An epidemiological study of temporomandibular joint ankylosis

PubMed Central

Gupta, Vinay Kumar; Mehrotra, Divya; Malhotra, Seema; Kumar, Sandeep; Agarwal, Girdhar Gopal; Pal, Uma Shanker

2012-01-01

Introduction: The temporomandibular joint (TMJ) forms the very cornerstone of craniofacial integrity and its ankylosis in a growing child may cause problems in daily food intake, speech, appearance, and oral hygiene is affected to a major extent. It is one of the common acquired pathologies afflicting the skeleton. It is also the most overlooked and under-managed problem in children. Materials and Methods: A house to house survey was conducted between 2010 and 2011 in rural and urban areas of Lucknow. A total of 21,720 children aged between 3-15 years from 9090 houses comprising a representative sample were included. Results: Ten TMJ ankylosis cases were identified in 21,720 children. Of these, six were bilateral and four were unilateral. Male to female ratio was 1:9, with most patients (70.0%) being in the 10-15 years’ age group (mean age was 11.1 years ± 3.34). The most common cause of ankylosis was trauma for 90.0% of cases. The majority of patients (70%) were reporting the condition for the first time, with 30% patients having had previous treatment. Conclusion: TMJ ankylosis is an acquired condition in most of the cases. Birth/childhood trauma would be the major causative factor. Knowledge amongst parents, providers of health about this entity was poor. Initial management of the causative factor was poor. Mere knowledge among the general population and healthcare providers can result in primary prevention and also secondary prevention along with its successful definitive treatment. PMID:23251054

Development of a methodology for accident causation research

DOT National Transportation Integrated Search

1983-06-01

The obj ective of this study was to fully develop and apply a me thodology to : study accident causation, uhich was outlined in a previous study . " Causal" factors : are those pre-crash factors, which are statistically related to the accident rate :...

Time, space and form: Necessary for causation in health, disease and intervention?

PubMed

Evans, David W; Lucas, Nicholas; Kerry, Roger

2016-06-01

Sir Austin Bradford Hill's 'aspects of causation' represent some of the most influential thoughts on the subject of proximate causation in health and disease. Hill compiled a list of features that, when present and known, indicate an increasing likelihood that exposure to a factor causes-or contributes to the causation of-a disease. The items of Hill's list were not labelled 'criteria', as this would have inferred every item being necessary for causation. Hence, criteria that are necessary for causation in health, disease and intervention processes, whether known, knowable, or not, remain undetermined and deserve exploration. To move beyond this position, this paper aims to explore factors that are necessary in the constitution of causative relationships between health, disease processes, and intervention. To this end, disease is viewed as a causative pathway through the often overlapping stages of aetiology, pathology and patho-physiology. Intervention is viewed as a second, independent causative pathway, capable of causing changes in health for benefit or harm. For the natural course of a disease pathway to change, we argue that intervention must not only occupy the same time and space, but must also share a common form; the point at which the two pathways converge and interact. This improved conceptualisation may be used to facilitate the interpretation of clinical observations and inform future research, particularly enabling predictions of the mechanistic relationship between health, disease and intervention.

Pediatric epilepsy: The Indian experience

PubMed Central

Gadgil, Pradnya; Udani, Vrajesh

2011-01-01

Epilepsy is a common clinical entity in neurology clinics. The understanding of the genetics of epilepsy has undergone a sea change prompting re-classification by the International league against epilepsy recently. The prevalence rates of epilepsy in India are similar to those of developed nations. However, the large treatment gap is a major challenge to our public health system. Perinatal injuries are a major causative factor in pediatric group. We have discussed a few common etiologies such as neurocysticercosis and newer genetic epilepsy syndromes. We have also briefly touched upon the Indian experience in pediatric epilepsy surgery. PMID:22069423

Zinc absorption from low phytic acid genotypes of maize (Zea mays L.), barley (Hordeum vulgare L.) and rice (Oryza sativa L.) assessed in a suckling rat pup model

USDA-ARS?s Scientific Manuscript database

Phytic acid (PA) is an inhibitor of zinc (Zn) absorption. Because dietary PA is a major causative factor for low Zn bioavailability from most diets, a reduction in the PA content of staple diets is likely to improve Zn nutrition in populations of risk of Zn deficiency. Reducing the PA content of mai...

Host, vehicular and environmental factors responsible for road traffic crashes in a Nigerian city: identifiable issues for road traffic injury control.

PubMed

Adeoye, Peter Oladapo; Kadri, Dotun Musiliu; Bello, Jibril Oyekunle; Ofoegbu, Chima Kingsley Pascal; Abdur-Rahman, Lukman Olajide; Adekanye, Adedeji Olugbenga; Solagberu, Babatunde Akeeb

2014-01-01

Road traffic injury (RTI) has assumed major public health importance world-wide and the burden is heavier on the health-care infrastructure of countries in Sub-Saharan Africa. In Nigeria, RTI is the leading cause of trauma related morbidity and mortality. While there are some published epidemiological reports on RTI in the region, studies on the mechanism of causation of road traffic crashes (RTC) are not available. Over a 9-month period, we prospectively captured the 571 victims of RTC presenting to a single tertiary health care center in Nigeria. Data collected include demographic data, Mechanism of causation of RTC, Injuries sustained and outcomes. Over three-quarters of the victims are young people and half were either traders (27.5%) or students (20%). Pedestrians, motorcycle riders and open truck occupants (people sitting at the rear loading compartment of trucks) often had fatal injuries. Analysis of collision patterns showed that lone crashes were the most frequent though car-to-motorcycle crashes caused a quarter of the deaths. Host factors (over-speeding driver, driver misjudgment, sleeping driver etc.) were responsible for four-fifths of the crashes while vehicular and environmental factors accounted for the remaining. On binary regression analysis, head injured victims had higher odds of dying than the non-head injured (Odds ratio = 6.5). This paper elucidates the mechanisms of causation of and types of injuries sustained following RTC in Nigeria and thus provide opportunities for prevention and control of this unacceptable situation.

Host, vehicular and environmental factors responsible for road traffic crashes in a nigerian city: identifiable issues for road traffic injury control

PubMed Central

Adeoye, Peter Oladapo; Kadri, Dotun Musiliu; Bello, Jibril Oyekunle; Ofoegbu, Chima Kingsley Pascal; Abdur-Rahman, Lukman Olajide; Adekanye, Adedeji Olugbenga; Solagberu, Babatunde Akeeb

2014-01-01

Introduction Road traffic injury (RTI) has assumed major public health importance world-wide and the burden is heavier on the health-care infrastructure of countries in Sub-Saharan Africa. In Nigeria, RTI is the leading cause of trauma related morbidity and mortality. While there are some published epidemiological reports on RTI in the region, studies on the mechanism of causation of road traffic crashes (RTC) are not available. Methods Over a 9-month period, we prospectively captured the 571 victims of RTC presenting to a single tertiary health care center in Nigeria. Data collected include demographic data, Mechanism of causation of RTC, Injuries sustained and outcomes. Results Over three-quarters of the victims are young people and half were either traders (27.5%) or students (20%). Pedestrians, motorcycle riders and open truck occupants (people sitting at the rear loading compartment of trucks) often had fatal injuries. Analysis of collision patterns showed that lone crashes were the most frequent though car-to-motorcycle crashes caused a quarter of the deaths. Host factors (over-speeding driver, driver misjudgment, sleeping driver etc.) were responsible for four-fifths of the crashes while vehicular and environmental factors accounted for the remaining. On binary regression analysis, head injured victims had higher odds of dying than the non-head injured (Odds ratio = 6.5). Conclusion This paper elucidates the mechanisms of causation of and types of injuries sustained following RTC in Nigeria and thus provide opportunities for prevention and control of this unacceptable situation. PMID:25780490

Do bus accidents cause nonepileptic seizures?: complex issues of medicolegal causation.

PubMed

LaFrance, W Curt; Self, Janet A

2008-01-01

The question of causation is approached through a case description and analysis. An alternative perspective is discussed for addressing neuropsychiatric cases in the medicolegal context. Viewing medical litigation from the perspective of risk factors, timeline, and baseline may add clarity to the difficulty of understanding causation.

Applying Bradford Hill's criteria for causation to neuropsychiatry: challenges and opportunities.

PubMed

van Reekum, R; Streiner, D L; Conn, D K

2001-01-01

Establishing an argument of causation is an important research activity with major clinical and scientific implications. Sir Austin Bradford Hill proposed criteria to establish such an argument. These criteria include the strength of the association, consistency, specificity, temporal sequence, biological gradient, biologic rationale, coherence, experimental evidence, and analogous evidence. These criteria are reviewed with the goal of facilitating an increase in rigor for establishing arguments of causation in neuropsychiatry. The challenges and opportunities related to these criteria in neuropsychiatry are reviewed, as are two important arguments for causation: one for poststroke depression and one for brain injury as a cause of psychiatric disorders.

Tendinopathy in diabetes mellitus patients-Epidemiology, pathogenesis, and management.

PubMed

Lui, P P Y

2017-08-01

Chronic tendinopathy is a frequent and disabling musculo-skeletal problem affecting the athletic and general populations. The affected tendon is presented with local tenderness, swelling, and pain which restrict the activity of the individual. Tendon degeneration reduces the mechanical strength and predisposes it to rupture. The pathogenic mechanisms of chronic tendinopathy are not fully understood and several major non-mutually exclusive hypotheses including activation of the hypoxia-apoptosis-pro-inflammatory cytokines cascade, neurovascular ingrowth, increased production of neuromediators, and erroneous stem cell differentiation have been proposed. Many intrinsic and extrinsic risk/causative factors can predispose to the development of tendinopathy. Among them, diabetes mellitus is an important risk/causative factor. This review aims to appraise the current literature on the epidemiology and pathology of tendinopathy in diabetic patients. Systematic reviews were done to summarize the literature on (a) the association between diabetes mellitus and tendinopathy/tendon tears, (b) the pathological changes in tendon under diabetic or hyperglycemic conditions, and (c) the effects of diabetes mellitus or hyperglycemia on the outcomes of tendon healing. The potential mechanisms of diabetes mellitus in causing and exacerbating tendinopathy with reference to the major non-mutually exclusive hypotheses of the pathogenic mechanisms of chronic tendinopathy as reported in the literature are also discussed. Potential strategies for the management of tendinopathy in diabetic patients are presented. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Leishmania major Infection Activates NF-κB and Interferon Regulatory Factors 1 and 8 in Human Dendritic Cells▿

PubMed Central

Jayakumar, Asha; Donovan, Michael J.; Tripathi, Vinita; Ramalho-Ortigao, Marcelo; McDowell, Mary Ann

2008-01-01

The salient feature of dendritic cells (DC) is the initiation of appropriate adaptive immune responses by discriminating between pathogens. Using a prototypic model of intracellular infection, we previously showed that Leishmania major parasites prime human DC for efficient interleukin-12 (IL-12) secretion. L. major infection is associated with self-limiting cutaneous disease and powerful immunity. In stark contrast, the causative agent of visceral leishmaniasis, Leishmania donovani, does not prime human DC for IL-12 production. Here, we report that DC priming by L. major infection results in the early activation of NF-κB transcription factors and the up-regulation and nuclear translocation of interferon regulatory factor 1 (IRF-1) and IRF-8. The inhibition of NF-κB activation by the pretreatment of DC with caffeic acid phenethyl ester blocks L. major-induced IRF-1 and IRF-8 activation and IL-12 expression. We further demonstrate that IRF-1 and IRF-8 obtained from L. major-infected human DC specifically bind to their consensus binding sites on the IL-12p35 promoter, indicating that L. major infection either directly stimulates a signaling cascade or induces an autocrine pathway that activates IRF-1 and IRF-8, ultimately resulting in IL-12 transcription. PMID:18316378

Integrating social science and behavioral genetics: testing the origin of socioeconomic disparities in depression using a genetically informed design.

PubMed

Mezuk, Briana; Myers, John M; Kendler, Kenneth S

2013-10-01

We tested 3 hypotheses-social causation, social drift, and common cause-regarding the origin of socioeconomic disparities in major depression and determined whether the relationship between socioeconomic status (SES) and major depression varied by genetic liability for major depression. Data were from a sample of female twins in the baseline Virginia Adult Twin Study of Psychiatric and Substance Use Disorders interviewed between 1987 and 1989 (n = 2153). We used logistic regression and structural equation twin models to evaluate these 3 hypotheses. Consistent with the social causation hypothesis, education (odds ratio [OR] = 0.78; 95% confidence interval [CI] = 0.66, 0.93; P < .01) and income (OR = 0.93; 95% CI = 0.89, 0.98; P < .01) were significantly related to past-year major depression. Upward social mobility was associated with lower risk of depression. There was no evidence that childhood SES was related to development of major depression (OR = 0.98; 95% CI = 0.89, 1.09; P > .1). Consistent with a common genetic cause, there was a negative correlation between the genetic components of major depression and education (r(2) = -0.22). Co-twin control analyses indicated a protective effect of education and income on major depression even after accounting for genetic liability. This study utilized a genetically informed design to address how social position relates to major depression. Results generally supported the social causation model.

Preventing skin cancer through behavior change. Implications for interventions.

PubMed

Rossi, J S; Blais, L M; Redding, C A; Weinstock, M A

1995-07-01

Sun exposure is the only major causative factor for skin cancer for which prevention is feasible. Both individual and community-based interventions have been effective in changing sun exposure knowledge and attitudes but generally have not been effective in changing behaviors. An integrative model of behavior change is described that has been successful in changing behavior across a wide range of health conditions. This model holds promise for developing a rational public health approach to skin cancer prevention based on sound behavioral science.

Are All Children Equal? Causative Factors of Child Labour in Selected Districts of South Punjab, Pakistan

ERIC Educational Resources Information Center

Haider, Syed Zubair; Qureshi, Ayesha

2016-01-01

The present study investigates the causative factors of child labour in selected districts of South Punjab, Pakistan. As a member of the International Labour Organization (ILO) Pakistan has a responsibility to stamp out child labour from its regions. Our sample was selected from seven working environments (workshops, hotels, tea stalls,…

The coagulopathy in acute promyelocytic leukaemia--what have we learned in the past twenty years.

PubMed

Kwaan, Hau C; Cull, Elizabeth H

2014-03-01

Coagulopathy is a unique component of the pathology of acute promyelocytic leukaemia (APL). Though many causative factors have been elucidated, therapies to rectify the coagulopathy are far from being realised. Thrombotic and bleeding complications remain the major causes of early deaths. In this chapter, the known causes of abnormalities in haemostatic function, namely the coagulopathy and changes in the fibrinolytic system, will be reviewed. Major risk factors for these complications are identified. Current available measures for correction of the coagulopathy and their effectiveness are critically examined. Unless the coagulopathy can be effectively controlled, bleeding complications will remain an obstacle to achieving a cure for this disease. The issues that need to be addressed in next phase of investigations are also discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Unveiling Members of Colletotrichum acutatum Species Complex Causing Colletotrichum Leaf Disease of Hevea brasiliensis in Sri Lanka.

PubMed

Hunupolagama, D M; Chandrasekharan, N V; Wijesundera, W S S; Kathriarachchi, H S; Fernando, T H P S; Wijesundera, R L C

2017-06-01

Colletotrichum is an important fungal genus with great diversity, which causes anthracnose of a variety of crop plants including rubber trees. Colletotrichum acutatum and Colletotrichum gloeosporioides have been identified as the major causative agents of Colletotrichum leaf disease of rubber trees in Sri Lanka based on morphology, pathogenicity, and the analysis of internally transcribed spacer sequences of the nuclear ribosomal DNA. This study has been conducted to investigate the members of the C. acutatum species complex causing rubber leaf disease using a morphological and multi gene approach. For the first time in Sri Lanka, Colletotrichum simmondsii, Colletotrichum laticiphilum, Colletotrichum nymphaeae, and Colletotrichum citri have been identified as causative agents of Colletotrichum leaf disease in addition to C. acutatum s. str. Among them, C. simmondsii has been recognized as the major causative agent.

Migraine and the social selection vs causation hypotheses: a question larger than either/or?

PubMed

Peterlin, B Lee; Scher, Ann I

2013-09-10

For decades, the question of social selection vs social causation has been raised by public health researchers and social scientists to explain the association between socioeconomic factors and mood disorders.(1,2) The social selection or "downward drift" theory postulates that the disease itself limits an individual's educational and occupational achievements, leading to a lower socioeconomic status (SES). In contrast, the social causation hypothesis suggests that factors associated with low SES (e.g., stressful life events, poor health care access) increase the likelihood of disease onset or prolonged disease duration.(3,4) Simply stated, the end result of each hypothesis is as follows:

Pedestrian injury causation parameters. Phase 2

DOT National Transportation Integrated Search

1981-10-01

This report describes data collection, quality control and data analysis procedures for a five-team program to study pedestrian injury causation factors. The data file contains 1,997 pedestrian accidents collected during a two and one-half year perio...

Questions on causality and responsibility arising from an outbreak of Pseudomonas aeruginosa infections in Norway

PubMed Central

Iversen, Bjørn G; Hofmann, Bjørn; Aavitsland, Preben

2008-01-01

In 2002, Norway experienced a large outbreak of Pseudomonas aeruginosa infections in hospitals with 231 confirmed cases. This fuelled intense public and professional debates on what were the causes and who were responsible. In epidemiology, other sciences, in philosophy and in law there is a long tradition of discussing the concept of causality. We use this outbreak as a case; apply various theories of causality from different disciplines to discuss the roles and responsibilities of some of the parties involved. Mackie's concept of INUS conditions, Hill's nine viewpoints to study association for claiming causation, deterministic and probabilistic ways of reasoning, all shed light on the issues of causality in this outbreak. Moreover, applying legal theories of causation (counterfactual reasoning and the "but-for" test and the NESS test) proved especially useful, but the case also illustrated the weaknesses of the various theories of causation. We conclude that many factors contributed to causing the outbreak, but that contamination of a medical device in the production facility was the major necessary condition. The reuse of the medical device in hospitals contributed primarily to the size of the outbreak. The unintended error by its producer – and to a minor extent by the hospital practice – was mainly due to non-application of relevant knowledge and skills, and appears to constitute professional negligence. Due to criminal procedure laws and other factors outside the discourse of causality, no one was criminally charged for the outbreak which caused much suffering and shortening the life of at least 34 people. PMID:18947429

Multiple Statistical Models Based Analysis of Causative Factors and Loess Landslides in Tianshui City, China

NASA Astrophysics Data System (ADS)

Su, Xing; Meng, Xingmin; Ye, Weilin; Wu, Weijiang; Liu, Xingrong; Wei, Wanhong

2018-03-01

Tianshui City is one of the mountainous cities that are threatened by severe geo-hazards in Gansu Province, China. Statistical probability models have been widely used in analyzing and evaluating geo-hazards such as landslide. In this research, three approaches (Certainty Factor Method, Weight of Evidence Method and Information Quantity Method) were adopted to quantitively analyze the relationship between the causative factors and the landslides, respectively. The source data used in this study are including the SRTM DEM and local geological maps in the scale of 1:200,000. 12 causative factors (i.e., altitude, slope, aspect, curvature, plan curvature, profile curvature, roughness, relief amplitude, and distance to rivers, distance to faults, distance to roads, and the stratum lithology) were selected to do correlation analysis after thorough investigation of geological conditions and historical landslides. The results indicate that the outcomes of the three models are fairly consistent.

Causality in cancer epidemiology.

PubMed

Lagiou, Pagona; Adami, Hans-Olov; Trichopoulos, Dimitrios

2005-01-01

In this review, issues of causality in epidemiologic research with emphasis on the aetiology of human cancer are considered. Principles of assessing causation in epidemiological studies of cancer are distinguished into those concerning an individual study, several studies and a particular person. Strengths and weaknesses of various approaches of documenting carcinogenicity in humans are examined and lists of major established causes of human cancer are presented. The review concludes with estimates of mortality from cancer around the world that can be attributed to specific factors under the light of the current scientific knowledge.

Cognitive error as the most frequent contributory factor in cases of medical injury: a study on verdict's judgment among closed claims in Japan.

PubMed

Tokuda, Yasuharu; Kishida, Naoki; Konishi, Ryota; Koizumi, Shunzo

2011-03-01

Cognitive errors in the course of clinical decision-making are prevalent in many cases of medical injury. We used information on verdict's judgment from closed claims files to determine the important cognitive factors associated with cases of medical injury. Data were collected from claims closed between 2001 to 2005 at district courts in Tokyo and Osaka, Japan. In each case, we recorded all the contributory cognitive, systemic, and patient-related factors judged in the verdicts to be causally related to the medical injury. We also analyzed the association between cognitive factors and cases involving paid compensation using a multivariable logistic regression model. Among 274 cases (mean age 49 years old; 45% women), there were 122 (45%) deaths and 67 (24%) major injuries (incomplete recovery within a year). In 103 cases (38%), the verdicts ordered hospitals to pay compensation (median; 8,000,000 Japanese Yen). An error in judgment (199/274, 73%) and failure of vigilance (177/274, 65%) were the most prevalent causative cognitive factors, and error in judgment was also significantly associated with paid compensation (odds ratio, 1.9; 95% confidence interval [CI], 1.0-3.4). Systemic causative factors including poor teamwork (11/274, 4%) and technology failure (5/274, 2%) were less common. The closed claims analysis based on verdict's judgment showed that cognitive errors were common in cases of medical injury, with an error in judgment being most prevalent and closely associated with compensation payment. Reduction of this type of error is required to produce safer healthcare. 2010 Society of Hospital Medicine.

Excessive Cap-dependent Translation as a Molecular Mechanism Underlying ASD

DTIC Science & Technology

2012-08-01

SUPPLEMENTARY NOTES 14. ABSTRACT We hypothesize that excessive cap-dependent translation is a causative factor in autism spectrum disorder...compounds to therapeutically target eIF4E-eIF4G interactions and eIF4A for treating patients with ASD. 15. SUBJECT TERMS autism spectrum...Introduction We hypothesize that excessive cap-dependent translation is a causative factor in autism spectrum disorder (ASD). To test this

Dermatoses of the male genital area.

PubMed

Eichmann, Alfred R

2005-01-01

This is an overview of dermatoses which are predominantly seen in the genital area. Five large groups of dermatoses can be distinguished: inflammatory dermatoses without any causative organism, infections and dermatoses originating from cutaneous appendages, precancerous lesions, pigmented lesions and genital pruritus. The etiology, causative factors, clinical features and newer treatment options are considered. Because of local environmental factors, genital dermatoses often present in a different way than in other localizations.

Environmental Risk Factors for Multiple Sclerosis: A Review with a Focus on Molecular Mechanisms

PubMed Central

O’Gorman, Cullen; Lucas, Robyn; Taylor, Bruce

2012-01-01

Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system commonly affecting young adults. Pathologically, there are patches of inflammation (plaques) with demyelination of axons and oligodendrocyte loss. There is a global latitude gradient in MS prevalence, and incidence of MS is increasing (particularly in females). These changes suggest a major role for environmental factors in causation of disease. We have reviewed the evidence and potential mechanisms of action for three exposures: vitamin D, Epstein Barr virus and cigarette smoking. Recent advances supporting gene-environment interactions are reviewed. Further research is needed to establish mechanisms of causality in humans and to explore preventative strategies. PMID:23109880

Integrating Social Science and Behavioral Genetics: Testing the Origin of Socioeconomic Disparities in Depression Using a Genetically Informed Design

PubMed Central

Myers, John M.; Kendler, Kenneth S.

2013-01-01

Objectives. We tested 3 hypotheses—social causation, social drift, and common cause—regarding the origin of socioeconomic disparities in major depression and determined whether the relationship between socioeconomic status (SES) and major depression varied by genetic liability for major depression. Methods. Data were from a sample of female twins in the baseline Virginia Adult Twin Study of Psychiatric and Substance Use Disorders interviewed between 1987 and 1989 (n = 2153). We used logistic regression and structural equation twin models to evaluate these 3 hypotheses. Results. Consistent with the social causation hypothesis, education (odds ratio [OR] = 0.78; 95% confidence interval [CI] = 0.66, 0.93; P < .01) and income (OR = 0.93; 95% CI = 0.89, 0.98; P < .01) were significantly related to past-year major depression. Upward social mobility was associated with lower risk of depression. There was no evidence that childhood SES was related to development of major depression (OR = 0.98; 95% CI = 0.89, 1.09; P > .1). Consistent with a common genetic cause, there was a negative correlation between the genetic components of major depression and education (r2 =  –0.22). Co-twin control analyses indicated a protective effect of education and income on major depression even after accounting for genetic liability. Conclusions. This study utilized a genetically informed design to address how social position relates to major depression. Results generally supported the social causation model. PMID:23927513

Risk Factor Analysis for Mastectomy Skin Flap Necrosis: Implications for Intraoperative Vascular Analysis.

PubMed

Reintgen, Christian; Leavitt, Adam; Pace, Elizabeth; Molas-Pierson, Justine; Mast, Bruce A

2016-06-01

Skin flap necrosis after mastectomy can be a devastating complication significantly affecting patient outcomes. Routine vascular analysis (fluorescein or laser angiography) of mastectomy skin flaps in all patients has been advocated but is of questionable cost-effectiveness. The purpose of this study was to identify the incidence and causative risk factors for mastectomy skin flap necrosis and thereby calculate the fiscal reality of intraoperative vascular screening. This is an institutional review board-approved retrospective study of all patients from 2007 to 2013 who underwent mastectomy related to breast cancer. Skin flap necrosis was defined as major if it necessitated return to the operating room. Data analysis was done for determination of causative factors of necrosis, including age, body mass index, smoking, previous irradiation, coronary artery disease, chronic obstructive pulmonary disorder, hypertension, gastroesophageal reflux disease, hyperlipidemia, obstructive sleep apnea, asthma, diabetes, thyroid disease, history of lumpectomy, and breast reduction or augmentation. During this time, intraoperative vascular screening was not done. Five hundred eighty-one patients underwent 616 mastectomies with a total of 34 necrotic events (5.5%)-16 major and 18 minor. Analyses via Student t tests, univariate analyses, χ testing, and logistic regression showed that history of smoking was the only patient factor associated with postoperative necrosis (P = 0.008). More frequently represented in the necrosis group, but without statistical significance, are previous lumpectomy (P = 0.069) and immediate reconstruction (P = 0.078).For the entire study period, the actual cost to the hospital for major necrotic events was $7,123.10 or $445.19 for each of the 16 major necrotic events and $209.50 for all 34 necrotic events. Per-patient cost-effective screening would need to be less than $11.54 for all patients, $100.33 for highest risk patients (smokers), and $21.65 for highest risk patients (smokers, previous lumpectomy, and immediate reconstruction). Vascular screening other than clinical judgment of all patients is not cost effective. However, intraoperative vascular evaluation of high-risk patients is recommended before reconstruction and/or closure. These financial data that incorporate true costs and revenue can guide the use of newer, more expensive technology such as laser angiography and can be extrapolated to other institutions.

Bacteriology of peritonsillar abscess: the changing trend and predisposing factors.

PubMed

Tsai, Yi-Wen; Liu, Yu-Hsi; Su, Hsing-Hao

2017-07-17

Peritonsillar abscess is the most common deep neck infection. The infectious microorganism may be different according to clinical factors. To identify the major causative pathogen of peritonsillar abscess and investigate the relationship between the causative pathogen, host clinical factors, and hospitalization duration. This retrospective study included 415 hospitalized patients diagnosed with peritonsillar abscess who were admitted to a tertiary medical center from June 1990 to June 2013. We collected data by chart review and analyzed variables such as demographic characteristics, underlying systemic disease, smoking, alcoholism, betel nut chewing, bacteriology, and hospitalization duration. A total of 168 patients had positive results for pathogen isolation. Streptococcus viridans (28.57%) and Klebsiella pneumoniae (23.21%) were the most common microorganisms identified through pus culturing. The isolation rate of anaerobes increased to 49.35% in the recent 6 years (p=0.048). Common anaerobes were Prevotella and Fusobacterium spp. The identification of K. pneumoniae increased among elderly patients (age>65 years) with an odds ratio (OR) of 2.76 (p=0.03), and decreased in the hot season (mean temperature>26°C) (OR=0.49, p=0.04). No specific microorganism was associated with prolonged hospital stay. The most common pathogen identified through pus culturing was S. viridans, followed by K. pneumoniae. The identification of anaerobes was shown to increase in recent years. The antibiotics initially selected should be effective against both aerobes and anaerobes. Bacterial identification may be associated with host clinical factors and environmental factors. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

SOIL FUMIGATION WITHIN MONOCULTURE AND ROTATIONS: RESPONSE OF CORN AND MYCORRIHZAE

EPA Science Inventory

The causative factors for corn (Zea mays L.) response to methyl bromide (CH₃Br) fumigation, in the absence of known specific pathogens, are unknown. This study was conducted to determine if deleterious nonspecific rhizosphere microorganisms are the causative age...

Role of Behavioural Risk Factors in Symptoms Related to UTI Among Nursing Students.

PubMed

Vyas, Shaili; Sharma, Parul; Srivastava, Kajal; Nautiyal, Vipul; Shrotriya, Ved Prakash

2015-09-01

UTI is a well known entity amongst young girls, and the majority of girls have recurrent infections within one year. Anything that disturbs the usual vaginal environment would result in conditions favouring the production of unwanted microorganisms leading to infections of this very sensitive area. Studies have shown that, there is an evident relation of UTI's among students and practices of personal hygiene. To determine association between the behavioural risk factors and UTI among nursing girls. The present study was undertaken amongst unmarried nursing students of a Medical College Hospital. A predesigned pretested questionnaire was used to know the personal hygiene of students and to find out its association with UTI in the last three months. Chi-square test was used to analyse the data. A significant association was observed between perineal hygiene and UTI. The major risk factors of UTI identified were incorrect perineal washing technique, use of synthetic/silk innerwears, not sundrying the innerwears, improper menstrual hygiene. There are still major gaps in the knowledge regarding causation of UTI among the nursing students. This calls for an urgent need for educational talks periodically addressing these gaps.

Role of Behavioural Risk Factors in Symptoms Related to UTI Among Nursing Students

PubMed Central

Sharma, Parul; Srivastava, Kajal; Nautiyal, Vipul; Shrotriya, Ved Prakash

2015-01-01

Introduction UTI is a well known entity amongst young girls, and the majority of girls have recurrent infections within one year. Anything that disturbs the usual vaginal environment would result in conditions favouring the production of unwanted microorganisms leading to infections of this very sensitive area. Studies have shown that, there is an evident relation of UTI’s among students and practices of personal hygiene. Aim To determine association between the behavioural risk factors and UTI among nursing girls. Materials and Methods The present study was undertaken amongst unmarried nursing students of a Medical College Hospital. A predesigned pretested questionnaire was used to know the personal hygiene of students and to find out its association with UTI in the last three months. Chi-square test was used to analyse the data. Results A significant association was observed between perineal hygiene and UTI. The major risk factors of UTI identified were incorrect perineal washing technique, use of synthetic/silk innerwears, not sundrying the innerwears, improper menstrual hygiene. Conclusion There are still major gaps in the knowledge regarding causation of UTI among the nursing students. This calls for an urgent need for educational talks periodically addressing these gaps. PMID:26500927

Micrococcus species-related peritonitis in patients receiving peritoneal dialysis.

PubMed

Kao, Chih-Chin; Chiang, Chih-Kang; Huang, Jenq-Wen

2014-01-01

Peritonitis is a major complication of peritoneal dialysis (PD) and remains the most common cause of PD failure. Micrococci are catalase-positive, coagulase-negative, and gram-positive cocci that are spherical, often found in tetrad, and belong to the family Micrococcaceae. Micrococcus species are commonly found in the environment, and it is now recognized that Micrococcus species can be opportunistic pathogens in immunocompromised patients. The only consistent predisposing factor for Micrococcus infection is an immunocompromised state. We report three cases of Micrococcus PD peritonitis. Improper practice of PD may have been the causative factor. Although Micrococcus species are low-virulence pathogens, infection could result in refractory peritonitis and subsequent PD failure. Intraperitoneal administration of vancomycin for at least 2 weeks is recommended for Micrococcus peritonitis.

Etiologic Ischemic Stroke Phenotypes in the NINDS Stroke Genetics Network

PubMed Central

Ay, Hakan; Arsava, Ethem Murat; Andsberg, Gunnar; Benner, Thomas; Brown, Robert D.; Chapman, Sherita N.; Cole, John W.; Delavaran, Hossein; Dichgans, Martin; Engström, Gunnar; Giralt-Steinhauer, Eva; Grewal, Raji P.; Gwinn, Katrina; Jern, Christina; Jimenez-Conde, Jordi; Jood, Katarina; Katsnelson, Michael; Kissela, Brett; Kittner, Steven J.; Kleindorfer, Dawn O.; Labovitz, Daniel L.; Lanfranconi, Silvia; Lee, Jin-Moo; Lehm, Manuel; Lemmens, Robin; Levi, Chris; Li, Linxin; Lindgren, Arne; Markus, Hugh S.; McArdle, Patrick F.; Melander, Olle; Norrving, Bo; Peddareddygari, Leema Reddy; Pedersén, Annie; Pera, Joanna; Rannikmäe, Kristiina; Rexrode, Kathryn M.; Rhodes, David; Rich, Stephen S.; Roquer, Jaume; Rosand, Jonathan; Rothwell, Peter M.; Rundek, Tatjana; Sacco, Ralph L.; Schmidt, Reinhold; Schürks, Markus; Seiler, Stephan; Sharma, Pankaj; Slowik, Agnieszka; Sudlow, Cathie; Thijs, Vincent; Woodfield, Rebecca; Worrall, Bradford B.; Meschia, James F.

2014-01-01

Background and Purpose NINDS Stroke Genetics Network (SiGN) is an international consortium of ischemic stroke studies that aims to generate high quality phenotype data to identify the genetic basis of etiologic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. Methods Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major etiologic groups without weighting towards the most likely cause) and causative ischemic stroke subtypes in 16,954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded re-adjudication of 1509 randomly selected cases. Results The distribution of etiologic categories varied by study, age, sex, and race (p<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke etiology (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (kappa 0.72, 95%CI:0.69-0.75) and phenotypic classifications (kappa 0.73, 95%CI:0.70-0.75). Conclusions This study demonstrates that etiologic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a stroke patient does not necessarily mean that it is the cause of stroke. PMID:25378430

Pain and flare-up after endodontic treatment procedures.

PubMed

Sipavičiūtė, Eglė; Manelienė, Rasmutė

2014-01-01

Flare-ups can occur after root canal treatment and consist of acute exacerbations of an asymptomatic pulpal and/or periradicular pathologic condition. The causative factors of interappointment pain encompass mechanical, chemical, and/or microbial injury to the pulp or periradicular tissues. Microorganisms can participate in causation of interappointment pain in the following situations: apical extrusion of debris; incomplete instrumentation leading to changes in the endodontic microbiota or in environmental conditions; and secondary intraradicular infections. Interappointment pain is almost exclusively due to the development of acute inflammation at the periradicular tissues in response to an increase in the intensity of injury coming from the root canal system. The mechanical irritation of apical periodontal tissue is caused by overinstrumentation of the root canal and filling material extrusion through the apical foramen. Incorrectly measured working length of the root canal has inherent connection with these causative factors of endodontic flare - up. This review article discusses these many facets of the flare-up: definition, incidence causes and predisposing factors.

Public Attitudes towards Prevention of Obesity

PubMed Central

Sikorski, Claudia; Luppa, Melanie; Schomerus, Georg; Werner, Perla; König, Hans-Helmut; Riedel-Heller, Steffi G.

2012-01-01

Objective To investigate obesity prevention support in the German general public and to assess determinants of general prevention support as well as support of specific prevention measures. Methods This study was a cross-sectional analysis of a telephone based representative German study (3,003 subjects (52.8% women, mean age 51.9, s.d. = 18.0, range 18–97 years). Likert scale-based questions on general prevention support and support of specific measures were used. Furthermore willingness to take part in preventive programs and willingness to pay were assessed. Stigmatizing attitudes were assessed with the Fat Phobia Scale (FPS). Causation of obesity was differentiated in three dimensions (internal, e.g. lack of exercise; external, e.g. social surroundings; and genetic factors). Results Obesity prevention was perceived as possible (98.2%), however, almost exclusively lifestyle changes were named. Participants with higher stigmatizing attitudes were less likely to believe obesity prevention is possible. The majority of participants would take part in preventive programs (59.6%) and pay at least partially themselves (86.9%). Factor analysis revealed three dimensions of preventive measures: promoting healthy eating, restrictive and financial, governmental prevention efforts. In regard to these, promoting healthy eating was the most supported measure. Higher age, female gender and external causation were associated with higher support for all three dimensions of preventive measures. Only for governmental regulation, higher age was associated with lower support. Conclusion Obesity prevention support in Germany is high. Structural prevention efforts are supported by the majority of the general public in Germany. The vast majority proclaims willingness to pay themselves for programs of weight gain prevention. This could be an indication of higher perceived self-responsibility in the German system but also for risen “fear of fat” in the population due to media coverage. For Germany, the government and communities ought to be encouraged by these results to start the implementation of structural obesity prevention. PMID:22723996

Esophageal cancer in high-risk areas of China: research progress and challenges.

PubMed

Lin, Yingsong; Totsuka, Yukari; Shan, Baoen; Wang, Chaochen; Wei, Wenqiang; Qiao, Youlin; Kikuchi, Shogo; Inoue, Manami; Tanaka, Hideo; He, Yutong

2017-03-01

The extremely high incidence of esophageal cancer in certain rural areas of China has prompted significant intellectual curiosity and research efforts both in China and abroad. We summarize the research progress over the past several decades in high-risk areas (Linxian, Cixian, Shexian, and Yanting) based on literature research and our field trip (2012-2013). Considerable progress in clarifying the environmental risk factors and pathogenesis of esophageal cancer in high-risk areas has been achieved over the past several decades. Epidemiologic evidence suggests that carcinogen exposure and nutritional deficiency, rather than smoking and drinking, may be the major risk factors for esophageal cancer in the Taihang Mountains region, where the incidence of esophageal cancer is among the highest in the world. Two genome-wide association studies have identified variants in PLCE1 at 10q23 that are significantly associated with esophageal cancer risk. Recent whole-exome studies have revealed a comprehensive mutation pattern, in which the C>T transition is the predominant mutation type. Despite extensive research, the main causative factors that contribute to esophageal cancer in high-risk areas have not yet been elucidated. Challenges in this research area include determining the causative role of nitrosamine, identifying other potential carcinogens, and conducting fruitful international collaborative studies based on a multidisciplinary approach. Increased international collaboration will contribute to a better understanding of the etiology of esophageal cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Inflammation as a causative factor in the aetiology of Parkinson's disease

PubMed Central

Whitton, P S

2007-01-01

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting mainly the elderly, although a small proportion of PD patients develop the illness at a much younger age. In the former group, idiopathic PD patients, the causes of the illness have been the subject of longstanding debate with environmental toxins, mitochondrial dysfunction, abnormal protein handling and oxidative stress being suggested. One problem has been that the epidemiology of PD has offered few clues to provide evidence for a single major causative factor. Comparatively recently it has been found that in both patients and experimental models of PD in animals neuroinflammation appears to be a ubiquitous finding. These cases present with all of the classical features of inflammation including phagocyte activation, increased synthesis and release of proinflammatory cytokines and complement activation. Although this process is vital for normal function and protection in both the CNS, as in the periphery, it is postulated that in the aetiology of PD this process may spiral out of control with over activation of microglia, over production of cytokines and other proinflammatory mediators as well as the release of destructive molecules such as reactive oxygen species. Given that dopaminergic neurons in the substantia nigra are relatively vulnerable to ‘stress' and the region has a large population of microglia in comparison to other CNS structures, these events may easily trigger neurodegeneration. These factors are examined in this review along with a consideration of the possible use of anti-inflammatory drugs in PD. PMID:17339843

Risk factors and causative organisms in microbial keratitis in daily disposable contact lens wear.

PubMed

Stapleton, Fiona; Naduvilath, Thomas; Keay, Lisa; Radford, Cherry; Dart, John; Edwards, Katie; Carnt, Nicole; Minassian, Darwin; Holden, Brien

2017-01-01

This study investigated independent risk factors and causative organisms in microbial keratitis in daily disposable contact lens (CL)-wearers. A multisite prospective case-control study was undertaken. Cases were daily disposable CL-wearers attending Moorfields Eye Hospital with microbial keratitis and those reported through a one-year surveillance study in Australia and in New Zealand. A population-based telephone survey identified daily disposable CL-wearing controls. Subjects completed a questionnaire describing CL-wear history, hygiene and demographics. The sample used for risk factor analysis was weighted in proportion to the CL-wearing population at each location. Corneal scrape results were accessed. Independent risk factors were determined using multiple binary logistic regression. Causative organisms in different CL-wear modalities were compared using a chi-squared test. 963 daily disposable CL-wearers were identified, from which 67 cases and 374 controls were sampled. Independent risk factors were; wearing CLs every day compared with less frequent use (OR 10.4x; 95% CI 2.9-56.4), any overnight wear (OR 1.8x; 95% CI 1.6-2.1), less frequent hand washing (OR 1.8x; 95% CI 1.6-2.0), and smoking (OR 1.3x; 95% CI 1.1-1.6). Certain daily disposable CLs (OR 0.2x; 95% CI 0.1-0.2) had protective effects. Environmental organisms were less frequently recovered with daily disposable CLs (20%), compared with other modalities (36%; p<0.02). Overnight wear, increased exposure in daily wear, smoking and poor hand hygiene are significant risk factors for microbial keratitis with daily disposable CLs. Risk varied with daily disposable CL type. The profile of causative organisms is consistent with less severe disease.

Students' Big Three Personality Traits, Perceptions of Teacher Interpersonal Behavior, and Mathematics Achievement: An Application of the Model of Reciprocal Causation

ERIC Educational Resources Information Center

Charalampous, Kyriakos; Kokkinos, Constantinos M.

2014-01-01

The purpose of the present study was to investigate the application of the Model of Reciprocal Causation (MRC) in examining the relationship between student personality (personal factors), student-perceived teacher interpersonal behavior (environment), and Mathematics achievement (behavior), with the simultaneous investigation of mediating effects…

Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis.

PubMed

Moghnieh, Rima; Estaitieh, Nour; Mugharbil, Anas; Jisr, Tamima; Abdallah, Dania I; Ziade, Fouad; Sinno, Loubna; Ibrahim, Ahmad

2015-01-01

Bacteremia remains a major cause of life-threatening complications in patients receiving anticancer chemotherapy. The spectrum and susceptibility profiles of causative microorganisms differ with time and place. Data from Lebanon are scarce. We aim at evaluating the epidemiology of bacteremia in cancer patients in a university hospital in Lebanon, emphasizing antibiotic resistance and risk factors of multi-drug resistant organism (MDRO)-associated bacteremia. This is a retrospective study of 75 episodes of bacteremia occurring in febrile neutropenic patients admitted to the hematology-oncology unit at Makassed General Hospital, Lebanon, from October 2009-January 2012. It corresponds to epidemiological data on bacteremia episodes in febrile neutropenic cancer patients including antimicrobial resistance and identification of risk factors associated with third generation cephalosporin resistance (3GCR) and MDRO-associated bacteremia. Out of 75 bacteremias, 42.7% were gram-positive (GP), and 57.3% were gram-negative (GN). GP bacteremias were mostly due to methicillin-resistant coagulase negative staphylococci (28% of total bacteremias and 66% of GP bacteremias). Among the GN bacteremias, Escherichia coli (22.7% of total, 39.5% of GN organisms) and Klebsiella pneumoniae(13.3% of total, 23.3% of GN organisms) were the most important causative agents. GN bacteremia due to 3GC sensitive (3GCS) bacteria represented 28% of total bacteremias, while 29% were due to 3GCR bacteria and 9% were due to carbapenem-resistant organisms. There was a significant correlation between bacteremia with MDRO and subsequent intubation, sepsis and mortality. Among potential risk factors, only broad spectrum antibiotic intake >4 days before bacteremia was found to be statistically significant for acquisition of 3GCR bacteria. Using carbapenems or piperacillin/tazobactam>4 days before bacteremia was significantly associated with the emergence of MDRO (p < 0.05). Our findings have major implications for the management of febrile neutropenia, especially in breakthrough bacteremia and fever when patients are already on broadspectrum antibiotics. Emergence of resistance to 3GCs and, to a lesser extent, to carbapenems in GN isolates has to be considered seriously in our local guidelines for empiric treatment of febrile neutropenia, especially given that their occurrence was proven to be associated with poorer outcomes.

Racism, society, and disease: an exploration of the social and biological mechanisms of differential mortality.

PubMed

Cooper, R; Steinhauer, M; Miller, W; David, R; Schatzkin, A

1981-01-01

Racial differentials in mortality provide important insight into the nature of mass disease in capitalist society. Not only are the differentials sizable in magnitude, they are consistent for multiple causes of death and appear to evolve in response to social development. The relationships among social factors and the biological and physical agents of disease can be identified through racial contrasts and a pattern of causation which applies to both the minority and majority populations described. Furthermore, the impact of exploitation as the primary disease-mediating factor under capitalist social relations can be estimated. This paper attempts to combine an analysis of bio-medical mechanisms with Marxist social theory in a comprehensive framework for the study of the social origins of racial differentials.

Update on genetics of essential tremor.

PubMed

Jiménez-Jiménez, F J; Alonso-Navarro, H; García-Martín, E; Lorenzo-Betancor, O; Pastor, P; Agúndez, J A G

2013-12-01

Despite the research, few advances in the etiopathogenesis on essential tremor (ET) have been made to date. The high frequency of positive family history of ET and the observed high concordance rates in monozygotic compared with dizygotic twins support a major role of genetic factors in the development of ET. In addition, a possible role of environmental factors has been suggested in the etiology of ET (at least in non-familial forms). Although several gene variants in the LINGO1 gene may increase the risk of ET, to date no causative mutated genes have been identified. In this review, we summarize the studies performed on families with tremor, twin studies, linkage studies, case-control association studies, and exome sequencing in familial ET. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Upper secondary and first-year university students' explanations of animal behaviour: to what extent are Tinbergen's four questions about causation, ontogeny, function and evolution, represented?

NASA Astrophysics Data System (ADS)

Pinxten, Rianne; Desclée, Mathieu; Eens, Marcel

2016-09-01

In 1963, the Nobel Prize-winning ethologist Niko Tinbergen proposed a framework for the scientific study of animal behaviour by outlining four questions that should be answered to have a complete understanding: causation, ontogeny, function and evolution. At present, Tinbergen's framework is still considered the best way to guide animal behavioural research. Given the importance in science instruction of demonstrating how scientists work and ask questions, we investigated to what extent Tinbergen's questions are addressed in biology textbooks in secondary education in Flanders, Belgium, and represented in upper-secondary and first-year university students' explanations of behaviour in general and of specific animal behaviours. Our results revealed that teaching of animal behaviour mainly addresses ontogeny and causation, and that Tinbergen's framework is not explicitly referred to. Students typically addressed only one or two questions, with the majority addressing causation or both causation and ontogeny when explaining behaviour in general, but function or causation and function when explaining specific animal behaviours. This high prevalence of function may be due to teleological thinking. Evolution was completely neglected, even in university students who had recently completed an evolution course. Our results revealed that transfer of the concepts of ontogeny and evolution was (almost) absent. We argue why Tinbergen's framework should be an integral part of any biology curriculum.

An ergonomic study on musculoskeletal health hazards among sawmill workers of West Bengal, India.

PubMed

Chandra, Ananga Mohan; Ghosh, Suhana; Barman, Sangita; Dev, Samrat; Gangopadhyay, Somnath

2011-12-01

The study was undertaken to determine the prevalence of musculoskeletal discomfort among the sawmill workers of Kolkata and to identify the causative factors behind the development of such discomfort. For this study 110 male workers were randomly selected. For the symptom survey, modified Nordic questionnaire on detail discomfort feelings was performed. Analysis of working posture, repetitiveness of work, measurement of handgrip strength, measurement of pre and post working heart rate, measurement of lower back muscle flexibility were performed on the selected sawmill workers suffering from musculoskeletal discomfort. The results revealed that musculoskeletal discomfort was a major problem among the sawmill workers, primarily involving the lower back (100%), neck (95.96%), wrist (87.78%), and shoulder (84.44%). Their activities were highly repetitive and the handgrip strength of these workers was significantly lower than that of the comparison group. The results also revealed that musculoskeletal discomfort was high among the sawmill workers who were doing the job for a longer period of time than those who are doing the same job for a shorter period of time. Based on these findings, it appears that repetitiveness in work, handling heavy load, sustained work activity, strenuous job, and uncomfortable posture might be the causative factors for the development of their discomfort feelings. Thus to ensure good health, safety and productivity of these workers, some ergonomic measures have to be taken as early as possible.

Acetylcholinesterase mutations and organophosphate resistance in sand flies and mosquitoes

USDA-ARS?s Scientific Manuscript database

The sand fly, Phlebotomus papatasi (Scopoli) is a major vector of Leishamnia major, the principle causative agent of human cutaneous leishmaniasis in the Middle East, southern Europe, northern Africa, and Southern Asia. Sand fly bites and leishmaniasis significantly impacted U.S. military operations...

The changing assessments of John Snow's and William Farr's cholera studies.

PubMed

Eyler, J M

2001-01-01

This article describes the epidemiological studies of cholera by two major British investigators of the mid-nineteenth century, John Snow and William Farr, and it asks why the assessments of their results by contemporaries was the reverse of our assessment today. In the 1840s and 1850s Farr's work was considered definitive, while Snow's was regarded as ingenious but flawed. Although Snow's conclusions ran contrary to the exceptations of his contemporaries, the major reservations about his cholera studies concerned his bold use of analogy, his thoroughgoing reductionism, and his willingness to ignore what seemed to be contrary evidence. Farr's electric use of current theories, his reliance multiple causation, and his discovery of a mathematical law to describe the outbreak in London in 1849 was much more convincing to his contemporaries. A major change in thinking about disease causation was needed before Snow's work could be widely accepted. William Farr's later studies contributed to that acceptance.

Causative factors of cost overrun in highway projects of Sindh province of Pakistan

NASA Astrophysics Data System (ADS)

Sohu, S.; Halid, A.; Nagapan, S.; Fattah, A.; Latif, I.; Ullah, K.

2017-11-01

Cost overrun is an increase of cost of project from approved budget which was signed by parties at the time of tender. Cost overrun in construction of highway projects is a common problem worldwide and construction industry of Pakistan is also facing this crucial problem of cost overrun in highway projects of Pakistan. The main objective of this research is to identify the causative factors of cost overrun in highway projects of Sindh province of Pakistan. A well designed questionnaire was developed based on 64 common factors of cost overrun from literature review. Developed questionnaire was distributed among selected 30 experts from owner/client, designer/consultant and contractor who have experience more than 20 years’ experience in highway projects. The collected data was statistical analyzed. After analysis results showed that delay process in payment by client, inadequate planning, client interference, poor contract management, delay of decision making, change of scope of project and financial problems faced by client were most causative factors of cost overrun in highway projects. This research will provide alertness to stakeholders of highway projects of Sindh province to avoid cost overrun in projects.

Student Financial Aid and Choice of Undergraduate Major. ASHE Annual Meeting Paper.

ERIC Educational Resources Information Center

Zito, Eileen H.

This study evaluated whether the use of educational loans has an impact upon student choice of majors. In addition, the study demonstrated that the statistical technique of two-stage least squares can be appropriately used with educational data when reciprocal causation exists in the theoretical model. It was hypothesized that, since a majority of…

Invited review: Mastitis in dairy heifers: nature of the disease, potential impact, prevention, and control.

PubMed

De Vliegher, S; Fox, L K; Piepers, S; McDougall, S; Barkema, H W

2012-03-01

Heifer mastitis is a disease that potentially threatens production and udder health in the first and subsequent lactations. In general, coagulase-negative staphylococci (CNS) are the predominant cause of intramammary infection and subclinical mastitis in heifers around parturition, whereas Staphylococcus aureus and environmental pathogens cause a minority of the cases. Clinical heifer mastitis is typically caused by the major pathogens. The variation in proportions of causative pathogens between studies, herds, and countries is considerable. The magnitude of the effect of heifer mastitis on an individual animal is influenced by the form of mastitis (clinical versus subclinical), the virulence of the causative pathogen(s) (major versus minor pathogens), the time of onset of infection relative to calving, cure or persistence of the infection when milk production has started, and the host's immunity. Intramammary infection in early lactation caused by CNS does not generally have a negative effect on subsequent productivity. At the herd level, the impact will depend on the prevalence and incidence of the disease, the nature of the problem (clinical, subclinical, nonfunctional quarters), the causative pathogens involved (major versus minor pathogens), the ability of the animals to cope with the disease, and the response of the dairy manager to control the disease through management changes. Specific recommendations to prevent and control mastitis in late gestation in periparturient heifers are not part of the current National Mastitis Council mastitis and prevention program. Control and prevention is currently based on avoidance of inter-sucking among young stock, fly control, optimal nutrition, and implementation of hygiene control and comfort measures, especially around calving. More risk factors for subclinical and clinical heifer mastitis have been identified (e.g., season, location of herd, stage of pregnancy) although they do not lend themselves to the development of specific intervention strategies designed to prevent the disease. Pathogen-specific risk factors and associated control measures need to be identified due to the pathogen-related variation in epidemiology and effect on future performance. Prepartum intramammary treatment with antibiotics has been proposed as a simple and effective way of controlling heifer mastitis but positive long-lasting effects on somatic cell count and milk yield do not always occur, ruling out universal recommendation of this practice. Moreover, use of antibiotics in this manner is off-label and results in an increased risk of antibiotic residues in milk. Prepartum treatment can be implemented only as a short-term measure to assist in the control of a significant heifer mastitis problem under supervision of the herd veterinarian. When CNS are the major cause of intramammary infection in heifers, productivity is not affected, making prepartum treatment redundant and even unwanted. In conclusion, heifer mastitis can affect the profitability of dairy farming because of a potential long-term negative effect on udder health and milk production and an associated culling risk, specifically when major pathogens are involved. Prevention and control is not easy but is possible through changes in young stock and heifer management. However, the pathogenesis and epidemiology of the disease remain largely unknown and more pathogen-specific risk factors should be identified to optimize current prevention programs. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Causation mechanism analysis for haze pollution related to vehicle emission in Guangzhou, China by employing the fault tree approach.

PubMed

Huang, Weiqing; Fan, Hongbo; Qiu, Yongfu; Cheng, Zhiyu; Xu, Pingru; Qian, Yu

2016-05-01

Recently, China has frequently experienced large-scale, severe and persistent haze pollution due to surging urbanization and industrialization and a rapid growth in the number of motor vehicles and energy consumption. The vehicle emission due to the consumption of a large number of fossil fuels is no doubt a critical factor of the haze pollution. This work is focused on the causation mechanism of haze pollution related to the vehicle emission for Guangzhou city by employing the Fault Tree Analysis (FTA) method for the first time. With the establishment of the fault tree system of "Haze weather-Vehicle exhausts explosive emission", all of the important risk factors are discussed and identified by using this deductive FTA method. The qualitative and quantitative assessments of the fault tree system are carried out based on the structure, probability and critical importance degree analysis of the risk factors. The study may provide a new simple and effective tool/strategy for the causation mechanism analysis and risk management of haze pollution in China. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tracing environmental aetiological factors of chronic kidney diseases in the dry zone of Sri Lanka-A hydrogeochemical and isotope approach.

PubMed

Wickramarathna, Sudeera; Balasooriya, Shyamalie; Diyabalanage, Saranga; Chandrajith, Rohana

2017-12-01

Chronic kidney disease of unknown aetiologies (CKDu) is increasingly recognized in tropical regions and is now considered a global health problem. A detailed hydrogeochemical investigation has been performed in three CKDu hotspots in Sri Lanka to assess the geo-environmental aetiological factors influencing this disease. A total of 71 ground- and 26 surface water samples were collected from Girandurukotte, Wilgamuwa and Nikawewa regions and analysed for major constituents and trace elements. The affected regions are dominated by Ca-Mg-HCO 3 facies groundwater that is mainly controlled by silicate weathering. Higher levels of fluoride associated with higher hardness is the main feature of groundwater from CKDu regions compared to non-CKDu regions. Results showed that 65% of the wells in the affected regions exceeded the fluoride concentration of 0.5mg/L. Environmental isotopes of groundwater in the CKDu regions are represented by the regression line of δ 2 H=5.42δ 18 O-3.59 (r 2 =0.916) with a clear isotopic differentiation between local precipitation and groundwater. None of the trace elements exceeded the recommended scales and in most cases levels are negligible in both surface and groundwater in study areas. Therefore, the involvement of trace elements such as Cd, As and Pb can be ignored as causative factors for CKDu. This study highlights the synergistic influence of fluoride and hardness that could enhance the disease, and thereby refute earlier theories that attribute trace elements as causative factors for CKDu. Higher hardness in drinking water also restricts sufficient water uptake, particularly by farmers and which affects the physiological, biochemical and nutritional requirements. Copyright © 2017 Elsevier GmbH. All rights reserved.

Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia.

PubMed

Shimada, T; Mizutani, S; Muto, T; Yoneya, T; Hino, R; Takeda, S; Takeuchi, Y; Fujita, T; Fukumoto, S; Yamashita, T

2001-05-22

Tumor-induced osteomalacia (TIO) is one of the paraneoplastic diseases characterized by hypophosphatemia caused by renal phosphate wasting. Because removal of responsible tumors normalizes phosphate metabolism, an unidentified humoral phosphaturic factor is believed to be responsible for this syndrome. To identify the causative factor of TIO, we obtained cDNA clones that were abundantly expressed only in a tumor causing TIO and constructed tumor-specific cDNA contigs. Based on the sequence of one major contig, we cloned 2,270-bp cDNA, which turned out to encode fibroblast growth factor 23 (FGF23). Administration of recombinant FGF23 decreased serum phosphate in mice within 12 h. When Chinese hamster ovary cells stably expressing FGF23 were s.c. implanted into nude mice, hypophosphatemia with increased renal phosphate clearance was observed. In addition, a high level of serum alkaline phosphatase, low 1,25-dihydroxyvitamin D, deformity of bone, and impairment of body weight gain became evident. Histological examination showed marked increase of osteoid and widening of growth plate. Thus, continuous production of FGF23 reproduced clinical, biochemical, and histological features of TIO in vivo. Analyses for recombinant FGF23 products produced by Chinese hamster ovary cells indicated proteolytic cleavage of FGF23 at the RXXR motif. Recent genetic study indicates that missense mutations in this RXXR motif of FGF23 are responsible for autosomal dominant hypophosphatemic rickets, another hypophosphatemic disease with similar features to TIO. We conclude that overproduction of FGF23 causes TIO, whereas mutations in the FGF23 gene result in autosomal dominant hypophosphatemic rickets possibly by preventing proteolytic cleavage and enhancing biological activity of FGF23.

Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia

PubMed Central

Shimada, Takashi; Mizutani, Satoru; Muto, Takanori; Yoneya, Takashi; Hino, Rieko; Takeda, Shu; Takeuchi, Yasuhiro; Fujita, Toshiro; Fukumoto, Seiji; Yamashita, Takeyoshi

2001-01-01

Tumor-induced osteomalacia (TIO) is one of the paraneoplastic diseases characterized by hypophosphatemia caused by renal phosphate wasting. Because removal of responsible tumors normalizes phosphate metabolism, an unidentified humoral phosphaturic factor is believed to be responsible for this syndrome. To identify the causative factor of TIO, we obtained cDNA clones that were abundantly expressed only in a tumor causing TIO and constructed tumor-specific cDNA contigs. Based on the sequence of one major contig, we cloned 2,270-bp cDNA, which turned out to encode fibroblast growth factor 23 (FGF23). Administration of recombinant FGF23 decreased serum phosphate in mice within 12 h. When Chinese hamster ovary cells stably expressing FGF23 were s.c. implanted into nude mice, hypophosphatemia with increased renal phosphate clearance was observed. In addition, a high level of serum alkaline phosphatase, low 1,25-dihydroxyvitamin D, deformity of bone, and impairment of body weight gain became evident. Histological examination showed marked increase of osteoid and widening of growth plate. Thus, continuous production of FGF23 reproduced clinical, biochemical, and histological features of TIO in vivo. Analyses for recombinant FGF23 products produced by Chinese hamster ovary cells indicated proteolytic cleavage of FGF23 at the RXXR motif. Recent genetic study indicates that missense mutations in this RXXR motif of FGF23 are responsible for autosomal dominant hypophosphatemic rickets, another hypophosphatemic disease with similar features to TIO. We conclude that overproduction of FGF23 causes TIO, whereas mutations in the FGF23 gene result in autosomal dominant hypophosphatemic rickets possibly by preventing proteolytic cleavage and enhancing biological activity of FGF23. PMID:11344269

Hypersensitivity pneumonitis: a complex lung disease.

PubMed

Riario Sforza, Gian Galeazzo; Marinou, Androula

2017-01-01

Hypersensitivity pneumonitis (HP), also called extrinsic allergic alveolitis, is a respiratory syndrome involving the lung parenchyma and specifically the alveoli, terminal bronchioli, and alveolar interstitium, due to a delayed allergic reaction. Such reaction is secondary to a repeated and prolonged inhalation of different types of organic dusts or other substances to which the patient is sensitized and hyper responsive, primarily consisting of organic dusts of animal or vegetable origin, more rarely from chemicals. The prevalence of HP is difficult to evaluate because of uncertainties in detection and misdiagnosis and lacking of widely accepted diagnostic criteria, and varies considerably depending on disease definition, diagnostic methods, exposure modalities, geographical conditions, agricultural and industrial practices, and host risk factors. HP can be caused by multiple agents that are present in work places and in the home, such as microbes, animal and plant proteins, organic and inorganic chemicals. The number of environment, settings and causative agents is increasing over time. From the clinical point of view HP can be divided in acute/subacute and chronic, depending on the intensity and frequency of exposure to causative antigens. The mainstay in managing HP is the avoidance of the causative antigen, though the complete removal is not always possible due to the difficulties to identify the agent or because its avoidance may lead to major changes in life style or occupational settings. HP is a complex syndrome that needs urgently for more stringent and selective diagnostic criteria and validation, including wider panels of IgG, and a closer collaboration with occupational physicians, as part of a multidisciplinary expertise.

Colonic cancer--hypotheses of causation, dietary prophylaxis, and future research.

PubMed

Walker, A R; Burkitt, D P

1976-10-01

Colonic cancer is rare in primitive populations. In western populations it was uncommon in the past, but now accounts for about 3% of all deaths. The cause almost certainly lies with dietary changes. Probably, alterations in bowel milieu interieur, from interaction between metabolites and microbacteria, promote carcinogenesis. Changes in intakes of protein, fat, sugar, refined cereal products, and crude fiber have been advanced as predisposing or causative factors. Evidence suggests that (i) fall in fiber intake, but (ii) rise in fat intake, in their ability to increase fecal concentrations of bile acids and sterols (possible precursors of carcinogens) are most likely to be culpable. As preventive measures, a significant rise in fiber intake is practicable only from regular bran ingestion. A major reduction in fat intake is grossly unlikely. Even were rigorous dietary changes implemented, an early fall in colonic cancer incidence is highly improbable due to the long-term character of the disease. Future research must include characterization of the diet, metabolism, and disease pattern of segments of western populations who have low colonic cancer mortality rates; also, elucidation of the bearing of various intakes of different food components on the biochemistry and microbiology of the feces.

Cumulative Causation of Rural Migration and Initial Peri-Urbanization in China.

PubMed

Hao, Lingxin

2012-01-01

This paper posits that rural migration feeds the high demand for cheap labor in peri-urbanization, which is driven by globalization, flows of foreign capital, and entrepreneurial local governments. While the gravity model and push/pull perspective ignore the dynamics of migratory course, we use the cumulative causation of migration theory to conceptualize social expectations for outmigration and social resources from migrant networks in destinations. Four major findings are drawn from this demographic analysis based on micro data from China's 2000 Census. First, the expectation of outmigration significantly increases outmigration, and this effect is independent of push factors. Second, foreign direct investment (FDI) contributes to attracting rural labor migrants from other provinces to peri-urban areas as it does to cities. Third, social resources from migrant networks play an important role in attracting rural labor migrants to both city and noncity destinations. Fourth, the importance of wage differentials declines in gravitating rural labor migrants to peri-urban areas. These findings provide tentative evidence that rural labor migration is indispensable during initial peri-urbanization. Infused with flows of FDI and entrepreneurial local governments, rural migration has created a favorable initial condition for peri-urbanization.

The Human Ureaplasma Species as Causative Agents of Chorioamnionitis.

PubMed

Sweeney, Emma L; Dando, Samantha J; Kallapur, Suhas G; Knox, Christine L

2017-01-01

The human Ureaplasma species are the most frequently isolated microorganisms from the amniotic fluid and placentae of women who deliver preterm and are also associated with spontaneous abortions or miscarriages, neonatal respiratory diseases, and chorioamnionitis. Despite the fact that these microorganisms have been habitually found within placentae of pregnancies with chorioamnionitis, the role of Ureaplasma species as a causative agent has not been satisfactorily explained. There is also controversy surrounding their role in disease, particularly as not all women infected with Ureaplasma spp. develop chorioamnionitis. In this review, we provide evidence that Ureaplasma spp. are associated with diseases of pregnancy and discuss recent findings which demonstrate that Ureaplasma spp. are associated with chorioamnionitis, regardless of gestational age at the time of delivery. Here, we also discuss the proposed major virulence factors of Ureaplasma spp., with a focus on the multiple-banded antigen (MBA), which may facilitate modulation/alteration of the host immune response and potentially explain why only subpopulations of infected women experience adverse pregnancy outcomes. The information presented within this review confirms that Ureaplasma spp. are not simply "innocent bystanders" in disease and highlights that these microorganisms are an often underestimated pathogen of pregnancy. Copyright © 2016 American Society for Microbiology.

The Human Ureaplasma Species as Causative Agents of Chorioamnionitis

PubMed Central

Sweeney, Emma L.; Kallapur, Suhas G.; Knox, Christine L.

2016-01-01

SUMMARY The human Ureaplasma species are the most frequently isolated microorganisms from the amniotic fluid and placentae of women who deliver preterm and are also associated with spontaneous abortions or miscarriages, neonatal respiratory diseases, and chorioamnionitis. Despite the fact that these microorganisms have been habitually found within placentae of pregnancies with chorioamnionitis, the role of Ureaplasma species as a causative agent has not been satisfactorily explained. There is also controversy surrounding their role in disease, particularly as not all women infected with Ureaplasma spp. develop chorioamnionitis. In this review, we provide evidence that Ureaplasma spp. are associated with diseases of pregnancy and discuss recent findings which demonstrate that Ureaplasma spp. are associated with chorioamnionitis, regardless of gestational age at the time of delivery. Here, we also discuss the proposed major virulence factors of Ureaplasma spp., with a focus on the multiple-banded antigen (MBA), which may facilitate modulation/alteration of the host immune response and potentially explain why only subpopulations of infected women experience adverse pregnancy outcomes. The information presented within this review confirms that Ureaplasma spp. are not simply “innocent bystanders” in disease and highlights that these microorganisms are an often underestimated pathogen of pregnancy. PMID:27974410

Cumulative Causation of Rural Migration and Initial Peri-Urbanization in China*

PubMed Central

Hao, Lingxin

2014-01-01

This paper posits that rural migration feeds the high demand for cheap labor in peri-urbanization, which is driven by globalization, flows of foreign capital, and entrepreneurial local governments. While the gravity model and push/pull perspective ignore the dynamics of migratory course, we use the cumulative causation of migration theory to conceptualize social expectations for outmigration and social resources from migrant networks in destinations. Four major findings are drawn from this demographic analysis based on micro data from China’s 2000 Census. First, the expectation of outmigration significantly increases outmigration, and this effect is independent of push factors. Second, foreign direct investment (FDI) contributes to attracting rural labor migrants from other provinces to peri-urban areas as it does to cities. Third, social resources from migrant networks play an important role in attracting rural labor migrants to both city and noncity destinations. Fourth, the importance of wage differentials declines in gravitating rural labor migrants to peri-urban areas. These findings provide tentative evidence that rural labor migration is indispensable during initial peri-urbanization. Infused with flows of FDI and entrepreneurial local governments, rural migration has created a favorable initial condition for peri-urbanization. PMID:25525564

Acute Bacterial Meningitis in Qatar: A Hospital-Based Study from 2009 to 2013.

PubMed

Khan, Fahmi Yousef; Abu-Khattab, Mohammed; Almaslamani, Eman Abdulrahman; Hassan, Abubaker Ahmed; Mohamed, Shehab Fareed; Elbuzdi, Abdurrahman Ali; Elmaki, Nada Yagoub; Anand, Deshmukh; Sanjay, Doiphode

2017-01-01

Bacterial meningitis is a common medical condition in Qatar. The aim of this study was to describe the clinical characteristics of bacterial meningitis, the frequency of each pathogen, and its sensitivity to antibiotics and risk factors for death. This retrospective study was conducted at Hamad General Hospital between January 1, 2009, and December 31, 2013. We identified 117 episodes of acute bacterial meningitis in 110 patients. Their mean age was 26.4 ± 22.3 years (range: 2-74) and 81 (69.2%) of them were male patients. Fifty-nine episodes (50.4%) were community-acquired infection and fever was the most frequent symptom (94%), whereas neurosurgery is the most common underlying condition. Coagulase-negative staphylococci were the most common causative agent, of which 95% were oxacillin-resistant, while 63.3% of Acinetobacter spp. showed resistance to meropenem. The in-hospital mortality was 14 (12%). Only the presence of underlying diseases, hypotension, and inappropriate treatment were found to be independent predictors of mortality. Acute bacterial meningitis predominantly affected adults and coagulase-negative staphylococci species were the common causative agent in Qatar with majority of infections occurring nosocomially. More than 90% of all implicated coagulase-negative staphylococci strains were oxacillin-resistant.

DNA methylation in inflammatory bowel disease and beyond

PubMed Central

Low, Daren; Mizoguchi, Atsushi; Mizoguchi, Emiko

2013-01-01

Inflammatory bowel disease (IBD) is a consequence of the complex, dysregulated interplay between genetic predisposition, environmental factors, and microbial composition in the intestine. Despite a great advancement in identifying host-susceptibility genes using genome-wide association studies (GWAS), the majority of IBD cases are still underrepresented. The immediate challenge in post-GWAS era is to identify other causative genetic factors of IBD. DNA methylation has received increasing attention for its mechanistical role in IBD pathogenesis. This stable, yet dynamic DNA modification, can directly affect gene expression that have important implications in IBD development. The alterations in DNA methylation associated with IBD are likely to outset as early as embryogenesis all the way until old-age. In this review, we will discuss the recent advancement in understanding how DNA methylation alterations can contribute to the development of IBD. PMID:23983426

Oral Cavity Cancer: Risk Factors, Pathology, and Management.

PubMed

Ernani, Vinicius; Saba, Nabil F

2015-01-01

Oral cavity cancers are predominantly squamous cell carcinomas, which arise from premalignant lesions through a multistep carcinogenesis process. Tobacco and alcohol are the major etiologic factors, although human papillomavirus has also recently been implicated as a causative agent. The possibility of a second primary malignancy should be considered during the diagnostic evaluation of head and neck cancers, as well as during the posttreatment surveillance phase. The goals of treatment are not only to improve survival outcomes but also to preserve organ function. These cancers are generally treated with a combination of surgery, radiation therapy, and chemotherapy. A multidisciplinary approach, involving surgeons, medical oncologists, and radiation oncologists, as well as dentists, dietitians, and rehabilitation therapists, is generally required for optimal treatment planning and management of patients with head and neck cancer. © 2015 S. Karger AG, Basel.

The Protective Role of Melanin Against UV Damage in Human Skin

PubMed Central

Brenner, Michaela; Hearing, Vincent J.

2009-01-01

Human skin is repeatedly exposed to ultraviolet radiation (UVR) that influences the function and survival of many cell types and is regarded as the main causative factor in the induction of skin cancer. It has been traditionally believed that skin pigmentation is the most important photoprotective factor, since melanin, besides functioning as a broadband UV absorbent, has antioxidant and radical scavenging properties. Besides, many epidemiological studies have shown a lower incidence for skin cancer in individuals with darker skin compared to those with fair skin. Skin pigmentation is of great cultural and cosmetic importance, yet the role of melanin in photoprotection is still controversial. This article outlines the major acute and chronic effects of UV radiation on human skin, the properties of melanin, the regulation of pigmentation and its effect on skin cancer prevention. PMID:18435612

The complete DNA sequence of lymphocystis disease virus.

PubMed

Tidona, C A; Darai, G

1997-04-14

Lymphocystis disease virus (LCDV) is the causative agent of lymphocystis disease, which has been reported to occur in over 100 different fish species worldwide. LCDV is a member of the family Iridoviridae and the type species of the genus Lymphocystivirus. The virions contain a single linear double-stranded DNA molecule, which is circularly permuted, terminally redundant, and heavily methylated at cytosines in CpG sequences. The complete nucleotide sequence of LCDV-1 (flounder isolate) was determined by automated cycle sequencing and primer walking. The genome of LCDV-1 is 102.653 bp in length and contains 195 open reading frames with coding capacities ranging from 40 to 1199 amino acids. Computer-assisted analyses of the deduced amino acid sequences led to the identification of several putative gene products with significant homologies to entries in protein data banks, such as the two major subunits of the viral DNA-dependent RNA polymerase, DNA polymerase, several protein kinases, two subunits of the ribonucleoside diphosphate reductase, DNA methyltransferase, the viral major capsid protein, insulin-like growth factor, and tumor necrosis factor receptor homolog.

Genetic and environmental melanoma models in fish

PubMed Central

Patton, E Elizabeth; Mitchell, David L; Nairn, Rodney S

2010-01-01

Experimental animal models are extremely valuable for the study of human diseases, especially those with underlying genetic components. The exploitation of various animal models, from fruitflies to mice, has led to major advances in our understanding of the etiologies of many diseases, including cancer. Cutaneous malignant melanoma is a form of cancer for which both environmental insult (i.e., UV) and hereditary predisposition are major causative factors. Fish melanoma models have been used in studies of both spontaneous and induced melanoma formation. Genetic hybrids between platyfish and swordtails, different species of the genus Xiphophorus, have been studied since the 1920s to identify genetic determinants of pigmentation and melanoma formation. Recently, transgenesis has been used to develop zebrafish and medaka models for melanoma research. This review will provide a historical perspective on the use of fish models in melanoma research, and an updated summary of current and prospective studies using these unique experimental systems. PMID:20230482

Does chaos theory have major implications for philosophy of medicine?

PubMed

Holm, S

2002-12-01

In the literature it is sometimes claimed that chaos theory, non-linear dynamics, and the theory of fractals have major implications for philosophy of medicine, especially for our analysis of the concept of disease and the concept of causation. This paper gives a brief introduction to the concepts underlying chaos theory and non-linear dynamics. It is then shown that chaos theory has only very minimal implications for the analysis of the concept of disease and the concept of causation, mainly because the mathematics of chaotic processes entail that these processes are fully deterministic. The practical unpredictability of chaotic processes, caused by their extreme sensitivity to initial conditions, may raise practical problems in diagnosis, prognosis, and treatment, but it raises no major theoretical problems. The relation between chaos theory and the problem of free will is discussed, and it is shown that chaos theory may remove the problem of predictability of decisions, but does not solve the problem of free will. Chaos theory may thus be very important for our understanding of physiological processes, and specific disease entities, without having any major implications for philosophy of medicine.

"Association or causation?" The debate on the scientific status of risk factor epidemiology, 1947-c. 1965.

PubMed

Berlivet, Luc

2005-01-01

In the second half of the twentieth century, epidemiology came to shape public health discourses and practices to an unprecedented extent. The chapter explores the transformation of the discipline after World War Two and analyses the crucial debate on the notion of "causation" that sprung from the growing interest in non-transmissible, chronic diseases. A landmark in this history was the controversy over the interpretation of the statistical relationship between smoking and lung cancer prompted by American and British publications in 1950. This sometimes heated debate also provided Austin Bradford Hill with the opportunity to set out his "pragmatics" of risk factor epidemiology.

Microbial causes of endodontic flare-ups.

PubMed

Siqueira, Jose F

2003-07-01

Inter-appointment flare-up is characterized by the development of pain, swelling or both, following endodontic intervention. The causative factors of flare-ups encompass mechanical, chemical and/or microbial injury to the pulp or periradicular tissues. Of these factors, microorganisms are arguably the major causative agents of flare-ups. Even though the host is usually unable to eliminate the root canal infection, mobilization and further concentration of defence components at the periradicular tissues impede spreading of infection, and a balance between microbial aggression and host defences is commonly achieved. There are some situations during endodontic therapy in which such a balance may be disrupted in favour of microbial aggression, and an acute periradicular inflammation can ensue. Situations include apical extrusion of infected debris, changes in the root canal microbiota and/or in environmental conditions caused by incomplete chemo-mechanical preparation, secondary intraradicular infections and perhaps the increase in the oxidation-reduction potential within the root canal favouring the overgrowth of the facultative bacteria. Based on these situations, preventive measures against infective flare-ups are proposed, including selection of instrumentation techniques that extrude lesser amounts of debris apically; completion of the chemo-mechanical procedures in a single visit; use of an antimicrobial intracanal medicament between appointments in the treatment of infected cases; not leaving teeth open for drainage and maintenance of the aseptic chain throughout endodontic treatment. Knowledge about the microbial causes of flare-ups and adoption of appropriate preventive measures can significantly reduce the incidence of this highly distressing and undesirable clinical phenomenon.

Flavonoid-Based Therapies in the Early Management of Neurodegenerative Diseases12

PubMed Central

Solanki, Isha; Parihar, Priyanka; Mansuri, Mohammad Lukman; Parihar, Mordhwaj S

2015-01-01

During the past several years, there has been enormous progress in the understanding of the causative factors that initiate neuronal damage in various neurodegenerative diseases, including Alzheimer disease, Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington disease. Preventing neuronal damage and neuronal death will have a huge clinical benefit. However, despite major advances in causative factors that trigger these neurodegenerative diseases, to date there have been no therapies available that benefit patients who suffer from these diseases. Because most neurodegenerative diseases are late-onset and remain asymptomatic for most of the phases, the therapies initiated in advanced stages of the disease have limited value to patients. It may be possible to prevent or halt the disease progression to a great extent if therapies start at the initial stage of the disease. Such therapies may restore neuronal function by reducing or even eliminating the primary stressor. Flavonoids are key compounds for the development of a new generation of therapeutic agents that are clinically effective in treating neurodegenerative diseases. Regular consumption of flavonoids has been associated with a reduced risk of neurodegenerative diseases. In addition to their antioxidant properties, these polyphenolic compounds exhibit neuroprotective properties by their interaction with cellular signaling pathways followed by transcription and translation that mediate cell function under both normal and pathologic conditions. This review focuses on human intervention studies as well as animal studies on the role of various flavonoids in the prevention of neurodegenerative diseases. PMID:25593144

Fatal light aircraft accidents in Ontario: a five year study.

PubMed

Shkrum, M J; Hurlbut, D J; Young, J G

1996-03-01

Fatal civil aviation crashes in Ontario from 1985 to 1989 were studied. Data regarding accident circumstances, injury patterns and medical factors (disease, alcohol/drugs) which could have contributed to accident causation was obtained from a review of the files of the Chief Coroner for Ontario in Toronto and the aviation occurrence reports of the Transportation Safety Board of Canada. Forty-seven crashes involving mainly general aviation type aircraft but also 2 gyroplanes, 2 ultralights and a glider were reviewed. About half occurred during the cruise phase of the flight. Seventy (40 pilots; 30 passengers) of the 98 occupants died. The bodies of 68 victims were recovered; 63 were dead at the scene and 5 survived up to ten hours after impact. Multiple trauma killed about half of all the victims (n = 34); 29% (n = 20) drowned; 16% (n = 11) and 3% (n = 2) died of head/neck injuries and coronary disease respectively. Neck trauma was observed mostly in pilots and was the most frequent major blunt trauma injury in drowning victims. Passengers sustained relatively more craniofacial fractures and abdominal/retroperitoneal trauma. Pilot error was the most frequent cause of crashes (55%; 26/47 impacts) followed by mechanical failure (15%; 7/47) and adverse weather/environmental conditions (11%; 5/47). Coronary artery disease incapacitated two pilots (4% of crashes) and ethanol intoxication was implicated in two other accidents. Other drugs did not appear to be a definite factor in accident causation.

Nutritional habits, lifestyle, and genetic predisposition in cardiovascular and metabolic traits in Turkish population.

PubMed

Karaca, Sefayet; Erge, Sema; Cesuroglu, Tomris; Polimanti, Renato

2016-06-01

Cardiovascular and metabolic traits (CMT) are influenced by complex interactive processes including diet, lifestyle, and genetic predisposition. The present study investigated the interactions of these risk factors in relation to CMTs in the Turkish population. We applied bootstrap agglomerative hierarchical clustering and Bayesian network learning algorithms to identify the causative relationships among genes involved in different biological mechanisms (i.e., lipid metabolism, hormone metabolism, cellular detoxification, aging, and energy metabolism), lifestyle (i.e., physical activity, smoking behavior, and metropolitan residency), anthropometric traits (i.e., body mass index, body fat ratio, and waist-to-hip ratio), and dietary habits (i.e., daily intakes of macro- and micronutrients) in relation to CMTs (i.e., health conditions and blood parameters). We identified significant correlations between dietary habits (soybean and vitamin B12 intakes) and different cardiometabolic diseases that were confirmed by the Bayesian network-learning algorithm. Genetic factors contributed to these disease risks also through the pleiotropy of some genetic variants (i.e., F5 rs6025 and MTR rs180508). However, we also observed that certain genetic associations are indirect since they are due to the causative relationships among the CMTs (e.g., APOC3 rs5128 is associated with low-density lipoproteins cholesterol and, by extension, total cholesterol). Our study applied a novel approach to integrate various sources of information and dissect the complex interactive processes related to CMTs. Our data indicated that complex causative networks are present: causative relationships exist among CMTs and are affected by genetic factors (with pleiotropic and non-pleiotropic effects) and dietary habits. Copyright © 2016 Elsevier Inc. All rights reserved.

Application of fault tree approach for the causation mechanism of urban haze in Beijing--Considering the risk events related with exhausts of coal combustion.

PubMed

Huang, Weiqing; Fan, Hongbo; Qiu, Yongfu; Cheng, Zhiyu; Qian, Yu

2016-02-15

Haze weather has become a serious environmental pollution problem which occurs in many Chinese cities. One of the most critical factors for the formation of haze weather is the exhausts of coal combustion, thus it is meaningful to figure out the causation mechanism between urban haze and the exhausts of coal combustion. Based on above considerations, the fault tree analysis (FAT) approach was employed for the causation mechanism of urban haze in Beijing by considering the risk events related with the exhausts of coal combustion for the first time. Using this approach, firstly the fault tree of the urban haze causation system connecting with coal combustion exhausts was established; consequently the risk events were discussed and identified; then, the minimal cut sets were successfully determined using Boolean algebra; finally, the structure, probability and critical importance degree analysis of the risk events were completed for the qualitative and quantitative assessment. The study results proved that the FTA was an effective and simple tool for the causation mechanism analysis and risk management of urban haze in China. Copyright © 2015 Elsevier B.V. All rights reserved.

FOOT ECZEMA: THE ROLE OF PATCH TEST IN DETERMINING THE CAUSATIVE AGENT USING STANDARD SERIES

PubMed Central

Priya, K S; Kamath, Ganesh; Martis, Jacintha; D, Sukumar; Shetty, Narendra J; Bhat, Ramesh M; Kishore, B Nanda

2008-01-01

Foot dermatitis refers to the predominant involvement of feet in the eczematous process. This study is undertaken to determine the clinical pattern and causative agent in foot eczema and to evaluate the role of patch testing in determining the causative agent of foot eczema. Data was collected from 50 patients with foot eczema, who attended the out-patient department. The patch test was performed using Indian standard series. Patch test was positive in 88% of the patients. The most common site affected was the dorsal aspect of the foot (48%) and scaly plaque was the predominant morphological pattern. The highest number of patients (24%) showed positive reactions to mercaptobenzothiazole (MBT) and the lowest (4%) to neomycin sulfate. Rubber and rubber chemicals have been reported worldwide to be the most common sensitizer causing foot eczema. Thus, patch test has a major role in finding out the cause of foot eczema. PMID:19881990

Warfarin-induced toxic epidermal necrolysis in combination therapy of Henoch-Schönlein purpura nephritis: a case report.

PubMed

Kasahara, Katsuaki; Gotoh, Yoshimitsu; Kuroyanagi, Yoshiyuki; Nagano, China

2017-07-14

Toxic epidermal necrolysis (TEN) is a rare life-threatening condition almost exclusively attributed to drugs. The main etiologic factors for TEN are sulphonamides, anticonvulsants, and antibiotics; however, there are no published reports of warfarin causing TEN. We present the case of a 3-year-old patient who developed TEN while receiving treatment for Henoch-Schönlein purpura nephritis (HSPN). With multiple-drug therapy comprising prednisolone, mizoribine, dipyridamole, and warfarin, it is difficult to detect which drug is the causative agent. While in most cases, diagnosis of the causative drug is based on clinical history without a lymphocyte transformation test (LTT), we performed the test three times and identified the causative drug as warfarin at the late phase. We continued HSPN treatment without warfarin, and results showed good renal function without life-threatening complications. To our knowledge, this is the first report about TEN caused by warfarin. Repeated LTTs could be useful for identifying TEN-causative drugs even in the late phase.

DNA from BK Virus and JC Virus and from KI, WU, and MC Polyomaviruses as Well as from Simian Virus 40 Is Not Detected in Non-UV-Light-Associated Primary Malignant Melanomas of Mucous Membranes ▿

PubMed Central

Giraud, Géraldine; Ramqvist, Torbjörn; Ragnarsson-Olding, Boel; Dalianis, Tina

2008-01-01

The single most important causative factor for malignant melanomas of the skin is UV radiation. However, this is not true for melanomas on body surfaces sheltered from the sun; thus, it is important to seek new causative factors of melanoma genesis. Human papillomaviruses and gammaherpesviruses are associated with human skin cancer; for example, human papillomavirus types 5 and 8 are associated with epidermodysplasia verruciformis, and human herpesvirus 8 is associated with Kaposi's sarcoma. Recently, a newly described human polyomavirus, Merkel cell polyomavirus (MCPyV), has been associated with Merkel cell carcinoma, an unusual form of neurotropic skin cancer. Moreover, melanocytes are of neuroepithelial origin. This background impelled us to investigate if human polyomavirus DNA could play a role in the development of extracutaneous melanomas. Sixty-four extracutaneous melanomas were initially collected and dissected. Of these, 38 could be successfully used for further testing for the presence of the five human polyomaviruses known so far—BK virus (BKV), JC virus (JCV), KI polyomavirus (KIPyV), WU polyomavirus (WUPyV), and MCPyV—and of simian virus 40 (SV40). No polyomavirus DNA could be detected in any of the samples tested by use of a nested PCR detecting BKV, JCV, and SV40; a newly designed PCR detecting KIPyV and WUPyV; or a newly designed PCR for MCPyV. We conclude that since no human polyomavirus DNA was detected in primary malignant melanomas on non-sun-exposed body surfaces, these polyomaviruses presumably are not major factors for the development of extracutaneous melanomas. PMID:18768658

Prognosis of chronic pulmonary aspergillosis in patients with pulmonary non-tuberculous mycobacterial disease.

PubMed

Naito, Maiko; Kurahara, Yu; Yoshida, Shiomi; Ikegami, Naoya; Kobayashi, Takehiko; Minomo, Shojiro; Tachibana, Kazunobu; Tsuyuguchi, Kazunari; Hayashi, Seiji; Suzuki, Katsuhiro

2018-05-11

Pulmonary non-tuberculous mycobacterial disease (PNTM) is a known risk factor for chronic pulmonary aspergillosis (CPA). However, few studies have focused on the prognosis of PNTM-associated CPA. In the present investigation, we aimed to elucidate the clinical course and prognostic factors of CPA in patients with PNTM. We retrospectively investigated the medical records of 62 patients with CPA and a history of PNTM who were admitted to Kinki-chuo Chest Medical Center between 2010 and 2015. Co-morbidities, causative microorganisms, radiological findings, and outcomes were evaluated. The patients' median age was 69.5 years, and the median follow-up period was 4.2 years. The major underlying diseases, other than PNTM and CPA, were old pulmonary tuberculosis, chronic obstructive pulmonary disease, and interstitial pneumonia. The most common causative NTM species were Mycobacterium avium complex (MAC; 37 patients; 59.7%) and Mycobacterium kansasii (20 patients; 32.3%). Survival was 83% after 1 year and 61% after 5 years. Use of systemic corticosteroids (hazard ratio: 3.32, 95% confidence interval: 1.23-9.51; P=0.00177) and C-reactive protein levels ≥ 5.0 mg/dL (hazard ratio: 8.96, 95% confidence interval: 2.15-62.9; P=0.0014) at the time of CPA diagnosis were associated with increased over-all mortality. CPA frequently developed in patients with MAC and M. kansasii PNTM. The treatment course of PNTM was not associated with all-cause mortality. However, systemic corticosteroid use and high CRP levels were negative prognostic factors of CPA in patients with PNTM. Since the prognosis is poor, early diagnosis and treatment of CPA are important in patients with PNTM. Copyright © 2018 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

TIA-1 and TIAR interact with 5'-UTR of enterovirus 71 genome and facilitate viral replication.

PubMed

Wang, Xiaohui; Wang, Huanru; Li, Yixuan; Jin, Yu; Chu, Ying; Su, Airong; Wu, Zhiwei

2015-10-16

Enterovirus 71 is one of the major causative pathogens of HFMD in children. Upon infection, the viral RNA is translated in an IRES-dependent manner and requires several host factors for effective replication. Here, we found that T-cell-restricted intracellular antigen 1 (TIA-1), and TIA-1 related protein (TIAR) were translocated from nucleus to cytoplasm after EV71 infection and localized to the sites of viral replication. We found that TIA-1 and TIAR can facilitate EV71 replication by enhancing the viral genome synthesis in host cells. We demonstrated that both proteins bound to the stem-loop I of 5'-UTR of viral genome and improved the stability of viral genomic RNA. Our results suggest that TIA-1 and TIAR are two new host factors that interact with 5-UTR of EV71 genome and positively regulate viral replication. Copyright © 2015 Elsevier Inc. All rights reserved.

Recent advances in the management of transient ischemic attacks

PubMed Central

Gomez, Camilo R.; Schneck, Michael J.; Biller, Jose

2017-01-01

Significant advances in our understanding of transient ischemic attack (TIA) have taken place since it was first recognized as a major risk factor for stroke during the late 1950's. Recently, numerous studies have consistently shown that patients who have experienced a TIA constitute a heterogeneous population, with multiple causative factors as well as an average 5–10% risk of suffering a stroke during the 30 days that follow the index event. These two attributes have driven the most important changes in the management of TIA patients over the last decade, with particular attention paid to effective stroke risk stratification, efficient and comprehensive diagnostic assessment, and a sound therapeutic approach, destined to reduce the risk of subsequent ischemic stroke. This review is an outline of these changes, including a discussion of their advantages and disadvantages, and references to how new trends are likely to influence the future care of these patients. PMID:29263784

Syphilis may be a confounding factor, not a causative agent, in syphilitic ALS.

PubMed

Tuk, Bert

2016-01-01

Based upon a review of published clinical observations regarding syphilitic amyotrophic lateral sclerosis (ALS), I hypothesize that syphilis is actually a confounding factor, not a causative factor, in syphilitic ALS. Moreover, I propose that the successful treatment of ALS symptoms in patients with syphilitic ALS using penicillin G and hydrocortisone is an indirect consequence of the treatment regimen and is not due to the treatment of syphilis. Specifically, I propose that the observed effect is due to the various pharmacological activities of penicillin G ( e.g ., a GABA receptor antagonist) and/or the multifaceted pharmacological activity of hydrocortisone. The notion that syphilis may be a confounding factor in syphilitic ALS is highly relevant, as it suggests that treating ALS patients with penicillin G and hydrocortisone-regardless of whether they present with syphilitic ALS or non-syphilitic ALS-may be effective at treating this rapidly progressive, highly devastating disease.

Making environmental health interesting for medical students-internet assisted facilitated collaborative learning approach.

PubMed

Sudharsanam, Manni Balasubramaniam

2014-01-01

Topics on environmental health are usually neglected by students and it is necessary for them to learn this area with a public health perspective as environment plays a vital role in multi-factorial causation of diseases. Hence there is a need for alternative teaching/learning methods to facilitate students in acquiring the required knowledge. To increase the student interest and enhance their participation in acquiring knowledge in public health perspective of environmental health. Teaching Objectives/Learning Were: At the end of the session students should know the importance of air as an environmental factor in disease causation in special reference to public health hazards, the major sources of air pollution, major pollutants causing the health hazards, the way to measure pollutants and control them. The whole class of students was divided into two batches and one session was planned for each batch. Each batch was divided into six small groups. The groups were given task of exploring the internet on the different topics mentioned in the learning objectives. All the students were asked to explore, compile information and collectively prepare a presentation and present their findings based on their reviews. Students' feedback was collected at the end of each session. Eighty five percent of them were clear about the learning objectives and interested about internet learning. Most of them gave a positive opinion about the newer teaching learning method. Internet assisted group study served as a valuable alternative, innovative, and interesting tool to teach and learn the environmental health as revealed by students' feedback.

Stroke subtyping for genetic association studies? A comparison of the CCS and TOAST classifications.

PubMed

Lanfranconi, Silvia; Markus, Hugh S

2013-12-01

A reliable and reproducible classification system of stroke subtype is essential for epidemiological and genetic studies. The Causative Classification of Stroke system is an evidence-based computerized algorithm with excellent inter-rater reliability. It has been suggested that, compared to the Trial of ORG 10172 in Acute Stroke Treatment classification, it increases the proportion of cases with defined subtype that may increase power in genetic association studies. We compared Trial of ORG 10172 in Acute Stroke Treatment and Causative Classification of Stroke system classifications in a large cohort of well-phenotyped stroke patients. Six hundred ninety consecutively recruited patients with first-ever ischemic stroke were classified, using review of clinical data and original imaging, according to the Trial of ORG 10172 in Acute Stroke Treatment and Causative Classification of Stroke system classifications. There was excellent agreement subtype assigned by between Trial of ORG 10172 in Acute Stroke Treatment and Causative Classification of Stroke system (kappa = 0·85). The agreement was excellent for the major individual subtypes: large artery atherosclerosis kappa = 0·888, small-artery occlusion kappa = 0·869, cardiac embolism kappa = 0·89, and undetermined category kappa = 0·884. There was only moderate agreement (kappa = 0·41) for the subjects with at least two competing underlying mechanism. Thirty-five (5·8%) patients classified as undetermined by Trial of ORG 10172 in Acute Stroke Treatment were assigned to a definite subtype by Causative Classification of Stroke system. Thirty-two subjects assigned to a definite subtype by Trial of ORG 10172 in Acute Stroke Treatment were classified as undetermined by Causative Classification of Stroke system. There is excellent agreement between classification using Trial of ORG 10172 in Acute Stroke Treatment and Causative Classification of Stroke systems but no evidence that Causative Classification of Stroke system reduced the proportion of patients classified to undetermined subtypes. The excellent inter-rater reproducibility and web-based semiautomated nature make Causative Classification of Stroke system suitable for multicenter studies, but the benefit of reclassifying cases already classified using the Trial of ORG 10172 in Acute Stroke Treatment system on existing databases is likely to be small. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

The causes of epilepsy: changing concepts of etiology of epilepsy over the past 150 years.

PubMed

Shorvon, Simon D

2011-06-01

This paper provides a survey of the changing concepts of the etiology of epilepsy from 1860 to 2010, focusing on the first two 50-year periods and outlining more briefly major developments in the past 50 years. Among the concepts reviewed in the first 100 years are: the division between predisposing and exciting causes, idiopathic and genuine epilepsy, organic epilepsy, the concept of "cause" being equivalent to "causal mechanism," Russell Reynolds etiological classification, the neurological taint and theories of degeneration, the self-perpetuating nature of seizures, reflex theories of etiology, autointoxication, heredity and eugenics, epilepsy due to brain disorders, the role of EEG and of hippocampal sclerosis, psychological theories of causation, and the multifactorial view of epilepsy etiology. In the past 50 years, the major advances in studying causation in epilepsy have been: clinical biochemistry, neuroimaging, molecular genetics, studies of mechanisms of epilepsy, better statistical methodologies and classification. A number of general observations can be made: the identification of "cause" is not as simple as it might at first appear; progress in the study of causation has been often erratic and travelled up many cul-de-sacs; theories of causation are heavily influenced by societal influences and fashion, and is also heavily dependent on applied methodologies; the recently explored possibility that the underlying inherited mechanisms of epilepsy are shared with other neuropsychiatric conditions is in effect a reinvention of the concept of the neurological trait, and this has ethical and social implications. Considering and classifying cause in terms of causal mechanism, as was suggested by Hughlings Jackson, is an ultimate goal. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

A Flexible Hierarchical Bayesian Modeling Technique for Risk Analysis of Major Accidents.

PubMed

Yu, Hongyang; Khan, Faisal; Veitch, Brian

2017-09-01

Safety analysis of rare events with potentially catastrophic consequences is challenged by data scarcity and uncertainty. Traditional causation-based approaches, such as fault tree and event tree (used to model rare event), suffer from a number of weaknesses. These include the static structure of the event causation, lack of event occurrence data, and need for reliable prior information. In this study, a new hierarchical Bayesian modeling based technique is proposed to overcome these drawbacks. The proposed technique can be used as a flexible technique for risk analysis of major accidents. It enables both forward and backward analysis in quantitative reasoning and the treatment of interdependence among the model parameters. Source-to-source variability in data sources is also taken into account through a robust probabilistic safety analysis. The applicability of the proposed technique has been demonstrated through a case study in marine and offshore industry. © 2017 Society for Risk Analysis.

Is susceptibility to tuberculosis acquired or inherited?

PubMed

Schurr, E

2007-02-01

Tuberculosis is an ongoing major public health problem on a global scale. One of the striking features of the disease is that only an estimated 10% of immunocompetent persons infected by the causative pathogen Mycobacterium tuberculosis will develop clinical signs of disease. This well-established epidemiological observation has prompted an intense search for the factors that trigger advancement of infection to disease in the small proportion of susceptible individuals. Central to this search is the questions if tuberculosis patients are inherently susceptible to the disease or if disease development is promoted by specific environmental factors. It is known that genetic and non-genetic factors of both the bacterium and the host have impact on the host response to M. tuberculosis. Yet, little is known about the interaction of these different factors and the resulting impact on disease development. Recent work suggests that in addition to common host susceptibility genes a second group of susceptibility loci exists the action of which strongly depends on the individual's clinical and exposure history. The latter genes may have a very strong effect on promoting advancement from infection to disease only in specific epidemiological settings. These findings suggest that a more detailed knowledge of gene-environment interactions in tuberculosis is necessary to understand why a small proportion of individuals are susceptible to the disease whilst the majority of humans are naturally resistant to tuberculosis.

Exploring inattention and distraction in the SafetyNet Accident Causation Database.

PubMed

Talbot, Rachel; Fagerlind, Helen; Morris, Andrew

2013-11-01

Distraction and inattention are considered to be very important and prevalent factors in the causation of road accidents. There have been many recent research studies which have attempted to understand the circumstances under which a driver becomes distracted or inattentive and how distraction/inattention can be prevented. Both factors are thought to have become more important in recent times partly due to the evolution of in-vehicle information and communication technology. This study describes a methodology that was developed to understand when factors such as distraction and inattention may have been contributors to crashes and also describes some of the consequences of distraction and inattention in terms of subsequent driver actions. The study uses data relating to distraction and inattention from the SafetyNet Accident Causation Database. This database was formulated as part of the SafetyNet project to address the lack of representative in-depth accident causation data within the European Union. Data were collected in 6 European countries using 'on-scene' and 'nearly on-scene' crash investigation methodologies. 32% of crashes recorded in the database, involved at least one driver, rider or pedestrian, who was determined to be 'Inattentive' or 'Distracted'. 212 of the drivers were assigned 'Distraction' and 140 drivers were given the code 'Inattention'. It was found that both distraction and inattention often lead to missed observations within the driving task and consequently 'Timing' or 'Direction' become critical events in the aetiology of crashes. In addition, the crash types and outcomes may differ according to the type and nature of the distraction and inattention as determined by the in-depth investigations. The development of accident coding methodology is described in this study as is its evolution into the Driver Reliability and Error Analysis Model (DREAM) version 3.0. Copyright © 2012 Elsevier Ltd. All rights reserved.

Post-craniotomy intracranial infection in patients with brain tumors: a retrospective analysis of 5723 consecutive patients.

PubMed

Shi, Zhong-Hua; Xu, Ming; Wang, Yong-Zhi; Luo, Xu-Ying; Chen, Guang-Qiang; Wang, Xin; Wang, Tao; Tang, Ming-Zhong; Zhou, Jian-Xin

2017-02-01

To determine the risk factors for and the incidence, outcomes, and causative pathogens of post-craniotomy intracranial infection (PCII) in patients with brain tumors. A retrospective study was performed of 5723 patients with brain tumors who were surgically treated between January 2012 and December 2013 in Beijing Tiantan Hospital. The patients' demographics, pathohistological diagnoses, surgical procedures, postoperative variables, causative pathogens, and outcomes were evaluated. The overall incidence of PCII was 6.8%, and 82.1% of all cases were diagnosed within two weeks after the craniotomy. Postoperative administration of antibiotics reduced the incidence of PCII. Independent risk factors included clean-contaminated craniotomy, prolonged operation (> 7 h), external cerebrospinal fluid (CSF) drainage/monitoring device placement, and postoperative CSF leakage. Patients ≤ 45 years old were more susceptible to infection. Compared with supratentorial tumors, tumors located in the infratentorial or intraventricular regions were more vulnerable to PCII. Gram-positive bacteria were the most common causative pathogens isolated from the CSF samples, accounting for 82.0% of the PCII cases. Risk factors for PCII can be identified early in the perioperative period. These findings raise the possibility of improving the clinical outcomes of patients with brain tumors who undergo craniotomy.

Analyzing the causation of a railway accident based on a complex network

NASA Astrophysics Data System (ADS)

Ma, Xin; Li, Ke-Ping; Luo, Zi-Yan; Zhou, Jin

2014-02-01

In this paper, a new model is constructed for the causation analysis of railway accident based on the complex network theory. In the model, the nodes are defined as various manifest or latent accident causal factors. By employing the complex network theory, especially its statistical indicators, the railway accident as well as its key causations can be analyzed from the overall perspective. As a case, the “7.23” China—Yongwen railway accident is illustrated based on this model. The results show that the inspection of signals and the checking of line conditions before trains run played an important role in this railway accident. In conclusion, the constructed model gives a theoretical clue for railway accident prediction and, hence, greatly reduces the occurrence of railway accidents.

Determination of bacterial activity by use of an evanescent-wave fiber-optic sensor

NASA Astrophysics Data System (ADS)

John, M. Shelly; Kishen, Anil; Sing, Lim Chu; Asundi, Anand

2002-12-01

A novel technique based on fiber-optic evanescent-wave spectroscopy is proposed for the detection of bacterial activity in human saliva. The sensor determines the specific concentration of Streptococcus mutans in saliva, which is a major causative factor in dental caries. In this design, one prepares the fiber-optic bacterial sensor by replacing a portion of the cladding region of a multimode fiber with a dye-encapsulated xerogel, using the solgel technique. The exponential decay of the evanescent wave at the core-cladding interface of a multimode fiber is utilized for the determination of bacterial activity in saliva. The acidogenic profile of Streptococcus mutans is estimated by use of evanescent-wave absorption spectra at various levels of bacterial activity.

Generation of transgenic corn-derived Actinobacillus pleuropneumoniae ApxIIA fused with the cholera toxin B subunit as a vaccine candidate

PubMed Central

Shin, Min-Kyoung; Jung, Myung Hwan; Lee, Won-Jung; Choi, Pil Son; Jang, Yong-Suk

2011-01-01

Corn, one of the most important forage crops worldwide, has proven to be a useful expression vehicle due to the availability of established transformation procedures for this well-studied plant. The exotoxin Apx, a major virulence factor, is recognized as a common antigen of Actinobacillus (A.) pleuropneumoniae, the causative agent of porcine pleuropneumonia. In this study, a cholera toxin B (CTB)-ApxIIA#5 fusion protein and full-size ApxIIA expressed in corn seed, as a subunit vaccine candidate, were observed to induce Apx-specific immune responses in mice. These results suggest that transgenic corn-derived ApxIIA and CTB-ApxIIA#5 proteins are potential vaccine candidates against A. pleuropneumoniae infection. PMID:22122907

Class I ADP-Ribosylation Factors Are Involved in Enterovirus 71 Replication

PubMed Central

Wang, Jianmin; Du, Jiang; Jin, Qi

2014-01-01

Enterovirus 71 is one of the major causative agents of hand, foot, and mouth disease in infants and children. Replication of enterovirus 71 depends on host cellular factors. The viral replication complex is formed in novel, cytoplasmic, vesicular compartments. It has not been elucidated which cellular pathways are hijacked by the virus to create these vesicles. Here, we investigated whether proteins associated with the cellular secretory pathway were involved in enterovirus 71 replication. We used a loss-of-function assay, based on small interfering RNA. We showed that enterovirus 71 RNA replication was dependent on the activity of Class I ADP-ribosylation factors. Simultaneous depletion of ADP-ribosylation factors 1 and 3, but not three others, inhibited viral replication in cells. We also demonstrated with various techniques that the brefeldin-A-sensitive guanidine nucleotide exchange factor, GBF1, was critically important for enterovirus 71 replication. Our results suggested that enterovirus 71 replication depended on GBF1-mediated activation of Class I ADP-ribosylation factors. These results revealed a connection between enterovirus 71 replication and the cellular secretory pathway; this pathway may represent a novel target for antiviral therapies. PMID:24911624

Locally aggressive and multifocal phosphaturic mesenchymal tumors: two unusual cases of tumor-induced osteomalacia.

PubMed

Higley, Meghan; Beckett, Brooke; Schmahmann, Sandra; Dacey, Elizabeth; Foss, Erik

2015-12-01

Tumor-induced osteomalacia (TIO) has long been recognized as a clinical paraneoplastic syndrome. The identification of a unique histopathologic entity, the phosphaturic mesenchymal tumor (PMT), as a distinct etiology for TIO has been a more recent discovery. The majority of published cases describe a solitary, non-aggressive appearing soft tissue or osseous lesions in patients with osteomalacia; aggressive appearing or multifocal lesions appear to be exceedingly rare. These tumors characteristically secrete fibroblast growth factor 23 (FGF23). Elevated serum levels of FGF23 result in phosphate wasting and osteomalacia. In the majority of cases, laboratory abnormalities and clinical signs and symptoms of osteomalacia precede identification of the causative lesion by years. Following diagnosis, complete resection with wide margins to prevent local recurrence is most often curative. Imaging characteristics of PMT are diverse and remain incompletely defined, as the majority of previous publications are outside of the radiologic literature. We present multiple imaging modalities in two cases of patients with debilitating osteomalacia and unusual appearing PMTs: one with a locally aggressive lesion leading to pathologic fracture, the second presenting with exceedingly rare multifocal PMT.

Knowledge about human papillomavirus (HPV) related oral cancers among oral health professionals in university setting-A cross sectional study.

PubMed

Arora, Shelly; Ramachandra, Srinivas Sulugodu; Squier, Christopher

2018-01-01

Scientific literature suggests that human papillomavirus (HPV) infection may be associated with oral squamous cell carcinoma (OSCC). However, knowledge regarding HPV-OSCC link among oral health professionals (OHP) has been insufficient. So, the aim of this study was to assess the knowledge about HPV associated OSCC among OHP working in dental faculties in Malaysia. Ethical committee of the University approved this study. A validated, pre-tested questionnaire was sent electronically to 224 OHP. Questionnaire collected information regarding demography, knowledge about HPV-OSCC link, HPV vaccine, and willingness to educate patients about HPV OSCC link among the participants of this cross-sectional study. Data collected was analysed using "Stata/IC-13" and was summarised using descriptive statistics like frequency, percentage, mean and standard deviation. Out of 179 participants, around 39% of the participant's opined virus was not a causative factor for OSCC. Around, 44% replied posterior portion of the tongue/oro-pharynx was the commonest site for HPV related OSCC, whereas 29% replied that lateral border of the tongue was the common site for HPV related OSCC. Forty one percent educated patients regarding HPV infection being a causative factor for OSCC. HPV vaccine can prevent OSCC was stated by 70% OHP. Only 12% were aware of the availability of HPV vaccine in Malaysia. Majority (99%), agreed that there is a need to offer continuing education programmes to dentists highlighting advances and preventive strategies in the fight against OSCC. Substantial increase in awareness is required among OHP regarding HPV-OSCC link.

Optimization of Causative Factors for Landslide Susceptibility Evaluation Using Remote Sensing and GIS Data in Parts of Niigata, Japan.

PubMed

Dou, Jie; Tien Bui, Dieu; Yunus, Ali P; Jia, Kun; Song, Xuan; Revhaug, Inge; Xia, Huan; Zhu, Zhongfan

2015-01-01

This paper assesses the potentiality of certainty factor models (CF) for the best suitable causative factors extraction for landslide susceptibility mapping in the Sado Island, Niigata Prefecture, Japan. To test the applicability of CF, a landslide inventory map provided by National Research Institute for Earth Science and Disaster Prevention (NIED) was split into two subsets: (i) 70% of the landslides in the inventory to be used for building the CF based model; (ii) 30% of the landslides to be used for the validation purpose. A spatial database with fifteen landslide causative factors was then constructed by processing ALOS satellite images, aerial photos, topographical and geological maps. CF model was then applied to select the best subset from the fifteen factors. Using all fifteen factors and the best subset factors, landslide susceptibility maps were produced using statistical index (SI) and logistic regression (LR) models. The susceptibility maps were validated and compared using landslide locations in the validation data. The prediction performance of two susceptibility maps was estimated using the Receiver Operating Characteristics (ROC). The result shows that the area under the ROC curve (AUC) for the LR model (AUC = 0.817) is slightly higher than those obtained from the SI model (AUC = 0.801). Further, it is noted that the SI and LR models using the best subset outperform the models using the fifteen original factors. Therefore, we conclude that the optimized factor model using CF is more accurate in predicting landslide susceptibility and obtaining a more homogeneous classification map. Our findings acknowledge that in the mountainous regions suffering from data scarcity, it is possible to select key factors related to landslide occurrence based on the CF models in a GIS platform. Hence, the development of a scenario for future planning of risk mitigation is achieved in an efficient manner.

Optimization of Causative Factors for Landslide Susceptibility Evaluation Using Remote Sensing and GIS Data in Parts of Niigata, Japan

PubMed Central

Dou, Jie; Tien Bui, Dieu; P. Yunus, Ali; Jia, Kun; Song, Xuan; Revhaug, Inge; Xia, Huan; Zhu, Zhongfan

2015-01-01

This paper assesses the potentiality of certainty factor models (CF) for the best suitable causative factors extraction for landslide susceptibility mapping in the Sado Island, Niigata Prefecture, Japan. To test the applicability of CF, a landslide inventory map provided by National Research Institute for Earth Science and Disaster Prevention (NIED) was split into two subsets: (i) 70% of the landslides in the inventory to be used for building the CF based model; (ii) 30% of the landslides to be used for the validation purpose. A spatial database with fifteen landslide causative factors was then constructed by processing ALOS satellite images, aerial photos, topographical and geological maps. CF model was then applied to select the best subset from the fifteen factors. Using all fifteen factors and the best subset factors, landslide susceptibility maps were produced using statistical index (SI) and logistic regression (LR) models. The susceptibility maps were validated and compared using landslide locations in the validation data. The prediction performance of two susceptibility maps was estimated using the Receiver Operating Characteristics (ROC). The result shows that the area under the ROC curve (AUC) for the LR model (AUC = 0.817) is slightly higher than those obtained from the SI model (AUC = 0.801). Further, it is noted that the SI and LR models using the best subset outperform the models using the fifteen original factors. Therefore, we conclude that the optimized factor model using CF is more accurate in predicting landslide susceptibility and obtaining a more homogeneous classification map. Our findings acknowledge that in the mountainous regions suffering from data scarcity, it is possible to select key factors related to landslide occurrence based on the CF models in a GIS platform. Hence, the development of a scenario for future planning of risk mitigation is achieved in an efficient manner. PMID:26214691

Landslide hazard mapping with selected dominant factors: A study case of Penang Island, Malaysia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tay, Lea Tien; Alkhasawneh, Mutasem Sh.; Ngah, Umi Kalthum

Landslide is one of the destructive natural geohazards in Malaysia. In addition to rainfall as triggering factos for landslide in Malaysia, topographical and geological factors play important role in the landslide susceptibility analysis. Conventional topographic factors such as elevation, slope angle, slope aspect, plan curvature and profile curvature have been considered as landslide causative factors in many research works. However, other topographic factors such as diagonal length, surface area, surface roughness and rugosity have not been considered, especially for the research work in landslide hazard analysis in Malaysia. This paper presents landslide hazard mapping using Frequency Ratio (FR) and themore » study area is Penang Island of Malaysia. Frequency ratio approach is a variant of probabilistic method that is based on the observed relationships between the distribution of landslides and each landslide-causative factor. Landslide hazard map of Penang Island is produced by considering twenty-two (22) landslide causative factors. Among these twenty-two (22) factors, fourteen (14) factors are topographic factors. They are elevation, slope gradient, slope aspect, plan curvature, profile curvature, general curvature, tangential curvature, longitudinal curvature, cross section curvature, total curvature, diagonal length, surface area, surface roughness and rugosity. These topographic factors are extracted from the digital elevation model of Penang Island. The other eight (8) non-topographic factors considered are land cover, vegetation cover, distance from road, distance from stream, distance from fault line, geology, soil texture and rainfall precipitation. After considering all twenty-two factors for landslide hazard mapping, the analysis is repeated with fourteen dominant factors which are selected from the twenty-two factors. Landslide hazard map was segregated into four categories of risks, i.e. Highly hazardous area, Hazardous area, Moderately hazardous area and Not hazardous area. The maps was assessed using ROC (Rate of Curve) based on the area under the curve method (AUC). The result indicates an increase of accuracy from 77.76% (with all 22 factors) to 79.00% (with 14 dominant factors) in the prediction of landslide occurrence.« less

Age-Based Causes and Clinical Characteristics of Immediate-Type Food Allergy in Korean Children

PubMed Central

Jeong, Kyunguk; Kim, Jihyun; Ahn, Kangmo; Lee, So-Yeon; Min, Taek Ki; Pyun, Bok Yang; Kim, Yoon Hee; Kim, Kyung Won; Sohn, Myung Hyun; Kim, Kyu-Earn; Jang, Gwang Cheon; Song, Tae-Won; Kim, Jung Hee; Jeon, You Hoon; Lee, Yong Ju; Park, Yong Mean; Yum, Hye Yung; Kim, Hyun Hee; Kim, Woo Kyung

2017-01-01

Purpose Age-based causes and clinical characteristics of immediate-type food allergy (FA) have not been sufficiently studied. Therefore, we investigated age-dependent clinical profiles of FA in Korean children through an extensive multicenter investigation. Methods Using a case report form developed by the authors, a retrospective medical record review was performed of patients (0-18 years old) diagnosed with immediate-type FA between September 2014 and August 2015 in 14 tertiary hospitals in Korea. Results A total of 1,353 children and adolescents, 93% younger than 7 years, were enrolled in the present study, and 1,661 cases of immediate-type FA were recorded in these patients. The 7 major causative foods were cow's milk (28.1%), hen's eggs (27.6%), wheat (7.9%), walnuts (7.3%), peanuts (5.3%), buckwheat (1.9%), and shrimps (1.9%). Categorizing the patients into 4 age groups revealed that the most common causative food was different for each age group: cow's milk (<2 years), walnuts (2–6 years), walnuts (7–12 years), and buckwheat (13-18 years). The onset time of symptoms was less than 10 minutes in 49%, between 10 and 30 minutes in 17%, and between 30 minutes and 2 hours in 34% of cases. Food-induced anaphylaxis was reported in 506 (30.5%) out of 1,661 cases, and the 7 major causes of food-induced anaphylaxis was cow's milk (27.5%), hen's eggs (21.9%), wheat (11.3%), walnuts (10.5%), peanuts (5.9%), buckwheat (4.2%), and pine nuts (3.0%). The proportion of anaphylaxis was highest in the patients allergic to buckwheat (67.7%), followed by those allergic to pine nuts (57.7%), walnuts (43.8%), wheat (43.5%), and peanuts (34.1%). Conclusions The 5 major causative foods of immediate-type FA in Korean children were cow's milk, hen's eggs, wheat, walnuts, and peanuts. The distribution of causative foods was considerably distinctive according to different age groups. Anaphylaxis was reported in 30.5% of immediate-type FA cases. PMID:28677356

Human gastroenteritis outbreak associated with Escherichia albertii, Japan.

PubMed

Ooka, Tadasuke; Tokuoka, Eisuke; Furukawa, Masato; Nagamura, Tetsuya; Ogura, Yoshitoshi; Arisawa, Kokichi; Harada, Seiya; Hayashi, Tetsuya

2013-01-01

Although Escherichia albertii is an emerging intestinal pathogen, it has been associated only with sporadic human infections. In this study, we determined that a human gastroenteritis outbreak at a restaurant in Japan had E. albertii as the major causative agent.

Systematic review of environmental risk factors for Obsessive-Compulsive Disorder: A proposed roadmap from association to causation.

PubMed

Brander, Gustaf; Pérez-Vigil, Ana; Larsson, Henrik; Mataix-Cols, David

2016-06-01

To synthesize the current knowledge on possible environmental risk factors for Obsessive-Compulsive Disorder (OCD). We conducted a systematic review following PRISMA guidelines. The Embase, PubMed and Scopus databases were searched up until October 6, 2015, employing relevant keywords and MeSH terms. 128 studies met inclusion criteria. Potential environmental risk factors for OCD have been identified in the broad areas of perinatal complications, reproductive cycle, and stressful life events. There is limited evidence regarding other potential risk factors, such as parental age, season of birth, socioeconomic status, parental rearing practices, infections, traumatic brain injury, substance use or vitamin deficiency. In general, studies were of limited methodological quality. At present, no environmental risk factors have convincingly been associated with OCD. We propose a roadmap for future studies, consisting of longitudinal, population-based research, employing quasi-experimental family and twin designs to identify risk factors that are not only associated with the disorder but also contribute to its causation either directly or moderating the effect of genes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cause or Effect? Selective Serotonin Reuptake Inhibitors and Falls in Older Adults: A Systematic Review

PubMed Central

Gebara, Marie Anne; Lipsey, Kim L.; Karp, Jordan F.; Nash, Maureen C.; Iaboni, Andrea; Lenze, Eric J.

2014-01-01

A 2012 update of the Beers criteria categorizes selective serotonin reuptake inhibitors (SSRIs) as potentially inappropriate medications in all older adults based on fall risk. The application of these recommendations, not only to frail nursing home residents, but also to all older adults, may lead to changes in health policy or clinical practice with harmful consequences. A systematic review of studies on the association between SSRIs and falls in older adults was conducted to examine the evidence for causation. Twenty-six studies met the inclusion criteria. The majority of studies were observational and suggest an association between SSRIs and falls. The direction of the relationship – causation or effect- cannot be discerned from this type of study. Standardized techniques for determining likely causation were then used to see if there was support for the hypothesis that SSRI’s lead to falls. This analysis did not suggest causation was likely. There is no Level 1 evidence that SSRIs cause falls. Therefore, changes in the current treatment guidelines or policies on the use of SSRIs in older adults based on fall risk may not be justified at this time given the lack of an established evidence base. Given its significance to public health, well-designed experimental studies are required to address this question definitively. PMID:25586602

Vocal fold nodules in adult singers: regional opinions about etiologic factors, career impact, and treatment. A survey of otolaryngologists, speech pathologists, and teachers of singing.

PubMed

Hogikyan, N D; Appel, S; Guinn, L W; Haxer, M J

1999-03-01

This study was undertaken to better understand current regional opinions regarding vocal fold nodules in adult singers. A questionnaire was sent to 298 persons representing the 3 professional groups most involved with the care of singers with vocal nodules: otolaryngologists, speech pathologists, and teachers of singing. The questionnaire queried respondents about their level of experience with this problem, and their beliefs about causative factors, career impact, and optimum treatment. Responses within and between groups were similar, with differences between groups primarily in the magnitude of positive or negative responses, rather than in the polarity of the responses. Prevailing opinions included: recognition of causative factors in both singing and speaking voice practices, optimism about responsiveness to appropriate treatment, enthusiasm for coordinated voice therapy and voice training as first-line treatment, and acceptance of microsurgical management as appropriate treatment if behavioral management fails.

If it is published in the peer-reviewed literature, it must be true?

PubMed

Wagner, Louis K

2014-10-01

Epidemiological research correlating cancer rates in a population of patients with radiation doses from medical X-rays is fraught with confounding factors that obfuscate the likelihood that any positive relationship is causal. This is a review of four studies involving some of those confounding factors. Comparisons of findings with other studies not encumbered by similar confounding factors can enhance assertions of causation between medical X-rays and cancer rates. Even so, such assertions rest significantly on opinions of researchers regarding the degree of consistency between findings among various studies. The question as to what degree any findings truly represent cause and effect will likely still meet with controversy. The importance of these findings to medicine should therefore not lie in any controversy regarding causation, but in what the findings potentially mean with regard to benefit and risk for patients and the professional practice of medicine.

RESIDENTIAL BUILDING STAKEHOLDERS’ ATTITUDES AND BELIEFS REGARDING NAIL GUN INJURY RISKS AND PREVENTION

PubMed Central

ALBERS, JAMES T.; HUDOCK, STEPHEN D.; LOWE, BRIAN D.

2015-01-01

Pneumatic nail guns are ubiquitous at residential construction sites across the United States. These tools are noted for the traumatic injuries that can occur from their operation. Different trigger mechanisms on these tools are associated with different levels of risk. Residential building subcontractors and workers, both native-born and immigrant, were brought together in focus groups to discuss their attitudes and beliefs regarding risk factors for nail gun injury as well as barriers to the adoption of safer technology. Participants’ comments are organized first by influences on traumatic injury occurrence or prevention and later by sociotechnical system category. Participants attributed influences on injury risk to personal and external causation factors in all sociotechnical system categories; however, participants more frequently described influences on injury prevention as related to workers’ behaviors, rather than to external factors. A discussion of these influences with respect to attribution theory and sociotechnical models of injury causation is presented. PMID:24704813

Alterations of serum macro-minerals and trace elements are associated with major depressive disorder: a case-control study.

PubMed

Islam, Md Rabiul; Islam, Md Reazul; Shalahuddin Qusar, M M A; Islam, Mohammad Safiqul; Kabir, Md Humayun; Mustafizur Rahman, G K M; Islam, Md Saiful; Hasnat, Abul

2018-04-10

Major depressive disorder (MDD) is a mixed disorder with the highly irregular course, inconsistent response to treatment and has no well-known mechanism for the pathophysiology. Major causes of depression are genetic, neurobiological, and environmental. However, over the past few years, altered serum levels of macro-minerals (MM) and trace elements (TE) have been recognized as major causative factors to the pathogenesis of many mental disorders. The purpose of this study was to determine the serum levels of MM (calcium and magnesium) and TE (copper, iron, manganese, selenium, and zinc) in MDD patients and find out their associations with depression risk. This prospective case-control study recruited 247 patients and 248 healthy volunteers matched by age and sex. The serum levels of MM and TE were analyzed by atomic absorption spectroscopy (AAS). Statistical analysis was performed with independent sample t-tests and Pearson's correlation test. We found significantly decreased concentrations of calcium and magnesium, iron, manganese, selenium, and zinc in MDD patients compared with control subjects (p < 0.05). But the concentration of copper was significantly increased in the patients than control subjects (p < 0.05). Data obtained from different inter-element relations in MDD patients and control subjects strongly suggest that there is a disturbance in the element homeostasis. Our study suggests that altered serum concentrations of MM and TE are major contributing factors for the pathogenesis of MDD. Alterations of these elements in serum levels of MDD patients arise independently and they may provide a prognostic tool for the assessment of depression risk.

Rapidly-growing mycobacterial infection: a recognized cause of early-onset prosthetic joint infection.

PubMed

Jitmuang, Anupop; Yuenyongviwat, Varah; Charoencholvanich, Keerati; Chayakulkeeree, Methee

2017-12-28

Prosthetic joint infection (PJI) is a major complication of total hip and total knee arthroplasty (THA, TKA). Although mycobacteria are rarely the causative pathogens, it is important to recognize and treat them differently from non-mycobacterial infections. This study aimed to compare the clinical characteristics, associated factors and long-term outcomes of mycobacterial and non-mycobacterial PJI. We conducted a retrospective case-control study of patients aged ≥18 years who were diagnosed with PJI of the hip or knee at Siriraj Hospital from January 2000 to December 2012. Patient characteristics, clinical data, treatments and outcomes were evaluated. A total of 178 patients were included, among whom 162 had non-mycobacterial PJI and 16 had mycobacterial PJI. Rapidly growing mycobacteria (RGM) (11) and M. tuberculosis (MTB) (5) were the causative pathogens of mycobacterial PJI. PJI duration and time until onset were significantly different between mycobacterial and non-mycobacterial PJI. Infection within 90 days of arthroplasty was significantly associated with RGM infection (OR 21.86; 95% CI 4.25-112.30; p < .001). Implant removal was associated with improved favorable outcomes at 6 months (OR 5.96; 95% CI 1.88-18.88; p < .01) and 12 months (OR 3.96; 95% CI 1.15-13.71; p = .03) after the infection. RGM were the major pathogens of early onset PJI after THA and TKA. Both a high clinical index of suspicion and mycobacterial cultures are recommended when medically managing PJI with negative cultures or non-response to antibiotics. Removal of infected implants was associated with favorable outcomes.

Perinatal asphyxia, hypoxia, ischemia and hearing loss. An overview.

PubMed

Borg, E

1997-01-01

Birth hypoxia, asphyxia and ischemia have often been thought to be major causes of early hearing loss or deafness. The purpose of the present review is to focus on the role of these particular factors for perinatal auditory disorders. On the whole, only a small proportion of neonatal hearing loss is caused by perinatal factors. The exact etiology of neonatal hearing loss in children with complicated deliveries is difficult to evaluate due to the large number of causative factors that might be involved. After reviewing the literature covering the past 15-20 years, it is not possible to say that we understand the relative importance of different factors and their interactions. However, in the majority of studies, birth asphyxia is not correlated with hearing loss in babies with complicated deliveries Prolonged artificial ventilation, the presence of severe hypoxic ischemic encephalopathy or persistent pulmonary hypertension are important factors. The brain is more susceptible to anoxia than the ear and both are more likely to be damaged after prolonged pre-, peri- and postnatal hypoxia-ischemia than pure hypoxia during delivery. Perinatal hypoxia is more likely to cause a temporary hearing loss than a permanent one. Preterm babies are more vulnerable than term babies. The total number of risk factors, e.g. medicated by total length of stay in the neonatal intensive care unit and length of artificial ventilation, is the best predictor of risk for hearing loss of perinatal origin. The similarities between hearing loss and cerebral palsy are pointed out; only 8% of the cases of cerebral palsy are considered to be caused by conditions during delivery.

Human Gastroenteritis Outbreak Associated with Escherichia albertii, Japan

PubMed Central

Ooka, Tadasuke; Tokuoka, Eisuke; Furukawa, Masato; Nagamura, Tetsuya; Ogura, Yoshitoshi; Arisawa, Kokichi; Harada, Seiya

2013-01-01

Although Escherichia albertii is an emerging intestinal pathogen, it has been associated only with sporadic human infections. In this study, we determined that a human gastroenteritis outbreak at a restaurant in Japan had E. albertii as the major causative agent. PMID:23260717

Geochemical and isotopic evidences from groundwater and surface water for understanding of natural contamination in chronic kidney disease of unknown etiology (CKDu) endemic zones in Sri Lanka.

PubMed

Edirisinghe, E A N V; Manthrithilake, H; Pitawala, H M T G A; Dharmagunawardhane, H A; Wijayawardane, R L

2018-06-01

Chronic kidney disease of unknown etiology (CKDu) is the main health issue in the dry zone of Sri Lanka. Despite many studies carried out, causative factors have not been identified yet clearly. According to the multidisciplinary researches carried out so far, potable water is considered as the main causative factor for CKDu. Hence, the present study was carried out with combined isotopic and chemical methods to understand possible relationships between groundwater; the main drinking water source, and CKDu in four endemic areas in the dry zone. Different water sources were evaluated isotopically ( 2 H, 3 H and 18 O) and chemically from 2013 to 2015. Results revealed that prevalence of CKDu is significantly low with the groundwater replenished by surface water inputs. It is significantly high with the groundwater stagnated as well as groundwater recharged from regional flow paths. Thus, the origin, recharge mechanism and flow pattern of groundwater, as well as geological conditions which would be responsible for natural contamination of groundwater appear as the main causative factors for CKDu. Therefore, detailed investigations should be made in order to identify the element(s) in groundwater contributing to CKDu. The study recommends providing drinking water to the affected zones using water sources associated with surface waters.

Screening of dementia genes by whole-exome sequencing in early-onset Alzheimer disease: input and lessons.

PubMed

Nicolas, Gaël; Wallon, David; Charbonnier, Camille; Quenez, Olivier; Rousseau, Stéphane; Richard, Anne-Claire; Rovelet-Lecrux, Anne; Coutant, Sophie; Le Guennec, Kilan; Bacq, Delphine; Garnier, Jean-Guillaume; Olaso, Robert; Boland, Anne; Meyer, Vincent; Deleuze, Jean-François; Munter, Hans Markus; Bourque, Guillaume; Auld, Daniel; Montpetit, Alexandre; Lathrop, Mark; Guyant-Maréchal, Lucie; Martinaud, Olivier; Pariente, Jérémie; Rollin-Sillaire, Adeline; Pasquier, Florence; Le Ber, Isabelle; Sarazin, Marie; Croisile, Bernard; Boutoleau-Bretonnière, Claire; Thomas-Antérion, Catherine; Paquet, Claire; Sauvée, Mathilde; Moreaud, Olivier; Gabelle, Audrey; Sellal, François; Ceccaldi, Mathieu; Chamard, Ludivine; Blanc, Frédéric; Frebourg, Thierry; Campion, Dominique; Hannequin, Didier

2016-05-01

Causative variants in APP, PSEN1 or PSEN2 account for a majority of cases of autosomal dominant early-onset Alzheimer disease (ADEOAD, onset before 65 years). Variant detection rates in other EOAD patients, that is, with family history of late-onset AD (LOAD) (and no incidence of EOAD) and sporadic cases might be much lower. We analyzed the genomes from 264 patients using whole-exome sequencing (WES) with high depth of coverage: 90 EOAD patients with family history of LOAD and no incidence of EOAD in the family and 174 patients with sporadic AD starting between 51 and 65 years. We found three PSEN1 and one PSEN2 causative, probably or possibly causative variants in four patients (1.5%). Given the absence of PSEN1, PSEN2 and APP causative variants, we investigated whether these 260 patients might be burdened with protein-modifying variants in 20 genes that were previously shown to cause other types of dementia when mutated. For this analysis, we included an additional set of 160 patients who were previously shown to be free of causative variants in PSEN1, PSEN2 and APP: 107 ADEOAD patients and 53 sporadic EOAD patients with an age of onset before 51 years. In these 420 patients, we detected no variant that might modify the function of the 20 dementia-causing genes. We conclude that EOAD patients with family history of LOAD and no incidence of EOAD in the family or patients with sporadic AD starting between 51 and 65 years have a low variant-detection rate in AD genes.

Drug discovery based on genetic and metabolic findings in schizophrenia.

PubMed

Dwyer, Donard S; Weeks, Kathrine; Aamodt, Eric J

2008-11-01

Recent progress in the genetics of schizophrenia provides the rationale for re-evaluating causative factors and therapeutic strategies for this disease. Here, we review the major candidate susceptibility genes and relate the aberrant function of these genes to defective regulation of energy metabolism in the schizophrenic brain. Disturbances in energy metabolism potentially lead to neurodevelopmental deficits, impaired function of the mature nervous system and failure to maintain neurites/dendrites and synaptic connections. Current antipsychotic drugs do not specifically address these underlying deficits; therefore, a new generation of more effective medications is urgently needed. Novel targets for future drug discovery are identified in this review. The coordinated application of structure-based drug design, systems biology and research on model organisms may greatly facilitate the search for next-generation antipsychotic drugs.

FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa.

PubMed

Shimada, Takashi; Urakawa, Itaru; Yamazaki, Yuji; Hasegawa, Hisashi; Hino, Rieko; Yoneya, Takashi; Takeuchi, Yasuhiro; Fujita, Toshiro; Fukumoto, Seiji; Yamashita, Takeyoshi

2004-02-06

Fibroblast growth factor (FGF)-23 was identified as a causative factor of tumor-induced osteomalacia and also as a responsible gene for autosomal dominant hypophosphatemic rickets. To clarify the pathophysiological roles of FGF-23 in these diseases, we generated its transgenic mice. The transgenic mice expressing human FGF-23 reproduced the common clinical features of these diseases such as hypophosphatemia probably due to increased renal phosphate wasting, inappropriately low serum 1,25-dihydroxyvitamin D level, and rachitic bone. The renal phosphate wasting in the transgenic mice was accompanied by the reduced expression of sodium phosphate cotransporter type IIa in renal proximal tubules. These results reinforce the notion that the excessive action of FGF-23 plays a causative role in the development of several hypophosphatemic rickets/osteomalacia.

Epidemiology of Diabetes Mellitus in the United Arab Emirates.

PubMed

Razzak, Hira Abdul; Harbi, Alya; Shelpai, Wael; Qawas, Ahmad

2017-09-20

Background/ Objective: Diabetes mellitus is a non-communicable disease which has become a major global public health issue. This systematic review summarized epidemiological studies related to the prevalence, risk factors, complications, incidence, knowledge, attitude and practices of Diabetes Mellitus (DM) among Arab population in the United Arab Emirates (UAE). PubMed, Scopus databases, Science direct, Wiley online library, and other local journals were searched to identify relevant literature using appropriate keywords to retrieve studies conducted in the UAE. Search limits were restricted to studies in English language, between 2007 and 2016, and on UAE population (both citizens and expatriates). Electronic database search yielded 24 studies about the prevalence, incidence, complications, risk factors, knowledge, attitudes and practices of diabetes, including cross sectional studies (n =18), population-based survey (n = 1), retrospective cohort studies (n = 3), qualitative (n=1), and randomized controlled trial (n = 1). Countrywide prevalence estimates of Diabetes Mellitus were reported to be high. The major determinants of Diabetes Mellitus involved hypertension, physical inactivity, sedentary lifestyle, and unhealthy diet. Even though past evidences have promulgated the role of numerous causative factors, the epidemiological implications of some of the risk factors including family history, educational level, and the use of alcohol remains elusive. This systematic review signifies epidemiology of Diabetes Mellitus in the United Arab Emirates and suggests that extra efforts are needed for preventive and curative strategies in order to decrease the burden of this non-communicable disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Lower urinary tract symptoms are associated with low levels of serum serotonin, high levels of adiponectin and fasting glucose, and benign prostatic enlargement.

PubMed

Haghsheno, Mohammad-Ali; Mellström, Dan; Peeker, Ralph; Hammarsten, Jan; Lorentzon, Mattias; Sundh, Valter; Karlsson, Magnus; Ohlsson, Claes; Damber, Jan-Erik

2015-04-01

The aim of this study was to test whether lower urinary tract symptoms (LUTS) and urinary incontinence are associated with the metabolic syndrome (MetS). The association between LUTS and benign prostatic enlargement (BPE) was also investigated. A cross-sectional, representative risk factor analysis of LUTS, as measured by the International Prostate Symptom Score (IPSS), and urinary incontinence was conducted. Among 950 representative individuals, aged 69-81 years, the association between clinical, anthropometric, endocrine, metabolic and inflammatory factors on the one hand, as both major and minor aspects of MetS, and LUTS and urinary incontinence, on the other hand, was analysed. The prostate gland volume was measured in a subgroup of 155 randomly selected individuals and the association between LUTS and BPE was estimated. No significant association was found between LUTS or urinary incontinence and the major aspects of the MetS. However, in a multivariate analysis, serum serotonin showed an independent negative correlation with LUTS and with urinary incontinence while fasting serum glucose and serum adiponectin showed a positive correlation with LUTS. Furthermore, in a subgroup of 155 individuals, the prostate gland volume correlated positively with LUTS. The study did not show an association between LUTS or urinary incontinence and the major components of the MetS. However, serum serotonin showed an independent negative correlation with LUTS and with urinary incontinence while fasting serum glucose and serum adiponectin showed a positive correlation with LUTS. The data confirm the general knowledge that BPE may be one of the causative factors of LUTS.

Current concepts on the sagittal balance and classification of spondylolysis and spondylolisthesis☆☆☆

PubMed Central

Tebet, Marcos Antonio

2014-01-01

Treatment of spondylolysis and spondylolisthesis remains a challenge for orthopaedic surgeons, neurosurgeons and paediatrics. In spondylolisthesis, it has been clearly demonstrated over the past decade that spino-pelvic morphology is abnormal and that it can be associated to an abnormal sacro-pelvic orientation as well as to a disturbed global sagittal balance of spine. This article presents the SDSG (Spinal Deformity Study Group) classification of lumbosacral spondylolisthesis. The proper treatment of spondylolisthesis is dependent on recognizing the type of slip, sacro-pelvic balance and overall sagittal balance and its natural history. Although a number of clinical radiographic features have been identified as risk factors, their role as primary causative factors or secondary adaptative changes is not clear. The conservative treatment of adult isthmic spondylolisthesis results in good outcome in the majority of cases. Of those patients who fail conservative treatment, success with surgery is quite good, with significant improvement in neurologic function in those patients with deficits, as well as improvement in patients with back pain. PMID:26229765

Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease.

PubMed

Sepe, Sara; Milanese, Chiara; Gabriels, Sylvia; Derks, Kasper W J; Payan-Gomez, Cesar; van IJcken, Wilfred F J; Rijksen, Yvonne M A; Nigg, Alex L; Moreno, Sandra; Cerri, Silvia; Blandini, Fabio; Hoeijmakers, Jan H J; Mastroberardino, Pier G

2016-05-31

The underlying relation between Parkinson's disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Overuse Injuries in Children and Adolescents.

ERIC Educational Resources Information Center

DiFiori, John P.

1999-01-01

With the growth in youth sports programs, overuse injuries in children and adolescents have become common. Physicians are challenged to make the diagnosis and identify the causes of injury. Growth-related factors require special consideration in injury management. Physicians must make a directed history assessing causative factors and a systematic…

Why an extended evolutionary synthesis is necessary

PubMed Central

2017-01-01

Since the last major theoretical integration in evolutionary biology—the modern synthesis (MS) of the 1940s—the biosciences have made significant advances. The rise of molecular biology and evolutionary developmental biology, the recognition of ecological development, niche construction and multiple inheritance systems, the ‘-omics’ revolution and the science of systems biology, among other developments, have provided a wealth of new knowledge about the factors responsible for evolutionary change. Some of these results are in agreement with the standard theory and others reveal different properties of the evolutionary process. A renewed and extended theoretical synthesis, advocated by several authors in this issue, aims to unite pertinent concepts that emerge from the novel fields with elements of the standard theory. The resulting theoretical framework differs from the latter in its core logic and predictive capacities. Whereas the MS theory and its various amendments concentrate on genetic and adaptive variation in populations, the extended framework emphasizes the role of constructive processes, ecological interactions and systems dynamics in the evolution of organismal complexity as well as its social and cultural conditions. Single-level and unilinear causation is replaced by multilevel and reciprocal causation. Among other consequences, the extended framework overcomes many of the limitations of traditional gene-centric explanation and entails a revised understanding of the role of natural selection in the evolutionary process. All these features stimulate research into new areas of evolutionary biology. PMID:28839929

[Formation of microbial biofilms in causative agents of acute and chronic pyelonephritis].

PubMed

Lagun, L V; Atanasova, Iu V; Tapal'skiĭ, D V

2013-01-01

Study the intensity of formation of microbial biofilms by Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus strains isolated during various forms of pyelonephritis. 150 clinical isolates of microorganisms isolated from urine ofpatientswith acute and chronic pyelonephritiswere included into the study. Determination of intensity of film-formation was carried out by staining of the formed biofilms by crystal violet with consequent extraction of the dye and measurement of its concentration in washout solution. Among causative agents ofpyelonephritis P. aeruginosa isolates had the maximum film-forming ability. The intensity of biofilm formation of these isolates was 2-3 time higher than staphylococcus and enterobacteria strains. Strains isolated from patients with chronic pyelonephritis by ability to form biofilms significantly surpassed strains isolated from acute pyelonephritis patients. A higher ability to form microbial biofilms for microorganisms--causative agents of pyelonephritis progressing against the background ofurolithiasis was noted. The ability to form biofilms is determined by both causative agent species and character of the infectious process in which this microorganism participates. Intensive formation of biofilms by E. coli, P. aeruginosa, K. pneumoniae, S. aureus clinical isolates may be an important factor of chronization of urinary tract infections.

Melasma treatment: A novel approach using a topical agent that contains an anti-estrogen and a vascular endothelial growth factor inhibitor.

PubMed

Cohen, Philip R

2017-04-01

Melasma is an acquired disorder of pigmentation that presents with asymptomatic symmetric darkening of the face. The pathogenesis of this condition is multifactorial and influenced by several factors including female sex hormones, genetic predisposition and ultraviolet light exposure. The management of melasma is usually directed at more than one of the causative etiologic factors and often incorporates a combination of topical agents, with or without the addition of physical modalities. Estrogen and angiogenesis are significant factors in the etiology of melasma. A useful addition to the therapeutic armentarium for treating melasma would include a topical agent that could effect both of these causative factors. Specifically, a topical preparation consisting of an anti-estrogen and a vascular endothelial growth factor inhibitor would accomplish this goal. Suitable candidates that target estrogen receptors and vascular endothelial growth factor are currently used in medical oncology as systemic antineoplastic agents. The anti-estrogen could be either a selective estrogen receptor modulator (such as tamoxifen or raloxifene) or an aromatase inhibitor (such as anastrozole or letrozole or exemestane). The vascular endothelial growth factor inhibitor would be bevacizumab. In conclusion, a novel-topically administered-therapy for melasma would combine an anti-estrogen and a vascular endothelial growth factor inhibitor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Peritonitis before Peritoneal Dialysis Training: Analysis of Causative Organisms, Clinical Outcomes, Risk Factors, and Long-Term Consequences

PubMed Central

Ma, Terry King-Wing; Chow, Kai Ming; Kwan, Bonnie Ching-Ha; Pang, Wing Fai; Leung, Chi Bon; Li, Philip Kam-Tao

2016-01-01

Background and objectives Peritonitis before peritoneal dialysis (PD) training (pretraining peritonitis [PTP]) is an uncommon event. The study aim was to examine the causative organisms, clinical outcomes, risk factors, and long-term consequences of PTP. Design, setting, participants, & measurements In this single–center, retrospective, observational study involving all incident patients on PD who developed PTP between 1998 and 2012, we examined the causative organisms, primary response rate, complete cure rate, risk factors, and associations of PTP with peritoneal equilibration test (PET) and patient survival. For each patient in the PTP group, the patients who underwent catheter insertion immediately before and after the index case were identified as controls. Results Among 1252 incident patients on PD, 52 (4.2%) patients developed PTP, and 104 patients were identified as controls. The two groups were similar in age, sex distribution, comorbidities, and residual renal function, but the PTP group had significantly lower hemoglobin and serum albumin. Patients were followed up for a median of 37.5 months (interquartile range [IQR], 16.3–62.2 months). The most common causative organisms of PTP were Staphylococcus aureus (30.8%) and polymicrobial (21.2%); 25% had negative growth. The primary response and complete cure rates were 82.7% and 78.8%, respectively. In the PTP group, 7.7% of patients died, 9.6% of patients required catheter removal, and PD training was significantly delayed (median =42.0; IQR, 26.0–65.8 days versus 27.5; IQR, 23.0–35.0 days; P=0.01). Multivariate logistic regression analysis showed that serum albumin was the only predictor of PTP (adjusted odds ratio, 0.89 per 1-g/dl increase; 95% confidence interval, 0.82 to 0.97). There were no differences in PET results and dialysis adequacy (measured around 1 month after PD training). The PTP group had significantly worse patient survival (median =41.2; IQR, 21.8–60.5 months versus 55.8; IQR, 40.4–71.2 months; P=0.02). Technique failure occurred in 11.5% and 10.6% of patients in the PTP and control groups, respectively. Conclusions S. aureus is the most common causative organism of PTP. Nutritional interventions in patients who are hypoalbuminemic before catheter insertion deserve additional study. PMID:27269302

Peritonitis before Peritoneal Dialysis Training: Analysis of Causative Organisms, Clinical Outcomes, Risk Factors, and Long-Term Consequences.

PubMed

Ma, Terry King-Wing; Chow, Kai Ming; Kwan, Bonnie Ching-Ha; Pang, Wing Fai; Leung, Chi Bon; Li, Philip Kam-Tao; Szeto, Cheuk Chun

2016-07-07

Peritonitis before peritoneal dialysis (PD) training (pretraining peritonitis [PTP]) is an uncommon event. The study aim was to examine the causative organisms, clinical outcomes, risk factors, and long-term consequences of PTP. In this single-center, retrospective, observational study involving all incident patients on PD who developed PTP between 1998 and 2012, we examined the causative organisms, primary response rate, complete cure rate, risk factors, and associations of PTP with peritoneal equilibration test (PET) and patient survival. For each patient in the PTP group, the patients who underwent catheter insertion immediately before and after the index case were identified as controls. Among 1252 incident patients on PD, 52 (4.2%) patients developed PTP, and 104 patients were identified as controls. The two groups were similar in age, sex distribution, comorbidities, and residual renal function, but the PTP group had significantly lower hemoglobin and serum albumin. Patients were followed up for a median of 37.5 months (interquartile range [IQR], 16.3-62.2 months). The most common causative organisms of PTP were Staphylococcus aureus (30.8%) and polymicrobial (21.2%); 25% had negative growth. The primary response and complete cure rates were 82.7% and 78.8%, respectively. In the PTP group, 7.7% of patients died, 9.6% of patients required catheter removal, and PD training was significantly delayed (median =42.0; IQR, 26.0-65.8 days versus 27.5; IQR, 23.0-35.0 days; P=0.01). Multivariate logistic regression analysis showed that serum albumin was the only predictor of PTP (adjusted odds ratio, 0.89 per 1-g/dl increase; 95% confidence interval, 0.82 to 0.97). There were no differences in PET results and dialysis adequacy (measured around 1 month after PD training). The PTP group had significantly worse patient survival (median =41.2; IQR, 21.8-60.5 months versus 55.8; IQR, 40.4-71.2 months; P=0.02). Technique failure occurred in 11.5% and 10.6% of patients in the PTP and control groups, respectively. S. aureus is the most common causative organism of PTP. Nutritional interventions in patients who are hypoalbuminemic before catheter insertion deserve additional study. Copyright © 2016 by the American Society of Nephrology.

p-Benzoquinone-induced aggregation and perturbation of structure and chaperone function of α-crystallin is a causative factor of cigarette smoke-related cataractogenesis.

PubMed

Chowdhury, Aritra; Choudhury, Aparajita; Chakraborty, Shruti; Ghosh, Arunava; Banerjee, Victor; Ganguly, Shinjini; Bhaduri, Gautam; Banerjee, Rajat; Das, Kalipada; Chatterjee, Indu B

2018-02-01

Cigarette smoking is a significant risk factor for cataract. However, the mechanism by which cigarette smoke (CS) causes cataract remains poorly understood. We had earlier shown that in CS-exposed guinea pig, p-benzoquinone (p-BQ) derived from CS in the lungs is carried by the circulatory system to distant organs and induces various smoke-related pathogeneses. Here, we observed that CS exposure caused accumulation of the p-BQ-protein adduct in the eye lens of guinea pigs. We also observed accumulation of the p-BQ-protein adduct in resected lens from human smokers with cataract. No such accumulation was observed in the lens of never smokers. p-BQ is a strong arylating agent that forms Michael adducts with serum albumin and haemoglobin resulting in alterations of structure and function. A major protein in the mammalian eye lens is αA-crystallin, which is a potent molecular chaperone. αA-crystallin plays a key role in maintaining the integrity and transparency of the lens. SDS-PAGE indicated that p-BQ induced aggregation of αA-crystallin. Various biophysical techniques including UV-vis spectroscopy, fluorescence spectroscopy, FT-IR, bis-ANS titration suggested a perturbation of structure and chaperone function of αA-crystallin upon p-BQ modification. Our results indicate that p-BQ is a causative agent involved in the modification of αA-crystallin and pathogenesis of CS-induced cataract. Our findings would educate public about the impacts of smoking on eye health and help to discourage them from smoking. The study might also help scientists to develop new drugs for the intervention of CS-induced cataract at an early stage. Copyright © 2017 Elsevier B.V. All rights reserved.

Portrayals of schizophrenia by entertainment media: a content analysis of contemporary movies.

PubMed

Owen, Patricia R

2012-07-01

Critics of entertainment media have indicated that cinematic depictions of schizophrenia are stereotypic and characterized by misinformation about symptoms, causes, and treatment. The pervasiveness and nature of misinformation are difficult to ascertain because of the lack of empirically based studies of movies portraying schizophrenia. This study analyzed portrayals of schizophrenia in contemporary movies to ascertain prevalence of stereotypes and misinformation about schizophrenia. English-language movies featuring at least one main character with schizophrenia that were released for showing in theaters between 1990 and 2010 were analyzed for depictions of schizophrenia. Two researchers independently rated each character with a checklist that assessed demographic characteristics, symptoms and stereotypes, causation, and treatment. Forty-two characters from 41 movies were identified, a majority of whom were male and Caucasian. Most characters displayed positive symptoms of schizophrenia. Delusions were featured most frequently, followed by auditory and visual hallucinations. A majority of characters displayed violent behavior toward themselves or others, and nearly one-third of violent characters engaged in homicidal behavior. About one-fourth of characters committed suicide. Causation of schizophrenia was infrequently noted, although about one-fourth of movies implied that a traumatic life event was significant in causation. Of movies alluding to or showing treatment, psychotropic medications were most commonly portrayed. The finding that misinformation and negative portrayals of schizophrenia in contemporary movies are common underscores the importance of determining how viewers interpret media messages and how these interpretations inform attitudes and beliefs both of the general public and of people with schizophrenia.

Microbial Keratitis in Kingdom of Bahrain: Clinical and Microbiology Study

PubMed Central

Al-Yousuf, Nada

2009-01-01

Background: Microbial keratitis is a potentially vision threatening condition worldwide. Knowing the predisposing factors and etiologic microorganism can help control and prevent this problem. This is the first study of its kind in Kingdom of Bahrain. Objective: To study the profile of microbial keratitis in Bahrain with special focus on risk factors, clinical outcome and microbilogical results. Methods: A retrospective analysis of all patients admitted in Salmaniya Medical Complex over a period of three years from January 2005 to January 2007 was performed. A total of 285 patients with keratitis were analysed. Non infectious corneal ulceration were excluded. Data collected from medical records were demographic features, predisposing factors, history of corneal trauma, associated ocular conditions, visual acuity at the time of presentation and the clinical course. Predisposing risk factors measured were contact lens use, presence of blepharitis, diabetes, lid abnormalities, dry eyes, keratoplasty and refractive surgery. For contact lens wearers any contact lens related risk factors that can lead to keratitis were measured. Pearson's chi-square test was used to carry out statistical analysis wherever required. Results: Contact lens wear, as a risk factor for microbial keratitis, formed 40% of the total study population. Other risk factors identified were dry eyes 24 cases (8%), 10 blepharitis (3%), 22 trauma (8%), abnormal lid position 14 cases (5%). 6 patients keratitis in a graft (2%), 3 had refractive surgery (1%). The most common causative organism isolated was pseudomonas aeroginosa (54%) followed by streptococcus 12%, staph 10%, other organisms 6%. 95% of contact lens wearers had pseudomonas Aeroginosa. This was statistically significant (p< 0.0001). The vast majority, 92% healed with scarring. 1% needed therapeutic keratoplasty and 7% lost to follow up. Risk factors in contact lens wearers were; 41 patients (36%) slept with the contact lenses. 12 (8%) had contact lens related trauma and 8 (7%) had poor hygiene. Sleeping with the contact lenses was statistically significant (p< 0.0001). Conclusion & Recommendation: Contact lens wear is the major risk factor for microbial keratitis in Bahrain. Pseudomonas aeroginosa was the commonest bacteria isolated. Sleeping with the contact lenses is the major risk factor among contact lens wearers. Majority of keratitis patients resulted in permanent scarring on the cornea. Educating the public, especially on contact lens care and precaution, can help reduce this visual morbidity. PMID:20142952

Observations on the Study of Crime Causation

ERIC Educational Resources Information Center

Gibbons, Don C.

1971-01-01

Although both genetic and situational factors are implicated in criminality, the thesis here is that the latter may well be more important and more frequently encountered than many criminologists have acknowledged to date. (JB)

Adaption and agronomic performance of Artemisia annua L. under lowland humid tropical conditions

USDA-ARS?s Scientific Manuscript database

Demand for new chemotherapies against malaria is increasing as Plasmodium, the causative organism of the disease, has shown a high degree of resistance against most standard anti-malarial drugs. One the few highly effective compounds is artemisinin, the major sesquiterpene for the production of art...

Characterization and Reactivity of Broiler Chicken Sera to Selected Recombinant Campylobacter jejuni Chemotactic Proteins

USDA-ARS?s Scientific Manuscript database

Campylobacter jejuni, a Gram-negative rod bacterium, is the leading causative agent of human acute bacterial gastroenteritis worldwide. Consumption and handling of raw or undercooked poultry are regarded as a major source for human infection. Because bacterial chemotaxis guides microorganisms to c...

Analysis of the Strategy to Combat Maritime Piracy

DTIC Science & Technology

2009-12-11

26  Contemporary Maritime Piracy: Causative Factors...NSC National Security Council PUC Persons Under Control viii SLOC Sea lines of communication SSA Ships Security Assessment SSP Ships Security Plan...UNCLOS United Nations Convention on the Law of the Sea USD United States Dollar U.S. United States ix ILLUSTRATIONS Page Figure 1.  Factors

Getting Them Speaking: Classroom Social Factors and Foreign Language Anxiety

ERIC Educational Resources Information Center

Effiong, Okon

2016-01-01

This study, which focuses on foreign language anxiety (FLA) experienced by Japanese learners of English in four universities, explores causative agents by looking into the classroom. The research questions aim to explore how FLA is influenced by classroom social factors. The study adopted qualitative data collection procedures, and the field work…

The contribution of molecular genetics to the understanding and management of cancer: potential future applications and implications for nurses.

PubMed

Bradley, A N

1999-06-01

Cancer is an immense medical problem and as a cause of mortality it is second only to cardiovascular disease. Much of the current understanding of cancer is owed to epidemiologists who have discovered a number of causative factors implicated in its development. These causative factors can be divided into genetic, chemical, physical, viral, radiation, immune and hormonal factors. Further advances in understanding have been made over the past decade from contributions made by the field of molecular biology. From investigation and examination of the molecular processes involved in the development of cancer it is becoming increasingly clear that changes in the genetic material of the cell nuclei are the final common pathway to cancer, whatever the initial aetiology. This article will attempt to elucidate the contribution of molecular genetics to the understanding of the likely mechanisms of carcinogenesis, the management of cancer, potential future applications and directions and the implications for nurses arising from this relatively new and evolving field of knowledge.

Vitamin-D Deficiency As a Potential Environmental Risk Factor in Multiple Sclerosis, Schizophrenia, and Autism.

PubMed

Kočovská, Eva; Gaughran, Fiona; Krivoy, Amir; Meier, Ute-Christiane

2017-01-01

In this short review, we want to summarize the current findings on the role of vitamin-D in multiple sclerosis (MS), schizophrenia, and autism. Many studies have highlighted hypovitaminosis-D as a potential environmental risk factor for a variety of conditions such as MS, asthma, cardiovascular disease, and, more recently, psychiatric diseases. However, whether hypovitaminosis-D is a potential causative factor for the development or activity in these conditions or whether hypovitaminosis-D may be due to increased vitamin-D consumption by an activated immune system (reverse causation) is the focus of intense research. Here, we will discuss current evidence exploring the role of vitamin-D in MS, schizophrenia, and autism and its impact on adaptive and innate immunity, antimicrobial defense, the microbiome, neuroinflammation, behavior, and neurogenesis. More work is needed to gain insight into its role in the underlying pathophysiology of these conditions as it may offer attractive means of intervention and prevention.

[FROM STATISTICAL ASSOCIATIONS TO SCIENTIFIC CAUSALITY].

PubMed

Golan, Daniel; Linn, Shay

2015-06-01

The pathogenesis of most chronic diseases is complex and probably involves the interaction of multiple genetic and environmental risk factors. One way to learn about disease triggers is from statistically significant associations in epidemiological studies. However, associations do not necessarily prove causation. Associations can commonly result from bias, confounding and reverse causation. Several paradigms for causality inference have been developed. Henle-Koch postulates are mainly applied for infectious diseases. Austin Bradford Hill's criteria may serve as a practical tool to weigh the evidence regarding the probability that a single new risk factor for a given disease is indeed causal. These criteria are irrelevant for estimating the causal relationship between exposure to a risk factor and disease whenever biological causality has been previously established. Thus, it is highly probable that past exposure of an individual to definite carcinogens is related to his cancer, even without proving an association between this exposure and cancer in his group. For multifactorial diseases, Rothman's model of interacting sets of component causes can be applied.

From Snow to Hill to ALS: An epidemiological odyssey in search of ALS causation.

PubMed

Armon, Carmel

2018-05-21

Establishing mechanisms of disease causation in neurodegenerative diseases has long seemed to be beyond the pale of traditional epidemiological tools. Establishing a plausible mechanism for initiation of amyotrophic lateral sclerosis (ALS) has appeared a particularly elusive goal. This review shows that a likely mechanism for ALS initiation may be inferred by applying classical methods of epidemiological inference. Advances in characterizing the biology of ALS suggest that most cases of ALS are cortically-generated, part of the ALS-FTD spectrum, with focal onset and spread by contiguity within the motor super-network. Evidence-based methods identified the most credible exogenous risk factor - smoking. AB Hill's nine viewpoints to inferring causation from association were invoked. The most likely mechanism consistent with smoking being a risk factor for ALS was inferred: cumulative DNA damage, akin to cumulative somatic mutations in carcinogenesis. Focal onset supports the concept that these changes, occurring in a single cell, may trigger the cascade leading to clinical ALS. The plausibility of this mechanism was affirmed by its coherence/consistency with other observations in sporadic, familial and western Pacific ALS. Application of traditional epidemiological reasoning suggests that cumulative DNA damage may contribute to disease onset in ALS. Copyright © 2018 Elsevier B.V. All rights reserved.

Separation from children as a specific risk factor to fathers' health and lifestyles.

PubMed

Grill, E; Weitkunat, R; Crispin, A

2001-01-01

The study was to examine whether fathers living apart from their children following divorce or separation ("fathers without children") differ in their health-related lifestyles and attitudes, and in their health status, from fathers in intact family settings ("fathers with children"). Data was acquired by means of a self-administered questionnaire within an exploratory cross-sectional survey. Fathers without children differed in their lifestyle patterns, parameters of satisfaction, health, and health related orientations from fathers with children. Negative lifestyles could be observed in fathers who had a low income and saw their children only rarely. Separation from their children is a major life crisis for fathers. Subgroups could be identified who had significant health risks. Due to study design, conclusions on causation are not possible. Longitudinal studies are necessary to yield more detailed impact for prevention.

An overview of burning mouth syndrome.

PubMed

Salerno, Carmen; Di Stasio, Dario; Petruzzi, Massimo; Lauritano, Dorina; Gentile, Enrica; Guida, Agostino; Maio, Claudio; Tammaro, Mariasofia; Serpico, Rosario; Lucchese, Alberta

2016-01-01

Burning mouth syndrome (BMS) is characterised by the presence of a burning sensation in the oral mucosa in the absence of any clinically apparent mucosal sign. It occurs more commonly in older women and often affects the tongue tip and lateral borders, lips, and hard and soft palates. Besides the burning sensation, patients with BMS may complain of unremitting oral mucosal pain, dysgeusia, and xerostomia. The exact pathophysiology of primary BMS remains unknown. A major challenge for the clinician is the treatment of BMS: identifying possible causative factors is the first step, but BMS is often idiopathic. Drug therapy, in addition to behavioural therapy and psychotherapy, may help to eliminate the symptoms. Considering the growing incidence of BMS in older people, further research is required to determine the true efficacy of current management strategies for patients with this disorder.

Synthetic Small Molecule Inhibitors of Hh Signaling As Anti-Cancer Chemotherapeutics

PubMed Central

Maschinot, C.A.; Pace, J.R.; Hadden, M.K.

2016-01-01

The hedgehog (Hh) pathway is a developmental signaling pathway that is essential to the proper embryonic development of many vertebrate systems. Dysregulation of Hh signaling has been implicated as a causative factor in the development and progression of several forms of human cancer. As such, the development of small molecule inhibitors of Hh signaling as potential anti-cancer chemotherapeutics has been a major area of research interest in both academics and industry over the past ten years. Through these efforts, synthetic small molecules that target multiple components of the Hh pathway have been identified and advanced to preclinical or clinical development. The goal of this review is to provide an update on the current status of several synthetic small molecule Hh pathway inhibitors and explore the potential of several recently disclosed inhibitory scaffolds. PMID:26310919

Human Factors Countermeasures to Improve Highway-Railway Intersection Safety

DOT National Transportation Integrated Search

1973-07-01

A field demonstration study in support of the evaluation of alternative railway-highway grade crossing accident countermeasures was conducted. Guidelines were provided for the development of countermeasure concepts. Investigations of the causative fa...

Onset of Hyperventilation during Incremental Exercise: A Brief Review.

ERIC Educational Resources Information Center

Powers, Scott K.; Beadle, Ralph E.

1985-01-01

This review discussed the various mechanisms that have been proposed to be causative of the hyperventilation that occurs during heavy exercise. The humoral hypothesis and nonhumoral hypothesis and secondary factors are reviewed. (MT)

Prevalence of musculoskeletal disorders and related occupational causative factors among electricity linemen: A narrative review.

PubMed

Padmanathan, Vinothini; Joseph, Leonard; Omar, Baharudin; Nawawi, Roslizawati

2016-01-01

Occupational tasks of linemen are highly associated with the development of work related musculoskeletal disorders (WRMDs). Although linemen are prone to develop WRMDs, there is paucity of information on the prevalence of WRMDs and related occupational causative factors. Therefore, the present review was conducted to report on the prevalence of WRMDs and to outline causative risk factors within occupational tasks in the lineman profession. Literature search was conducted in various databases such as Scopus, PubMed and ScienceDirect for articles published between 1996-2013. The articles were analyzed, selected and retrieved based on predetermined objectives, inclusion criteria and Medical Subject Headings (MeSH). In the review process only articles published in English were considered. The review identified moderate to high prevalence of WRMDs among the linemen population. Back and shoulder regions were highly affected compared to the other body regions. The review also reported occupational tasks such as bar installation, insulator fixation and manual handling of tools as high risk tasks that lead to the development of WRMDs. In addition, occupational tools such as ladders, manual cutters and manual presses were also identified as a potential ergonomic hazard. In conclusion, the current review identified that WRMDs are common in the back and shoulder regions among linemen. Also, a number of occupational risk factors were identified to be associated with WRMDs among the linemen. Hence, future research on prevention and intervention studies concerning lineman profession population in order to develop a good job practice are recommended. Int J Occup Med Environ Health 2016;29(5):725-734. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Mechanisms of Endothelial Dysfunction in Hypertensive Pregnancy and Preeclampsia

PubMed Central

Possomato-Vieira, José S.; Khalil, Raouf A.

2016-01-01

Preeclampsia is a pregnancy-related disorder characterized by hypertension, and could lead to maternal and fetal morbidity and mortality. Although the causative factors and pathophysiological mechanisms are unclear, endothelial dysfunction is a major hallmark of preeclampsia. Clinical tests and experimental research have suggested that generalized endotheliosis in the systemic, renal, cerebral and hepatic circulation could decrease endothelium-derived vasodilators such as nitric oxide, prostacyclin and hyperpolarization factor and increase vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction, hypertension and other manifestation of preeclampsia. In search for the upstream mechanisms that could cause endothelial dysfunction, certain genetic, demographic and environmental risk factors have been suggested to cause abnormal expression of uteroplacental integrins, cytokines and matrix metalloproteinases, leading to decreased maternal tolerance, apoptosis of invasive trophoblast cells, inadequate spiral arteries remodeling, reduced uterine perfusion pressure (RUPP), and placental ischemia/hypoxia. RUPP may cause imbalance between the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin and the pro-angiogenic factors vascular endothelial growth factor and placental growth factor, or stimulate the release of other circulating bioactive factors such as inflammatory cytokines, hypoxia-inducible factor-1, reactive oxygen species, and angiotensin AT1 receptor agonistic autoantibodies. These circulating factors could then target endothelial cells and cause generalized endothelial dysfunction. Therapeutic options are currently limited, but understanding the factors involved in endothelial dysfunction could help design new approaches for prediction and management of preeclampsia. PMID:27451103

Causes of highway road dust toxicity to an estuarine amphipod: Evaluating the effects of nicotine.

PubMed

Hiki, Kyoshiro; Nakajima, Fumiyuki; Tobino, Tomohiro

2017-02-01

Urban road dust can potentially have adverse effects on ecosystems if it is discharged into receiving waters. This study investigated the causes of highway road dust toxicity by performing sediment toxicity identification evaluation (TIE) tests with an estuarine amphipod, Grandidierella japonica. In addition to metals and polycyclic aromatic hydrocarbons, which are traditionally considered to be the major toxicants in road runoff, we focused on dissolved nicotine as a causative toxicant. The sediment TIE results suggested that organic contaminants contributed to the majority of toxicity, and that the contribution of unionized nicotine to the toxicity was the highest among the chemicals considered. However, additional mortality tests with 48-h pulsed nicotine exposure demonstrated that exposure to nicotine at the same concentration as the baseline level in TIE tests did not cause significant 10-day amphipod mortality. Thus, the road dust toxicity could not be explained only by unionized nicotine, thereby suggesting contributions from joint effects of the measured toxicants and the presence of other unmeasured factors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of Constitutional and Replication Stress-Induced Genome Structural Variation by SNP Array and Mate-Pair Sequencing

PubMed Central

Arlt, Martin F.; Ozdemir, Alev Cagla; Birkeland, Shanda R.; Lyons, Robert H.; Glover, Thomas W.; Wilson, Thomas E.

2011-01-01

Copy-number variants (CNVs) are a major source of genetic variation in human health and disease. Previous studies have implicated replication stress as a causative factor in CNV formation. However, existing data are technically limited in the quality of comparisons that can be made between human CNVs and experimentally induced variants. Here, we used two high-resolution strategies—single nucleotide polymorphism (SNP) arrays and mate-pair sequencing—to compare CNVs that occur constitutionally to those that arise following aphidicolin-induced DNA replication stress in the same human cells. Although the optimized methods provided complementary information, sequencing was more sensitive to small variants and provided superior structural descriptions. The majority of constitutional and all aphidicolin-induced CNVs appear to be formed via homology-independent mechanisms, while aphidicolin-induced CNVs were of a larger median size than constitutional events even when mate-pair data were considered. Aphidicolin thus appears to stimulate formation of CNVs that closely resemble human pathogenic CNVs and the subset of larger nonhomologous constitutional CNVs. PMID:21212237

Copy number variations of six and seven α-globin genes in a family with intermedia and major thalassemia phenotypes.

PubMed

Farashi, Samaneh; Vakili, Shadi; Faramarzi Garous, Negin; Ashki, Mehri; Imanian, Hashem; Azarkeivan, Azita; Najmabadi, Hossein

2015-10-01

Copy number variations in α-globin genes are results of unequal crossover between homologous segments in the α-globin gene cluster that misalign during the meiosis phase of the gametogenesis process. Reduction or augmentation of α-globin genes leads to imbalance of α/β chains in hemoglobin tetramer and consequently attenuate or worsen the β-thal clinical symptoms, respectively. Multiplications in α-globin genes have been found in some populations, justifying unexpected severe phenotype of β-thal carriers. Unexpected severe phenotype in the family members may result from coexistence of extra α-globin genes, which is an important factor in the causation of thalassemia intermedia and major in heterozygous β-thalassemia. We described different multiplications in α-globin locus in an Iranian family with one, two or three extra α-globin genes (ααα/αα, αααα/αα and αααα/ααα). The excess α-globin gene/genes cause increment in β/α chain imbalance and leads to worsening pathophysiology and clinical severity of β-thalassemia carriers.

The GRADE approach and Bradford Hill's criteria for causation.

PubMed

Schünemann, Holger; Hill, Suzanne; Guyatt, Gordon; Akl, Elie A; Ahmed, Faruque

2011-05-01

This article describes how the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to grading the quality of evidence and strength of recommendations considers the Bradford Hill criteria for causation and how GRADE may relate to questions in public health. A primary concern in public health is that evidence from non-randomised studies may provide a more adequate or best available measure of a public health strategy's impact, but that such evidence might be graded as lower quality in the GRADE framework. GRADE, however, presents a framework that describes both criteria for assessing the quality of research evidence and the strength of recommendations that includes considerations arising from the Bradford Hill criteria. GRADE places emphasis on recommendations and in assessing quality of evidence; GRADE notes that randomisation is only one of many relevant factors. This article describes how causation may relate to developing recommendations and how the Bradford Hill criteria are considered in GRADE, using examples from the public health literature with a focus on immunisation.

An epidemiological examination of the subluxation construct using Hill's criteria of causation.

PubMed

Mirtz, Timothy A; Morgan, Lon; Wyatt, Lawrence H; Greene, Leon

2009-12-02

Chiropractors claim to locate, analyze and diagnose a putative spinal lesion known as subluxation and apply the mode of spinal manipulation (adjustment) for the correction of this lesion. The purpose of this examination is to review the current evidence on the epidemiology of the subluxation construct and to evaluate the subluxation by applying epidemiologic criteria for it's significance as a causal factor. The databases of PubMed, Cinahl, and Mantis were searched for studies using the keywords subluxation, epidemiology, manipulation, dose-response, temporality, odds ratio, relative risk, biological plausibility, coherence, and analogy. The criteria for causation in epidemiology are strength (strength of association), consistency, specificity, temporality (temporal sequence), dose response, experimental evidence, biological plausibility, coherence, and analogy. Applied to the subluxation all of these criteria remain for the most part unfulfilled. There is a significant lack of evidence to fulfill the basic criteria of causation. This lack of crucial supportive epidemiologic evidence prohibits the accurate promulgation of the chiropractic subluxation.

An epidemiological examination of the subluxation construct using Hill's criteria of causation

PubMed Central

2009-01-01

Background Chiropractors claim to locate, analyze and diagnose a putative spinal lesion known as subluxation and apply the mode of spinal manipulation (adjustment) for the correction of this lesion. Aim The purpose of this examination is to review the current evidence on the epidemiology of the subluxation construct and to evaluate the subluxation by applying epidemiologic criteria for it's significance as a causal factor. Methods The databases of PubMed, Cinahl, and Mantis were searched for studies using the keywords subluxation, epidemiology, manipulation, dose-response, temporality, odds ratio, relative risk, biological plausibility, coherence, and analogy. Results The criteria for causation in epidemiology are strength (strength of association), consistency, specificity, temporality (temporal sequence), dose response, experimental evidence, biological plausibility, coherence, and analogy. Applied to the subluxation all of these criteria remain for the most part unfulfilled. Conclusion There is a significant lack of evidence to fulfill the basic criteria of causation. This lack of crucial supportive epidemiologic evidence prohibits the accurate promulgation of the chiropractic subluxation. PMID:19954544

Effectiveness and efficiencies in police traffic services programs

DOT National Transportation Integrated Search

1982-03-01

Traffic law violations were causative factors in about 90 percent of all motor vehicle crashes. Primary responsibility for deterring traffic law violations and for apprehending violators of these laws rest with State, county and municipal police agen...

Perioperative spontaneous bilateral suprachoroidal hemorrhage

PubMed Central

Haridas, Anjana; Litwin, Andre S.; Coker, Timothy

2011-01-01

Summary Suprachoroidal hemorrhage is a rare condition, occurring most commonly in the perioperative period, although cases of unilateral spontaneous hemorrhages have been reported. We report a case of bilateral spontaneous suprachoroidal hemorrhage and discuss the potential causative factors. PMID:23362387

Witchcraft and Biopsychosocial Causes of Mental Illness: Attitudes and Beliefs About Mental Illness Among Health Professionals in Five Countries.

PubMed

Stefanovics, Elina A; He, Hongbo; Cavalcanti, Maria; Neto, Helio; Ofori-Atta, Angelo; Leddy, Meaghan; Ighodaro, Adesuwa; Rosenheck, Robert

2016-03-01

This study examines the intercorrelation of measures reflecting beliefs about and attitudes toward people with mental illness in a sample of health professionals (N = 902) from five countries: Brazil, China, Ghana, Nigeria, and the United States, and, more specifically, the association of beliefs in supernatural as contrasted with biopsychosocial causes of mental illness. Factor analysis of a 43-item questionnaire identified four factors favoring a) socializing with people with mental illness; b) normalizing their roles in society; c) belief in supernatural causes of mental illness (e.g., witchcraft, curses); and d) belief in biopsychosocial causes of mental illness. Unexpectedly, a hypothesized negative association between belief in supernatural and biopsychosocial causation of mental illness was not found. Belief in the biopsychosocial causation was weakly associated with less stigmatized attitudes towards socializing and normalized roles.

Correlation not Causation: The Relationship between Personality Traits and Political Ideologies

PubMed Central

Verhulst, Brad; Eaves, Lindon J.; Hatemi, Peter K.

2013-01-01

The assumption in the personality and politics literature is that a person's personality motivates them to develop certain political attitudes later in life. This assumption is founded on the simple correlation between the two constructs and the observation that personality traits are genetically influenced and develop in infancy, whereas political preferences develop later in life. Work in psychology, behavioral genetics, and recently political science, however, has demonstrated that political preferences also develop in childhood and are equally influenced by genetic factors. These findings cast doubt on the assumed causal relationship between personality and politics. Here we test the causal relationship between personality traits and political attitudes using a direction of causation structural model on a genetically informative sample. The results suggest that personality traits do not cause people to develop political attitudes; rather, the correlation between the two is a function of an innate common underlying genetic factor. PMID:22400142

Correlation not causation: the relationship between personality traits and political ideologies.

PubMed

Verhulst, Brad; Eaves, Lindon J; Hatemi, Peter K

2012-01-01

The assumption in the personality and politics literature is that a person's personality motivates them to develop certain political attitudes later in life. This assumption is founded on the simple correlation between the two constructs and the observation that personality traits are genetically influenced and develop in infancy, whereas political preferences develop later in life. Work in psychology, behavioral genetics, and recently political science, however, has demonstrated that political preferences also develop in childhood and are equally influenced by genetic factors. These findings cast doubt on the assumed causal relationship between personality and politics. Here we test the causal relationship between personality traits and political attitudes using a direction of causation structural model on a genetically informative sample. The results suggest that personality traits do not cause people to develop political attitudes; rather, the correlation between the two is a function of an innate common underlying genetic factor.

Candidate causative mutation on BTA18 associated with calving and conformation traits in Holstein bulls

USDA-ARS?s Scientific Manuscript database

Complementing quantitative methods with sequence data analysis is a major goal of the post-genome era of biology. In this study, we analyzed Illumina HiSeq sequence data derived from 11 US Holstein bulls in order to identify putative causal mutations associated with calving and conformation traits. ...

Novel monoclonal antibodies against Stx1d and 1e and their use for improvement of immunoassays

USDA-ARS?s Scientific Manuscript database

Shiga toxins (Stxs) are major causative agents for bloody diarrhea and hemolytic uremic syndrome, a life-threatening disease in humans. No effective treatment is available. Early detection of Stxs in clinical samples is critical for disease management. As bacteria evolve, new Stxs are produced; ther...

Measuring bovine gamma delta T cell function at the site of Mycobacterium bovis infection

USDA-ARS?s Scientific Manuscript database

The causative agent of tuberculosis (TB) in cattle is Mycobacterium bovis. The characteristic lesions of bovine TB are well-organized pulmonary granulomas. Gamma delta T cells are a unique subset of nonconventional T cells that play major roles in both the innate and adaptive arms of the immune sys...

Low cost bioluminescence imaging as an alternative to in vivo bioassays for quantifying biologically active staphylococcal enterotoxin type E

USDA-ARS?s Scientific Manuscript database

Staphylococcus aureus is a major causative agent implicated in outbreaks of food poisoning, acting through the production of a range of toxins including staphylococcal enterotoxin type E (SEE). While tests such as enzyme-linked immunosorbent (ELISA) exist to detect the toxin molecules, existing meth...

Evaluation of Iranian microbiology laboratories for identification of etiologic agents of bacterial meningitidis. Survey results of an external quality assessment scheme (EQAS) programme.

PubMed

Marandi, Farinaz Rashed; Rahbar, Mohammad; Sabourian, Roghieh; Saremi, Mahnaz

2010-01-01

To determine the ability of Iranian microbiology laboratories for identification and susceptibility testing of Streptococcus pneumoniae and Haemophilus influenzae as causative agents of bacterial meningitides. Two strains of bacteria including Haemophilus influenzae and Streptococcus pneumoniae as a common causative agents of meningitides were chosen and coded as strain number 1 and number 2. The strains were distributed among 679 microbiology laboratories. All laboratories were requested for identification of each unknown microorganism and susceptibility testing of S. pneumoniae against five commonly used antibiotics. Of 679 microbiology laboratories 310 (46%) laboratories participated in the survey and among these, 258 laboratories completely identified S. pneumoniae. About 85% laboratories produced correct susceptibility testing against oxacillin, erythromycin, tetracycline, and vancomycin. Of 310 received responses only 50 laboratories identified H. influenza correctly. The majority of the laboratories did not have the capacity to identification H. influenza. Microbiology laboratories in our country are qualified for identification and susceptibility testing of S. pneumoniae. However, majority of laboratories are not qualified for identification of H. influenzae.

Burkholderia gladioli sepsis in newborns.

PubMed

Dursun, Arzu; Zenciroglu, Aysegul; Karagol, Belma Saygili; Hakan, Nilay; Okumus, Nurullah; Gol, Nese; Tanir, Gonul

2012-10-01

Burkholderia gladioli is a rare cause of bacteremia and sepsis in the absence of such predisposing factors as chronic granulomatous disease, cystic fibrosis, and immunosuppression. Little is known about B. gladioli infection in newborns. The aim of this study was to present the features of B. gladioli infection in newborns. Clinicopathological characteristics, patterns of antimicrobial susceptibility, predisposing factors, and outcomes of B. gladioli bloodstream infection were retrospectively analyzed in newborns treated between 2008 and 2011. During the 3-year study period, B. gladioli was isolated from the blood cultures of 14 patients (3.7 per 1,000 admissions). In all, 5 (35.7 %) of the 14 cases had a positive blood culture at the time of initial admission. Primary diagnoses in the neonates were severe major congenital anomalies, congenital leukemia, prematurity with respiratory distress syndrome, pneumonia, and parapneumonic pleural effusion. In total, 10 (71.4 %) of the patients underwent ≥2 invasive procedures. The overall in-hospital mortality rate was 21.4 %, whereas the mortality rate due to B. gladioli infection was 7 %. B. gladioli might be a causative microorganism of both early neonatal and nosocomial sepsis in newborns. To the best of our knowledge, this is the first study on B. gladioli infection in newborns. Invasive procedures and severe major congenital anomalies may be predisposing factors for B. gladioli bloodstream infection in neonates. Although it appears to have low pathogenic potential and an insidious clinical course in newborns, resistance to antibiotics may be a potential problem. Mortality was primarily associated with underlying diseases.

Population-based health promotion perspective for older driver safety: Conceptual framework to intervention plan

PubMed Central

Classen, Sherrilene; Lopez, Ellen DS; Winter, Sandra; Awadzi, Kezia D; Ferree, Nita; Garvan, Cynthia W

2007-01-01

The topic of motor vehicle crashes among the elderly is dynamic and multi-faceted requiring a comprehensive and synergistic approach to intervention planning. This approach must be based on the values of a given population as well as health statistics and asserted through community, organizational and policy strategies. An integrated summary of the predictors (quantitative research), and views (qualitative research) of the older drivers and their stakeholders, does not currently exist. This study provided an explicit socio-ecological view explaining the interrelation of possible causative factors, an integrated summary of these causative factors, and empirical guidelines for developing public health interventions to promote older driver safety. Using a mixed methods approach, we were able to compare and integrate main findings from a national crash dataset with perspectives of stakeholders. We identified: 11 multi-causal factors for safe elderly driving; the importance of the environmental factors - previously underrated in the literature- interacting with behavioral and health factors; and the interrelatedness among many socio-ecological factors. For the first time, to our knowledge, we conceptualized the fundamental elements of a multi-causal health promotion plan, with measurable intermediate and long-term outcomes. After completing the detailed plan we will test the effectiveness of this intervention on multiple levels. PMID:18225470

A systematic review exploring the relationship between infection and sudden unexpected death between 2000 and 2016: A forensic perspective.

PubMed

Kruger, Mia M; Martin, Lorna J; Maistry, Sairita; Heathfield, Laura J

2018-05-21

Death due to infectious diseases is a major health concern worldwide. This is of particular concern in developing countries where poor-socio economic status and a lack of healthcare resources contribute to the high burden of disease. In some cases death due to infection can be acute and aggressive, and death may occur without a diagnosis whilst the person is still alive. These deaths may ultimately lead to a medico-legal autopsy being performed. There are various mechanisms by which sudden death due to infection may occur. In addition, there are many risk factors associated with sudden death due to infection, which differ between infants and older individuals. However, it is unclear which pathogens and risk factors are most frequently associated with sudden death due to infection. Therefore a systematic review of articles and case reports published between 1 January 2000 and 30 June 2016 was undertaken in order to (1) explore the relationship between pathogens and their causative role and (2) identify the relationship between predisposing and/or risk factors associated with sudden death due to infection. Major databases were searched and after critical appraisal 143 articles were identified. It was found that respiratory infections and deaths involving bacterial pathogens were most commonly associated with these deaths. In addition the most common risk factors in infants were exposure to tobacco smoke and co-sleeping. In adults the most common risk factors were co-morbid conditions and illnesses. This information aids in a better understanding of these deaths and highlights the need for more research in this field, particularly in developing countries. Copyright © 2018 Elsevier B.V. All rights reserved.

Characterization of odorants in inflatable aquatic toys and swimming learning devices-which substances are causative for the characteristic odor and potentially harmful?

PubMed

Wiedmer, Christoph; Velasco-Schön, Cristina; Buettner, Andrea

2017-06-01

Based on the observation of intense and offensive smells in the product group of aquatic toys, four representative products were exemplarily chosen and sensorially characterized by an expert panel. Panellists reported mostly almond- and rubber-like notes for three of the four samples, whereas the smell of the fourth sample was dominated by organic solvent-associated notes such as "nail polish-like." To elucidate the molecular reasons of these smells, we isolated the volatile fraction of the product by solvent extraction and high vacuum distillation, and identified the main odorants by aroma extract dilution analysis (AEDA), followed by one- and two-dimensional gas chromatography, with parallel mass spectrometric and olfactometric detection. Additionally, the materials of the samples were identified by means of differential scanning calorimetry (DSC), attenuated total reflectance spectroscopy (ATR-spectroscopy), and Beilstein halogen test. Between 32 and 46 odors could be detected in each sample by means of AEDA, whereby five to 13 of these compounds were detectable with by far the highest dilution factors, and were found to primarily correlate with the smells of the respective products. Focussing the subsequent identification on these causative substances led to the successful identification of the majority of these odorants. Among them were several mono- or di-unsaturated carbonyl compounds and their epoxidized derivatives, which are typical odorous artefacts from fatty acid oxidation, but also odor-active organic solvents such as cyclohexanone, isophorone, and phenol.

Viral Etiology of Encephalitis in Children in Southern Vietnam: Results of a One-Year Prospective Descriptive Study

PubMed Central

Tan, Le Van; Qui, Phan Tu; Ha, Do Quang; Hue, Nguyen Bach; Bao, Lam Quoi; Cam, Bach Van; Khanh, Truong Huu; Hien, Tran Tinh; Vinh Chau, Nguyen Van; Tram, Tran Tan; Hien, Vo Minh; Nga, Tran Vu Thieu; Schultsz, Constance; Farrar, Jeremy; van Doorn, H. Rogier; de Jong, Menno D.

2010-01-01

Background Acute encephalitis is an important and severe disease in children in Vietnam. However, little is known about the etiology while such knowledge is essential for optimal prevention and treatment. To identify viral causes of encephalitis, in 2004 we conducted a one-year descriptive study at Children's Hospital Number One, a referral hospital for children in southern Vietnam including Ho Chi Minh City. Methodology/Principal Findings Children less than 16 years of age presenting with acute encephalitis of presumed viral etiology were enrolled. Diagnostic efforts included viral culture, serology and real time (RT)-PCRs. A confirmed or probable viral causative agent was established in 41% of 194 enrolled patients. The most commonly diagnosed causative agent was Japanese encephalitis virus (n = 50, 26%), followed by enteroviruses (n = 18, 9.3%), dengue virus (n = 9, 4.6%), herpes simplex virus (n = 1), cytomegalovirus (n = 1) and influenza A virus (n = 1). Fifty-seven (29%) children died acutely. Fatal outcome was independently associated with patient age and Glasgow Coma Scale (GCS) on admission. Conclusions/Significance Acute encephalitis in children in southern Vietnam is associated with high mortality. Although the etiology remains unknown in a majority of the patients, the result from the present study may be useful for future design of treatment and prevention strategies of the disease. The recognition of GCS and age as predictive factors may be helpful for clinicians in managing the patient. PMID:21049060

Breast Gangrene

PubMed Central

2011-01-01

Background Breast gangrene is rare in surgical practice. Gangrene of breast can be idiopathic or secondary to some causative factor. Antibiotics and debridement are used for management. Acute inflammatory infiltrate, severe necrosis of breast tissue, necrotizing arteritis, and venous thrombosis is observed on histopathology. The aim of was to study patients who had breast gangrene. Methods A prospective study of 10 patients who had breast gangrene over a period of 6 years were analyzed Results All the patients in the study group were female. Total of 10 patients were encountered who had breast gangrene. Six patients presented with breast gangrene on the right breast whereas four had on left breast. Out of 10 patients, three had breast abscess after teeth bite followed by gangrene, one had iatrogenic trauma by needle aspiration of erythematous area of breast under septic conditions. Four had history of application of belladonna on cutaneous breast abscess and had then gangrene. All were lactating female. Amongst the rest two were elderly, one of which was a diabetic who had gangrene of breast and had no application of belladonna. All except one had debridement under cover of broad spectrum antibiotics. Three patients had grafting to cover the raw area. Conclusion Breast gangrene occurs rarely. Etiology is variable and mutifactorial. Teeth bite while lactation and the iatrogenic trauma by needle aspiration of breast abscess under unsterlised conditions could be causative. Uncontrolled diabetes can be one more causative factor for the breast gangrene. Belladonna application as a topical agent could be inciting factor. Sometimes gangrene of breast can be idiopathic. Treatment is antibiotics and debridement. PMID:21854557

Qualitative cross-sectional study of the perceived causes of depression in South Asian origin women in Toronto

PubMed Central

Ekanayake, Samanthika; Ahmad, Farah

2012-01-01

Objective To explore how South Asian origin women in Toronto, Canada, understand and explain the causes of their depression. Design Cross-sectional in-depth qualitative interviews. Setting Outpatient service in Toronto, Ontario. Participants Ten women with symptoms of depression aged between 22 and 65 years of age. Seven were from India, two from Sri Lanka and one from Pakistan. Four were Muslim, three Hindu and three Catholic. Two participants had university degrees, one a high school diploma and seven had completed less than a high school education. Eight were married, one was unmarried and one a widow. Results Three main factors emerged from the participant narratives as the causes of depression: family and relationships, culture and migration and socioeconomic. The majority of the participants identified domestic abuse, marital problems and interpersonal problems in the family as the cause of their depression. Culture and migration and socioeconomic factors were considered contributory. None of our study participants reported spiritual, supernatural or religious factors as causes of depression. Conclusion A personal–social–cultural model emerged as the aetiological paradigm for depression. Given the perceived causation, psycho-social treatment methods may be more acceptable for South Asian origin women. PMID:22337816

Qualitative cross-sectional study of the perceived causes of depression in South Asian origin women in Toronto.

PubMed

Ekanayake, Samanthika; Ahmad, Farah; McKenzie, Kwame

2012-01-01

To explore how South Asian origin women in Toronto, Canada, understand and explain the causes of their depression. Cross-sectional in-depth qualitative interviews. Outpatient service in Toronto, Ontario. Ten women with symptoms of depression aged between 22 and 65 years of age. Seven were from India, two from Sri Lanka and one from Pakistan. Four were Muslim, three Hindu and three Catholic. Two participants had university degrees, one a high school diploma and seven had completed less than a high school education. Eight were married, one was unmarried and one a widow. Three main factors emerged from the participant narratives as the causes of depression: family and relationships, culture and migration and socioeconomic. The majority of the participants identified domestic abuse, marital problems and interpersonal problems in the family as the cause of their depression. Culture and migration and socioeconomic factors were considered contributory. None of our study participants reported spiritual, supernatural or religious factors as causes of depression. A personal-social-cultural model emerged as the aetiological paradigm for depression. Given the perceived causation, psycho-social treatment methods may be more acceptable for South Asian origin women.

Cognitive and Neural Correlates of Mathematical Giftedness in Adults and Children: A Review

PubMed Central

Myers, Timothy; Carey, Emma; Szűcs, Dénes

2017-01-01

Most mathematical cognition research has focused on understanding normal adult function and child development as well as mildly and moderately impaired mathematical skill, often labeled developmental dyscalculia and/or mathematical learning disability. In contrast, much less research is available on cognitive and neural correlates of gifted/excellent mathematical knowledge in adults and children. In order to facilitate further inquiry into this area, here we review 40 available studies, which examine the cognitive and neural basis of gifted mathematics. Studies associated a large number of cognitive factors with gifted mathematics, with spatial processing and working memory being the most frequently identified contributors. However, the current literature suffers from low statistical power, which most probably contributes to variability across findings. Other major shortcomings include failing to establish domain and stimulus specificity of findings, suggesting causation without sufficient evidence and the frequent use of invalid backward inference in neuro-imaging studies. Future studies must increase statistical power and neuro-imaging studies must rely on supporting behavioral data when interpreting findings. Studies should investigate the factors shown to correlate with math giftedness in a more specific manner and determine exactly how individual factors may contribute to gifted math ability. PMID:29118725

Management of asthma: the essentials of good clinical practice.

PubMed

Aït-Khaled, N; Enarson, D A

2006-02-01

Asthma is a condition that affects all countries worldwide. It is a chronic, disabling condition that diminishes the quality of life and the economic prosperity of those who live with it. The majority of persons living with asthma are from developing countries. Asthma management necessitates long-term treatment that is expensive, making it less accessible to poor people. The cost of medications is the key factor preventing people living with asthma from having access to care that has the potential to relieve their suffering, improve their quality of life and enhance their economic status. Asthma is a disease caused by environmental exposures. Genetic factors predispose certain people to developing asthma once they are exposed to the causative agents, and certain factors can trigger symptomatic episodes of asthma in those who have already developed the disease. Certain clinical characteristics differentiate asthma from other chronic lung conditions. The most important of these is that the symptoms and functional disability caused by asthma vary from one occasion to another. In those with less severe asthma, they may be present on some occasions and not others; in those with more severe asthma, their degree of severity varies from one time to another.

Mycobacterium tuberculosis TlyA Protein Negatively Regulates T Helper (Th) 1 and Th17 Differentiation and Promotes Tuberculosis Pathogenesis*

PubMed Central

Rahman, Md. Aejazur; Sobia, Parveen; Dwivedi, Ved Prakash; Bhawsar, Aakansha; Singh, Dhiraj Kumar; Sharma, Pawan; Moodley, Prashini; Van Kaer, Luc; Bishai, William R; Das, Gobardhan

2015-01-01

Mycobacterium tuberculosis, the causative agent of tuberculosis, is an ancient pathogen and a major cause of death worldwide. Although various virulence factors of M. tuberculosis have been identified, its pathogenesis remains incompletely understood. TlyA is a virulence factor in several bacterial infections and is evolutionarily conserved in many Gram-positive bacteria, but its function in M. tuberculosis pathogenesis has not been elucidated. Here, we report that TlyA significantly contributes to the pathogenesis of M. tuberculosis. We show that a TlyA mutant M. tuberculosis strain induces increased IL-12 and reduced IL-1β and IL-10 cytokine responses, which sharply contrasts with the immune responses induced by wild type M. tuberculosis. Furthermore, compared with wild type M. tuberculosis, TlyA-deficient M. tuberculosis bacteria are more susceptible to autophagy in macrophages. Consequently, animals infected with the TlyA mutant M. tuberculosis organisms exhibited increased host-protective immune responses, reduced bacillary load, and increased survival compared with animals infected with wild type M. tuberculosis. Thus, M. tuberculosis employs TlyA as a host evasion factor, thereby contributing to its virulence. PMID:25847237

Seroprevalence of Burkholderia pseudomallei among Adults in Coastal Areas in Southwestern India

PubMed Central

Vandana, Kalwaje Eshwara; Mukhopadhyay, Chiranjay; Tellapragada, Chaitanya; Kamath, Asha; Tipre, Meghan; Bhat, Vinod; Sathiakumar, Nalini

2016-01-01

Background Although melioidosis, is an important disease in many Southeast Asian countries and Australia, there is limited data on its prevalence and disease burden in India. However, an increase in case reports of melioidosis in recent years indicates its endemicity in India. Aims and methods A population-based cross-sectional seroprevalence study was undertaken to determine the seroprevalence of B. pseudomallei by indirect haemagglutination assay and to investigate the associated risk determinants. Subjects were 711 adults aged 18 to 65 years residing in Udupi district, located in south-western coast of India. Key results Overall, 29% of the study subjects were seropositive (titer ≥20). Females were twice as likely to be seropositive compared to males. Rates of seroprevalence were similar in farmers and non-farmers. Besides gardening, other factors including socio-demographic, occupational and environmental factors did not show any relationship with seropositive status. Major conclusions There is a serological evidence of exposure to B. pseudomallei among adults in India. While the bacterium inhabits soil, exposure to the agent is not limited to farmers. Non-occupational exposure might play an important role in eliciting antibody response to the bacterium and may also be an important factor in disease causation. PMID:27078156

Obesity, metabolic syndrome and adipocytes

USDA-ARS?s Scientific Manuscript database

Obesity and metabolic syndrome are examples whereby excess energy consumption and energy flux disruptions are causative agents of increased fatness. Because other, as yet elucidated, cellular factors may be involved and because potential treatments of these metabolic problems involve systemic agents...

Social and financial resources and high-risk alcohol consumption among older adults.

PubMed

Moos, Rudolf H; Brennan, Penny L; Schutte, Kathleen K; Moos, Bernice S

2010-04-01

This study examined long-term mutual predictive associations between social and financial resources and high-risk alcohol consumption in later life. A sample of 55- to 65-year-old older adults (n = 719) was surveyed at baseline and 10 years and 20 years later. At each contact point, participants completed an inventory that assessed social and financial resources and alcohol consumption. Over the 20-year interval, there was evidence of both social causation and social selection processes in relation to high-risk alcohol consumption. In support of a social causation perspective, higher levels of some social resources, such as participation in social activities, friends' approval of drinking, quality of relationship with spouse, and financial resources, were associated with a subsequent increased likelihood of high-risk alcohol consumption. Conversely, indicating the presence of social selection, high-risk alcohol consumption was associated with subsequent higher levels of friends' approval of drinking and quality of the spousal relationship, but lower quality of relationships with extended family members. These findings reflect mutual influence processes in which older adults' social resources and high-risk alcohol consumption can alter each other. Older adults may benefit from information about how social factors can affect their drinking habits; accordingly, information about social causation effects could be used to guide effective prevention and intervention efforts aimed at reducing the risk that late-life social factors may amplify their excessive alcohol consumption.

Medical negligence. An overview of legal theory and neurosurgical practice: causation.

PubMed

Todd, Nicholas V

2014-06-01

This article discusses the principles of the law in relation to legal causation as applied to neurosurgical practice. Causation is a causal link between a breach of duty of care and the final harm. The fundamental "but-for" test for causation will be discussed, together with Chester v Afshar modified causation, prospective and retrospective probabilities of harm, loss of a chance, causation following breach of duty of care by omission, breaking the chain of causation, material contribution and the law in relation to multiple defendants, with neurosurgical examples.

MTHFR and ACE Gene Polymorphisms and Risk of Vascular and Degenerative Dementias in the Elderly

ERIC Educational Resources Information Center

Pandey, Pratima; Pradhan, Sunil; Modi, Dinesh Raj; Mittal, Balraj

2009-01-01

Focal lacunar infarctions due to cerebral small vessel atherosclerosis or single/multiple large cortical infarcts lead to vascular dementia, and different genes and environmental factors have been implicated in causation or aggravation of the disease. Previous reports suggest that some of the risk factors may be common to both vascular as well as…

Genome-wide characterization of monomeric transcriptional regulators in Mycobacterium tuberculosis.

PubMed

Feng, Lipeng; Chen, Zhenkang; Wang, Zhongwei; Hu, Yangbo; Chen, Shiyun

2016-05-01

Gene transcription catalysed by RNA polymerase is regulated by transcriptional regulators, which play central roles in the control of gene transcription in both eukaryotes and prokaryotes. In regulating gene transcription, many regulators form dimers that bind to DNA with repeated motifs. However, some regulators function as monomers, but their mechanisms of gene expression control are largely uncharacterized. Here we systematically characterized monomeric versus dimeric regulators in the tuberculosis causative agent Mycobacterium tuberculosis. Of the >160 transcriptional regulators annotated in M. tuberculosis, 154 transcriptional regulators were tested, 22 % probably act as monomers and most are annotated as hypothetical regulators. Notably, all members of the WhiB-like protein family are classified as monomers. To further investigate mechanisms of monomeric regulators, we analysed the actions of these WhiB proteins and found that the majority interact with the principal sigma factor σA, which is also a monomeric protein within the RNA polymerase holoenzyme. Taken together, our study for the first time globally classified monomeric regulators in M. tuberculosis and suggested a mechanism for monomeric regulators in controlling gene transcription through interacting with monomeric sigma factors.

Fat, Sugar, Whole Grains and Heart Disease: 50 Years of Confusion.

PubMed

Temple, Norman J

2018-01-04

During the 1970s some investigators proposed that refined carbohydrates, especially sugar and a low intake of dietary fiber, were major factors in coronary heart disease (CHD). This suggestion was eclipsed by the belief that an excess intake of saturated fatty acids (SFA) was the key dietary factor, a view that prevailed from roughly 1974 to 2014. Findings that have accumulated since 1990 inform us that the role of SFA in the causation of CHD has been much exaggerated. A switch from SFA to refined carbohydrates does not lower the ratio of total cholesterol to HDL-cholesterol in the blood and therefore does not prevent CHD. A reduced intake of SFA combined with an increased intake of polyunsaturated fatty acids lowers the ratio of total cholesterol to HDL-cholesterol; this may reduce the risk of CHD. The evidence linking carbohydrate-rich foods with CHD has been steadily strengthening. Refined carbohydrates, especially sugar-sweetened beverages, increase the risk of CHD. Conversely, whole grains and cereal fiber are protective. An extra one or 2 servings per day of these foods increases or decreases risk by approximately 10% to 20%.

Epidemiology of Helicobacter pylori infection in Malaysia--observations in a multiracial Asian population.

PubMed

Goh, K L

2009-09-01

Observations of racial differences in the prevalence of Helicobacter pylori in Malaysia have been intriguing. The Indians and Chinese consistently have a higher prevalence compared to the Malays. The racial cohort theory has been proposed to explain these differences where transmission and perpetuation of infection takes place within a racial group rather than between races, races being separate owing to the low rate of interracial marriages. Studies have demonstrated distinctive bacterial strains between races. Phylogenetic studies have shown that H. pylori isolates amongst Chinese and Indians are distinctive while Malays have Indian and other strains suggesting a more recent acquisition of the bacterium from Indians. H. pylori is recognized as the major causative factor in peptic ulcer disease and gastric cancer. Despite the high prevalence of H. pylori, Indians have a relatively low prevalence of peptic ulcer disease and a low incidence of gastric cancer. This paradox with regards to gastric cancer has been termed the "Indian enigma". Bacterial strain differences between races may be putative but this observation may also indicate gastroprotective environmental factors or a lower genetic susceptibility to develop cancer in the Indians.

Cholesterol as a Causative Factor in Alzheimer Disease: A Debatable Hypothesis

PubMed Central

Wood, W. Gibson; Li, Ling; Müller, Walter E.; Eckert, Gunter P.

2014-01-01

High serum/plasma cholesterol levels have been suggested as a risk factor for Alzheimer disease (AD). Some reports, mostly retrospective epidemiological studies, have observed a decreased prevalence of AD in patients taking the cholesterol lowering drugs, statins. The strongest evidence causally linking cholesterol to AD is provided by experimental studies showing that adding/reducing cholesterol alters amyloid precursor protein (APP) and amyloid beta-protein (Aβ) levels. However, there are problems with the cholesterol-AD hypothesis. Cholesterol levels in serum/plasma and brain of AD patients do not support cholesterol as a causative factor in AD. Prospective studies on statins and AD have largely failed to show efficacy. Even the experimental data are open to interpretation given that it is well-established that modification of cholesterol levels has effects on multiple proteins, not only APP and Aβ. The purpose of this review, therefore, is to examine the above-mentioned issues and discuss the pros and cons of the cholesterol-AD hypothesis, and the involvement of other lipids in the mevalonate pathway, such as isoprenoids and oxysterols, in AD. PMID:24329875

Infective Endocarditis in Children in Italy from 2000 to 2015.

PubMed

Esposito, Susanna; Mayer, Alessandra; Krzysztofiak, Andrzej; Garazzino, Silvia; Lipreri, Rita; Galli, Luisa; Osimani, Patrizia; Fossali, Emilio; Di Gangi, Maria; Lancella, Laura; Denina, Marco; Pattarino, Giulia; Montagnani, Carlotta; Salvini, Filippo; Villani, Alberto; Principi, Nicola; Italian Pediatric Infective Endocarditis Registry

2016-01-01

The Italian Society for Pediatric Infectious Diseases created a registry on children with infective endocarditis (IE) hospitalized in Italy. A cross-sectional survey was conducted on patients hospitalized due to IE in Italian paediatric wards between January 1, 2000, and June 30, 2015. Over the 15-year study period, 47 IE episodes were observed (19 males; age range, 2-17 years). Viridans Streptococci were the most common pathogens among patients with predisposing cardiac conditions and Staphylococcus aureus among those without (37.9% vs. 5.5%, p = 0.018, and 6.9% vs. 27.8%, p = 0.089, respectively). Six of the 7 (85.7%) S. aureus strains were methicillin-resistant. The majority of patients with and without predisposing cardiac conditions recovered without any complications. In Italy, paediatric IE develops without any previous predisposing factors in a number of children, methicillin-resistant S. aureus has emerged as a common causative agent and the therapeutic approach is extremely variable.

Yersinia pestis: still a plague in the 21st century.

PubMed

Josko, Deborah

2004-01-01

Yersinia pestis, the causative agent of plague, is an aerobic, non-motile, gram-negative bacillus belonging to the family Enterobacteriacea. It is a zoonotic infection transmitted to humans via the bite of a flea. Three clinical forms of human plague exist: bubonic, pneumonic, and septicemic. Many important virulence factors associated with this organism are responsible for its extreme pathogenicity and high mortality rates. The bubonic form of plague is usually not transmitted human to human but the pneumonic form is--through inhalation of contaminated aerosol droplets. The pneumonic plague would be the form most likely implicated in the event of an intentional attack. Inhalation of aerosols can cause devastating consequences resulting in many casualties. Unless antibiotics are administered within 24 hours of the initial symptoms, death is inevitable. Its potential for use as a biological weapon is of major concern to public health officials.

Respiratory Disorders in Aluminum Smelter Workers

PubMed Central

Søyseth, Vidar

2014-01-01

Objectives: Summarizing the knowledge status, including the morphology, possible etiological factors, and clinical expression of aluminum potroom asthma and chronic obstructive pulmonary disease related to aluminum potroom exposure. Methods: A review of the literature from the last two decades as it appears in PubMed. Results: There is substantial evidence for the existence of potroom asthma, although the incidence seems to decline over the last 10 years. Increased mortality from chronic obstructive pulmonary disease and longitudinal decline in forced expiratory volume in the first second of expiration has been shown in aluminum potroom workers. Morphological manifestations in bronchial biopsies and the inflammatory markers NO and eosinophils in airway tissue and blood are consistent with asthma in general. The causative agent(s) is (are) not known. Conclusions: Reduction of exposure and cessation of smoking seem to be the major preventive measures to avoid respiratory disorders in the aluminum industry. PMID:24806727

Neurological disease in man following administration of suckling mouse brain antirabies vaccine.

PubMed

Held, J R; Adaros, H L

1972-01-01

In Latin America, suckling mouse brain (SMB) vaccine has become the most commonly used vaccine for immunization of both man and animals against rabies. This vaccine is highly immunogenic, is relatively economical and easy to produce, and is believed to be free of the immunoencephalitogenic factor. From 1964 to the end of 1969, there were 40 reported cases of neurological disease following administration of SMB vaccine, 32 of which met the criteria for inclusion in this report. These 32 cases occurred in 8 different countries. In contrast to neurological disease following the administration of other types of nervous tissue vaccine, the majority of the cases following vaccination with SMB vaccine had a Guillain-Barré-type syndrome with peripheral nervous system involvement and a higher case-fatality rate. The causative agent has not been demonstrated. Modifications in the production and handling of the vaccine may be producing changes that are responsible.

[Nutritional problems in children from 3 to 12 years].

PubMed

Hankard, Régis

2011-04-01

Assessing the nutritional status is like the bottom line of children's health. The first step is to measure height and weight in proper conditions and to calculate the body mass index (BMI). BMI for sex and age allows identifying overweight and obese as well as underweight children. Both situations lead to a clinical exam in order to find causative disease (obesity of endocrine or genetic origin, malnutrition from somatic or behavioral disease). Routine lab study might help whenever referral to specialist is necessary. Nutritional anemia and vitamin D deficiency are two common situations in children that have to be screened and treated. The general practitioner has a central role in nutritional problems in children since he can manage the care within the whole family. This is particularly the case for obesity but also for dyslipidemia, that has to be screened around 8 years, both being major familial risk factor for cardiovascular diseases.

The contribution of applied social sciences to obesity stigma-related public health approaches.

PubMed

Bombak, Andrea E

2014-01-01

Obesity is viewed as a major public health concern, and obesity stigma is pervasive. Such marginalization renders obese persons a "special population." Weight bias arises in part due to popular sources' attribution of obesity causation to individual lifestyle factors. This may not accurately reflect the experiences of obese individuals or their perspectives on health and quality of life. A powerful role may exist for applied social scientists, such as anthropologists or sociologists, in exploring the lived and embodied experiences of this largely discredited population. This novel research may aid in public health intervention planning. Through these studies, applied social scientists could help develop a nonstigmatizing, salutogenic approach to public health that accurately reflects the health priorities of all individuals. Such an approach would call upon applied social science's strengths in investigating the mundane, problematizing the "taken for granted" and developing emic (insiders') understandings of marginalized populations.

Helicobacter pylori virulence factors in relation to gastrointestinal diseases in Iran.

PubMed

Safaralizadeh, Reza; Dastmalchi, Narges; Hosseinpourfeizi, MohammadAli; Latifi-Navid, Saeid

2017-04-01

Helicobacter pylori as an important pathogenic bacterium that colonizes in gastric mucosa, is one of the causative agents in development of some types of gastric diseases, such as chronic active gastritis, peptic ulcer disease (PUD) and gastric cancer (GC). In this review, the aim is studying different genotypes of H. pylori, and the extent of their participation in the pathogenesis of this bacterium which creates gastroduodenal disorders. Some genotypes of H. pylori have a major role in creation of gastroduodenal diseases, whereas some other genotypes of the bacterium do not cause gastric diseases in Iran. It was also reported that some genotypes of this bacterium in different conditions and among different ethnic groups demonstrate different effectiveness. Role of genotypes of H. pylori in creation of gastroduodenal diseases is different among various regions and ethnic groups of Iran. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigation of an outbreak of "humidifier fever" in a print shop.

PubMed

Mamolen, M; Lewis, D M; Blanchet, M A; Satink, F J; Vogt, R L

1993-03-01

An outbreak of "humidifier fever" affected 16 (57%) of 28 workers in a print shop. The most common symptoms were myalgia, chills or subjective fever, and cough. Illness began 5-13 hours after entering the workplace, and lasted 2-24 hours. A humidifier in use the day of the outbreak was found to be contaminated with fungi, amebae, and Gram-negative bacteria. The risk of illness was highest for those who had been on the job 3 months before the outbreak, a time when the humidifier was in constant use. Serologic studies of print shop workers showed positive reactions to extracts of organisms isolated from the humidifier, but could neither distinguish ill from well workers, nor identify causative organisms. The presence of endotoxin-producing bacteria and the clinical syndrome are consistent with an organic dust toxic syndrome. Previous exposure appeared to be the major risk factor for illness.

Functional (psychogenic) movement disorders: merging mind and brain.

PubMed

Edwards, Mark J; Bhatia, Kailash P

2012-03-01

Functional (psychogenic) movement disorders (FMD) are part of the wide spectrum of functional neurological disorders, which together account for over 16% of patients referred to neurology clinics. FMD have been described as a "crisis for neurology" and cause major challenges in terms of diagnosis and treatment. As with other functional disorders, a key issue is the absence of pathophysiological understanding. There has been an influential historical emphasis on causation by emotional trauma, which is not supported by epidemiological studies. The similarity between physical signs in functional disorders and those that occur in feigned illness has also raised important challenges for pathophysiological understanding and has challenged health professionals' attitudes toward patients with these disorders. However, physical signs and selected investigations can help clinicians to reach a positive diagnosis, and modern pathophysiological research is showing an appreciation of the importance of both physical and psychological factors in FMD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Extra-corporeal membrane oxygenation-associated infections: implication of extra-intestinal pathogenic Escherichia coli clones.

PubMed

Messika, Jonathan; Clermont, Olivier; Landraud, Luce; Schmidt, Matthieu; Aubry, Alexandra; Sougakoff, Wladimir; Fernandes, Romain; Combes, Alain; Denamur, Erick; Ricard, Jean-Damien

2017-08-01

Extra-corporeal membrane oxygenation (ECMO) is a promising life-saving technique for critically ill patients. Bacterial infection is a frequent complication, and Escherichia coli the predominant causative pathogen, but little is known about the characteristics of E. coli strains in these infections. We therefore conducted a retrospective study of 33 E. coli strains responsible for 33 ECMO-related infections, in 30 subjects. Antimicrobial susceptibility, phylotyping, O-typing, clonal relatedness determination and the screening for four virulence factor genes were conducted. Polymicrobial infections were evidenced in 61.6 % of episodes, irrespective of E. coli characteristics. Extra-intestinal pathogenic strains represented the large majority (69.7 %) of all E. coli isolates. Their advantageous genetic background may explain their predominance in this context. The potential for targeted digestive decontamination should be investigated in these patients for whom infectious complications are a heavy burden.

Genome Sequences of Four Staphylococcus aureus Strains Isolated from Bovine Mastitis

PubMed Central

Taponen, Suvi; Koort, Joanna; Paulin, Lars; Åvall-Jääskeläinen, Silja

2015-01-01

Staphylococcus aureus is a major causative agent of mastitis in dairy cows. The pathogenicity of S. aureus may vary; it is able to cause severe clinical mastitis, but most often it is associated with chronic subclinical mastitis. Here, we present the genome assemblies of four S. aureus strains from bovine mastitis. PMID:25908141

Convergent evolution in peptidoglycan cut sites of phage endolysins protecting mice from methicillin-resistant Staphylococcus aureus septicemia

USDA-ARS?s Scientific Manuscript database

Staphylococcus S. aureus is a Gram-positive pathogen relevant for both human and animal health. It is one of the most common causes of nosocomial infections and associated with a wide range of life-threatening human diseases. As the major causative agent of bovine mastitis, it also has significant ...

Kill or Die: Moral Judgment Alters Linguistic Coding of Causality

ERIC Educational Resources Information Center

De Freitas, Julian; DeScioli, Peter; Nemirow, Jason; Massenkoff, Maxim; Pinker, Steven

2017-01-01

What is the relationship between the language people use to describe an event and their moral judgments? We test the hypothesis that moral judgment and causative verbs rely on the same underlying mental model of people's actions. Experiment 1a finds that participants choose different verbs to describe the major variants of a moral dilemma, the…

Multiple mutations in the para-sodium channel gene are associated with pyrethroid resistance in Rhipicephalus microplus from the United States and Mexico

USDA-ARS?s Scientific Manuscript database

Rhipicephalus microplus is an invasive tick vector that transmits the protozoan parasites Babesia bovis and B. bigemina, the causative agents of bovine babesiosis (cattle fever). Acaricide resistant R. microplus populations have become a major problem for many cattle producing areas of the world. Py...

Battle of Kasserine Pass: Defeat is a Matter of Scale

DTIC Science & Technology

2016-05-26

battle. Conclusions from this study recommend the application of critical analysis of historical examples to identify lessons learned . The...44 v Acknowledgements I would like to thank my wife and children for...in the first battles of major conflict without probing deeply into causation beyond the immediate tactical action. In order to learn lessons from

Functional insights from proteome-wide structural modeling of Treponema pallidum subspecies pallidum, the causative agent of syphilis.

PubMed

Houston, Simon; Lithgow, Karen Vivien; Osbak, Kara Krista; Kenyon, Chris Richard; Cameron, Caroline E

2018-05-16

Syphilis continues to be a major global health threat with 11 million new infections each year, and a global burden of 36 million cases. The causative agent of syphilis, Treponema pallidum subspecies pallidum, is a highly virulent bacterium, however the molecular mechanisms underlying T. pallidum pathogenesis remain to be definitively identified. This is due to the fact that T. pallidum is currently uncultivatable, inherently fragile and thus difficult to work with, and phylogenetically distinct with no conventional virulence factor homologs found in other pathogens. In fact, approximately 30% of its predicted protein-coding genes have no known orthologs or assigned functions. Here we employed a structural bioinformatics approach using Phyre2-based tertiary structure modeling to improve our understanding of T. pallidum protein function on a proteome-wide scale. Phyre2-based tertiary structure modeling generated high-confidence predictions for 80% of the T. pallidum proteome (780/978 predicted proteins). Tertiary structure modeling also inferred the same function as primary structure-based annotations from genome sequencing pipelines for 525/605 proteins (87%), which represents 54% (525/978) of all T. pallidum proteins. Of the 175 T. pallidum proteins modeled with high confidence that were not assigned functions in the previously annotated published proteome, 167 (95%) were able to be assigned predicted functions. Twenty-one of the 175 hypothetical proteins modeled with high confidence were also predicted to exhibit significant structural similarity with proteins experimentally confirmed to be required for virulence in other pathogens. Phyre2-based structural modeling is a powerful bioinformatics tool that has provided insight into the potential structure and function of the majority of T. pallidum proteins and helped validate the primary structure-based annotation of more than 50% of all T. pallidum proteins with high confidence. This work represents the first T. pallidum proteome-wide structural modeling study and is one of few studies to apply this approach for the functional annotation of a whole proteome.

Investigating the Role of Twist1 in Diabetes Pathogenesis

DTIC Science & Technology

Several genes associated with diabetes have been identified in genome wide association studies, but their genetic validation as causative factors...of insulin. Loss-of-function genetic experiments demonstrated that Twist1 deletion against fatty pancreas formation driven by obesity, thereby

Knowledge, barriers, and motivators related to cervical cancer screening among Korean-American women. A focus group approach.

PubMed

Lee, M C

2000-06-01

Cervical cancer is a significant health problem for Korean-American women. It currently is the number one female cancer diagnosed among women in South Korea. Despite this fact, Korean-American women have very low rates of cervical cancer screening. The purpose of this research were to gain an understanding of Korean women's knowledge about cervical cancer, and to identify major barriers to early screening for cervical cancer and the motivators for prevention and early detection. It is hoped that the findings will guide the development of community-based cervical cancer education and screening programs for adult Korean-American women. The health belief model (HBM) provided the theoretical basis for the study. A qualitative study with eight focus groups (n = 102) was conducted using 11 questions derived from the HBM. Focus group discussions revealed that there was misinformation and a lack of knowledge about cervical cancer. The women therefore were confused about the causative factors and preventive strategies related to cervical cancer. The findings showed that major structural barriers were economic and time factors along with language problems. Many participants were recent immigrants with no medical insurance and long work hours. The main psychosocial barriers were fear/fatalism, denial, and Confucian thinking. Participants stated that medical advice and education would influence them most to undergo a Pap test. Recommendations were made to reduce certain barriers and to increase knowledge and motivations.

Development of a PCR-RFLP method based on the transcription elongation factor 1-α gene to differentiate Fusarium graminearum from other species within the Fusarium graminearum species complex.

PubMed

Garmendia, Gabriela; Umpierrez-Failache, Mariana; Ward, Todd J; Vero, Silvana

2018-04-01

Fusarium head blight (FHB) is a destructive disease of cereals crops worldwide and a major food safety concern due to grain contamination with trichothecenes and other mycotoxins. Fusarium graminearum, a member of the Fusarium graminearum species complex (FGSC) is the dominant FHB pathogen in many parts of the world. However, a number of other Fusarium species, including other members of the FGSC, may also be present for example in Argentina, New Zealand, Ethiopia, Nepal, Unites States in cereals such as wheat and barley. Proper species identification is critical to research aimed at improving disease and mycotoxin control programs. Identification of Fusarium species is are often unreliable by traditional, as many species are morphologically cryptic. DNA sequence-based methods offer a reliable means of species identification, but can be expensive when applied to the analyses of population samples. To facilitate identification of the major causative agent of FHB, this work describes an easy and inexpensive method to differentiate F. graminearum from the remaining species within the FGSC and from the other common Fusarium species causing FHB in cereals. The developed method is based on a PCR-RFLP of the transcription elongation factor (TEF 1-α) gene using the restriction enzyme BsaHI. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identifying the controls of wildfire activity in Namibia using multivariate statistics

NASA Astrophysics Data System (ADS)

Mayr, Manuel; Le Roux, Johan; Samimi, Cyrus

2015-04-01

Despite large areas of Namibia being unaffected by fires due to aridity, substantial burning in the northern and north-eastern parts of the country is observed every year. Within the fire-affected regions, a strong spatial and inter-annual variability characterizes the dry-season fire situation. In order to understand these patterns, it appears critical to identify the causative factors behind fire occurrence and to examine their interactions in detail. Furthermore, most studies dealing with causative factor examination focus either on the local or the regional scale. However, these scales seem to be inappropriate from a management perspective, as fire-related strategic action plans are most often set up nationwide. Here, we will present an examination of the fire regimes of Namibia based on a dataset conducted by Le Roux (2011). A decade-spanning fire record (1994-2003) derived from NOAA's Advanced Very High Resolution Radiometer (AVHRR) imagery was used to generate four fire regime metrics (Burned Area, Fire Season Length, Month of Peak Fire Season, and Fire Return Period) and quantitative information on vegetation and phenology derived from Normalized Difference Vegetation Index (NDVI) time series. Further variables contained by this dataset are related to climate, biodiversity, and human activities. Le Roux (2011) analyzed the correlations between the fire metrics mentioned above and the predictor variables. We hypothesize that linear correlations (as estimated by correlation coefficients) simplify the interactions between response and predictor variables. For instance, moderate population densities could induce the highest number of fires, whereas the complete absence of humans lacks one major source of ignition. Around highly populated areas, in contrary, fuels are usually reduced and space is more fragmented - thus, the initiation and spread of a potential fire could as well be inhibited. From a total of over 40 explanatory variables, we will initially use data mining techniques to select a conceivable set of variables by their explanatory value and to remove redundancy. We will then apply two multivariate statistical methods suitable to a large variety of data types and frequently used for (non-linear) causative factor identification: Non-metric Multidimensional Scaling (NMDS) and Regression Trees. The assumed value of these analyses is i) to determine the most important predictor variables of fire activity in Namibia, ii) to decipher their complex interactions in driving fire variability in Namibia, and iii) to compare the performance of two state-of-the-art statistical methods. References: Le Roux, J. (2011): The effect of land use practices on the spatial and temporal characteristics of savanna fires in Namibia. Doctoral thesis at the University of Erlangen-Nuremberg/Germany - 155 pages.

Respiratory syncytial virus outbreak in the basic military training cAMP of the republic of Korea Air Force.

PubMed

Park, Won-Ju; Yoo, Seok-Ju; Lee, Suk-Ho; Chung, Jae-Woo; Jang, Keun-Ho; Moon, Jai-Dong

2015-01-01

An outbreak of acute febrile illness occurred in the Republic of Korea Air Force boot camp from May to July 2011. An epidemiological investigation of the causative agent, which was of a highly infective nature, was conducted. Throat swabs were carried out and a multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) assay was performed to identify possible causative factors. The mean age of patients who had febrile illness during the study period was 20.24 years. The multiplex RT-PCR assay identified respiratory syncytial virus (RSV) as the causative agent. The main symptoms were sore throat (76.0%), sputum (72.8%), cough (72.1%), tonsillar hypertrophy (67.9%), and rhinorrhea (55.9%). The mean temperature was 38.75°C and the attack rate among the recruits was 15.7% (588 out of 3750 recruits), while the mean duration of fever was 2.3 days. The prognosis was generally favorable with supportive care but recurrent fever occurred in 10.1% of the patients within a month. This is the first epidemiological study of an RSV outbreak that developed in a healthy young adult group. In the event of an outbreak of an acute febrile illness of a highly infective nature in facilities used by a young adult group, RSV should be considered among the possible causative agents.

[MANIFESTATIONS OF EPIDEMIC PROCESS AND TRANSMISSION ROUTES OF CAUSATIVE AGENT OF ENTEROVIRUS SEROUS MENINGITIS].

PubMed

Sergevnin, V I; Tryasolobova, M A; Kudrevatykh, E V; Kuzovnikova, E Zh

2015-01-01

Study the manifestations of epidemic process and leading transmission routes of causative agents of enterovirus serous meningitis (SM) by results of laboratory studies and epidemiologic examination of epidemic nidi. During 2010 - 2014 a study for enterovirus was carried out in cerebrospinal fluid in 743 patients, hospitalized into medical organizations of Perm with primary diagnosis "serous meningitis", feces of 426 individuals, that had communicated with patients with SM of enterovirus etiology; 827 water samples from the distribution network, 295 water samples from open water and 57 washes from surface of vegetables and fruits. All the samples were studied in polymerase chain reaction, part--by a virological method. Epidemiologic examination of 350 epidemic nidi of SM was carried out. Enterovirus and (or) its RNA were detected in 62.0% of patients and 61.9% of individuals that had communicated with patients with enteroviris SM. ECHO 6 serotype enterovirus dominated among the causative agents. Maximum intensity of epidemic process of enterovirus SM, based on data from laboratory examination of patients, was detected in a group of organized pre-school and school age children during summer-autumn period. . Examination of epidemic nidi and laboratory control of environmental objects have shown that CV causative agent transmission factors are, in particular, unboiled water from decentralized sources (boreholes, wells, springs), water from open waters during bathing, as well as fresh vegetables, fruits, berries and meals produced from them. .

An Investigation of the Spanish Causatives: "Hacer Ver, Hacer Creer, Hacer Pensar, Hacer Saber."

ERIC Educational Resources Information Center

Dowling, Lee H.

1981-01-01

Presents study which shows that although these causatives have same surface structure as productive causative constructions they differ in several ways, e.g., unlike other productive causatives their meaning changes when "que" subjunctive is substituted for the infinitive, and they function like lexical causatives which involve agent-patient, not…

Gene-environment interplay in internalizing disorders: consistent findings across six environmental risk factors.

PubMed

Hicks, Brian M; DiRago, Ana C; Iacono, William G; McGue, Matt

2009-10-01

Behavior genetic methods can help to elucidate gene-environment (G-E) interplay in the development of internalizing (INT) disorders (i.e., major depression and anxiety disorders). To date, however, no study has conducted a comprehensive analysis examining multiple environmental risk factors with the purpose of delineating general mechanisms of G-E influence in the development of INT disorders. The sample consisted of 1315 male and female twin pairs participating in the age 17 assessment of the Minnesota Twin Family Study. Quantitative G-E interplay models were used to examine how genetic and environmental risk for INT disorders changes as a function of environmental context. Multiple measures and informants were employed to construct composite measures of INT disorders and six environmental risk factors including: stressful life events, mother-child and father-child relationship problems, antisocial and prosocial peer affiliation, and academic achievement and engagement. Significant moderation effects were detected between each environmental risk factor and INT such that in the context of greater environmental adversity, nonshared environmental factors became more important in the etiology of INT symptoms. Our results are consistent with the interpretation that environmental stressors have a causative effect on the emergence of INT disorders. The consistency of our results suggests a general mechanism of environmental influence on INT disorders regardless of the specific form of environmental risk.

Rett Syndrome.

ERIC Educational Resources Information Center

Culbert, Linda A.

This pamphlet reviews the historical process involved in initially recognizing Rett Syndrome as a specific disorder in girls. Its etiology is unknown, but studies have considered factors as hyperammonemia, a two-step mutation, a fragile X chromosome, metabolic disorder, environmental causation, dopamine deficiency, and an inactive X chromosome.…

Characterization of the effect of serum and chelating agents on Staphylococcus aureus biofilm formation; chelating agents augment biofilm formation through clumping factor B

NASA Astrophysics Data System (ADS)

Abraham, Nabil Mathew

Staphylococcus aureus is the causative agent of a diverse array of acute and chronic infections, and some these infections, including infective endocarditis, joint infections, and medical device-associated bloodstream infections, depend upon its capacity to form tenacious biofilms on surfaces. Inserted medical devices such as intravenous catheters, pacemakers, and artificial heart valves save lives, but unfortunately, they can also serve as a substrate on which S. aureus can form a biofilm, attributing S. aureus as a leading cause of medical device-related infections. The major aim of this work was take compounds to which S. aureus would be exposed during infection and to investigate their effects on its capacity to form a biofilm. More specifically, the project investigated the effects of serum, and thereafter of catheter lock solutions on biofilm formation by S. aureus. Pre-coating polystyrene with serum is frequently used as a method to augment biofilm formation. The effect of pre-coating with serum is due to the deposition of extracellular matrix components onto the polystyrene, which are then recognized by MSCRAMMs. We therefore hypothesized that the major component of blood, serum, would induce biofilm formation. Surprisingly, serum actually inhibited biofilm formation. The inhibitory activity was due to a small molecular weight, heat-stable, non-proteinaceous component/s of serum. Serum-mediated inhibition of biofilm formation may represent a previously uncharacterized aspect of host innate immunity that targets the expression of a key bacterial virulence factor: the ability to establish a resistant biofilm. Metal ion chelators like sodium citrate are frequently chosen to lock intravenous catheters because they are regarded as potent inhibitors of bacterial biofilm formation and viability. We found that, while chelating compounds abolished biofilm formation in most strains of S. aureus, they actually augmented the phenotype in a subset of strains. We investigated the molecular basis of this phenomenon. Deletion and complementation analysis and thereafter antibody based inhibition assays confirmed a functional role for the surface adhesin clumping factor B as the causative determinant associated with the increased biofilm phenotype. Finally, we investigated the regulation of clumping factor B-mediated biofilm formation and the basis for the strain dependence. Regulation was determined to occur via two novel post-translational networks- one affecting ClfB activity, mediated by Ca2+ binding to the EF-Hand domain, and the other affecting protein stability, mediated by the enzymatic activity of the metalloprotease-aureolysin. Polymorphisms within the aureolysin gene sequence, between strains, was identified as the basis for some strains forming robust biofilms within chelated media versus other than do not exhibit this phenotype.

Epidemiology and causation: a realist view.

PubMed Central

Renton, A

1994-01-01

In this paper the controversy over how to decide whether associations between factors and diseases are causal is placed within a description of the public health and scientific relevance of epidemiology. It is argued that the rise in popularity of the Popperian view of science, together with a perception of the aims of epidemiology as being to identify appropriate public health interventions, have focussed this debate on unresolved questions of inferential logic, leaving largely unanalysed the notions of causation and of disease at the ontological level. A realist ontology of causation of disease and pathogenesis is constructed within the framework of "scientific materialism", and is shown to provide a coherent basis from which to decide causes and to deal with problems of confounding and interaction in epidemiological research. It is argued that a realist analysis identifies a richer role for epidemiology as an integral part of an ontologically unified medical science. It is this unified medical science as a whole rather than epidemiological observation or experiment which decides causes and, in turn, provides a key element to the foundations of rational public health decision making. PMID:8138775

A retrospective study of health care-associated pneumonia patients at Aichi Medical University hospital.

PubMed

Yamagishi, Yuka; Mikamo, Hiroshige

2011-12-01

Health care-associated pneumonia (HCAP) was defined in the American Thoracic Society/Infectious Disease Society of America guidelines on hospital-acquired pneumonia in 2005. However, little is known about the occurrence of HCAP in Japan. A retrospective review of background characteristics, pathological conditions, causative organisms, initial treatments, and risk factors for HCAP was conducted to determine the relationship of HCAP to community-acquired pneumonia and hospital-acquired pneumonia. Thirty-five patients who were admitted to our hospital for pneumonia acquired outside our hospital were included and were stratified by disease severity according to the Japanese Respiratory Society risk stratification guidelines (A-DROP [age, dehydration, respiratory failure, orientation disturbance, and shock blood pressure] criteria). All patients had an underlying disease. A total of 70 microbial strains (25 gram-positive, 37 gram-negative, 6 anaerobic, and 2 causative of atypical pneumonia) were isolated from sputum cultures, showing high isolation frequencies of Pseudomonas aeruginosa and Staphylococcus aureus and extremely low isolation frequencies of Streptococcus pneumoniae and Haemophilus influenzae. "History of hospitalization within 90 days before the onset of pneumonia" was the most common risk factor, and most of the patients had two or three risk factors. Initially, monotherapy [mainly tazobactam/piperacillin (TAZ/PIPC), sulbactam/ampicillin (SBT/ABPC), ceftriaxone (CTRX), cefepime (CPFM), carbapenems, or fluoroquinolones] or combination therapy (beta-lactam and fluoroquinolone) were administered and gave clinical effects in 63% (22/35) of cases. Bacteriological effects were seen in most strains (57%; 40/70). Since the causative organisms of HCAP were closely related to those of hospital-acquired pneumonia and not to community-acquired pneumonia, we believe that aggressive chemotherapy using broad-spectrum antimicrobials is needed in the initial treatment.

Injury protection and accident causation parameters for vulnerable road users based on German In-Depth Accident Study GIDAS.

PubMed

Otte, Dietmar; Jänsch, Michael; Haasper, Carl

2012-01-01

Within a study of accident data from GIDAS (German In-Depth Accident Study), vulnerable road users are investigated regarding injury risk in traffic accidents. GIDAS is the largest in-depth accident study in Germany. Due to a well-defined sampling plan, representativeness with respect to the federal statistics is also guaranteed. A hierarchical system ACASS (Accident Causation Analysis with Seven Steps) was developed in GIDAS, describing the human causation factors in a chronological sequence. The accordingly classified causation factors - derived from the systematic of the analysis of human accident causes ("7 steps") - can be used to describe the influence of accident causes on the injury outcome. The bases of the study are accident documentations over ten years from 1999 to 2008 with 8204 vulnerable road users (VRU), of which 3 different groups were selected as pedestrians n=2041, motorcyclists n=2199 and bicyclists n=3964, and analyzed on collisions with cars and trucks as well as vulnerable road users alone. The paper will give a description of the injury pattern and injury mechanisms of accidents. The injury frequencies and severities are pointed out considering different types of VRU and protective measures of helmet and clothes of the human body. The impact points are demonstrated on the car, following to conclusion of protective measures on the vehicle. Existing standards of protection devices as well as interdisciplinary research, including accident and injury statistics, are described. With this paper, a summarization of the existing possibilities on protective measures for pedestrians, bicyclists and motorcyclists is given and discussed by comparison of all three groups of vulnerable road users. Also the relevance of special impact situations and accident causes mainly responsible for severe injuries are pointed out, given the new orientation of research for the avoidance and reduction of accident patterns. 2010 Elsevier Ltd. All rights reserved.

Physical Causation. Phil Dowe, Physical causation (Cambridge Studies in Probability, Induction, and Decision Theory), Cambridge University Press, Cambridge, 2000, pp. ix+224, price US60.00, ISBN: 0-521-78049-7 hbk

NASA Astrophysics Data System (ADS)

Hausman, Daniel M.

Causation is a frustrating subject. Suppose one begins with some promising idea such as that causation is counterfactual dependence or statistical relevance. One then develops this idea with care and intelligence, revises and improves it to cope with criticisms, and by the time one is finished, sane people will be looking elsewhere. If one wants conclusive reasons to reject the counterfactual theory of causation, one can do no better than to read Lewis' (1986) many postscripts. If one wants the best refutation of a probabilistic theory of causation, then one should read my colleague, Ellery Eells' (1991) magisterial defense. In Physical Causation, Phil Dowe performs the same service for physical process/interaction theories of causation.

Triatominae Biochemistry Goes to School: Evaluation of a Novel Tool for Teaching Basic Biochemical Concepts of Chagas Disease Vectors

ERIC Educational Resources Information Center

Cunha, Leonardo Rodrigues; de Oliveria Cudischevitch, Cecília; Carneiro, Alan Brito; Macedo, Gustavo Bartholomeu; Lannes, Denise; da Silva-Neto, Mário Alberto Cardoso

2014-01-01

We evaluate a new approach to teaching the basic biochemistry mechanisms that regulate the biology of Triatominae, major vectors of "Trypanosoma cruzi," the causative agent of Chagas disease. We have designed and used a comic book, "Carlos Chagas: 100 years after a hero's discovery" containing scientific information obtained by…

An Overview of the Processes of Social Transition in Rural Appalachia. Discussion Paper.

ERIC Educational Resources Information Center

Photiadis, John D.

There are two very distinct schools of thought concerning the causation of many of Appalachia'a problems. One school treats the region's socio-cultural pecularities as the major cause of developmental problems; the other blames the coal industry. This paper suggests that, at the base, both schools of thought are valid in explaining cause and…

Functional and structural characterization of soluble recombinant epsilon toxin of Clostridium perfringens D, causative agent of enterotoxaemia.

PubMed

Mathur, Deepika Dayal; Deshmukh, Sachin; Kaushik, Himani; Garg, Lalit C

2010-10-01

Clostridium perfringens types B and D are responsible for enterotoxaemia, one of the major causes of cattle mortality and is therefore of great economic concern. The epsilon toxin produced by the organism is the major antigenic determinant and has been directly implicated for the disease causation. In the present paper, we evaluated the biological activity of the recombinant epsilon toxin (rEtx) produced as soluble protein in Escherichia coli. The rEtx was purified to near homogeneity by a one-step anion-exchange chromatography. The immunological identity of purified rEtx was confirmed by Western blotting using a monoclonal antibody against the native toxin. The rEtx formed heptamer in the Madin-Darby canine kidney (MDCK) cells and synaptosomal membrane of mouse brain and was cytotoxic to the MDCK cells with a CT(50) of 30 ng/ml. The rEtx was highly stable and its thermostability profile related well with its biological activity. The rEtx was purified in large amounts and exhibited all the properties of native toxin and therefore can be used for the development of vaccine against the pathogen.

Anatomy of an Accident.

ERIC Educational Resources Information Center

Mobley, Michael

1984-01-01

The findings of industrial safety engineers in the areas of accident causation and prevention are wholly applicable to adventure programs. Adventure education instructors can use safety engineering concepts to assess the risk in a particular activity, understand factors that cause accidents, and intervene to minimize injuries and damages if…

Drugs and Addictions.

ERIC Educational Resources Information Center

Smith, S. Mae; Miller, Eva

The effects of drug abuse and dependence vary, depending on the type of drug, polydrug use, and characteristics of the user. The influence of genetic, neurochemical, neuropsyiological, sociocultural, and economic factors suggest that the etiology of substance abuse and dependence is multiply determined. Models explaining the causation of substance…

Why do dental implants fail? Part I.

PubMed

el Askary, A S; Meffert, R M; Griffin, T

1999-01-01

Many factors are attributed to failure of the dental implant, either directly or indirectly. The focus of this article is to define the causation of dental implant failure, as well as to present an evaluation of the implant literature regarding etiology, classification, management, and treatment of implant failures. This article will highlight the initial signs of implant failure with a view of some clinical cases in terms of classification and degrees of implant failure. Finally, a dental implant failure checklist is formulated to guide the practitioner in defining the cause of implant failure, be it infective or noninfective, and to establish percentages and frequency of occurrence. The checklist applies to all implant systems and will help to determine the factors responsible for causation and the repair procedures, whether they are at the surgical or restorative phases. The definition of implant failure is set forth in terms of ailing, failing, failed, and surviving implants, and the appropriate treatments and dispositions are outlined.

Incidence, Causative Mechanisms, and Anatomic Localization of Stroke in Pituitary Adenoma Patients Treated With Postoperative Radiation Therapy Versus Surgery Alone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sattler, Margriet G.A., E-mail: g.a.sattler@umcg.nl; Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON; Vroomen, Patrick C.

Purpose: To assess and compare the incidence of stroke and stroke subtype in pituitary adenoma patients treated with postoperative radiation therapy (RT) and surgery alone. Methods and Materials: A cohort of 462 pituitary adenoma patients treated between 1959 and 2008 at the University Medical Center Groningen in The Netherlands was studied. Radiation therapy was administered in 236 patients. The TOAST (Trial of ORG 10172 in Acute Stroke Treatment) and the Oxfordshire Community Stroke Project classification methods were used to determine causative mechanism and anatomic localization of stroke. Stroke incidences in patients treated with RT were compared with that observed aftermore » surgery alone. Risk factors for stroke incidence were studied by log–rank test, without and with stratification for other significant risk factors. In addition, the stroke incidence was compared with the incidence rate in the general Dutch population. Results: Thirteen RT patients were diagnosed with stroke, compared with 12 surgery-alone patients. The relative risk (RR) for stroke in patients treated with postoperative RT was not significantly different compared with surgery-alone patients (univariate RR 0.62, 95% confidence interval [CI] 0.28-1.35, P=.23). Stroke risk factors were coronary or peripheral artery disease (univariate and multivariate RR 10.4, 95% CI 4.7-22.8, P<.001) and hypertension (univariate RR 3.9, 95% CI 1.6-9.8, P=.002). There was no difference in TOAST and Oxfordshire classification of stroke. In this pituitary adenoma cohort 25 strokes were observed, compared with 16.91 expected (standard incidence ratio 1.48, 95% CI 1.00-1.96, P=.049). Conclusions: In pituitary adenoma patients, an increased incidence of stroke was observed compared with the general population. However, postoperative RT was not associated with an increased incidence of stroke or differences in causative mechanism or anatomic localization of stroke compared with surgery alone. The primary stroke risk factor was pre-existent coronary or peripheral artery disease.« less

Head injury causation scenarios for belted, rear-seated children in frontal impacts.

PubMed

Bohman, Katarina; Arbogast, Kristy B; Bostrom, Ola

2011-02-01

Head injuries are the most common serious injuries sustained by children in motor vehicle crashes and are of critical importance with regard to long-term disability. There is a lack of understanding of how seat belt-restrained children sustain head injuries in frontal impacts. The aim of the study was to identify the AIS2+ head injury causation scenarios for rear-seated, belt-restrained children in frontal impacts, including the set of parameters contributing to the injury. In-depth crash investigations from two National Highway Traffic Safety Administration (NHTSA) databases, the National Automotive Sampling System-Crashworthiness Data System (NASS-CDS; 1997-2008) and the Crash Injury Research and Engineering Network (CIREN; 1996-2009), were collected and analyzed in detail. Selection criteria were all frontal impacts with principal direction of force (PDOF) of 11, 12, and 1 o'clock involving rear-seated, three-point belt-restrained, with or without booster cushion, children from 3 to 13 years with an AIS2+ head injury. Cases were analyzed using the BioTab method of injury causation assessment in order to systematically analyze the injury causation scenario for each case. There were 27 cases meeting the inclusion criteria, 19 cases with MAIS2 head injuries and 8 cases with MAIS3+ head injuries, including 2 fatalities. Three major injury causation scenarios were identified, including head contact with seatback (10 cases), head contact with side interior (7 cases,) and no evidence of head contact (9 cases). Head injuries with seatback or side interior contact typically included a PDOF greater than 10 degree (similar to the Insurance Institute for Highway Safety [IIHS] and EuroNCAP offset frontal testing) and vehicle maneuvers. For seatback contact, the vehicle's movements contributed to occupant kinematics inboard the vehicle, causing a less than optimal restraint of the torso and/or torso roll out of the shoulder belt. For side interior contact, the PDOF and/or maneuvers forced the occupant toward the side interior. The cases without evidence of head/face contact were characterized by high crash severity and accompanied by severe injuries to the thorax and spine. These data lead to increased understanding of the injury patterns and causation in this crash restraint scenario so that interventions to mitigate the burden of injury can be advanced.

Evolution of sexual dimorphism in bill size and shape of hermit hummingbirds (Phaethornithinae): a role for ecological causation

PubMed Central

Temeles, Ethan J.; Miller, Jill S.; Rifkin, Joanna L.

2010-01-01

Unambiguous examples of ecological causation of sexual dimorphism are rare, and the best evidence involves sexual differences in trophic morphology. We show that moderate female-biased sexual dimorphism in bill curvature is the ancestral condition in hermit hummingbirds (Phaethornithinae), and that it is greatly amplified in species such as Glaucis hirsutus and Phaethornis guy, where bills of females are 60 per cent more curved than bills of males. In contrast, bill curvature dimorphism is lost or reduced in a lineage of short-billed hermit species and in specialist Eutoxeres sicklebill hermits. In the hermits, males tend to be larger than females in the majority of species, although size dimorphism is typically small. Consistent with earlier studies of hummingbird feeding performance, both raw regressions of traits and phylogenetic independent contrasts supported the prediction that dimorphism in bill curvature of hermits is associated with longer bills. Some evidence indicates that differences between sexes of hermit hummingbirds are associated with differences in the use of food plants. We suggest that some hermit hummingbirds provide model organisms for studies of ecological causation of sexual dimorphism because their sexual dimorphism in bill curvature provides a diagnostic clue for the food plants that need to be monitored for studies of sexual differences in resource use. PMID:20194168

Adjudicating non-knowledge in the Omnibus Autism Proceedings.

PubMed

Decoteau, Claire Laurier; Underman, Kelly

2015-08-01

After 5600 families of children diagnosed with autism filed claims with the National Vaccine Injury Compensation Program in the United States, the court selected 'test' cases consolidated into the Omnibus Autism Proceedings, held from 2007 to 2008, to examine claims that vaccines caused the development of autism. The court found all of the causation theories presented to be untenable and did not award damages to any parents. We analyze the Omnibus Autism Proceedings as a struggle within the scientific field between the scientific orthodoxy of the respondents and the heterodox position taken by the plaintiffs, suggesting that the ruling in these cases helped to shore up hegemony on autism causation. Drawing on the literature on non-knowledge, we suggest that only the respondents had enough scientific capital to strategically direct non-knowledge toward genetic research, thereby foreclosing the possibility of environmental causation of autism. The plaintiffs, who promote a non-standard ontology of autism, suggest that the science on autism remains undone and should not be circumscribed. In analyzing the Omnibus Autism Proceedings with field theory, we highlight the way in which scientific consensus-building and the setting of research agendas are the result of struggle, and we show that the strategic deployment of non-knowledge becomes a major stake in battles for scientific legitimacy and the settling of scientific controversies.

How unemployment and precarious employment affect the health of young people: A scoping study on social determinants.

PubMed

Vancea, Mihaela; Utzet, Mireia

2017-02-01

The impact of unemployment and precarious employment on the health of young people is not well understood. However, according to social causation, higher socio-economic positions and thus better working conditions are beneficial to health in general. We tried to synthesize the results of studies that test this hypothesis in the case of young people. We conducted a scoping study mapping all the academic articles published in the period 2006-2016 in Europe. The literature was searched in PubMed/Medline, Science Direct, Web of Science and Scopus. We identified 1770 studies, of which only 46 met the inclusion criteria. There are more studies that focus on the relationship between unemployment and health than between precarious employment and health (28 and 16, respectively). The vast majority of the studies (44) found support for the social causation hypothesis, the most common health outcomes being mental health disorders, health risk behaviour, poor quality of life and occupational injuries. The causal mechanisms behind this association relied mainly on the life-course perspective, the breadwinner model, and the lack of social and economic benefits provided by standard employment. There is evidence that young people are especially vulnerable to health problems when unemployed or working in precarious conditions. Active labour market and training programmes, inclusive social security measures, improved working conditions and targeted health programmes are important for addressing this vulnerability. Further research should strive to enhance the causal model by including a gender perspective, longitudinal data, more indicators on precariousness and third factor explanations.

Effects of truck traffic on crash injury severity on rural highways in Wyoming using Bayesian binary logit models.

PubMed

Ahmed, Mohamed M; Franke, Rebecca; Ksaibati, Khaled; Shinstine, Debbie S

2018-08-01

Roadway safety is an integral part of a functioning infrastructure. A major use of the highway system is the transport of goods. The United States has experienced constant growth in the amount of freight transported by truck in the last few years. Wyoming is experiencing a large increase in truck traffic on its local and county roads due to an increase in oil and gas production. This study explores the involvement of heavy trucks in crashes and their significance as a predictor of crash severity and addresses the effect that large truck traffic is having on the safety of roadways for various road classifications. Studies have been done on the factors involved in and the causation of heavy truck crashes, but none address the causation and effect of roadway classifications on truck crashes. Binary Logit Models (BLM) with Bayesian inferences were utilized to classify heavy truck involvement in severe and non-severe crashes using ten years (2002-2011) of historical crash data in the State of Wyoming. From the final main effects model, various interactions proved to be significant in predicting the severity of crashes and varied depending on the roadway classification. The results indicated the odds of a severe crash increase to 2.3 and 4.5 times when a heavy truck is involved on state and interstate highways respectively. The severity of crashes is significantly increased when road conditions were not clear, icy, and during snowy weather conditions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Multi-compartmental modeling of SORLA’s influence on amyloidogenic processing in Alzheimer’s disease

PubMed Central

2012-01-01

Background Proteolytic breakdown of the amyloid precursor protein (APP) by secretases is a complex cellular process that results in formation of neurotoxic Aβ peptides, causative of neurodegeneration in Alzheimer’s disease (AD). Processing involves monomeric and dimeric forms of APP that traffic through distinct cellular compartments where the various secretases reside. Amyloidogenic processing is also influenced by modifiers such as sorting receptor-related protein (SORLA), an inhibitor of APP breakdown and major AD risk factor. Results In this study, we developed a multi-compartment model to simulate the complexity of APP processing in neurons and to accurately describe the effects of SORLA on these processes. Based on dose–response data, our study concludes that SORLA specifically impairs processing of APP dimers, the preferred secretase substrate. In addition, SORLA alters the dynamic behavior of β-secretase, the enzyme responsible for the initial step in the amyloidogenic processing cascade. Conclusions Our multi-compartment model represents a major conceptual advance over single-compartment models previously used to simulate APP processing; and it identified APP dimers and β-secretase as the two distinct targets of the inhibitory action of SORLA in Alzheimer’s disease. PMID:22727043

Single nucleotide polymorphisms in the bovine MHC region of Japanese Black cattle are associated with bovine leukemia virus proviral load.

PubMed

Takeshima, Shin-Nosuke; Sasaki, Shinji; Meripet, Polat; Sugimoto, Yoshikazu; Aida, Yoko

2017-04-04

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis, a malignant B cell lymphoma that has spread worldwide and causes serious problems for the cattle industry. The BLV proviral load, which represents the BLV genome integrated into host genome, is a useful index for estimating disease progression and transmission risk. Here, we conducted a genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with BLV proviral load in Japanese Black cattle. The study examined 93 cattle with a high proviral load and 266 with a low proviral load. Three SNPs showed a significant association with proviral load. One SNP was detected in the CNTN3 gene on chromosome 22, and two (which were not in linkage disequilibrium) were detected in the bovine major histocompatibility complex region on chromosome 23. These results suggest that polymorphisms in the major histocompatibility complex region affect proviral load. This is the first report to detect SNPs associated with BLV proviral load in Japanese Black cattle using whole genome association study, and understanding host factors may provide important clues for controlling the spread of BLV in Japanese Black cattle.

Undesirable Enzymatic Browning in Crustaceans: Causative Effects and Its Inhibition by Phenolic Compounds.

PubMed

Nirmal, Nilesh Prakash; Benjakul, Soottawat; Ahmad, Mehraj; Arfat, Yasir Ali; Panichayupakaranant, Pharkphoom

2015-01-01

Undesirable enzymatic browning mediated by polyphenol oxidase (E.C. 1.14.18.1) on the surface of seafood from crustaceans have been a great concern to food processors, causing quality losses of seafood products. Seafoods especially from crustaceans are worldwide consumed due to their delicacy and nutritional value. However, black spot formation (melanosis) is the major problem occurring in crustaceans during postmortem handling and refrigerated storage induce deleterious changes in organoleptic properties and, therefore, decreases commercial value. Polyphenoloxidase (PPO), the copper-containing metalloprotein involved in oxidation of phenol to quinone is the major biochemical reaction of melanosis formation. This enzymatic mechanism causes unappealing blackening in postharvest crustaceans. To alleviate the melanosis formation in crustaceans, use of phenolic compounds from plant extract can serve as antimelanotics and appears to be a good alternative to the conventional sulfites which are associated with health-related disorders. In this review, we focuses on the unique features about the structure, distribution, and properties of PPO as well as mechanism of melanosis formation and provide a comprehensive deeper insight on the factors affecting melanosis formation and its inhibition by various antimelanotics including newly discovered plant phenolic compounds.

Novel Burkholderia mallei Virulence Factors Linked to Specific Host-Pathogen Protein Interactions

DTIC Science & Technology

2013-06-23

Wallqvist‡ Burkholderia mallei is an infectious intracellular pathogen whose virulence and resistance to antibiotics makes it a potential bioterrorism agent ...experimental Burkholderia data to ini- tially select a small number of proteins as putative viru- lence factors. We then used yeast two-hybrid assays...causative agent of glan- ders, a disease primarily affecting horses but transmittable to humans; and Burkholderia pseudomallei, which is responsible for

Excessive Cap-dependent Translation as a Molecular Mechanism Underlying ASD

DTIC Science & Technology

2013-08-01

dependent translation is a causative factor in autism spectrum disorder (ASD). To test this hypothesis, we have been studying transgenic mice that...determine whether eIF4E transgenic mice display cellular and molecular abnormalities due to excessive cap-dependent translation. mice. Our studies ...will provide information concerning whether overexpression of eIF4E is a biological risk factor for ASD. Our studies also will provide important

Breast cancer: critical data analysis concludes that estrogens are not the cause, however lifestyle changes can alter risk rapidly.

PubMed

Wiseman, Richard A

2004-08-01

The theory that estrogens are causally associated with increased risk of breast cancer and the question of whether lifetime cumulative exposure is necessary are critically reviewed. Systematic search was made of published epidemiological and clinical data relating to estrogen concentrations at different times and situations, and of breast cancer incidence with age and after lifestyle changes. Breast cancer incidence increases with age, although the rate of increase slows. Reproductive factors are known to affect risk, but data that do not fit the theory of estrogen causation include low estradiol levels and decline of estrogen excretion postmenopausally, rates in HRT-takers, absence of increased rate during or after pregnancy, and breast cancer in men. Breast cancer risk can be altered by external factors within a few years, as shown by studies in both Norway and England during World War II, by changing rates in migrant populations, and by the effect on rates of recent adiposity. It is probable that estrogens act as promoters rather than being directly causal. Even as promoters, lifetime exposure to estrogens is not necessary. The cause is most probably a lifestyle factor, changes in which can rapidly alter risk. This has important implications in the search for a causative factor.

Circulating species of Leishmania at microclimate area of Boulemane Province, Morocco: impact of environmental and human factors.

PubMed

Hmamouch, Asmae; El Alem, Mahmoud Mohamed; Hakkour, Maryam; Amarir, Fatima; Daghbach, Hassan; Habbari, Khalid; Fellah, Hajiba; Bekhti, Khadija; Sebti, Faiza

2017-02-22

Cutaneous leishmaniasis (CL) is widely distributed in Morocco where its geographical range and incidence are related to environmental factors. This study aimed to examine the impact of several factors on the distribution of CL in Boulemane Province, which is characterized by several microclimates, and to identify the Leishmania species circulating in these areas. Ordinary least squares regression (OLSR) analysis was performed to study the impact of poverty, vulnerability, population density, urbanization and bioclimatic factors on the distribution of CL in this province. Molecular characterization of parasites was performed using a previously described PCR-RFLP method targeting the ITS1 of ribosomal DNA of Leishmania. A total of 1009 cases were declared in Boulemane Province between the years 2000 and 2015 with incidences fluctuating over the years (P = 0.007). Analyzing geographical maps of the study region identified four unique microclimate areas; sub-humid, semi-arid, arid and Saharan. The geographical distribution and molecular identification of species shows that the Saharan microclimate, characterized by the presence of Leishmania major was the most affected (47.78%) followed by semi-arid area where Leishmania tropica was identified in three districts. Among several environmental factors included in the study, poverty had the greatest influence on the spatial extension of the disease in this province. The incidence of CL in Boulemane Province varies between microclimate areas, and environmental factors partly explain this variation. However, the existence of CL in the most affected districts is mainly related to poverty, population movement and human behavior. To our knowledge, this the first study utilizing molecular techniques to confirm L. tropica and L. major as the causative agents of CL in Boulemane Province. Our findings indicate that the spatial and temporal distribution of CL in Boulemane Province is strongly related to poverty and population movement.

Serum from Diesel Exhaust-Exposed Rats with Cardiac Dysfunction Alters Aortic Endothelial Cell Function In Vitro: Circulating Mediators as Causative Factors?

EPA Science Inventory

Although circulating inflammatory mediators are strongly associated with adverse cardiovascular outcomes triggered by inhaled air pollution, direct cause-effect linkage has not been established. Given that endothelial toxicity often precedes and precipitates cardiac dysfunction, ...

Identification of the Gifted: A Prospective View.

ERIC Educational Resources Information Center

Salles, Jose Ferraz

1987-01-01

A psychiatrist describes causative factors (e.g., difficult childbirth, cerebral hypoxemy), behaviors (e.g., motor instability, irritability, enuresis), and abilities (e.g., extrasensory perception, telepathy) that he has associated with giftedness but that are not widely recognized. He also advocates the use of ambidextrous training and Losanov…

Environmental enteric dysfunction and the fecal microbiota in Malawian children

USDA-ARS?s Scientific Manuscript database

Environmental enteric dysfunction (EED) is often measured with a dual sugar absorption test and implicated as a causative factor in childhood stunting. Disturbances in the gut microbiota are hypothesized to be a mechanism by which EED is exacerbated, although this supposition lacks support. We perfo...

Beliefs and perception of ill-health causation: a socio-cultural qualitative study in rural North-Eastern Ethiopia.

PubMed

Kahissay, Mesfin H; Fenta, Teferi G; Boon, Heather

2017-01-26

Understanding perceptions of the causes of ill-health common in indigenous communities may help policy makers to design effective integrated primary health care strategies to serve these communities. This study explored the indigenous beliefs of ill-health causation among those living in the Tehuledere Woreda /district/ in North East Ethiopia from a socio-cultural perspective. The study employed a qualitative ethnographic method informed by Murdock's Theory of Illness. Participatory observation, over a total of 5 months during the span of one year, was supplemented by focus group discussions (n = 96 participants in 10 groups) and in-depth interviews (n = 20) conducted with key informants. Data were analyzed thematically using narrative strategies. In these communities, illness is perceived to have supernatural (e.g., almighty God/ Allah, nature spirits, and human agents of the supernatural), natural (e.g., environmental sanitation and personal hygiene, poverty, biological and psychological factors) and societal causes (e.g., social trust, experiences of family support and harmony; and violation of social taboos). Therefore, the explanatory model of illness causation in this community was very similar to that of the Murdock model with one key difference: social elements need to be added to the model. Members of the study community believes that supernatural, natural and social elements are linked to ill-health causation. A successful integrated primary health care strategy should include strategies for supporting patients' needs in all three of these domains.

Identification of a novel splicing mutation within SLC17A8 in a Korean family with hearing loss by whole-exome sequencing.

PubMed

Ryu, Nari; Lee, Seokwon; Park, Hong-Joon; Lee, Byeonghyeon; Kwon, Tae-Jun; Bok, Jinwoong; Park, Chan Ik; Lee, Kyu-Yup; Baek, Jeong-In; Kim, Un-Kyung

2017-09-05

Hereditary hearing loss (HHL) is a common genetically heterogeneous disorder, which follows Mendelian inheritance in humans. Because of this heterogeneity, the identification of the causative gene of HHL by linkage analysis or Sanger sequencing have shown economic and temporal limitations. With recent advances in next-generation sequencing (NGS) techniques, rapid identification of a causative gene via massively parallel sequencing is now possible. We recruited a Korean family with three generations exhibiting autosomal dominant inheritance of hearing loss (HL), and the clinical information about this family revealed that there are no other symptoms accompanied with HL. To identify a causative mutation of HL in this family, we performed whole-exome sequencing of 4 family members, 3 affected and an unaffected. As the result, A novel splicing mutation, c.763+1G>T, in the solute carrier family 17, member 8 (SLC17A8) gene was identified in the patients, and the genotypes of the mutation were co-segregated with the phenotype of HL. Additionally, this mutation was not detected in 100 Koreans with normal hearing. Via NGS, we detected a novel splicing mutation that might influence the hearing ability within the patients with autosomal dominant non-syndromic HL. Our data suggests that this technique is a powerful tool to discover causative genetic factors of HL and facilitate diagnoses of the primary cause of HHL. Copyright © 2017 Elsevier B.V. All rights reserved.

Causation or selection - examining the relation between education and overweight/obesity in prospective observational studies: a meta-analysis.

PubMed

Kim, T J; Roesler, N M; von dem Knesebeck, O

2017-06-01

Numerous studies have investigated the association between education and overweight/obesity. Yet less is known about the relative importance of causation (i.e. the influence of education on risks of overweight/obesity) and selection (i.e. the influence of overweight/obesity on the likelihood to attain education) hypotheses. A systematic review was performed to assess the linkage between education and overweight/obesity in prospective studies in general populations. Studies were searched within five databases, and study quality was appraised with the Newcastle-Ottawa scale. In total, 31 studies were considered for meta-analysis. Regarding causation (24 studies), the lower educated had a higher likelihood (odds ratio: 1.33, 1.21-1.47) and greater risk (risk ratio: 1.34, 1.08-1.66) for overweight/obesity, when compared with the higher educated. However, these associations were no longer statistically significant when accounting for publication bias. Concerning selection (seven studies), overweight/obese individuals had a greater likelihood of lower education (odds ratio: 1.57, 1.10-2.25), when contrasted with the non-overweight or non-obese. Subgroup analyses were performed by stratifying meta-analyses upon different factors. Relationships between education and overweight/obesity were affected by study region, age groups, gender and observation period. In conclusion, it is necessary to consider both causation and selection processes in order to tackle educational inequalities in obesity appropriately. © 2017 World Obesity Federation.

Causation's nuclear future: applying proportional liability to the Price-Anderson Act.

PubMed

O'Connell, William D

2014-11-01

For more than a quarter century, public discourse has pushed the nuclear-power industry in the direction of heavier regulation and greater scrutiny, effectively halting construction of new reactors. By focusing on contemporary fear of significant accidents, such discourse begs the question of what the nation's court system would actually do should a major nuclear incident cause radiation-induced cancers. Congress's attempt to answer that question is the Price-Anderson Act, a broad statute addressing claims by the victims of a major nuclear accident. Lower courts interpreting the Act have repeatedly encountered a major stumbling block: it declares that judges must apply the antediluvian preponderance-of-the-evidence logic of state tort law, even though radiation science insists that the causes of radiation-induced cancers are more complex. After a major nuclear accident, the Act's paradoxically outdated rules for adjudicating "causation" would make post-incident compensation unworkable. This Note urges that nuclear-power-plant liability should not turn on eighteenth-century tort law. Drawing on modern scientific conclusions regarding the invariably "statistical" nature of cancer, this Note suggests a unitary federal standard for the Price-Anderson Act--that a defendant be deemed to have "caused" a plaintiff's injury in direct proportion to the increased risk of harm the defendant has imposed. This "proportional liability" rule would not only fairly evaluate the costs borne by injured plaintiffs and protect a reawakening nuclear industry from the prospect of bank-breaking litigation, but would prove workable with only minor changes to the Price-Anderson Act's standards of "injury" and "fault."

Familial pachygyria in both genders related to a DCX mutation.

PubMed

Kim, Young Ok; Nam, Tai-Seung; Park, Chungoo; Kim, Seul Kee; Yoon, Woong; Choi, Seok-Yong; Kim, Myeong-Kyu; Woo, Young Jong

2016-06-01

Doublecortin (DCX) and tubulin play critical roles in neuronal migration. DCX mutations usually cause anterior dominant lissencephaly in males and subcortical band heterotopia (SBH) in females. We used whole-exome sequencing to investigate causative gene variants in a large family with late-childhood-onset focal epilepsy and anterior dominant pachygyria without SBH in both genders. Two potential variants were found for the genes encoding DCX and beta tubulin isotype 1 (TUBB1). The novel DCX mutation (p.D90G, NP_000546.2) appeared to be a major causative variant, whereas the novel mutation of TUBB1 (p.R62fsX, NP_110400.1) was found only in patients with more-severe intellectual disability after gender matching. We report an unusual DCX-related disorder exhibiting familial pachygyria without SBH in both genders. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Pleural mesothelioma: epidemiological and public health issues. Report from the Second Italian Consensus Conference on Pleural Mesothelioma.

PubMed

Magnani, Corrado; Fubini, Bice; Mirabelli, Dario; Bertazzi, Pier Alberto; Bianchi, Claudio; Chellini, Elisabetta; Gennaro, Valerio; Marinaccio, Alessandro; Menegozzo, Massimo; Merler, Enzo; Merletti, Franco; Musti, Marina; Pira, Enrico; Romanelli, Antonio; Terracini, Benedetto; Zona, Amerigo

2013-01-01

Malignant mesothelioma is closely connected to asbestos exposure, with epidemiological patterns closely reshaping the geography and history of asbestos exposure. Mechanisms of causation and of interaction of asbestos fibres with pleura are complex and currently not yet completely understood. Curative efforts so far provided little results. Italy shows one of the highest incidence of MM and developed a network of specialized cancer registries in order to monitor disease occurrence and describe its epidemiology in details. The second Italian Consensus Conference on Pleural Mesothelioma convened in Torino on November 24th-25th, 2011. Besides the main consensus report summarizing the contribution of the different expertises, that was published elsewhere, the participants in 'Public Health and Epidemiology' section decided to report in major details the evidence and the conclusions regarding epidemiology, causative mechanisms and the public health impact of the disease.

Fifteen years of quantitative trait loci studies in fish: challenges and future directions.

PubMed

Ashton, David T; Ritchie, Peter A; Wellenreuther, Maren

2017-03-01

Understanding the genetic basis of phenotypic variation is a major challenge in biology. Here, we systematically evaluate 146 quantitative trait loci (QTL) studies on teleost fish over the last 15 years to investigate (i) temporal trends and (ii) factors affecting QTL detection and fine-mapping. The number of fish QTL studies per year increased over the review period and identified a cumulative number of 3632 putative QTLs. Most studies used linkage-based mapping approaches and were conducted on nonmodel species with limited genomic resources. A gradual and moderate increase in the size of the mapping population and a sharp increase in marker density from 2011 onwards were observed; however, the number of QTLs and variance explained by QTLs changed only minimally over the review period. Based on these findings, we discuss the causative factors and outline how larger sample sizes, phenomics, comparative genomics, epigenetics and software development could improve both the quantity and quality of QTLs in future genotype-phenotype studies. Given that the technical limitations on DNA sequencing have mostly been overcome in recent years, a renewed focus on these and other study design factors will likely lead to significant improvements in QTL studies in the future. © 2016 John Wiley & Sons Ltd.

Role of Uropathogenic Escherichia coli Virulence Factors in Development of Urinary Tract Infection and Kidney Damage

PubMed Central

Bien, Justyna; Sokolova, Olga; Bozko, Przemyslaw

2012-01-01

Uropathogenic Escherichia coli (UPEC) is a causative agent in the vast majority of urinary tract infections (UTIs), including cystitis and pyelonephritis, and infectious complications, which may result in acute renal failure in healthy individuals as well as in renal transplant patients. UPEC expresses a multitude of virulence factors to break the inertia of the mucosal barrier. In response to the breach by UPEC into the normally sterile urinary tract, host inflammatory responses are triggered leading to cytokine production, neutrophil influx, and the exfoliation of infected bladder epithelial cells. Several signaling pathways activated during UPEC infection, including the pathways known to activate the innate immune response, interact with calcium-dependent signaling pathways. Some UPEC isolates, however, might possess strategies to delay or suppress the activation of components of the innate host response in the urinary tract. Studies published in the recent past provide new information regarding how virulence factors of uropathogenic E. coli are involved in activation of the innate host response. Despite numerous host defense mechanisms, UPEC can persist within the urinary tract and may serve as a reservoir for recurrent infections and serious complications. Presentation of the molecular details of these events is essential for development of successful strategies for prevention of human UTIs and urological complications associated with UTIs. PMID:22506110

Food-dependent exercise-induced anaphylaxis in Japanese elementary school children.

PubMed

Manabe, Tetsuharu; Oku, Norihiro; Aihara, Yukoh

2018-04-01

In 2012, we clarified that the prevalence of food-dependent exercise-induced anaphylaxis (FDEIA) was 0.018% in junior-high students in Yokohama, Japan. Furthermore, although different from FDEIA, one student who had completed oral immunotherapy developed anaphylaxis during exercise after eating causative food. There have been few large-scale epidemiological studies of FDEIA, however, in elementary school children, therefore we conducted an epidemiological study in elementary school children in Yokohama to clarify the frequency and characteristic of FDEIA. We sent a questionnaire regarding the occurrence of FDEIA to all 348 public elementary school nurses in Yokohama. We also compared the results with those for junior-high school that we previously reported. We excluded those children with a past history of immediate food allergy who had achieved desensitization status after oral immunotherapy, from FDEIA, and instead defined them as having desensitization status and exercise-induced anaphylaxis (DEIA). Of 348 school nurses, 317 responded (91.1%). Overall, eight of 170 146 children were diagnosed with FDEIA, which was significantly lower than the prevalence in junior-high school students (0.0047% vs 0.018%, P = 0.0009). The causative foods were wheat (n = 4), and soy, fruit, crustaceans, and squid (n = 1 each). Four children had DEIA and the causative foods were wheat and milk (n = 2 each). Multiple episodes occurred in five children with FDEIA and in three children with DEIA. FDEIA was far less common in elementary school than in junior-high school, and wheat was the major causative food. The new appearance of DEIA was notable. Decreasing episode recurrence remains an issue that needs to be resolved. © 2018 Japan Pediatric Society.

Gene Augmentation Therapy for a Missense Substitution in the cGMP-Binding Domain of Ovine CNGA3 Gene Restores Vision in Day-Blind Sheep.

PubMed

Gootwine, Elisha; Abu-Siam, Mazen; Obolensky, Alexey; Rosov, Alex; Honig, Hen; Nitzan, Tali; Shirak, Andrey; Ezra-Elia, Raaya; Yamin, Esther; Banin, Eyal; Averbukh, Edward; Hauswirth, William W; Ofri, Ron; Seroussi, Eyal

2017-03-01

Applying CNGA3 gene augmentation therapy to cure a novel causative mutation underlying achromatopsia (ACHM) in sheep. Impaired vision that spontaneously appeared in newborn lambs was characterized by behavioral, electroretinographic (ERG), and histologic techniques. Deep-sequencing reads of an affected lamb and an unaffected lamb were compared within conserved genomic regions orthologous to human genes involved in similar visual impairment. Observed nonsynonymous amino acid substitutions were classified by their deleteriousness score. The putative causative mutation was assessed by producing compound CNGA3 heterozygotes and applying gene augmentation therapy using the orthologous human cDNA. Behavioral assessment revealed day blindness, and subsequent ERG examination showed attenuated photopic responses. Histologic and immunohistochemical examination of affected sheep eyes did not reveal degeneration, and cone photoreceptors expressing CNGA3 were present. Bioinformatics and sequencing analyses suggested a c.1618G>A, p.Gly540Ser substitution in the GMP-binding domain of CNGA3 as the causative mutation. This was confirmed by genetic concordance test and by genetic complementation experiment: All five compound CNGA3 heterozygotes, carrying both p.Arg236* and p.Gly540Ser mutations in CNGA3, were day-blind. Furthermore, subretinal delivery of the intact human CNGA3 gene using an adeno-associated viral vector (AAV) restored photopic vision in two affected p.Gly540Ser homozygous rams. The c.1618G>A, p.Gly540Ser substitution in CNGA3 was identified as the causative mutation for a novel form of ACHM in Awassi sheep. Gene augmentation therapy restored vision in the affected sheep. This novel mutation provides a large-animal model that is valid for most human CNGA3 ACHM patients; the majority of them carry missense rather than premature-termination mutations.

Causative Pathogens of Febrile Neutropaenia in Children Treated for Acute Lymphoblastic Leukaemia.

PubMed

Lam, Joyce Cm; Chai, Jie Yang; Wong, Yi Ling; Tan, Natalie Wh; Ha, Christina Tt; Chan, Mei Yoke; Tan, Ah Moy

2015-11-01

Treatment of acute lymphoblastic leukaemia (ALL) using intensive chemotherapy has resulted in high cure rates but also substantial morbidity. Infective complications represent a significant proportion of treatment-related toxicity. The objective of this study was to describe the microbiological aetiology and clinical outcome of episodes of chemotherapy-induced febrile neutropaenia in a cohort of children treated for ALL at our institution. Patients with ALL were treated with either the HKSGALL93 or the Malaysia-Singapore (Ma-Spore) 2003 chemotherapy protocols. The records of 197 patients who completed the intensive phase of treatment, defined as the period of treatment from induction, central nervous system (CNS)-directed therapy to reinduction from June 2000 to January 2010 were retrospectively reviewed. There were a total of 587 episodes of febrile neutropaenia in 197 patients, translating to an overall rate of 2.98 episodes per patient. A causative pathogen was isolated in 22.7% of episodes. An equal proportion of Gram-positive bacteria (36.4%) and Gram-negative bacteria (36.4%) were most frequently isolated followed by viral pathogens (17.4%), fungal pathogens (8.4%) and other bacteria (1.2%). Fungal organisms accounted for a higher proportion of clinically severe episodes of febrile neutropaenia requiring admission to the high-dependency or intensive care unit (23.1%). The overall mortality rate from all episodes was 1.5%. Febrile neutropaenia continues to be of concern in ALL patients undergoing intensive chemotherapy. The majority of episodes will not have an identifiable causative organism. Gram-positive bacteria and Gram-negative bacteria were the most common causative pathogens identified. With appropriate antimicrobial therapy and supportive management, the overall risk of mortality from febrile neutropaenia is extremely low.

Waardenburg syndrome: Novel mutations in a large Brazilian sample.

PubMed

Bocángel, Magnolia Astrid Pretell; Melo, Uirá Souto; Alves, Leandro Ucela; Pardono, Eliete; Lourenço, Naila Cristina Vilaça; Marcolino, Humberto Vicente Cezar; Otto, Paulo Alberto; Mingroni-Netto, Regina Célia

2018-06-01

This paper deals with the molecular investigation of Waardenburg syndrome (WS) in a sample of 49 clinically diagnosed probands (most from southeastern Brazil), 24 of them having the type 1 (WS1) variant (10 familial and 14 isolated cases) and 25 being affected by the type 2 (WS2) variant (five familial and 20 isolated cases). Sequential Sanger sequencing of all coding exons of PAX3, MITF, EDN3, EDNRB, SOX10 and SNAI2 genes, followed by CNV detection by MLPA of PAX3, MITF and SOX10 genes in selected cases revealed many novel pathogenic variants. Molecular screening, performed in all patients, revealed 19 causative variants (19/49 = 38.8%), six of them being large whole-exon deletions detected by MLPA, seven (four missense and three nonsense substitutions) resulting from single nucleotide substitutions (SNV), and six representing small indels. A pair of dizygotic affected female twins presented the c.430delC variant in SOX10, but the mutation, imputed to gonadal mosaicism, was not found in their unaffected parents. At least 10 novel causative mutations, described in this paper, were found in this Brazilian sample. Copy-number-variation detected by MLPA identified the causative mutation in 12.2% of our cases, corresponding to 31.6% of all causative mutations. In the majority of cases, the deletions were sporadic, since they were not present in the parents of isolated cases. Our results, as a whole, reinforce the fact that the screening of copy-number-variants by MLPA is a powerful tool to identify the molecular cause in WS patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Gene-Environment Interplay in Internalizing Disorders: Consistent Findings across Six Environmental Risk Factors

PubMed Central

Hicks, Brian M.; DiRago, Ana C.; Iacono, William G.; McGue, Matt

2009-01-01

Background Newer behavior genetic methods can better elucidate gene-environment (G-E) interplay in the development of internalizing (INT) disorders (i.e., major depression and anxiety disorders). However, no study to date has conducted a comprehensive analysis examining multiple environmental risks with the purpose of delineating how general G-E mechanisms influence the development of INT disorders. Methods The sample consisted of 1315 male and female twin pairs participating in the age 17 assessment of the Minnesota Twin Family Study. Quantitative G-E interplay models were used to examine how genetic and environmental risk for INT disorders changes as a function of environmental context. Multiple measures and informants were employed to construct composite measures of INT disorders and 6 environmental risk factors including: stressful life events, mother-child and father-child relationship problems, antisocial and prosocial peer affiliation, and academic achievement and engagement. Results Significant moderation effects were detected between each environmental risk factor and INT such that in the context of greater environmental adversity, nonshared environmental factors became more important in the etiology of INT symptoms. Conclusion Our results are consistent with the interpretation that environmental stressors have a causative effect on the emergence of INT disorders. The consistency of our results suggests a general mechanism of environmental influence on INT disorders regardless of the specific form of environmental risk. PMID:19594836

Insect venom hypersensitivity: experience in a clinical immunology/allergy service in Singapore.

PubMed

Thong, B Y H; Leong, K P; Chng, H H

2005-10-01

To study the profile of patients with allergy to the venom of insect stings. 31 consecutive cases referred to our clinical immunology/allergy outpatient service from June 1, 1998 to June 30, 2002 were reviewed. These patients comprised 3.5 percent of 889 cases referred during the study period. Their mean age was 28.8 +/- 10.5 (range 19-57) years and the majority were males (90.3 percent). Of these, 20 (64.5 percent) were Chinese, four (12.9 percent) were Malays and seven (22.6 percent) were of other races. 19 patients (61.3 percent) were men from the uniformed services including 12 (63.2 percent) full-time National Servicemen. 71 percent (22 patients) were stung for the first time. Urticaria (22 cases, 71.0 percent), dyspnoea (13, 41.9 percent), angioedema (12, 38.7 percent) and syncope (ten, 32.3 percent) were the most common manifestations of insect allergy. Anaphylaxis occurred in 22 (71.0 percent) cases, constituting 30.1 percent of all cases of anaphylaxis referred to our service during the study period. Although the causative insect was identified as honeybee (12, 38.7 percent), ant (four, 12.9 percent), wasp (three, 9.7 percent), and fire ant (two, 6.5 percent) by the majority of patients, ten (32.2 percent) patients were unable to identify the causative insect. The two patients stung by fire ants were Americans working in Singapore who had been stung while in the United States. Among those with anaphylaxis, honeybee, wasp and fire ant venom, for which specific immunotherapy is available, were identified as the cause in 40.9 percent, 4.5 percent, and 4.5 percent, respectively. Insect venom hypersensitivity made up 3.5 percent of allergy/immunology referrals and 32.8 percent of cases of anaphylaxis referred to our institution. The majority were military servicemen who developed allergic reactions during the course of duty. The inability to identify the causative insect in 50 percent with sting anaphylaxis limits the role of specific immunotherapy in our patients.

The Importance of Qualitative Research for Causal Explanation in Education

ERIC Educational Resources Information Center

Maxwell, Joseph A.

2012-01-01

The concept of causation has long been controversial in qualitative research, and many qualitative researchers have rejected causal explanation as incompatible with an interpretivist or constructivist approach. This rejection conflates causation with the positivist "theory" of causation, and ignores an alternative understanding of causation,…

Restraint Procedures and Challenging Behaviours in Intellectual Disability: An Analysis of Causative Factors

ERIC Educational Resources Information Center

Matson, Johnny L.; Boisjoli, Jessica A.

2009-01-01

Background: Persons with intellectual disability often evince challenging behaviours. Efforts have been underway for some time to develop prosocial or positive skill acquisition treatments to address challenging behaviours. However, physical/mechanical and chemical restraint is still commonly used in many clinical and community settings. Such…

Analysis of driver critical reason and years of driving experience in large truck crashes, analysis brief.

DOT National Transportation Integrated Search

2017-01-01

The 2005 Large Truck Crash Causation Study (LTCCS)i was the first-ever national study to attempt to determine the critical reasons and associated factors that contribute to serious large truck crashes. The LTCCS defines critical reason as the r...

Personality Variables in Foreign Policy Decision Making Studies.

ERIC Educational Resources Information Center

Johnson, Karen S.

Described and critiqued are studies that attempt to describe how personality factors affect foreign policy decision making. Political behavior cannot be explained in terms of personality alone. Such an attempt is a psychological reductionism that ignores the chains of causation that run from underlying personality construct to social and political…

Cultivation of Candidatus Liberibacter asiaticus and Ca. L. americanus associated with Huanglongbing

USDA-ARS?s Scientific Manuscript database

A new medium designated Liber A has been designed and used to successfully cultivate all three Candidatus Liberibacter species, the suspect causative agents of Huanglongbing (HLB) in citrus. The medium containing citrus vein extract and a growth factor sustained growth of Ca. Liberibacter species fo...

Causative factors and countermeasures for rural and suburban pedestrian accidents : accident data collection and analysis

DOT National Transportation Integrated Search

1977-03-01

The objectives of the study were to collect and analyze data on rural pedestrian accidents and to identify potential countermeasures. Data on a stratified random sample of over 1,500 rural and suburban accidents from six states was collected during i...

Nature and Causes of Locomotor Disabilities in India

ERIC Educational Resources Information Center

Halder, Santoshi; Talukdar, Arindam

2013-01-01

A large proportion of disability around the world is preventable. Levels of disability in many poor countries can be reduced by achieving the international development targets for economic, social and human development. In this paper, the author studied the different contributory and causative factors of locomotor disability, disease states and…

Sadness, Depression, and Avoidance Behavior

ERIC Educational Resources Information Center

Leventhal, Allan M.

2008-01-01

Research into genetic, psychosocial, and cognitive explanations for depression (biopsychosocial models) provides support for the role of these variables in the etiology of depression. Regularly identified as basic to depression is loss, and the experience of loss has been found to be more influential than genetic factors in the causation of…

Causative factors and countermeasures for rural and suburban pedestrian accidents : accident data collection and analysis--appendices

DOT National Transportation Integrated Search

1977-06-01

The objectives of the study were to collect and analyze data on rural pedestrian accidents and to identify potential countermeasures. Data on a stratified random sample of over 1,500 rural and suburban accidents from six states was collected during i...

Submission of nucleotide sequence clostridium perfringens elongation factor-tu to genbank database

USDA-ARS?s Scientific Manuscript database

Clostridium perfringens (CP) is ubiquitous in the nature, and a normal inhabitant in the intestinal tracts of animals and humans. However, pathogenic CP is also a causative agent of poultry disease necrotic enteritis (NE). Clostridium-related poultry diseases such as necrotic enteritis (NE) and gang...

Disseminated sporotrichosis in an immunocompetent patient.

PubMed

Hassan, Kareem; Turker, Tolga; Zangeneh, Tirdad

2016-01-01

Sporothrix schenckii, the causative agent of sporotrichosis, is a relatively rare infection. Local infection usually occurs through direct inoculation of the organism through the skin; disseminated disease is rarely seen. This article describes a case of disseminated sporotrichosis in a middle-aged man without the commonly seen risk factors for dissemination.

Pedestrian accidents in Arizona : an investigation of causative factor and recommendation for safety improvements, Volume 2 : final report

DOT National Transportation Integrated Search

1985-12-01

This research investigated the causes of pedestrian accidents in Arizona to discover why Arizona's pedestrian accident rate if higher than the national average. All pedestrian accidents for 1981, 1982, and 1983 that were computerized in the state acc...

Early Endothelial Bioactivity of Serum after Diesel Exhaust Inhalation: A Driver of Latent Impairment in Left Ventricular Pressure in the Heart?

EPA Science Inventory

Adverse cardiovascular effects of air pollution are often associated with a spike in systemic proinflammatory biomarkers, but causative linkage between circulating factors and deleterious outcomes following exposure remains elusive. Endothelial dysfunction is a consequence of sys...

Remarks on Causative Verbs and Object Deletion in English

ERIC Educational Resources Information Center

Onozuka, Hiromi

2007-01-01

Rappaport Hovav and Levin [Rappaport Hovav, M., Levin, B., 1998. "Building verb meanings." In: Butt, M., Geuder, W. (Eds.), "The Projection of Arguments: Lexical and Compositional Factors." CSLI Publications, Stanford, pp. 97-134] contend that result verbs disallow object deletion because of their lexical semantic properties. Their point is that…

Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function

PubMed Central

Ivaskevicius, Vytautas; Biswas, Arijit; Bevans, Carville; Schroeder, Verena; Kohler, Hans Peter; Rott, Hannelore; Halimeh, Susan; Petrides, Petro E.; Lenk, Harald; Krause, Manuele; Miterski, Bruno; Harbrecht, Ursula; Oldenburg, Johannes

2010-01-01

Background Severe hereditary coagulation factor XIII deficiency is a rare homozygous bleeding disorder affecting one person in every two million individuals. In contrast, heterozygous factor XIII deficiency is more common, but usually not associated with severe hemorrhage such as intracranial bleeding or hemarthrosis. In most cases, the disease is caused by F13A gene mutations. Causative mutations associated with the F13B gene are rarer. Design and Methods We analyzed ten index patients and three relatives for factor XIII activity using a photometric assay and sequenced their F13A and F13B genes. Additionally, structural analysis of the wild-type protein structure from a previously reported X-ray crystallographic model identified potential structural and functional effects of the missense mutations. Results All individuals except one were heterozygous for factor XIIIA mutations (average factor XIII activity 51%), while the remaining homozygous individual was found to have severe factor XIII deficiency (<5% of normal factor XIII activity). Eight of the 12 heterozygous patients exhibited a bleeding tendency upon provocation. Conclusions The identified missense (Pro289Arg, Arg611His, Asp668Gly) and nonsense (Gly390X, Trp664X) mutations are causative for factor XIII deficiency. A Gly592Ser variant identified in three unrelated index patients, as well as in 200 healthy controls (minor allele frequency 0.005), and two further Tyr167Cys and Arg540Gln variants, represent possible candidates for rare F13A gene polymorphisms since they apparently do not have a significant influence on the structure of the factor XIIIA protein. Future in vitro expression studies of the factor XIII mutations are required to confirm their pathological mechanisms. PMID:20179087

Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function.

PubMed

Ivaskevicius, Vytautas; Biswas, Arijit; Bevans, Carville; Schroeder, Verena; Kohler, Hans Peter; Rott, Hannelore; Halimeh, Susan; Petrides, Petro E; Lenk, Harald; Krause, Manuele; Miterski, Bruno; Harbrecht, Ursula; Oldenburg, Johannes

2010-06-01

Severe hereditary coagulation factor XIII deficiency is a rare homozygous bleeding disorder affecting one person in every two million individuals. In contrast, heterozygous factor XIII deficiency is more common, but usually not associated with severe hemorrhage such as intracranial bleeding or hemarthrosis. In most cases, the disease is caused by F13A gene mutations. Causative mutations associated with the F13B gene are rarer. We analyzed ten index patients and three relatives for factor XIII activity using a photometric assay and sequenced their F13A and F13B genes. Additionally, structural analysis of the wild-type protein structure from a previously reported X-ray crystallographic model identified potential structural and functional effects of the missense mutations. All individuals except one were heterozygous for factor XIIIA mutations (average factor XIII activity 51%), while the remaining homozygous individual was found to have severe factor XIII deficiency (<5% of normal factor XIII activity). Eight of the 12 heterozygous patients exhibited a bleeding tendency upon provocation. The identified missense (Pro289Arg, Arg611His, Asp668Gly) and nonsense (Gly390X, Trp664X) mutations are causative for factor XIII deficiency. A Gly592Ser variant identified in three unrelated index patients, as well as in 200 healthy controls (minor allele frequency 0.005), and two further Tyr167Cys and Arg540Gln variants, represent possible candidates for rare F13A gene polymorphisms since they apparently do not have a significant influence on the structure of the factor XIIIA protein. Future in vitro expression studies of the factor XIII mutations are required to confirm their pathological mechanisms.

[Causation in the court: the complex case of malignant mesothelioma].

PubMed

Lageard, Giovanni

2011-01-01

The aim of this paper is to carry out an analysis of the legal evolution in Italy of the assessment of causation i.e. cause and effect, in oncological diseases, a question taken into consideration by the High Court almost exclusively with reference to pleural mesothelioma. The most debated question when defining the causal association between asbestos exposure and mesothelioma is the possible role that any multiple potentially causative exposures could assume in the induction and development of the disease, and in particular the role of any asbestos exposure over the successive employment periods. Indeed, this is a subject on which, to date, no agreement has yet been reached in scientific doctrine: these divergences bear important practical significance from a legal point of view, since sustaining one thesis or another may constitute determining factors when ascertaining responsibility for individuals who, in the past, had decisional statuses in the workplace. Jurisprudence in the High Court took on an oscillating position on this question as from the early 2000s, which was divided into those who sustained the thesis of the relevance of any asbestos exposure over the successive employment periods and those who were of a different opinion, i.e. only the first exposure period has relevant causative effect. The point under discussion concerns, in particular, the adequacy of a probabilistic law only governing such a question. An important turning point was made in the year 2010 when two sentences were announced in the High Court, reiterating, in strict compliance with the principles affirmed by the United Sections in 2002, that a judge cannot, and must not, be satisfied with a general causation, but must rather reach a judgment on the basis of an individual causation. In particular, not only did the second of these two sentences recognise the multifactorial nature of mesothelioma, something which had almost always been denied in jurisprudence in the past, but it also established some very clear legal principles of law. Essentially, when ascertaining the causation, a judge should verify whether or not there is a sufficiently well established scientific law covering the question and whether such a law is universal or probabilistic. Should the latter be the case, then it is necessary to establish if the accelerating effect has been determined in the case in question, on the basis of the factual acquisitions. We must now wait for the concrete application of these principles by juridical bodies.

Self-care interventions for the school-aged child with encopresis.

PubMed

Vitito, L M

2000-01-01

Encopresis, an elimination disorder in children, presents as a challenging problem for gastroenterology nurses working with patients and families confronted with this disorder. This article offers a summary of the literature on encopresis, including pathogenesis, causative factors, early treatment, and clinical interventions focused on self-care. The antecedent factors that facilitate the child's participation in self-care are summarized, along with the intended outcomes of the self-care intervention plan.

A longitudinal examination of stress generation in depressive and anxiety disorders.

PubMed

Uliaszek, Amanda A; Zinbarg, Richard E; Mineka, Susan; Craske, Michelle G; Griffith, James W; Sutton, Jonathan M; Epstein, Alyssa; Hammen, Constance

2012-02-01

The current study compared two competing theories of the stress generation model of depression (stress causation vs. stress continuation) using interview-based measures of episodic life stress, as well as interpersonal and noninterpersonal chronic life stress. We also expanded on past research by examining anxiety disorders as well as depressive disorders. In addition, we examined the role of neuroticism and extraversion in these relationships. Participants were 627 adolescents enrolled in a two-site, longitudinal study of risk factors for depressive and anxiety disorders. Baseline and follow-up assessments were approximately one year apart. Results supported the stress causation theory for episodic stress generation for anxiety disorders, with neuroticism partially accounting for this relationship. The stress causation theory was also supported for depression, but only for more moderate to severe stressors; neuroticism partially accounted for this relationship as well. Finally, we found evidence for interpersonal and noninterpersonal chronic life stress continuation in both depressive and anxiety disorders. The present findings have implications regarding the specificity of the stress generation model to depressive disorders, as well as variables involved in the stress generation process. PsycINFO Database Record (c) 2012 APA, all rights reserved.

A conservative assessment of the major genetic causes of idiopathic chronic pancreatitis: data from a comprehensive analysis of PRSS1, SPINK1, CTRC and CFTR genes in 253 young French patients.

PubMed

Masson, Emmanuelle; Chen, Jian-Min; Audrézet, Marie-Pierre; Cooper, David N; Férec, Claude

2013-01-01

Idiopathic chronic pancreatitis (ICP) has traditionally been defined as chronic pancreatitis in the absence of any obvious precipitating factors (e.g. alcohol abuse) and family history of the disease. Studies over the past 15 years have revealed that ICP has a highly complex genetic architecture involving multiple gene loci. Here, we have attempted to provide a conservative assessment of the major genetic causes of ICP in a sample of 253 young French ICP patients. For the first time, conventional types of mutation (comprising coding sequence variants and variants at intron/exon boundaries) and gross genomic rearrangements were screened for in all four major pancreatitis genes, PRSS1, SPINK1, CTRC and CFTR. For the purposes of the study, synonymous, intronic and 5'- or 3'-untranslated region variants were excluded from the analysis except where there was persuasive evidence of functional consequences. The remaining sequence variants/genotypes were classified into causative, contributory or neutral categories by consideration of (i) their allele frequencies in patient and normal control populations, (ii) their presumed or experimentally confirmed functional effects, (iii) the relative importance of their associated genes in the pathogenesis of chronic pancreatitis and (iv) gene-gene interactions wherever applicable. Adoption of this strategy allowed us to assess the pathogenic relevance of specific variants/genotypes to their respective carriers to an unprecedented degree. The genetic cause of ICP could be assigned in 23.7% of individuals in the study group. A strong genetic susceptibility factor was also present in an additional 24.5% of cases. Taken together, up to 48.2% of the studied ICP patients were found to display evidence of a genetic basis for their pancreatitis. Whereas these particular proportions may not be extrapolable to all ICP patients, the approach employed should serve as a useful framework for acquiring a better understanding of the role of genetic factors in causing this oligogenic disease.

Genetic heterogeneity in cholangiocarcinoma: a major challenge for targeted therapies

PubMed Central

Brandi, Giovanni; Farioli, Andrea; Astolfi, Annalisa; Biasco, Guido; Tavolari, Simona

2015-01-01

Cholangiocarcinoma (CC) encompasses a group of related but distinct malignancies whose lack of a stereotyped genetic signature makes challenging the identification of genomic landscape and the development of effective targeted therapies. Accumulated evidences strongly suggest that the remarkable genetic heterogeneity of CC may be the result of a complex interplay among different causative factors, some shared by most human cancers while others typical of this malignancy. Currently, considerable efforts are ongoing worldwide for the genetic characterization of CC, also using advanced technologies such as next-generation sequencing (NGS). Undoubtedly this technology could offer an unique opportunity to broaden our understanding on CC molecular pathogenesis. Despite this great potential, however, the high complexity in terms of factors potentially contributing to genetic variability in CC calls for a more cautionary application of NGS to this malignancy, in order to avoid possible biases and criticisms in the identification of candidate actionable targets. This approach is further justified by the urgent need to develop effective targeted therapies in this disease. A multidisciplinary approach integrating genomic, functional and clinical studies is therefore mandatory to translate the results obtained by NGS into effective targeted therapies for this orphan disease. PMID:26142706

Infection of orthopedic implants with emphasis on bacterial adhesion process and techniques used in studying bacterial-material interactions

PubMed Central

Ribeiro, Marta; Monteiro, Fernando J.; Ferraz, Maria P.

2012-01-01

Staphylococcus comprises up to two-thirds of all pathogens in orthopedic implant infections and they are the principal causative agents of two major types of infection affecting bone: septic arthritis and osteomyelitis, which involve the inflammatory destruction of joint and bone. Bacterial adhesion is the first and most important step in implant infection. It is a complex process influenced by environmental factors, bacterial properties, material surface properties and by the presence of serum or tissue proteins. Properties of the substrate, such as chemical composition of the material, surface charge, hydrophobicity, surface roughness and the presence of specific proteins at the surface, are all thought to be important in the initial cell attachment process. The biofilm mode of growth of infecting bacteria on an implant surface protects the organisms from the host immune system and antibiotic therapy. The research for novel therapeutic strategies is incited by the emergence of antibiotic-resistant bacteria. This work will provide an overview of the mechanisms and factors involved in bacterial adhesion, the techniques that are currently being used studying bacterial-material interactions as well as provide insight into future directions in the field. PMID:23507884

Prevalence of Tinea Capitis Infection Among Primary School Children in a Rural Setting in South-West Nigeria

PubMed Central

Ayanlowo, Olusola; Oladele, Rita; Balogun, Mobolanle

2014-01-01

Dermatophyte infection is a common skin disorder. Tinea capitis, infection of the scalp and hair shaft, is the most common dermatophytosis in children aged between six months and pre-pubertal age. The aim of the study was to determine the prevalence, causative agents and to identify predisposing factors among primary school children in a rural community in Sagamu, Ogun state, Nigeria. This was a descriptive cross sectional study. Interviewer administered questionnaire was used. Following a physical examination, children with a clinical diagnosis of tinea capitis had scalp and hair scrapings for microscopy and culture. Tinea capitis was confirmed in 15.4%. Trichophyton mentagrophyte (51.7%) and Microsporum aoudouinii (20.7%) were the most prevalent organisms in this study. The most common predisposing factors were carrying of objects on the scalp; sharing of hair clippers, scissors, combs, towels and fomites. Low socioeconomic status coupled with overcrowding and poor hygiene was the major determinant of tinea capitis among the children. Tinea capitis remains a common infection among Nigerian school children. Health promotion and health education interventions are recommended to promote good hygiene, better living conditions, early identification and treatment. PMID:28299118

Differential Establishment of Bifidobacteria in the Breastfed Infant Gut

PubMed Central

Lewis, Zachery T.; Mills, David A.

2017-01-01

The composition of an infant’s gut microbiome can impact their immediate and long-term health. Bifdobacteria play a major role in structuring the gut microbiome of breastfed infants due to their ability to consume oligosaccharides found in human milk. However, recent studies have revealed that bifidobacteria are often absent in the gut microbiome of breastfed infants in some locations. This lack of colonization may be due either to differences in the environmental conditions in the gastrointestinal tract of uncolonized infants which prohibit the growth of bifidobacteria or a dearth of sources from which infants may acquire these specialized bacterial species. Potential mechanisms by which these broad factors may lead to lower colonization of infants by bifidobacteria are discussed herein. Environmental conditions which may select against bifidobacteria include low rates/duration of breastfeeding, milk glycan composition, and antimicrobial use. Routes of colonization by bifidobacteria which may be disrupted include maternal transfer via vaginal birth, fecal-oral routes, or via breast milk itself. A careful contemplation of the conditions experienced by bifidobacteria over human evolutionary history may lead to further hypotheses as to the causative factors of the differential colonization by this foundation genus in some contemporary locations. PMID:28346936

Loss of PAFR prevents neuroinflammation and brain dysfunction after traumatic brain injury

PubMed Central

Yin, Xiang-Jie; Chen, Zhen-Yan; Zhu, Xiao-Na; Hu, Jin-Jia

2017-01-01

Traumatic brain injury (TBI) is a principal cause of death and disability worldwide, which is a major public health problem. Death caused by TBI accounts for a third of all damage related illnesses, which 75% TBI occurred in low and middle income countries. With the increasing use of motor vehicles, the incidence of TBI has been at a high level. The abnormal brain functions of TBI patients often show the acute and long-term neurological dysfunction, which mainly associated with the pathological process of malignant brain edema and neuroinflammation in the brain. Owing to the neuroinflammation lasts for months or even years after TBI, which is a pivotal causative factor that give rise to neurodegenerative disease at late stage of TBI. Studies have shown that platelet activating factor (PAF) inducing inflammatory reaction after TBI could not be ignored. The morphological and behavioral abnormalities after TBI in wild type mice are rescued by general knockout of PAFR gene that neuroinflammation responses and cognitive ability are improved. Our results thus define a key inflammatory molecule PAF that participates in the neuroinflammation and helps bring about cerebral dysfunction during the TBI acute phase. PMID:28094295

Impaired visuocortical discrimination learning of socially conditioned stimuli in social anxiety

PubMed Central

Mühlberger, Andreas; Pauli, Paul; Wieser, Matthias J.

2015-01-01

In search of causative factors of social anxiety disorder (SAD), classical conditioning has been discussed as a potential trigger mechanism for many years. Recent findings suggest that the social relevance of the unconditioned stimulus (US) might play a major role in learning theories of SAD. Thus, this study applied a social conditioning paradigm with disorder-relevant US to examine the electrocortical correlates of affective learning. Twenty-four high socially anxious (HSA) and 23 age- and gender-matched low socially anxious (LSA) subjects were conditioned to 3 different faces flickering at a frequency of 15 Hz which were paired with auditory insults, compliments or neutral comments (US). The face-evoked electrocortical response was measured via steady-state visually evoked potentials and subjective measures of valence and arousal were obtained. Results revealed a significant interaction of social anxiety and conditioning, with LSA showing highest cortical activity to faces paired with insults and lowest activity to faces paired with compliments, while HSA did not differentiate between faces. No group differences were discovered in the affective ratings. The findings indicate a potentially impaired ability of HSA to discriminate between relevant and irrelevant social stimuli, which may constitute a perpetuating factor of SAD. PMID:25338634

A pan-European epidemiological study reveals honey bee colony survival depends on beekeeper education and disease control.

PubMed

Jacques, Antoine; Laurent, Marion; Ribière-Chabert, Magali; Saussac, Mathilde; Bougeard, Stéphanie; Budge, Giles E; Hendrikx, Pascal; Chauzat, Marie-Pierre

2017-01-01

Reports of honey bee population decline has spurred many national efforts to understand the extent of the problem and to identify causative or associated factors. However, our collective understanding of the factors has been hampered by a lack of joined up trans-national effort. Moreover, the impacts of beekeeper knowledge and beekeeping management practices have often been overlooked, despite honey bees being a managed pollinator. Here, we established a standardised active monitoring network for 5 798 apiaries over two consecutive years to quantify honey bee colony mortality across 17 European countries. Our data demonstrate that overwinter losses ranged between 2% and 32%, and that high summer losses were likely to follow high winter losses. Multivariate Poisson regression models revealed that hobbyist beekeepers with small apiaries and little experience in beekeeping had double the winter mortality rate when compared to professional beekeepers. Furthermore, honey bees kept by professional beekeepers never showed signs of disease, unlike apiaries from hobbyist beekeepers that had symptoms of bacterial infection and heavy Varroa infestation. Our data highlight beekeeper background and apicultural practices as major drivers of honey bee colony losses. The benefits of conducting trans-national monitoring schemes and improving beekeeper training are discussed.

Prevalence of Tinea Capitis Infection Among Primary School Children in a Rural Setting in South-West Nigeria.

PubMed

Ayanlowo, Olusola; Akinkugbe, Ayesha; Oladele, Rita; Balogun, Mobolanle

2014-02-04

Dermatophyte infection is a common skin disorder. Tinea capitis , infection of the scalp and hair shaft, is the most common dermatophytosis in children aged between six months and pre-pubertal age. The aim of the study was to determine the prevalence, causative agents and to identify predisposing factors among primary school children in a rural community in Sagamu, Ogun state, Nigeria. This was a descriptive cross sectional study. Interviewer administered questionnaire was used. Following a physical examination, children with a clinical diagnosis of tinea capitis had scalp and hair scrapings for microscopy and culture. Tinea capitis was confirmed in 15.4%. Trichophyton mentagrophyte (51.7%) and Microsporum aoudouinii (20.7%) were the most prevalent organisms in this study. The most common predisposing factors were carrying of objects on the scalp; sharing of hair clippers, scissors, combs, towels and fomites. Low socioeconomic status coupled with overcrowding and poor hygiene was the major determinant of tinea capitis among the children. Tinea capitis remains a common infection among Nigerian school children. Health promotion and health education interventions are recommended to promote good hygiene, better living conditions, early identification and treatment.

Molecular pathogenesis of infections caused by Legionella pneumophila.

PubMed

Newton, Hayley J; Ang, Desmond K Y; van Driel, Ian R; Hartland, Elizabeth L

2010-04-01

The genus Legionella contains more than 50 species, of which at least 24 have been associated with human infection. The best-characterized member of the genus, Legionella pneumophila, is the major causative agent of Legionnaires' disease, a severe form of acute pneumonia. L. pneumophila is an intracellular pathogen, and as part of its pathogenesis, the bacteria avoid phagolysosome fusion and replicate within alveolar macrophages and epithelial cells in a vacuole that exhibits many characteristics of the endoplasmic reticulum (ER). The formation of the unusual L. pneumophila vacuole is a feature of its interaction with the host, yet the mechanisms by which the bacteria avoid classical endosome fusion and recruit markers of the ER are incompletely understood. Here we review the factors that contribute to the ability of L. pneumophila to infect and replicate in human cells and amoebae with an emphasis on proteins that are secreted by the bacteria into the Legionella vacuole and/or the host cell. Many of these factors undermine eukaryotic trafficking and signaling pathways by acting as functional and, in some cases, structural mimics of eukaryotic proteins. We discuss the consequences of this mimicry for the biology of the infected cell and also for immune responses to L. pneumophila infection.

Epidemiological Study on Cutaneous Leishmaniasis in an Endemic Area, of Qom Province, Central Iran.

PubMed

Saghafipour, Abedin; Vatandoost, Hassan; Zahraei-Ramazani, Ali Reza; Yaghoobi-Ershadi, Mohammad Reza; Jooshin, Moharram Karami; Rassi, Yavar; Shirzadi, Mohammad Reza; Akhavan, Amir Ahmad; Hanafi-Bojd, Ahmad Ali

2017-09-01

Cutaneous leishmaniasis (CL) is one of the most important health problems in many areas of Iran. There are two forms of the disease in Iran, anthroponotic and zoonotic CL. This study conducted to assess the epidemiological situation of CL in an endemic area of Qom Province, central Iran from Apr to Nov 2015. The sticky paper traps and aspirating tubes were used for collecting adult sand flies. Sherman traps and small insect nets were used to capture rodents and small mammals. Giemsa staining was used for preparing the expanded smear and followed by PCR for identifying the causative agent in human, vectors, and reservoirs. In this study, relative frequency of CL was also calculated. Fourteen species of Phlebotomine sand flies were collected. Phlebotomus papatasi (61.74%) was the predominant species through the period of activity. Overall, 62 Meriones libycus , 8 Nesokia indica , 4 Mus musculus , 16 Allactaga elater and 2 Hemiechinus auritis were caught. PCR technique showed 6 out of 150 P. papatasi (2%), two out of 62 M. libycus (3.23%) and all of suspected human's skin tissue samples (100%) were infected with Leishmania major . The relative frequency of CL was 0.30%. This is the first detection of L. major within P. papatasi , M. libycus and human in Kahak District in Qom Province of Iran. Zoonotic cycle of CL exists in this area, L. major is the causative agent, P. papatasi is the main vector and M. libycus is the main reservoir of the disease.

Ventilator associated pneumonia: perspectives on the burden of illness.

PubMed

Cook, D

2000-01-01

The objective of this narrative review is to summarize selected current concepts and clinical evidence regarding the burden of illness of VAP, including its epidemiology, diagnosis, attributable mortality and risk factors. Studies were identified through MEDLINE, EMBASE, bibliographies of primary and review articles and personal files. While cross sectional studies inform us about VAP prevalence, longitudinal studies inform us of the cumulative risk and conditional risk of developing VAP. Reported VAP rates are modulated by factors related to case mix, causative microorganisms, interventions that influence risk over time, and VAP definitions employed. Population-specific and organism-specific VAP rates are needed to avoid misleading benchmarking between different ICUs, and to minimize inappropriate between-study comparisons. Observational studies have shown that invasive sampling techniques versus non-invasive approaches to diagnose VAP facilitates more targeted antibiotic treatment; however, the influence of the diagnostic method on endpoints such as mortality is less clear. VAP is associated with approximately a 4 day increase in length of ICU stay and an attributable mortality of approximately 20-30%. Fixed VAP risk factors include underlying cardiorespiratory disease, neurologic injury and trauma. Modifiable VAP risk factors include supine body position, witnessed aspiration, paralytic agents and antibiotic exposure. If modifiable risk factors tested in randomized trials lower VAP rates, such as semirecumbency versus supine positioning, these represent effective VAP prevention strategies. Ventilator-associated pneumonia is a major morbid outcome among critically ill patients. Studies evaluating more effective prevention and treatment strategies are needed.

Factual causation in medical negligence.

PubMed

Manning, Joanna

2007-12-01

The conventional approach to causation in negligence is the "but for" test, decided on the balance of probabilities. Even when supplemented by the "material contribution" principle, satisfying the onus of proof of causation can be an insuperable obstacle for plaintiffs, particularly in medical cases. Yet, having found a breach of duty, a court's sympathies may gravitate toward the plaintiff at this point in the case. Accordingly, courts have sometimes accepted a relaxation of strict causation principles. The judicial devices are described: a special principle of causation in particular duties of care; a shifting burden of proof; "bridging the evidentiary gap" by drawing a robust inference of causation; treating a material increase in risk as sufficient proof of causation; and permitting causation to be established on the basis of the loss of a material chance of achieving a better outcome and discounting damages. In Accident Compensation Corp v Ambros [2007] NZCA 304 the New Zealand Court of Appeal recognised the need for a legal device to ameliorate the injustice sometimes caused by the strict rules of causation, and preferred the "inferential reasoning" approach favoured by the Canadian common law for use in the context of the accident compensation scheme. It is hoped that the New Zealand Supreme Court approves Ambros if the opportunity arises.

Top-down causation and emergence: some comments on mechanisms

PubMed Central

Ellis, George F. R.

2012-01-01

Both bottom-up and top-down causation occur in the hierarchy of structure and causation. A key feature is multiple realizability of higher level functions, and consequent existence of equivalence classes of lower level variables that correspond to the same higher level state. Five essentially different classes of top-down influence can be identified, and their existence demonstrated by many real-world examples. They are: algorithmic top-down causation; top-down causation via non-adaptive information control, top-down causation via adaptive selection, top-down causation via adaptive information control and intelligent top-down causation (the effect of the human mind on the physical world). Through the mind, abstract entities such as mathematical structures have causal power. The causal slack enabling top-down action to take place lies in the structuring of the system so as to attain higher level functions; in the way the nature of lower level elements is changed by context, and in micro-indeterminism combined with adaptive selection. Understanding top-down causation can have important effects on society. Two cases will be mentioned: medical/healthcare issues, and education—in particular, teaching reading and writing. In both cases, an ongoing battle between bottom-up and top-down approaches has important consequences for society. PMID:23386967

[Elevated blood pressure as cardiovascular risk factor].

PubMed

Kowalewski, Wiesław; Hebel, Kazimiera

2013-01-01

Cardiovascular diseases for decades have been and still are the main and current health problem of the Polish society and there are many reasons for these diseases. Hypertension is one of the major risk factors for developing cardiovascular disease. The factors significantly increasing risk the of cardiovascular disease are in addition to high blood pressure, smoking (also passive), high blood fats (cholesterol and its HDL, LDL fractions as well as triglyceride levels, obesity, lack of exercise, diabetes and hereditary features. Other important factors which play an important role are external factors such as e.g. environmental pollution, lifestyle, stress. Prediction of cardiovascular disease should start from the evaluation of the fetal period because low birth weight may be a risk of coronary heart disease, hypertension, obesity or diabetes in adulthood. The authors of the referred tests showed that the level of blood pressure observed during childhood is closely associated with the level of blood pressure in adults and is also dependent on the body weight. Since the issue of the effects of high pressure on the cardiovascular system is inherent in the issue of the metabolic syndrome, it should be mentioned also that another causative factor may be an irregularity in the removal of urine from the body and the amount of insulin. The control of hypertension is a complex problem, at least in view of the wide range of adverse factors affecting the human body: hypertension is often either a constituent of other lesions. Therefore, it is difficult to treat high blood pressure in the strict sense; more often it is a combination therapy based on pharmacology caused for other reasons.

Clinical and Microbiological Characteristics of Breakthrough Candidemia in Allogeneic Hematopoietic Stem Cell Transplant Recipients in a Japanese Hospital

PubMed Central

Kimura, Muneyoshi; Yamamoto, Hisashi; Asano-Mori, Yuki; Nakamura, Shigeki; Yamagoe, Satoshi; Ohno, Hideaki; Miyazaki, Yoshitsugu; Abe, Masahiro; Yuasa, Mitsuhiro; Kaji, Daisuke; Kageyama, Kosei; Nishida, Aya; Ishiwata, Kazuya; Takagi, Shinsuke; Yamamoto, Go; Uchida, Naoyuki; Izutsu, Koji; Wake, Atsushi; Taniguchi, Shuichi; Yoneyama, Akiko

2017-01-01

ABSTRACT Few data on breakthrough candidemia (BC), defined as candidemia that develops on administration of antifungal agents (AFAs), in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are available. The medical and microbiological records of recipients of an allo-HSCT obtained between December 2008 and December 2014 were reviewed. Of 768 allo-HSCT cases, 26 developed BC. Among the 26 causative strains, 22 strains were stored and identified by sequencing. The following species were isolated: Candida parapsilosis (9 strains), C. glabrata (4 strains), C. guilliermondii (3 strains), and other Candida species (6 strains). The AFAs being used when BC developed were micafungin (17 cases), liposomal amphotericin B (5 cases), itraconazole (2 cases), and voriconazole (2 cases). All 17 cases who developed BC during micafungin administration were administered 150 mg/day of micafungin. The susceptibilities of the causative Candida species to the administered AFAs when breakthrough occurred ranged from susceptible to resistant. Especially, 85% of the Candida species that caused BC during micafungin administration were susceptible to micafungin. Additionally, 75% of the strains were wild type for susceptibility to the administered AFAs when breakthrough occurred. Systemic steroid administration and a longer severe neutropenic phase (≥5 days) were independent risk factors for BC (P = 0.016 and P = 0.015, respectively). BC developed in allo-HSCT recipients even when they received a sufficient dose of AFA, including micafungin, to which the causative Candida species were susceptible and/or had wild-type susceptibility in vitro. Systemic steroid administration and a longer severe neutropenic phase were host-based factors associated with BC. PMID:28115352

Events in the Grammar of Direct and Indirect Causation

ERIC Educational Resources Information Center

Vecchiato, Antonella

2011-01-01

This work investigates the differences between two widespread types of causative constructions: the so called lexical causative as in Gianna opened the door or the corresponding Italian sentence Gianna ha aperto la porta, and the periphrastic causative, as in the Italian Gianna ha fatto aprire la porta (Gianna had the door opened/made the door…

Herpes simplex type 2 encephalitis and methotrexate medication: a fortuitous or causative association in a patient with spondyloarthritis?

PubMed

Lupo, Julien; Dos Santos, Ophélie; Germi, Raphaele; Baccard-Longère, Monique; Stahl, Jean-Paul; Epaulard, Olivier; Morand, Patrice

2017-01-01

It is unclear whether immunosuppression is a risk factor for herpes encephalitis. Herein, we describe a rare case of herpes simplex virus type 2 encephalitis in a patient treated with low-dose methotrexate for HLA-B27-associated spondyloarthritis. The patient was successfully treated with acyclovir but presented sequelae of encephalitis. Here we discuss the possible role of low-dose methotrexate therapy as a risk factor of neurological herpes reactivation and severe disease. The host-related and viral risk factors are also addressed.

What are the factors that contribute to road accidents? An assessment of law enforcement views, ordinary drivers' opinions, and road accident records.

PubMed

Rolison, Jonathan J; Regev, Shirley; Moutari, Salissou; Feeney, Aidan

2018-06-01

What are the main contributing factors to road accidents? Factors such as inexperience, lack of skill, and risk-taking behaviors have been associated with the collisions of young drivers. In contrast, visual, cognitive, and mobility impairment have been associated with the collisions of older drivers. We investigated the main causes of road accidents by drawing on multiple sources: expert views of police officers, lay views of the driving public, and official road accident records. In Studies 1 and 2, police officers and the public were asked about the typical causes of road traffic collisions using hypothetical accident scenarios. In Study 3, we investigated whether the views of police officers and the public about accident causation influence their recall accuracy for factors reported to contribute to hypothetical road accidents. The results show that both expert views of police officers and lay views of the driving public closely approximated the typical factors associated with the collisions of young and older drivers, as determined from official accident records. The results also reveal potential underreporting of factors in existing accident records, identifying possible inadequacies in law enforcement practices for investigating driver distraction, drug and alcohol impairment, and uncorrected or defective eyesight. Our investigation also highlights a need for accident report forms to be continuously reviewed and updated to ensure that contributing factor lists reflect the full range of factors that contribute to road accidents. Finally, the views held by police officers and the public on accident causation influenced their memory recall of factors involved in hypothetical scenarios. These findings indicate that delay in completing accident report forms should be minimised, possibly by use of mobile reporting devices at the accident scene. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Beliefs about cancer causation and prevention as a function of personal and family history of cancer: a national, population-based study.

PubMed

Lykins, Emily L B; Graue, Lili O; Brechting, Emily H; Roach, Abbey R; Gochett, Celestine G; Andrykowski, Michael A

2008-10-01

Research suggests individuals possess multifaceted cognitive representations of various diseases. These illness representations consist of various beliefs, including causal attributions for the disease, and are believed to motivate, guide, and shape health-related behavior. As little research has examined factors associated with beliefs about cancer causation, this study examined the relationship between personal and family history of cancer and beliefs about the causes and prevention of malignant disease. Data were obtained from 6369 adult respondents to the 2003 Health Information National Trends Survey, a national population-based survey. Information about personal and family history of cancer and beliefs regarding cancer causation and prevention was obtained. Results showed both a personal and family history of cancer were associated with differences in beliefs about the causes of cancer. In general, a personal history of cancer was not significantly linked to causal attributions for cancer relative to those without a personal history. In contrast, a family history of cancer tended to increase the likelihood a respondent viewed a particular cause as increasing cancer risk. Thus, personal and vicarious experience with cancer had dramatically diverging influences on attributions of cancer causation, which may be due to differing self-protection motives. Results support the belief that illness representations, in this case the causal belief component, are influenced by both personal and vicarious experience with a disease and also suggest illness representations may influence receptivity to messages and interventions designed to increase appropriate cancer risk reduction behavior. Copyright (c) 2007 John Wiley & Sons, Ltd.

Cerebral palsy: causes, pathways, and the role of genetic variants.

PubMed

MacLennan, Alastair H; Thompson, Suzanna C; Gecz, Jozef

2015-12-01

Cerebral palsy (CP) is heterogeneous with different clinical types, comorbidities, brain imaging patterns, causes, and now also heterogeneous underlying genetic variants. Few are solely due to severe hypoxia or ischemia at birth. This common myth has held back research in causation. The cost of litigation has devastating effects on maternity services with unnecessarily high cesarean delivery rates and subsequent maternal morbidity and mortality. CP rates have remained the same for 50 years despite a 6-fold increase in cesarean birth. Epidemiological studies have shown that the origins of most CP are prior to labor. Increased risk is associated with preterm delivery, congenital malformations, intrauterine infection, fetal growth restriction, multiple pregnancy, and placental abnormalities. Hypoxia at birth may be primary or secondary to preexisting pathology and international criteria help to separate the few cases of CP due to acute intrapartum hypoxia. Until recently, 1-2% of CP (mostly familial) had been linked to causative mutations. Recent genetic studies of sporadic CP cases using new-generation exome sequencing show that 14% of cases have likely causative single-gene mutations and up to 31% have clinically relevant copy number variations. The genetic variants are heterogeneous and require function investigations to prove causation. Whole genome sequencing, fine scale copy number variant investigations, and gene expression studies may extend the percentage of cases with a genetic pathway. Clinical risk factors could act as triggers for CP where there is genetic susceptibility. These new findings should refocus research about the causes of these complex and varied neurodevelopmental disorders. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Parkinson’s disease and pesticides: a toxicological perspective

PubMed Central

Hatcher, Jaime M.; Pennell, Kurt D.; Miller, Gary W.

2017-01-01

Environmental factors have been shown to contribute to the incidence of Parkinson’s disease (PD). Pesticides, which represent one of the primary classes of environmental agents associated with PD, share the common feature of being intentionally released into the environment to control or eliminate pests. Pesticides consist of multiple classes and subclasses of insecticides, herbicides, rodenticides, fungicides, fumigants and others and exhibit a vast array of chemically diverse structures. In this review we examine the evidence regarding the ability of each of the major pesticide subclasses to increase the incidence of PD. We propose that, from a toxicological perspective, it would be beneficial to identify specific subclasses, common structural features and the propensity for widespread human exposure when considering the potential role in PD, rather than using the overly broad term of ‘pesticides’ to describe this diverse group of chemicals. Furthermore, these chemicals and their environmentally relevant combinations should be evaluated for their ability to promote or accelerate PD and not merely for being singular causative agents. PMID:18453001

Viral infection--a cure for type 1 diabetes?

PubMed

Hintermann, Edith; Christen, Urs

2007-01-01

Autoimmune diseases are thought to arise as a detrimental combination of genetic predisposition and environmental factors. Because of their potential for direct cellular damage and causing extensive inflammation, viruses are one of the major candidates for triggering autoimmunity. Although there is epidemiological evidence, direct proof for viruses as causative agents for autoimmune disease is hard to get since most viruses have been eliminated from the system by the time of diagnosis. However, evidence from various animal models suggests that viruses can indeed initiate or accelerate autoimmune diseases, such as type 1 diabetes or experimental allergic encephalomyelitis. In contrast, viruses have been also demonstrated to abrogate autoimmune disease in animal models. These observations might offer one explanation why increased frequencies of allergies and autoimmune diseases parallel with higher hygienic standards. This review reflects on the epidemiological evidence for the association of viruses with autoimmune diseases, the experimental evidence for viruses to abrogate an ongoing autoimmune destruction and evaluates the possibility for a therapeutic application.

Overview on association of different types of leukemias with radiation exposure.

PubMed

Gluzman, D F; Sklyarenko, L M; Zavelevich, M P; Koval, S V; Ivanivska, T S; Rodionova, N K

2015-06-01

Exposure to ionizing radiation is associated with increasing risk of various types of hematological malignancies. The results of major studies on association of leukemias and radiation exposure of large populations in Japan and in Ukraine are analyzed. The patterns of different types of leukemia in 295 Chernobyl clean-up workers diagnosed according to the criteria of up-to-date World Health Organization classification within 10-25 years following Chernobyl catastrophe are summarized. In fact, a broad spectrum of radiation-related hematological malignancies has been revealed both in Life Span Study in Japan and in study of Chernobyl clean-up workers in Ukraine. The importance of the precise diagnosis of tumors of hematopoietic and lymphoid tissues according to up-to-date classifications for elucidating the role of radiation as a causative factor of leukemias is emphasized. Such studies are of high importance since according to the recent findings, radiation-associated excess risks of several types of leukemias seem to persist throughout the follow-up period up to 55 years after the radiation exposure.

Chancroid and Haemophilus ducreyi.

PubMed Central

Morse, S A

1989-01-01

Haemophilus ducreyi is the causative agent of chancroid, one of the genital ulcerative diseases. H. ducreyi is the major cause of genital ulcer disease in Africa and Southeast Asia and is of increasing concern in the United States. Definitive diagnosis of chancroid requires the isolation and identification of H. ducreyi, but isolation of this organism is difficult and the available medium is not optimal for all strains. Fluorescent antibody and serologic tests are of limited value. In general, our knowledge of this organism is rather limited, and indeed, recent studies have questioned the placement of H. ducreyi in the genus Haemophilus. H. ducreyi has relatively few biochemical activities, and epidemiologic studies are limited because there are limited phenotypic markers available for strain typing. Specific virulence factors of H. ducreyi have yet to be identified. Antimicrobial resistance in H. ducreyi is of special concern, as this organism has acquired both gram-negative and gram-positive resistance determinants. In addition, some of these determinants can be mobilized and transferred to other Haemophilus species or to Neisseria gonorrhoeae. Images PMID:2650859

Expression profiling identifies novel Hh/Gli regulated genes in developing zebrafish embryos.

PubMed Central

Bergeron, Sadie A.; Milla, Luis A.; Villegas, Rosario; Shen, Meng-Chieh; Burgess, Shawn M.; Allende, Miguel L.; Karlstrom, Rolf O.; Palma, Verónica

2008-01-01

The Hedgehog (Hh) signaling pathway plays critical instructional roles during embryonic development. Mis-regulation of Hh/Gli signaling is a major causative factor in human congenital disorders and in a variety of cancers. The zebrafish is a powerful genetic model for the study of Hh signaling during embryogenesis, as a large number of mutants have been identified affecting different components of the Hh/Gli signaling system. By performing global profiling of gene expression in different Hh/Gli gain- and loss-of-function scenarios we identified several known (e.g. ptc1 and nkx2.2a) as well as a large number of novel Hh regulated genes that are differentially expressed in embryos with altered Hh/Gli signaling function. By uncovering changes in tissue specific gene expression, we revealed new embryological processes that are influenced by Hh signaling. We thus provide a comprehensive survey of Hh/Gli regulated genes during embryogenesis and we identify new Hh-regulated genes that may be targets of mis-regulation during tumorogenesis. PMID:18055165

Host-pathogen redox dynamics modulate Mycobacterium tuberculosis pathogenesis.

PubMed

Pacl, Hayden T; Reddy, Vineel P; Saini, Vikram; Chinta, Krishna C; Steyn, Adrie J C

2018-07-01

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, encounters variable and hostile environments within the host. A major component of these hostile conditions is reductive and oxidative stresses induced by factors modified by the host immune response, such as oxygen tension, NO or CO gases, reactive oxygen and nitrogen intermediates, the availability of different carbon sources and changes in pH. It is therefore essential for Mtb to continuously monitor and appropriately respond to the microenvironment. To this end, Mtb has developed various redox-sensitive systems capable of monitoring its intracellular redox environment and coordinating a response essential for virulence. Various aspects of Mtb physiology are regulated by these systems, including drug susceptibility, secretion systems, energy metabolism and dormancy. While great progress has been made in understanding the mechanisms and pathways that govern the response of Mtb to the host's redox environment, many questions in this area remain unanswered. The answers to these questions are promising avenues for addressing the tuberculosis crisis.

Tracing the source of difficult to settle fine particles which cause turbidity in the Hitotsuse Reservoir, Japan.

PubMed

Murakami, Toshiki; Suzuki, Yoshihiro; Oishi, Hiroyuki; Ito, Kenichi; Nakao, Toshio

2013-05-15

A unique method to trace the source of "difficult-to-settle fine particles," which are a causative factor of long-term turbidity in reservoirs was developed. This method is characterized by cluster analysis of XRD (X-ray diffraction) data and homology comparison of major component compositions between "difficult-to-settle fine particles" contained in landslide soil samples taken from the upstream of a dam, and suspended "long-term turbid water particles" in the reservoir, which is subject to long-term turbidity. The experiment carried out to validate the proposed method, demonstrated a high possibility of being able to make an almost identical match between "difficult-to-settle fine particles" taken from landslide soils at specific locations and "long-term turbid water particles" taken from a reservoir. This method has the potential to determine substances causing long-term turbidity and the locations of soils from which those substances came. Appropriate countermeasures can then be taken at those specific locations. Copyright © 2013 Elsevier Ltd. All rights reserved.

Spatacsin and spastizin act in the same pathway required for proper spinal motor neuron axon outgrowth in zebrafish.

PubMed

Martin, Elodie; Yanicostas, Constantin; Rastetter, Agnès; Alavi Naini, Seyedeh Maryam; Maouedj, Alissia; Kabashi, Edor; Rivaud-Péchoux, Sophie; Brice, Alexis; Stevanin, Giovanni; Soussi-Yanicostas, Nadia

2012-12-01

Hereditary spastic paraplegias (HSPs) are rare neurological conditions caused by degeneration of the long axons of the cerebrospinal tracts, leading to locomotor impairment and additional neurological symptoms. There are more than 40 different causative genes, 24 of which have been identified, including SPG11 and SPG15 mutated in complex clinical forms. Since the vast majority of the causative mutations lead to loss of function of the corresponding proteins, we made use of morpholino-oligonucleotide (MO)-mediated gene knock-down to generate zebrafish models of both SPG11 and SPG15 and determine how invalidation of the causative genes (zspg11 and zspg15) during development might contribute to the disease. Micro-injection of MOs targeting each gene caused locomotor impairment and abnormal branching of spinal cord motor neurons at the neuromuscular junction. More severe phenotypes with abnormal tail developments were also seen. Moreover, partial depletion of both proteins at sub-phenotypic levels resulted in the same phenotypes, suggesting for the first time, in vivo, a genetic interaction between these genes. In conclusion, the zebrafish orthologues of the SPG11 and SPG15 genes are important for proper development of the axons of spinal motor neurons and likely act in a common pathway to promote their proper path finding towards the neuromuscular junction. Copyright © 2012 Elsevier Inc. All rights reserved.

Reading Difficulty and the Intelligent Under-Achiever.

ERIC Educational Resources Information Center

Specific Learning Difficulties Association of Victoria (Australia).

Presented are five papers given at a 1970 seminar on reading difficulty and the intelligent underachiever. In the first paper, Dr. T. D. Hagger discusses the concept of specific learning disabilities and stresses the trend to search for causation in organic factors within the child, the importance of early identification, and the need for…

Recording and cataloging hazards information, revision A

NASA Technical Reports Server (NTRS)

Stein, R. J.

1974-01-01

A data collection process is described for the purpose of discerning causation factors of accidents, and the establishment of boundaries or controls aimed at mitigating and eliminating accidents. A procedure is proposed that suggests a discipline approach to hazard identification based on energy interrelationships together with an integrated control technique which takes the form of checklists.

A Research Trilogy: American and Mexican Vision Studies.

ERIC Educational Resources Information Center

Hinds, Lillian R.

1983-01-01

Describes three studies relating to visual functioning. Finds that reading retardation is the result of a clustering of factors, of multiple causation. Discusses the need to determine whether or not a student has the necessary lateral and other functional vision skills to maintain sufficient body energy for the demands of the reading task. (MG)

Should I Let My Child Watch Television?

ERIC Educational Resources Information Center

Bharadwaj, Balaji

2013-01-01

While the prevalence of autism has been increasing globally, there is a search for the causative factors behind the rise. The point of view presented here examines the possibility of children brought up in social deprivation and watching television being at higher risk for developing autistic symptoms. The association is evident in the clinical…

Juvenile Delinquency and Some Measures to Control Its Increasing Trends.

ERIC Educational Resources Information Center

Baginda, Abdullah Malim

Based mainly on personal experience and conditions prevailing in Malaysia, this discussion of juvenile delinquency explores (1) the extent of the problem; (2) some causative factors from a theoretical viewpoint; (3) criminal justice system provisions for dealing with the problem; and (4) preventive measures. In Malaysia, between 1960 and 1980 the…

Disseminated sporotrichosis in an immunocompetent patient

PubMed Central

Hassan, Kareem; Turker, Tolga; Zangeneh, Tirdad

2016-01-01

Abstract Sporothrix schenckii, the causative agent of sporotrichosis, is a relatively rare infection. Local infection usually occurs through direct inoculation of the organism through the skin; disseminated disease is rarely seen. This article describes a case of disseminated sporotrichosis in a middle-aged man without the commonly seen risk factors for dissemination. PMID:27583270

Erythema after laser skin resurfacing.

PubMed

Ruiz-Esparza, J; Barba Gomez, J M; Gomez de la Torre, O L; David, L

1998-01-01

Erythema after laser skin resurfacing is seen by many as a necessary evil in order to get good results from the procedure. A critical review of widely accepted concepts may lead to diminishing the length of postoperative erythema in patients undergoing laser resurfacing. The authors report on two previously unrecognized factors in the causation of this problem.

Anchoring for Self-Efficacy and Success: An Anchored Asynchronous Online Discussion Case

ERIC Educational Resources Information Center

Alrushiedat, Nimer; Olfman, Lorne

2014-01-01

In recent years, we have observed a rising interest in studying the effects of Web 2.0 technologies on student learning. We learned that human behavior can be influenced by personal and environmental factors as in Bandura's concept of "reciprocal causation." For business statistics students, we implemented online discussions to extend…

[Asthma--a condition of our time, a condition in change?].

PubMed

Carlsen, K H

2001-03-10

This article reviews causative factors for asthma and allergy during childhood and describes current trends in prevalence and hospitalisation for childhood asthma. A review of the prevalence of childhood asthma in Norway over the last 50 years together with recent trends in hospitalisation for childhood asthma, is given. Possible causative factors for childhood asthma are reviewed, and recent theories for the current increase in prevalence are discussed. During the last 50 years, a steady increase in the prevalence of childhood asthma has been documented through published studies from 1948 and onwards. From 1980 and until 1990, an increase in hospital admissions due to acute asthma was observed; later, admissions have leveled off, particularly as regards readmissions. Smoking during pregnancy and childhood decreases lung function. Allergic sensitisation is related to asthma development and may occur already during pregnancy. Increased allergic sensitisation may occur due to reduced load of infections. However, respiratory virus infections, and especially RS virus and rhinovirus infections, are closely related to asthma development and symptoms during childhood. A reduction in readmissions for asthma may be related to increased use of antiinflammatory therapy for asthma.

Neuroprotective-Neurotrophic Effect of Endogenous Dehydroepiandrosterone Sulfate During Intense Stress Exposure

DTIC Science & Technology

2014-06-02

22 May 2014 Available online 2 June 2014 Keywords: DHEA sulfate Neurotrophin Nerve growth factor Testosterone Cortisol Stressa b s t r a c t Recent... neurotrophin salivary nerve growth factor (sNGF). In terms of total hormone output, the effect of DHEAS on sNGF was mediated by testosterone. Unlike...established criteria for causation. Published by Elsevier Inc.1. Introduction Neurotrophins are proteins found within a broad range of cell types in the

Sexual Victimization and the Military Environment: Contributing Factors, Vocational, Psychological, and Medical Sequelae

DTIC Science & Technology

1997-10-01

social attitudes are an important causative factor in sexual victimization. A multicultural study found that acceptance of rape myths ("all women want...included attempted or completed sexual penetration of the victim’s vagina , mouth or rectum. Physical assault was defined as any act not occurring during...before the 95th Congress, 2nd Session), Jan. 10-12. Washington, DC, Government Printing Office. Burt, M. R. (1980). "Cultural myths and supports for

Evidence-Based Revised View of the Pathophysiology of Preeclampsia.

PubMed

Ahmed, Asif; Rezai, Homira; Broadway-Stringer, Sophie

2017-01-01

Preeclampsia is a life-threatening vascular disorder of pregnancy due to a failing stressed placenta. Millions of women risk death to give birth each year and globally each year, almost 300,000 lose their life in this process and over 500,000 babies die as a consequence of preeclampsia. Despite decades of research, we lack pharmacological agents to treat it. Maternal endothelial oxidative stress is a central phenomenon responsible for the preeclampsia phenotype of high maternal blood pressure and proteinuria. In 1997, it was proposed that preeclampsia arises due to the loss of VEGF activity, possibly due to elevation in anti-angiogenic factor, soluble Flt-1 (sFlt-1). Researchers showed that high sFlt-1 and soluble endoglin (sEng) elicit the severe preeclampsia phenotype in pregnant rodents. We demonstrated that heme oxygenase-1 (HO-1)/carbon monoxide (CO) pathway prevents placental stress and suppresses sFlt-1 and sEng release. Likewise, hydrogen sulphide (H 2 S)/cystathionine-γ-lyase (Cth) systems limit sFlt-1 and sEng and protect against the preeclampsia phenotype in mice. Importantly, H 2 S restores placental vasculature, and in doing so improves lagging fetal growth. These molecules act as the inhibitor systems in pregnancy and when they fail, preeclampsia is triggered. In this review, we discuss what are the hypotheses and models for the pathophysiology of preeclampsia on the basis of Bradford Hill causation criteria for disease causation and how further in vivo experimentation is needed to establish 'proof of principle'. Hypotheses that fail to meet the Bradford Hill causation criteria include abnormal spiral artery remodelling and inflammation and should be considered associated or consequential to the disorder. In contrast, the protection against cellular stress hypothesis that states that the protective pathways mitigate cellular stress by limiting elevation of anti-angiogenic factors or oxidative stress and the subsequent clinical signs of preeclampsia appear to fulfil most of Bradford Hill causation criteria. Identifying the candidates on the roadmap to this pathway is essential in developing diagnostics and therapeutics to target the pathogenesis of preeclampsia.

Structural equation modeling in environmental risk assessment.

PubMed

Buncher, C R; Succop, P A; Dietrich, K N

1991-01-01

Environmental epidemiology requires effective models that take individual observations of environmental factors and connect them into meaningful patterns. Single-factor relationships have given way to multivariable analyses; simple additive models have been augmented by multiplicative (logistic) models. Each of these steps has produced greater enlightenment and understanding. Models that allow for factors causing outputs that can affect later outputs with putative causation working at several different time points (e.g., linkage) are not commonly used in the environmental literature. Structural equation models are a class of covariance structure models that have been used extensively in economics/business and social science but are still little used in the realm of biostatistics. Path analysis in genetic studies is one simplified form of this class of models. We have been using these models in a study of the health and development of infants who have been exposed to lead in utero and in the postnatal home environment. These models require as input the directionality of the relationship and then produce fitted models for multiple inputs causing each factor and the opportunity to have outputs serve as input variables into the next phase of the simultaneously fitted model. Some examples of these models from our research are presented to increase familiarity with this class of models. Use of these models can provide insight into the effect of changing an environmental factor when assessing risk. The usual cautions concerning believing a model, believing causation has been proven, and the assumptions that are required for each model are operative.

Top-down causation and social structures

PubMed Central

Elder-Vass, Dave

2012-01-01

Top-down causation has been implicit in many sociological accounts of social structure and its influence on social events, but the social sciences have struggled to provide a coherent account of top-down causation itself. This paper summarizes a critical realist view of causation and emergence, shows how it supports a plausible account of top-down causation and then applies this account to the social world. The argument is illustrated by an examination of the concept of a norm circle, a kind of social entity that, it is argued, is causally responsible for the influence of normative social institutions. Nevertheless, social entities are structured rather differently from ordinary material ones, with the result that the compositional level structure of reality implicit in the concept of top-down causation has some limitations in the social world. The paper closes by considering what might be involved in examining how top-down causation can be shown to be at work in the social domain. PMID:23386963

The incidence and significance of accidental hypothermia in major trauma--a prospective observational study.

PubMed

Ireland, Sharyn; Endacott, Ruth; Cameron, Peter; Fitzgerald, Mark; Paul, Eldho

2011-03-01

Serious sequelae have been associated with injured patients who are hypothermic (<35°C) including coagulopathy, acidosis, decreased myocardial contractility and risk of mortality. Establish the incidence of accidental hypothermia in major trauma patients and identify causative factors. Prospective identification and subsequent review of 732 medical records of major trauma patients presenting to an Adult Major Trauma Centre was undertaken between January and December 2008. Multivariate analysis was performed using logistic regression. Significant and clinically relevant variables from univariate analysis were entered into multivariate models to evaluate determinants for hypothermia and for death. Goodness of fit was determined with the use of the Hosmer-Lemeshow statistic. Overall mortality was 9.15%. The incidence of hypothermia was 13.25%. The mortality of patients with hypothermia was 29.9% with a threefold independent risk of death: OR (CI 95%) 3.44 (1.48-7.99), P = 0.04. Independent determinants for hypothermia were pre-hospital intubation: OR (CI 95%) 5.18 (2.77-9.71), P < 0.001, Injury Severity Score (ISS): 1.04 (1.01-1.06), P = 0.01, Arrival Systolic Blood Pressure (ASBP) < 100 mm Hg: 3.04 (1.24-7.44), P = 0.02, and winter time: 1.84 (1.06-3.21), P = 0.03. Of the 87 hypothermic patients who had repeat temperatures recorded in the Emergency Department, 77 (88.51%) patients had a temperature greater than the recorded arrival temperature. There was no change in recorded temperature for four (4.60%) patients, whereas six (6.90%) patients were colder at Emergency Department discharge. Seriously injured patients with accidental hypothermia have a higher mortality independent of measured risk factors. For patients with multiple injuries a coordinated effort by paramedics, nurses and doctors is required to focus efforts toward early resolution of hypothermia aiming to achieve a temperature >35 °C. Crown Copyright © 2010. Published by Elsevier Ireland Ltd. All rights reserved.

Probiotics prophylaxis in pyelonephritis infants with normal urinary tracts.

PubMed

Lee, Seung Joo; Cha, Jihae; Lee, Jung Won

2016-11-01

Pyelonephritis in infants is considered as a major factor for the formation of renal scar. To prevent recurrent pyelonephritis and renal damage, prophylaxis is extremely important. The aim of this study was to compare the effectiveness of probiotic and antibiotic prophylaxis or no-prophylaxis in infants with pyelonephritis and normal urinary tract. Altogether 191 infants, who were diagnosed with acute pyelonephritis, proven to have normal urinary tracts and followed up for 6 months on prophylaxis, were retrospectively evaluated. According to the types of prophylaxis, the infants were divided into three groups [probiotics (Lactobacillus species), antibiotics (trimethoprim/sulfamethoxazole, TMP/SMX), and noprophylaxis]. The incidence of recurrent urinary tract infection (UTI) during 6 months after the development of pyelonephritis, main causative uropathogens, and its antimicrobial sensitivities were compared. The incidence of recurrent UTI in the probiotic group was 8.2%, which was significantly lower than 20.6% in the no-prophylaxis group (P=0.035) and was not significantly different from 10.0% of the antibiotic group (P=0.532). The significant difference between the probiotic and no-prophylaxis groups was seen only in male infants (P=0.032). The main causative organism of recurrent UTI was Escherichia coli (E.coli), which was not different among the three groups (P=0.305). The resistance rate of E. coli to TMP/SMX was 100% in the antibiotic group, which was significantly higher than 25.0% in the probiotic group and 41.7% in the no-prophylaxis group (P=0.008). Probiotic prophylaxis was more effective in infants with pyelonephritis and normal urinary tract than in those with no-prophylaxis. It could be used as a natural alternative to antibiotic prophylaxis.

Correlation versus Causation? Pharmacovigilance of the Analgesic Flupirtine Exemplifies the Need for Refined Spontaneous ADR Reporting

PubMed Central

Anderson, Nora; Borlak, Juergen

2011-01-01

Annually, adverse drug reactions result in more than 2,000,000 hospitalizations and rank among the top 10 causes of death in the United States. Consequently, there is a need to continuously monitor and to improve the safety assessment of marketed drugs. Nonetheless, pharmacovigilance practice frequently lacks causality assessment. Here, we report the case of flupirtine, a centrally acting non-opioid analgesic. We re-evaluated the plausibility and causality of 226 unselected, spontaneously reported hepatobiliary adverse drug reactions according to the adapted Bradford-Hill criteria, CIOMS score and WHO-UMC scales. Thorough re-evaluation showed that only about 20% of the reported cases were probable or likely for flupirtine treatment, suggesting an incidence of flupirtine-related liver injury of 1∶ 100,000 when estimated prescription data are considered, or 0.8 in 10,000 on the basis of all 226 reported adverse drug reactions. Neither daily or cumulative dose nor duration of treatment correlated with markers of liver injury. In the majority of cases (151/226), an average of 3 co-medications with drugs known for their liver liability was observed that may well be causative for adverse drug reactions, but were reported under a suspected flupirtine ADR. Our study highlights the need to improve the quality and standards of ADR reporting. This should be done with utmost care taking into account contributing factors such as concomitant medications including over-the-counter drugs, the medical history and current health conditions, in order to avoid unjustified flagging and drug warnings that may erroneously cause uncertainty among healthcare professionals and patients, and may eventually lead to unjustified safety signals of useful drugs with a reasonable risk to benefit ratio. PMID:22022383

Andean cutaneous leishmaniasis (Andean-CL, uta) in Peru and Ecuador: the causative Leishmania parasites and clinico-epidemiological features.

PubMed

Hashiguchi, Yoshihisa; Gomez, Eduardo A L; Cáceres, Abraham G; Velez, Lenin N; Villegas, Nancy V; Hashiguchi, Kazue; Mimori, Tatsuyuki; Uezato, Hiroshi; Kato, Hirotomo

2018-01-01

This study provides comprehensive information on the past and current status of the Andean cutaneous leishmaniasis (Andean-CL, uta) in Peru and Ecuador, mainly focusing on the causative Leishmania parasites and clinico-epidemiological features. Available information and data including our unpublished works were analyzed thoroughly. Endemic regions of the Andean-CL (uta) in Peru run from the north Piura/Cajamarca to the south Ayacucho at a wide range of the Pacific watersheds of the Andes through several departments, while in Ecuador those exist at limited and spotted areas in the country's mid-southwestern two provinces, Azuay and Chimborazo. The principal species of the genus Leishmania are completely different at subgenus level, L. (Viannia) peruviana in Peru, and L. (Leishmania) mexicana and L. (L.) major-like (infrequent occurrence) in Ecuador. The Peruvian uta is now prevalent in different age and sex groups, being not clearly defined as found in the past. The precise reasons are not known and should be elucidated further, though probable factors, such as emergence of other Leishmania parasites, non-immune peoples' migration into the areas, etc., were discussed briefly in the text. The Andean-CL cases in Ecuador are more rural than before, probably because of a rapid development of the Leishmania-positive communities and towns, and the change of life-styles of the inhabitants, including newly constructed houses and roads in the endemic areas. Such information is helpful for future management of the disease, not only for Leishmania-endemic areas in the Andes but also for other endemic areas. Copyright © 2017 Elsevier B.V. All rights reserved.

Environmental immune disruptors, inflammation and cancer risk

PubMed Central

Thompson, Patricia A.; Khatami, Mahin; Baglole, Carolyn J.; Sun, Jun; Harris, Shelley; Moon, Eun-Yi; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Brown, Dustin; Colacci, Annamaria; Mondello, Chiara; Raju, Jayadev; Ryan, Elizabeth; Woodrick, Jordan; Scovassi, Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K.; Amedei, Amedeo; Hamid, Roslida A.; Lowe, Leroy; Guarnieri, Tiziana

2015-01-01

An emerging area in environmental toxicology is the role that chemicals and chemical mixtures have on the cells of the human immune system. This is an important area of research that has been most widely pursued in relation to autoimmune diseases and allergy/asthma as opposed to cancer causation. This is despite the well-recognized role that innate and adaptive immunity play as essential factors in tumorigenesis. Here, we review the role that the innate immune cells of inflammatory responses play in tumorigenesis. Focus is placed on the molecules and pathways that have been mechanistically linked with tumor-associated inflammation. Within the context of chemically induced disturbances in immune function as co-factors in carcinogenesis, the evidence linking environmental toxicant exposures with perturbation in the balance between pro- and anti-inflammatory responses is reviewed. Reported effects of bisphenol A, atrazine, phthalates and other common toxicants on molecular and cellular targets involved in tumor-associated inflammation (e.g. cyclooxygenase/prostaglandin E2, nuclear factor kappa B, nitric oxide synthesis, cytokines and chemokines) are presented as example chemically mediated target molecule perturbations relevant to cancer. Commentary on areas of additional research including the need for innovation and integration of systems biology approaches to the study of environmental exposures and cancer causation are presented. PMID:26106141

42 CFR 81.6 - Use of radiation dose information.

Code of Federal Regulations, 2010 CFR

2010-10-01

... AND HEALTH RESEARCH AND RELATED ACTIVITIES GUIDELINES FOR DETERMINING PROBABILITY OF CAUSATION UNDER... Probability of Causation § 81.6 Use of radiation dose information. Determining probability of causation will...

On Reciprocal Causation in the Evolutionary Process.

PubMed

Svensson, Erik I

2018-01-01

Recent calls for a revision of standard evolutionary theory (SET) are based partly on arguments about the reciprocal causation. Reciprocal causation means that cause-effect relationships are bi-directional, as a cause could later become an effect and vice versa. Such dynamic cause-effect relationships raise questions about the distinction between proximate and ultimate causes, as originally formulated by Ernst Mayr. They have also motivated some biologists and philosophers to argue for an Extended Evolutionary Synthesis (EES). The EES will supposedly expand the scope of the Modern Synthesis (MS) and SET, which has been characterized as gene-centred, relying primarily on natural selection and largely neglecting reciprocal causation. Here, I critically examine these claims, with a special focus on the last conjecture. I conclude that reciprocal causation has long been recognized as important by naturalists, ecologists and evolutionary biologists working in the in the MS tradition, although it it could be explored even further. Numerous empirical examples of reciprocal causation in the form of positive and negative feedback are now well known from both natural and laboratory systems. Reciprocal causation have also been explicitly incorporated in mathematical models of coevolutionary arms races, frequency-dependent selection, eco-evolutionary dynamics and sexual selection. Such dynamic feedback were already recognized by Richard Levins and Richard Lewontin in their bok The Dialectical Biologist . Reciprocal causation and dynamic feedback might also be one of the few contributions of dialectical thinking and Marxist philosophy in evolutionary theory. I discuss some promising empirical and analytical tools to study reciprocal causation and the implications for the EES. Finally, I briefly discuss how quantitative genetics can be adapated to studies of reciprocal causation, constructive inheritance and phenotypic plasticity and suggest that the flexibility of this approach might have been underestimated by critics of contemporary evolutionary biology.

Application of calcifying bacteria for remediation of stones and cultural heritages

PubMed Central

Dhami, Navdeep Kaur; Reddy, M. Sudhakara; Mukherjee, Abhijit

2014-01-01

Since ages, architects and artists worldwide have focused on usage of durable stones as marble and limestone for construction of beautiful and magnificent historic monuments as European Cathedrals, Roman, and Greek temples, Taj Mahal etc. But survival of these irreplaceable cultural and historical assets is in question these days due to their degradation and deterioration caused by number of biotic and abiotic factors. These causative agents have affected not only the esthetic appearance of these structures, but also lead to deterioration of their strength and durability. The present review emphasizes about different causative agents leading to deterioration and application of microbially induced calcium carbonate precipitation as a novel and potential technology for dealing with these problems. The study also sheds light on benefits of microbial carbonate binders over the traditional agents and future directions. PMID:25018751

Application of calcifying bacteria for remediation of stones and cultural heritages.

PubMed

Dhami, Navdeep Kaur; Reddy, M Sudhakara; Mukherjee, Abhijit

2014-01-01

Since ages, architects and artists worldwide have focused on usage of durable stones as marble and limestone for construction of beautiful and magnificent historic monuments as European Cathedrals, Roman, and Greek temples, Taj Mahal etc. But survival of these irreplaceable cultural and historical assets is in question these days due to their degradation and deterioration caused by number of biotic and abiotic factors. These causative agents have affected not only the esthetic appearance of these structures, but also lead to deterioration of their strength and durability. The present review emphasizes about different causative agents leading to deterioration and application of microbially induced calcium carbonate precipitation as a novel and potential technology for dealing with these problems. The study also sheds light on benefits of microbial carbonate binders over the traditional agents and future directions.

Applying New Methods to Diagnose Coral Diseases

USGS Publications Warehouse

Kellogg, Christina A.; Zawada, David G.

2009-01-01

Coral disease, one of the major causes of reef degradation and coral death, has been increasing worldwide since the 1970s, particularly in the Caribbean. Despite increased scientific study, simple questions about the extent of disease outbreaks and the causative agents remain unanswered. A component of the U.S. Geological Survey Coral Reef Ecosystem STudies (USGS CREST) project is focused on developing and using new methods to approach the complex problem of coral disease.

Rocky Mountain spotted fever.

PubMed

Lacz, N L; Schwartz, R A; Kapila, R

2006-04-01

Rocky Mountain spotted fever (RMSF) is an unusual but important dermatological condition to identify without hesitation. The classic triad of headache, fever, and a rash that begins on the extremities and travels proximally to involve the trunk is found in a majority of patients. The cutaneous centripetal pattern is a result of cell to cell migration by the causative organism Rickettsia rickettsii. Such individuals should receive prompt antimicrobial therapy and supportive care to avoid serious and potentially fatal complications.

Vaccine Development for Biothreat Alpha Viruses

DTIC Science & Technology

2011-09-25

gaviridae, are causative agents of debilitative, acute, and sometimes fatal encephalitis in North, Central, and South America [1]. These viruses are...and can be lyophilized. VEEV was tested as a biowarfare agent during the U.S. offensive program in the 1950’s and 1960’s, and may have been...MD 21702, USA Abstract The majority of alpha virus is non-pathogenic to humans. However, select alpha viruses can cause severe disease in humans

After 40 Years Why Hasn’t the Computer Replaced the Wind Tunnel?

DTIC Science & Technology

2010-09-01

transform the aerodynamic design process. Many of his CFD projections have been exceeded over the last 30 years. (He was forecasting breakthroughs only...frequently found late in the development cycle for a flight system usually occur at the interface of major subsystems (e.g., aerodynamically induced...the causative relations between aerodynamic shapes and vehicle performance. The tools also allow relatively rapid evaluation of changes to the design

Uncompetitive Inhibition of Yeast Alcohol Dehydrogenase by Diacetoxyscirpenol.

DTIC Science & Technology

1986-10-01

PREFACE The work described in this report was authorized under Project No. 1L161102A71A, Research in Chemical & Biological Defense, Biotechnology . This...Epoxytrichothecenes are the major components of the Fusarium myco- toxins identified as the causative agents for the epidemic outbreak of the alimentary ...The quaternary complex may have the structure such as NAD ~A EtOH ADS 14 LITERATURE CITED 1. Joffe, A.Z. Alimentary Toxic Aleukia. In Microbial Toxins

The secreted polyketide boydone A is responsible for the anti-Staphylococcus aureus activity of Scedosporium boydii.

PubMed

Staerck, Cindy; Landreau, Anne; Herbette, Gaëtan; Roullier, Catherine; Bertrand, Samuel; Siegler, Benjamin; Larcher, Gérald; Bouchara, Jean-Philippe; Fleury, Maxime J J

2017-12-01

Usually living as a soil saprophyte, the filamentous fungus Scedosporium boydii may also cause various infections in human. Particularly, it is one of the major causative agents of fungal colonization of the airways in patients with cystic fibrosis (CF). To compete with other microorganisms in the environment, fungi have evolved sophisticated strategies, including the production of secondary metabolites with antimicrobial activity that may also help them to establish successfully within the respiratory tract of receptive hosts. Here, the culture filtrate from a human pathogenic strain of S. boydii was investigated searching for an antibacterial activity, mainly against the major CF bacterial pathogens. A high antibacterial activity against Staphylococcus aureus, including methicillin-resistant strains of this species, was observed. Bio-guided fractionation and analysis of the active fractions by nuclear magnetic resonance or by high-performance liquid chromatography and high-resolution electrospray ionization-mass spectrometry allowed us to identify boydone A as responsible for this antibacterial activity. Together, these results suggest that this six-membered cyclic polyketide could be one of the virulence factors of the fungus. Genes involved in the synthesis of this secreted metabolite are currently being identified in order to confirm the role of this polyketide in pathogenesis. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

In vivo Raman spectroscopy for oral cancers diagnosis

NASA Astrophysics Data System (ADS)

Singh, S. P.; Deshmukh, Atul; Chaturvedi, Pankaj; Krishna, C. Murali

2012-01-01

Oral squamous cell carcinoma is sixth among the major malignancies worldwide. Tobacco habits are known as major causative factor in tumor carcinogenesis in oral cancer. Optical spectroscopy methods, including Raman, are being actively pursued as alternative/adjunct for cancer diagnosis. Earlier studies have demonstrated the feasibility of classifying normal, premalignant and malignant oral ex-vivo tissues. In the present study we have recorded in vivo spectra from contralateral normal and diseased sites of 50 subjects with pathologically confirmed lesions of buccal mucosa using fiber-optic-probe-coupled HE-785 Raman spectrometer. Spectra were recorded on similar points as per teeth positions with an average acquisition time of 8 seconds. A total of 215 and 225 spectra from normal and tumor sites, respectively, were recorded. Finger print region (1200-1800 cm-1) was utilized for classification using LDA. Standard-model was developed using 125 normal and 139 tumor spectra from 27 subjects. Two separate clusters with an efficiency of ~95% were obtained. Cross-validation with leave-one-out yielded ~90% efficiency. Remaining 90 normal and 86 tumor spectra were used as test data and predication efficiency of model was evaluated. Findings of the study indicate that Raman spectroscopic methods in combination with appropriate multivariate tool can be used for objective, noninvasive and rapid diagnosis.

Rheumatoid arthritis: identifying and characterising polymorphisms using rat models

PubMed Central

2016-01-01

ABSTRACT Rheumatoid arthritis is a chronic inflammatory joint disorder characterised by erosive inflammation of the articular cartilage and by destruction of the synovial joints. It is regulated by both genetic and environmental factors, and, currently, there is no preventative treatment or cure for this disease. Genome-wide association studies have identified ∼100 new loci associated with rheumatoid arthritis, in addition to the already known locus within the major histocompatibility complex II region. However, together, these loci account for only a modest fraction of the genetic variance associated with this disease and very little is known about the pathogenic roles of most of the risk loci identified. Here, we discuss how rat models of rheumatoid arthritis are being used to detect quantitative trait loci that regulate different arthritic traits by genetic linkage analysis and to positionally clone the underlying causative genes using congenic strains. By isolating specific loci on a fixed genetic background, congenic strains overcome the challenges of genetic heterogeneity and environmental interactions associated with human studies. Most importantly, congenic strains allow functional experimental studies be performed to investigate the pathological consequences of natural genetic polymorphisms, as illustrated by the discovery of several major disease genes that contribute to arthritis in rats. We discuss how these advances have provided new biological insights into arthritis in humans. PMID:27736747

Multifaceted Role of Pneumolysin in the Pathogenesis of Myocardial Injury in Community-Acquired Pneumonia.

PubMed

Anderson, Ronald; Nel, Jan G; Feldman, Charles

2018-04-11

Pneumolysin (PLY), a member of the family of Gram-positive bacterial, cholesterol-dependent, β-barrel pore-forming cytolysins, is the major protein virulence factor of the dangerous respiratory pathogen, Streptococcus pneumoniae (pneumococcus). PLY plays a major role in the pathogenesis of community-acquired pneumonia (CAP), promoting colonization and invasion of the upper and lower respiratory tracts respectively, as well as extra-pulmonary dissemination of the pneumococcus. Notwithstanding its role in causing acute lung injury in severe CAP, PLY has also been implicated in the development of potentially fatal acute and delayed-onset cardiovascular events, which are now recognized as being fairly common complications of this condition. This review is focused firstly on updating mechanisms involved in the immunopathogenesis of PLY-mediated myocardial damage, specifically the direct cardiotoxic and immunosuppressive activities, as well as the indirect pro-inflammatory/pro-thrombotic activities of the toxin. Secondly, on PLY-targeted therapeutic strategies including, among others, macrolide antibiotics, natural product antagonists, cholesterol-containing liposomes, and fully humanized monoclonal antibodies, as well as on vaccine-based preventive strategies. These sections are preceded by overviews of CAP in general, the role of the pneumococcus as the causative pathogen, the occurrence and types of CAP-associated cardiac complication, and the structure and biological activities of PLY.

Mycoplasma fermentans glycolipid-antigen as a pathogen of rheumatoid arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawahito, Yutaka; Ichinose, Sizuko; Sano, Hajime

Mycoplasma fermentans has been suspected as one of the causative pathogenic microorganisms of rheumatoid arthritis (RA) however, the pathogenic mechanism is still unclear. We, previously, reported that glycolipid-antigens (GGPL-I and III) are the major antigens of M. fermentans. Monoclonal antibody against the GGPL-III could detect the existence of the GGPL-III antigens in synovial tissues from RA patients. GGPL-III antigens were detected in 38.1% (32/84) of RA patient's tissues, but not in osteoarthritis (OA) and normal synovial tissues. Immunoelectron microscopy revealed that a part of GGPL-III antigens are located at endoplasmic reticulum. GGPL-III significantly induced TNF-{alpha} and IL-6 production from peripheralmore » blood mononulear cells, and also proliferation of synovial fibroblasts. Further study is necessary to prove that M. fermentans is a causative microorganism of RA; however, the new mechanisms of disease pathogenesis provides hope for the development of effective and safe immunotherapeutic strategies based on the lipid-antigen, GGPL-III, in the near future.« less

Anaplasma phagocytophilum Infection Subverts Carbohydrate Metabolic Pathways in the Tick Vector, Ixodes scapularis.

PubMed

Cabezas-Cruz, Alejandro; Alberdi, Pilar; Valdés, James J; Villar, Margarita; de la Fuente, José

2017-01-01

The obligate intracellular pathogen, Anaplasma phagocytophilum , is the causative agent of human, equine, and canine granulocytic anaplasmosis and tick-borne fever (TBF) in ruminants. A. phagocytophilum has become an emerging tick-borne pathogen in the United States, Europe, Africa, and Asia, with increasing numbers of infected people and animals every year. It has been recognized that intracellular pathogens manipulate host cell metabolic pathways to increase infection and transmission in both vertebrate and invertebrate hosts. However, our current knowledge on how A. phagocytophilum affect these processes in the tick vector, Ixodes scapularis is limited. In this study, a genome-wide search for components of major carbohydrate metabolic pathways was performed in I. scapularis ticks for which the genome was recently published. The enzymes involved in the seven major carbohydrate metabolic pathways glycolysis, gluconeogenesis, pentose phosphate, tricarboxylic acid cycle (TCA), glyceroneogenesis, and mitochondrial oxidative phosphorylation and β-oxidation were identified. Then, the available transcriptomics and proteomics data was used to characterize the mRNA and protein levels of I. scapularis major carbohydrate metabolic pathway components in response to A. phagocytophilum infection of tick tissues and cultured cells. The results showed that major carbohydrate metabolic pathways are conserved in ticks. A. phagocytophilum infection inhibits gluconeogenesis and mitochondrial metabolism, but increases the expression of glycolytic genes. A model was proposed to explain how A. phagocytophilum could simultaneously control tick cell glucose metabolism and cytoskeleton organization, which may be achieved in part by up-regulating and stabilizing hypoxia inducible factor 1 alpha in a hypoxia-independent manner. The present work provides a more comprehensive view of the major carbohydrate metabolic pathways involved in the response to A. phagocytophilum infection in ticks, and provides the basis for further studies to develop novel strategies for the control of granulocytic anaplasmosis.

Abilities of 4-7 Years Old Children to Provide Independent Explanations and Generalisations of Causality

ERIC Educational Resources Information Center

Daugirdiene, Ausra; Petrulyte, Aiste; Brandisauskiene, Agne

2018-01-01

The understanding and generalisation of causality are important thinking abilities, as they form the basis for a person's activity. Researchers exploring these abilities do not have a unified opinion regarding the age of children when they develop causative understanding and its determinant factors (e.g. age, prior knowledge, the content of a…

Stress and adjustment in diabetes mellitus.

PubMed

Parveen, S; Singh, S B

1999-01-01

Stress and adjustment in diabetics is studied in order to know the influence of maladjustment and stress in the causation of the disease. The sample of study consists of 100 diabetics patients, 100 nonpsychosomatic and 100 normal person. Results obtained are discussed in detail. It is concluded that maladjustment and stress are important contributing factors in' diabetes mellitus.

Inbreeding among pen-reared quail

USGS Publications Warehouse

Nestler, R.B.; Nelson, A.L.

1945-01-01

The effect of inbreeding in wildlife species has received attention from several sources. Recently the 'inbreeding theory' as a possible explanation of cycles in game populations was given careful consideration by a group of wildlife experts and geneticists. Scott's symposium (1944) consisting of comments received from eight authorities revealed unanimity in a decision that inbreeding is not the causative factor.

A Novel Cell Wall Lipopeptide Is Important for Biofilm Formation and Pathogenicity of Mycobacterium avium subspecies paratuberculosis

USDA-ARS?s Scientific Manuscript database

Biofilm formation by pathogenic bacteria plays a key role in their pathogenesis. Previously, the pstA gene was shown to be involved in the virulence of Mycobacterium avium subspecies paratuberculosis (M. ap), the causative agent of Johne's disease in cattle and a potential risk factor for Crohn's d...

Understanding Early Communication Signals in Autism: A Study of the Perception of Infants' Cry

ERIC Educational Resources Information Center

Esposito, G.; Venuti, P.

2010-01-01

Background: Previous studies have highlighted that episodes of crying of children with autistic disorder (AD) were perceived as inexplicable from their parents who could not identify causative factors. These results supported the view of AD as related to a problem of expressing and sharing emotions. Moreover, no evidence has been presented on…

Cryptococcus neoformans Requires the ESCRT Protein Vps23 for Iron Acquisition from Heme, for Capsule Formation, and for Virulence

PubMed Central

Hu, Guanggan; Caza, Mélissa; Cadieux, Brigitte; Chan, Vivienne; Liu, Victor

2013-01-01

Iron availability is a key regulator of virulence factor elaboration in Cryptococcus neoformans, the causative agent of fungal meningoencephalitis in HIV/AIDS patients. In addition, iron is an essential nutrient for pathogen proliferation in mammalian hosts but little is known about the mechanisms of iron sensing and uptake in fungal pathogens that attack humans. In this study, we mutagenized C. neoformans by Agrobacterium-mediated T-DNA insertion and screened for mutants with reduced growth on heme as the sole iron source. Among 34 mutants, we identified a subset with insertions in the gene for the ESCRT-I (endosomal sorting complex required for transport) protein Vps23 that resulted in a growth defect on heme, presumably due to a defect in uptake via endocytosis or misregulation of iron acquisition from heme. Remarkably, vps23 mutants were also defective in the elaboration of the cell-associated capsular polysaccharide that is a major virulence factor, while overexpression of Vps23 resulted in cells with a slightly enlarged capsule. These phenotypes were mirrored by a virulence defect in the vps23 mutant in a mouse model of cryptococcosis and by hypervirulence of the overexpression strain. Overall, these results reveal an important role for trafficking via ESCRT functions in both heme uptake and capsule formation, and they further reinforce the connection between iron and virulence factor deployment in C. neoformans. PMID:23132495

Persistent parasites and immunologic memory in cutaneous leishmaniasis: implications for vaccine designs and vaccination strategies.

PubMed

Okwor, Ifeoma; Uzonna, Jude

2008-01-01

Despite a plethora of publications on the murine model of cutaneous leishmaniasis and their contribution to our understanding of the factors that regulate the development of CD4+ T cell immunity in vivo, there is still no effective vaccine against the human disease. While recovery from natural or experimental infection with Leishmania major, the causative agent of human cutaneous leishmaniasis, results in persistence of parasites at the primary infection site and the development of long-lasting immunity to reinfection, vaccination with killed parasites or recombinant proteins induces only short-term protection. The reasons for the difference in protective immunity following recovery from live infection and vaccination with heat-killed parasites are not known. This may in part be related to persistence of live parasites following healing of primary cutaneous lesions, because complete clearance of parasites leads to rapid loss of infection-induced immunity. Recent reports indicate that in addition to persistent parasites, IL-10-producing natural regulatory T cells may also play critical roles in the maintenance and loss of infection-induced immunity. This review focuses on current understanding of the factors that regulate the development, maintenance and loss of anti-Leishmania memory responses and highlights the role of persistent parasites and regulatory T cells in this process. Understanding these factors is crucial for designing effective vaccines and vaccination strategies against cutaneous leishmaniasis.

Cryptococcus neoformans requires the ESCRT protein Vps23 for iron acquisition from heme, for capsule formation, and for virulence.

PubMed

Hu, Guanggan; Caza, Mélissa; Cadieux, Brigitte; Chan, Vivienne; Liu, Victor; Kronstad, James

2013-01-01

Iron availability is a key regulator of virulence factor elaboration in Cryptococcus neoformans, the causative agent of fungal meningoencephalitis in HIV/AIDS patients. In addition, iron is an essential nutrient for pathogen proliferation in mammalian hosts but little is known about the mechanisms of iron sensing and uptake in fungal pathogens that attack humans. In this study, we mutagenized C. neoformans by Agrobacterium-mediated T-DNA insertion and screened for mutants with reduced growth on heme as the sole iron source. Among 34 mutants, we identified a subset with insertions in the gene for the ESCRT-I (endosomal sorting complex required for transport) protein Vps23 that resulted in a growth defect on heme, presumably due to a defect in uptake via endocytosis or misregulation of iron acquisition from heme. Remarkably, vps23 mutants were also defective in the elaboration of the cell-associated capsular polysaccharide that is a major virulence factor, while overexpression of Vps23 resulted in cells with a slightly enlarged capsule. These phenotypes were mirrored by a virulence defect in the vps23 mutant in a mouse model of cryptococcosis and by hypervirulence of the overexpression strain. Overall, these results reveal an important role for trafficking via ESCRT functions in both heme uptake and capsule formation, and they further reinforce the connection between iron and virulence factor deployment in C. neoformans.

Bluetongue virus spread in Europe is a consequence of climatic, landscape and vertebrate host factors as revealed by phylogeographic inference

PubMed Central

Palmarini, Massimo; Mertens, Peter

2017-01-01

Spatio-temporal patterns of the spread of infectious diseases are commonly driven by environmental and ecological factors. This is particularly true for vector-borne diseases because vector populations can be strongly affected by host distribution as well as by climatic and landscape variables. Here, we aim to identify environmental drivers for bluetongue virus (BTV), the causative agent of a major vector-borne disease of ruminants that has emerged multiple times in Europe in recent decades. In order to determine the importance of climatic, landscape and host-related factors affecting BTV diffusion across Europe, we fitted different phylogeographic models to a dataset of 113 time-stamped and geo-referenced BTV genomes, representing multiple strains and serotypes. Diffusion models using continuous space revealed that terrestrial habitat below 300 m altitude, wind direction and higher livestock densities were associated with faster BTV movement. Results of discrete phylogeographic analysis involving generalized linear models broadly supported these findings, but varied considerably with the level of spatial partitioning. Contrary to common perception, we found no evidence for average temperature having a positive effect on BTV diffusion, though both methodological and biological reasons could be responsible for this result. Our study provides important insights into the drivers of BTV transmission at the landscape scale that could inform predictive models of viral spread and have implications for designing control strategies. PMID:29021180

Patterns of Bacillary Dysentery in China, 2005-2010.

PubMed

Zhang, Han; Si, Yali; Wang, Xiaofeng; Gong, Peng

2016-01-27

Although the incidence of bacillary dysentery in China has been declining progressively, a considerable disease burden still exists. Few studies have analyzed bacillary dysentery across China and knowledge gaps still exist in the aspects of geographic distribution and ecological drivers, seasonality and its association with meteorological factors, urban-rural disparity, prevalence and distribution of Shigella species. Here, we performed nationwide analyses to fill the above gaps. Geographically, we found that incidence increased along an east-west gradient which was inversely related to the economic conditions of China. Two large endemically high-risk regions in western China and their ecological drivers were identified for the first time. We characterized seasonality of bacillary dysentery incidence and assessed its association with meteorological factors, and saw that it exhibits north-south differences in peak duration, relative amplitude and key meteorological factors. Urban and rural incidences among China's cities were compared, and disparity associated with urbanization level was invariant in most cities. Balanced decrease of urban and rural incidence was observed for all provinces except Hunan. S. flexneri and S. sonnei were identified as major causative species. Increasing prevalence of S. sonnei and geographic distribution of Shigella species were associated with economic status. Findings and inferences from this study draw broader pictures of bacillary dysentery in mainland China and could provide useful information for better interventions and public health planning.

Cardiac Expression of ms1/STARS, a Novel Gene Involved in Cardiac Development and Disease, Is Regulated by GATA4

PubMed Central

Kobayashi, Satoru; Peterson, Richard E.; He, Aibin; Motterle, Anna; Samani, Nilesh J.; Menick, Donald R.; Pu, William T.; Liang, Qiangrong

2012-01-01

Ms1/STARS is a novel muscle-specific actin-binding protein that specifically modulates the myocardin-related transcription factor (MRTF)-serum response factor (SRF) regulatory axis within striated muscle. This ms1/STARS-dependent regulatory axis is of central importance within the cardiac gene regulatory network and has been implicated in cardiac development and postnatal cardiac function/homeostasis. The dysregulation of ms1/STARS is associated with and causative of pathological cardiac phenotypes, including cardiac hypertrophy and cardiomyopathy. In order to gain an understanding of the mechanisms governing ms1/STARS expression in the heart, we have coupled a comparative genomic in silico analysis with reporter, gain-of-function, and loss-of-function approaches. Through this integrated analysis, we have identified three evolutionarily conserved regions (ECRs), α, SINA, and DINA, that act as cis-regulatory modules and confer differential cardiac cell-specific activity. Two of these ECRs, α and DINA, displayed distinct regulatory sensitivity to the core cardiac transcription factor GATA4. Overall, our results demonstrate that within embryonic, neonatal, and adult hearts, GATA4 represses ms1/STARS expression with the pathologically associated depletion of GATA4 (type 1/type 2 diabetic models), resulting in ms1/STARS upregulation. This GATA4-dependent repression of ms1/STARS expression has major implications for MRTF-SRF signaling in the context of cardiac development and disease. PMID:22431517

Patterns of Bacillary Dysentery in China, 2005–2010

PubMed Central

Zhang, Han; Si, Yali; Wang, Xiaofeng; Gong, Peng

2016-01-01

Although the incidence of bacillary dysentery in China has been declining progressively, a considerable disease burden still exists. Few studies have analyzed bacillary dysentery across China and knowledge gaps still exist in the aspects of geographic distribution and ecological drivers, seasonality and its association with meteorological factors, urban-rural disparity, prevalence and distribution of Shigella species. Here, we performed nationwide analyses to fill the above gaps. Geographically, we found that incidence increased along an east-west gradient which was inversely related to the economic conditions of China. Two large endemically high-risk regions in western China and their ecological drivers were identified for the first time. We characterized seasonality of bacillary dysentery incidence and assessed its association with meteorological factors, and saw that it exhibits north-south differences in peak duration, relative amplitude and key meteorological factors. Urban and rural incidences among China’s cities were compared, and disparity associated with urbanization level was invariant in most cities. Balanced decrease of urban and rural incidence was observed for all provinces except Hunan. S. flexneri and S. sonnei were identified as major causative species. Increasing prevalence of S. sonnei and geographic distribution of Shigella species were associated with economic status. Findings and inferences from this study draw broader pictures of bacillary dysentery in mainland China and could provide useful information for better interventions and public health planning. PMID:26828503

Foodborne Infectious Diseases Mediated by Inappropriate Infection Control in Food Service Businesses and Relevant Countermeasures in Korea.

PubMed

Park, Jong Myong; You, Young-Hyun; Cho, Hyun-Min; Hong, Ji Won; Ghim, Sa-Youl

2017-06-01

The objective of this review is to propose an appropriate course of action for improving the guidelines followed by food handlers for control of infection. For this purpose, previous epidemiological reports related to acute gastroenteritis in food service businesses mediated by food handlers were intensively analyzed. Relevant studies were identified in international databases. We selected eligible papers reporting foodborne infectious disease outbreaks. Among primary literature collection, the abstract of each article was investigated to find cases that absolutely identified a causative factor to be food handlers' inappropriate infection control and the taxon of causative microbial agents by epidemiological methodologies. Information about the sites (type of food business) where the outbreaks occurred was investigated. A wide variety of causative microbial agents has been investigated, using several epidemiological methods. These agents have shown diverse propagation pathways based on their own molecular pathogenesis, physiology, taxonomy, and etiology. Depending on etiology, transmission, propagation, and microbiological traits, we can predict the transmission characteristics of pathogens in food preparation areas. The infected food workers have a somewhat different ecological place in infection epidemiology as compared to the general population. However, the current Korean Food Safety Act cannot propose detailed guidelines. Therefore, different methodologies have to be made available to prevent further infections.

Foodborne Infectious Diseases Mediated by Inappropriate Infection Control in Food Service Businesses and Relevant Countermeasures in Korea

PubMed Central

Park, Jong Myong; You, Young-Hyun; Cho, Hyun-Min; Hong, Ji Won; Ghim, Sa-Youl

2017-01-01

Objectives The objective of this review is to propose an appropriate course of action for improving the guidelines followed by food handlers for control of infection. For this purpose, previous epidemiological reports related to acute gastroenteritis in food service businesses mediated by food handlers were intensively analyzed. Methods Relevant studies were identified in international databases. We selected eligible papers reporting foodborne infectious disease outbreaks. Among primary literature collection, the abstract of each article was investigated to find cases that absolutely identified a causative factor to be food handlers’ inappropriate infection control and the taxon of causative microbial agents by epidemiological methodologies. Information about the sites (type of food business) where the outbreaks occurred was investigated. Results A wide variety of causative microbial agents has been investigated, using several epidemiological methods. These agents have shown diverse propagation pathways based on their own molecular pathogenesis, physiology, taxonomy, and etiology. Conclusion Depending on etiology, transmission, propagation, and microbiological traits, we can predict the transmission characteristics of pathogens in food preparation areas. The infected food workers have a somewhat different ecological place in infection epidemiology as compared to the general population. However, the current Korean Food Safety Act cannot propose detailed guidelines. Therefore, different methodologies have to be made available to prevent further infections. PMID:28781938

Epidemiological Study on Cutaneous Leishmaniasis in an Endemic Area, of Qom Province, Central Iran

PubMed Central

Saghafipour, Abedin; Vatandoost, Hassan; Zahraei-Ramazani, Ali Reza; Yaghoobi-Ershadi, Mohammad Reza; Jooshin, Moharram Karami; Rassi, Yavar; Shirzadi, Mohammad Reza; Akhavan, Amir Ahmad; Hanafi-Bojd, Ahmad Ali

2017-01-01

Background: Cutaneous leishmaniasis (CL) is one of the most important health problems in many areas of Iran. There are two forms of the disease in Iran, anthroponotic and zoonotic CL. This study conducted to assess the epidemiological situation of CL in an endemic area of Qom Province, central Iran from Apr to Nov 2015. Methods: The sticky paper traps and aspirating tubes were used for collecting adult sand flies. Sherman traps and small insect nets were used to capture rodents and small mammals. Giemsa staining was used for preparing the expanded smear and followed by PCR for identifying the causative agent in human, vectors, and reservoirs. In this study, relative frequency of CL was also calculated. Results: Fourteen species of Phlebotomine sand flies were collected. Phlebotomus papatasi (61.74%) was the predominant species through the period of activity. Overall, 62 Meriones libycus, 8 Nesokia indica, 4 Mus musculus, 16 Allactaga elater and 2 Hemiechinus auritis were caught. PCR technique showed 6 out of 150 P. papatasi (2%), two out of 62 M. libycus (3.23%) and all of suspected human’s skin tissue samples (100%) were infected with Leishmania major. The relative frequency of CL was 0.30%. Conclusion: This is the first detection of L. major within P. papatasi, M. libycus and human in Kahak District in Qom Province of Iran. Zoonotic cycle of CL exists in this area, L. major is the causative agent, P. papatasi is the main vector and M. libycus is the main reservoir of the disease. PMID:29322057

Historical Perspectives of the Causation of Lung Cancer

PubMed Central

2015-01-01

Lung cancer is the leading cause of cancer deaths worldwide. Less-known forces are involved in the etiology of lung cancer and have relevant implications for providers in ameliorating care. The purpose of this article is to discuss theories of causation of lung cancer using historical analyses of the evolution of the disease and incorporating related explanations integrating the relationships of science, nursing, medicine, and society. Literature from 160 years was searched and Thagard’s model of causation networks was used to exhibit how nursing and medicine were significant influences in lung cancer causation theory. Disease causation interfaces with sociological norms of behavior to form habits and rates of health behavior. Historically, nursing was detrimentally manipulated by the tobacco industry, engaging in harmful smoking behaviors, thus negatively affecting patient care. Understanding the underlying history behind lung cancer causation may empower nurses to play an active role in a patient’s health. PMID:28462309

Observational goals for Max '91 to identify the causative agent for impulsive bursts

NASA Technical Reports Server (NTRS)

Batchelor, D. A.

1989-01-01

Recent studies of impulsive hard x ray and microwave bursts suggest that a propagating causative agent with a characteristic velocity of the order of 1000 km/s is responsible for these bursts. The results of these studies are summarized and observable distinguishing characteristics of the various possible agents are highlighted, with emphasis on key observational goals for the Max '91 campaigns. The most likely causative agents suggested by the evidence are shocks, thermal conduction fronts, and propagating modes of magnetic reconnection in flare plasmas. With new instrumentation planned for Max '91, high spatial resolution observations of hard x ray sources have the potential to identify the agent by revealing detailed features of source spatial evolution. Observations with the Very Large Array and other radio imaging instruments are of great importance, as well as detailed modeling of coronal loop structures to place limits on their density and temperature profiles. With the combined hard x ray and microwave imaging observations, aided by loop model results, the simplest causative agent to rule out would be the propagating modes of magnetic reconnection. To fit the observational evidence, reconnection modes would need to travel at approximately the same velocity (the Alfven velocity) in different coronal structures that vary in length by a factor of 10(exp 3). Over such a vast range in loop lengths, it is difficult to believe that the Alfven velocity is constant. Thermal conduction fronts would be suggested by sources that expand along the direction of B and exhibit relatively little particle precipitation. Particle acceleration due to shocks could produce more diverse radially expanding source geometries with precipitation at loop footprints.

Depressive disorder, coronary heart disease, and stroke: dose-response and reverse causation effects in the Whitehall II cohort study.

PubMed

Brunner, Eric J; Shipley, Martin J; Britton, Annie R; Stansfeld, Stephen A; Heuschmann, Peter U; Rudd, Anthony G; Wolfe, Charles D A; Singh-Manoux, Archana; Kivimaki, Mika

2014-03-01

Systematic reviews examining associations of depressive disorder with coronary heart disease and stroke produce mixed results. Failure to consider reverse causation and dose-response patterns may have caused inconsistencies in evidence. This prospective cohort study on depressive disorder, coronary heart disease, and stroke analysed reverse causation and dose-response effects using four 5-year and three 10-year observation cycles (total follow up 24 years) based on multiple repeat measures of exposure. Participants in the Whitehall II study (n = 10,036, 31,395 person-observations, age at start 44.4 years) provided up to six repeat measures of depressive symptoms via the 30-item General Health Questionnaire (GHQ-30) and one measure via Center for Epidemiologic Studies Depression Scale (CES-D). The cohort was followed up for major coronary events (coronary death/nonfatal myocardial infarction) and stroke (stroke death/morbidity) through the national mortality register Hospital Episode Statistics, ECG-screening, medical records, and self-report questionnaires. GHQ-30 caseness predicted stroke over 0-5 years (age-, sex- and ethnicity-adjusted HR 1.60, 95% CI 1.1-2.3) but not over 5-10 years (HR 0.94, 95% CI 0.6-1.4). Using the last 5-year observation cycle, cumulative GHQ-30 caseness was associated with incident coronary heart disease in a dose-response manner (1-2 times a case: HR 1.12, 95% CI 0.7-1.7; 3-4 times: HR 2.06, 95% CI 1.2-3.7), and CES-D caseness predicted coronary heart disease (HR 1.81, 95% CI 1.1-3.1). There was evidence of a dose-response effect of depressive symptoms on risk of coronary heart disease. In contrast, prospective associations of depressive symptoms with stroke appeared to arise wholly or partly through reverse causation.

Gene Augmentation Therapy for a Missense Substitution in the cGMP-Binding Domain of Ovine CNGA3 Gene Restores Vision in Day-Blind Sheep

PubMed Central

Gootwine, Elisha; Abu-Siam, Mazen; Obolensky, Alexey; Rosov, Alex; Honig, Hen; Nitzan, Tali; Shirak, Andrey; Ezra-Elia, Raaya; Yamin, Esther; Banin, Eyal; Averbukh, Edward; Hauswirth, William W.; Ofri, Ron; Seroussi, Eyal

2017-01-01

Purpose Applying CNGA3 gene augmentation therapy to cure a novel causative mutation underlying achromatopsia (ACHM) in sheep. Methods Impaired vision that spontaneously appeared in newborn lambs was characterized by behavioral, electroretinographic (ERG), and histologic techniques. Deep-sequencing reads of an affected lamb and an unaffected lamb were compared within conserved genomic regions orthologous to human genes involved in similar visual impairment. Observed nonsynonymous amino acid substitutions were classified by their deleteriousness score. The putative causative mutation was assessed by producing compound CNGA3 heterozygotes and applying gene augmentation therapy using the orthologous human cDNA. Results Behavioral assessment revealed day blindness, and subsequent ERG examination showed attenuated photopic responses. Histologic and immunohistochemical examination of affected sheep eyes did not reveal degeneration, and cone photoreceptors expressing CNGA3 were present. Bioinformatics and sequencing analyses suggested a c.1618G>A, p.Gly540Ser substitution in the GMP-binding domain of CNGA3 as the causative mutation. This was confirmed by genetic concordance test and by genetic complementation experiment: All five compound CNGA3 heterozygotes, carrying both p.Arg236* and p.Gly540Ser mutations in CNGA3, were day-blind. Furthermore, subretinal delivery of the intact human CNGA3 gene using an adeno-associated viral vector (AAV) restored photopic vision in two affected p.Gly540Ser homozygous rams. Conclusions The c.1618G>A, p.Gly540Ser substitution in CNGA3 was identified as the causative mutation for a novel form of ACHM in Awassi sheep. Gene augmentation therapy restored vision in the affected sheep. This novel mutation provides a large-animal model that is valid for most human CNGA3 ACHM patients; the majority of them carry missense rather than premature-termination mutations. PMID:28282490

[Gastrointestinal lesions and characteristics of acute gastrointestinal bleeding in acenocoumarol-treated patients].

PubMed

Nantes, Óscar; Zozaya, José Manuel; Montes, Ramón; Hermida, José

2014-01-01

In the last few years, the number of anticoagulated patients has significantly increased and, as a consequence, so have hemorrhagic complications due to this therapy. We analyzed gastrointestinal (GI) bleeding because it is the most frequent type of major bleeding in these patients, and we hypothesized that they would have lesions responsible for GI bleeding regardless of the intensity of anticoagulation, although excessively anticoagulated patients would have more serious hemorrhages. To study the characteristics of anticoagulated patients with GI bleeding and the relationship between the degree of anticoagulation and a finding of causative lesions and bleeding severity. We prospectively studied 96 patients, all anticoagulated with acenocoumarol and consecutively admitted to hospital between 01/01/2003 and 09/30/2005 because of acute GI bleeding. We excluded patients with severe liver disease, as well as nine patients with incomplete details. The incidence of GI bleeding requiring hospitalization was 19.6 cases/100,000 inhabitants-year. In 90% of patients, we found a causative (85% of upper GI bleeding and 50% of lower GI bleeding) or potentially causative lesion, and 30% of them required endoscopic treatment, without differences depending on the intensity of anticoagulation. No relationship was found between the type of lesions observed and the degree of anticoagulation in these patients. Patients who received more intense anticoagulation therapy had more severe hemorrhages (23% of patients with an INR ≥4 had a life-threatening bleed versus only 4% of patients with INR <4). We found an incidence of 20 severe GI bleeding episodes in anticoagulated patients per 100,000 inhabitants-year, with no difference in localization or in the frequency of causative lesions depending on the intensity of anticoagulation. Patients receiving more intense anticoagulation had more severe GI bleeding episodes. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

Fine-Scale Variation and Genetic Determinants of Alternative Splicing across Individuals

PubMed Central

Coulombe-Huntington, Jasmin; Lam, Kevin C. L.; Dias, Christel; Majewski, Jacek

2009-01-01

Recently, thanks to the increasing throughput of new technologies, we have begun to explore the full extent of alternative pre–mRNA splicing (AS) in the human transcriptome. This is unveiling a vast layer of complexity in isoform-level expression differences between individuals. We used previously published splicing sensitive microarray data from lymphoblastoid cell lines to conduct an in-depth analysis on splicing efficiency of known and predicted exons. By combining publicly available AS annotation with a novel algorithm designed to search for AS, we show that many real AS events can be detected within the usually unexploited, speculative majority of the array and at significance levels much below standard multiple-testing thresholds, demonstrating that the extent of cis-regulated differential splicing between individuals is potentially far greater than previously reported. Specifically, many genes show subtle but significant genetically controlled differences in splice-site usage. PCR validation shows that 42 out of 58 (72%) candidate gene regions undergo detectable AS, amounting to the largest scale validation of isoform eQTLs to date. Targeted sequencing revealed a likely causative SNP in most validated cases. In all 17 incidences where a SNP affected a splice-site region, in silico splice-site strength modeling correctly predicted the direction of the micro-array and PCR results. In 13 other cases, we identified likely causative SNPs disrupting predicted splicing enhancers. Using Fst and REHH analysis, we uncovered significant evidence that 2 putative causative SNPs have undergone recent positive selection. We verified the effect of five SNPs using in vivo minigene assays. This study shows that splicing differences between individuals, including quantitative differences in isoform ratios, are frequent in human populations and that causative SNPs can be identified using in silico predictions. Several cases affected disease-relevant genes and it is likely some of these differences are involved in phenotypic diversity and susceptibility to complex diseases. PMID:20011102

Polycyclic Aromatic Hydrocarbons and digestive tract cancers - a perspective

PubMed Central

Diggs, Deacqunita L.; Huderson, Ashley C.; Harris, Kelly L.; Myers, Jeremy N.; Banks, Leah D.; Rekhadevi, Perumalla V.; Niaz, Mohammad S.; Ramesh, Aramandla

2011-01-01

Cancers of the colon are most common in the Western world. In majority of these cases, there is no familial history and sporadic gene damage seems to play an important role in the development of tumors in the colon. Studies have shown that environmental factors, especially diet, play an important role in susceptibility to GI tract cancers. Consequently, environmental chemicals that contaminate food or diet during its preparation becomes important in the development of GI cancers. Polycyclic aromatic hydrocarbons (PAHs) are one such family of ubiquitous environmental toxicants. These pollutants enter the human body through consumption of contaminated food, drinking water, inhalation of cigarette smoke, automobile exhausts, and contaminated air from occupational settings. Among these pathways, dietary intake of PAHs constitutes a major source of exposure in humans. Although many reviews and books on PAHs and their ability to cause toxicity and breast or lung cancer have been published, aspects on contribution of diet, smoking and other factors towards development of digestive tract cancers and strategies to assess risk from exposure to PAHs have received much less attention. This review, therefore, focuses on dietary intake of PAHs in humans, animal models, and cell cultures used for GI cancer studies along with epidemiological findings. Bioavailability and biotransformation processes, which influence the disposition of PAHs in body and the underlying causative mechanisms of GI cancers, are also discussed. The existing data gaps and scope for future studies is also emphasized. This information is expected to stimulate research on mechanisms of sporadic GI cancers caused by exposure to environmental carcinogens. PMID:22107166

Dally Proteoglycan Mediates the Autonomous and Nonautonomous Effects on Tissue Growth Caused by Activation of the PI3K and TOR Pathways

PubMed Central

Ferreira, Ana; Milán, Marco

2015-01-01

How cells acquiring mutations in tumor suppressor genes outcompete neighboring wild-type cells is poorly understood. The phosphatidylinositol 3-kinase (PI3K)–phosphatase with tensin homology (PTEN) and tuberous sclerosis complex (TSC)-target of rapamycin (TOR) pathways are frequently activated in human cancer, and this activation is often causative of tumorigenesis. We utilized the Gal4-UAS system in Drosophila imaginal primordia, highly proliferative and growing tissues, to analyze the impact of restricted activation of these pathways on neighboring wild-type cell populations. Activation of these pathways leads to an autonomous induction of tissue overgrowth and to a remarkable nonautonomous reduction in growth and proliferation rates of adjacent cell populations. This nonautonomous response occurs independently of where these pathways are activated, is functional all throughout development, takes place across compartments, and is distinct from cell competition. The observed autonomous and nonautonomous effects on tissue growth rely on the up-regulation of the proteoglycan Dally, a major element involved in modulating the spreading, stability, and activity of the growth promoting Decapentaplegic (Dpp)/transforming growth factor β(TGF-β) signaling molecule. Our findings indicate that a reduction in the amount of available growth factors contributes to the outcompetition of wild-type cells by overgrowing cell populations. During normal development, the PI3K/PTEN and TSC/TOR pathways play a major role in sensing nutrient availability and modulating the final size of any developing organ. We present evidence that Dally also contributes to integrating nutrient sensing and organ scaling, the fitting of pattern to size. PMID:26313758

Joint analysis of quantitative trait loci and major-effect causative mutations affecting meat quality and carcass composition traits in pigs.

PubMed

Cherel, Pierre; Pires, José; Glénisson, Jérôme; Milan, Denis; Iannuccelli, Nathalie; Hérault, Frédéric; Damon, Marie; Le Roy, Pascale

2011-08-29

Detection of quantitative trait loci (QTLs) affecting meat quality traits in pigs is crucial for the design of efficient marker-assisted selection programs and to initiate efforts toward the identification of underlying polymorphisms. The RYR1 and PRKAG3 causative mutations, originally identified from major effects on meat characteristics, can be used both as controls for an overall QTL detection strategy for diversely affected traits and as a scale for detected QTL effects. We report on a microsatellite-based QTL detection scan including all autosomes for pig meat quality and carcass composition traits in an F2 population of 1,000 females and barrows resulting from an intercross between a Pietrain and a Large White-Hampshire-Duroc synthetic sire line. Our QTL detection design allowed side-by-side comparison of the RYR1 and PRKAG3 mutation effects seen as QTLs when segregating at low frequencies (0.03-0.08), with independent QTL effects detected from most of the same population, excluding any carrier of these mutations. Large QTL effects were detected in the absence of the RYR1 and PRKGA3 mutations, accounting for 12.7% of phenotypic variation in loin colour redness CIE-a* on SSC6 and 15% of phenotypic variation in glycolytic potential on SSC1. We detected 8 significant QTLs with effects on meat quality traits and 20 significant QTLs for carcass composition and growth traits under these conditions. In control analyses including mutation carriers, RYR1 and PRKAG3 mutations were detected as QTLs, from highly significant to suggestive, and explained 53% to 5% of the phenotypic variance according to the trait. Our results suggest that part of muscle development and backfat thickness effects commonly attributed to the RYR1 mutation may be a consequence of linkage with independent QTLs affecting those traits. The proportion of variation explained by the most significant QTLs detected in this work is close to the influence of major-effect mutations on the least affected traits, but is one order of magnitude lower than effect on variance of traits primarily affected by these causative mutations. This suggests that uncovering physiological traits directly affected by genetic polymorphisms would be an appropriate approach for further characterization of QTLs.

Joint analysis of quantitative trait loci and major-effect causative mutations affecting meat quality and carcass composition traits in pigs

PubMed Central

2011-01-01

Background Detection of quantitative trait loci (QTLs) affecting meat quality traits in pigs is crucial for the design of efficient marker-assisted selection programs and to initiate efforts toward the identification of underlying polymorphisms. The RYR1 and PRKAG3 causative mutations, originally identified from major effects on meat characteristics, can be used both as controls for an overall QTL detection strategy for diversely affected traits and as a scale for detected QTL effects. We report on a microsatellite-based QTL detection scan including all autosomes for pig meat quality and carcass composition traits in an F2 population of 1,000 females and barrows resulting from an intercross between a Pietrain and a Large White-Hampshire-Duroc synthetic sire line. Our QTL detection design allowed side-by-side comparison of the RYR1 and PRKAG3 mutation effects seen as QTLs when segregating at low frequencies (0.03-0.08), with independent QTL effects detected from most of the same population, excluding any carrier of these mutations. Results Large QTL effects were detected in the absence of the RYR1 and PRKGA3 mutations, accounting for 12.7% of phenotypic variation in loin colour redness CIE-a* on SSC6 and 15% of phenotypic variation in glycolytic potential on SSC1. We detected 8 significant QTLs with effects on meat quality traits and 20 significant QTLs for carcass composition and growth traits under these conditions. In control analyses including mutation carriers, RYR1 and PRKAG3 mutations were detected as QTLs, from highly significant to suggestive, and explained 53% to 5% of the phenotypic variance according to the trait. Conclusions Our results suggest that part of muscle development and backfat thickness effects commonly attributed to the RYR1 mutation may be a consequence of linkage with independent QTLs affecting those traits. The proportion of variation explained by the most significant QTLs detected in this work is close to the influence of major-effect mutations on the least affected traits, but is one order of magnitude lower than effect on variance of traits primarily affected by these causative mutations. This suggests that uncovering physiological traits directly affected by genetic polymorphisms would be an appropriate approach for further characterization of QTLs. PMID:21875434

Next-Generation Vaccines Based on Bacille Calmette–Guérin

PubMed Central

Nieuwenhuizen, Natalie E.; Kaufmann, Stefan H. E.

2018-01-01

Tuberculosis (TB), caused by the intracellular bacterium Mycobacterium tuberculosis (Mtb), remains a major health threat. A live, attenuated mycobacterium known as Bacille Calmette–Guérin (BCG), derived from the causative agent of cattle TB, Mycobacterium bovis, has been in clinical use as a vaccine for 90 years. The current incidence of TB demonstrates that BCG fails to protect sufficiently against pulmonary TB, the major disease manifestation and source of dissemination. The protective efficacy of BCG is on average 50% but varies substantially with geographical location and is poorer in those with previous exposure to mycobacteria. BCG can also cause adverse reactions in immunocompromised individuals. However, BCG has contributed to reduced infant TB mortality by protecting against extrapulmonary TB. In addition, BCG has been associated with reduced general childhood mortality by stimulating immune responses. In order to improve the efficacy of BCG, two major strategies have been employed. The first involves the development of recombinant live mycobacterial vaccines with improved efficacy and safety. The second strategy is to boost BCG with subunit vaccines containing Mtb antigens. This article reviews recombinant BCG strains that have been tested against TB in animal models. This includes BCG strains that have been engineered to induce increased immune responses by the insertion of genes for Mtb antigens, mammalian cytokines, or host resistance factors, the insertion of bacterial toxin-derived adjuvants, and the manipulation of bacterial genes in order to increase antigen presentation and immune activation. Subunit vaccines for boosting BCG are also briefly discussed. PMID:29459859

Phylogenomics and the Dynamic Genome Evolution of the Genus Streptococcus

PubMed Central

Richards, Vincent P.; Palmer, Sara R.; Pavinski Bitar, Paulina D.; Qin, Xiang; Weinstock, George M.; Highlander, Sarah K.; Town, Christopher D.; Burne, Robert A.; Stanhope, Michael J.

2014-01-01

The genus Streptococcus comprises important pathogens that have a severe impact on human health and are responsible for substantial economic losses to agriculture. Here, we utilize 46 Streptococcus genome sequences (44 species), including eight species sequenced here, to provide the first genomic level insight into the evolutionary history and genetic basis underlying the functional diversity of all major groups of this genus. Gene gain/loss analysis revealed a dynamic pattern of genome evolution characterized by an initial period of gene gain followed by a period of loss, as the major groups within the genus diversified. This was followed by a period of genome expansion associated with the origins of the present extant species. The pattern is concordant with an emerging view that genomes evolve through a dynamic process of expansion and streamlining. A large proportion of the pan-genome has experienced lateral gene transfer (LGT) with causative factors, such as relatedness and shared environment, operating over different evolutionary scales. Multiple gene ontology terms were significantly enriched for each group, and mapping terms onto the phylogeny showed that those corresponding to genes born on branches leading to the major groups represented approximately one-fifth of those enriched. Furthermore, despite the extensive LGT, several biochemical characteristics have been retained since group formation, suggesting genomic cohesiveness through time, and that these characteristics may be fundamental to each group. For example, proteolysis: mitis group; urea metabolism: salivarius group; carbohydrate metabolism: pyogenic group; and transcription regulation: bovis group. PMID:24625962

Segregation analysis reveals evidence of a major gene for Alzheimer disease.

PubMed Central

Farrer, L A; Myers, R H; Connor, L; Cupples, L A; Growdon, J H

1991-01-01

In an attempt to resolve the relative influences of major genes, multifactorial heritability, and cohort effects on the susceptibility to Alzheimer disease (AD), complex segregation analysis was performed on 232 nuclear families. All families were consecutively ascertained through a single proband who was referred for diagnostic evaluation of a memory disorder. The results suggest that susceptibility to AD is determined, in part, by a major autosomal dominant allele with an additional multifactorial component. Single-locus, polygenic, sporadic, and no-transmission models, as well as recessive inheritance of the major effect, were significantly rejected. Excess transmission from the heterozygote was marginally significant and probably reflects the presence of phenocopies or perhaps the existence of two or more major loci for AD. The frequency of the AD susceptibility allele was estimated to be .038, but the major locus accounts for only 24% of the transmission variance, indicating a substantial role for other genetic and nongenetic mechanisms in the causation of AD. PMID:2035523

[EXPERIENCE OF STUDY AND POSSIBLE WAYS OF ELIMINATION OF FALSE POSITIVE AND FALSE NEGATIVE RESULTS DURING EXECUTION OF POLYMERASE CHAIN REACTION ON AN EXAMPLE OF JUNIN VIRUS RNA DETECTION].

PubMed

Sizikova, T E; Lebedev, V N; Pantyukhov, V B; Borisevich, S V; Merkulov, V A

2015-01-01

Experience of study and possible ways of elimination of false positive and false negative results during execution of polymerase chain reaction on an example of Junin virus RNA detection. MATERIALSS AND METHODS: Junin virus--causative agent of Argentine hemorrhagic fever (AHF) strain XJpR37/5787 was obtained from the State collection of pathogenicity group I causative agents of the 48th Central Research Institute. Reagent kit for detection of Junin virus RNA by RT-PCR was developed in the Institute and consists of 4 sets: for isolation of RNA, execution of reverse-transcription reaction, execution of PCR and electrophoretic detection of PCR products. RT-PCR was carried out by a standard technique. Continuous cell cultures of African green monkey Vero B, GMK-AH-1(D) were obtained from the museum of cell culture department of the Centre. An experimental study of the effect of various factors of impact on the sample under investigation ("thawing-freezing", presence of formaldehyde, heparin) on the obtaining of false negative results during Junin virus RNA detection by using RT-PCR was studied. Addition of 0.01% heparin to the samples was shown to completely inhibit PCR. Addition of 0.05% formaldehyde significantly reduces sensitivity of the method. A possibility of reduction of analysis timeframe from 15 to 5 days was shown during detection of the causative agent in samples with low concentration of the latter by growing the samples and subsequent analysis of the material obtained by using RT-PCR. During detection of causative agent by using RT-PCR false negative results could appear in the presence of formaldehyde and heparin in the sample. A possibility of elimination of false negative PCR results due to concentration of the causative agent in the sample under investigation at a level below sensitivity threshold was shown on the example of Junin virus RNA detection by using growing of the pathogen in appropriate accumulation system with subsequent analysis of the material obtained using PCR.

Cyst infection in autosomal dominant polycystic kidney disease: causative microorganisms and susceptibility to lipid-soluble antibiotics.

PubMed

Suwabe, T; Araoka, H; Ubara, Y; Kikuchi, K; Hazue, R; Mise, K; Hamanoue, S; Ueno, T; Sumida, K; Hayami, N; Hoshino, J; Imafuku, A; Kawada, M; Hiramatsu, R; Hasegawa, E; Sawa, N; Takaichi, K

2015-07-01

Cyst infection is a frequent and serious complication of autosomal dominant polycystic kidney disease (ADPKD). Lipid-soluble antibiotics like fluoroquinolones show good penetration into cysts and are recommended for cyst infection, but causative microorganisms are often resistant to these agents. This study investigated the profile of the microorganisms causing cyst infection in ADPKD, their susceptibility to lipid-soluble antibiotics, and clinical outcomes. This retrospective study reviewed all ADPKD patients admitted to Toranomon Hospital with a diagnosis of cyst infection from January 2004 to March 2014. All patients who underwent cyst drainage and had positive cyst fluid cultures were enrolled. Patients with positive blood cultures who satisfied our criteria for cyst infection or probable infection were also enrolled. There were 99 episodes with positive cyst fluid cultures and 93 episodes with positive blood cultures. The majority of patients were on dialysis. The death rate was high when infection was caused by multiple microorganisms or when there were multiple infected cysts. Gram-negative bacteria accounted for 74-79 % of the isolates in all groups, except for patients with positive hepatic cyst fluid cultures. The susceptibility of Escherichia coli to fluoroquinolones was very low in patients with hepatic cyst infection, especially those with frequent episodes and those with hepatomegaly. Fungi were detected in two episodes. Fluoroquinolone-resistant microorganisms showed a high prevalence in cyst infection. It is important to identify causative microorganisms to avoid the overuse of fluoroquinolones and to improve the outcome of cyst infection in ADPKD.

ZMYND10--Mutation Analysis in Slavic Patients with Primary Ciliary Dyskinesia.

PubMed

Kurkowiak, Małgorzata; Ziętkiewicz, Ewa; Greber, Agnieszka; Voelkel, Katarzyna; Wojda, Alina; Pogorzelski, Andrzej; Witt, Michał

2016-01-01

Primary ciliary dyskinesia (PCD) is a rare recessive disease with a prevalence of 1/10,000; its symptoms are caused by a kinetic dysfunction of motile cilia in the respiratory epithelium, flagella in spermatozoids, and primary cilia in the embryonic node. PCD is genetically heterogeneous: genotyping the already known PCD-related genes explains the genetic basis in 60-65% of the cases, depending on the population. While identification of new genes involved in PCD pathogenesis remains crucial, the search for new, population-specific mutations causative for PCD is equally important. The Slavs remain far less characterized in this respect compared to West European populations, which significantly limits diagnostic capability. The main goal of this study was to characterize the profile of causative genetic defects in one of the PCD-causing genes, ZMYND10, in the cohort of PCD patients of Slavic origin. The study was carried out using biological material from 172 unrelated PCD individuals of Polish origin, with no causative mutation found in nine major PCD genes. While none of the previously described mutations was found using the HRM-based screening, a novel frameshift mutation (c.367delC) in ZMYND10, unique for Slavic PCD population, was found in homozygous state in two unrelated PCD patients. Immunofluorescence analysis confirmed the absence of outer and inner dynein arms from the ciliary axoneme, consistent with the already published ZMYND10-mutated phenotype; cDNA analysis revealed the lack of ZMYND10 mRNA, indicating nonsense-mediated decay of the truncated transcript.

Near-source high-rate GPS, strong motion and InSAR observations to image the 2015 Lefkada (Greece) Earthquake rupture history.

PubMed

Avallone, Antonio; Cirella, Antonella; Cheloni, Daniele; Tolomei, Cristiano; Theodoulidis, Nikos; Piatanesi, Alessio; Briole, Pierre; Ganas, Athanassios

2017-09-04

The 2015/11/17 Lefkada (Greece) earthquake ruptured a segment of the Cephalonia Transform Fault (CTF) where probably the penultimate major event was in 1948. Using near-source strong motion and high sampling rate GPS data and Sentinel-1A SAR images on two tracks, we performed the inversion for the geometry, slip distribution and rupture history of the causative fault with a three-step self-consistent procedure, in which every step provided input parameters for the next one. Our preferred model results in a ~70° ESE-dipping and ~13° N-striking fault plane, with a strike-slip mechanism (rake ~169°) in agreement with the CTF tectonic regime. This model shows a bilateral propagation spanning ~9 s with the activation of three main slip patches, characterized by rise time and peak slip velocity in the ranges 2.5-3.5 s and 1.4-2.4 m/s, respectively, corresponding to 1.2-1.8 m of slip which is mainly concentrated in the shallower (<10 km) southern half of the causative fault. The inferred slip distribution and the resulting seismic moment (M 0  = 1.05 × 10 19 N m) suggest a magnitude of M w 6.6. Our best solution suggests that the occurrence of large (M w  > 6) earthquakes to the northern and to the southern boundaries of the 2015 causative fault cannot be excluded.

Destructin-1 is a collagen-degrading endopeptidase secreted by Pseudogymnoascus destructans, the causative agent of white-nose syndrome.

PubMed

O'Donoghue, Anthony J; Knudsen, Giselle M; Beekman, Chapman; Perry, Jenna A; Johnson, Alexander D; DeRisi, Joseph L; Craik, Charles S; Bennett, Richard J

2015-06-16

Pseudogymnoascus destructans is the causative agent of white-nose syndrome, a disease that has caused the deaths of millions of bats in North America. This psychrophilic fungus proliferates at low temperatures and targets hibernating bats, resulting in their premature arousal from stupor with catastrophic consequences. Despite the impact of white-nose syndrome, little is known about the fungus itself or how it infects its mammalian host. P. destructans is not amenable to genetic manipulation, and therefore understanding the proteins involved in infection requires alternative approaches. Here, we identify hydrolytic enzymes secreted by P. destructans, and use a novel and unbiased substrate profiling technique to define active peptidases. These experiments revealed that endopeptidases are the major proteolytic activities secreted by P. destructans, and that collagen, the major structural protein in mammals, is actively degraded by the secretome. A serine endopeptidase, hereby-named Destructin-1, was subsequently identified, and a recombinant form overexpressed and purified. Biochemical analysis of Destructin-1 showed that it mediated collagen degradation, and a potent inhibitor of peptidase activity was identified. Treatment of P. destructans-conditioned media with this antagonist blocked collagen degradation and facilitated the detection of additional secreted proteolytic activities, including aminopeptidases and carboxypeptidases. These results provide molecular insights into the secretome of P. destructans, and identify serine endopeptidases that have the clear potential to facilitate tissue invasion and pathogenesis in the mammalian host.

Anticancer and antibacterial secondary metabolites from the endophytic fungus Penicillium sp. CAM64 against multi-drug resistant Gram-negative bacteria.

PubMed

Jouda, Jean-Bosco; Tamokou, Jean-de-Dieu; Mbazoa, Céline Djama; Sarkar, Prodipta; Bag, Prasanta Kumar; Wandji, Jean

2016-09-01

The emergence of multiple-drug resistance bacteria has become a major threat and thus calls for an urgent need to search for new effective and safe anti-bacterial agents. This study aims to evaluate the anticancer and antibacterial activities of secondary metabolites from Penicillium sp., an endophytic fungus associated with leaves of Garcinia nobilis. The culture filtrate from the fermentation of Penicillium sp. was extracted and analyzed by liquid chromatography-mass spectrometry, and the major metabolites were isolated and identified by spectroscopic analyses and by comparison with published data. The antibacterial activity of the compounds was assessed by broth microdilution method while the anticancer activity was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The fractionation of the crude extract afforded penialidin A-C (1-3), citromycetin (4), p-hydroxyphenylglyoxalaldoxime (5) and brefelfin A (6). All of the compounds tested here showed antibacterial activity (MIC = 0.50 - 128 µg/mL) against Gramnegative multi-drug resistance bacteria, Vibrio cholerae (causative agent of dreadful disease cholera) and Shigella flexneri (causative agent of shigellosis), as well as the significant anticancer activity (LC 50 = 0.88 - 9.21 µg/mL) against HeLa cells. The results obtained indicate that compounds 1-6 showed good antibacterial and anticancer activities with no toxicity to human red blood cells and normal Vero cells.

Caring for medically unexplained physical symptoms after toxic environmental exposures: effects of contested causation.

PubMed Central

Engel, Charles C; Adkins, Joyce A; Cowan, David N

2002-01-01

Medically unexplained physical symptoms (MUPS) are persistent idiopathic symptoms that drive patients to seek medical care. MUPS syndromes include chronic fatigue syndrome, fibromyalgia syndrome, and multiple chemical sensitivities. When MUPS occur after an environmental exposure or injury, an adversarial social context that we call "contested causation" may ensue. Contested causation may occur publicly and involve media controversy, scientific disagreement, political debate, and legal struggles. This adversarial social context may diminish the effectiveness of the provider-patient relationship. Contested causation also may occur privately, when disagreement over the causes of MUPS takes place in the patient-provider context. These patient-provider disagreements over causation often occur because of the enigmatic nature of MUPS. We suggest that a context of contested causation may have serious negative effects on healthcare for individuals with MUPS. Context plays a larger role in MUPS care than it does for most medical care because of the uncertain nature of MUPS, the reliance of standard MUPS therapies on a potentially tenuous patient-provider partnership, and the clinical need to rely routinely on subjective MUPS assessments that often yield discordant patient and provider conclusions. Contested causation may erode patient-provider trust, test the provider's self-assurance and capacity to share power with the patient, and raise problematic issues of compensation, reparation, and blame. These issues may distract patients and providers from therapeutic goals. In occupational and military settings, the adverse impact of contested causation on the patient-provider partnership may diminish therapeutic effectiveness to a greater degree than it does in other medical settings. Contested causation therefore raises questions regarding generalizability of standard therapies for MUPS and related syndromes to these settings. Future research is needed to learn whether intuitively sensible and evidence-based MUPS therapies benefit occupational and military medical patients who are afforded care in the context of contested causation. PMID:12194900

Child physical punishment, injury and abuse (part two).

PubMed

Watkins, Dianne; Cousins, Judy

2005-09-01

This is the second paper in a series of two that focus on causational factors that contribute to child physical punishment, injury and child physical abuse. Paper one concentrated on the extent of child physical punishment, injuries sustained and the relationship between macrotheoretical factors. It highlighted a continuum between child physical discipline, injuries and child physical abuse. Paper two introduces the reader to microtheoretical factors that contribute to child physical punishment and its relationship with child physical injuries and abuse. The focus is on parental and child influences, lifestyle factors and socialisation of parents. It will integrate macrotheroretical factors highlighted in paper one and microtheroretical factors presented in this paper into a framework for the prevention of child physical injury and abuse based on an ecological model.

The Conundrum of Causality in Tumor Virology: The Cases of KSHV and MCV

PubMed Central

Moore, Patrick S.; Chang, Yuan

2014-01-01

Controversy has plagued tumor virology since the first tumor viruses were described over 100 years ago. Methods to establish cancer causation, such as Koch’s postulates, work poorly or not at all for these viruses. Kaposi’s sarcoma herpesvirus (KSHV/HHV8) and Merkel cell polyomavirus (MCV) were both found using nucleic acid identification methods but they represent opposite poles in the patterns for tumor virus epidemiology. KSHV is uncommon and has specific risk factors that contribute to infection and subsequent cancers. MCV and Merkel cell carcinoma (MCC), in contrast, is an example in which mutations to our normal viral flora contribute to cancer. Given the near-ubiquity of human MCV infection, establishing cancer causality relies on molecular evidence that does not fit comfortably within traditional infectious disease epidemiological models. These two viruses reveal some of the challenges and opportunities for inferring viral cancer causation in the age of molecular biology. PMID:24304907

A case of bullous dermatitis artefacta possibly induced by a deodorant spray.

PubMed

Ikenaga, Satsuki; Nakano, Hajime; Umegaki, Noriko; Moritsugu, Ryuta; Aizu, Takayuki; Kuribayashi, Michihito; Hanada, Katsumi

2006-01-01

Dermatitis artefacta is one of a spectrum of factitious diseases etiologically responsible for skin lesions denied by patients. These factors often make it difficult to identify the causative agents of the condition. Herein, we report a case of bullous dermatitis artefacta in a 12-year-old girl, for which a deodorant spray was suspected as the probable cause. Pathological examination revealed subepidermal blistering with full-thickness necrosis of the epidermis, suggesting a thermo- or cryo-induced injury. Psychological testing demonstrated her immaturity and dependence. In searching for the causative agent, we suspected a deodorant spray as a blister-inducing agent. We succeeded in reproducing a similar blister lesion on the volunteer's healthy skin using the same spray. Psychiatric involvement significantly complicates the treatment of factitious diseases, including dermatitis artefacta. Cooperation among dermatologists, psychiatrists and the patient's family members is required for ensuring a favorable prognosis.

Mendelian randomization in nutritional epidemiology

PubMed Central

Qi, Lu

2013-01-01

Nutritional epidemiology aims to identify dietary and lifestyle causes for human diseases. Causality inference in nutritional epidemiology is largely based on evidence from studies of observational design, and may be distorted by unmeasured or residual confounding and reverse causation. Mendelian randomization is a recently developed methodology that combines genetic and classical epidemiological analysis to infer causality for environmental exposures, based on the principle of Mendel’s law of independent assortment. Mendelian randomization uses genetic variants as proxiesforenvironmentalexposuresofinterest.AssociationsderivedfromMendelian randomization analysis are less likely to be affected by confounding and reverse causation. During the past 5 years, a body of studies examined the causal effects of diet/lifestyle factors and biomarkers on a variety of diseases. The Mendelian randomization approach also holds considerable promise in the study of intrauterine influences on offspring health outcomes. However, the application of Mendelian randomization in nutritional epidemiology has some limitations. PMID:19674341

Crystallization and preliminary X-ray analysis of Leishmania major glyoxalase I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ariza, Antonio; Vickers, Tim J.; Greig, Neil

2005-08-01

The detoxification enzyme glyoxalase I from L. major has been crystallized. Preliminary molecular-replacement calculations indicate the presence of three glyoxalase I dimers in the asymmetric unit. Glyoxalase I (GLO1) is a putative drug target for trypanosomatids, which are pathogenic protozoa that include the causative agents of leishmaniasis. Significant sequence and functional differences between Leishmania major and human GLO1 suggest that it may make a suitable template for rational inhibitor design. L. major GLO1 was crystallized in two forms: the first is extremely disordered and does not diffract, while the second, an orthorhombic form, produces diffraction to 2.0 Å. Molecular-replacement calculationsmore » indicate that there are three GLO1 dimers in the asymmetric unit, which take up a helical arrangement with their molecular dyads arranged approximately perpendicular to the c axis. Further analysis of these data are under way.« less

Using an in vitro system for maintaining Varroa destructor mites on Apis mellifera hosts: Studies of mite longevity and feeding behavior

USDA-ARS?s Scientific Manuscript database

Varroa destructor mites (Vd) are ectoparasites of Apis mellifera honey bees, and the damage they inflict on hosts is a likely causative factor of recent poor honey bee colony performance. Much research has produced an arsenal of control agents against Vd, which have become resistant to many chemical...

Using "Spinal Shrinkage" as a Trigger for Motivating Students to Learn about Obesity and Adopt a Healthy Lifestyle

ERIC Educational Resources Information Center

Yar, Talay

2008-01-01

Obesity is a global problem; however, relatively little attention is directed toward preparing and inspiring students of medicine and allied medical sciences to address this serious matter. Students are not routinely exposed to the assessment methods for obesity, its overall prevalence, causative factors, short- and long-term consequences, and its…

Gender and General Strain Theory: A Comparison of Strains, Mediating, and Moderating Effects Explaining Three Types of Delinquency

ERIC Educational Resources Information Center

Moon, Byongook; Morash, Merry

2017-01-01

The present study of 659 Korean adolescents tests General Strain Theory's (GST) utility in explaining gender differences in delinquency causation. It models the effects of key strains, negative emotions, and a composite measure of several conditioning factors separately for boys and girls and for delinquency. Consistent with the theory, males and…

Deconstructing, Reconstructing, Preserving Paul E. Meehl's Legacy of Construct Validity

ERIC Educational Resources Information Center

Maher, Brendan A.; Gottesman, Irving I.

2005-01-01

The question of the status of cause-and-effect explanations of human behavior that posit physically existing causative factors and those that, on the other hand, posit hypothetical entities in the form of "useful fictions" has a long history. The influence of the works of Jeremy Bentham and Hans Vaihinger, as well as the later influence of Francis…

Identifying Molecular Culprits of Cervical Cancer Progression | Center for Cancer Research

Cancer.gov

Human papillomavirus (HPV) DNA is found in 99.7% of invasive cervical carcinomas, providing strong evidence that the virus is a causative agent in the development of this disease. However, most women who become infected with HPV do not develop invasive cervical lesions, indicating that additional exogenous or genetic factors may determine whether HPV preclinical lesions will

Farm Owners' Reluctance to Embrace Family Succession and the Implications for Extension: The Case of Family Farms in New Zealand

ERIC Educational Resources Information Center

Nuthall, P. L.; Old, K. M.

2017-01-01

Purpose: Despite the benefits of early planning for business succession, and plan implementation, many owners/managers fail to act expeditiously. Factors such as a reluctance to accept ageing, a concern over the risks involved and inappropriate objectives may be causative. This research moves towards explaining this reluctance and, consequently,…

Integrating Geo-Spatial Data for Regional Landslide Susceptibility Modeling in Consideration of Run-Out Signature

NASA Astrophysics Data System (ADS)

Lai, J.-S.; Tsai, F.; Chiang, S.-H.

2016-06-01

This study implements a data mining-based algorithm, the random forests classifier, with geo-spatial data to construct a regional and rainfall-induced landslide susceptibility model. The developed model also takes account of landslide regions (source, non-occurrence and run-out signatures) from the original landslide inventory in order to increase the reliability of the susceptibility modelling. A total of ten causative factors were collected and used in this study, including aspect, curvature, elevation, slope, faults, geology, NDVI (Normalized Difference Vegetation Index), rivers, roads and soil data. Consequently, this study transforms the landslide inventory and vector-based causative factors into the pixel-based format in order to overlay with other raster data for constructing the random forests based model. This study also uses original and edited topographic data in the analysis to understand their impacts to the susceptibility modeling. Experimental results demonstrate that after identifying the run-out signatures, the overall accuracy and Kappa coefficient have been reached to be become more than 85 % and 0.8, respectively. In addition, correcting unreasonable topographic feature of the digital terrain model also produces more reliable modelling results.

Raised incidence of ankylosing spondylitis among Inuit populations could be due to high HLA-B27 association and starch consumption.

PubMed

Rashid, Taha; Wilson, Clyde; Ebringer, Alan

2015-06-01

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis mainly affecting the spinal joints. It would appear that the most likely causative agent in the development of AS is an environmental factor in the genetically susceptible, HLA-B27 positive, individuals. Extensive data from several countries support the notion that Klebsiella pneumonia bacteria are the most likely culprit in the causation of AS. These microbes possess antigens which resemble HLA-B27 and spinal collagens. Increased intake of high-starch diet is directly proportional to the gut-associated bacterial load, especially in the large intestine, and among these microbial agents, Klebsiella is considered as one of the main constituting components. Therefore, a low-starch diet intake alongside the currently used medical therapeutic modalities could be beneficial in the management of patients with early AS. It is suggested that a change in the dietary habits from high protein, low-starch marine components to the Westernized high-starch diet among the Inuit peoples of Alaska and Canada could be considered as one of the main contributing factors in the increased prevalence of AS during the last few decades within this genetically unmixed native population.

Chronic kidney disease as a cardiovascular risk factor: lessons from kidney donors.

PubMed

Price, Anna M; Edwards, Nicola C; Hayer, Manvir K; Moody, William E; Steeds, Richard P; Ferro, Charles J; Townend, Jonathan N

2018-07-01

Chronic kidney disease (CKD) is a major risk factor for cardiovascular disease but is often associated with other risks such as diabetes and hypertension and can be both a cause and an effect of cardiovascular disease. Although epidemiologic data of an independent association of reduced glomerular filtration rate with cardiovascular risk are strong, causative mechanisms are unclear. Living kidney donors provide a useful model for assessing the "pure" effects of reduced kidney function on the cardiovascular system. After nephrectomy, the glomerular filtration rate ultimately falls by about one-third so many can be classified as having chronic kidney disease stages 2 or 3. This prompts concern based on the data showing an elevated cardiovascular risk with these stages of chronic kidney disease. However, initial data suggested no increase in adverse cardiovascular effects compared with control populations. Recent reports have shown a possible late increase in cardiovascular event rates and an early increase in left ventricular mass and markers of risk such as urate and albuminuria. The long-term significance of these small changes is unknown. More detailed and long-term research is needed to determine the natural history of these changes and their clinical significance. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Vegetarian Diet and Cardiometabolic Risk among Asian Indians in the United States.

PubMed

Misra, Ranjita; Balagopal, Padmini; Raj, Sudha; Patel, Thakor G

2018-01-01

Research studies have shown that plant-based diets confer cardiovascular and metabolic health benefits. Asian Indians (AIs) in the US (who have often followed plant-based diets) have elevated risk for chronic diseases such as diabetes, metabolic syndrome, and obesity suggesting ethnic vulnerability that imply genetic and/or lifestyle causative links. This study explored the association between this ethnic group and diabetes, obesity, and metabolic syndrome after controlling for demographics, acculturation, family history of diabetes, and lifestyle and clinical risk factors. The sample comprised of 1038 randomly selected adult AIs in seven US sites. Prevalence and metabolic syndrome was estimated, and obesity was calculated using the WHO Asian criteria. Multivariate analysis included multinomial logistic regression. The mean age and length of residency in the US were 47 and 18.5 years, respectively. The majority of respondents were vegetarians (62%) and educated. A vegetarian lifestyle was associated with females, food label users, respondents with poor/fair current health status, less acculturated, and those who reported their diet had not changed after coming to the US. Vegetarian status was a protective factor and lowered the risk for diabetes but not for metabolic syndrome and obesity in the regression model. Results provide a firm basis for educational programs.

A pan-European epidemiological study reveals honey bee colony survival depends on beekeeper education and disease control

PubMed Central

Jacques, Antoine; Laurent, Marion; Ribière-Chabert, Magali; Saussac, Mathilde; Bougeard, Stéphanie; Budge, Giles E.; Hendrikx, Pascal; Chauzat, Marie-Pierre

2017-01-01

Reports of honey bee population decline has spurred many national efforts to understand the extent of the problem and to identify causative or associated factors. However, our collective understanding of the factors has been hampered by a lack of joined up trans-national effort. Moreover, the impacts of beekeeper knowledge and beekeeping management practices have often been overlooked, despite honey bees being a managed pollinator. Here, we established a standardised active monitoring network for 5 798 apiaries over two consecutive years to quantify honey bee colony mortality across 17 European countries. Our data demonstrate that overwinter losses ranged between 2% and 32%, and that high summer losses were likely to follow high winter losses. Multivariate Poisson regression models revealed that hobbyist beekeepers with small apiaries and little experience in beekeeping had double the winter mortality rate when compared to professional beekeepers. Furthermore, honey bees kept by professional beekeepers never showed signs of disease, unlike apiaries from hobbyist beekeepers that had symptoms of bacterial infection and heavy Varroa infestation. Our data highlight beekeeper background and apicultural practices as major drivers of honey bee colony losses. The benefits of conducting trans-national monitoring schemes and improving beekeeper training are discussed. PMID:28278255

Vegetarian Diet and Cardiometabolic Risk among Asian Indians in the United States

PubMed Central

Balagopal, Padmini; Patel, Thakor G.

2018-01-01

Research studies have shown that plant-based diets confer cardiovascular and metabolic health benefits. Asian Indians (AIs) in the US (who have often followed plant-based diets) have elevated risk for chronic diseases such as diabetes, metabolic syndrome, and obesity suggesting ethnic vulnerability that imply genetic and/or lifestyle causative links. This study explored the association between this ethnic group and diabetes, obesity, and metabolic syndrome after controlling for demographics, acculturation, family history of diabetes, and lifestyle and clinical risk factors. The sample comprised of 1038 randomly selected adult AIs in seven US sites. Prevalence and metabolic syndrome was estimated, and obesity was calculated using the WHO Asian criteria. Multivariate analysis included multinomial logistic regression. The mean age and length of residency in the US were 47 and 18.5 years, respectively. The majority of respondents were vegetarians (62%) and educated. A vegetarian lifestyle was associated with females, food label users, respondents with poor/fair current health status, less acculturated, and those who reported their diet had not changed after coming to the US. Vegetarian status was a protective factor and lowered the risk for diabetes but not for metabolic syndrome and obesity in the regression model. Results provide a firm basis for educational programs. PMID:29670913

Edible Plants and Their Influence on the Gut Microbiome and Acne

PubMed Central

Clark, Ashley K.; Haas, Kelly N.; Sivamani, Raja K.

2017-01-01

Acne vulgaris affects most people at some point in their lives. Due to unclear etiology, likely with multiple factors, targeted and low-risk treatments have yet to be developed. In this review, we explore the multiple causes of acne and how plant-based foods and supplements can control these. The proposed causative factors include insulin resistance, sex hormone imbalances, inflammation and microbial dysbiosis. There is an emerging body of work on the human gut microbiome and how it mediates feedback between the foods we eat and our bodies. The gut microbiome is also an important mediator of inflammation in the gut and systemically. A low-glycemic load diet, one rich in plant fibers and low in processed foods, has been linked to an improvement in acne, possibly through gut changes or attenuation of insulin levels. Though there is much interest in the human microbiome, there is much more unknown, especially along the gut-skin axis. Collectively, the evidence suggests that approaches such as plant-based foods and supplements may be a viable alternative to the current first line standard of care for moderate acne, which typically includes antibiotics. Though patient compliance with major dietary changes is likely much lower than with medications, it is a treatment avenue that warrants further study and development. PMID:28513546

A mutli-omic systems approach to elucidating Yersinia virulence mechanisms

PubMed Central

Ansong, Charles; Schrimpe-Rutledge, Alexandra C.; Mitchell, Hugh; Chauhan, Sadhana; Jones, Marcus B.; Kim, Young-Mo; McAteer, Kathleen; Deatherage Kaiser, Brooke L.; Dubois, Jennifer L.; Brewer, Heather M.; Frank, Bryan C.; McDermott, Jason E.; Metz, Thomas O.; Peterson, Scott N.; Smith, Richard D.; Motin, Vladimir L.; Adkins, Joshua N.

2012-01-01

The underlying mechanisms that lead to dramatic differences between closely related pathogens are not always readily apparent. For example, the genomes of Yersinia pestis (YP) the causative agent of plague with a high mortality rate and Yersinia pseudotuberculosis (YPT) an enteric pathogen with a modest mortality rate are highly similar with some species specific differences; however the molecular causes of their distinct clinical outcomes remain poorly understood. In this study, a temporal multi-omic analysis of YP and YPT at physiologically relevant temperatures was performed to gain insights into how an acute and highly lethal bacterial pathogen, YP, differs from its less virulent progenitor, YPT. This analysis revealed higher gene and protein expression levels of conserved major virulence factors in YP relative to YPT, including the Yop virulon and the pH6 antigen. This suggests that adaptation in the regulatory architecture, in addition to the presence of unique genetic material, may contribute to the increased pathogenenicity of YP relative to YPT. Additionally, global transcriptome and proteome responses of YP and YPT revealed conserved post-transcriptional control of metabolism and the translational machinery including the modulation of glutamate levels in Yersiniae. Finally, the omics data was coupled with a computational network analysis, allowing an efficient prediction of novel Yersinia virulence factors based on gene and protein expression patterns. PMID:23147219

Clinical factors associated with shock in bacteremic UTI.

PubMed

Shigemura, Katsumi; Tanaka, Kazushi; Osawa, Kayo; Arakawa, Sochi; Miyake, Hideaki; Fujisawa, Masato

2013-06-01

Urinary tract infection (UTI) often causes bacteremia, resulting in shock. The purpose of this study is to investigate urological bacteremia and bacteremia shock cases and seek for the clinical factors associated with urological bacteremic shock. Seventy consecutive cases with bacteremia caused by UTI from the Department of Urology, Kobe University Hospital were studied. These cases were diagnosed from 2000 to 2010 and had full data available for analysis. We investigated the potential clinical factors associated with bacteremic shock (systolic blood pressure ≤ 90 mmHg with UTI), including: (1) the number of basal general diseases (such as diabetes, malignancy, immune diseases, heart diseases, liver diseases, and kidney diseases), (2) causative bacteria, (3) antibiotics and therapeutic intervention, (4) gram-negative bacteria, (5) resistance to imipenem (which is often used in this infection), and (6) serum white blood cell counts and C-reactive protein (CRP) at the time of diagnosis of bacteremic UTI. A total of 81 causative bacteria were isolated: 42 cases were gram-negative and 39 were gram-positive bacteria. In detail, Escherichia coli was the most common, followed by Methicillin-resistant Staphylococcus aureus. The comparison data revealed that urological bacteremic shock cases had significantly increased CRP (p < 0.001). Our univariate analyses showed indwelling urinary tract catheters (p = 0.02) as a significant clinical factor associated with urological bacteremic shock and multivariate analyses showed that the presence of indwelling urinary tract catheters before UTI was a significant clinical factor associated with urological bacteremic shock (p = 0.04). Indwelling urinary catheters before UTI and high CRP were clinical factors associated with urological bacteremic shock. This result should be considered during decision-making for UTI treatments in high risk cases or urological bacteremia cases.

Whiplash and the compensation hypothesis.

PubMed

Spearing, Natalie M; Connelly, Luke B

2011-12-01

Review article. To explain why the evidence that compensation-related factors lead to worse health outcomes is not compelling, either in general, or in the specific case of whiplash. There is a common view that compensation-related factors lead to worse health outcomes ("the compensation hypothesis"), despite the presence of important, and unresolved sources of bias. The empirical evidence on this question has ramifications for the design of compensation schemes. Using studies on whiplash, this article outlines the methodological problems that impede attempts to confirm or refute the compensation hypothesis. Compensation studies are prone to measurement bias, reverse causation bias, and selection bias. Errors in measurement are largely due to the latent nature of whiplash injuries and health itself, a lack of clarity over the unit of measurement (specific factors, or "compensation"), and a lack of appreciation for the heterogeneous qualities of compensation-related factors and schemes. There has been a failure to acknowledge and empirically address reverse causation bias, or the likelihood that poor health influences the decision to pursue compensation: it is unclear if compensation is a cause or a consequence of poor health, or both. Finally, unresolved selection bias (and hence, confounding) is evident in longitudinal studies and natural experiments. In both cases, between-group differences have not been addressed convincingly. The nature of the relationship between compensation-related factors and health is unclear. Current approaches to testing the compensation hypothesis are prone to several important sources of bias, which compromise the validity of their results. Methods that explicitly test the hypothesis and establish whether or not a causal relationship exists between compensation factors and prolonged whiplash symptoms are needed in future studies.

Environmental immune disruptors, inflammation and cancer risk.

PubMed

Thompson, Patricia A; Khatami, Mahin; Baglole, Carolyn J; Sun, Jun; Harris, Shelley A; Moon, Eun-Yi; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Brown, Dustin G; Colacci, Annamaria; Mondello, Chiara; Raju, Jayadev; Ryan, Elizabeth P; Woodrick, Jordan; Scovassi, A Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K; Amedei, Amedeo; Hamid, Roslida A; Lowe, Leroy; Guarnieri, Tiziana; Bisson, William H

2015-06-01

An emerging area in environmental toxicology is the role that chemicals and chemical mixtures have on the cells of the human immune system. This is an important area of research that has been most widely pursued in relation to autoimmune diseases and allergy/asthma as opposed to cancer causation. This is despite the well-recognized role that innate and adaptive immunity play as essential factors in tumorigenesis. Here, we review the role that the innate immune cells of inflammatory responses play in tumorigenesis. Focus is placed on the molecules and pathways that have been mechanistically linked with tumor-associated inflammation. Within the context of chemically induced disturbances in immune function as co-factors in carcinogenesis, the evidence linking environmental toxicant exposures with perturbation in the balance between pro- and anti-inflammatory responses is reviewed. Reported effects of bisphenol A, atrazine, phthalates and other common toxicants on molecular and cellular targets involved in tumor-associated inflammation (e.g. cyclooxygenase/prostaglandin E2, nuclear factor kappa B, nitric oxide synthesis, cytokines and chemokines) are presented as example chemically mediated target molecule perturbations relevant to cancer. Commentary on areas of additional research including the need for innovation and integration of systems biology approaches to the study of environmental exposures and cancer causation are presented. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Contrasting Causatives: A Minimalist Approach

ERIC Educational Resources Information Center

Tubino Blanco, Mercedes

2010-01-01

This dissertation explores the mechanisms behind the linguistic expression of causation in English, Hiaki (Uto-Aztecan) and Spanish. Pylkkanen's (2002, 2008) analysis of causatives as dependent on the parameterization of the functional head v[subscript CAUSE] is chosen as a point of departure. The studies conducted in this dissertation confirm…

Skin cancer: an overview of epidemiology and risk factors.

PubMed

Gordon, Randy

2013-08-01

To provide a general overview of malignant melanoma and non-melanoma skin cancer, with an emphasis on epidemiology, clinical presentation, and the multiple and varied risk factors associated with skin cancer. Peer-reviewed journal articles, government health reports, book chapters, and Web-based resources. Skin cancer is the most common carcinoma, affecting millions worldwide. Incidence is increasing yearly, making it a pre-eminent public health threat. Myriad factors increase the risk of skin cancer and may serve as important prognostic indicators for the disease. To provide nurses with a clearer understanding of the causative mechanisms of skin cancer and an improved awareness of the risk factors associated with the disease. Copyright © 2013 Elsevier Inc. All rights reserved.

A retrospective analysis of employee turnover in the health care setting.

PubMed

Bednar, B; McMullen, N

1998-02-01

Significant factors implicated in staff turnover include: variables in organizational structure; employee characteristics; needs and values, and the nature of tasks performed. This article will present the causative factors related to turnover and the conceptual models of the motivational theorists Maslow, Herzberg, Adams, and Mobley. No quantitative or qualitative research could be found on the potential causes of turnover in freestanding dialysis clinics. The staff turnover of a for-profit dialysis company for a 12 month period will be reported by job title, tenure, and level of job satisfaction.

42 CFR 81.22 - General guidelines for use of NIOSH-IREP.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GUIDELINES FOR DETERMINING PROBABILITY OF CAUSATION... Probability of Causation § 81.22 General guidelines for use of NIOSH-IREP. DOL will use procedures specified in the NIOSH-IREP Operating Guide to calculate probability of causation estimates under EEOICPA. The...

Modality and Causation in Serbian Dative Anticausatives: A Crosslinguistic Perspective

ERIC Educational Resources Information Center

Ilic, Tatjana

2013-01-01

In this dissertation I provide a principled, unified account of modality and causation in Serbian dative anticausatives using a typological, cognitive approach. This analysis is set within a larger claim that the causative and modal meanings crosslinguistically arise in the same morphosyntactic environments, indicating a shared conceptual base…

Health effects of urea formaldehyde foam insulation: evidence of causation.

PubMed Central

Norman, G R; Newhouse, M T

1986-01-01

Studies of health effects of urea formaldehyde foam insulation (UFFI) were critically reviewed by means of accepted rules for evidence of causation. Three categories of health effects were examined: reported symptoms, primarily of the upper respiratory tract, lower respiratory tract disease and cancer. Most of the studies purporting to demonstrate health effects of UFFI failed to meet minimal methodologic criteria for evidence of causation. Evidence from the adequate studies provides little support for the hypothesis of a causative role of UFFI in health problems. PMID:3512066

A computable expression of closure to efficient causation.

PubMed

Mossio, Matteo; Longo, Giuseppe; Stewart, John

2009-04-07

In this paper, we propose a mathematical expression of closure to efficient causation in terms of lambda-calculus; we argue that this opens up the perspective of developing principled computer simulations of systems closed to efficient causation in an appropriate programming language. An important implication of our formulation is that, by exhibiting an expression in lambda-calculus, which is a paradigmatic formalism for computability and programming, we show that there are no conceptual or principled problems in realizing a computer simulation or model of closure to efficient causation. We conclude with a brief discussion of the question whether closure to efficient causation captures all relevant properties of living systems. We suggest that it might not be the case, and that more complex definitions could indeed create crucial some obstacles to computability.

Incorporation of causative quantitative trait nucleotides in single-step GBLUP.

PubMed

Fragomeni, Breno O; Lourenco, Daniela A L; Masuda, Yutaka; Legarra, Andres; Misztal, Ignacy

2017-07-26

Much effort is put into identifying causative quantitative trait nucleotides (QTN) in animal breeding, empowered by the availability of dense single nucleotide polymorphism (SNP) information. Genomic selection using traditional SNP information is easily implemented for any number of genotyped individuals using single-step genomic best linear unbiased predictor (ssGBLUP) with the algorithm for proven and young (APY). Our aim was to investigate whether ssGBLUP is useful for genomic prediction when some or all QTN are known. Simulations included 180,000 animals across 11 generations. Phenotypes were available for all animals in generations 6 to 10. Genotypes for 60,000 SNPs across 10 chromosomes were available for 29,000 individuals. The genetic variance was fully accounted for by 100 or 1000 biallelic QTN. Raw genomic relationship matrices (GRM) were computed from (a) unweighted SNPs, (b) unweighted SNPs and causative QTN, (c) SNPs and causative QTN weighted with results obtained with genome-wide association studies, (d) unweighted SNPs and causative QTN with simulated weights, (e) only unweighted causative QTN, (f-h) as in (b-d) but using only the top 10% causative QTN, and (i) using only causative QTN with simulated weight. Predictions were computed by pedigree-based BLUP (PBLUP) and ssGBLUP. Raw GRM were blended with 1 or 5% of the numerator relationship matrix, or 1% of the identity matrix. Inverses of GRM were obtained directly or with APY. Accuracy of breeding values for 5000 genotyped animals in the last generation with PBLUP was 0.32, and for ssGBLUP it increased to 0.49 with an unweighted GRM, 0.53 after adding unweighted QTN, 0.63 when QTN weights were estimated, and 0.89 when QTN weights were based on true effects known from the simulation. When the GRM was constructed from causative QTN only, accuracy was 0.95 and 0.99 with blending at 5 and 1%, respectively. Accuracies simulating 1000 QTN were generally lower, with a similar trend. Accuracies using the APY inverse were equal or higher than those with a regular inverse. Single-step GBLUP can account for causative QTN via a weighted GRM. Accuracy gains are maximum when variances of causative QTN are known and blending is at 1%.

A critical review of food-associated factors proposed in the etiology of feline hyperthyroidism.

PubMed

van Hoek, Ingrid; Hesta, Myriam; Biourge, Vincent

2015-10-01

Since the first description of feline hyperthyroidism (HT) in 1979, several studies have been undertaken to define the etiology of the disease. Epidemiologic studies, after investigating non-food- and food-associated factors, suggest a multifactorial etiology. However, in the absence of prospective cohort studies that can confirm a cause-and-effect relationship between HT and associated risk factors, no causative factor for HT has been identified to date. Feline HT resembles toxic nodular goiter in humans, with autonomously functioning upregulated iodide uptake systems. Contribution of the diet to HT development remains controversial. The purpose of this paper is to review critically the reported food-associated risk factors for HT. © ISFM and AAFP 2014.

A Heated Debate: Theoretical Perspectives of Sexual Exploitation and Sex Work

PubMed Central

Gerassi, Lara

2015-01-01

The theoretical and often political framework of sexual exploitation and sex work among women is widely and enthusiastically debated among academic and legal scholars alike. The majority of theoretical literature in this area focuses on the macro perspective, while the micro-level perspective as to theory and causation remains sparse. This article provides a comprehensive overview of the philosophical, legal, and political perspectives pertaining to sexual exploitation of women and girls while addressing the subsequent controversies in the field. PMID:26834302

A text analysis of the poems of Sylvia Plath.

PubMed

Lester, David; McSwain, Stephanie

2011-08-01

Changes in the words used in the poems of Sylvia Plath were examined using the Linguistic Inquiry and Word Count, a computer program for analyzing the content of texts. Major changes in the content of her poems were observed over the course of Plath's career, as well as in the final year of her life. As the time of her suicide came closer, words expressing positive emotions became more frequent, while words concerned with causation and insight became less frequent.

Geography, ecology and emerging infectious diseases.

PubMed

Mayer, J D

2000-04-01

Emerging infectious diseases are the focus of increased attention and even alarm in the scholarly and popular literature. The emergence of new diseases and the resurgence of older and previously recognized infectious diseases both in developing and developed country poses challenges for understanding the ecological web of causation, including social, economic, environmental and biological components. This paper is a synthesis of the major characteristics of emerging diseases, in an interdisciplinary context. Political ecology is one framework for analysis that is promising in developing a modified ecology of disease.

A novel frameshift mutation of CHD7 in a Japanese patient with CHARGE syndrome

PubMed Central

Kohmoto, Tomohiro; Shono, Miki; Naruto, Takuya; Watanabe, Miki; Suga, Ken-ichi; Nakagawa, Ryuji; Kagami, Shoji; Masuda, Kiyoshi; Imoto, Issei

2016-01-01

CHARGE syndrome is a rare autosomal dominant developmental disorder involving multiple organs. CHD7 is a major causative gene of CHARGE syndrome. We performed targeted-exome sequencing using a next-generation sequencer for molecular diagnosis of a 4-month-old male patient who was clinically suspected to have CHARGE syndrome, and report a novel monoallelic mutation in CHD7, NM_017780.3(CHD7_v001):c.2966del causing a reading frameshift [p.(Cys989Serfs*3)]. PMID:27081570

A novel frameshift mutation of CHD7 in a Japanese patient with CHARGE syndrome.

PubMed

Kohmoto, Tomohiro; Shono, Miki; Naruto, Takuya; Watanabe, Miki; Suga, Ken-Ichi; Nakagawa, Ryuji; Kagami, Shoji; Masuda, Kiyoshi; Imoto, Issei

2016-01-01

CHARGE syndrome is a rare autosomal dominant developmental disorder involving multiple organs. CHD7 is a major causative gene of CHARGE syndrome. We performed targeted-exome sequencing using a next-generation sequencer for molecular diagnosis of a 4-month-old male patient who was clinically suspected to have CHARGE syndrome, and report a novel monoallelic mutation in CHD7, NM_017780.3(CHD7_v001):c.2966del causing a reading frameshift [p.(Cys989Serfs*3)].

Carpal tunnel syndrome: the role of occupational factors.

PubMed

Palmer, Keith T

2011-02-01

Carpal tunnel syndrome (CTS) is a fairly common condition in working-aged people, sometimes caused by physical occupational activities, such as repeated and forceful movements of the hand and wrist or use of hand-held, powered, vibratory tools. Symptoms may be prevented or alleviated by primary control measures at work, and some cases of disease are compensable. Following a general description of the disorder, its epidemiology and some of the difficulties surrounding diagnosis, this review focusses on the role of occupational factors in causation of CTS and factors that can mitigate risk. Areas of uncertainty, debate and research interest are emphasised where relevant. Copyright © 2011 Elsevier Ltd. All rights reserved.

Driver behavior in car-to-pedestrian incidents: An application of the Driving Reliability and Error Analysis Method (DREAM).

PubMed

Habibovic, Azra; Tivesten, Emma; Uchida, Nobuyuki; Bärgman, Jonas; Ljung Aust, Mikael

2013-01-01

To develop relevant road safety countermeasures, it is necessary to first obtain an in-depth understanding of how and why safety-critical situations such as incidents, near-crashes, and crashes occur. Video-recordings from naturalistic driving studies provide detailed information on events and circumstances prior to such situations that is difficult to obtain from traditional crash investigations, at least when it comes to the observable driver behavior. This study analyzed causation in 90 video-recordings of car-to-pedestrian incidents captured by onboard cameras in a naturalistic driving study in Japan. The Driving Reliability and Error Analysis Method (DREAM) was modified and used to identify contributing factors and causation patterns in these incidents. Two main causation patterns were found. In intersections, drivers failed to recognize the presence of the conflict pedestrian due to visual obstructions and/or because their attention was allocated towards something other than the conflict pedestrian. In incidents away from intersections, this pattern reoccurred along with another pattern showing that pedestrians often behaved in unexpected ways. These patterns indicate that an interactive advanced driver assistance system (ADAS) able to redirect the driver's attention could have averted many of the intersection incidents, while autonomous systems may be needed away from intersections. Cooperative ADAS may be needed to address issues raised by visual obstructions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Development and evaluation of a Naïve Bayesian model for coding causation of workers' compensation claims.

PubMed

Bertke, S J; Meyers, A R; Wurzelbacher, S J; Bell, J; Lampl, M L; Robins, D

2012-12-01

Tracking and trending rates of injuries and illnesses classified as musculoskeletal disorders caused by ergonomic risk factors such as overexertion and repetitive motion (MSDs) and slips, trips, or falls (STFs) in different industry sectors is of high interest to many researchers. Unfortunately, identifying the cause of injuries and illnesses in large datasets such as workers' compensation systems often requires reading and coding the free form accident text narrative for potentially millions of records. To alleviate the need for manual coding, this paper describes and evaluates a computer auto-coding algorithm that demonstrated the ability to code millions of claims quickly and accurately by learning from a set of previously manually coded claims. The auto-coding program was able to code claims as a musculoskeletal disorders, STF or other with approximately 90% accuracy. The program developed and discussed in this paper provides an accurate and efficient method for identifying the causation of workers' compensation claims as a STF or MSD in a large database based on the unstructured text narrative and resulting injury diagnoses. The program coded thousands of claims in minutes. The method described in this paper can be used by researchers and practitioners to relieve the manual burden of reading and identifying the causation of claims as a STF or MSD. Furthermore, the method can be easily generalized to code/classify other unstructured text narratives. Published by Elsevier Ltd.

Dynamics and impact of homologous recombination on the evolution of Legionella pneumophila.

PubMed

David, Sophia; Sánchez-Busó, Leonor; Harris, Simon R; Marttinen, Pekka; Rusniok, Christophe; Buchrieser, Carmen; Harrison, Timothy G; Parkhill, Julian

2017-06-01

Legionella pneumophila is an environmental bacterium and the causative agent of Legionnaires' disease. Previous genomic studies have shown that recombination accounts for a high proportion (>96%) of diversity within several major disease-associated sequence types (STs) of L. pneumophila. This suggests that recombination represents a potentially important force shaping adaptation and virulence. Despite this, little is known about the biological effects of recombination in L. pneumophila, particularly with regards to homologous recombination (whereby genes are replaced with alternative allelic variants). Using newly available population genomic data, we have disentangled events arising from homologous and non-homologous recombination in six major disease-associated STs of L. pneumophila (subsp. pneumophila), and subsequently performed a detailed characterisation of the dynamics and impact of homologous recombination. We identified genomic "hotspots" of homologous recombination that include regions containing outer membrane proteins, the lipopolysaccharide (LPS) region and Dot/Icm effectors, which provide interesting clues to the selection pressures faced by L. pneumophila. Inference of the origin of the recombined regions showed that isolates have most frequently imported DNA from isolates belonging to their own clade, but also occasionally from other major clades of the same subspecies. This supports the hypothesis that the possibility for horizontal exchange of new adaptations between major clades of the subspecies may have been a critical factor in the recent emergence of several clinically important STs from diverse genomic backgrounds. However, acquisition of recombined regions from another subspecies, L. pneumophila subsp. fraseri, was rarely observed, suggesting the existence of a recombination barrier and/or the possibility of ongoing speciation between the two subspecies. Finally, we suggest that multi-fragment recombination may occur in L. pneumophila, whereby multiple non-contiguous segments that originate from the same molecule of donor DNA are imported into a recipient genome during a single episode of recombination.

Stroke in Saudi children. Epidemiology, clinical features and risk factors.

PubMed

Salih, Mustafa A; Abdel-Gader, Abdel-Galil M; Al-Jarallah, Ahmed A; Kentab, Amal Y; Alorainy, Ibrahim A; Hassan, Hamdy H; Bahakim, Hassan M; Kurbaan, Khadija M; Zahraa, Jihad N; Al-Nasser, Mohammed N; Nasir, Ali A; Khoja, Waleed A; Kabiraj, Mohammad M

2006-03-01

To describe the epidemiology and clinical features of stroke in a prospective and retrospective cohort of Saudi children and ascertain the causes, pathogenesis, and risk factors. The Retrospective Study Group (RSG) included children with stroke who were evaluated at the Division of Pediatric Neurology, or admitted to King Khalid University Hospital, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia during the period July 1992 to February 2001. The Prospective Study Group (PSG) included those seen between February 2001 and March 2003. During the combined study periods of 10 years and 7 months, 117 children (61 males and 56 females, aged one month-12 years) were evaluated; the majority (89%) of these were Saudis. The calculated annual hospital frequency rate of stroke was 27.1/100,000 of the pediatric (1 month-12 years) population. The mean age at onset of the initial stroke in the 104 Saudi children was 27.1 months (SD = 39.3 months) and median was 6 months. Ischemic strokes accounted for the majority of cases (76%). Large-vessel infarcts (LVI, 51.9%) were more common than small-vessel lacunar lesions (SVLL, 19.2%). Five patients (4.8%) had combined LVI and SVLL. Intracranial hemorrhage was less common (18.2%), whereas sinovenous thrombosis was diagnosed in 6 (5.8%) patients. A major risk factor was identified in 94 of 104 (89.4%) Saudi children. Significantly more hematologic disorders and coagulopathies were identified in the PSG compared to the RSG (p=0.001), reflecting a better yield following introduction of more comprehensive hematologic and coagulation laboratory tests during the prospective study period. Hematologic disorders were the most common risk factor (46.2%), presumed perinatal ischemic cerebral injury was a risk factor in 23 children (22.1%) and infectious and inflammatory disorders of the circulatory system in 18 (17.3%). Congenital and genetic cerebrovascular anomalies were the underlying cause in 7 patients (6.7%) and cardiac diseases in 6 (5.8%). Six patients (5.8%) had moyamoya syndrome, which was associated with another disease in all of them. Inherited metabolic disorders (3.8%) included 3 children with Leigh syndrome and a 29-month-old girl with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. Systemic vascular disease was a risk factor in 3 children (2.9%) including 2 who had hypernatremic dehydration; and post-traumatic arterial dissection was causative in 3 cases (2.9%). Several patients had multiple risk factors, whereas no risk factor could be identified in 11 (10.6%). Due to the high prevalence and importance of multiple risk factors, a comprehensive investigation, including hematologic, neuroimaging and metabolic studies should be considered in every child with stroke.

Reducing Cumulative Arm Overuse Injuries in Young Throwers.

PubMed

Schlechter, John A

2016-01-01

As year-round participation in youth sports continues to increase, health care practitioners treating child and adolescent athletes will commonly see injuries that are secondary to overuse. Starting with a clinical vignette, this article describes proximal humeral physeal injuries in youth throwers, examines causative factors, reviews common therapeutic modalities, and focuses on preventive measures aimed at reducing such cumulative arm overuse injuries. Copyright 2016, SLACK Incorporated.

Etiology and sequelae of root resorption.

PubMed

Vlaskalic, V; Boyd, R L; Baumrind, S

1998-06-01

This article reviews the current status of investigation into apical root resorption within the context of orthodontic treatment. Treatment and patient factors that have traditionally been investigated are discussed, along with the results of current research in this area. The need for rethinking traditional research strategies in the quest for identifying both control and causative mechanisms is explored. Finally, proposals for key areas of future interest are highlighted.

The Effects of Academic and Interpersonal Stress on Dating Violence among College Students: A Test of Classical Strain Theory

ERIC Educational Resources Information Center

Mason, Brandon; Smithey, Martha

2012-01-01

This study examines Merton's Classical Strain Theory (1938) as a causative factor in intimate partner violence among college students. We theorize that college students experience general life strain and cumulative strain as they pursue the goal of a college degree. We test this strain on the likelihood of using intimate partner violence. Strain…

Red River of the North, Reconnaissance Report: Bois de Sioux-Mustinka Rivers Subbasin.

DTIC Science & Technology

1980-12-01

24 Climate . . . . . . . . . . . . . . . . . . . . 24 WaeorSy pp.................... 28 Water Supply . . .• 28 Cultural Elements . . . . 32...favored rough fish populations. Additionally, algal blooms and high turbidities have tended to limit habitat and spawning sites for game and pan fish...point where algal blooms occur in summer and early fall. Causative factors include (1) nutrients in runoff from surrounding farmlands; (2) run- off from

Colony failure linked to low sperm viability in honey bee (Apis mellifera) queens and an exploration of potential causative factors

USDA-ARS?s Scientific Manuscript database

Queen health is closely linked to colony performance in honey bees as a single queen is normally responsible for all egg laying and brood production within the colony. In the U. S. in recent years, queens have been failing at a high rate; with 50% or greater of queens replaced in colonies within 6 m...

Radiation-induced schwannomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rubinstein, A.B.; Reichenthal, E.; Borohov, H.

1989-06-01

The histopathology and clinical course of three patients with schwannomas of the brain and high cervical cord after therapeutic irradiation for intracranial malignancy and for ringworm of the scalp are described. Earlier reports in the literature indicated that radiation of the scalp may induce tumors in the head and neck. It is therefore suggested that therapeutic irradiation in these instances was a causative factor in the genesis of these tumors.

A Potential for Violent Injury: Guns and Knives in the Schools. Oregon Health Trends, Series No. 56.

ERIC Educational Resources Information Center

Hopkins, David

This report focuses on the causative factors of violence in school children. It summarizes information about the demographic and mental health characteristics of students who carry weapons to school and includes comments from students on the reasons why they carry them, as well as what the research says. Results of the 1999 Youth Risk Behavior…

Contact dermatitis to training toilet seat (potty seat dermatitis).

PubMed

Dorfman, Claire O; Barros, Mark A; Zaenglein, Andrea L

2018-05-29

Allergic contact dermatitis from various components of toilet seats has been well described. We report a case of a young boy presenting with an atypical pattern of dermatitis who was found to be allergic to his training toilet seat. This case highlights the importance of recognizing this diagnosis and the role of potty seats as the causative factor. © 2018 Wiley Periodicals, Inc.

A review of best management practices and the mitigation of stream-breeding salamanders in the eastern deciduous forest

Treesearch

Thomas A. Maigret; John J. Cox

2014-01-01

Timber harvest has been implicated as a causative factor in the decline of amphibian populations and diversity in many areas of the world. The adoption of best management practices (BMPs) is intended to minimize the impacts of timber harvest on the biotic community, including amphibians and their habitat requirements. Herein, we synthesize the current scientific...

Conducting a surveillance problem analysis on poor feedback from Reference Laboratory, Liberia, February 2016.

PubMed

Frimpong, Joseph Asamoah; Amo-Addae, Maame Pokuah; Adewuyi, Peter Adebayo; Hall, Casey Daniel; Park, Meeyoung Mattie; Nagbe, Thomas Knue

2017-01-01

The laboratory plays a major role in surveillance, including confirming the start and end of an outbreak. Knowing the causative agent for an outbreak informs the development of response strategies and management plans for a public health event. However, issues and challenges may arise that limit the effectiveness or efficiency of laboratories in surveillance. This case study applies a systematic approach to analyse gaps in laboratory surveillance, thereby improving the ability to mitigate these gaps. Although this case study concentrates on factors resulting in poor feedback from the laboratory, practise of this general approach to problem analysis will confer skills required in analysing most public health issues. This case study was developed based on a report submitted by the district surveillance officer in Grand Bassa County, Liberia, as a resident of the Liberian Frontline Field Epidemiology Training Program in 2016. This case study will serve as a training tool to reinforce lectures on surveillance problem analysis using the fishbone approach. It is designed for public health training in a classroom setting and can be completed within 2 hours 30 minutes.

Health-Related Quality of Life and Quality of Sexual Life in Obese Subjects

PubMed Central

Di Lazzaro, Luca; Pinto, Alessandro; Migliaccio, Silvia; Lenzi, Andrea; Donini, Lorenzo M.

2014-01-01

The increased prevalence of obesity represents, currently, one of the major public health issues, due to its consequences on physical and psychological health status as well as on the psychosocial functioning. As defined by the World Health Organization, sexual health is “a state of physical, emotional, mental, and social well-being in relation to sexuality.” The aim of the present study was to explore the relationship between sexual life in obese subjects and quality of life, psychological status, and disability. Methods. 95 obese subjects were recruited from June 2012 to February 2013 and underwent physical examination and measures for the assessment of quality of life, sexual life, psychological status, and disability. Results. In obese subjects sexual life was related to gender, age, psychological status, disability, and quality of life. Conclusion. As obesity is a multifactorial disease, and is accompanied by multiple comorbidities, it is difficult to identify a single causative factor responsible for the impairment of sexual life in obese subjects; thus, a thorough, multidimensional evaluation including sexual function assessment should be performed in obese people. PMID:24707290

Loss of Actin-Based Motility Impairs Ectromelia Virus Release In Vitro but Is Not Critical to Spread In Vivo.

PubMed

Duncan, Melanie Laura; Horsington, Jacquelyn; Eldi, Preethi; Al Rumaih, Zahrah; Karupiah, Gunasegaran; Newsome, Timothy P

2018-03-05

Ectromelia virus (ECTV) is an orthopoxvirus and the causative agent of mousepox. Like other poxviruses such as variola virus (agent of smallpox), monkeypox virus and vaccinia virus (the live vaccine for smallpox), ECTV promotes actin-nucleation at the surface of infected cells during virus release. Homologs of the viral protein A36 mediate this function through phosphorylation of one or two tyrosine residues that ultimately recruit the cellular Arp2/3 actin-nucleating complex. A36 also functions in the intracellular trafficking of virus mediated by kinesin-1. Here, we describe the generation of a recombinant ECTV that is specifically disrupted in actin-based motility allowing us to examine the role of this transport step in vivo for the first time. We show that actin-based motility has a critical role in promoting the release of virus from infected cells in vitro but plays a minor role in virus spread in vivo. It is likely that loss of microtubule-dependent transport is a major factor for the attenuation observed when A36R is deleted.

DNA from human polyomaviruses, TSPyV, MWPyV, HPyV6, 7 and 9 was not detected in primary mucosal melanomas.

PubMed

Ramqvist, Torbjörn; Nordfors, Cecilia; Dalianis, Tina; Ragnarsson-Olding, Boel

2014-02-01

Mucosal melanomas arise in non UV-light exposed areas and causative factors are yet unknown. Human polyomaviruses (HPyVs) are rapidly increasing in numbers and are potentially oncogenic, as has been established for MCPyV in Merkel cell carcinoma, an unusual skin cancer type. The aim of the present study was to investigate the association between TSPyV, MWPyV, HPyV6, 7 and 9 and mucosal melanoma. Fifty-five mucosal melanomas, were analyzed by a Luminex assay, for the presence of 10 HPyVs (BKPyV, JCPyV, KIPyV, WUPyV, TSPyV, MWPyV, HPyV6, 7 and 9) and two primate viruses (SV40 and LPyV). In 37 samples the DNA quality was satisfactory for analysis. However, none of the samples analyzed were positive for any of the examined viruses. None of the above-analyzed HPyVs were detected in mucosal melanoma samples, and they are for this reason unlikely to play a major role in the development of this tumor type.

Saccharomyces boulardii expresses neuraminidase activity selective for α2,3-linked sialic acid that decreases Helicobacter pylori adhesion to host cells.

PubMed

Sakarya, Serhan; Gunay, Necati

2014-10-01

Helicobacter pylori is a major causative agent of gastritis and peptic ulcer disease and is an established risk factor for gastric malignancy. Antibiotic combination therapy can eradicate H. pylori. As these same regimens can evoke adverse effects and resistance, new alternative therapies or adjunctive treatments are needed. A probiotic approach may provide a novel strategy for H. pylori treatment. In the current study, two probiotic bacteria, Lactobacillus acidophilus and Lactobacillus reuteri, and a probiotic yeast, Saccharomyces boulardii, were evaluated for their ability to influence H. pylori viability, adherence to gastric and duodenal cells, as well as the effect of S. boulardii on cell surface expression of sialic acid. Our results indicate that S. boulardii contains neuraminidase activity selective for α(2-3)-linked sialic acid. This neuraminidase activity removes surface α(2-3)-linked sialic acid, the ligand for the sialic acid-binding H. pylori adhesin, which in turn, inhibits H. pylori adherence to duodenal epithelial cells. © 2014 APMIS. Published by John Wiley & Sons Ltd.

Candida Species Biofilms’ Antifungal Resistance

PubMed Central

Silva, Sónia; Rodrigues, Célia F.; Araújo, Daniela; Rodrigues, Maria Elisa; Henriques, Mariana

2017-01-01

Candida infections (candidiasis) are the most prevalent opportunistic fungal infection on humans and, as such, a major public health problem. In recent decades, candidiasis has been associated to Candida species other than Candida albicans. Moreover, biofilms have been considered the most prevalent growth form of Candida cells and a strong causative agent of the intensification of antifungal resistance. As yet, no specific resistance factor has been identified as the sole responsible for the increased recalcitrance to antifungal agents exhibited by biofilms. Instead, biofilm antifungal resistance is a complex multifactorial phenomenon, which still remains to be fully elucidated and understood. The different mechanisms, which may be responsible for the intrinsic resistance of Candida species biofilms, include the high density of cells within the biofilm, the growth and nutrient limitation, the effects of the biofilm matrix, the presence of persister cells, the antifungal resistance gene expression and the increase of sterols on the membrane of biofilm cells. Thus, this review intends to provide information on the recent advances about Candida species biofilm antifungal resistance and its implication on intensification of the candidiasis. PMID:29371527

[ON THE ORIGIN OF HYPERVIRULENCE OF THE CAUSATIVE AGENT OF PLAGUE].

PubMed

Anisimov, N V; Kislichkina, A A; Platonov, M E; Evseeva, V V; Kadnikova, L A; Lipatnikova, N A; Bogun, A G; Dentovskaya, S V; Anisimov, A P

2016-01-01

The attempt to combine Yersinia pseudotuberculosis and Yersinia pestis into one species has been unsupported by microbiologists due to the specific features of the epidemiology and clinical presentations of their induced diseases and to basic differences in their virulence. Pseudotuberculosis is predominantly a relatively mild human intestinal infection transmitted through contaminated food and plague is an acute generalized disease with high mortality, which is most frequently transmitted by the bites of infected fleas. Y. pestis hypervirulence, the ability of single bacteria to ensure the development of predagonal bacteriemia in rodents, which is sufficient to contaminate the fleas, is one of the main events during pathogen adaptation to a new ecological niche. By analyzing the data of molecular typing of the representative kits of naturally occurring Y. pestis isolates, the authois consider the issues of formation of intraspecies groups with universal hypervirulence, as well as biovars that are highly virulent only to their major host. A strategy for searching for selective virulence factors, the potential molecular targets for vaccination and etiotropic treatment of plague, is discussed.

Layer 2/3 pyramidal cells in the medial prefrontal cortex moderate stress induced depressive behaviors

PubMed Central

Shrestha, Prerana; Mousa, Awni; Heintz, Nathaniel

2015-01-01

Major depressive disorder (MDD) is a prevalent illness that can be precipitated by acute or chronic stress. Studies of patients with Wolfram syndrome and carriers have identified Wfs1 mutations as causative for MDD. The medial prefrontal cortex (mPFC) is known to be involved in depression and behavioral resilience, although the cell types and circuits in the mPFC that moderate depressive behaviors in response to stress have not been determined. Here, we report that deletion of Wfs1 from layer 2/3 pyramidal cells impairs the ability of the mPFC to suppress stress-induced depressive behaviors, and results in hyperactivation of the hypothalamic–pituitary–adrenal axis and altered accumulation of important growth and neurotrophic factors. Our data identify superficial layer 2/3 pyramidal cells as critical for moderation of stress in the context of depressive behaviors and suggest that dysfunction in these cells may contribute to the clinical relationship between stress and depression. DOI: http://dx.doi.org/10.7554/eLife.08752.001 PMID:26371510

Ureaplasma-associated prenatal, perinatal, and neonatal morbidities.

PubMed

Silwedel, Christine; Speer, Christian P; Glaser, Kirsten

2017-11-01

Ureaplasma species (spp.) have been acknowledged as major causative pathogens in chorioamnionitis and prematurity, but may also contribute to key morbidities in preterm infants. Several epidemiological and experimental data indicate an association of neonatal Ureaplasma colonization and/or infection with bronchopulmonary dysplasia. Furthermore, a potential causal relation with other inflammation-induced morbidities, such as intraventricular hemorrhage, white matter injury, necrotizing enterocolitis, and retinopathy of prematurity, has been debated. Areas covered: This review will summarize current knowledge on the role of Ureaplasma spp. in prenatal, perinatal, and neonatal morbidities, while furthermore examining mutual underlying mechanisms. We try to elaborate who is at particular risk of Ureaplasma-induced inflammation and subsequent secondary morbidities. Expert commentary: Most likely by complex interactions with immunological processes, Ureaplasma spp. can induce pro-inflammation, but may also downregulate the immune system. Tissue damage, possibly causing the above mentioned complications, is likely to result from both ways: either directly cytokine-associated, or due to a higher host vulnerability to secondary impact factors. These events are very likely to begin in prenatal stages, with the most immature preterm infants being most susceptible and at highest risk.

Human cathelicidin peptide LL37 inhibits both attachment capability and biofilm formation of Staphylococcus epidermidis.

PubMed

Hell, E; Giske, C G; Nelson, A; Römling, U; Marchini, G

2010-02-01

The aim of this work was to investigate the possible effect of human cathelicidin antimicrobial peptide LL37 on biofilm formation of Staphylococcus epidermidis, a major causative agent of indwelling device-related infections. We performed initial attachment assay and biofilm formation solid surface assay in microtitre plates, as well as growth experiment in liquid medium using laboratory strain Staph. epidermidis ATCC35984. We found that already a low concentration of the peptide LL37 (1 mg l(-1)) significantly decreased both the attachment of bacteria to the surface and also the biofilm mass. No growth inhibition was observed even at 16 mg l(-1) concentration of LL37, indicating a direct effect of the peptide on biofilm production. As biofilm protects bacteria during infections in humans and allows their survival in a hostile environment, inhibition of biofilm formation by LL37 may have a key role to prevent bacterial colonization on indwelling devices. Our findings suggest that this host defence factor can be a potential candidate in prevention and treatment strategies of Staph. epidermidis infections in humans.

Magnesium in drinking water - a case for prevention?

PubMed

Rylander, Ragnar

2014-03-01

Studies in many countries have demonstrated a relationship between drinking water mineral content and the risk of death in cardiovascular disease (CVD). Particularly strong relationships have been found for magnesium and it has been suggested that magnesium be added to drinking water. The aim of this article is to evaluate the validity of this suggestion by reviewing information on possible causative agents. Major epidemiological studies on the drinking water content of calcium, magnesium, and hardness were analysed regarding exposure specificity, confounding factors, dose-response relationships and biological plausibility. Intervention experiments were analysed. The risk of death in CVD was related to the content of Ca, Mg and HCO(3-). The data demonstrate that Ca and Mg need to be considered together, and that HCO(3-) could play a role by intervening with the body acid load. There is no evidence to justify the addition of magnesium only to drinking water for preventive purposes. The data suggest that Ca and Mg could be administered together but no data are available regarding the relative proportions for an optimal effect.

Loss of Actin-Based Motility Impairs Ectromelia Virus Release In Vitro but Is Not Critical to Spread In Vivo

PubMed Central

Duncan, Melanie Laura; Horsington, Jacquelyn; Eldi, Preethi; Al Rumaih, Zahrah; Karupiah, Gunasegaran

2018-01-01

Ectromelia virus (ECTV) is an orthopoxvirus and the causative agent of mousepox. Like other poxviruses such as variola virus (agent of smallpox), monkeypox virus and vaccinia virus (the live vaccine for smallpox), ECTV promotes actin-nucleation at the surface of infected cells during virus release. Homologs of the viral protein A36 mediate this function through phosphorylation of one or two tyrosine residues that ultimately recruit the cellular Arp2/3 actin-nucleating complex. A36 also functions in the intracellular trafficking of virus mediated by kinesin-1. Here, we describe the generation of a recombinant ECTV that is specifically disrupted in actin-based motility allowing us to examine the role of this transport step in vivo for the first time. We show that actin-based motility has a critical role in promoting the release of virus from infected cells in vitro but plays a minor role in virus spread in vivo. It is likely that loss of microtubule-dependent transport is a major factor for the attenuation observed when A36R is deleted. PMID:29510577

[Fegelers syndrome, acquired port-wine stain or acquired capillary malformation: three cases and a literature review].

PubMed

Freysz, M; Cribier, B; Lipsker, D

2013-05-01

Port-wine stains or capillary malformations are generally congenital. Very few cases of acquired port-wine stains in adults have been described, and these occur particularly after trauma. We report three cases of acquired port-wine stains and we performed a review of the literature using the keywords "port-wine stain", "capillary malformation", "angioma" and "acquired" in the Medline database PubMed. All relevant articles were included. Two male patients and one female patient consulted for one or more angiomatous lesions, located respectively on the upper rear part of the right thigh (case 1), the left leg (case 2) and the right side of the face, skull and chest (case 3). Each patient's skin biopsy was consistent with port-wine stain. The three patients asserted the acquired nature of the lesions: the male patients were respectively 17 and 38 years old, and the female patient was 11 years old. No causative factors were evident preceding the lesion, and there was no family history of port-wine stain. The topography was systematic in patients 2 and 3. The lesions were light red in patient 1, dark red in patient 2 and pale pink in patient 3. The remainder of the physical examination was unremarkable, except for benign angiokeratoma of the scrotum in case 1 and pigmented leucoderma-type macules in case 3. LITERATURE RESULTS: Sixty-six cases of acquired port-wine stains were reported in the literature. The average age was 25 years (3-69) with a sex-ratio of 0.88. Generally, no causative factor was given. However, trauma (30.5%), estrogenic impregnation (16.5%), and more rarely, medication, solar damage, frostbite, cluster headache, herpes zoster and acoustic neuroma were reported as causatives factors. Acquired port-wine stain is rare. Although often idiopathic, it can result from spinal trauma, which must be explored if suggested by the history. In our series, the clinical presentation suggested a latent congenital vascular malformation of late onset, in particular in patients 2 and 3, because of the segmental distribution. Copyright © 2013. Published by Elsevier Masson SAS.

The Development of the Causative Construction in Persian Child Language

ERIC Educational Resources Information Center

Family, Neiloufar; Allen, Shanley E. M.

2015-01-01

The acquisition of systematic patterns and exceptions in different languages can be readily examined using the causative construction. Persian allows four types of causative structures, including one productive multiword structure (i.e. the light verb construction). In this study, we examine the development of all four structures in Persian child…

Landmarks in the history of cancer epidemiology.

PubMed

Greenwald, Peter; Dunn, Barbara K

2009-03-15

The application of epidemiology to cancer prevention is relatively new, although observations of the potential causes of cancer have been reported for more than 2,000 years. Cancer was generally considered incurable until the late 19th century. Only with a refined understanding of the nature of cancer and strategies for cancer treatment could a systematic approach to cancer prevention emerge. The 20th century saw the elucidation of clues to cancer causation from observed associations with population exposures to tobacco, diet, environmental chemicals, and other exogenous factors. With repeated confirmation of such associations, researchers entertained for the first time the possibility that cancer, like many of the infectious diseases of the time, might be prevented. By the mid-20th century, with antibiotics successfully addressing the majority of infectious diseases and high blood pressure treatment beginning to affect the prevalence of heart disease in a favorable direction, the focus of much of epidemiology shifted to cancer. The early emphasis was on exploring, in greater depth, the environmental, dietary, hormonal, and other exogenous exposures for their potential associations with increased cancer risk. The first major breakthrough in identifying a modifiable cancer risk factor was the documentation of an association between tobacco smoking and lung cancer. During the past four decades, epidemiologic studies have generated population data identifying risk factors for cancers at almost every body site, with many cancers having multiple risk factors. The development of technologies to identify biological molecules has facilitated the incorporation of these molecular manifestations of biological variation into epidemiologic studies, as markers of exposure as well as putative surrogate markers of cancer outcome. This technological trend has, during the past two decades, culminated in emphasis on the identification of genetic variants and their products as correlates of cancer risk, in turn, creating opportunities to incorporate the discipline of molecular/genetic epidemiology into the study of cancer prevention. Epidemiology will undoubtedly continue contributing to cancer prevention by using traditional epidemiologic study designs to address broad candidate areas of interest, with molecular/genetic epidemiology investigations honing in on promising areas to identify specific factors that can be modified with the goal of reducing risk.

Depressive symptoms as a cause and effect of job loss in men and women: evidence in the context of organisational downsizing from the Swedish Longitudinal Occupational Survey of Health.

PubMed

Andreeva, Elena; Magnusson Hanson, Linda L; Westerlund, Hugo; Theorell, Töres; Brenner, M Harvey

2015-10-12

Few studies have examined depression as both a cause and effect of unemployment, but no prior work investigated these relationships in the context of organisational downsizing. We explored whether the exposure to downsizing is associated with subsequent depression (social causation), and whether pre-existing depression increases the risk of being laid off when organisations downsize (health selection). Two successive waves of the nationally representative Swedish Longitudinal Occupational Survey of Health represented the baseline (2008) and follow-up (2010) of this study. Analyses included 196 workers who lost their jobs through downsizing, 1462 layoff survivors remaining in downsized organisations and 1845 employees of non-downsized workplaces. The main outcomes were: (1) Depressive symptoms at follow-up, assessed with a brief subscale from the Symptom Checklist 90, categorised by severity levels ("major depression", "less severe symptoms" and "no depression") and analysed in relation to earlier downsizing exposure; (2) Job loss in persons with downsizing in relation to earlier depressive symptoms. The associations were assessed by means of multinomial logistic regression. Job loss consistently predicted subsequent major depression among men and women, with a somewhat greater effect size in men. Surviving a layoff was significantly associated with subsequent major depression in women but not in men. Women with major depression have increased risks of exclusion from employment when organisations downsize, whereas job loss in men was not significantly influenced by their health. The evidence from this study suggests that the relative importance of social causation and health selection varies by gender in the context of organisational downsizing. Strategies for handling depression among employees should be sensitive to gender-specific risks during layoffs. Policies preventing social exclusion can be important for female workers at higher risk of depression.

A review of human factors causations in commercial air transport accidents and incidents: From to 2000-2016

NASA Astrophysics Data System (ADS)

Kharoufah, Husam; Murray, John; Baxter, Glenn; Wild, Graham

2018-05-01

Human factors have been defined by the International Civil Aviation Organization (ICAO) as "about people in their living and working situations; about their relationship with machines, with procedures and with the environment about them; and about their relationships with other people (at work)". Human factors contribute to approximately 75% of aircraft accidents and incidents. As such, understanding their influence is essential to improve safety in the aviation industry. This study examined the different human factors causations in a random sample of over 200 commercial air transport accidents and incidents from 2000 to 2016. The main objective of this study was to identify the principal human factor contributions to aviation accidents and incidents. An exploratory research design was utilised. The qualitative data were recorded in a database, and were coded into categories about the flights (including date, manufacturer, carrier, state of occurrence, etc). These categories were then analysed using Chi-Squared tests to determine which were statistically significant in terms of having an influence on the accidents/incidents. The most significant human factor was found to be situational awareness followed by non-adherence to procedures. In addition, charter operations proved to have a significantly higher rate of human factor related occurrence as compared to other type of operations. A significant finding was that Africa has a high rate of accidents/incidents relative to the amount of traffic and aircraft movements. These findings reflect some of the more noteworthy incidents that have received significant media attention, including Air Asia 8501 on the 28th of December 2014, TransAsia Airways 235 on the 4th of February 2015, and Air France 447 on the 1st of June 2009; these accidents resulted in a significant loss of lives where situational awareness and non-adherence to procedures were significant contributing factors.

Species Origin of Genomic Factors in Nicotiana nudicaulis Watson Controlling Hybrid Lethality in Interspecific Hybrids between N. nudicaulis Watson and N. tabacum L

PubMed Central

Liu, Hongshuo; Marubashi, Wataru

2014-01-01

Hybrid lethality is expressed at 28°C in the cross Nicotiana nudicaulis×N. tabacum. The S subgenome of N. tabacum has been identified as controlling this hybrid lethality. To clarify the responsible genomic factor(s) of N. nudicaulis, we crossed N. trigonophylla (paternal progenitor of N. nudicaulis) with N. tabacum, because hybrids between N. sylvestris (maternal progenitor of N. nudicaulis) and N. tabacum are viable when grown in a greenhouse. In the cross N. trigonophylla×N. tabacum, approximately 50% of hybrids were vitrified, 20% were viable, and 20% were nonviable at 28°C. To reveal which subgenome of N. tabacum was responsible for these phenotypes, we crossed N. trigonophylla with two progenitors of N. tabacum, N. sylvestris (SS) and N. tomentosiformis (TT). In the cross N. sylvestris×N. trigonophylla, we confirmed that over half of hybrids of N. sylvestris×N. trigonophylla were vitrified, and none of the hybrids of N. trigonophylla×N. tomentosiformis were. The results imply that the S subgenome, encoding a gene or genes inducing hybrid lethality in the cross between N. nudicaulis and N. tabacum, has one or more genomic factors that induce vitrification. Furthermore, in vitrified hybrids of N. trigonophylla×N. tabacum and N. sylvestris×N. trigonophylla, we found that nuclear fragmentation, which progresses during expression of hybrid lethality, was accompanied by vitrification. This observation suggests that vitrification has a relationship to hybrid lethality. Based on these results, we speculate that when N. nudicaulis was formed approximately 5 million years ago, several causative genomic factors determining phenotypes of hybrid seedlings were inherited from N. trigonophylla. Subsequently, genome downsizing and various recombination-based processes took place. Some of the causative genomic factors were lost and some became genomic factor(s) controlling hybrid lethality in extant N. nudicaulis. PMID:24806486

Airline chair-rest deconditioning: induction of immobilisation thromboemboli?

PubMed

Greenleaf, John E; Rehrer, Nancy J; Mohler, Stanley R; Quach, David T; Evans, David G

2004-01-01

Air passenger miles will likely double by year 2020. The altered and restrictive environment in an airliner cabin can influence haematological homeostasis in passengers and crew. Flight-related deep venous thromboemboli (DVT) have been associated with at least 577 deaths on 42 of 120 airlines from 1977 to 1984 (25 deaths/million departures), whereas many such cases go unreported. However, there are four major factors that could influence formation of possible flight-induced DVT: sleeping accommodations (via sitting immobilisation); travellers' medical history (via tissue injury); cabin environmental factors (via lower partial pressure of oxygen and lower relative humidity); and the more encompassing chair-rest deconditioning (C-RD) syndrome. There is ample evidence that recent injury and surgery (especially in deconditioned hospitalised patients) facilitate thrombophlebitis and formation of DVT that may be exacerbated by the immobilisation of prolonged air travel. In the healthy flying population, immobilisation factors associated with prolonged (>5 hours) C-RD such as total body dehydration, hypovolaemia and increased blood viscosity, and reduced venous blood flow (pooling) in the legs may facilitate formation of DVT. However, data from at least four case-controlled epidemiological studies did not confirm a direct causative relationship between air travel and DVT, but factors such as a history of vascular thromboemboli, venous insufficiency, chronic heart failure, obesity, immobile standing position, more than three pregnancies, infectious disease, long-distance travel, muscular trauma and violent physical effort were significantly more frequent in DVT patients than in controls. Thus, there is no clear, direct evidence yet that prolonged sitting in airliner seats, or prolonged experimental chair-rest or bed-rest deconditioning treatments cause DVT in healthy people.

Scabies among primary schoolchildren in Egypt: sociomedical environmental study in Kafr El-Sheikh administrative area

PubMed Central

Hegab, Doaa Salah; Kato, Abdullah Mahfouz; Kabbash, Ibrahim Ali; Dabish, Ghada Maged

2015-01-01

Background/objectives Scabies is a major global public health issue that might affect people from all socioeconomic levels. The primary contributing factors in contracting scabies seem to be poverty and overcrowded living conditions. Scabies often spreads among schoolchildren quite rapidly, owing to their close contact and overcrowding within the schools. However, limited information is available about its risk factors and the socioeconomic correlates among schoolchildren in Egypt. This study aimed to assess the prevalence of scabies and its risk factors among primary schoolchildren in Kafr El-Sheikh administrative area, Egypt. Methods This cross-sectional descriptive study was performed on primary schoolchildren in urban and rural areas of Kafr El-Sheikh administrative area. A predesigned questionnaire was used for data collection from the randomly selected 2,104 children, and clinical dermatological examination was done for them. Results Out of 2,104 children studied, there were 92 cases of scabies with a prevalence of 4.4%. The prevalence of scabies infestation in male students was 3.9%, while it was 4.8% in females, with no statistical significance. The results showed significant variations in the risk of scabies infestation by factors such as residence, paternal education and occupation, maternal education, sleeping with others, having animals at home, dealing with animals outside the house, type of building for living, family history of itchy rash, and sharing clothes with others. Conclusion In our community, scabies is still an important health problem affecting schoolchildren, especially in rural areas. It is characterized by a complex web of causation, particularly poor living conditions and low level of parents’ education. PMID:25759594

Scabies among primary schoolchildren in Egypt: sociomedical environmental study in Kafr El-Sheikh administrative area.

PubMed

Hegab, Doaa Salah; Kato, Abdullah Mahfouz; Kabbash, Ibrahim Ali; Dabish, Ghada Maged

2015-01-01

Scabies is a major global public health issue that might affect people from all socioeconomic levels. The primary contributing factors in contracting scabies seem to be poverty and overcrowded living conditions. Scabies often spreads among schoolchildren quite rapidly, owing to their close contact and overcrowding within the schools. However, limited information is available about its risk factors and the socioeconomic correlates among schoolchildren in Egypt. This study aimed to assess the prevalence of scabies and its risk factors among primary schoolchildren in Kafr El-Sheikh administrative area, Egypt. This cross-sectional descriptive study was performed on primary schoolchildren in urban and rural areas of Kafr El-Sheikh administrative area. A predesigned questionnaire was used for data collection from the randomly selected 2,104 children, and clinical dermatological examination was done for them. Out of 2,104 children studied, there were 92 cases of scabies with a prevalence of 4.4%. The prevalence of scabies infestation in male students was 3.9%, while it was 4.8% in females, with no statistical significance. The results showed significant variations in the risk of scabies infestation by factors such as residence, paternal education and occupation, maternal education, sleeping with others, having animals at home, dealing with animals outside the house, type of building for living, family history of itchy rash, and sharing clothes with others. In our community, scabies is still an important health problem affecting schoolchildren, especially in rural areas. It is characterized by a complex web of causation, particularly poor living conditions and low level of parents' education.

Airline chair-rest deconditioning: induction of immobilisation thromboemboli?

NASA Technical Reports Server (NTRS)

Greenleaf, John E.; Rehrer, Nancy J.; Mohler, Stanley R.; Quach, David T.; Evans, David G.

2004-01-01

Air passenger miles will likely double by year 2020. The altered and restrictive environment in an airliner cabin can influence haematological homeostasis in passengers and crew. Flight-related deep venous thromboemboli (DVT) have been associated with at least 577 deaths on 42 of 120 airlines from 1977 to 1984 (25 deaths/million departures), whereas many such cases go unreported. However, there are four major factors that could influence formation of possible flight-induced DVT: sleeping accommodations (via sitting immobilisation); travellers' medical history (via tissue injury); cabin environmental factors (via lower partial pressure of oxygen and lower relative humidity); and the more encompassing chair-rest deconditioning (C-RD) syndrome. There is ample evidence that recent injury and surgery (especially in deconditioned hospitalised patients) facilitate thrombophlebitis and formation of DVT that may be exacerbated by the immobilisation of prolonged air travel.In the healthy flying population, immobilisation factors associated with prolonged (>5 hours) C-RD such as total body dehydration, hypovolaemia and increased blood viscosity, and reduced venous blood flow (pooling) in the legs may facilitate formation of DVT. However, data from at least four case-controlled epidemiological studies did not confirm a direct causative relationship between air travel and DVT, but factors such as a history of vascular thromboemboli, venous insufficiency, chronic heart failure, obesity, immobile standing position, more than three pregnancies, infectious disease, long-distance travel, muscular trauma and violent physical effort were significantly more frequent in DVT patients than in controls. Thus, there is no clear, direct evidence yet that prolonged sitting in airliner seats, or prolonged experimental chair-rest or bed-rest deconditioning treatments cause DVT in healthy people.

Multidrug Efflux Pumps from Enterobacteriaceae, Vibrio cholerae and Staphylococcus aureus Bacterial Food Pathogens

PubMed Central

Andersen, Jody L.; He, Gui-Xin; Kakarla, Prathusha; KC, Ranjana; Kumar, Sanath; Lakra, Wazir Singh; Mukherjee, Mun Mun; Ranaweera, Indrika; Shrestha, Ugina; Tran, Thuy; Varela, Manuel F.

2015-01-01

Foodborne illnesses caused by bacterial microorganisms are common worldwide and constitute a serious public health concern. In particular, microorganisms belonging to the Enterobacteriaceae and Vibrionaceae families of Gram-negative bacteria, and to the Staphylococcus genus of Gram-positive bacteria are important causative agents of food poisoning and infection in the gastrointestinal tract of humans. Recently, variants of these bacteria have developed resistance to medically important chemotherapeutic agents. Multidrug resistant Escherichia coli, Salmonella enterica, Vibrio cholerae, Enterobacter spp., and Staphylococcus aureus are becoming increasingly recalcitrant to clinical treatment in human patients. Of the various bacterial resistance mechanisms against antimicrobial agents, multidrug efflux pumps comprise a major cause of multiple drug resistance. These multidrug efflux pump systems reside in the biological membrane of the bacteria and actively extrude antimicrobial agents from bacterial cells. This review article summarizes the evolution of these bacterial drug efflux pump systems from a molecular biological standpoint and provides a framework for future work aimed at reducing the conditions that foster dissemination of these multidrug resistant causative agents through human populations. PMID:25635914

Multidrug efflux pumps from Enterobacteriaceae, Vibrio cholerae and Staphylococcus aureus bacterial food pathogens.

PubMed

Andersen, Jody L; He, Gui-Xin; Kakarla, Prathusha; K C, Ranjana; Kumar, Sanath; Lakra, Wazir Singh; Mukherjee, Mun Mun; Ranaweera, Indrika; Shrestha, Ugina; Tran, Thuy; Varela, Manuel F

2015-01-28

Foodborne illnesses caused by bacterial microorganisms are common worldwide and constitute a serious public health concern. In particular, microorganisms belonging to the Enterobacteriaceae and Vibrionaceae families of Gram-negative bacteria, and to the Staphylococcus genus of Gram-positive bacteria are important causative agents of food poisoning and infection in the gastrointestinal tract of humans. Recently, variants of these bacteria have developed resistance to medically important chemotherapeutic agents. Multidrug resistant Escherichia coli, Salmonella enterica, Vibrio cholerae, Enterobacter spp., and Staphylococcus aureus are becoming increasingly recalcitrant to clinical treatment in human patients. Of the various bacterial resistance mechanisms against antimicrobial agents, multidrug efflux pumps comprise a major cause of multiple drug resistance. These multidrug efflux pump systems reside in the biological membrane of the bacteria and actively extrude antimicrobial agents from bacterial cells. This review article summarizes the evolution of these bacterial drug efflux pump systems from a molecular biological standpoint and provides a framework for future work aimed at reducing the conditions that foster dissemination of these multidrug resistant causative agents through human populations.

Australian tort law reform: statutory principles of causation and the common law.

PubMed

Mendelson, Danuta

2004-05-01

By mid-2004, Parliaments in each Australian jurisdiction will either complete or will be in the process of partial codification of the law of torts. The reforms, including those to the law of negligence, are extensive. This article focuses on codification of the law of causation as an element of the cause of action in negligence. It examines the background to "tort reform", as the process has been labelled, and discusses the common law paradigm of negligence and various approaches to causation. It then analyses and compares the causation provisions in each jurisdiction.

A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease.

PubMed

Mente, Andrew; de Koning, Lawrence; Shannon, Harry S; Anand, Sonia S

2009-04-13

Although a wealth of literature links dietary factors and coronary heart disease (CHD), the strength of the evidence supporting valid associations has not been evaluated systematically in a single investigation. We conducted a systematic search of MEDLINE for prospective cohort studies or randomized trials investigating dietary exposures in relation to CHD. We used the Bradford Hill guidelines to derive a causation score based on 4 criteria (strength, consistency, temporality, and coherence) for each dietary exposure in cohort studies and examined for consistency with the findings of randomized trials. Strong evidence supports valid associations (4 criteria satisfied) of protective factors, including intake of vegetables, nuts, and "Mediterranean" and high-quality dietary patterns with CHD, and associations of harmful factors, including intake of trans-fatty acids and foods with a high glycemic index or load. Among studies of higher methodologic quality, there was also strong evidence for monounsaturated fatty acids and "prudent" and "western" dietary patterns. Moderate evidence (3 criteria) of associations exists for intake of fish, marine omega-3 fatty acids, folate, whole grains, dietary vitamins E and C, beta carotene, alcohol, fruit, and fiber. Insufficient evidence (< or =2 criteria) of association is present for intake of supplementary vitamin E and ascorbic acid (vitamin C); saturated and polyunsaturated fatty acids; total fat; alpha-linolenic acid; meat; eggs; and milk. Among the dietary exposures with strong evidence of causation from cohort studies, only a Mediterranean dietary pattern is related to CHD in randomized trials. The evidence supports a valid association of a limited number of dietary factors and dietary patterns with CHD. Future evaluation of dietary patterns, including their nutrient and food components, in cohort studies and randomized trials is recommended.

Does angiotensin-converting enzyme-1 (ACE-1) gene polymorphism lead to chronic kidney disease among hypertensive patients?

PubMed

Sarkar, Taposh; Singh, Narinder Pal; Kar, Premashish; Husain, Syed Akhtar; Kapoor, Seema; Pollipalli, Sunil Kumar; Kumar, Anish; Garg, Neena

2016-06-01

Hypertension is one of the important contributing factors linked with both causation and development of kidney disease. It is a multifactorial, polygenic, and complex disorder due to interaction of several risk genes with environmental factors. The present study was aimed to explore genetic polymorphism in ACE-1 gene as a risk factor for CKD among hypertensive patients. Three hundred patients were enrolled in the study. Ninety were hypertensive patients with CKD taken as cases, whereas 210 hypertensive patients without CKD were taken as controls. Demographic data including age, sex, Body mass index (BMI), and other risk factors were also recorded. DNA was extracted from blood by salting out method. Genotyping of ACE gene was done by PCR technique. All the statistical analysis was done by using Epi Info and SPSS version 16 software (SPSS Inc., Chicago, IL). Mean age was higher in the control group (p < 0.05). Variables among two groups were compared out of which age, BMI, hemoglobin (Hb) was found to be statistically significant whereas other variables like systolic blood pressure, triglyceride and low-density lipoprotein were not. Blood urea and serum creatinine levels were statistically significant in the two genotypes (p < 0.05). Total and HDL cholesterol were statistically significant for DD genotype of ACE gene (OR = 1.42, 95% CI = 0.72-2.81). Similarly, the risk for CKD among hypertensive patients was also associated with D allele of ACE gene (OR = 1.25, 95% CI = 0.86-1.79). It is concluded that ACE-DD genotype may be a risk factor for the causation and development of chronic kidney failure among hypertensive patients.

Abfraction, abrasion, biocorrosion, and the enigma of noncarious cervical lesions: a 20-year perspective.

PubMed

Grippo, John O; Simring, Marvin; Coleman, Thomas A

2012-02-01

Hitherto, noncarious cervical lesions (NCCLs) of teeth have been generally ascribed to either toothbrush-dentifrice abrasion or acid "erosion." The last two decades have provided a plethora of new studies concerning such lesions. The most significant studies are reviewed and integrated into a practical approach to the understanding and designation of these lesions. A paradigm shift is suggested regarding use of the term "biocorrosion" to supplant "erosion" as it continues to be misused in the United States and many other countries of the world. Biocorrosion embraces the chemical, biochemical, and electrochemical degradation of tooth substance caused by endogenous and exogenous acids, proteolytic agents, as well as the piezoelectric effects only on dentin. Abfraction, representing the microstructural loss of tooth substance in areas of stress concentration, should not be used to designate all NCCLs because these lesions are commonly multifactorial in origin. Appropriate designation of a particular NCCL depends upon the interplay of the specific combination of three major mechanisms: stress, friction, and biocorrosion, unique to that individual case. Modifying factors, such as saliva, tongue action, and tooth form, composition, microstructure, mobility, and positional prominence are elucidated. By performing a comprehensive medical and dental history, using precise terms and concepts, and utilizing the Revised Schema of Pathodynamic Mechanisms, the dentist may successfully identify and treat the etiology of root surface lesions. Preventive measures may be instituted if the causative factors are detected and their modifying factors are considered. © 2011 Wiley Periodicals, Inc.

Diet, microbiota, and colorectal cancer.

PubMed

Akin, Hakan; Tözün, Nurdan

2014-01-01

Colorectal cancer (CRC) is the third most common cancer in the world causing nearly 500,000 deaths every year. In addition to genetic background, environmental factors including diet and lifestyle are accepted as major contributors to adenoma and CRC development. Lifestyle factors include high BMI, obesity, and reduced physical activity. Growing interest and accumulating data on human microbiota implicate that host-microbe interplay has an important role in the development of metabolic, neoplastic, and inflammatory diseases. Findings from recent studies suggest that colon cancer risk is determined by the interaction between diet and gut microbiota. Dietary changes affect gut microbiota and conversely microbiota mediates the generation of dietary factors triggering colon cancer. Identification of the microbial communities associated with carcinogenesis is of crucial importance. Nowadays, with the evolvement of culture-independent molecular techniques, it has become possible to identify main bacterial species in healthy individuals, inflammatory conditions, and CRC. Some recent studies have shown the differences in intestinal microbiota between colon cancer patients and healthy individuals. Animal studies have provided a better understanding of interaction between pathobionts and symbionts in the development of colon cancer. There is no single causative organism identified in CRC; however, there is strong evidence that reduction of protective bacteria, increase in some bacteria (ie, fusobacterium members; Bacteroides/Prevotella), and age-related changes in microbiota have an impact on adenoma or cancer development. Future studies will enable us to understand procarcinogenic and anticarcinogenic mechanisms and give insights to rational manipulation of the microbiota with prebiotics, probiotics, or dietary modifications.

Low maternal melatonin level increases autism spectrum disorder risk in children.

PubMed

Braam, Wiebe; Ehrhart, Friederike; Maas, Anneke P H M; Smits, Marcel G; Curfs, Leopold

2018-02-28

It is assumed that autism spectrum disorder (ASD) is caused by a combination of de novo inherited variation and common variation as well as environmental factors. It often co-occurs with intellectual disability (ID). Almost eight hundred potential causative genetic variations have been found in ASD patients. However, not one of them is responsible for more than 1% of ASD cases. Low melatonin levels are a frequent finding in ASD patients. Melatonin levels are negatively correlated with severity of autistic impairments, it is important for normal neurodevelopment and is highly effective in protecting DNA from oxidative damage. Melatonin deficiency could be a major factor, and well a common heritable variation, that increases the susceptibility to environmental risk factors for ASD. ASD is already present at birth. As the fetus does not produce melatonin, low maternal melatonin levels may be involved. We measured 6-sulfatoxymelatonin in urine of 60 mothers of a child with ASD and controls. 6-sulfatoxymelatonin levels were significantly lower in mothers with an ASD child than in controls (p = 0.012). Low parental melatonin levels could be one of the contributors to ASD and possibly ID etiology. Our findings need to be duplicated on a larger scale. If our hypothesis is correct, this could lead to policies to detect future parents who are at risk and to treatment strategies to ASD and intellectual disability risk. Copyright © 2018 Elsevier Ltd. All rights reserved.

Animal models to improve our understanding and treatment of suicidal behavior.

PubMed

Gould, T D; Georgiou, P; Brenner, L A; Brundin, L; Can, A; Courtet, P; Donaldson, Z R; Dwivedi, Y; Guillaume, S; Gottesman, I I; Kanekar, S; Lowry, C A; Renshaw, P F; Rujescu, D; Smith, E G; Turecki, G; Zanos, P; Zarate, C A; Zunszain, P A; Postolache, T T

2017-04-11

Worldwide, suicide is a leading cause of death. Although a sizable proportion of deaths by suicide may be preventable, it is well documented that despite major governmental and international investments in research, education and clinical practice suicide rates have not diminished and are even increasing among several at-risk populations. Although nonhuman animals do not engage in suicidal behavior amenable to translational studies, we argue that animal model systems are necessary to investigate candidate endophenotypes of suicidal behavior and the neurobiology underlying these endophenotypes. Animal models are similarly a critical resource to help delineate treatment targets and pharmacological means to improve our ability to manage the risk of suicide. In particular, certain pathophysiological pathways to suicidal behavior, including stress and hypothalamic-pituitary-adrenal axis dysfunction, neurotransmitter system abnormalities, endocrine and neuroimmune changes, aggression, impulsivity and decision-making deficits, as well as the role of critical interactions between genetic and epigenetic factors, development and environmental risk factors can be modeled in laboratory animals. We broadly describe human biological findings, as well as protective effects of medications such as lithium, clozapine, and ketamine associated with modifying risk of engaging in suicidal behavior that are readily translatable to animal models. Endophenotypes of suicidal behavior, studied in animal models, are further useful for moving observed associations with harmful environmental factors (for example, childhood adversity, mechanical trauma aeroallergens, pathogens, inflammation triggers) from association to causation, and developing preventative strategies. Further study in animals will contribute to a more informed, comprehensive, accelerated and ultimately impactful suicide research portfolio.

Case-control analysis of truncating mutations in DNA damage response genes connects TEX15 and FANCD2 with hereditary breast cancer susceptibility.

PubMed

Mantere, Tuomo; Tervasmäki, Anna; Nurmi, Anna; Rapakko, Katrin; Kauppila, Saila; Tang, Jiangbo; Schleutker, Johanna; Kallioniemi, Anne; Hartikainen, Jaana M; Mannermaa, Arto; Nieminen, Pentti; Hanhisalo, Riitta; Lehto, Sini; Suvanto, Maija; Grip, Mervi; Jukkola-Vuorinen, Arja; Tengström, Maria; Auvinen, Päivi; Kvist, Anders; Borg, Åke; Blomqvist, Carl; Aittomäki, Kristiina; Greenberg, Roger A; Winqvist, Robert; Nevanlinna, Heli; Pylkäs, Katri

2017-04-06

Several known breast cancer susceptibility genes encode proteins involved in DNA damage response (DDR) and are characterized by rare loss-of-function mutations. However, these explain less than half of the familial cases. To identify novel susceptibility factors, 39 rare truncating mutations, identified in 189 Northern Finnish hereditary breast cancer patients in parallel sequencing of 796 DDR genes, were studied for disease association. Mutation screening was performed for Northern Finnish breast cancer cases (n = 578-1565) and controls (n = 337-1228). Mutations showing potential cancer association were analyzed in additional Finnish cohorts. c.7253dupT in TEX15, encoding a DDR factor important in meiosis, associated with hereditary breast cancer (p = 0.018) and likely represents a Northern Finnish founder mutation. A deleterious c.2715 + 1G > A mutation in the Fanconi anemia gene, FANCD2, was over two times more common in the combined Finnish hereditary cohort compared to controls. A deletion (c.640_644del5) in RNF168, causative for recessive RIDDLE syndrome, had high prevalence in majority of the analyzed cohorts, but did not associate with breast cancer. In conclusion, truncating variants in TEX15 and FANCD2 are potential breast cancer risk factors, warranting further investigations in other populations. Furthermore, high frequency of RNF168 c.640_644del5 indicates the need for its testing in Finnish patients with RIDDLE syndrome symptoms.

Incidence, epidemiology, and treatment of aneurysmal subarachnoid hemorrhage in 12 midwest communities.

PubMed

Ziemba-Davis, Mary; Bohnstedt, Bradley N; Payner, Troy D; Leipzig, Thomas J; Palmer, Erin; Cohen-Gadol, Aaron A

2014-01-01

Only 8 studies have investigated the incidence and epidemiology of aneurysmal subarachnoid hemorrhage (aSAH) in the United States. This is the first investigation in Indiana, which has some of the highest rates of tobacco smoking and obesity in the nation. The authors prospectively identified 441 consecutive patients with aSAH from 2005 to 2010 at 2 hospitals where the majority of cases are treated. Incidence calculations were based on US Census populations. Epidemiologic variables included demography; risk factors; Hunt and Hess scale; Fisher grade; number, location, and size of aneurysms; treatment type; and complications. Overall incidence was 21.8 per 100,000 population. Incidence was higher in women, increased with age, and did not vary by race. One third to half of patients were hypertensive and/or smoked cigarettes at the time of ictus. Variations by count were partially explained by Health Factor and Morbidity Rankings. Complications varied by treatment. These findings deviate from estimates that 6-16 per 100,000 people in the United States will develop aSAH and are double the incidence in a Minnesota population between 1945 and 1974. The results also deviate from the worldwide estimate of 9.0 aSAHs per 100,000 person-years. The predictive value of variations in Health Factor and Morbidity Rankings implicates the importance of future research on multivariate biopsychosocial causation of aSAH. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Environmental Monitoring of Endemic Cholera

NASA Astrophysics Data System (ADS)

ElNemr, W.; Jutla, A. S.; Constantin de Magny, G.; Hasan, N. A.; Islam, M.; Sack, R.; Huq, A.; Hashem, F.; Colwell, R.

2012-12-01

Cholera remains a major public health threat. Since Vibrio cholerae, the causative agent of the disease, is autochthonous to riverine, estuarine, and coastal waters, it is unlikely the bacteria can be eradicated from its natural habitat. Prediction of disease, in conjunction with preventive vaccination can reduce the prevalence rate of a disease. Understanding the influence of environmental parameters on growth and proliferation of bacteria is an essential first step in developing prediction methods for outbreaks. Large scale geophysical variables, such as SST and coastal chlorophyll, are often associated with conditions favoring growth of V. cholerae. However, local environmental factors, meaning biological activity in ponds from where the bulk of populations in endemic regions derive water for daily usage, are either neglected or oversimplified. Using data collected from several sites in two geographically distinct locations in South Asia, we have identified critical local environmental factors associated with cholera outbreak. Of 18 environmental variables monitored for water sources in Mathbaria (a coastal site near the Bay of Bengal) and Bakergonj (an inland site) of Bangladesh, water depth and chlorophyll were found to be important factors associated with initiation of cholera outbreaks. Cholera in coastal regions appears to be related to intrusion. However, monsoonal flooding creates conditions for cholera epidemics in inland regions. This may be one of the first attempts to relate in-situ environmental observations with cholera. We anticipate that it will be useful for further development of prediction models in the resource constrained regions.

Mechanisms of Drug Resistance in Veterinary Oncology—A Review with an Emphasis on Canine Lymphoma

PubMed Central

Zandvliet, Maurice; Teske, Erik

2015-01-01

Drug resistance (DR) is the major limiting factor in the successful treatment of systemic neoplasia with cytotoxic chemotherapy. DR can be either intrinsic or acquired, and although the development and clinical implications are different, the underlying mechanisms are likely to be similar. Most causes for DR are pharmacodynamic in nature, result from adaptations within the tumor cell and include reduced drug uptake, increased drug efflux, changes in drug metabolism or drug target, increased capacity to repair drug-induced DNA damage or increased resistance to apoptosis. The role of active drug efflux transporters, and those of the ABC-transporter family in particular, have been studied extensively in human oncology and to a lesser extent in veterinary medicine. Methods reported to assess ABC-transporter status include detection of the actual protein (Western blot, immunohistochemistry), mRNA or ABC-transporter function. The three major ABC-transporters associated with DR in human oncology are ABCB1 or P-gp, ABCC1 or MRP1, and ABCG2 or BCRP, and have been demonstrated in canine cell lines, healthy dogs and dogs with cancer. Although this supports a causative role for these ABC-transporters in DR cytotoxic agents in the dog, the relative contribution to the clinical phenotype of DR in canine cancer remains an area of debate and requires further prospective studies. PMID:29061939

Contemporary issues: diseases with a food vector.

PubMed

Archer, D L; Young, F E

1988-10-01

Foodborne disease has become a contemporary issue. Several large, well-publicized outbreaks of foodborne disease have heightened public awareness that harmful microorganisms may be present in food and that chronic as well as acute disease may be caused by foodborne microbes. The field of food microbiology has likewise experienced a resurgence of interest. New tools, such as recombinant deoxyribonucleic acid technology and monoclonal antibody production, used to elucidate microbial virulence factors have facilitated identification of disease-causing microbes once thought to be harmless and demonstrated the complexity of individual virulence mechanisms previously considered to be well understood. Foodborne pathogens are also causing disease via some surprising food vectors, such as chopped, bottled garlic and sauteed onions. In addition to acute gastrointestinal disturbances, certain microorganisms may, through complex interactions with the human immune response, cause chronic diseases that affect several major organ systems. These microbes are serving as models in studies of molecular mimicry and genetic interrelatedness of procaryotes and eucaryotes. Other recently recognized attributes of foodborne microorganisms, such as the heat shock phenomenon and the possible nonculturability of some bacteria, may affect their ability to cause disease in humans. Because foodborne disease is a major cause of morbidity and mortality, the study of these diseases and their causative microorganisms presents a unique challenge to many professionals in the subdisciplines of microbiology, epidemiology, and clinical medicine.

Effectiveness of Sleep-Based Interventions for Children with Autism Spectrum Disorder: A Meta-Synthesis.

PubMed

Cuomo, Belinda M; Vaz, Sharmila; Lee, Elinda Ai Lim; Thompson, Craig; Rogerson, Jessica M; Falkmer, Torbjorn

2017-05-01

Sleep problems are common in children with autism spectrum disorder (ASD). This meta-synthesis collated eight previously published systematic reviews examining the efficacy of sleep interventions in children with ASD in an attempt to present a clear analysis of trialed interventions. The collated reviews consider five major groups of sleep interventions for children with ASD: melatonin therapy, pharmacologic treatments other than melatonin, behavioral interventions, parent education/education programs, and alternative therapies (massage therapy, aromatherapy, and multivitamin and iron supplementation). These eight reviews were based on 38 original studies and address the efficacy of interventions across 17 sleep problem domains. The results of this meta-synthesis suggest that no single intervention is effective across all sleep problems in children with ASD. However, melatonin, behavioral interventions, and parent education/education program interventions appear the most effective at ameliorating multiple domains of sleep problems compared with other interventions. Due to the heterogeneous causative factors and presentations of disordered sleep, further research into the effectiveness of sleep interventions may target specific phenotypic subgroups rather than a broad analysis across the general ASD population. Similarly, future research needs to consider the efficacy of different polytherapeutic approaches in order to provide clinicians with evidence to inform best practice. In the meantime, this review supports clinicians' decision making for a majority of the identified sleep problems in the ASD population. © 2017 Pharmacotherapy Publications, Inc.

Contemporary issues: diseases with a food vector.

PubMed Central

Archer, D L; Young, F E

1988-01-01

Foodborne disease has become a contemporary issue. Several large, well-publicized outbreaks of foodborne disease have heightened public awareness that harmful microorganisms may be present in food and that chronic as well as acute disease may be caused by foodborne microbes. The field of food microbiology has likewise experienced a resurgence of interest. New tools, such as recombinant deoxyribonucleic acid technology and monoclonal antibody production, used to elucidate microbial virulence factors have facilitated identification of disease-causing microbes once thought to be harmless and demonstrated the complexity of individual virulence mechanisms previously considered to be well understood. Foodborne pathogens are also causing disease via some surprising food vectors, such as chopped, bottled garlic and sauteed onions. In addition to acute gastrointestinal disturbances, certain microorganisms may, through complex interactions with the human immune response, cause chronic diseases that affect several major organ systems. These microbes are serving as models in studies of molecular mimicry and genetic interrelatedness of procaryotes and eucaryotes. Other recently recognized attributes of foodborne microorganisms, such as the heat shock phenomenon and the possible nonculturability of some bacteria, may affect their ability to cause disease in humans. Because foodborne disease is a major cause of morbidity and mortality, the study of these diseases and their causative microorganisms presents a unique challenge to many professionals in the subdisciplines of microbiology, epidemiology, and clinical medicine. PMID:3069199

For Want of a Nail: How Absences Cause Events

ERIC Educational Resources Information Center

Wolff, Phillip; Barbey, Aron K.; Hausknecht, Matthew

2010-01-01

Causation by omission is instantiated when an effect occurs from an absence, as in "The absence of nicotine causes withdrawal" or "Not watering the plant caused it to wilt." The phenomenon has been viewed as an insurmountable problem for process theories of causation, which specify causation in terms of conserved quantities, like force, but not…

When Russians Learn English: How the Semantics of Causation May Change

ERIC Educational Resources Information Center

Wolff, Phillip; Ventura, Tatyana

2009-01-01

We examined how the semantics of causal expressions in Russian and English might differ and how these differences might lead to changes in the way second language learners understand causal expressions in their first language. According to the dynamics model of causation (Wolff, 2007), expressions of causation based on CAUSE verbs (make, force)…

Phosphatase of Regenerating Liver 3 (PRL3) Provokes a Tyrosine Phosphoproteome to Drive Prometastatic Signal Transduction*

PubMed Central

Walls, Chad D.; Iliuk, Anton; Bai, Yunpeng; Wang, Mu; Tao, W. Andy; Zhang, Zhong-Yin

2013-01-01

Phosphatase of regenerating liver 3 (PRL3) is suspected to be a causative factor toward cellular metastasis when in excess. To date, the molecular basis for PRL3 function remains an enigma, making efforts at distilling a concerted mechanism for PRL3-mediated metastatic dissemination very difficult. We previously discovered that PRL3 expressing cells exhibit a pronounced increase in protein tyrosine phosphorylation. Here we take an unbiased mass spectrometry-based approach toward identifying the phosphoproteins exhibiting enhanced levels of tyrosine phosphorylation with a goal to define the “PRL3-mediated signaling network.” Phosphoproteomic data support intracellular activation of an extensive signaling network normally governed by extracellular ligand-activated transmembrane growth factor, cytokine, and integrin receptors in the PRL3 cells. Additionally, data implicate the Src tyrosine kinase as the major intracellular kinase responsible for “hijacking” this network and provide strong evidence that aberrant Src activation is a major consequence of PRL3 overexpression. Importantly, the data support a PDGF(α/β)-, Eph (A2/B3/B4)-, and Integrin (β1/β5)-receptor array as being the predominant network coordinator in the PRL3 cells, corroborating a PRL3-induced mesenchymal-state. Within this network, we find that tyrosine phosphorylation is increased on a multitude of signaling effectors responsible for Rho-family GTPase, PI3K-Akt, STAT, and ERK activation, linking observations made by the field as a whole under Src as a primary signal transducer. Our phosphoproteomic data paint the most comprehensive picture to date of how PRL3 drives prometastatic molecular events through Src activation. PMID:24030100

Biopersistence and Brain Translocation of Aluminum Adjuvants of Vaccines

PubMed Central

Gherardi, Romain Kroum; Eidi, Housam; Crépeaux, Guillemette; Authier, François Jerome; Cadusseau, Josette

2015-01-01

Aluminum oxyhydroxide (alum) is a crystalline compound widely used as an immunological adjuvant of vaccines. Concerns linked to the use of alum particles emerged following recognition of their causative role in the so-called macrophagic myofasciitis (MMF) lesion detected in patients with myalgic encephalomyelitis/chronic fatigue/syndrome. MMF revealed an unexpectedly long-lasting biopersistence of alum within immune cells in presumably susceptible individuals, stressing the previous fundamental misconception of its biodisposition. We previously showed that poorly biodegradable aluminum-coated particles injected into muscle are promptly phagocytosed in muscle and the draining lymph nodes, and can disseminate within phagocytic cells throughout the body and slowly accumulate in brain. This strongly suggests that long-term adjuvant biopersistence within phagocytic cells is a prerequisite for slow brain translocation and delayed neurotoxicity. The understanding of basic mechanisms of particle biopersistence and brain translocation represents a major health challenge, since it could help to define susceptibility factors to develop chronic neurotoxic damage. Biopersistence of alum may be linked to its lysosome-destabilizing effect, which is likely due to direct crystal-induced rupture of phagolysosomal membranes. Macrophages that continuously perceive foreign particles in their cytosol will likely reiterate, with variable interindividual efficiency, a dedicated form of autophagy (xenophagy) until they dispose of alien materials. Successful compartmentalization of particles within double membrane autophagosomes and subsequent fusion with repaired and re-acidified lysosomes will expose alum to lysosomal acidic pH, the sole factor that can solubilize alum particles. Brain translocation of alum particles is linked to a Trojan horse mechanism previously described for infectious particles (HIV, HCV), that obeys to CCL2, signaling the major inflammatory monocyte chemoattractant. PMID:25699008

Causation in epidemiology

PubMed Central

Parascandola, M; Weed, D

2001-01-01

Causation is an essential concept in epidemiology, yet there is no single, clearly articulated definition for the discipline. From a systematic review of the literature, five categories can be delineated: production, necessary and sufficient, sufficient-component, counterfactual, and probabilistic. Strengths and weaknesses of these categories are examined in terms of proposed characteristics of a useful scientific definition of causation: it must be specific enough to distinguish causation from mere correlation, but not so narrow as to eliminate apparent causal phenomena from consideration. Two categories—production and counterfactual—are present in any definition of causation but are not themselves sufficient as definitions. The necessary and sufficient cause definition assumes that all causes are deterministic. The sufficient-component cause definition attempts to explain probabilistic phenomena via unknown component causes. Thus, on both of these views, heavy smoking can be cited as a cause of lung cancer only when the existence of unknown deterministic variables is assumed. The probabilistic definition, however, avoids these assumptions and appears to best fit the characteristics of a useful definition of causation. It is also concluded that the probabilistic definition is consistent with scientific and public health goals of epidemiology. In debates in the literature over these goals, proponents of epidemiology as pure science tend to favour a narrower deterministic notion of causation models while proponents of epidemiology as public health tend to favour a probabilistic view. The authors argue that a single definition of causation for the discipline should be and is consistent with both of these aims. It is concluded that a counterfactually-based probabilistic definition is more amenable to the quantitative tools of epidemiology, is consistent with both deterministic and probabilistic phenomena, and serves equally well for the acquisition and the application of scientific knowledge.


Keywords: causality; counterfactual; philosophy PMID:11707485

Destructin-1 is a collagen-degrading endopeptidase secreted by Pseudogymnoascus destructans, the causative agent of white-nose syndrome

PubMed Central

O’Donoghue, Anthony J.; Knudsen, Giselle M.; Beekman, Chapman; Perry, Jenna A.; Johnson, Alexander D.; DeRisi, Joseph L.; Craik, Charles S.; Bennett, Richard J.

2015-01-01

Pseudogymnoascus destructans is the causative agent of white-nose syndrome, a disease that has caused the deaths of millions of bats in North America. This psychrophilic fungus proliferates at low temperatures and targets hibernating bats, resulting in their premature arousal from stupor with catastrophic consequences. Despite the impact of white-nose syndrome, little is known about the fungus itself or how it infects its mammalian host. P. destructans is not amenable to genetic manipulation, and therefore understanding the proteins involved in infection requires alternative approaches. Here, we identify hydrolytic enzymes secreted by P. destructans, and use a novel and unbiased substrate profiling technique to define active peptidases. These experiments revealed that endopeptidases are the major proteolytic activities secreted by P. destructans, and that collagen, the major structural protein in mammals, is actively degraded by the secretome. A serine endopeptidase, hereby-named Destructin-1, was subsequently identified, and a recombinant form overexpressed and purified. Biochemical analysis of Destructin-1 showed that it mediated collagen degradation, and a potent inhibitor of peptidase activity was identified. Treatment of P. destructans-conditioned media with this antagonist blocked collagen degradation and facilitated the detection of additional secreted proteolytic activities, including aminopeptidases and carboxypeptidases. These results provide molecular insights into the secretome of P. destructans, and identify serine endopeptidases that have the clear potential to facilitate tissue invasion and pathogenesis in the mammalian host. PMID:25944934

Diabetic retinopathy pathogenesis and the ameliorating effects of melatonin; involvement of autophagy, inflammation and oxidative stress.

PubMed

Dehdashtian, Ehsan; Mehrzadi, Saeed; Yousefi, Bahman; Hosseinzadeh, Azam; Reiter, Russel J; Safa, Majid; Ghaznavi, Habib; Naseripour, Masood

2018-01-15

Diabetic retinopathy (DR), a microvascular complication of diabetes mellitus (DM), remains as one of the major causes of vision loss worldwide. The release of pro-inflammatory cytokines and the adhesion of leukocytes to retinal capillaries are initial events in DR development. Inflammation, ER stress, oxidative stress and autophagy are major causative factors involved in the pathogenesis of DR. Diabetes associated hyperglycemia leads to mitochondrial electron transport chain dysfunction culminating in a rise in ROS generation. Since mitochondria are the major source of ROS production, oxidative stress induced by mitochondrial dysfunction also contributes to the development of diabetic retinopathy. Autophagy increases in the retina of diabetic patients and is regulated by ER stress, oxidative stress and inflammation-related pathways. Autophagy functions as a double-edged sword in DR. Under mild stress, autophagic activity can lead to cell survival while during severe stress, dysregulated autophagy results in massive cell death and may have a role in initiation and exacerbation of DR. Melatonin and its metabolites play protective roles against inflammation, ER stress and oxidative stress due to their direct free radical scavenger activities and indirect antioxidant activity via the stimulation antioxidant enzymes including glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase. Melatonin also acts as a cell survival agent by modulating autophagy in various cell types and under different conditions through amelioration of oxidative stress, ER stress and inflammation. Herein, we review the possible effects of melatonin on diabetic retinopathy, focusing on its ability to regulate autophagy processes. Copyright © 2017. Published by Elsevier Inc.

Coarse-graining as a downward causation mechanism

NASA Astrophysics Data System (ADS)

Flack, Jessica C.

2017-11-01

Downward causation is the controversial idea that `higher' levels of organization can causally influence behaviour at `lower' levels of organization. Here I propose that we can gain traction on downward causation by being operational and examining how adaptive systems identify regularities in evolutionary or learning time and use these regularities to guide behaviour. I suggest that in many adaptive systems components collectively compute their macroscopic worlds through coarse-graining. I further suggest we move from simple feedback to downward causation when components tune behaviour in response to estimates of collectively computed macroscopic properties. I introduce a weak and strong notion of downward causation and discuss the role the strong form plays in the origins of new organizational levels. I illustrate these points with examples from the study of biological and social systems and deep neural networks. This article is part of the themed issue 'Reconceptualizing the origins of life'.

Coarse-graining as a downward causation mechanism

PubMed Central

2017-01-01

Downward causation is the controversial idea that ‘higher’ levels of organization can causally influence behaviour at ‘lower’ levels of organization. Here I propose that we can gain traction on downward causation by being operational and examining how adaptive systems identify regularities in evolutionary or learning time and use these regularities to guide behaviour. I suggest that in many adaptive systems components collectively compute their macroscopic worlds through coarse-graining. I further suggest we move from simple feedback to downward causation when components tune behaviour in response to estimates of collectively computed macroscopic properties. I introduce a weak and strong notion of downward causation and discuss the role the strong form plays in the origins of new organizational levels. I illustrate these points with examples from the study of biological and social systems and deep neural networks. This article is part of the themed issue ‘Reconceptualizing the origins of life’. PMID:29133440

Fault tree analysis of the causes of waterborne outbreaks.

PubMed

Risebro, Helen L; Doria, Miguel F; Andersson, Yvonne; Medema, Gertjan; Osborn, Keith; Schlosser, Olivier; Hunter, Paul R

2007-01-01

Prevention and containment of outbreaks requires examination of the contribution and interrelation of outbreak causative events. An outbreak fault tree was developed and applied to 61 enteric outbreaks related to public drinking water supplies in the EU. A mean of 3.25 causative events per outbreak were identified; each event was assigned a score based on percentage contribution per outbreak. Source and treatment system causative events often occurred concurrently (in 34 outbreaks). Distribution system causative events occurred less frequently (19 outbreaks) but were often solitary events contributing heavily towards the outbreak (a mean % score of 87.42). Livestock and rainfall in the catchment with no/inadequate filtration of water sources contributed concurrently to 11 of 31 Cryptosporidium outbreaks. Of the 23 protozoan outbreaks experiencing at least one treatment causative event, 90% of these events were filtration deficiencies; by contrast, for bacterial, viral, gastroenteritis and mixed pathogen outbreaks, 75% of treatment events were disinfection deficiencies. Roughly equal numbers of groundwater and surface water outbreaks experienced at least one treatment causative event (18 and 17 outbreaks, respectively). Retrospective analysis of multiple outbreaks of enteric disease can be used to inform outbreak investigations, facilitate corrective measures, and further develop multi-barrier approaches.

Analysis of potential flooding in the education Jatinangor based approach morphology, land cover, and geology

NASA Astrophysics Data System (ADS)

Rifai, Achmad; Hadian, Sapari Dwi; Mufti, Iqbal Jabbari; Fathoni, Azmi Rizqi; Azy, Fikri Noor; Jihadi, Lutfan Harisan

2017-07-01

Jatinangor formerly an agricultural area dominated by rice field. Water in Jatinangor comes from a spring located in north Jatinangor or proximal region of Manglayang mountain to flow to the south and southwest Jatinangor up to Citarum River. Jatinangor plain that was once almost all the rice fields, but now become a land settlement that grew very rapidly since its founding colleges. Flow and puddle were originally be used for agricultural land, but now turned into a disaster risks for humans. The research method using qualitative methods with the weighing factor, scoring, and overlay maps. The cause of the flood is distinguished into two: the first is the natural factors such as the condition of landform, lithology, river flow patterns, and annual rainfall. The second is non-natural factors such as land cover of settlement, irrigation, and land use. The amount of flood risks using probability Gilbert White frequency, magnitude and duration of existing events then correlated with these factors. Based on the results of the study, were divided into 3 zones Jatinangor disaster-prone (high, medium, and safe). High flood zone is located in the South Jatinangor which covers an area Cikeruh Village, Sayang Village, Cipacing village, Mekargalih village, Cintamulya village, west of Jatimukti village, and South Hegarmanah village, has a dominant causative factor is the use of solid land, poor drainage, lithology lacustrine conditions with low permeability, and flat topography. Medium flood zone was located in the central and western regions covering Cibeusi village, Cileles village, south of Cilayung village, Hegarmanah village and Padjadjaran Region, has a dominant causative factor is rather dense land use, lithology breccias and Tuffaceous Sand with moderate permeability, topography is moderately steep. Safe flood zone is located in the east Jatinangor covering Jatiroke village, Cisepur village, east Hegarmanah village, has a dominant factor in the form of a rather steep topography, lithology breccias and lava with moderate permeability, land use rather dense, but there is a dense natural drainage.

Atypical aetiology in patients hospitalised with community-acquired pneumonia is associated with age, gender and season; a data-analysis on four Dutch cohorts.

PubMed

Raeven, Vivian M; Spoorenberg, Simone M C; Boersma, Wim G; van de Garde, Ewoudt M W; Cannegieter, Suzanne C; Voorn, G P Paul; Bos, Willem Jan W; van Steenbergen, Jim E

2016-06-17

Microorganisms causing community-acquired pneumonia (CAP) can be categorised into viral, typical and atypical (Legionella species, Coxiella burnetii, Mycoplasma pneumoniae, and Chlamydia species). Extensive microbiological testing to identify the causative microorganism is not standardly recommended, and empiric treatment does not always cover atypical pathogens. In order to optimize epidemiologic knowledge of CAP and to improve empiric antibiotic choice, we investigated whether atypical microorganisms are associated with a particular season or with the patient characteristics age, gender, or chronic obstructive pulmonary disease (COPD). A data-analysis was performed on databases from four prospective studies, which all included adult patients hospitalised with CAP in the Netherlands (N = 980). All studies performed extensive microbiological testing. A main causative agent was identified in 565/980 (57.7 %) patients. Of these, 117 (20.7 %) were atypical microorganisms. This percentage was 40.4 % (57/141) during the non-respiratory season (week 20 to week 39, early May to early October), and 67.2 % (41/61) for patients under the age of 60 during this season. Factors that were associated with atypical causative agents were: CAP acquired in the non-respiratory season (odds ratio (OR) 4.3, 95 % CI 2.68-6.84), age <60 year (OR 2.9, 95 % CI 1.83-4.66), male gender (OR 1.7, 95 % CI 1.06-2.71) and absence of COPD (OR 0.2, 95 % CI 0.12-0.52). Atypical causative agents in CAP are associated with respectively non-respiratory season, age <60 years, male gender and absence of COPD. Therefore, to maximise its yield, extensive microbiological testing should be considered in patients <60 years old who are admitted with CAP from early May to early October. NCT00471640 , NCT00170196 (numbers of original studies).

Decreasing Skin Graft Contraction through Topical Wound Bed Preparation with Anti-Inflammatory Agents

DTIC Science & Technology

2015-10-01

This proposal aims to identify topically applied anti-inflammatory drugs that will reduce recipient site inflammation and skin graft contraction. We...hypothesize that the elevated and prolonged inflammatory state of the recipient wound bed is a causative factor in the development of skin graft contraction...Using a porcine model of skin graft contraction, we will screen for anti-inflammatory agents (dose, schedule of administration, drug class

Septic monoarthritis of the first carpo-metacarpal joint caused by Mycobacterium kansasii.

PubMed

Brutus, J P; Lamraski, G; Zirak, C; Hauzeur, J P; Thys, J P; Schuind, F

2005-02-01

A case of septic carpal monoarthritis due to Mycobacterium kansasii developing 16 months after accidental inoculation in a healthy laboratory technician is reported. No predisposing factor such as immunosuppression, preexisting degenerative, inflammatory arthritis or cortisone injection was present. Treatment with antituberculous oral medication alone resulted in resolution of the disease. Synovectomy was unnecessary. Ten years after the initial causative event, the patient remains free of symptoms.

Detection of Tetrodotoxin Shellfish Poisoning (TSP) Toxins and Causative Factors in Bivalve Molluscs from the UK

PubMed Central

Turner, Andrew D.; Dhanji-Rapkova, Monika; Coates, Lewis; Bickerstaff, Lesley; Milligan, Steve; O’Neill, Alison; Faulkner, Dermot; McEneny, Hugh; Baker-Austin, Craig; Lees, David N.; Algoet, Myriam

2017-01-01

Tetrodotoxins (TTXs) are traditionally associated with the occurrence of tropical Pufferfish Poisoning. In recent years, however, TTXs have been identified in European bivalve mollusc shellfish, resulting in the need to assess prevalence and risk to shellfish consumers. Following the previous identification of TTXs in shellfish from southern England, this study was designed to assess the wider prevalence of TTXs in shellfish from around the coast of the UK. Samples were collected between 2014 and 2016 and subjected to analysis using HILIC-MS/MS. Results showed the continued presence of toxins in shellfish harvested along the coast of southern England, with the maximum concentration of total TTXs reaching 253 µg/kg. TTX accumulation was detected in Pacific oysters (Crassostrea gigas), native oysters (Ostrea edulis) common mussels (Mytilus edulis) and hard clams (Mercenaria mercenaria), but not found in cockles (Cerastoderma edule), razors (Ensis species) or scallops (Pecten maximus). Whilst the highest concentrations were quantified in samples harvested during the warmer summer months, TTXs were still evident during the winter. An assessment of the potential causative factors did not reveal any links with the phytoplankton species Prorocentrum cordatum, instead highlighting a greater level of risk in areas of shallow, estuarine waters with temperatures above 15 °C. PMID:28867772

The cell cycle in Alzheimer disease: a unique target for neuropharmacology.

PubMed

Webber, Kate M; Raina, Arun K; Marlatt, Michael W; Zhu, Xiongwei; Prat, María I; Morelli, Laura; Casadesus, Gemma; Perry, George; Smith, Mark A

2005-10-01

Several hypotheses have been proposed attempting to explain the pathogenesis of Alzheimer disease including, among others, theories involving amyloid deposition, tau phosphorylation, oxidative stress, metal ion dysregulation and inflammation. While there is strong evidence suggesting that each one of these proposed mechanisms contributes to disease pathogenesis, none of these mechanisms are able to account for all the physiological changes that occur during the course of the disease. For this reason, we and others have begun the search for a causative factor that predates known features found in Alzheimer disease, and that might therefore be a fundamental initiator of the pathophysiological cascade. We propose that the dysregulation of the cell cycle that occurs in neurons susceptible to degeneration in the hippocampus during Alzheimer disease is a potential causative factor that, together with oxidative stress, would initiate all known pathological events. Neuronal changes supporting alterations in cell cycle control in the etiology of Alzheimer disease include the ectopic expression of markers of the cell cycle, organelle kinesis and cytoskeletal alterations including tau phosphorylation. Such mitotic alterations are not only one of the earliest neuronal abnormalities in the disease, but as discussed herein, are also intimately linked to all of the other pathological hallmarks of Alzheimer disease including tau protein, amyloid beta protein precursor and oxidative stress, and even risk factors such as mutations in the presenilin genes. Therefore, therapeutic interventions targeted toward ameliorating mitotic changes would be predicted to have a profound and positive impact on Alzheimer disease progression.

Alzheimer’s and ABC transporters - new opportunities for diagnostics and treatment

PubMed Central

Pahnke, Jens; Langer, Oliver; Krohn, Markus

2014-01-01

Much has been said about the increasing number of demented patients and the main risk factor ‘age’. Frustratingly, we do not know the precise pattern and all modulating factors that provoke the pathologic changes in the brains of affected elderly. We have to diagnose early to be able to stop the progression of diseases that irreversibly destroy brain substance. Familiar AD cases have mislead some researchers for almost 20 years, which has unfortunately narrowed the scientific understanding and has, thus, lead to insufficient funding of independent approaches. Therefore, basic researchers hardly have been able to develop causative treatments and clinicians still do not have access to prognostic and early diagnostic tools. During the recent years it became clear that insufficient Aβ export, physiologically facilitated by the ABC transporter superfamily at the brain’s barriers, plays a fundamental role in disease initiation and progression. Furthermore, export mechanisms that are deficient in affected elderly are new targets for activation and, thus, treatment, but ideally also for prevention. In sporadic AD disturbed clearance of β-amyloid from the brain is so far the most important factor for its accumulation in the parenchyma and vessel walls. Here, we review findings about the contribution of ABC transporters and of the perivascular drainage/glymphatic system on β-amyloid clearance. We highlight their potential value for innovative early diagnostics using PET and describe recently described, effective ABC transporter-targeting agents as potential causative treatment for neurodegenerative proteopathies/dementias. PMID:24746857

Alzheimer's and ABC transporters--new opportunities for diagnostics and treatment.

PubMed

Pahnke, Jens; Langer, Oliver; Krohn, Markus

2014-12-01

Much has been said about the increasing number of demented patients and the main risk factor 'age'. Frustratingly, we do not know the precise pattern and all modulating factors that provoke the pathologic changes in the brains of affected elderly. We have to diagnose early to be able to stop the progression of diseases that irreversibly destroy brain substance. Familiar AD cases have mislead some researchers for almost 20 years, which has unfortunately narrowed the scientific understanding and has, thus, lead to insufficient funding of independent approaches. Therefore, basic researchers hardly have been able to develop causative treatments and clinicians still do not have access to prognostic and early diagnostic tools. During the recent years it became clear that insufficient Aβ export, physiologically facilitated by the ABC transporter superfamily at the brain's barriers, plays a fundamental role in disease initiation and progression. Furthermore, export mechanisms that are deficient in affected elderly are new targets for activation and, thus, treatment, but ideally also for prevention. In sporadic AD disturbed clearance of β-amyloid from the brain is so far the most important factor for its accumulation in the parenchyma and vessel walls. Here, we review findings about the contribution of ABC transporters and of the perivascular drainage/glymphatic system on β-amyloid clearance. We highlight their potential value for innovative early diagnostics using PET and describe recently described, effective ABC transporter-targeting agents as potential causative treatment for neurodegenerative proteopathies/dementias. Copyright © 2014 Elsevier Inc. All rights reserved.

Missed opportunities in antipneumococcal vaccination. Can something more be done for prevention?

PubMed

Arencibia Jiménez, Mercedes; Navarro Gracia, Juan Francisco; Delgado de Los Reyes, José Antonio; Pérez Torregrosa, Gerardo; López Parra, David; López García, Pilar

2014-03-01

Vaccination is the most effective measure in the prevention of invasive pneumococcal disease (IPD). High-risk patients immunized during medical visits would benefit from the vaccine. To describe the IPD cases. To assess the most prevalent causative serotypes and to evaluate the missed opportunities for vaccination. This is a descriptive retrospective study of the incidence of IPD cases in Elche during 5 years. It was reviewed the vaccination status and the visits to specialized care prior to disease. It was also calculated the vaccine effectiveness with the 23-valent pneumococcal vaccine in our population. Between 2007 and 2011 were notified 181 of IPD, the most frequent medical conditions were pneumonia and sepsis, with a mortality rate of 12%. 80% of the causative serotypes are included in the vaccine. More than the half of the cases had at least one of the risk factor for indicating the vaccination. This percentage decreases by 6.2% in cases below 65 years of age with any risk factor. After 10 years of introducing the vaccine into the adult immunization schedule the coverage it is still low among the patients with risk factors. In our study, 75% of the cases were not vaccinated. Taking in count the vaccine effectiveness for preventing IPD, among the patients attended at the hospital by the specialist prior their IPD, it could have been prevented in the best assumption (85% vaccine effectiveness) 60 IPD cases. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Social causation and neighborhood selection underlie associations of neighborhood factors with illicit drug-using social networks and illicit drug use among adults relocated from public housing.

PubMed

Linton, Sabriya L; Haley, Danielle F; Hunter-Jones, Josalin; Ross, Zev; Cooper, Hannah L F

2017-07-01

Theories of social causation and social influence, which posit that neighborhood and social network characteristics are distal causes of substance use, are frequently used to interpret associations among neighborhood characteristics, social network characteristics and substance use. These associations are also hypothesized to result from selection processes, in which substance use determines where people live and who they interact with. The potential for these competing selection mechanisms to co-occur has been underexplored among adults. This study utilizes path analysis to determine the paths that relate census tract characteristics (e.g., economic deprivation), social network characteristics (i.e., having ≥ 1 illicit drug-using network member) and illicit drug use, among 172 African American adults relocated from public housing in Atlanta, Georgia and followed from 2009 to 2014 (7 waves). Individual and network-level characteristics were captured using surveys. Census tract characteristics were created using administrative data. Waves 1 (pre-relocation), 2 (1st wave post-relocation), and 7 were analyzed. When controlling for individual-level sociodemographic factors, residing in census tracts with prior economic disadvantage was significantly associated with illicit drug use at wave 1; illicit drug use at wave 1 was significantly associated with living in economically-disadvantaged census tracts at wave 2; and violent crime at wave 2 was associated with illicit drug-using social network members at wave 7. Findings from this study support theories that describe social causation and neighborhood selection processes as explaining relationships of neighborhood characteristics with illicit drug use and illicit drug-using social networks. Policies that improve local economic and social conditions of neighborhoods may discourage substance use. Future studies should further identify the barriers that prevent substance users from obtaining housing in less disadvantaged neighborhoods. Copyright © 2017 Elsevier Ltd. All rights reserved.

Baseline Geochemical Data for Medical Researchers in Kentucky

NASA Astrophysics Data System (ADS)

Anderson, W.

2017-12-01

According to the Centers for Disease Control, Kentucky has the highest cancer incidence and death rates in the country. New efforts by geochemists and medical researchers are examining ways to diagnose the origin and sources of carcinogenesis. In an effort to determine if naturally occurring geochemical or mineral elements contributes to the cancer causation, the Kentucky Geological Survey has established a Minerals and Geochemical Database that is available to medical researchers for examination of baseline geochemistry and determine if naturally occurring mineral or chemical elements contribute to the high rate of cancers in the state. Cancer causation is complex, so if natural sources can be accounted for, then researchers can focus on the true causation. Naturally occurring minerals, metals and elements occur in many parts of the state, and their presence is valuable for evaluating causation. For example, some data in the database contain maps showing (a) statewide elemental geochemistry, (b) areas of black shale oxidation occurrence, which releases metals in soil and surface waters, (c) some clay deposits in the state that can contain high content of rare earth elements, and (d) site-specific uranium occurrences. Knowing the locations of major ore deposits in the state can also provide information related to mineral and chemical anomalies, such as for base metals and mercury. Radionuclide data in soil and water analyses are limited, so future research may involve obtaining more analyses to determine radon potential. This database also contains information on faulting and geology in the state. Although the metals content of trees may not seem relevant, the ash and humus content of degraded trees affects soil, stream sediment and water geochemistry. Many rural homes heat with wood, releasing metals into the surrounding biosphere. Stressed vegetation techniques can be used to explore for ore deposits and look for high metal contents in soils and rocks. These naturally occurring elements could be used for baseline information related to new collaborative research that integrates medicine, geology, forestry, and botany to predict metal contents of stream sediments, soil residuum, trees, plants, and forest cover and determine their relation to carcinogenesis.

Burning mouth syndrome.

PubMed

Crow, Heidi C; Gonzalez, Yoly

2013-02-01

Pain in the tongue or oral tissues described as "burning" has been referred to by many terms including burning mouth syndrome. When a burning sensation in the mouth is caused by local or systemic factors, it is called secondary burning mouth syndrome and when these factors are treated the pain will resolve. When burning mouth syndrome occurs in the absence of identified risk indicators, the term primary burning mouth syndrome is utilized. This article focuses on descriptions, etiologic theories, and management of primary burning mouth syndrome, a condition for which underlying causative agents have been ruled out. Copyright © 2013. Published by Elsevier Inc.

Risk factors for Propionibacterium acnes infection after neurosurgery: A case-control study.

PubMed

Haruki, Yuto; Hagiya, Hideharu; Takahashi, Yu; Yoshida, Hideyuki; Kobayashi, Kazuki; Yukiue, Tadato; Tsuboi, Nobushige; Sugiyama, Tetsuhiro

2017-04-01

Propionibacterium acnes is increasingly known as a causative organism for post-neurosurgical infection; however, no clinical studies have examined the risk factors associated with P. acnes infections. Clinical data obtained from 14 cases of P. acnes infection and 28 controls infected with other pathogens were analyzed. Craniotomy, malignancy, and prolonged duration of operation were significantly associated with the onset of P. acnes infection. No fatal cases were reported. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Movie portrayals of juvenile delinquency: Part II--Sociology and psychology.

PubMed

Snyder, S

1995-01-01

The visual media, especially movies, are appealing to youth with their rapid presentation of visual images of immediate gratification and unbridled pursuit of materialism. As social class differences in America widen, movies may serve both as a reflection of the social psychology of juvenile delinquency and as an etiologic factor in the development of such wayward youth. This paper examines some current aspects of the sociology and psychology of juvenile delinquency, and presents the historical significance of movies since the 1930s as both a visual representation and causative factor in the social psychology of delinquent youth.

The role of ions, heavy metals, fluoride, and agrochemicals: critical evaluation of potential aetiological factors of chronic kidney disease of multifactorial origin (CKDmfo/CKDu) and recommendations for its eradication.

PubMed

Wimalawansa, Sunil J

2016-06-01

The pollution of water and food through human waste and anthropogenic activities, including industrial waste and agricultural runoff, is a mounting problem worldwide. Water pollution from microbes causes identifiable diarrhoeal illnesses. The consumption of water contaminated with heavy metals, fluoride, and other toxins causes insidious illnesses that lead to protracted, non-communicable diseases and death. Chronic kidney disease of unusual/uncertain/unknown aetiology is one such example, began to manifest in the mid-1960s in several dry-zonal agricultural societies in developing economies that are located around the equator. In Sri Lanka, such a disease is affecting the North Central Province, the rice bowl of the country that first appeared in the mid-1990s. Several potential causes have been postulated, including heavy metals, fluoride, cyanobacterial and algae toxins, agrochemicals, and high salinity and ionicity in water, but no specific source or causative factor has been identified for CKD of multifactorial origin (CKDmfo). Three large studies conducted in the recent past failed to find any of the postulated components (heavy metals, cyanobacterial toxins, fluoride, salinity, or agrochemicals) at levels higher than those deemed safe by the World Health Organization and the US Environmental Protection Agency. At the reported low levels in water and with the heterogeneous geographical distribution, it is unrealistic to expect any of these components individually could cause this disease. However, the additive or synergistic effects of a combination of factors and components, even at lower exposure levels, together with malnutrition and harmful behaviours, and/or a yet-unidentified (or not investigated) toxin, can cause this epidemic. Because the cause is unknown, scientists need to work on broader hypotheses, so that key causative elements are not missed. Taken together the plausibility of multiple factors in the genesis of this disease, the appropriate terminology is CKDmfo, a name that also indicates the need for multi-disciplinary research programs to facilitate identifying the cause(s) and the need for multiple approaches to eradicate it. While some potential causes remain to be investigated, existing data point to polluted water as the main source of this disease. This article evaluates pros and cons of each hypothesis and highlights the importance of among others, providing clean water to all affected and surrounding communities. Available data do not support any of the postulated agents, chemicals, heavy metals, fluoride, salinity/ionicity, or individual agrochemical components, such as phosphate or glyphosate, as causative factors for CKDmfo in Sri Lanka. However, as the CKDmfo name implies, a combination of these factors (or an unknown toxin) together with harmful behaviour and chronic dehydration may cause this disease. Irrespective of the cause, prevention is the only way forward for eradication.

Natural Products as a Source for Treating Neglected Parasitic Diseases

PubMed Central

Ndjonka, Dieudonné; Rapado, Ludmila Nakamura; Silber, Ariel M.; Liebau, Eva; Wrenger, Carsten

2013-01-01

Infectious diseases caused by parasites are a major threat for the entire mankind, especially in the tropics. More than 1 billion people world-wide are directly exposed to tropical parasites such as the causative agents of trypanosomiasis, leishmaniasis, schistosomiasis, lymphatic filariasis and onchocerciasis, which represent a major health problem, particularly in impecunious areas. Unlike most antibiotics, there is no “general” antiparasitic drug available. Here, the selection of antiparasitic drugs varies between different organisms. Some of the currently available drugs are chemically de novo synthesized, however, the majority of drugs are derived from natural sources such as plants which have subsequently been chemically modified to warrant higher potency against these human pathogens. In this review article we will provide an overview of the current status of plant derived pharmaceuticals and their chemical modifications to target parasite-specific peculiarities in order to interfere with their proliferation in the human host. PMID:23389040

Columnaris as a disease of cold-water fishes

USGS Publications Warehouse

1945-01-01

A natural outbreak of columnaris disease among wild adult and hatchery-reared fingerling salmon in the State of Washington is described. The disease is identified by the recovery of the causative organism, Bacillus columnaris Davis, which may be readily identified by its characteristic action in forming columns on the surfaces of infected material held in a water mount on a microscope slide. The gross lesions vary in appearance according to the particular organ affected but are formed, essentially, by the progressive necrosis and disintegration of the tissues. The tissues primarily affected are skin, body musculature, and the gills. Cultivation of the causative organism in tryptone solutions is recorded. Controlled, laboratory-induced infections indicate that among the cold-water fishes, columnaris disease is of little consequence to fingerlings at water temperatures below 55° F., but becomes highly pathogenic at temperatures in excess of 70° F. Between these temperature thresholds, the degree and severity of the infection is markedly influenced by factors adverse to the host. No effective control measures have been found.

[5-0xoproline (pyroglutamic acid) acidosis and acetaminophen- a differential diagnosis in high anion gap metabolic acidosis].

PubMed

Weiler, Stefan; Bellmann, Romuald; Kullak-Ublick, Gerd A

2015-12-01

Rare cases of high anion gap metabolic acidosis during long-term paracetamol administration in therapeutic doses with causative 5-oxoproline (pyroglutamic acid} accumulation have been reported. Other concomitant risk factors such as malnutrition, alcohol abuse, renal or hepatic dysfunction, comedication with flue/oxacillin, vigabatrin, netilmicin or sepsis have been described. The etiology seems to be a drug-induced reversible inhibition of glutathione synthetase or 5-oxoprolinase leading to elevated serum and urine levels of 5-oxoproline. Other more frequent differential diagnoses, such as intoxications, ketoacidosis or lactic acidosis should be excluded. Causative substances should be stopped. 5-oxoproline concentrations in urine can be quantified to establish the diagnosis. Adverse drug reactions, which are not listed or insufficiently described in the respective Swiss product information, should be reported to the regional pharmacovigilance centres for early signal detection. 5-0 xoproline acidosis will be integrated as a potential adverse drug reaction in the Swiss product information for paracetamol.

Serious Injury and Fatality Investigations Involving Pneumatic Nail Guns, 1985-2012

PubMed Central

Lowe, Brian D.; Albers, James T.; Hudock, Stephen D.; Krieg, Edward F.

2016-01-01

Background This paper examines serious and fatal pneumatic nail gun (PNG) injury investigations for workplace, tool design, and human factors relevant to causation and resulting OS&H authorities’ responses in terms of citations and penalties. Methods The U.S. OSHA database of Fatality and Catastrophe Investigation Summaries (F&CIS) were reviewed (1985 - 2012) to identify n=258 PNG accidents. Results 79.8% of investigations, and 100% of fatalities, occurred in the Construction industry. Between 53-71% of injuries appear preventable had a safer sequential trigger tool been used. Citations and monetary penalties were related to injury severity, body part injured, disabling of safety devices, and insufficient personal protective equipment (PPE). Conclusions Differences may exist between Construction and other industries in investigators interpretations of PNG injury causation and resulting citations/penalties. Violations of PPE standards were penalized most severely, yet the preventive effect of PPE would likely have been less than that of a safer sequential trigger. PMID:26725335

The conundrum of causality in tumor virology: the cases of KSHV and MCV.

PubMed

Moore, Patrick S; Chang, Yuan

2014-06-01

Controversy has plagued tumor virology since the first tumor viruses were described over 100 years ago. Methods to establish cancer causation, such as Koch's postulates, work poorly or not at all for these viruses. Kaposi's sarcoma herpesvirus (KSHV/HHV8) and Merkel cell polyomavirus (MCV) were both found using nucleic acid identification methods but they represent opposite poles in the patterns for tumor virus epidemiology. KSHV is uncommon and has specific risk factors that contribute to infection and subsequent cancers. MCV and Merkel cell carcinoma (MCC), in contrast, is an example in which mutations to our normal viral flora contribute to cancer. Given the near-ubiquity of human MCV infection, establishing cancer causality relies on molecular evidence that does not fit comfortably within traditional infectious disease epidemiological models. These two viruses reveal some of the challenges and opportunities for inferring viral cancer causation in the age of molecular biology. Copyright © 2013 Elsevier Ltd. All rights reserved.

Resistance of different stocks and transferrin genotypes of coho salmon, Oncorhynchus kisutch, and steelhead trout, Salmo gairdneri, to bacterial kidney disease and vibriosis

USGS Publications Warehouse

Winter , Gary W.; Schreck, Carl B.; McIntyre, John D.

1979-01-01

Juvenile coho salmon and steelhead trout ofdifferentstocks and three transferrin genotypes(AA, AC, and CCl, all reared in identical or similar environments, were experimentally infected with Corynebacterium sp., the causative agent ofbacterial kidney disease, or with Vibrio anguillarum, the causative agent of vibriosis. Mortality due to the pathogens was compared among stocks within a species and among transferrin genotypes within a stock to determine whetherthere was a geneticbasis for resistance to disease. Differences in resistance to bacterial kidney disease among coho salmon stocks had a genetic basis. Stock susceptibility to vibriosis was strongly influenced by environmental factors. Coho salmon orsteelhead trout of one stock may be resistant to one disease but susceptible to another. The importance of transferrin genotype of coho salmon in resistance to bacterial kidney disease was stock specific; in stocks that showed differential resistance of genotypes, the AA was the most susceptible. No differencesin resistance to vibriosis were observed among transferrin genotypes.

Fluid convection, constraint and causation

PubMed Central

Bishop, Robert C.

2012-01-01

Complexity—nonlinear dynamics for my purposes in this essay—is rich with metaphysical and epistemological implications but is receiving sustained philosophical analysis only recently. I will explore some of the subtleties of causation and constraint in Rayleigh–Bénard convection as an example of a complex phenomenon, and extract some lessons for further philosophical reflection on top-down constraint and causation particularly with respect to causal foundationalism. PMID:23386955

Molecular findings and clinical data in a cohort of 150 patients with anophthalmia/microphthalmia.

PubMed

Chassaing, N; Causse, A; Vigouroux, A; Delahaye, A; Alessandri, J-L; Boespflug-Tanguy, O; Boute-Benejean, O; Dollfus, H; Duban-Bedu, B; Gilbert-Dussardier, B; Giuliano, F; Gonzales, M; Holder-Espinasse, M; Isidor, B; Jacquemont, M-L; Lacombe, D; Martin-Coignard, D; Mathieu-Dramard, M; Odent, S; Picone, O; Pinson, L; Quelin, C; Sigaudy, S; Toutain, A; Thauvin-Robinet, C; Kaplan, Josseline; Calvas, Patrick

2014-10-01

Anophthalmia and microphthalmia (AM) are the most severe malformations of the eye, corresponding respectively to reduced size or absent ocular globe. Wide genetic heterogeneity has been reported and different genes have been demonstrated to be causative of syndromic and non-syndromic forms of AM. We screened seven AM genes [GDF6 (growth differentiation factor 6), FOXE3 (forkhead box E3), OTX2 (orthodenticle protein homolog 2), PAX6 (paired box 6), RAX (retina and anterior neural fold homeobox), SOX2 (SRY sex determining region Y-box 2), and VSX2 (visual system homeobox 2 gene)] in a cohort of 150 patients with isolated or syndromic AM. The causative genetic defect was identified in 21% of the patients (32/150). Point mutations were identified by direct sequencing of these genes in 25 patients (13 in SOX2, 4 in RAX, 3 in OTX2, 2 in FOXE3, 1 in VSX2, 1 in PAX6, and 1 in GDF6). In addition eight gene deletions (five SOX2, two OTX2 and one RAX) were identified using a semi-quantitative multiplex polymerase chain reaction (PCR) [quantitative multiplex PCR amplification of short fluorescent fragments (QMPSF)]. The causative genetic defect was identified in 21% of the patients. This result contributes to our knowledge of the molecular basis of AM, and will facilitate accurate genetic counselling. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

How rapidly does the excess risk of lung cancer decline following quitting smoking? A quantitative review using the negative exponential model.

PubMed

Fry, John S; Lee, Peter N; Forey, Barbara A; Coombs, Katharine J

2013-10-01

The excess lung cancer risk from smoking declines with time quit, but the shape of the decline has never been precisely modelled, or meta-analyzed. From a database of studies of at least 100 cases, we extracted 106 blocks of RRs (from 85 studies) comparing current smokers, former smokers (by time quit) and never smokers. Corresponding pseudo-numbers of cases and controls (or at-risk) formed the data for fitting the negative exponential model. We estimated the half-life (H, time in years when the excess risk becomes half that for a continuing smoker) for each block, investigated model fit, and studied heterogeneity in H. We also conducted sensitivity analyses allowing for reverse causation, either ignoring short-term quitters (S1) or considering them smokers (S2). Model fit was poor ignoring reverse causation, but much improved for both sensitivity analyses. Estimates of H were similar for all three analyses. For the best-fitting analysis (S1), H was 9.93 (95% CI 9.31-10.60), but varied by sex (females 7.92, males 10.71), and age (<50years 6.98, 70+years 12.99). Given that reverse causation is taken account of, the model adequately describes the decline in excess risk. However, estimates of H may be biased by factors including misclassification of smoking status. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.