Stroke is the second most common cause of seizures in term neonates and is associated with abnormal long-term neurodevelopmental outcome in some cases.
Objective
To aid diagnosis earlier in the postnatal period, our aim was to describe the characteristic EEG patterns in term neonates with perinatal arterial ischaemic stroke (PAIS) seizures.
Design
Retrospective observational study.
Patients
Neonates >37 weeks born between 2003 and 2011 in two hospitals.
Method
Continuous multichannel video-EEG was used to analyze the background patterns and characteristics of seizures. Each EEG was assessed for continuity, symmetry, characteristic features and sleep cycling; morphology of electrographic seizures was also examined. Each seizure was categorized as electrographic-only or electroclinical; the percentage of seizure events for each seizure type was also summarized.
Results
Nine neonates with PAIS seizures and EEG monitoring were identified. While EEG continuity was present in all cases, the background pattern showed suppression over the infarcted side; this was quite marked (>50% amplitude reduction) when the lesion was large. Characteristic unilateral bursts of theta activity with sharp or spike waves intermixed were seen in all cases. Sleep cycling was generally present but was more disturbed over the infarcted side. Seizures demonstrated a characteristic pattern; focal sharp waves/spike-polyspikes were seen at frequency of 1–2 Hz and phase reversal over the central region was common. Electrographic-only seizure events were more frequent compared to electroclinical seizure events (78 vs 22%).
Conclusions
Focal electrographic and electroclinical seizures with ipsilateral suppression of the background activity and focal sharp waves are strong indicators of PAIS. Approximately 80% of seizure events were the result of clinically unsuspected seizures in neonates with PAIS. Prolonged and continuous multichannel video-EEG monitoring is advocated for adequate seizure surveillance.
doi:10.1371/journal.pone.0100973
PMCID: PMC4106759  PMID: 25051161
10.  In vitro efficacy of N-acetylcysteine on bacteria associated with chronic suppurative otitis media 
Background
The safety and efficacy of Ciprodex® has been demonstrated for treatment of chronic suppurative otitis media (CSOM). However, symptoms fail to resolve in 9-15% of patients. The objective of this study is to evaluate the efficacy of N-acetylcysteine (NAC) on S. aureus, and planktonic and sessile (biofilm forming) P. aeruginosa in vitro using clinical isolates from patients with CSOM.
Methods
1) Stability was assessed using liquid chromatography-mass spectrometry for each component in a prepared mixture of Ciprodex® and NAC over 15 days. Sterility was assessed by measuring bacterial growth on a blood agar plate. Efficacy was assessed using a disc diffusion method by inoculating plates with S. aureus ATCC 29513 and P. aeruginosa ATCC 27853, and measuring the clearance zone.
2) Fifteen P. aeruginosa strains were isolated from patients with CSOM and tested in vitro using the bioFILM PA™ antimicrobial susceptibility assay. Treatment solutions included Ciprodex® & ciprofloxacin +/- NAC, and NAC alone (0.25%, 0.5% & 1.25%).
Results
1) NAC combined with Ciprodex® demonstrated stability, sterility, and efficacy over a two-week period
2) P. aeruginosa strains in the sessile (33%-40%) and planktonic (13%) state demonstrated resistance to Ciprodex® and ciprofloxacin. When NAC ≥0.5% was used in isolation or as an adjunct to either of these medications, no resistance was found in the sessile or planktonic state among all 15 strains.
Conclusion
1) Ciprodex® combined with NAC has a shelf life of at least two weeks given the documented preservation of stability, sterility, and clinical efficacy of the mixed compounds.
2) P. aeruginosa strains demonstrated resistance to both Ciprodex® and ciprofloxacin. NAC ≥0.5% overcomes issues with resistance and shows promise in the treatment of CSOM.
doi:10.1186/1916-0216-43-20
PMCID: PMC4094889  PMID: 25001062
Otitis media, suppurative; Antibacterial agents; Microbial sensitivity tests; N-acetylcysteine; Ciprodex®; Ciprofloxacin; Administration, topical; Pseudomonas aeruginosa; Staphylococcus aureus
11.  Chronic Obstructive Pulmonary Disease Self-Management Activation Research Trial (COPD-SMART): Design and Methods 
Contemporary clinical trials  2013;35(2):77-86.
Background
Treatment of COPD requires multiple pharmacological and non-pharmacological intervention strategies. One target is physical inactivity because it leads to disability and contributes to poor physical and mental health. Unfortunately, less than one percent of eligible patients have access to gold-standard pulmonary rehabilitation.
Methods
A single-site parallel group randomized trial was designed to determine if a self-management lifestyle physical activity intervention would improve physical functioning and dyspnea. During the first six weeks after enrollment patients receive COPD self-management education delivered by a health coach using a workbook and weekly telephone calls. Patients are then randomized to usual care or the physical activity intervention. The 20 week physical activity intervention is delivered by the health coach using a workbook supported by alternating one-on-one telephone counseling and computer assisted telephone calls. Theoretical foundations include social cognitive theory and the transtheoretical model.
Results
Primary outcomes include change in Chronic Respiratory Questionnaire (CRQ) dyspnea domain and 6-minute walk distance measured at 6-, 12-, and 18-months after randomization. Secondary outcomes include other CRQ domains (fatigue, emotion, and mastery), SF-12, and health care utilization. Other measures include process outcomes and clinical characteristics.
Conclusions
This theory driven self-management lifestyle physical activity intervention is designed to reach patients unable to complete center-based pulmonary rehabilitation. Results will advance knowledge and methods for dissemination of a potentially cost-effective program for patients with COPD.
doi:10.1016/j.cct.2013.05.004
PMCID: PMC3703772  PMID: 23680985
chronic obstructive pulmonary disease; self-management; physical activity; lifestyle; pulmonary rehabilitation; randomized trial
12.  Ether-Bond-Containing Ionic Liquids as Supercapacitor Electrolytes 
Electrochemical capacitors (ECs) are electrical energy storage devices that have the potential to be very useful in a wide range of applications, especially where there is a large disparity between peak and average power demands. The use of ionic liquids (ILs) as electrolytes in ECs can increase the energy density of devices; however, the viscosity and conductivity of ILs adversely influence the power density of the device. We present experimental results where several ILs containing different cations have been employed as the electrolyte in cells containing mesoporous carbon electrodes. Specifically, the behavior of ILs containing an ether bond in an alkyl side chain are compared with those of a similar structure and size but containing purely alkyl side chains. Using electrochemical impedance spectroscopy and constant current cycling, we show that the presence of the ether bond can dramatically increase the specific capacitance and reduce device resistance. These results have the important implication that such ILs can be used to tailor the physical properties and electrochemical performance of IL-based electrolytes.
doi:10.1021/jz4016553
PMCID: PMC4047568  PMID: 24920995
13.  STarMir: a web server for prediction of microRNA binding sites 
Nucleic Acids Research  2014;42(Web Server issue):W114-W118.
STarMir web server predicts microRNA (miRNA) binding sites on a target ribonucleic acid (RNA). STarMir is an implementation of logistic prediction models developed with miRNA binding data from crosslinking immunoprecipitation (CLIP) studies (Liu,C., Mallick, B., Long, D., Rennie, W.A., Wolenc, A., Carmack, C.S. and Ding, Y. (2013). CLIP-based prediction of mammalian microRNA binding sites. Nucleic Acids Res., 41(14), e138). In both intra-dataset and inter-dataset validations, the models showed major improvements over established algorithms in predictions of both seed and seedless sites. General applicability of the models was indicated by good performance in cross-species validations. The input data for STarMir is processed by the web server to perform prediction of miRNA binding sites, compute comprehensive sequence, thermodynamic and target structure features and a logistic probability as a measure of confidence for each predicted site. For each of seed and seedless sites and for all three regions of a mRNA (3′ UTR, CDS and 5′ UTR), STarMir output includes the computed binding site features, the logistic probability and a publication-quality diagram of the predicted miRNA:target hybrid. The prediction results are available through both an interactive viewer and downloadable text files. As an application module of the Sfold RNA package (http://sfold.wadsworth.org), STarMir is freely available to all at http://sfold.wadsworth.org/starmir.html.
doi:10.1093/nar/gku376
PMCID: PMC4086099  PMID: 24803672
14.  Comparative cervical profiles of adult and under-18 front-row rugby players: implications for playing policy 
BMJ Open  2014;4(5):e004975.
Objective
To compare the cervical isometric strength, fatigue endurance and range of motion of adult and under-18 age-grade front-row rugby players to inform the development of a safe age group policy with particular reference to scrummaging.
Design
Cross-sectional cohort study.
Setting
‘Field testing’ at Murrayfield stadium.
Participants
30 high-performance under-18 players and 22 adult front-row rugby players.
Outcome measures
Isometric neck strength, height, weight and grip strength.
Results
Youth players demonstrated the same height and grip strength as the adult players; however, the adults were significantly heavier and demonstrated substantially greater isometric strength (p<0.001). Only two of the ‘elite’ younger players could match the adult mean cervical isometric strength value. In contrast to school age players in general, grip strength was poorly associated with neck strength (r=0.2) in front-row players; instead, player weight (r=0.4) and the number of years’ experience of playing in the front row (r=0.5) were the only relevant factors in multivariate modelling of cervical strength (R2=0.3).
Conclusions
Extreme forces are generated between opposing front rows in the scrum and avoidance of mismatch is important if the risk of injury is to be minimised. Although elite youth front-row rugby players demonstrate the same peripheral strength as their adult counterparts on grip testing, the adults demonstrate significantly greater cervical strength. If older youths and adults are to play together, such findings have to be noted in the development of age group policies with particular reference to the scrum.
doi:10.1136/bmjopen-2014-004975
PMCID: PMC4025467  PMID: 24797427
Sports Medicine; Rugby; Neck
15.  Social support during the postpartum period: Mothers’ views on needs, expectations, and mobilization of support 
Maternal and child health journal  2013;17(4):616-623.
Objectives
Research has indicated that social support is a major buffer of postpartum depression. Yet little is known concerning women’s perceptions on social support during the postpartum period. The objective of this study was to explore postpartum women’s views and experiences with social support following childbirth.
Methods
Four focus groups were conducted with an ethnically diverse sample of women (n=33) in a large urban teaching hospital in New York City. Participants had completed participation in a postpartum depression randomized trial and were 6 to 12 months postpartum. Data transcripts were reviewed and analyzed for themes.
Results
The main themes identified in the focus group discussions were mother’s major needs and challenges postpartum, social support expectations and providers of support, how mothers mobilize support, and barriers to mobilizing support. Women across all groups identified receipt of instrumental support as essential to their physical and emotional recovery. Support from partners and families was expected and many women believed this support should be provided without asking. Racial/ethnic differences existed in the way women from different groups mobilized support from their support networks.
Conclusions
Instrumental support plays a significant role in meeting women’s basic needs during the postpartum period. In addition, women’s expectations surrounding support can have an impact on their ability to mobilize support among their social networks. The results of this study suggest that identifying support needs and expectations of new mothers is important for mothers’ recovery after childbirth. Future postpartum depression prevention efforts should integrate a strong focus on social support.
doi:10.1007/s10995-012-1037-4
PMCID: PMC3518627  PMID: 22581378
16.  Supraciliary space breast metastasis 
Eye  2013;27(5):673-675.
doi:10.1038/eye.2013.36
PMCID: PMC3650281  PMID: 23519276
17.  Three cases of intraocular mesectodermal leiomyoma expressing progesterone and androgen receptors 
Eye  2013;27(5):669-672.
Background/Aims
A prospective study identified three patients between 2004 and 2010 with mesectodermal leiomyoma. The study was conducted to analyse the presence or absence of sex steroid hormone receptors in mesectodermal leiomyomas.
Methods
The clinical features were collated. All three patients had operative procedures to either remove or sample the mesectodermal leiomyomas. The tissue was fixed in formalin and exposed to conventional histological processing. Immunohistochemistry using antibodies to androgen (AR), oestrogen (ER), and progesterone (PR) receptors was performed, followed by stain scoring to assess for expression status.
Results
All three cases were confirmed by histology to be examples of mesectodermal leiomyomas. All three expressed sex steroid hormone receptors. One case expressed both PR and AR, one case PR only and another case AR only. None of the cases expressed ER receptors.
Conclusion
All three cases displayed some sex steroid hormone receptor expression. This is supportive evidence that sex steroid hormones may have a role in the pathogenesis of this tumour and suggest that it may be amenable to hormonal manipulation therapy, in a manner similar to conventional uterine leiomyomas.
doi:10.1038/eye.2013.37
PMCID: PMC3650282  PMID: 23519275
mexectodermal; leiomyoma; androgen receptor; progesterone receptor
18.  Intra-lesional interferon injection for recurrent conjunctival MALT lymphoma 
Eye  2013;27(5):680-682.
doi:10.1038/eye.2013.46
PMCID: PMC3650287  PMID: 23558211
19.  Hypertensive iridocyclitis associated with delayed onset biopsy proven Cytomegalovirus retinitis 
Indian Journal of Ophthalmology  2014;62(5):656-658.
We describe a case of primary hypertensive iridocyclitis with biopsy-proven Cytomegaloviral retinitis. It is an observational case report of a 69-year-old diabetic gentleman on azathioprine for Crohn's disease who presented with recurrent episodes of hypertensive iridocyclitis. On the 4th attendance in 5 months, a granular white lesion was noted in the temporal periphery of the mid-peripheral fundus and a chorioretinal and vitreous biopsy performed. Vitreous PCR was positive for Cytomegalovirus (CMV). Hematoxylin and eosin staining revealed cytomegalic-like inclusions within necrotic neural retina. Transmission electron microscopy revealed herpes family virus particles and immunohistochemistry demonstrated CMV protein. This case provides further evidence implicating CMV infection in the etiology of hypertensive iridocyclitis. With hindsight, the cumulative effect of diabetes and azathioprine on the immune surveillance system proved sufficient to render the patient susceptible to CMV retinitis.
doi:10.4103/0301-4738.97086
PMCID: PMC4065529  PMID: 23548320
Cytomegalovirus retinitis; hypertensive iridocyclitis; vitreous polymerace chain reaction
20.  Measurement of Muscle Protein Fractional Synthetic Rate by Capillary Gas Chromatography/Combustion Isotope Ratio Mass Spectrometry 
Biological mass spectrometry  1992;21(10):486-490.
The measurement of skeletal muscle protein fractional synthetic rate using an infusion of (1-13C)leucine and measuring the isotopic abundance of the tracer in skeletal muscle protein by preparative gas chromatography (GC)/ninhydrin isotope ratio mass spectrometry (IRMS) is laborious and subject to errors owing to contamination by 12C. The purpose of this study was to compare muscle (13C)leucine enrichment measured with the conventional preparative GC/ninhydrin IRMS approach to a new, continuous-flow technique using capillary GC/combustion IRMS. Quadriceps muscles were removed from four Sprague–Dawley rats after each was infused at a different rate with (1-13C)leucine for 6–8 h. Muscle leucine enrichment (at.% excess) measured by both methods differed by less than 4%, except at low (13C)leucine enrichments (<0.03 at.% excess). In addition, capillary GC/combustion IRMS was used to assess muscle (13C)leucine enrichment and fractional muscle protein synthesis rate in ten normal young men and women infused with (1,2-13C2)leucine for 12–14 h. This approach reduced the variability of the isotope abundance measure and gave estimates of muscle protein synthesis rate (0.050 ± 0.011% h−1 (mean ± SEM); range = 0.023–0.147% h−1) that agree with published values determined using the standard analytical approach. The measurement of (13C)leucine enrichment from skeletal muscle protein by capillary GC/combustion IRMS provides a simple, acceptable and practical alternative to preparative GC/ninhydrin IRMS.
doi:10.1002/bms.1200211004
PMCID: PMC4003887  PMID: 1420371
21.  20(S)-Protopanaxadiol-aglycone Downregulation of the Full-length and Splice Variants of Androgen Receptor 
As a public health problem, prostate cancer engenders huge economic and life-quality burden. Developing effective chemopreventive regimens to alleviate the burden remains a major challenge. Androgen signaling is vital to the development and progression of prostate cancer. Targeting androgen signaling via blocking the production of the potent ligand dihydrotestosterone has been shown to decrease prostate cancer incidence. However, the potential of increasing the incidence of high-grade prostate cancers has been a concern. Mechanisms of disease progression after the intervention may include increased expression of androgen receptor (AR) in prostate tissue and expression of the constitutively-active AR splice variants (AR-Vs) lacking the ligand-binding domain. Thus, novel agents targeting the receptor, preferentially both the full-length and AR-Vs, are urgently needed. In the present study, we show that ginsenoside 20(S)-protopanaxadiol-aglycone (PPD) effectively downregulates the expression and activity of both the full-length AR and AR-Vs. The effects of PPD on AR and AR-Vs are manifested by an immediate drop in proteins followed by a reduction in transcripts, attributed to PPD induction of proteasome-mediated degradation and inhibition of the transcription of the AR gene. We further show that although PPD inhibits the growth as well as AR expression and activity in LNCaP xenograft tumors, the morphology and AR expression in normal prostates are not affected. This study is the first to show that PPD suppresses androgen signaling through downregulating both the full-length AR and AR-Vs, and provides strong rationale for further developing PPD as a promising agent for the prevention and/or treatment of prostate cancer.
doi:10.1002/ijc.27754
PMCID: PMC3509250  PMID: 22907191
20(S)-protopanaxadiol-aglycone; androgen receptor; prostate cancer
23.  The antiviral effect of sorafenib in hepatitis c-related hepatocellular carcinoma 
Background and Aim
Sorafenib is currently the only approved systemic therapy shown to have efficacy in the treatment of advanced hepatocellular carcinoma (HCC). Recent studies suggest that hepatitis C (HCV)-related HCC patients derive more clinical benefit from sorafenib than other subgroups, but the mechanism for this effect is unknown. In-vitro data suggest that sorafenib may exert antiviral properties and thus our aim in this study, was to evaluate potential antiviral activity of sorafenib in patients with HCV-related HCC.
Methods
We prospectively enrolled patients with HCV-related HCC treated with sorafenib for up to six months. Baseline clinical, viral, and oncologic data were collected. Patients’ HCV viral loads were obtained at various timepoints, and compared to their baseline viral levels. No patients received any known antiviral therapy during this time.
Results
Thirty-three patients were identified with baseline and subsequent HCV levels available for analysis. Six patients completed six months of full dose sorafenib, and comparisons of their HCV viral loads showed no significant change at week 24 (difference of means = 0.3500, C.I. = −0.1799 to 0.8799, p = 0.150), or the interim time points. Similarly, the HCV viral loads of all patients who received sorafenib and the viral loads of those patients who had tumor response to sorafenib showed no significant changes at any time point.
Conclusion
Despite preclinical data and previous subgroup analyses suggesting that sorafenib has antiviral effect against HCV, this study suggests that sorafenib lacks significant anti-viral activity in HCV patients with HCC.
doi:10.1111/apt.12098
PMCID: PMC3682667  PMID: 23094860
hepatitis; viral suppression; hepatoma; virological response; cirrhosis
24.  Medical students as EMTs: skill building, confidence and professional formation 
Medical Education Online  2014;19:10.3402/meo.v19.24829.
Objective
The first course of the medical curriculum at the Hofstra North Shore-LIJ School of Medicine, From the Person to the Professional: Challenges, Privileges and Responsibilities, provides an innovative early clinical immersion. The course content specific to the Emergency Medical Technician (EMT) curriculum was developed using the New York State Emergency Medical Technician curriculum. Students gain early legitimate clinical experience and practice clinical skills as team members in the pre-hospital environment. We hypothesized this novel curriculum would increase students’ confidence in their ability to perform patient care skills and enhance students’ comfort with team-building skills early in their training.
Methods
Quantitative and qualitative data were collected from first-year medical students (n=97) through a survey developed to assess students’ confidence in patient care and team-building skills. The survey was completed prior to medical school, during the final week of the course, and at the end of their first year. A paired-samples t-test was conducted to compare self-ratings on 12 patient care and 12 team-building skills before and after the course, and a theme analysis was conducted to examine open-ended responses.
Results
Following the course, student confidence in patient care skills showed a significant increase from baseline (p<0.05) for all identified skills. Student confidence in team-building skills showed a significant increase (p<0.05) in 4 of the 12 identified skills. By the end of the first year, 84% of the first-year students reported the EMT curriculum had ‘some impact’ to ‘great impact’ on their patient care skills, while 72% reported the EMT curriculum had ‘some impact’ to ‘great impact’ on their team-building skills.
Conclusions
The incorporation of EMT training early in a medical school curriculum provides students with meaningful clinical experiences that increase their self-reported level of confidence in the performance of patient care skills early in their medical education.
doi:10.3402/meo.v19.24829
PMCID: PMC4108757  PMID: 25056855
undergraduate medical education; curriculum; pre-hospital care; clinical skills; team building; professional role
25.  Hyperpolarization-Activated Current (Ih) in Vestibular Calyx Terminals: Characterization and Role in Shaping Postsynaptic Events 
Calyx afferent terminals engulf the basolateral region of type I vestibular hair cells, and synaptic transmission across the vestibular type I hair cell/calyx is not well understood. Calyces express several ionic conductances, which may shape postsynaptic potentials. These include previously described tetrodotoxin-sensitive inward Na+ currents, voltage-dependent outward K+ currents and a K(Ca) current. Here, we characterize an inwardly rectifying conductance in gerbil semicircular canal calyx terminals (postnatal days 3–45), sensitive to voltage and to cyclic nucleotides. Using whole-cell patch clamp, we recorded from isolated calyx terminals still attached to their type I hair cells. A slowly activating, noninactivating current (Ih) was seen with hyperpolarizing voltage steps negative to the resting potential. External Cs+ (1–5 mM) and ZD7288 (100 μM) blocked the inward current by 97 and 83 %, respectively, confirming that Ih was carried by hyperpolarization-activated, cyclic nucleotide gated channels. Mean half-activation voltage of Ih was −123 mV, which shifted to −114 mV in the presence of cAMP. Activation of Ih was well described with a third order exponential fit to the current (mean time constant of activation, τ, was 190 ms at −139 mV). Activation speeded up significantly (τ = 136 and 127 ms, respectively) when intracellular cAMP and cGMP were present, suggesting that in vivo Ih could be subject to efferent modulation via cyclic nucleotide-dependent mechanisms. In current clamp, hyperpolarizing current steps produced a time-dependent depolarizing sag followed by either a rebound afterdepolarization or an action potential. Spontaneous excitatory postsynaptic potentials (EPSPs) became larger and wider when Ih was blocked with ZD7288. In a three-dimensional mathematical model of the calyx terminal based on Hodgkin–Huxley type ionic conductances, removal of Ih similarly increased the EPSP, whereas cAMP slightly decreased simulated EPSP size and width.
doi:10.1007/s10162-012-0342-3
PMCID: PMC3505587  PMID: 22825486
HCN channel; balance; crista; cAMP; efferent

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