Infection of swine ex vivo tissues with avian viruses including H7N9 and correlation with glycomic analysis

OBJECTIVES: Swine have been regarded as intermediate hosts in the spread of influenza from birds to humans but studies of the sialylated glycans that comprise their respiratory tract have not been extensively studied in the past. This study analyzed the sialylated N-glycan and O-glycan profile of swine trachea and lung and correlated this with ex-vivo infection of swine explants with avian influenza viruses. SAMPLE: Lungs and tracheal samples were obtained from normal farm and laboratory raised swine and used for ex vivo infection as well as mass spectrometric analysis. Infection of the ex vivo tissues used high pathogenic and low pathogenic avian viruses including the novel H7N9 virus that emerged in China in early 2013. MAIN OUTCOME MEASURES: Assessment of successful replication was determined by TCID50 as well as virus immunohistochemistry. The N-glycan and O-glycan profiles were measured by MALDI-TOF and sialylated linkages were determined by sialidase treatment. Lectin binding histochemistry was also performed on formalin fixed tissue samples with positive binding detected by chromogen staining. RESULTS: The swine respiratory tract glycans differed from the human respiratory tact glycans in two main areas. There was a greater abundance of Gal-α-Gal linkages resulting in a relative decrease in sialylated glycans. The swine respiratory tract also had a greater proportion of glycans containing Neu5Gc and Siaα2-6 glycans than the human respiratory tract. Infection with avian viruses was confined primarily to lung bronchioles rather than trachea and parenchyma. CONCLUSIONS: In contrast to previous studies we found that there was not as much expression of Siaα2-3 glycans on the surface of the trachea. Infection of Siaα2-3 binding avian viruses was restricted to the lower respiratory tract bronchioles. This finding may diminish the ability of the swine to act as an intermediary in the transmission of avian viruses to humans.published_or_final_versio

Comparative Analysis of Clinical and Patient-Reported Outcomes of a New Enhanced Monofocal IOL and a Conventional Monofocal IOL

Steven J Dell,1 Stephen J Hannan,2 Jan A Venter,2 David Teenan,2 Noelle C Hannan,2 Dasi Raju,2 Colin W Berry,2 Huba J Kiss,2 Julie M Schallhorn3,4 1Dell Laser Consultants, Austin, TX, USA; 2Optical Express, Glasgow, UK; 3University of California, San Francisco, Department of Ophthalmology, San Francisco, CA, USA; 4F.I. Proctor Foundation, University of California, San Francisco, CA, USACorrespondence: Steven J Dell, Dell Laser Consultants, 901 Mopac Expressway South, Barton Oaks Plaza IV, Suite 350, Austin, TX, 78746, USA, Email [email protected]: To compare the outcomes of the Tecnis Eyhance ICB00 IOL, designed to enhance intermediate vision, to a conventional Tecnis Monofocal ZCB00 IOL.Methods: This retrospective analysis compared two cohorts of patients undergoing lens replacement surgery with bilateral implantation of the Tecnis ICB00 or the Tecnis ZCB00 IOL (383 patients in each group). Monocular and binocular uncorrected distance (UDVA), intermediate (UIVA; 66cm), and near (UNVA; 40cm) visual acuities, refractive predictability, and patient-reported outcomes were compared. A sub-analysis of patients with the Eyhance IOL was performed to compare patients who achieved bilateral emmetropia to those with mini-monovision. One-month postoperative outcomes were analyzed.Results: Both groups had comparable UDVA outcomes. On average, both monocular and binocular UIVAs were approximately one Snellen line better in patients implanted with Eyhance IOL (monocular UIVA: ICB00 0.23 ± 0.18 logMAR, ZCB00 0.33 ± 0.19 logMAR; binocular UIVA: ICB00 0.18 ± 0.18 logMAR, ZCB00 0.26 ± 0.20 logMAR, p < 0.01). Likewise, the mean UNVA was also one Snellen line better with the ICB00 model (monocular UNVA: ICB00 0.51 ± 0.20 logMAR, ZCB00 0.61 ± 0.18 logMAR; binocular UNVA: ICB00 0.42 ± 0.19 logMAR, ZCB00 0.51 ± 0.22 logMAR, p < 0.01). There was no difference between the two groups in overall satisfaction or visual phenomena. A subgroup of patients who achieved mini-monovision with Eyhance IOL had, on average, one Snellen line better UIVA and UNVA compared to patients with bilateral emmetropia.Conclusion: Patients receiving the enhanced monofocal IOL had better intermediate and near vision compared to those receiving the conventional monofocal IOL, with similar levels of patient-reported photic phenomena in both groups.Keywords: enhanced monofocal IOL, Eyhance, patient-reported outcome

"It's a can of worms": understanding primary care practitioners' behaviours in relation to HPV using the Theoretical Domains Framework

Background: The relationship between infection with high-risk human papillomavirus (HPV) and cervical cancer is transforming cervical cancer prevention. HPV tests and vaccinations have recently become available. In Ireland, as elsewhere, primary care practitioners play a key role in prevention. ATHENS (A Trial of HPV Education and Support) aims to develop a theorybased intervention to support primary care practitioners in their HPV-related practice. This study, the first step in the intervention development process, aimed to: identify HPV-related clinical behaviours that the intervention will target; clarify general practitioners’ (GPs’) and practice nurses’ roles and responsibilities; and determine factors that potentially influence clinical behaviour. A secondary objective was to informally assess the utility of the Theoretical Domains Framework (TDF) in understanding clinical behaviours in an area with an evolving evidence-base. Methods: In-depth semi-structured telephone interviews were conducted with GPs and practice nurses. The topic guide, which contained open questions and HPV-related clinical scenarios, was developed through literature review and clinical experience. Interview transcripts were content-analysed using the TDF as the coding framework. Results: 19 GPs and 14 practice nurses were interviewed. The major HPV-related clinical behaviours were: initiating a discussion about HPV infection with female patients; offering/recommending HPV vaccination to appropriate patients; and answering patients’ questions about HPV testing. While the responsibility for taking smears was considered a female role, both male and female practitioners dealt with HPV-related issues. All 12 theoretical domains arose in relation to HPV infection; the domains judged to be most important were: knowledge, emotion, social influences, beliefs about capabilities and beliefs about consequences. Eleven domains emerged in relation to HPV vaccination, with beliefs about consequences, social influences, knowledge and environmental context and resources judged to be the most important. Nine domains were relevant to HPV testing, with knowledge and beliefs about capabilities judged to be the most important. Conclusions: The findings confirm the need for an intervention to support primary care practitioners around HPV and suggest it should target a range of theoretical domains. The TDF proved valuable in analysing qualitative data collected using a topic guide not specifically designed to capture TDF domains and understanding clinical behaviours in an area with an evolving evidence-base

A survey of the clinical acceptability of screening for postnatal depression in depressed and non-depressed women

BACKGROUND: Information on clinical acceptability is needed when making cost-utility decisions about health screening implementation. Despite being in use for two decades, most data on the clinical acceptability of the Edinburgh Postnatal Depression Scale (EPDS) come from qualitative reports, or include relatively small samples of depressed women. This study aimed to measure acceptability in a survey of a relatively large, community sample with a high representation of clinically depressed women. METHODS: Using mail, telephone and face-to-face interview, 920 postnatal women were approached to take part in a survey on the acceptability of the EPDS, including 601 women who had screened positive for depression and 245 who had received DSM-IV diagnoses of depression. Acceptability was measured on a 5-point Likert scale of comfort ranging from "Not Comfortable", through "Comfortable" to "Very Comfortable". RESULTS: The response rate was just over half for postal surveys (52%) and was 100% for telephone and face-to-face surveys (432, 21 and 26 respondents for postal, telephone and face-to-face surveys respectively) making 479 respondents in total. Of these, 81.2% indicated that screening with the EPDS had been in the range of "Comfortable" to "Very Comfortable". The other 18.8 % rated screening below the "Comfortable" point, including a small fraction (4.3%) who rated answering questions on the EPDS as "Not Comfortable" at the extreme end of the scale. Comfort was inversely related to EPDS score, but the absolute size of this effect was small. Almost all respondents (97%) felt that screening was desirable. CONCLUSION: The EPDS had good acceptability in this study for depressed and non-depressed women. Women's views on the desirability of postnatal depression screening appear to be largely independent of personal level of comfort with screening. These results should be useful to policy-makers and are broadly supportive of the Edinburgh Postnatal Depression Scale as a suitable tool for universal perinatal depression screening

From benzos to berries: treatment offered at an Aboriginal youth solvent abuse treatment centre relays the importance of culture.

First Nations and Inuit youth who abuse solvents are one of the most highly stigmatized substance-abusing groups in Canada. Drawing on a residential treatment response that is grounded in a culture-based model of resiliency, this article discusses the cultural implications for psychiatry's individualized approach to treating mental disorders. A systematic review of articles published in The Canadian Journal of Psychiatry during the past decade, augmented with a review of Canadian and international literature, revealed a gap in understanding and practice between Western psychiatric disorder-based and Aboriginal culture-based approaches to treatment and healing from substance abuse and mental disorders. Differing conceptualizations of mental health and substance abuse are discussed from Western psychiatric and Aboriginal worldviews, with a focus on connection to self, community, and political context. Applying an Aboriginal method of knowledge translation-storytelling-experiences from front-line workers in a youth solvent abuse treatment centre relay the difficulties with applying Western responses to Aboriginal healing. This lends to a discussion of how psychiatry can capitalize on the growing debate regarding the role of culture in the treatment of Aboriginal youth who abuse solvents. There is significant need for culturally competent psychiatric research specific to diagnosing and treating First Nations and Inuit youth who abuse substances, including solvents. Such understanding for front-line psychiatrists is necessary to improve practice. A health promotion perspective may be a valuable beginning point for attaining this understanding, as it situates psychiatry's approach to treating mental disorders within the etiology for Aboriginal Peoples

Crossing Paths with Hans Bodlaender:A Personal View on Cross-Composition for Sparsification Lower Bounds

On the occasion of Hans Bodlaender’s 60th birthday, I give a personal account of our history and work together on the technique of cross-composition for kernelization lower bounds. I present several simple new proofs for polynomial kernelization lower bounds using cross-composition, interlaced with personal anecdotes about my time as Hans’ PhD student at Utrecht University. Concretely, I will prove that Vertex Cover, Feedback Vertex Set, and the H-Factor problem for every graph H that has a connected component of at least three vertices, do not admit kernels of (formula presented) bits when parameterized by the number of vertices n for any (formula presented), unless (formula presented). These lower bounds are obtained by elementary gadget constructions, in particular avoiding the use of the Packing Lemma by Dell and van Melkebeek.</p

A retrospective analysis of bilateral fractures over sixteen years: localisation and variation in treatment of second hip fractures

The aim of this study was the evaluation of contralateral hip fractures after a previous hip fracture. For this retrospective analysis patients were selected from the database of the LUMC, a teaching hospital in the south-west of the Netherlands. We analyzed all patients with a second fracture of a hip between 1992 and 2007. The exclusion criteria were high impact trauma and patients with diseases or medication known to have a negative effect on bone metabolism. A total of 1,604 hip fractures were identified. The possible predictive factors for the second fracture and descriptive statistics related to surgery (Hb and HT before and after the operation, total amount of intra- and postoperative blood loss, type of osteosynthesis, complications, time of death after the last fracture, time between arrival in the hospital and operation and hospital stay for both fractures) were recorded. A total of 32 second hip fractures were identified (2%) at a mean of 27.5 (SD 28.9) months after the initial hip fracture. The mean age at the first fracture was 77.2 years (SD 11.7), and 27 of 32 patients were female. Of these 32 patients (64 bilateral hip fractures), 32 fractures were intracapsular (1 femoral neck, 31 subcapital) and 32 were extracapsular fractures (6 subtrochanteric, 26 transtrochanteric). Although 24 of the 32 patients had identical first and second hip fractures, only eight out of 32 hips were treated with the same implants. There was a significant difference in Singh index between both hips at the time of the first fracture. There was also a significant difference in Singh index between the hip which was not fractured compared with its subsequent index when it was broken. All other studied patient and fracture characteristics were not significantly different. In this population the percentage of second hip fractures was relatively low compared to other studies. The choice of implants in this study shows that implants were chosen randomly. Because there is a significant difference in the Singh index during first and second hip fracture, osteoporosis medication might help reduce the incidence of second hip fractures

Attitudinal and socio-structural determinants of cervical cancer screening and HPV vaccination uptake: a quantitative multivariate analysis

Aim: The introduction of the human papillomavirus (HPV) vaccine enables for the first time in the history of cancer prevention the possibility of combating the major cause of a cancer even before its onset. The secondary prevention measure of cervical cancer screening has thus been complemented by a primary prevention measure. The aim of this study is to analyse the determinants of uptake of preventive measures against cervical cancer as a basis for comparing the determinants of screening attendance with those of HPV vaccination attendance. Subject and methods: A population-based representative survey comprising 760 randomly selected women aged 14 to 65 was performed in the German federal state of Mecklenburg-Western Pomerania. Prevention behaviour, attitudes towards cervical cancer screening and HPV vaccination, and knowledge about cervical cancer and HPV were investigated by means of a structured questionnaire. Descriptive analyses and multivariate logistic regression analyses were conducted to identify the determinants of screening and HPV vaccine uptake. Results: Attendance both at screening and at HPV vaccination was best predicted by attitudinal factors. Positive connotations of cancer prevention measures and utility expectations, fear of cancer and high subjective risk perception were conducive to attendance at screening and HPV vaccination. Screening attendance was less regular among women of lower socioeconomic status. In contrast, HPV vaccination uptake was higher for young women with lower educational attainment and lower social class. Knowledge did not impact prevention behaviour significantly. There is no trade-off between screening and vaccination attendance; the vast majority of respondents was aware of the necessity of regular screening attendance even when vaccinated against HPV. Conclusions: Uptake rates for existing primary and secondary prevention measures against cervical cancer can be enhanced by fostering perceptions of utility and positive connotations of regular screening and becoming vaccinated against HPV. Elderly women in particular should be encouraged to attend screening by means of a recall system. Given the low overall level of knowledge about cervical cancer and its risk factors, there is a need for education about the necessity and utility of prevention to reach women of all social classes

N-glycans of Human Protein C Inhibitor: Tissue-Specific Expression and Function

Protein C inhibitor (PCI) is a serpin type of serine protease inhibitor that is found in many tissues and fluids in human, including blood plasma, seminal plasma and urine. This inhibitor displays an unusually broad protease specificity compared with other serpins. Previous studies have shown that the N-glycan(s) and the NH2-terminus affect some blood-related functions of PCI. In this study, we have for the first time determined the N-glycan profile of seminal plasma PCI, by mass spectrometry. The N-glycan structures differed markedly compared with those of both blood-derived and urinary PCI, providing evidence that the N-glycans of PCI are expressed in a tissue-specific manner. The most abundant structure (m/z 2592.9) had a composition of Fuc3Hex5HexNAc4, consistent with a core fucosylated bi-antennary glycan with terminal Lewisx. A major serine protease in semen, prostate specific antigen (PSA), was used to evaluate the effects of N-glycans and the NH2-terminus on a PCI function related to the reproductive tract. Second-order rate constants for PSA inhibition by PCI were 4.3±0.2 and 4.1±0.5 M−1s−1 for the natural full-length PCI and a form lacking six amino acids at the NH2-terminus, respectively, whereas these constants were 4.8±0.1 and 29±7 M−1s−1 for the corresponding PNGase F-treated forms. The 7–8-fold higher rate constants obtained when both the N-glycans and the NH2-terminus had been removed suggest that these structures jointly affect the rate of PSA inhibition, presumably by together hindering conformational changes of PCI required to bind to the catalytic pocket of PSA

Psychosis with paranoid delusions after a therapeutic dose of mefloquine: a case report

BACKGROUND: Convenient once-a-week dosing has made mefloquine a popular choice as malaria prophylaxis for travel to countries with chloroquine-resistant malaria. However, the increased use of mefloquine over the past decade has resulted in reports of rare, but severe, neuropsychiatric adverse reactions, such as anxiety, depression, hallucinations and psychosis. A direct causality between mefloquine and severe reactions among travelers has been partly confounded by factors associated with foreign travel and, in the case of therapeutic doses of mefloquine, the central nervous system manifestations of Plasmodium infection itself. The present case provides a unique natural history of mefloquine-induced neuropsychiatric toxicity and revisits its dose-dependent nature. CASE PRESENTATION: This report describes an acute exacerbation of neuropsychiatric symptoms after an unwarranted therapeutic dose (1250 mg) of mefloquine in a 37-year-old male previously on a once-a-week prophylactic regimen. Neuropsychiatric symptoms began as dizziness and insomnia of several days duration, which was followed by one week of escalating anxiety and subtle alterations in behaviour. The patient's anxiety culminated into a panic episode with profound sympathetic activation. One week later, he was hospitalized after developing frank psychosis with psychomotor agitation and paranoid delusions. His psychosis remitted with low-dose quetiapine. CONCLUSION: This report suggests that an overt mefloquine-induced psychosis can be preceded by a prodromal phase of moderate symptoms such as dizziness, insomnia, and generalized anxiety. It is important that physicians advise patients taking mefloquine prophylaxis and their relatives to recognize such symptoms, especially when they are accompanied by abrupt, but subtle, changes in behaviour. Patients with a history of psychiatric illness, however minor, may be at increased risk for a mefloquine-induced neuropsychiatric toxicity. Physicians must explicitly caution patients not to self-medicate with a therapeutic course of mefloquine when a malaria diagnosis has not been confirmed