670 research outputs found
Osteochondritis dissecans and Osgood Schlatter disease in a family with Stickler syndrome
<p>Abstract</p> <p>Purpose</p> <p>Stickler syndrome is among the most common autosomal dominant connective tissue disorders but is often unrecognised and therefore not diagnosed by clinicians. Despite much speculation, the cause of osteochondrosis in general and osteochondritis dissecans (OCD) and Osgood Schlatter syndrome (OSS) in particular remain unclear. Etiological understanding is essential. We describe a pair of family subjects presented with OCD and OSS as a symptom complex rather than a diagnosis.</p> <p>Methods</p> <p>Detailed clinical and radiographic examinations were undertaken with emphasis on the role of MRI imaging. Magnetic resonance imaging may allow early prediction of articular lesion healing potential in patients with Stickler syndrome.</p> <p>Results</p> <p>The phenotype of Stickler syndrome can be diverse and therefore misleading. The expectation that the full clinical criteria of any given genetic disorder such as Stickler syndrome will always be present can easily lead to an underestimation of these serious inheritable disorders. We report here two family subjects, a male proband and his aunt (paternal sister), both presented with the major features of Stickler syndrome. Tall stature with marfanoid habitus, astigmatism/congenital vitreous abnormality and submucus cleft palate/cleft uvula, and enlarged painful joints with early onset osteoarthritis. Osteochondritis dissecans (OCD) and Osgood Schlatter syndrome (OSS) were the predominating joint abnormalities.</p> <p>Conclusion</p> <p>We observed that the nature of the articular and physeal abnormalities was consistent with a localised manifestation of a more generalised epiphyseal dysplasia affecting the weight-bearing joints. In these two patients, OCD and OSS appeared to be the predominant pathologic musculoskeletal consequences of an underlying Stickler's syndrome. It is empirical to consider generalised epiphyseal dysplasia as a major underlying causation that might drastically affect the weight-bearing joints.</p
A Systematic Review of Mosquito Coils and Passive Emanators: Defining Recommendations for Spatial Repellency Testing Methodologies.
Mosquito coils, vaporizer mats and emanators confer protection against mosquito bites through the spatial action of emanated vapor or airborne pyrethroid particles. These products dominate the pest control market; therefore, it is vital to characterize mosquito responses elicited by the chemical actives and their potential for disease prevention. The aim of this review was to determine effects of mosquito coils and emanators on mosquito responses that reduce human-vector contact and to propose scientific consensus on terminologies and methodologies used for evaluation of product formats that could contain spatial chemical actives, including indoor residual spraying (IRS), long lasting insecticide treated nets (LLINs) and insecticide treated materials (ITMs). PubMed, (National Centre for Biotechnology Information (NCBI), U.S. National Library of Medicine, NIH), MEDLINE, LILAC, Cochrane library, IBECS and Armed Forces Pest Management Board Literature Retrieval System search engines were used to identify studies of pyrethroid based coils and emanators with key-words "Mosquito coils" "Mosquito emanators" and "Spatial repellents". It was concluded that there is need to improve statistical reporting of studies, and reach consensus in the methodologies and terminologies used through standardized testing guidelines. Despite differing evaluation methodologies, data showed that coils and emanators induce mortality, deterrence, repellency as well as reduce the ability of mosquitoes to feed on humans. Available data on efficacy outdoors, dose-response relationships and effective distance of coils and emanators is inadequate for developing a target product profile (TPP), which will be required for such chemicals before optimized implementation can occur for maximum benefits in disease control
Concurrence of Danish Dementia and Cataract: Insights from the Interactions of Dementia Associated Peptides with Eye Lens α-Crystallin
Familial Danish Dementia (FDD) is an autosomal disease, which is distinguished by gradual loss of vision, deafness, progressive ataxia and dementia. Cataract is the first manifestation of the disease. In this article, we demonstrate a specific correlation between the poisoning of the chaperone activity of the rat eye lens α-crystallins, loss of lens transparency in organ culture by the pathogenic form of the Danish dementia peptide, i.e. the reduced Danish dementia peptide (redADan peptide), by a combination of ex vivo, in vitro, biophysical and biochemical techniques. The interaction of redADan peptide and lens crystallins are very specific when compared with another chaperone, HSP-70, underscoring the specificity of the pathogenic form of Danish dementia peptide, redADan, for the early onset of cataract in this disease
Outdoor host seeking behaviour of Anopheles gambiae mosquitoes following initiation of malaria vector control on Bioko Island, Equatorial Guinea
<p>Abstract</p> <p>Background</p> <p>Indoor-based anti-vector interventions remain the preferred means of reducing risk of malaria transmission in malaria endemic areas around the world. Despite demonstrated success in reducing human-mosquito interactions, these methods are effective solely against endophilic vectors. It may be that outdoor locations serve as an important venue of host seeking by <it>Anopheles gambiae </it>sensu lato (s.l.) mosquitoes where indoor vector suppression measures are employed. This paper describes the host seeking activity of anopheline mosquito vectors in the Punta Europa region of Bioko Island, Equatorial Guinea. In this area, <it>An. gambiae </it>sensu stricto (s.s.) is the primary malaria vector. The goal of the paper is to evaluate the importance of <it>An gambiae </it>s.l. outdoor host seeking behaviour and discuss its implications for anti-vector interventions.</p> <p>Methods</p> <p>The venue and temporal characteristics of host seeking by anopheline vectors in a hyperendemic setting was evaluated using human landing collections conducted inside and outside homes in three villages during both the wet and dry seasons in 2007 and 2008. Additionally, five bi-monthly human landing collections were conducted throughout 2009. Collections were segregated hourly to provide a time distribution of host-seeking behaviour.</p> <p>Results</p> <p>Surprisingly high levels of outdoor biting by <it>An. gambiae </it>senso stricto and <it>An. melas </it>vectors were observed throughout the night, including during the early evening and morning hours when human hosts are often outdoors. As reported previously, <it>An. gambiae </it>s.s. is the primary malaria vector in the Punta Europa region, where it seeks hosts outdoors at least as much as it does indoors. Further, approximately 40% of <it>An. gambiae </it>s.l. are feeding at times when people are often outdoors, where they are not protected by IRS or LLINs. Repeated sampling over two consecutive dry-wet season cycles indicates that this result is independent of seasonality.</p> <p>Conclusions</p> <p><it>An. gambiae </it>s.l. mosquitoes currently seek hosts in outdoor venues as much as indoors in the Punta Europa region of Bioko Island. This contrasts with an earlier pre-intervention observation of exclusive endophagy of <it>An. gambiae </it>in this region. In light of this finding, it is proposed that the long term indoor application of insecticides may have resulted in an adaptive shift toward outdoor host seeking in <it>An. gambiae </it>s.s. on Bioko Island.</p
Recurrence of Diabetic Pedal Ulcerations Following Tendo-Achilles Lengthening
Foot and ankle surgeons are frequently challenged by the devastating systemic consequences of diabetes mellitus manifested through neuropathy, integumentary and joint breakdown, delayed healing, decreased ability to fight infection, and fragile tendon/ligaments. Diabetic neuropathic pedal ulcerations lead to amputations at an alarming rate and also carry a high mortality rate. This article will discuss causes of diabetic pedal ulcerations that persist or recur after tendo-Achilles lengthening and will highlight areas that need to be addressed by the practitioner such as infection, vascular and nutritional status, glucose control, off-loading, biomechanics, and patient compliance
Time-aging time-stress superposition in soft glass under tensile deformation field
We have studied the tensile deformation behaviour of thin films of aging
aqueous suspension of Laponite, a model soft glassy material, when subjected to
a creep flow field generated by a constant engineering normal stress. Aqueous
suspension of Laponite demonstrates aging behaviour wherein it undergoes time
dependent enhancement of its elastic modulus as well as its characteristic
relaxation time. However, under application of the normal stress, the rate of
aging decreases and in the limit of high stress, the aging stops with the
suspension now undergoing a plastic deformation. Overall, it is observed that
the aging that occurs over short creep times at small normal stresses is same
as the aging that occurs over long creep times at large normal stresses. This
observation allows us to suggest an aging time - process time - normal stress
superposition principle, which can predict rheological behaviour at longer
times by carrying out short time tests.Comment: 26 pages, 7 figures, To appear in Rheologica Act
Cardiac resynchronization therapy guided by late gadolinium-enhancement cardiovascular magnetic resonance
Telomerase activity as an adjunct to high-risk human papillomavirus types 16 and 18 and cytology screening in cervical cancer
Telomerase is a ribonucleoprotein comprising an RNA template, the telomerase-associated protein and its catalytic subunit, human telomerase reverse transcriptase (hTERT). Telomerase activation is a critical step in cellular immortalisation and development of cancer. Enhanced telomerase activity has been demonstrated in cervical cancer. In the present study telomerase activity and hTERT mRNA expression were evaluated and correlated with the presence of human papillomavirus (HPV) infection and cytological changes in the cervical lesions. Telomerase activity was assayed by telomeric repeat amplification protocol, hTERT mRNA expression by reverse transcriptase polymerase chain reaction and presence of high risk HPV (HR-HPV) infection by polymerase chain reaction. Out of 154 cervical samples of different cytology, 90 (58.44%) were positive for HR-HPV types 16/18, while among 55 normal cervical scrapes, 10 (18.18%) were HPV DNA positive. All 59 invasive cancer samples showed a very high telomerase activity. Among dysplasia, seven (63.6%) mild dysplasia, 18 (100%) of moderate, 20 (100%) of severe dysplasia and 6 (100%) carcinoma in situ (CIS) samples were positive with mild to moderate to high to very high telomerase activity respectively. Seven (12.7%) samples of apparently normal cervical scrapes were weakly positive for telomerase activity. We observed a good correlation (P<0.001) between telomerase activity and HR-HPV 16/18 positivity with a sensitivity of 88.1% for HPV and 100% for telomerase activity. It is suggested that telomerase activity may be used as an adjunct to cytology and HPV DNA testing in triaging women with cervical lesions
The zinc finger domain of Wilms' tumor 1 suppressor gene (WT1) behaves as a dominant negative, leading to abrogation of WT1 oncogenic potential in breast cancer cells
Abstract
Introduction
There is growing evidence that the Wilms' tumor 1 suppressor gene (WT1) behaves as an oncogene in some forms of breast cancer. Previous studies have demonstrated that the N-terminal domain of WT1 can act as a dominant negative through self-association. In the studies presented here we have explored the potential for the zinc finger domain (ZF) of WT1 to also have dominant-negative effects, and thus further our understanding of this protein.
Methods
Using full-length and ZF-only forms of WT1 we assessed their effect on the WT1 and c-myc promoter using luciferase and chromatin immunoprecipitation assays. The gene expression levels were determined by quantitative real-time RT-PCR, northern blot and western blot. We also assessed the effect of the ZF-only form on the growth of breast cancer cell lines in culture.
Results
Transfection with WT1–ZF plasmids resulted in a stronger inhibition of WT1 promoter than full-length WT1 in breast cancer cells. The WT1–ZF form lacking the lysine–threonine–serine (KTS) insert (ZF - KTS) can bind to the majority of WT1 consensus sites throughout the WT1 promoter region, while the ZF containing the insert (ZF + KTS) form only binds to sites in the proximal promoter. The abundances of endogenous WT1 mRNA and protein were markedly decreased following the stable expression of ZF - KTS in breast cancer cells. The expressions of WT1 target genes, including c-myc, Bcl-2, amphiregulin and TERT, were similarly suppressed by ZF - KTS. Moreover, WT1–ZF - KTS abrogated the transcriptional activation of c-myc mediated by all four predominant isoforms of WT1 (including or lacking alternatively spliced exons 5 and 9). Finally, WT1–ZF - KTS inhibited colony formation and cell division, but induced apoptosis in MCF-7 cells.
Conclusion
Our observations strongly argue that the WT1–ZF plasmid behaves as a dominant-negative regulator of the endogenous WT1 in breast cancer cells. The inhibition on proliferation of breast cancer cells by WT1–ZF - KTS provides a potential candidate of gene therapy for breast cancer
Modelling reconfigurable manufacturing systems with coloured timed Petri nets
International audienceReconfigurable manufacturing systems (RMSs) have been acknowledged as a promising means of providing manufacturing companies with the required production capacities and capabilities. This is accomplished through reconfiguring system elements over time for a diverse set of individualized products often required in small quantities and with short delivery lead times. Recognizing the importance of dynamic modeling and visualization in decision-making support in RMSs and the limitations of current research, we propose in this work to model RMSs with Petri net (PN) techniques focusing on the process of reconfiguring system elements while considering constraints and system performance. In view of the modeling challenges, including variety handling, production variation accommodation, machine selection, and constraint satisfaction, we develop a new formalism of colored timed PNs. In conjunction with colored tokens and timing in colored and timed PNs, we also define a reconfiguration mechanism to meet modeling challenges. An application case from an electronics company producing mobile phone vibration motors is presented. Also reported are system analysis and application results, which show how the proposed formalism can be used in the reconfiguration decision making process
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