Entry pathways of herpes simplex virus type 1 into human keratinocytes are dynamin- and cholesterol-dependent

Herpes simplex virus type 1 (HSV-1) can enter cells via endocytic pathways or direct fusion at the plasma membrane depending on the cell line and receptor(s). Most studies into virus entry have used cultured fibroblasts but since keratinocytes represent the primary entry site for HSV-1 infection in its human host, we initiated studies to characterize the entry pathway of HSV-1 into human keratinocytes. Electron microscopy studies visualized free capsids in the cytoplasm and enveloped virus particles in vesicles suggesting viral uptake both by direct fusion at the plasma membrane and by endocytic vesicles. The ratio of the two entry modes differed in primary human keratinocytes and in the keratinocyte cell line HaCaT. Inhibitor studies further support a role for endocytosis during HSV-1 entry. Infection was inhibited by the cholesterol-sequestering drug methyl-beta-cyclodextrin, which demonstrates the requirement for host cholesterol during virus entry. Since the dynamin-specific inhibitor dynasore and overexpression of a dominant-negative dynamin mutant blocked infection, we conclude that the entry pathways into keratinocytes are dynamin-mediated. Electron microscopy studies confirmed that virus uptake is completely blocked when the GTPase activity of dynamin is inhibited. Ex vivo infection of murine epidermis that was treated with dynasore further supports the essential role of dynamin during entry into the epithelium. Thus, we conclude that HSV-1 can enter human keratinocytes by alternative entry pathways that require dynamin and host cholesterol

Natural history of small asymptomatic kidney and residual stones over a long-term follow-up: systematic review over 25 years

Objective: To systematically review the natural history of small asymptomatic kidney and residual stones, as the incidental identification of small, asymptomatic renal calculi has risen with increasing use of high-resolution imaging. Materials and methods: We reviewed the natural history of small asymptomatic kidney and residual stones using the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. We searched MEDLINE, Scopus, EMBASE, EBSCO, Cochrane library and Clinicaltrials.gov using themes of ‘asymptomatic’, ‘nephrolithiasis’, ‘observation’, ‘symptoms’, ‘admission’, ‘intervention’ and similar allied terms for all English language articles from 1996 to 2020 (25 years). Inclusion criteria were studies with ≥50 patients, stones ≤10 mm, and a mean follow-up of ≥24 months. Primary outcomes were occurrence of symptoms, emergency admission, and interventions. Results: Our literature search returned 2247 results of which 10 papers were included in the final review. Risk of symptomatic episodes ranged from 0% to 59.4%. Meta-analysis did not identify any significant difference in the likelihood of developing symptoms when comparing stones 5 mm, nor those 10 mm. Risk of admission varied from 14% to 19% and the risk of intervention from 12% to 35%. Meta-analysis showed a significantly decreased likelihood of intervention for stones 5 mm and 10 mm. Studies had variable risk of bias due to heterogeneous reporting of outcome measures with significant likelihood that observed differences in results were compatible with chance alone (Symptoms: I2=0%, Cochran’s Q = 3.09, P = 0.69; Intervention: I2=0%, Cochran’s Q = 1.76, P = 0.88). Conclusions: The present systematic review indicates that stone size is not a reliable predictor of symptoms; however, risk of intervention is greater for stones >5mm vs 10 vs <10 mm. This review will inform urologists as they discuss management strategies with patients who have asymptomatic renal stones and offer insight to committees during the development of evidence-based guidelines

'Surely the most natural scenario in the world’: Representations of ‘Family’ in BBC Pre-school Television

Historically, the majority of work on British children’s television has adopted either an institutional or an audience focus, with the texts themselves often overlooked. This neglect has meant that questions of representation in British children’s television – including issues such as family, gender, class or ethnicity - have been infrequently analysed in the UK context. In this article, we adopt a primarily qualitative methodology and analyse the various textual manifestations of ‘family’, group, or community as represented in a selected number of BBC pre-school programmes. In doing so, we question the (limited amount of) international work that has examined representations of the family in children’s television, and argue that nuclear family structures do not predominate in this sphere

Doing it for the kids?: The discursive construction of the teenager and teenage sexuality in E4’s Skins

The teen series is often regarded by television scholars as an inherently American genre. Indeed, the genre is marked by US constructs, such as the cheerleader, jock, homecoming dance and prom and, in turn, teen television scholarship has focused almost exclusively on US texts. However, more recent years have seen the emergence of British teen drama series, most notably Skins (E4, 2007-), which has been so successful that it has spawned an (albeit short-lived) US version which aired on MTV. In an attempt to redress the dearth of academic study of British teen dramas, this article explores Skins in more detail. Journalistic discourse on the programme has frequently emphasised the series' nihilism in contrast to the didacticism that characterises its US generic counterparts, which the series' creators justify by claims for its authenticity. This article moves beyond the authentic/inauthentic debate to explore instead the discursive construction of the teenager and teenage sexuality in the specific context of broadcasting in the UK. Thus, after situating Skins in relation to the history of youth programming in Britain and, specifically, on Channel 4, the article will explore issue-led storylines involving teenage sexuality in more detail. It will argue that despite the programme's nihilistic ethos, Skins is underpinned by more conservative ideologies, particularly regarding the depiction of gender and sexuality. In turn, this ambivalence makes it difficult to discern the programme's ideological stance on sexual issues

Exploring Patients' Experiences of Internet-Based Self-Management Support for Low Back Pain in Primary Care

OBJECTIVE: We explored patients' experiences of using Internet-based self-management support for low back pain (LBP) in primary care, with and without physiotherapist telephone guidance. DESIGN: Exploratory descriptive qualitative study using thematic analysis, nested within a randomized feasibility trial. METHODS: Patients with LBP who participated in a feasibility trial of the SupportBack Internet intervention (ISRCTN: 31034004) were invited to take part in semistructured telephone interviews after the three-month intervention period (a convenience sample from within the trial population). Fifteen participants took part (age range = 36-87 years, 66.7% female, characteristics representative of the trial population). Data were analyzed thematically. RESULTS: Analysis resulted in the development of six themes (subthemes in parentheses): Perceptions of SupportBack's design (Clarity and ease of use, Variety and range of information provided, Need for specificity and flexibility), Engaging with the SupportBack intervention, Promoting positive thought processes (Reassurance, Awareness of self-management), Managing behavior with SupportBack (Motivation and goal setting, Using activity as a pain management strategy, Preferences for walking or gentle back exercises), Feeling supported by telephone physiotherapists (Provision of reassurances and clarity, Physiotherapists are motivating), Severity and comorbidity as barriers (Preexisting condition or severity acting as a barrier, Less useful for mild low back pain). CONCLUSIONS: The Internet intervention SupportBack appeared to feasibly support self-management of LBP. Reassurance and ongoing support to implement behavioral changes were central to reported benefits. The addition of physiotherapist telephone support further enhanced the patient experience and the potential utility of the intervention

New generalized fuzzy metrics and fixed point theorem in fuzzy metric space

In this paper, in fuzzy metric spaces (in the sense of Kramosil and Michalek (Kibernetika 11:336-344, 1957)) we introduce the concept of a generalized fuzzy metric which is the extension of a fuzzy metric. First, inspired by the ideas of Grabiec (Fuzzy Sets Syst. 125:385-389, 1989), we define a new G-contraction of Banach type with respect to this generalized fuzzy metric, which is a generalization of the contraction of Banach type (introduced by M Grabiec). Next, inspired by the ideas of Gregori and Sapena (Fuzzy Sets Syst. 125:245-252, 2002), we define a new GV-contraction of Banach type with respect to this generalized fuzzy metric, which is a generalization of the contraction of Banach type (introduced by V Gregori and A Sapena). Moreover, we provide the condition guaranteeing the existence of a fixed point for these single-valued contractions. Next, we show that the generalized pseudodistance J:X×X→[0,∞) (introduced by Włodarczyk and Plebaniak (Appl. Math. Lett. 24:325-328, 2011)) may generate some generalized fuzzy metric NJ on X. The paper includes also the comparison of our results with those existing in the literature

Fixed points for cyclic R-contractions and solution of nonlinear Volterra integro-differential equations

In this paper, we introduce the notion of cyclic R-contraction mapping and then study the existence of fixed points for such mappings in the framework of metric spaces. Examples and application are presented to support the main result. Our result unify, complement, and generalize various comparable results in the existing literature.http://link.springer.com/journal/11784am2016Mathematics and Applied Mathematic

Mediating the Presence of Others: Reconceptualising Co-Presence as Mediated Intimacy

Drawing insight from queer and media studies, this article analyses data from the UK study Adults’ Media Lives. The authors claim that this study reveals the significance of people’s intimate relationships to their media practices, highlighting in particular how people’s media practices mediate the ‘presence’ of others. The authors put forward the concept of mediated intimacy to capture both the cultural intimacy people have with media and the mediation of intimacy by media practices. Mediating intimacy has implications for normative conceptions of intimate life, including the significance of ‘time’ to the values of ‘home’ and ‘work’