Chilblains in immune-mediated inflammatory diseases: a review.

Chilblains were first described over a hundred years ago as cutaneous inflammatory lesions, typically on the digits, occurring on cold exposure. Chilblains can be primary, or secondary to a number of conditions such as infections, including COVID-19, and immune-mediated inflammatory disorders (IMIDs) with SLE being the commonest. Chilblain lupus erythematosus (CHLE) was first described in 1888 as cold-induced erythematous lesions before the terms 'chilblains' or 'perniosis' were coined. Diagnostic criteria exist for both chilblains and CHLE. Histopathologically, CHLE lesions show interface dermatitis with perivascular lymphocytic infiltrate. Immunofluorescence demonstrates linear deposits of immunoglobulins and complement in the dermo-epidermal junction. This narrative review focuses on chilblains secondary to immune-mediated inflammatory disorders, primarily the epidemiology, pathogenesis and treatment of CHLE.

Women's empowerment: Finding strength in self-compassion.

Empowerment is often a desired outcome for health programs; however, it is rarely evaluated. One way to increase empowerment may be through self-compassion. The authors of the current study aimed to determine whether self-compassion and empowerment were positively related. Two hundred and five women (ages 18 to 48 years) were recruited from a pool of undergraduate students at a university in the southeastern United States in the summer/fall of 2012. Participants completed the study using Qualtrics, an online survey system. Participants wrote about a fight in a romantic relationship and were randomly assigned to write about the fight either self-compassionately or generally. Empowerment and perceptions of the fight were assessed as dependent measures. Hierarchical regression analyses investigated the relation of self-compassion, manipulated self-compassion, and their interaction with empowerment. A significant positive relationship was found between self-compassion and empowerment. However, manipulated self-compassion was not significantly related to empowerment. These findings suggested that self-compassion and empowerment were strongly related, but using a short-term self-compassion intervention may not be strong enough to influence empowerment. Empowerment-based practitioners may find empowerment increases more easily in women who are self-compassionate. If self-compassion is incorporated into empowerment settings, a long-term intervention may be necessary.

'No news today': talk of witnessing with families of missing people.

The paper contributes new ways of thinking about and responding to interview talk in the context of recent scholarship on interviewing, orality and witnessing. We proceed by paying attention to specific examples of interview talk on the experience of absence via the collecting of narratives from families of missing people. We highlight how ambiguous emotions are bound up with broader ways of recognizing such talk, largely exercised here as reflections on what is involved in witnessing those who are missing in communications with police. Tensions that may be produced by official ways of regarding and responding to family character witness of the missing are discussed in the context of two case studies. In response to these tensions, we offer suggestions for finding different spaces through which to value such 'witness talk' by families, particularly via ideas from grief scholarship. The paper concludes by briefly reflecting on how interviewing encounters might produce versions of praxis in which the content of talk is not just, and simply, 'apprehended' as academic evidence.

Sophie's story: writing missing journeys.

'Sophie's story' is a creative rendition of an interview narrative gathered in a research project on missing people. The paper explains why Sophie's story was written and details the wider intention to provide new narrative resources for police officer training, families of missing people and returned missing people. We contextualize this cultural intervention with an argument about the transformative potential of writing trauma stories. It is suggested that trauma stories produce difficult and unknown affects, but ones that may provide new ways of talking about unspeakable events. Sophie's story is thus presented as a hopeful cultural geography in process, and one that seeks to help rewrite existing social scripts about missing people.

Effectiveness of PrEPTECH: Findings From a 180-Day Randomized Controlled Trial of a Pre-Exposure Prophylaxis Telehealth Intervention.

BACKGROUND: Telehealth approaches are increasingly being used to provide access to pre-exposure prophylaxis (PrEP), an effective but underused HIV prevention modality. This randomized controlled trial of PrEPTECH, a telehealth intervention for the provision of HIV PrEP, seeks to assess its effects on PrEP access. METHODS: Young men who have sex with men and transgender women in Florida and California with an indication for PrEP were randomly assigned in a 1:1 allocation to receive access to PrEPTECH or a control condition, access to an online listing of PrEP resources in their communities. This intent-to-treat analysis used logistic and linear regression to compare self-reported PrEP initiation, use, and coverage between control and intervention arm participants at 90 days and 180 days of follow-up. RESULTS: A total of 229 participants with a mean age of 23.7 years, 77.3% people of color enrolled in PrEPTECH. At 90 days, postbaseline initiation of PrEP was significantly higher among those in the PrEPTECH arm than among controls (odds ratio [OR]: 6.63, 95% confidence interval [CI]: 2.54 to 17.35), and this held true by 180 days post baseline. The count of sex acts for which participants were not protected by PrEP, PrEP adherence, and recent PrEP use at 180 days post baseline were not significantly different between the study arms. CONCLUSIONS: Receiving access to a telehealth platform for PrEP access increased PrEP initiation in this cohort of young, predominantly non-White sexual and gender minorities. PrEP telehealth may be a worthy avenue for providing access to PrEP for these populations, but additional strategies may be needed to promote adherence and persistence of PrEP use.

Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans.

Recent success in identifying gene-regulatory elements in the context of recombinant adeno-associated virus vectors has enabled cell-type-restricted gene expression. However, within the cerebral cortex these tools are largely limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple new enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we discovered enhancers selective for parvalbumin (PV) and vasoactive intestinal peptide-expressing interneurons. Demonstrating the functional utility of these elements, we show that the PV-specific enhancer allowed for the selective targeting and manipulation of these neurons across vertebrate species, including humans. Finally, we demonstrate that our selection method is generalizable and characterizes additional PV-specific enhancers with exquisite specificity within distinct brain regions. Altogether, these viral tools can be used for cell-type-specific circuit manipulation and hold considerable promise for use in therapeutic interventions.

Single-molecule measurement of the stiffness of the rigor myosin head.

The force-extension curve of single myosin subfragment-1 molecules, interacting in the rigor state with an actin filament, has been investigated at low [ATP] by applying a slow triangle-wave movement to the optical traps holding a bead-actin-bead dumbbell. In combination with a measurement of the overall stiffness of the dumbbell, this allowed characterization of the three extensible elements, the actin-bead links and the myosin. Simultaneously, another method, based on an analysis of bead position covariance, gave satisfactory agreement. The mean covariance-based estimate for the myosin stiffness was 1.79 pN/nm (SD = 0.7 pN/nm; SE = 0.06 pN/nm (n = 166 myosin molecules)), consistent with a recent report (1.7 pN/nm) from rabbit muscle fibers. In the triangle-wave protocol, the motion of the trapped beads during interactions was linear within experimental error over the physiological range of force applied to myosin (+/-10 pN), consistent with a Hookean model; any nonlinear terms could not be characterized. Bound states subjected to forces that resisted the working stroke (i.e., positive forces) detached at a significantly lower force than when subjected to negative forces, which is indicative of a strain-dependent dissociation rate.

Who Owns the Data? Open Data for Healthcare.

Research on large shared medical datasets and data-driven research are gaining fast momentum and provide major opportunities for improving health systems as well as individual care. Such open data can shed light on the causes of disease and effects of treatment, including adverse reactions side-effects of treatments, while also facilitating analyses tailored to an individual's characteristics, known as personalized or "stratified medicine." Developments, such as crowdsourcing, participatory surveillance, and individuals pledging to become "data donors" and the "quantified self" movement (where citizens share data through mobile device-connected technologies), have great potential to contribute to our knowledge of disease, improving diagnostics, and delivery of -healthcare and treatment. There is not only a great potential but also major concerns over privacy, confidentiality, and control of data about individuals once it is shared. Issues, such as user trust, data privacy, transparency over the control of data ownership, and the implications of data analytics for personal privacy with potentially intrusive inferences, are becoming increasingly scrutinized at national and international levels. This can be seen in the recent backlash over the proposed implementation of care.data, which enables individuals' NHS data to be linked, retained, and shared for other uses, such as research and, more controversially, with businesses for commercial exploitation. By way of contrast, through increasing popularity of social media, GPS-enabled mobile apps and tracking/wearable devices, the IT industry and MedTech giants are pursuing new projects without clear public and policy discussion about ownership and responsibility for user-generated data. In the absence of transparent regulation, this paper addresses the opportunities of Big Data in healthcare together with issues of responsibility and accountability. It also aims to pave the way for public policy to support a balanced agenda that safeguards personal information while enabling the use of data to improve public health.

Lentigo maligna : prognosis and treatment options.

Lentigo maligna is a premalignant melanocytic neoplasm occurring on the sun-exposed skin of the middle-aged and elderly. It is believed to represent the in situ phase of lentigo maligna melanoma and, as such, cure is usually the aim of treatment. However, factors such as site and size of lesion and patient co-morbidities may influence the treatment modality undertaken. Surgical excision is the treatment of choice to obtain clinical and histologic clearance, but many other modalities have been used with variable success. Mohs micrographic surgery is associated with the lowest recurrence rate at 4-5%, but conventional surgery, cryotherapy and radiotherapy also yield good results, with recurrence rates in the order of 7-10%. Other treatments have been tried but currently there are not enough data to support their routine use. In order to make the best decision regarding appropriate management of lentigo maligna, the dermatologist or surgeon must be aware of all the options available and the evidence supporting their use.