Classical dendritic cells mediate fibrosis directly via the retinoic acid pathway in severe eye allergy

Fibrosis is a shared end-stage pathway to lung, liver, and heart failure. In the ocular mucosa (conjunctiva), fibrosis leads to blindness in trachoma, pemphigoid, and allergy. The indirect fibrogenic role of DCs via T cell activation and inflammatory cell recruitment is well documented. However, here we demonstrate that DCs can directly induce fibrosis. In the mouse model of allergic eye disease (AED), classical CD11b(+) DCs in the ocular mucosa showed increased activity of aldehyde dehydrogenase (ALDH), the enzyme required for retinoic acid synthesis. In vitro, CD11b(+) DC-derived ALDH was associated with 9-cis-retinoic acid ligation to retinoid x receptor (RXR), which induced conjunctival fibroblast activation. In vivo, stimulating RXR led to rapid onset of ocular mucosal fibrosis, whereas inhibiting ALDH activity in DCs or selectively depleting DCs markedly reduced fibrosis. Collectively, these data reveal a profibrotic ALDH-dependent pathway by DCs and uncover a role for DC retinoid metabolism

Chondrosarcoma presenting as dyspnea in a 19-year-old man: a case report

<p>Abstract</p> <p>Introduction</p> <p>Acute pulmonary embolism has varied presentations ranging from asymptomatic, incidentally discovered emboli to massive embolism, causing immediate death. Tumor embolism is a rare but unique complication of malignancies. This uncommon catastrophe of a malignant tumor in a young patient, culminating as a pulmonary embolism, is being reported for the first time.</p> <p>Case presentation</p> <p>A 19-year-old Asian man presented to the emergency service at our hospital with acute onset dyspnea. His clinical examination led to the suspicion of an acute pulmonary embolism with a lower lumbosacral radiculopathy. A magnetic resonance imaging scan of the pelvis demonstrated a chondrosarcoma arising from the right iliac wing, eroding into the common iliac vein and creeping up the inferior vena cava to lodge in the pulmonary artery, thus producing a saddle embolus.</p> <p>Conclusion</p> <p>The importance of exploring for malignancies in the event of an idiopathic pulmonary embolism is highlighted. Early detection of such malignancies can substantially affect the outcome in young patients.</p

Geophysical Survey in Sub-Saharan Africa: magnetic and Electromagnetic Investigation of the UNESCO World Heritage Site of Songo Mnara, Tanzania

Magnetometry and Slingram electromagnetic surveys were conducted at the UNESCO World Heritage Site of Songo Mnara, Tanzania, as part of a multi-national programme of investigation to examine the uses of space within and outside of this stonetown. The town was a major Islamic trading port during the 14th and 15th centuries.The surveys detected significant evidence for the containment of activities within the town walls, and previously unknown anthropogenic activity was revealed between the existing coral rag buildings, as well as within the open areas inside the town. Over 40 areas of magnetic disturbance were identified that corresponded directly with areas of high magnetic susceptibility in the Slingram electromagnetic in-phase responses.On excavation many of these anomalies were found to correlate with wattle and daub structures, indicating a hitherto unidentified population, and the location of the anomalies also suggests a potentially deliberate delineation of space within the open areas of the stonetown. The combined results of the three geophysical data sets indicate that there are clear delineations in the use of space within Songo Mnara. This coupled with the presence of industrial activities and evidence of more ephemeral occupation, neither of which had previously been recorded at the site, indicates that the pre-existing town plan is in need of significant reappraisal. The current plan, based upon the remains of extant and collapsed coral buildings, can now be updated to incorporate the more ephemeral aspects of Swahili sites including activity areas, and notably, the homes of the ‘hidden majority’of the population.The results establish the benefit of a combined approach at these sites, and demonstrate that further invasive and non-invasive exploration is required in order to fully exploit the significance of the role of geophysical techniques in understanding Swahili towns

Hearing loss in Pompe disease revisited: results from a study of 24 children

Little information is available regarding the auditory function in Pompe patients. Hearing loss has been reported in classic infantile patients, but it is still unknown whether central nervous system involvement interferes with auditory function and whether enzyme replacement therapy can improve hearing. Audi

Apraxia and motor dysfunction in corticobasal syndrome

Background: Corticobasal syndrome (CBS) is characterized by multifaceted motor system dysfunction and cognitive disturbance; distinctive clinical features include limb apraxia and visuospatial dysfunction. Transcranial magnetic stimulation (TMS) has been used to study motor system dysfunction in CBS, but the relationship of TMS parameters to clinical features has not been studied. The present study explored several hypotheses; firstly, that limb apraxia may be partly due to visuospatial impairment in CBS. Secondly, that motor system dysfunction can be demonstrated in CBS, using threshold-tracking TMS, and is linked to limb apraxia. Finally, that atrophy of the primary motor cortex, studied using voxel-based morphometry analysis (VBM), is associated with motor system dysfunction and limb apraxia in CBS.   Methods: Imitation of meaningful and meaningless hand gestures was graded to assess limb apraxia, while cognitive performance was assessed using the Addenbrooke's Cognitive Examination - Revised (ACE-R), with particular emphasis placed on the visuospatial subtask. Patients underwent TMS, to assess cortical function, and VBM.   Results: In total, 17 patients with CBS (7 male, 10 female; mean age 64.4+/2 6.6 years) were studied and compared to 17 matched control subjects. Of the CBS patients, 23.5% had a relatively inexcitable motor cortex, with evidence of cortical dysfunction in the remaining 76.5% patients. Reduced resting motor threshold, and visuospatial performance, correlated with limb apraxia. Patients with a resting motor threshold <50% performed significantly worse on the visuospatial sub-task of the ACE-R than other CBS patients. Cortical function correlated with atrophy of the primary and pre-motor cortices, and the thalamus, while apraxia correlated with atrophy of the pre-motor and parietal cortices.   Conclusions: Cortical dysfunction appears to underlie the core clinical features of CBS, and is associated with atrophy of the primary motor and pre-motor cortices, as well as the thalamus, while apraxia correlates with pre-motor and parietal atrophy

Cervical cancer screening: target age bracket, screening frequency and screening method: review of recent evidence and comparison with the Portuguese performance indicator

Esta revisão teve por objetivo avaliar a força de evidência do indicador de desempenho português relativo ao rastreio do Câncer do Colo do Útero (CCU): (1) limites etários das mulheres da população geral que o devem realizar, a (2) periodicidade com que deve ser realizado e (3) qual o melhor exame de rastreio. Foram pesquisados os seguintes termos MeSH: vaginal smears, age groups, periodicity, methods, uterine cervical cancer. Foram excluídos os artigos que não abordavam o objetivo da investigação ou que não fossem redigidos em Inglês, Português ou Espanhol. Para interpretar os artigos selecionados foi utilizada a classificação SORT. Foram encontrados 197 artigos, dos quais seleccionados 9: 1 revisão sistemática (RS), 1 estudo clínico controlado aleatorizado, 2 estudos observacionais retrospectivos e 5 normas de orientação clínica (NOC). Os autores optaram por incluir nesta revisão mais 4 NOCs e 2 RSs por considerarem ser relevantes para a população Portuguesa, apesar de não resultarem da pesquisa efectuada. Os estudos sugerem realização do rastreio entre os 21 e 25 até aos 65 anos, com uma periodicidade trienal usando a citologia convencional. Existe ainda controvérsia no que toca aos 3 objetivos deste artigo (limites etários, frequência e método).The scope of this review was to assess the strength of evidence of Portuguese performance indicators on Cervical Cancer screening: (1) age group of the women that should be screened for cervical cancer; (2) frequency of screening; and (3) the best method for screening. The following MeSH terms were searched: vaginal smears, age groups, periodicity, methods, uterine cervical cancer. Articles not reflecting the study objectives or not available in English, Portuguese or Spanish were excluded. The SORT classification was used to rate the articles selected.Of the 197 articles found, 9 that met all study criteria were selected for inclusion in this review. These included 1 systematic review, 1 randomized controlled clinical trial, 2 retrospective studies and 5 clinical guidelines. The authors also chose to include 4 clinical guidelines and two systematic reviews relevant to the Portuguese population even though they did not appear in the initial search of the literature. The studies suggest screening women between the ages of 21 to 25 years and 65 years of age, once every three years using conventional cytology. There is still controversy regarding the three objectives of this study (target age bracket, screening frequency and screening method)

Polymorphisms in the Mn-SOD and EC-SOD Genes and Their Relationship to Diabetic Neuropathy in Type 1 Diabetes Mellitus

BACKGROUND: Oxidative stress, resulting in a marked increase in the level of oxygen free radicals (OFR), has been implicated in the etiology of diabetic neuropathy (DN). Antioxidant enzymes may protect against the rapid onset and progression of DN, by reducing the excess of OFR and peroxide. Mutations and polymorphisms in the genes encoding such enzymes may therefore result in predisposition to DN. We investigated the role of genes encoding two antioxidant enzymes, mitochondrial (Mn-SOD) and extracellular (EC-SOD) superoxide dismutase, in DN pathogenesis in a Russian population. We studied Ala(-9)Val and Ile58Thr polymorphisms of the Mn-SOD gene and Arg213Gly dimorphism of the EC-SOD gene in type 1 diabetic patients with (n = 82) and without DN (n = 84). RESULTS: We developed and used a new polymerase chain reaction (PCR) assays for rapid detection of polymorphisms. These assays involved the use of mismatch PCR primers to create restriction sites in the amplified product only in presence of the polymorphic base. The PCR product was than digested with BshTI, Eco32I or Eco52I to detect Ala(-9)Val, Ile58Thr or Arg213Gly polymorphic site respectively. The frequencies of the Ala allele (50.6% vs. 68.5%, p < 0.002) and the Ala/Ala genotype (17.1% vs. 39.3%, p < 0.005) of the Mn-SOD gene were significantly lower in DN patients than in diabetic subjects without DN. In contrast, the Val allele (49.4% vs. 31.5%, p < 0.002) and the Val/Val genotype (15.9% vs. 2.4%, p < 0.01) were significantly more frequent in the DN patients than in the control group. CONCLUSIONS: Ala(-9)Val substitution in the Mn-SOD gene was associated with DN in a Russian populatio

Loss of heterozygosity at chromosome 1p in different solid human tumours: association with survival

The distal half of chromosome 1p was analysed with 15 polymorphic microsatellite markers in 683 human solid tumours at different locations. Loss of heterozygosity (LOH) was observed at least at one site in 369 cases or 54% of the tumours. LOHs detected ranged from 30–64%, depending on tumour location. The major results regarding LOH at different tumour locations were as follows: stomach, 20/38 (53%); colon and rectum, 60/109 (55%); lung, 38/63 (60%); breast, 145/238 (61%); endometrium, 18/25 (72%); ovary, 17/31 (55%); testis, 11/30 (37%); kidney, 22/73 (30%); thyroid, 4/14 (29%); and sarcomas, 9/14 (64%). High percentages of LOH were seen in the 1p36.3, 1p36.1, 1p35–p34.3, 1p32 and 1p31 regions, suggesting the presence of tumour-suppressor genes. All these regions on chromosome 1p show high LOH in more than one tumour type. However, distinct patterns of LOH were detected at different tumour locations. There was a significant separation of survival curves, with and without LOH at chromosome 1p, in the breast cancer patients. Multivariate analysis showed that LOH at 1p in breast tumours is a better indicator for prognosis than the other variables tested in our model, including nodal metastasis. © 1999 Cancer Research Campaig

Improving tribological properties of cast Al-Si alloys through application of wear-resistant thermal spray coatings

Flame Spray Thermal Spray coatings are low-cost, high-wear surface-treatment technologies. However, little has been reported on their potential effects on cast automotive aluminum alloys. The aim of this research was to investigate the tribological properties of as-sprayed NiCrBSi and WC/12Co Flame Spray coatings applied to two cast aluminum alloys: high-copper LM24 (AlSi8Cu3Fe), and low-copper LM25 (AlSi7Mg). Potential interactions between the mechanical properties of the substrate and the deposited coatings were deemed to be significant. Microstructural, microhardness, friction, and wear (pin-on-disk, microabrasion, Taber abrasion, etc.) results are reported, and the performance differences between coatings on the different substrates were noted. The coefficient of friction was reduced from 0.69-0.72 to 0.12-0.35. Wear (pin-on-disk) was reduced by a factor of 103-104, which was related to the high surface roughness of the coatings. Microabrasion wear was dependent on coating hardness and applied load. Taber abrasion results showed a strong dependency on the substrate, coating morphology, and homogeneity

A systematic review of rodent pest research in Afro-Malagasy small-holder farming systems: Are we asking the right questions?

Rodent pests are especially problematic in terms of agriculture and public health since they can inflict considerable economic damage associated with their abundance, diversity, generalist feeding habits and high reproductive rates. To quantify rodent pest impacts and identify trends in rodent pest research impacting on small-holder agriculture in the Afro-Malagasy region we did a systematic review of research outputs from 1910 to 2015, by developing an a priori defined set of criteria to allow for replication of the review process. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We reviewed 162 publications, and while rodent pest research was spatially distributed across Africa (32 countries, including Madagascar), there was a disparity in number of studies per country with research biased towards four countries (Tanzania [25%], Nigeria [9%], Ethiopia [9%], Kenya [8%]) accounting for 51% of all rodent pest research in the Afro-Malagasy region. There was a disparity in the research themes addressed by Tanzanian publications compared to publications from the rest of the Afro-Malagasy region where research in Tanzania had a much more applied focus (50%) compared to a more basic research approach (92%) in the rest of the Afro-Malagasy region. We found that pest rodents have a significant negative effect on the Afro-Malagasy small-holder farming communities. Crop losses varied between cropping stages, storage and crops and the highest losses occurred during early cropping stages (46% median loss during seedling stage) and the mature stage (15% median loss). There was a scarcity of studies investigating the effectiveness of various management actions on rodent pest damage and population abundance. Our analysis highlights that there are inadequate empirical studies focused on developing sustainable control methods for rodent pests and rodent pests in the Africa-Malagasy context is generally ignored as a research topic