Plos One
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The Cav3.2 isoform of the T-type calcium channel is expressed in primary sensory neurons of the dorsal root ganglion (DRG), and these channels contribute to nociceptive and neuropathic pain in rats. However, there are conflicting reports on the roles of these channels in pain processing in rats and mice. In addition, the function of T-type channels in persistent inflammatory hyperalgesia is poorly understood. ⋯ The increased Cav3.2 expression partially resulted from an increased number of Cav3.2-immunoreactive neurons; this increase in number was particularly significant for TRPV1-positive neurons. Finally, preceding and periodic intraplantar treatment with the T-type calcium channel blockers mibefradil and NNC 55-0396 markedly reduced and reversed mechanical hyperalgesia during the acute and sub-acute phases, respectively, in mice. These data suggest that Cav3.2 T-type channels participate in the development of inflammatory hyperalgesia, and this channel might play an even greater role in the sub-acute phase of inflammatory pain due to increased co-localization with TRPV1 receptors compared with that in the normal state.
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Ventilator-induced lung injury is a form of acute lung injury that develops in critically ill patients on mechanical ventilation and has a high degree of mortality. Nicotinamide phosphoribosyltransferase is an enzyme that is highly upregulated in ventilator-induced lung injury and exacerbates the injury when given exogenously. Nicotinamide (vitamin B3) directly inhibits downstream pathways activated by Nicotinamide phosphoribosyltransferase and is protective in other models of acute lung injury. ⋯ Nicotinamide treatment during VILI inhibits neutrophil infiltration of the lungs consistent with a strong anti-inflammatory effect, but paradoxically also leads to the development of significant hypoxemia. These findings suggest that pulmonary neutrophilia is not linked to hypoxemia in ventilator-induced lung injury, and that nicotinamide exacerbates hypoxemia during VILI.
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Although researchers have worked in collaboration since the origins of modern science and the publication of the first scientific journals in the eighteenth century, this phenomenon has acquired exceptional importance in the last several decades. Since the mid-twentieth century, new knowledge has been generated from within an ever-growing network of investigators, working cooperatively in research groups across countries and institutions. Cooperation is a crucial determinant of academic success. ⋯ Our study reveals the existence of a growing research community in which collaboration is increasingly important. We can highlight an essential feature associated with scientific collaboration: multi-authored papers, with growing numbers of collaborators contributing to them, are becoming more and more common, therefore the formation of research groups of increasing depth (specialization) and breadth (multidisciplinarity) is now a cornerstone of research success.
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Development and Validation of the Keele Musculoskeletal Patient Reported Outcome Measure (MSK-PROM).
To develop and validate a patient report outcome measure (PROM) for clinical practice that can monitor health status of patients with a range of musculoskeletal (MSK) disorders. ⋯ We have validated a brief patient reported outcome measure (MSK-PROM) for use in clinical practice to measure musculoskeletal health status and monitor outcomes over time using domains that are meaningful to patients and sensitive to change. Further work will establish whether the MSK-PROM is useful in other musculoskeletal healthcare settings.
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High rates of partner change in sex work-whether in professional, 'transactional' or other context-disproportionately drive transmission of HIV and other sexually transmitted infections. Several countries in Asia have demonstrated that reducing transmission in sex work can reverse established epidemics among sex workers, their clients and the general population. Experience and emerging research from Africa reaffirms unprotected sex work to be a key driver of sexual transmission in different contexts and regardless of stage or classification of HIV epidemic. This validation of the epidemiology behind sexual transmission carries an urgent imperative to realign prevention resources and scale up effective targeted interventions in sex work settings, and, given declining HIV resources, to do so efficiently. Eighteen articles in this issue highlight the importance and feasibility of such interventions under four themes: 1) epidemiology, data needs and modelling of sex work in generalised epidemics; 2) implementation science addressing practical aspects of intervention scale-up; 3) community mobilisation and 4) the treatment cascade for sex workers living with HIV. ⋯ Decades of empirical evidence, extended by analyses in this collection, argue that protecting sex work is, without exception, feasible and necessary for controlling HIV/STI epidemics. In addition, the disproportionate burden of HIV borne by sex workers calls for facilitated access to ART, care and support. The imperative for Africa is rapid scale-up of targeted prevention and treatment, facilitated by policies and action to improve conditions where sex work takes place. The opportunity is a wealth of accumulated experience working with sex workers in diverse settings, which can be tapped to make up for lost time. Elsewhere, even in countries with strong interventions and services for sex workers, an emerging challenge is to find ways to sustain them in the face of declining global resources.