EnzyMiner: automatic identification of protein level mutations and their impact on target enzymes from PubMed abstracts

BACKGROUND: A better understanding of the mechanisms of an enzyme's functionality and stability, as well as knowledge and impact of mutations is crucial for researchers working with enzymes. Though, several of the enzymes' databases are currently available, scientific literature still remains at large for up-to-date source of learning the effects of a mutation on an enzyme. However, going through vast amounts of scientific documents to extract the information on desired mutation has always been a time consuming process. In this paper, therefore, we describe an unique method, termed as EnzyMiner, which automatically identifies the PubMed abstracts that contain information on the impact of a protein level mutation on the stability and/or the activity of a given enzyme. RESULTS: We present an automated system which identifies the abstracts that contain an amino-acid-level mutation and then classifies them according to the mutation's effect on the enzyme. In the case of mutation identification, MuGeX, an automated mutation-gene extraction system has an accuracy of 93.1% with a 91.5 F-measure. For impact analysis, document classification is performed to identify the abstracts that contain a change in enzyme's stability or activity resulting from the mutation. The system was trained on lipases and tested on amylases with an accuracy of 85%. CONCLUSION: EnzyMiner identifies the abstracts that contain a protein mutation for a given enzyme and checks whether the abstract is related to a disease with the help of information extraction and machine learning techniques. For disease related abstracts, the mutation list and direct links to the abstracts are retrieved from the system and displayed on the Web. For those abstracts that are related to non-diseases, in addition to having the mutation list, the abstracts are also categorized into two groups. These two groups determine whether the mutation has an effect on the enzyme's stability or functionality followed by displaying these on the web

Double-plating of ovine critical sized defects of the tibia: a low morbidity model enabling continuous in vivo monitoring of bone healing

<p>Abstract</p> <p>Background</p> <p>Recent studies using sheep critical sized defect models to test tissue engineered products report high morbidity and complications rates. This study evaluates a large bone defect model in the sheep tibia, stabilized with two, a novel Carbon fibre Poly-ether-ether-ketone (CF-PEEK) and a locking compression plate (LCP) which could sustain duration for up to 6 month with an acceptable low complication rate.</p> <p>Methods</p> <p>A large bone defect of 3 cm was performed in the mid diaphysis of the right tibia in 33 sheep. The defect was stabilised with the CF - PEEK plate and an LCP. All sheep were supported with slings for 8 weeks after surgery. The study was carried out for 3 months in 6 and for 6 months in 27 animals.</p> <p>Results</p> <p>The surgical procedure could easily be performed in all sheep and continuous in vivo radiographic evaluation of the defect was possible. This long bone critical sized defect model shows with 6.1% a low rate of complications compared with numbers mentioned in the literature.</p> <p>Conclusions</p> <p>This experimental animal model could serve as a standard model in comparative research. A well defined standard model would reduce the number of experimental animals needed in future studies and would therefore add to ethical considerations.</p

Unilateral optic neuropathy following subdural hematoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Unilateral optic neuropathy is commonly due to a prechiasmatic affliction of the anterior visual pathway, while losses in visual hemifields result from the damage to brain hemispheres. Here we report the unusual case of a patient who suffered from acute optic neuropathy following hemispherical subdural hematoma. Although confirmed up to now only through necropsy studies, our case strongly suggests a local, microcirculatory deficit identified through magnetic resonance imaging <it>in vivo</it>.</p> <p>Case presentation</p> <p>A 70-year-old Caucasian German who developed a massive left hemispheric subdural hematoma under oral anticoagulation presented with acute, severe visual impairment on his left eye, which was noticed after surgical decompression. Neurologic and ophthalmologic examinations indicated sinistral optic neuropathy with visual acuity reduced nearly to amaurosis. Ocular pathology such as vitreous body hemorrhage, papilledema, and central retinal artery occlusion were excluded. An orbital lesion was ruled out by means of orbital magnetic resonance imaging. However, cerebral diffusion-weighted imaging and T2 maps of magnetic resonance imaging revealed a circumscribed ischemic lesion within the edematous, slightly herniated temporomesial lobe within the immediate vicinity of the affected optic nerve. Thus, the clinical course and morphologic magnetic resonance imaging findings suggest the occurrence of pressure-induced posterior ischemic optic neuropathy due to microcirculatory compromise.</p> <p>Conclusion</p> <p>Although lesions of the second cranial nerve following subdural hematoma have been reported individually, their pathogenesis was preferentially proposed from autopsy studies. Here we discuss a dual, pressure-induced and secondarily ischemic pathomechanism on the base of <it>in vivo </it>magnetic resonance imaging diagnostics which may remain unconsidered by computed tomography.</p

The association of health literacy with adherence in older 2 adults, and its role in interventions: a systematic meta-review

Background: Low health literacy is a common problem among older adults. It is often suggested to be associated with poor adherence. This suggested association implies a need for effective adherence interventions in low health literate people. However, previous reviews show mixed results on the association between low health literacy and poor adherence. A systematic meta-review of systematic reviews was conducted to study the association between health literacy and adherence in adults above the age of 50. Evidence for the effectiveness of adherence interventions among adults in this older age group with low health literacy was also explored. Methods: Eight electronic databases (MEDLINE, ERIC, EMBASE, PsycINFO, CINAHL, DARE, the Cochrane Library, and Web of Knowledge) were searched using a variety of keywords regarding health literacy and adherence. Additionally, references of identified articles were checked. Systematic reviews were included if they assessed the association between health literacy and adherence or evaluated the effectiveness of interventions to improve adherence in adults with low health literacy. The AMSTAR tool was used to assess the quality of the included reviews. The selection procedure, data-extraction, and quality assessment were performed by two independent reviewers. Seventeen reviews were selected for inclusion. Results: Reviews varied widely in quality. Both reviews of high and low quality found only weak or mixed associations between health literacy and adherence among older adults. Reviews report on seven studies that assess the effectiveness of adherence interventions among low health literate older adults. The results suggest that some adherence interventions are effective for this group. The interventions described in the reviews focused mainly on education and on lowering the health literacy demands of adherence instructions. No conclusions could be drawn about which type of intervention could be most beneficial for this population. Conclusions: Evidence on the association between health literacy and adherence in older adults is relatively weak. Adherence interventions are potentially effective for the vulnerable population of older adults with low levels of health literacy, but the evidence on this topic is limited. Further research is needed on the association between health literacy and general health behavior, and on the effectiveness of interventions

Spatio-temporal Models of Lymphangiogenesis in Wound Healing

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total

Predictors of early sexual initiation among a nationally representative sample of Nigerian adolescents

<p>Abstract</p> <p>Background</p> <p>Early sexual debut among adolescents is associated with considerable negative heath and development outcomes. An understanding of the determinants or predictors of the timing of sexual debut is important for effective intervention, but very few studies to date have addressed this issue in the Nigerian context. The aim of the present study is to examine predictors of adolescent sexual initiation among a nationally representative sample of adolescents in Nigeria.</p> <p>Methods</p> <p>Interviewer-collected data of 2,070 never-married adolescents aged 15–19 years were analysed to determine association between age of sexual debut and demographic, psychosocial and community factors. Using Cox proportional hazards regression multivariate analysis was carried out with two different models – one with and the other without psychosocial factors. Hazard ratio (HR) and 95% confidence interval (CI) were calculated separately for males and females.</p> <p>Results</p> <p>A fifth of respondents (18% males; 22% females) were sexually experienced. In the South 24.3% males and 28.7% females had initiated sex compared to 12.1% of males and 13.1% females in the North (p < 0.001). In the first model, only region was significantly associated with adolescent sexual initiation among both males and females; however, educational attainment and age were also significant among males. In the second (psychosocial) model factors associated with adolescent sexual debut for both genders included more positive attitudes regarding condom efficacy (males: HR = 1.28, 95% CI = 1.07–1.53; females: HR = 1.24, 95% CI = 1.05–1.46) and more positive attitudes to family planning use (males: HR = 1.19, 95% CI = 1.09–1.31; females: HR = 1.18, 95% CI = 1.07–1.30). A greater perception of condom access (HR = 1.42, 95% CI = 1.14–1.76) and alcohol use (HR = 1.90, 95% CI = 1.38–2.62) among males and positive gender-related attitudes (HR = 1.13, 95% CI = 1.04–1.23) among females were also associated with increased likelihood of adolescent sexual initiation. Conversely, personal attitudes in favour of delayed sexual debut were associated with lower sexual debut among both males (males: HR = 0.36, 95% CI = 0.25–0.52) and females (HR = 0.38, 95% CI = 0.25–0.57). Higher level of religiosity was associated with lower sexual debut rates only among females (HR = 0.59, 95% CI = 0.37–0.94).</p> <p>Conclusion</p> <p>Given the increased risk for a number of sexually transmitted health problems, understanding the factors that are associated with premarital sexual debut will assist programmes in developing more effective risk prevention interventions.</p

Prevalence of Mistreatment or Belittlement among Medical Students – A Cross Sectional Survey at a Private Medical School in Karachi, Pakistan

Background: Mistreatment or belittlement of medical students either by faculty or fellow students has often been reported. Perception of mistreatment has also been associated with increased degree of psychological morbidity. There is a lack of such studies being conducted amongst the medical students of Pakistan. The aim of this study was to determine the prevalence and forms of perceived mistreatment and presence of mental health morbidity in a private medical school in Pakistan. Also, any association between mental health morbidity and mistreatment was to be identified. Methods: A cross sectional study was carried out on medical students from Aga Khan University Hospital, Karachi, Pakistan during the period of June-September 2007. A self administered questionnaire, adapted from Frank et al and Baldwin et al was distributed to a total of 350 students. The questionnaire consisted of three parts: the first dealing with the demographics of the population, the second concerning the various forms of mistreatment, while the third assessed the mental health of students using the General Health Questionnaire 12(GHQ12). Descriptive statistics were performed. The Chi-square test and Fisher\u27s exact tests were applied. Results: A total of 350 students were approached out of which 232 completed the questionnaire giving a response rate of 66.2%. Mistreatment was reported by 62.5% (145/232) of the respondents. Of these, 69.7% (83/145) were males and 54.9% (62/145) were females. There was a significant relationship between gender, year division, stress at medical school and possible use of drugs/alcohol and reported mistreatment but no statistical relationship was seen with psychiatric morbidity. The overall prevalence of psychological morbidity was 34.8% (77/221). Conclusion: This study suggests high prevalence of perceived mistreatment and psychological morbidity among Pakistani medical students. However, no association was found between these two aspects of medical student education. There is a need to bring about changes to make the medical education environment conducive to learning. Increased student feedback, support systems and guidance about progress throughout the year and the provision of adequate learning resources may provide help with resolving both of these issues

The Relative Role of Perceived Partner Risks in Promoting Condom Use in a Three-City Sample of High-Risk, Low-Income Women

We examined the effect of women’s perceptions of sexual partner risks on condom use. Women from three US cities (n = 1,967) were recruited to provide data on HIV risks. In univariate models, increased odds of condom use were associated with perceiving that partners had concurrent partners and being unaware of partners': (a) HIV status, (b) bisexuality, (c) concurrency; and/or (d) injection drug use. In multivariate models, neither being unaware of the four partner risk factors nor perceiving a partner as being high risk was associated with condom use. Contextual factors associated with decreased odds of condom use were having sex with a main partner, homelessness in the past year, alcohol use during sex, and crack use in the past 30 days. Awareness of a partner’s risks may not be sufficient for increasing condom use. Contextual factors, sex with a main partner in particular, decrease condom use despite awareness of partner risk factors

c-di-AMP Is a New Second Messenger in Staphylococcus aureus with a Role in Controlling Cell Size and Envelope Stress.

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