Human T-cell lymphotropic virus (HTLV)-associated encephalopathy: an under-recognised cause of acute encephalitis? Case series and literature review

Human T-cell lymphotropic virus (HTLV)-1-associated myelopathy (HAM) is well described. Clinical features are predominantly consistent with cord pathology, though imaging and autopsy studies also demonstrate brain inflammation. In general, this is subclinical; however, six cases have previously been reported of encephalopathy in HTLV-1-infected patients, without alternative identified aetiology. We describe three further cases of encephalitis in the UK HAM cohort (n = 142), whereas the annual incidence of acute encephalitis in the general population is 0.07-12.6 per 100,000. Clinical features included reduced consciousness, fever/hypothermia, headaches, seizures, and focal neurology. Investigation showed: raised CSF protein; pleocytosis; raised CSF:peripheral blood mononuclear cell HTLV-1 proviral load ratio; and MRI either normal or showing white matter changes in brain and cord. Four of the six previous case reports of encephalopathy in HTLV-infected patients also had HAM. Histopathology, reported in three, showed perivascular predominantly CD8+ lymphocytic infiltrates in the brain. One had cerebral demyelination, and all had cord demyelination. We have reviewed the existing six cases in the literature, together with our three new cases. In all seven with HAM, the spastic paraparesis deteriorated sub-acutely preceding encephalitis. Eight of the nine were female, and four of the seven treated with steroids improved. We propose that HTLV-associated encephalopathy may be part of the spectrum of HTLV-1-induced central nervous system disease

Different in Vivo Reactivity Profile in Health Care Workers and Patients with Spina Bifida to Internal and External Latex Glove Surface-Derived Allergen Extracts

BACKGROUND: Allergy to natural rubber latex is a well-recognized health problem, especially among health care workers and patients with spina bifida. Despite latex sensitization being acquired in health institutions in both health care workers and patients with spina bifida, differences in allergen sensitization profiles have been described between these two risk groups. OBJECTIVE: To investigate the in vivo reactivity of health care workers and patients with spina bifida to extracts of internal and external surfaces of latex gloves and also to specific extracts enriched in major allergens for these risk groups. METHODS: Gloves from different manufacturers were used for protein extraction, and salt precipitation and hydrophobic interaction chromatography (HIC) were applied to obtain the enriched latex extracts. The major latex allergens were quantified by an enzyme immunoassay. The extracts obtained were tested in 14 volunteers using skin prick tests (SPT). RESULTS: Latex glove extracts enriched in the hydrophobic allergens that are most often seen in patients with spina bifida were obtained by selective precipitation, whereas HIC produced extracts enriched in the hydrophilic allergens commonly found in health care workers. The health care workers had positive SPTs to glove extracts from internal surfaces and to the hydrophilic allergen-enriched extracts. By contrast, patients with spina bifida had larger skin reactions both to external glove extracts and to the extracts enriched with the hydrophobic major allergens for this risk group. Despite the protein concentration of these extracts being less than half the concentration of the commercial extract, the weal-and-flare reactions were of similar magnitude. CONCLUSION: Using novel latex extracts, our study showed a different in vivo reactivity pattern in health care workers and in patients with spina bifida to extracts of the internal and external surfaces of gloves, which suggests that sensitization may occur by different routes of exposure, and that this influences the allergen reactivity profiles of these risk group

Unforeseen misuses of bed nets in fishing villages along Lake Victoria

<p>Abstract</p> <p>Background</p> <p>To combat malaria, the Kenya Ministry of Health and nongovernmental organizations (NGOs) have distributed insecticide-treated nets (ITNs) for use over beds, with coverage for children under five years of age increasing rapidly. Nevertheless, residents of fishing villages have started to use these bed nets for drying fish and fishing in Lake Victoria. This study investigated the extent of bed net misuse in fishing villages.</p> <p>Methods</p> <p>Seven fishing villages along the lake were surveyed to estimate how widely bed nets were being used for fishing and drying fish. Villagers were asked why they used the bed nets for such purposes.</p> <p>Results</p> <p>In total, 283 bed nets were being used for drying fish. Of these, 239 were long-lasting insecticidal bed nets (LLIN) and 44 were non-long-lasting insecticidal bed nets (NLLIN). Further, 72 of the 283 bed nets were also being used for fishing. The most popular reasons were because the bed nets were inexpensive or free and because fish dried faster on the nets. LLINs were preferred to NLLINs for fishing and drying fish.</p> <p>Conclusion</p> <p>There is considerable misuse of bed nets for drying fish and fishing. Many villagers are not yet fully convinced of the effectiveness of LLINs for malaria prevention. Such misuses may hamper the efforts of NGOs and governmental health organizations.</p

Building Thriving Workforces from the Top Down: A Call and Research Agenda for Organizations to Proactively Support Employee Well-Being

Organizational researchers studying well-being – as well as organizations themselves – often place much of the burden on employees to manage and preserve their own well-being. Missing from this discussion is how – from a human resources management (HRM) perspective – organizations and managers can directly and positively shape the well-being of their employees. The authors use this review to paint a picture of what organizations could be like if they valued people holistically and embraced the full experience of employees’ lives to promote well-being at work. In so doing, the authors tackle five challenges that managers may have to help their employees navigate, but to date have received more limited empirical and theoretical attention from an HRM perspective: (1) recovery at work; (2) women’s health; (3) concealable stigmas; (4) caregiving; and (5) coping with socio-environmental jolts. In each section, the authors highlight how past research has treated managerial or organizational support on these topics, and pave the way for where research needs to advance from an HRM perspective. The authors conclude with ideas for tackling these issues methodologically and analytically, highlighting ways to recruit and support more vulnerable samples that are encapsulated within these topics, as well as analytic approaches to study employee experiences more holistically. In sum, this review represents a call for organizations to now – more than ever – build thriving organizations

The correct prednisone starting dose in polymyalgia rheumatica is related to body weight but not to disease severity

<p>Abstract</p> <p>Background</p> <p>the mainstay of treatment of polymyalgia rheumatica (PMR) is oral glucocorticoids, but randomized controlled trials of treatment are lacking. As a result, there is no evidence from controlled studies on the efficacy of different initial doses or glucocorticoid tapering. The aim of this study is to test if 12.5 mg prednisone/day is an adequate starting dose in PMR and to evaluate clinical predictors of drug response.</p> <p>Methods</p> <p>60 consecutive PMR patients were treated with a starting dose of 12,5 mg/day prednisone. Clinical, laboratory, and, in a subset of 25 patients, ultrasonographic features were recorded as possible predictors of response to prednisone. Remission was defined as disappearance of at least 75% of the signs and symptoms of PMR and normalization of ESR and CRP within the first month, a scenario allowing steroid tapering.</p> <p>Results</p> <p>47/60 (78.3%) patients responded to 12.5 mg of prednisone after a mean interval of 6.6 ± 5.2 days. In univariate analysis, body weight and gender discriminated the two groups. In multivariate analysis, the only factor predicting a good response was low weight (p = 0.004); the higher response rate observed in women was explained by their lower weight. The mean prednisone dose per kg in the responders was 0.19 ± 0.03 mg in comparison with 0.16 ± 0.03 mg for non responders (p = 0.007).</p> <p>Conclusions</p> <p>12.5 mg prednisone is a sufficient starting dose in ¾ of PMR patients. The main factor driving response to prednisone in PMR was weight, a finding that could help in the clinical care of PMR patients and in designing prospective studies of treatment.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01169597">NCT01169597</a></p

Occurrence and impact of delayed cerebral ischemia after coiling and after clipping in the International Subarachnoid Aneurysm Trial (ISAT)

Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). We studied differences in incidence and impact of DCI as defined clinically after coiling and after clipping in the International Subarachnoid Aneurysm Trial. We calculated odds ratios (OR) for DCI for clipping versus coiling with logistic regression analysis. With coiled patients without DCI as the reference group, we calculated ORs for poor outcome at 2 months and 1 year for coiled patients with DCI and for clipped patients without, and with DCI. With these ORs, we calculated relative excess risk due to Interaction (RERI). Clipping increased the risk of DCI compared to coiling in the 2,143 patients OR 1.24, 95% confidence interval (95% CI 1.01–1.51). Coiled patients with DCI, clipped patients without DCI, and clipped patients with DCI all had higher risks of poor outcome than coiled patients without DCI. Clipping and DCI showed no interaction for poor outcome at 2 months: RERI 0.12 (95% CI −1.16 to 1.40) or 1 year: RERI −0.48 (95% CI −1.69 to 0.74). Only for patients treated within 4 days, coiling and DCI was associated with a poorer outcome at 1 year than clipping and DCI (RERI −2.02, 95% CI −3.97 to −0.08). DCI was more common after clipping than after coiling in SAH patients in ISAT. Impact of DCI on poor outcome did not differ between clipped and coiled patients, except for patients treated within 4 days, in whom DCI resulted more often in poor outcome after coiling than after clipping

Interaction Between Convection and Pulsation

This article reviews our current understanding of modelling convection dynamics in stars. Several semi-analytical time-dependent convection models have been proposed for pulsating one-dimensional stellar structures with different formulations for how the convective turbulent velocity field couples with the global stellar oscillations. In this review we put emphasis on two, widely used, time-dependent convection formulations for estimating pulsation properties in one-dimensional stellar models. Applications to pulsating stars are presented with results for oscillation properties, such as the effects of convection dynamics on the oscillation frequencies, or the stability of pulsation modes, in classical pulsators and in stars supporting solar-type oscillations.Comment: Invited review article for Living Reviews in Solar Physics. 88 pages, 14 figure

Physics and Applications of Laser Diode Chaos

An overview of chaos in laser diodes is provided which surveys experimental achievements in the area and explains the theory behind the phenomenon. The fundamental physics underpinning this behaviour and also the opportunities for harnessing laser diode chaos for potential applications are discussed. The availability and ease of operation of laser diodes, in a wide range of configurations, make them a convenient test-bed for exploring basic aspects of nonlinear and chaotic dynamics. It also makes them attractive for practical tasks, such as chaos-based secure communications and random number generation. Avenues for future research and development of chaotic laser diodes are also identified.Comment: Published in Nature Photonic

Lymph Node Negative Colorectal Cancers with Isolated Tumor Deposits Should Be Classified and Treated As Stage III

BACKGROUND: The prognostic role of pericolic or perirectal isolated tumor deposits (ITDs) in node-negative colorectal cancer (CRC) patients is unclear. Rules to define ITDs as regional lymph node metastases changed in subsequent editions of the TNM staging without substantial evidence. Aim of this study was to investigate the correlation between ITDs and disease recurrence in stage II and III CRC patients. MATERIALS AND METHODS: The medical files of 870 CRC patients were reviewed. Number, size, shape, and location pattern of all ITDs in node-negative patients were examined in relation to involvement of vascular structures and nerves. The correlation between ITDs and the development of recurrent disease was investigated. RESULTS: Disease recurrence was observed in 50.0% of stage II patients with ITDs (13 of 26), compared with 24.4% of stage II patients without ITDs (66 of 270) (P <.01). Disease-free survival of ITD-positive stage II patients was comparable with that of stage III patients. Also within stage III, more recurrences were observed in ITD-positive patients compared with ITD-negative patients (65.1 vs. 39.1%, respectively). No correlation was found between size of ITDs and disease recurrence. More recurrences were seen in patients with irregularly shaped ITDs compared with patients with 1 or more smooth ITDs present. CONCLUSIONS: Because of the high risk of disease recurrence, all node-negative stage II patients with ITDs, regardless of size and shape, should be classified as stage III, for whom adjuvant chemotherapy should be considere

Direct Visualization of Protease Action on Collagen Triple Helical Structure

Enzymatic processing of extracellular matrix (ECM) macromolecules by matrix metalloproteases (MMPs) is crucial in mediating physiological and pathological cell processes. However, the molecular mechanisms leading to effective physiological enzyme-ECM interactions remain elusive. Only scant information is available on the mode by which matrix proteases degrade ECM substrates. An example is the enzymatic degradation of triple helical collagen II fragments, generated by the collagenase MMP-8 cleavage, during the course of acute inflammatory conditions by gelatinase B/MMP-9. As is the case for many other matrix proteases, it is not clear how MMP-9 recognizes, binds and digests collagen in this important physiological process. We used single molecule imaging to directly visualize this protease during its interaction with collagen fragments. We show that the initial binding is mediated by the diffusion of the protease along the ordered helix on the collagen ¾ fragment, with preferential binding of the collagen tail. As the reaction progressed and prior to collagen degradation, gelatin-like morphologies resulting from the denaturation of the triple helical collagen were observed. Remarkably, this activity was independent of enzyme proteolysis and was accompanied by significant conformational changes of the working protease. Here we provide the first direct visualization of highly complex mechanisms of macromolecular interactions governing the enzymatic processing of ECM substrates by physiological protease