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Sample records for adversely affect prognosis

  1. Minor serous and clear cell components adversely affect prognosis in ''mixed-type'' endometrial carcinomas: a clinicopathologic study of 36 stage-I cases.

    PubMed

    Quddus, M Ruhul; Sung, C James; Zhang, Cunxian; Lawrence, W Dwayne

    2010-07-01

    Most endometrial carcinomas contain only 1 Müllerian cell type although the presence of 2 or more cell types within 1 tumor, for example a predominantly low-grade endometrioid carcinoma with a minor component (arbitrarily defined as 30% or less) of high-grade serous and/or clear cell carcinoma, is not uncommon. The current study attempts to evaluate whether the presence of minor serous or clear cell components exerts an adverse effect on the prognosis in stage-I endometrial carcinomas of ''mixed-type.'' The study cases include 22 cases of stage-I endometrioid carcinoma with a minor component of serous carcinoma and 14 cases of endometrioid carcinoma with a minor component of clear cell carcinoma. Minor components were arbitrarily defined as representing anywhere between 5% and 30% of the total tumor. The study cases were compared with 56 cases of histologically pure age-matched and stage-matched endometrioid carcinomas, 6 pure serous carcinomas, and 13 pure clear cell carcinomas. All study and control cases were fully staged. Treatment history and outcome status were obtained and follow-up ranged from 56 to 140 months. Our study suggests that the presence of minor components of serous and clear cell carcinoma, defined as between 5% and 30%, within a mixed-type endometrial carcinoma appears to adversely influence the long-term survival of stage-I tumors, although a larger study is needed to corroborate our findings.

  2. Diagnosis of potential stressors adversely affecting benthic ...

    EPA Pesticide Factsheets

    Greenwich Bay is an urbanized embayment of Narragansett Bay potentially impacted by multiple stressors. The present study identified the important stressors affecting Greenwich Bay benthic fauna. First, existing data and information were used to confirm that the waterbody was impaired. Second, the presence of source, stressor, and effect were established. Then linkages between source, stressor, and effect were developed. This allows identification of probable stressors adversely affecting the waterbody. Three pollutant categories were assessed: chemicals, nutrients, and suspended sediments. This weight of evidence approach indicated that Greenwich Bay was primarily impacted by eutrophication-related stressors. The sediments of Greenwich Bay were carbon enriched and low dissolved oxygen concentrations were commonly seen, especially in the western portions of Greenwich Bay. The benthic community was depauperate, as would be expected under oxygen stress. Although our analysis indicated that contaminant loads in Greenwich Bay were at concentrations where adverse effects might be expected, no toxicity was observed, as a result of high levels of organic carbon in these sediments reducing contaminant bioavailability. Our analysis also indicated that suspended sediment impacts were likely nonexistent for much of the Bay. This analysis demonstrates that the diagnostic procedure was useful to organize and assess the potential stressors impacting the ecological well-being

  3. Hyperinsulinemia adversely affects lung structure and function.

    PubMed

    Singh, Suchita; Bodas, Manish; Bhatraju, Naveen K; Pattnaik, Bijay; Gheware, Atish; Parameswaran, Praveen Kolumam; Thompson, Michael; Freeman, Michelle; Mabalirajan, Ulaganathan; Gosens, Reinoud; Ghosh, Balaram; Pabelick, Christina; Linneberg, Allan; Prakash, Y S; Agrawal, Anurag

    2016-05-01

    There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly (P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype.

  4. Mitochondrial cytochrome c oxidase subunit II variations predict adverse prognosis in cytogenetically normal acute myeloid leukaemia.

    PubMed

    Silkjaer, Trine; Nyvold, Charlotte Guldborg; Juhl-Christensen, Caroline; Hokland, Peter; Nørgaard, Jan Maxwell

    2013-10-01

    Alterations in the two catalytic genes cytochrome c oxidase subunits I and II (COI and COII) have recently been suggested to have an adverse impact on prognosis in patients with acute myeloid leukaemia (AML). In order to explore this in further detail, we sequenced these two mitochondrial genes in diagnostic bone marrow or blood samples in 235 patients with AML. In 37 (16%) patients, a non-synonymous variation in either COI or COII could be demonstrated. No patients harboured both COI and COII non-synonymous variations. Twenty-four (10%) patients had non-synonymous variations in COI, whereas 13 (6%) patients had non-synonymous variations in COII. The COI and COII are essential subunits of cytochrome c oxidase that is the terminal enzyme in the oxidative phosphorylation complexes. In terms of disease course, we observed that in patients with a normal cytogenetic analysis at disease presentation (CN-AML) treated with curative intent, the presence of a non-synonymous variation in the COII was an adverse prognostic marker for both overall survival and disease-free survival (DFS) in both univariate (DFS; hazard ratio (HR) 4.4, P = 0.006) and multivariate analyses (DFS; HR 7.2, P = 0.001). This is the first demonstration of a mitochondrial aberration playing an adverse prognostic role in adult AML, and we argue that its role as a potentially novel adverse prognostic marker in the subset of CN-AML should be explored further.

  5. FACTORS ADVERSELY AFFECTING AMPHIBIAN POPULATIONS IN THE US

    EPA Science Inventory

    Factors known or suspected to be adversely affecting native amphibian populations in the US were identified using information from species accounts written in a standardized format by multiple authors in a forthcoming book. Specific adverse factors were identified for 53 (58%) of...

  6. Overexpression of Fli-1 is associated with adverse prognosis of endometrial cancer.

    PubMed

    Song, Wei; Zhang, Tianyang; Li, Wei; Mu, Rui; Zhang, Lingyi; Li, Yan; Jin, Baofeng; Wang, Na; Li, Ailing; Cui, Jiuwei

    2015-01-01

    This study aimed to investigate the expression of Friend leukemia virus integration 1 (Fli-1) and its correlation with the prognosis of endometrial cancer (EC). Thirty-two EC tissue samples were evaluated for Fli-1 expression using immunohistochemistry. Fli-1 showed significantly high expression in EC cells, followed by hyperplasia cells, and was negative in adjacent normal tissues. The high expression of Fli-1 was significantly associated with a high differentiation grade, mutated P53 expression, and histological subtype (p < .05). Downregulation of Fli-1 in AN3CN cells using RNA interference inhibited cell clone formation and proliferation but did not affect apoptosis and migration of the cells. This study provides the first evidence that Fli-1 expression gradually increases in parallel with disease progression, and its overexpression might predict poor prognosis in EC.

  7. Adversity before Conception Will Affect Adult Progeny in Rats

    ERIC Educational Resources Information Center

    Shachar-Dadon, Alice; Schulkin, Jay; Leshem, Micah

    2009-01-01

    The authors investigated whether adversity in a female, before she conceives, will influence the affective and social behavior of her progeny. Virgin female rats were either undisturbed (controls) or exposed to varied, unpredictable, stressors for 7 days (preconceptual stress [PCS]) and then either mated immediately after the end of the stress…

  8. 6q deletion in Waldenström macroglobulinemia is associated with features of adverse prognosis.

    PubMed

    Ocio, E M; Schop, R F J; Gonzalez, B; Van Wier, S A; Hernandez-Rivas, J M; Gutierrez, N C; Garcia-Sanz, R; Moro, M J; Aguilera, C; Hernandez, J; Xu, R; Greipp, P R; Dispenzieri, A; Jalal, S M; Lacy, M Q; Gonzalez-Paz, N; Gertz, M A; San Miguel, J F; Fonseca, R

    2007-01-01

    Fluorescence in situ hybridisation (FISH) is an effective technique for the cytogenetic analysis of Waldenström macroglobulinemia (WM), but the potential impact of molecular cytogenetics on disease evolution and as a prognostic marker is still unknown. Deletion of the long arm of chromosome 6 (6q-) is the most frequent cytogenetic abnormality in WM. This study analysed the prevalence of this aberration in 102 WM patients, and correlated it with disease characteristics. The incidence of 6q21 deletion was 7% by conventional cytogenetics and 34% when analysed by FISH (54% when cytoplasmic immunoglobulin M-FISH was used). Patients with deletion of 6q displayed features of adverse prognosis, such as higher levels of beta2-microglobulin and monoclonal paraprotein and a greater tendency to display anaemia and hypoalbuminemia. Interestingly, there was a correlation between the presence of 6q deletion and the International Staging System prognostic index (incidence of 6q- among patients stratified in stages 1, 2 and 3 was 24%, 42% and 67% respectively). Those patients diagnosed with smouldering WM who displayed the abnormality showed a trend to an earlier requirement of treatment. Finally, the survival analysis did not show differences between the two groups of patients, probably due to the short follow up of our series.

  9. Factors affecting the development of adverse drug reactions (Review article)

    PubMed Central

    Alomar, Muaed Jamal

    2013-01-01

    Objectives To discuss the effect of certain factors on the occurrence of Adverse Drug Reactions (ADRs). Data Sources A systematic review of the literature in the period between 1991 and 2012 was made based on PubMed, the Cochrane database of systematic reviews, EMBASE and IDIS. Key words used were: medication error, adverse drug reaction, iatrogenic disease factors, ambulatory care, primary health care, side effects and treatment hazards. Summary Many factors play a crucial role in the occurrence of ADRs, some of these are patient related, drug related or socially related factors. Age for instance has a very critical impact on the occurrence of ADRs, both very young and very old patients are more vulnerable to these reactions than other age groups. Alcohol intake also has a crucial impact on ADRs. Other factors are gender, race, pregnancy, breast feeding, kidney problems, liver function, drug dose and frequency and many other factors. The effect of these factors on ADRs is well documented in the medical literature. Taking these factors into consideration during medical evaluation enables medical practitioners to choose the best drug regimen. Conclusion Many factors affect the occurrence of ADRs. Some of these factors can be changed like smoking or alcohol intake others cannot be changed like age, presence of other diseases or genetic factors. Understanding the different effects of these factors on ADRs enables healthcare professionals to choose the most appropriate medication for that particular patient. It also helps the healthcare professionals to give the best advice to patients. Pharmacogenomics is the most recent science which emphasizes the genetic predisposition of ADRs. This innovative science provides a new perspective in dealing with the decision making process of drug selection. PMID:24648818

  10. Does Ramadan Fasting Adversely Affect Cognitive Function in Young Females?

    PubMed Central

    Ghayour Najafabadi, Mahboubeh; Rahbar Nikoukar, Laya; Memari, Amir; Ekhtiari, Hamed; Beygi, Sara

    2015-01-01

    We examined the effects of Ramadan fasting on cognitive function in 17 female athletes. Data were obtained from participants of two fasting (n = 9) and nonfasting (n = 8) groups at three periods of the study (before Ramadan, at the third week in Ramadan, and after Ramadan). Digit span test (DST) and Stroop color test were employed to assess short-term memory and inhibition/cognitive flexibility at each time point. There were no significant changes for DST and Stroop task 1 in both groups, whereas Stroop task 2 and task 3 showed significant improvements in Ramadan condition (p < 0.05). Interference indices did not change significantly across the study except in post-Ramadan period of fasting group (p < 0.05). Group × week interaction was significant only for error numbers (p < 0.05). Athletes in nonfasting showed a significant decrease in number of errors in Ramadan compared to baseline (p < 0.05). The results suggest that Ramadan fasting may not adversely affect cognitive function in female athletes. PMID:26697263

  11. California's racial and ethnic minorities more adversely affected by asthma.

    PubMed

    Meng, Ying-Ying; Babey, Susan H; Hastert, Theresa A; Brown, E Richard

    2007-02-01

    In California, nearly 2.8 million adults and children (8%) had active asthma in 2003. Of Californians with active asthma, 890,000 are children (ages 0-17) and 1.8 million are adults (age 18 and above). The prevalence of active asthma varies by racial and ethnic group, with racial and ethnic minority groups affected more adversely by asthma. They are more likely to go to the emergency department for asthma care, miss more school and work days because of asthma, and have poorer health status. They are also more likely to lack access to health care and to live in conditions associated with asthma exacerbations. Among California children, the prevalence of active asthma varies by racial and ethnic groups-with the highest prevalence among African Americans (17%) and American Indians/Alaska Natives (17%), followed by whites (10%), Latinos (7%) and Asians (7%; Exhibit 1). Among adults, American Indians/Alaska Natives have the highest prevalence of active asthma (13%), followed by African Americans (10%), whites (9%), Asians (5%) and Latinos (5%). The National data similarly show that both African Americans and American Indians have higher current asthma prevalence rates than non- Hispanic whites.

  12. Toxins and adverse drug reactions affecting the equine nervous system.

    PubMed

    Dawson, Dominic R

    2011-12-01

    This article provides an overview of the more common toxins and adverse drug reactions, along with more rare toxins and reactions (Table 1), that result in neurologic dysfunction in horses. A wide variety of symptoms, treatments, and outcomes are seen with toxic neurologic disease in horses. An in-depth history and thorough physical examination are needed to determine if a toxin or adverse drug reaction is responsible for the clinical signs. Once a toxin or adverse drug reaction is identified, the specific antidote, if available, and supportive care should be administered promptly.

  13. The AXL receptor tyrosine kinase is associated with adverse prognosis and distant metastasis in esophageal squamous cell carcinoma

    PubMed Central

    Wong, Li-Fan; Lee, Jang-Ming

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is a frequently recurrent deadly cancer for which no efficient targeted drug exists. AXL is an adverse prognostic factor in some cancers. Strong clinical evidence to support the prognostic role of AXL in ESCC is lacking. A total of 116 patients diagnosed with operable primary ESCC were enrolled. Both AXL and HER2 expression were detected by immunohistochemistry (IHC) in esophageal tissue and were correlated with the clinical outcome of patients. The efficacy of the AXL targeted drug foretinib was also evaluated in ESCC cells. Expression of AXL was found in about 80 % of ESCC tissue, and was significantly correlated with progression of tumor (P<0.001), increased risk of death (Hazard ratio HR [95 % CI=2.09[1.09-4.04], P=0.028], and distant metastasis (odds ratio OR [95 %CI]=3.96 (1.16-13.60), P=0.029). The adverse clinical impact of AXL was more evident when cumulatively expressed with HER2. In cell model, ESCC cells were more sensitive to AXL inhibitor foretinib than to the HER2 inhibitor lapatinib. Meanwhile, the AXL inhibitor foretinib showed a synergistic effect with HER2 inhibitors and the potential to overcome drug resistance to lapatinib. We thus concluded that AXL is a strong adverse prognostic factor for ESCC. Therapeutic agents targeting AXL have great potential to improve prognosis of ESCC patients. PMID:27172793

  14. Does mild COPD affect prognosis in the elderly?

    PubMed Central

    2010-01-01

    Background Chronic obstructive pulmonary disease (COPD) affects independence and survival in the general population, but it is unknown to which extent this conclusion applies to elderly people with mild disease. The aim of this study was to verify whether mild COPD, defined according to different classification systems (ATS/ERS, BTS, GOLD) impacts independence and survival in elderly (aged 65 to 74 years) or very elderly (aged 75 years or older) patients. Methods We used data coming from the Respiratory Health in the Elderly (Salute Respiratoria nell'Anziano, SaRA) study and compared the differences between the classification systems with regards to personal capabilities and 5-years survival, focusing on the mild stage of COPD. Results We analyzed data from 1,159 patients (49% women) with a mean age of 73.2 years (SD: 6.1). One third of participants were 75 years or older. Mild COPD, whichever was its definition, was not associated with worse personal capabilities or increased mortality after adjustment for potential confounders in both age groups. Conclusions Mild COPD may not affect survival or personal independence of patients over 65 years of age if the reference group consists of patients with a comparable burden of non respiratory diseases. Comorbidity and age itself likely are main determinants of both outcomes. PMID:20529281

  15. Dectin-1 predicts adverse postoperative prognosis of patients with clear cell renal cell carcinoma

    PubMed Central

    Xia, Yu; Liu, Li; Bai, Qi; Wang, Jiajun; Xi, Wei; Qu, Yang; Xiong, Ying; Long, Qilai; Xu, Jiejie; Guo, Jianming

    2016-01-01

    Dectin-1, a classical pattern-recognition receptor, was now identified as an important regulator in immune homeostasis and cancer immunity through its extensive ligands binding functions and subsequent cytokines production. The aim of this study was to assess the clinical significance of dectin-1 expression in 290 patients with clear cell renal cell carcinoma (ccRCC) through immunohistochemistry on tissue microarrays. We found that dectin-1 was predominantly expressed on ccRCC cells, in accordance with several other online databases. Moreover, Kaplan-Meier method was conducted and high expression of tumoral dectin-1 was associated with shorter patient recurrence free survival (RFS) and overall survival (OS) (P < 0.001 for both). In multivariate analyses, tumoral dectin-1 expression was also confirmed as an independent prognostic factor for patients’ survival together with other clinical parameters (P < 0.001 for RFS and OS). After incorporating these characteristics including tumoral dectin-1 expression, two nomograms were constructed to predict ccRCC patients’ RFS and OS (c-index 0.796 and 0.812, respectively) and performed better than existed integrated models (P < 0.001 for all models comparisons). In conclusion, high tumoral dectin-1 expression was an independent predictor of adverse clinical outcome in ccRCC patients. This molecule and established nomograms might help clinicians in future decision making and therapeutic developments. PMID:27600310

  16. Childhood lymphoblastic leukemia adverse drug reactions: study of risk factors and therapy prognosis by optical methods

    NASA Astrophysics Data System (ADS)

    Zyubin, A.; Lavrova, A.; Babak, S.; Malaschenko, V.; Borisova, A.; Opryshko, N.

    2016-10-01

    The treatment of acute lymphoblastic leukemia (ALL) can result in the side-effects such as kidney affection, hepatic failure and tissue hypoxia. We study dynamics of special biochemical marker of these pathologies - adenosine triphosphate, that is well-known substance of energy metabolism. We use methods of confocal microscopy for determining the cellular and mitochondrial concentration of adenosine triphosphate (ATP). Quantitative values of adenosine triphosphate were calculated for each patient and correlation with degree of side-effects had been done. The application of confocal microscopy for studying of side-effects and therapy of lymphoblastic leukemia is discussed.

  17. 47 CFR 73.4157 - Network signals which adversely affect affiliate broadcast service.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....4157 Network signals which adversely affect affiliate broadcast service. See Public Notice, FCC 79-387... 47 Telecommunication 4 2010-10-01 2010-10-01 false Network signals which adversely affect affiliate broadcast service. 73.4157 Section 73.4157 Telecommunication FEDERAL COMMUNICATIONS...

  18. Biologic features and prognosis of ductal carcinoma in situ are not adversely impacted by initial large body mass.

    PubMed

    Kuerer, Henry M; Lari, Sara A; Arun, Banu K; Hu, Chung-Yuan; Brewster, Abenaa; Mittendorf, Elizabeth A; Albarracin, Constance T; Babiera, Gildy V; Caudle, Abigail S; Wagner, Jamie L; Litton, Jennifer K; Bedrosian, Isabelle; Meric-Bernstam, Funda; Lucci, Anthony; Hunt, Kelly K

    2012-06-01

    Obesity is associated with adverse biologic features and poor outcome in patients with invasive breast cancer, yet this relationship has not been evaluated in patients with ductal carcinoma in situ (DCIS). From 1996 to 2009, body mass index (BMI) was recorded at initial diagnosis for 1,885 patients with DCIS treated at our institution. Patients were categorized as obese (BMI ≥ 30 kg/m(2)), overweight (BMI 25 to <30 kg/m(2)), or of normal weight or underweight (BMI < 25 kg/m(2)). Logistic regression was used to examine associations between BMI and patient, clinical, and pathologic features and treatment. Local-regional recurrence was calculated using the Kaplan-Meier method. All statistical tests were two-sided. Of the 1,885 patients, 514 (27.7%) were obese, 510 (27.5%) were overweight, and 831 (44.8%) were normal/underweight. In multivariate analysis, overweight and obese patients were significantly more likely to be African American (odds ratio [OR], 3.93; 95% confidence interval [CI], 2.66-5.80) or Hispanic (OR, 1.44; CI, 1.02-2.04), be postmenopausal (OR, 1.63; CI, 1.28-2.07), have diabetes (OR, 4.60; CI, 2.60-8.12), have estrogen-receptor-positive DCIS (OR, 1.39; CI, 1.00-192), and present with a radiologic abnormality rather than clinical symptoms (OR, 1.35; CI, 1.01-1.80). At a median follow-up time of 4.96 years (range, 1.0-14.34 years), no significant differences in local recurrence rates were detected based on patients' initial BMI category. Furthermore, there was no significant difference in risk of recurrence between diabetic patients receiving metformin or not. In conclusion, higher BMI is not associated with adverse biologic features or prognosis in patients with DCIS.

  19. Overexpression of Ku80 correlates with aggressive clinicopathological features and adverse prognosis in esophageal squamous cell carcinoma

    PubMed Central

    WANG, SHUAI; WANG, ZHOU; YANG, YU; SHI, MO; SUN, ZHENGUO

    2015-01-01

    Ku80, a subunit of the heterodymeric Ku protein, is clearly implicated in nonhomologous end joining DNA repair, chemoresistance and radioresistance in malignant tumors. In the present study, the clinicopathological significance of Ku80 in esophageal squamous cell carcinoma (ESCC) was investigated. The expression levels of Ku80 were determined by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry in ESCC specimens and normal esophageal mucosa. The mRNA and protein levels of Ku80 were significantly higher in ESCC tissues than in normal esophageal mucosa, and were significantly associated with tumor differentiation, local invasion, lymph node metastasis and tumor-node-metastasis (TNM) stage. However, overexpression of Ku80 mRNA and protein levels were not significantly correlated with age, gender, tumor site or tumor size. Cox proportional hazards regression model demonstrated that tumor local invasion, lymph node metastasis, TNM stage and Ku80 mRNA and protein levels were independent risk factors indicating the overall survival of patients with ESCC. The present study demonstrated that aberrant Ku80 overexpression is observed in ESCC. In addition, high expression levels of Ku80 are associated with adverse clinicopathological features and unfavorable prognosis in ESCC patients. PMID:26722230

  20. Root-Zone Glyphosate Exposure Adversely Affects Two Ditch Species

    PubMed Central

    Saunders, Lyndsay E.; Koontz, Melissa B.; Pezeshki, Reza

    2013-01-01

    Glyphosate, one of the most applied herbicides globally, has been extensively studied for its effects on non-target organisms. In the field, following precipitation, glyphosate runs off into agricultural ditches where it infiltrates into the soil and thus may encounter the roots of vegetation. These edge-of-field ditches share many characteristics with wetlands, including the ability to reduce loads of anthropogenic chemicals through uptake, transformation, and retention. Different species within the ditches may have a differential sensitivity to exposure of the root zone to glyphosate, contributing to patterns of abundance of ruderal species. The present laboratory experiment investigated whether two species commonly found in agricultural ditches in southcentral United States were affected by root zone glyphosate in a dose-dependent manner, with the objective of identifying a sublethal concentration threshold. The root zone of individuals of Polygonum hydropiperoides and Panicum hemitomon were exposed to four concentrations of glyphosate. Leaf chlorophyll content was measured, and the ratio of aboveground biomass to belowground biomass and survival were quantified. The findings from this study showed that root zone glyphosate exposure negatively affected both species including dose-dependent reductions in chlorophyll content. P. hydropiperdoides showed the greatest negative response, with decreased belowground biomass allocation and total mortality at the highest concentrations tested. PMID:24833234

  1. Urban sprawl and you: how sprawl adversely affects worker health.

    PubMed

    Pohanka, Mary; Fitzgerald, Sheila

    2004-06-01

    Urban sprawl, once thought of as just an environmental issue, is currently gaining momentum as an emerging public health issue worthy of research and political attention. Characteristics seen in sprawling communities include increasing traffic volumes; inadequate public transportation; pedestrian unfriendly streets; and the division of businesses, shops, and homes. These characteristics can affect health in many ways. Greater air pollution contributes to higher asthma and other lung disorder rates. An increased dependence on the automobile encourages a more sedentary lifestyle and can potentially contribute to obesity. The increased danger and stress of long commutes can lead to more accidents, anxiety, and social isolation. Occupational health nurses can become involved by promoting physical activity in the workplace, creating programs for injury prevention and stress management, becoming involved in political smart growth measures, and educating and encouraging colleagues to become active in addressing this issue.

  2. Biologic features and prognosis of ductal carcinoma in situ are not adversely impacted by initial large body mass

    PubMed Central

    Lari, Sara A.; Arun, Banu K.; Hu, Chung-Yuan; Brewster, Abenaa; Mittendorf, Elizabeth A.; Albarracin, Constance T.; Babiera, Gildy V.; Caudle, Abigail S.; Wagner, Jamie L.; Litton, Jennifer K.; Bedrosian, Isabelle; Meric-Bernstam, Funda; Lucci, Anthony; Hunt, Kelly K.

    2013-01-01

    Obesity is associated with adverse biologic features and poor outcome in patients with invasive breast cancer, yet this relationship has not been evaluated in patients with ductal carcinoma in situ (DCIS). From 1996 to 2009, body mass index (BMI) was recorded at initial diagnosis for 1,885 patients with DCIS treated at our institution. Patients were categorized as obese (BMI ≥ 30 kg/m2), overweight (BMI 25 to<30 kg/m2), or of normal weight or underweight (BMI <25 kg/m2). Logistic regression was used to examine associations between BMI and patient, clinical, and pathologic features and treatment. Local–regional recurrence was calculated using the Kaplan–Meier method. All statistical tests were two-sided. Of the 1,885 patients, 514 (27.7%) were obese, 510 (27.5%) were overweight, and 831 (44.8%) were normal/underweight. In multivariate analysis, overweight and obese patients were significantly more likely to be African American (odds ratio [OR], 3.93; 95% confidence interval [CI], 2.66–5.80) or Hispanic (OR, 1.44; CI, 1.02–2.04), be postmenopausal (OR, 1.63; CI, 1.28–2.07), have diabetes (OR, 4.60; CI, 2.60–8.12), have estrogen-receptor-positive DCIS (OR, 1.39; CI, 1.00–192), and present with a radiologic abnormality rather than clinical symptoms (OR, 1.35; CI, 1.01–1.80). At a median follow-up time of 4.96 years (range, 1.0–14.34 years), no significant differences in local recurrence rates were detected based on patients’ initial BMI category. Furthermore, there was no significant difference in risk of recurrence between diabetic patients receiving metformin or not. In conclusion, higher BMI is not associated with adverse biologic features or prognosis in patients with DCIS. PMID:22392043

  3. Negative affect predicts adults' ratings of the current, but not childhood, impact of adverse childhood events.

    PubMed

    LaNoue, Marianna; Graeber, David A; Helitzer, Deborah L; Fawcett, Jan

    2013-10-01

    Adverse childhood events (ACE's) have been empirically related to a wide range of negative health and mental health outcomes. However, not all individuals who experience ACE's follow a trajectory of poor outcomes, and not all individuals perceive the impact of ACE's as necessarily negative. The purpose of this study was to investigate positive and negative affect as predictors of adults' ratings of both the childhood and adult impact of their childhood adversity. Self-report data on ACE experiences, including number, severity, and 'impact' were collected from 158 community members recruited on the basis of having adverse childhood experiences. Results indicated that, regardless of event severity and number of different types of adverse events experienced, high levels of negative affect were the strongest predictor of whether the adult impact of the adverse childhood events was rated as negative. All individuals rated the childhood impact of events the same. Implications are discussed.

  4. Is there evidence that recent consolidation in the health insurance industry has adversely affected premiums?

    PubMed

    Kopit, William G

    2004-01-01

    James Robinson suggests that recent consolidation in the insurance market has been a cause of higher health insurance prices (premiums). Although the recent consolidation among health insurers and rising premiums are indisputable, it is unlikely that consolidation has had any adverse effect on premiums nationwide, and Robinson provides no data that suggest otherwise. Specifically, he does not present data showing an increase in concentration in any relevant market during the past few years, let alone any resulting increase in premiums. Health insurance consolidation in certain local markets could adversely affect premiums, but it seems clear that it is not a major national antitrust issue.

  5. Adverse psychosocial factors predict poorer prognosis in HIV disease: a meta-analytic review of prospective investigations.

    PubMed

    Chida, Yoichi; Vedhara, Kavita

    2009-05-01

    There is a growing epidemiological literature focusing on the association between psychosocial stress and human immunodeficiency virus (HIV) disease progression or acquired immunodeficiency syndrome (AIDS), but inconsistent findings have been published. We aimed to quantify the association between adverse psychosocial factors and HIV disease progression. We searched Medline; PsycINFO; Web of Science; PubMed up to 19 January 2009, and included population studies with a prospective design that investigated associations between adverse psychosocial factors and HIV disease progression or AIDS. Two reviewers independently extracted data on study characteristics, quality, and estimates of associations. The overall meta-analysis examined 36 articles including 100 psychosocial and disease related relationships. It exhibited a small, but robust positive association between adverse psychosocial factors and HIV progression (correlation coefficient as combined size effect 0.059, 95% confidence interval 0.043-0.074, p<0.001). Notably, sensitivity analyses showed that personality types or coping styles and psychological distress were more strongly associated with greater HIV disease progression than stress stimuli per se, and that all of the immunological and clinical outcome indicators (acquired immunodeficiency syndrome stage, CD4+ T-cell decline, acquired immunodeficiency syndrome diagnosis, acquired immunodeficiency syndrome mortality, and human immunodeficiency virus disease or acquired immunodeficiency syndrome symptoms) except for viral load exhibited detrimental effects by adverse psychosocial factors. In conclusion, the current review reveals a robust relationship between adverse psychosocial factors and HIV disease progression. Furthermore, there would appear to be some evidence for particular psychosocial factors to be most strongly associated with HIV disease progression.

  6. High Expression of p300 in Human Breast Cancer Correlates with Tumor Recurrence and Predicts Adverse Prognosis

    PubMed Central

    Xiao, Xiang-sheng; Cai, Mu-yan; Chen, Jie-wei; Guan, Xin-yuan; Kung, Hsiang-fu; Zeng, Yi-xin; Xie, Dan

    2011-01-01

    Objective Transcriptional coactivator p300 has been shown to play a variety of roles in the transcription process and mutation of p300 has been found in certain types of human cancers. However, the expression dynamics of p300 in breast cancer (BC) and its effect on BC patients’ prognosis are poorly understood. Methods In the present study, the methods of tissue microarray and immunohistochemistry (IHC) were used to investigate the protein expression of p300 in BCs. Receiver operating characteristic (ROC) curve analysis, Spearman’s rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were utilized to analyze the data. Results Based on the ROC curve analysis, the cutoff value for p300 high expression was defined when the H score for p300 was more than 105. High expression of p300 could be observed in 105/193 (54.4%) of BCs, in 6/25 (24.0%) of non-malignant breast tissues, respectively (P=0.004). Further correlation analysis showed that high expression of p300 was positively correlated with higher histological grade, advanced clinical stage and tumor recurrence (P<0.05). In univariate survival analysis, a significant association between high expression of p300 and shortened patients’ survival and poor progression-free survival was found (P<0.05). Importantly, p300 expression was evaluated as an independent prognostic factor in multivariate analysis (P<0.05). Conclusion Our findings provide a basis for the concept that high expression of p300 in BC may be important in the acquisition of a recurrence phenotype, suggesting that p300 high expression, as examined by IHC, is an independent biomarker for poor prognosis of patients with BC. PMID:23467396

  7. Family Adversity and Autonomic Reactivity Association With Immune Changes in HIV-Affected School Children

    PubMed Central

    Thomas, Melanie; Wara, Diane; Saxton, Katherine; Truskier, Mary; Chesney, Margaret; Boyce, W. Thomas

    2013-01-01

    Objective To explore whether primary school entry is associated with changes in immune system parameters in HIV-affected children. HIV-affected children are vulnerable to psychosocial stressors, regardless of their own HIV serological status. Methods Data from 38 HIV+ and 29 HIV− children born to seropositive women were obtained before and after school entry. Measures included family adversity questionnaires, autonomic nervous system (ANS) reactivity (based on mean arterial responses to challenge tasks), and enumerative and functional changes in peripheral blood immune parameters. Results In comparison to children who were HIV−, children who were HIV+ at baseline had fewer CD4+ T lymphocytes (M = 916 vs. 1206 cells/mm3 × 103; F = 7.8, p = .007), more CD8+ cells (M = 1046 vs. 720 cells/mm3 ×103; F = 7.98, p = .006), and diminished NK cell cytotoxicity (M =−.29 vs. .41; F = 8.87, p = .004). School entry was associated with changes in immune parameters, but HIV status was not associated with the magnitude of changes. Changes in immune parameters following school entry were associated with family stress and pre school entry ANS reactivity. Highly ANS reactive children had either the greatest increase in CD8+ cells following school entry or the greatest decrease, depending upon reported levels of family adversity (B = 215.35; t = 3.74, p < .001). Changes in functional immune assays were significantly associated with the interactions between HIV status and ANS reactivity. Conclusions These results suggest that autonomic reactivity is associated with increased immunological sensitivity to adverse or challenging social contexts among children affected by HIV. PMID:23766380

  8. VNN1 overexpression is associated with poor response to preoperative chemoradiotherapy and adverse prognosis in patients with rectal cancers

    PubMed Central

    Chai, Chi-Yung; Zhang, Yimin; Song, Junlong; Lin, Shih-Chun; Sun, Shengrong; Chang, I-Wei

    2016-01-01

    Background: Colorectal cancer is prevalent worldwide and it is also the fourth most common cause of cancer mortality. For rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) followed by radical proctectomy is gold standard treatment for patients with stage II/III rectal cancer. By data mining a public dataset of rectal cancer transcriptome (GSE35452) from Gene Expression Omnibus, National Center of Biotechnology Information (GEO, NCBI), we identified that VNN1 was the most significantly upregulated gene among those related to nitrogen compound metabolic process (GO:0006807). Therefore, we analyzed the clinicopathological correlation and prognostic impact of VNN1 protein (pantetheinase), which encoded by VNN1 gene. Methods: VNN1 immunostaining was performed in 172 rectal adenocarcinomas treated with preoperative CCRT followed by surgery, which were bisected into high- and low-expression subgroups. Furthermore, statistical analyses were performed to correlate the relationship between VNN1 immunoreactivity and clinicopathological features, as well as three survival indices: disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS). Results: High VNN1 immunoexpression was significantly associated with advanced pre-treatment and post-treatment disease and poor response to CCRT (all P ≤ .026). In addition, VNN1 overexpression was linked to adverse DSS, LRFS and MeFS in univariate analysis and served as an independent prognosticator indicating worse DSS and LRFS in multivariate analysis (all P ≤ .019). Conclusion: VNN1 may play a crucial role in rectal cancer progression and responsiveness to CCRT, and serve as a novel prognostic biomarker. Additional studies to clarify the molecular pathway are essential for developing potential VNN1-targeted therapies for rectal cancer. PMID:27830030

  9. Mancozeb adversely affects meiotic spindle organization and fertilization in mouse oocytes.

    PubMed

    Rossi, Gianna; Palmerini, Maria Grazia; Macchiarelli, Guido; Buccione, Roberto; Cecconi, Sandra

    2006-07-01

    In this study the effects of mancozeb, a widely used ethylenebisdithiocarbamate fungicide, on mouse oocyte meiotic maturation and fertilization were analyzed. Oocyte cumulus cell-complexes were matured in vitro with or without increasing concentrations of the fungicide (from 0.001 to 1 microg/ml) that, due to its different stability in organic solvents and in water, was resuspended either in dimethyl sulfoxide or in culture medium. Although, about 95% of oocytes reached the metaphase II stage; mancozeb-exposed oocytes showed a dose-dependent increase of alterations in spindle morphology, and this negative effect was more evident when the fungicide was resuspended in culture medium. Under the latter culture condition, oocytes matured in the presence of 0.1 and 1 microg/ml mancozeb showed a significant reduction also in the formation of male and female pronuclei. These results indicate that mancozeb can adversely affect mammalian reproductive performance, likely by perturbing microtubular organization during meiotic maturation.

  10. Factors Affecting the Timing of Signal Detection of Adverse Drug Reactions.

    PubMed

    Hashiguchi, Masayuki; Imai, Shungo; Uehara, Keiko; Maruyama, Junya; Shimizu, Mikiko; Mochizuki, Mayumi

    2015-01-01

    We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2-10 months for known ADRs and 19-44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0-122.5 days and 185.5-306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release.

  11. Catheterization of Intestinal Loops in Ruminants Does Not Adversely Affect Loop Function

    PubMed Central

    Inglis, G Douglas; Kastelic, John P; Uwiera, Richard R E

    2010-01-01

    Catheterized intestinal loops may be a valuable model to elucidate key components of the host response to various treatments within the small intestine of ruminants. We examined whether catheterizing ileal loops in sheep affected the overall health of animals and intestinal function, whether a bacterial treatment could be introduced into the loops through the catheters, and whether broad-spectrum antibiotics could sterilize the loops. Escherichia coli cells transformed to express the GFP gene were introduced readily into the loops through the catheters, and GFP E. coli cells were localized within the injected loops. Catheterized loops, interspaces, and intact ileum exhibited no abnormalities in tissue appearance or electrical resistance. Expression of the IFNγ, IL1α, IL4, IL6, IL12p40, IL18, TGFβ1, and TNFα cytokine genes did not differ significantly among the intact ileum, catheterized loops, and interspaces, nor did the expression of the gene for inducible nitric oxide synthase. Broad-spectrum antibiotics administered during surgery did not sterilize the loops or interspaces and did not substantively change the composition of the microbiota. However, antibiotics reduced the overall number of bacterial cells within the loop and the relative abundance of community constituents. We concluded that catheterization of intestinal loops did not adversely affect health or loop function in sheep. Furthermore, allowing animals to recover fully from surgery and to clear pharmaceuticals will remove any confounding effects due to these factors, making catheterized intestinal loops a feasible model for studying host responses in ruminants. PMID:21262134

  12. Sexually Dimorphic Responses to Early Adversity: Implications for Affective Problems and Autism Spectrum Disorder

    PubMed Central

    Davis, Elysia Poggi; Pfaff, Donald

    2014-01-01

    During gestation, development proceeds at a pace that is unmatched by any other stage of the lifecycle. For these reason the human fetus is particularly susceptible not only to organizing influences, but also to pathogenic disorganizing influences. Growing evidence suggests that exposure to prenatal adversity leads to neurological changes that underlie lifetime risks for mental illness. Beginning early in gestation, males and females show differential developmental trajectories and responses to stress. It is likely that sex-dependent organization of neural circuits during the fetal period influences differential vulnerability to mental health problems. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two developmental disorders: affective problems (greater female prevalence) and autism spectrum disorder (greater male prevalence). Recent prospective studies illustrating the neurodevelopmental consequences of fetal exposure to stress and stress hormones for males and females are considered here. Plausible biological mechanisms including the role of the sexually differentiated placenta are discussed. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two sets of developmental disorders: affective problems (greater female prevalence) and autism spectrum disorders (greater male prevalence). PMID:25038479

  13. 42 CFR 137.445 - Will an immediate reassumption appeal adversely affect the Self-Governance Tribe's rights in...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... affect the Self-Governance Tribe's rights in other self-governance negotiations? 137.445 Section 137.445..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Appeals Appeals of An Immediate Reassumption of A Self-Governance Program § 137.445 Will an immediate reassumption appeal adversely affect...

  14. NDST4 Is a Novel Candidate Tumor Suppressor Gene at Chromosome 4q26 and Its Genetic Loss Predicts Adverse Prognosis in Colorectal Cancer

    PubMed Central

    Tzeng, Sheng-Tai; Tsai, Ming-Hong; Chen, Chi-Long; Lee, Jing-Xing; Jao, Tzu-Ming; Yu, Sung-Liang; Yen, Sou-Jhy; Yang, Ya-Chien

    2013-01-01

    Background Genomic deletion at tumor suppressor loci is a common genetic aberration in human cancers. The study aimed to explore candidate tumor suppressor genes at chromosome 4q25-q28.2 and to delineate novel prognostic biomarkers associated with colorectal cancer (CRC). Methods Deletion mapping of chromosome 4q25-q28.2 was conducted in 114 sporadic CRC by loss of heterozygosity study with 11 microsatellite markers. A novel candidate tumor suppressor gene, namely NDST4, was identified at 4q26. Gene expression of NDST4 was investigated in 52 pairs of primary CRC tissues by quantitative reverse transcription-polymerase chain reaction. Allelic loss of NDST4 gene was further determined in 174 colorectal carcinomas by loss of heterozygosity analysis, and then was assessed for clinical relevance. Results One minimal deletion region was delineated between D4S2297 and D4S2303 loci at 4q26, where NDST4 was the only gene that had markedly been downregulated in CRC tumors. By laser capture microdissection, NDST4 RNA expression was demonstrated in colonic epithelial cells, but was undetectable in tumor cells. In total, 30 (57.7%) of 52 colorectal carcinomas showed a dramatic reduction in NDST4 gene expression compared with matched normal mucosae. The genetic loss of NDST4 was significantly associated with advanced pathological stage (P = 0.039) and poorer overall survival of patients (P = 0.036). Conclusions NDST4 gene is a novel candidate tumor suppressor gene in human cancer, and the loss of its function might be involved in CRC progression. In addition, the loss of heterozygosity assay, which was established to determine the allelic loss of NDST4 gene, could be a cost-effective tool for providing a useful biomarker of adverse prognosis in CRC. PMID:23825612

  15. Exposing physicians to reduced residency work hours did not adversely affect patient outcomes after residency.

    PubMed

    Jena, Anupam B; Schoemaker, Lena; Bhattacharya, Jay

    2014-10-01

    In 2003, work hours for physicians-in-training (residents) were capped by regulation at eighty hours per week, leading to the hotly debated but unexplored issue of whether physicians today are less well trained as a result of these work-hour reforms. Using a unique database of nearly all hospitalizations in Florida during 2000-09 that were linked to detailed information on the medical training history of the physician of record for each hospitalization, we studied whether hospital mortality and patients' length-of-stay varied according to the number of years a physician was exposed to the 2003 duty-hour regulations during his or her residency. We examined this database of practicing Florida physicians, using a difference-in-differences analysis that compared trends in outcomes of junior physicians (those with one-year post-residency experience) pre- and post-2003 to a control group of senior physicians (those with ten or more years of post-residency experience) who were not exposed to these reforms during their residency. We found that the duty-hour reforms did not adversely affect hospital mortality and length-of-stay of patients cared for by new attending physicians who were partly or fully exposed to reduced duty hours during their own residency. However, assessment of the impact of the duty-hour reforms on other clinical outcomes is needed.

  16. A systematic review of early life factors which adversely affect subsequent lung function.

    PubMed

    Kouzouna, A; Gilchrist, F J; Ball, V; Kyriacou, T; Henderson, J; Pandyan, A D; Lenney, W

    2016-09-01

    It has been known for many years that multiple early life factors can adversely affect lung function and future respiratory health. This is the first systematic review to attempt to analyse all these factors simultaneously. We adhered to strict a priori criteria for inclusion and exclusion of studies. The initial search yielded 29,351 citations of which 208 articles were reviewed in full and 25 were included in the review. This included 6 birth cohorts and 19 longitudinal population studies. The 25 studies reported the effect of 74 childhood factors (on their own or in combinations with other factors) on subsequent lung function reported as percent predicted forced expiration in one second (FEV1). The childhood factors that were associated with a significant reduction in future FEV1 could be grouped as: early infection, bronchial hyper-reactivity (BHR) / airway lability, a diagnosis of asthma, wheeze, family history of atopy or asthma, respiratory symptoms and prematurity / low birth weight. A complete mathematical model will only be possible if the raw data from all previous studies is made available. This highlights the need for increased cooperation between researchers and the need for international consensus about the outcome measures for future longitudinal studies.

  17. Early Life in a Barren Environment Adversely Affects Spatial Cognition in Laying Hens (Gallus gallus domesticus)

    PubMed Central

    Tahamtani, Fernanda M.; Nordgreen, Janicke; Nordquist, Rebecca E.; Janczak, Andrew M.

    2015-01-01

    Spatial cognition in vertebrates is adversely affected by a lack of environmental complexity during early life. However, to our knowledge, no previous studies have tested the effect of early exposure to varying degrees of environmental complexity on specific components of spatial cognition in chickens. There are two main rearing systems for laying hens in the EU: aviaries and cages. These two systems differ from one another in environmental complexity. The aim of the present study was to test the hypothesis that rearing in a barren cage environment relative to a complex aviary environment causes long-lasting deficits in the ability to perform spatial tasks. For this purpose, 24 white Dekalb laying hens, half of which had been reared in an aviary system and the other half in a conventional cage system, were tested in a holeboard task. Birds from both treatment groups learnt the task; however, the cage-reared hens required more time to locate rewards and had poorer levels of working memory. The latter finding supports the hypothesis that rearing in a barren environment causes long-term impairment of short-term memory in chickens. PMID:26664932

  18. No adverse affect after harvesting of free fibula osteoseptocutaneous flaps on gait function.

    PubMed

    Maurer-Ertl, Werner; Glehr, Mathias; Friesenbichler, Joerg; Sadoghi, Patrick; Wiedner, Maria; Haas, Franz; Leithner, Andreas; Windhager, Reinhard; Zwick, Ernst B

    2012-07-01

    The aim of this study was to analyze gait function and muscular strength on donor site after harvesting of a vascularized fibula osteoseptocutaneous flap. Nine patients with a mean follow-up of 33 months (range, 7-59) and a mean resection length of the middle portion of the fibula of 18.0 cm (range, 14.0-23.0) underwent an instrumented three-dimensional gait analysis to evaluate gait function. Furthermore, CYBEX II extremity system was used for muscular strength measurements. Subjective muscle strength measurements were performed according to Kendall et al. and were classified according to the British Medical Research Council. Intraindividual comparison between the operated and the nonoperated leg revealed no significant differences for gait function parameters (cadence, velocity, and stride length, P > 1.00) and for muscular strength measurements for flexion (knee: P = 0.93, ankle: P = 0.54) and extension (knee: P = 0.97, ankle: P= 0.21), respectively. In conclusion, intraindividual comparison of the operated and nonoperated sides after harvesting of the middle portion of the fibula for gaining a free fibula osteoseptocutaneous flap has no adverse affect on gait function or muscular flexion and extension strength on donor site at a mean follow-up of 33 months.

  19. Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees.

    PubMed

    Di Prisco, Gennaro; Cavaliere, Valeria; Annoscia, Desiderato; Varricchio, Paola; Caprio, Emilio; Nazzi, Francesco; Gargiulo, Giuseppe; Pennacchio, Francesco

    2013-11-12

    Large-scale losses of honey bee colonies represent a poorly understood problem of global importance. Both biotic and abiotic factors are involved in this phenomenon that is often associated with high loads of parasites and pathogens. A stronger impact of pathogens in honey bees exposed to neonicotinoid insecticides has been reported, but the causal link between insecticide exposure and the possible immune alteration of honey bees remains elusive. Here, we demonstrate that the neonicotinoid insecticide clothianidin negatively modulates NF-κB immune signaling in insects and adversely affects honey bee antiviral defenses controlled by this transcription factor. We have identified in insects a negative modulator of NF-κB activation, which is a leucine-rich repeat protein. Exposure to clothianidin, by enhancing the transcription of the gene encoding this inhibitor, reduces immune defenses and promotes the replication of the deformed wing virus in honey bees bearing covert infections. This honey bee immunosuppression is similarly induced by a different neonicotinoid, imidacloprid, but not by the organophosphate chlorpyriphos, which does not affect NF-κB signaling. The occurrence at sublethal doses of this insecticide-induced viral proliferation suggests that the studied neonicotinoids might have a negative effect at the field level. Our experiments uncover a further level of regulation of the immune response in insects and set the stage for studies on neural modulation of immunity in animals. Furthermore, this study has implications for the conservation of bees, as it will contribute to the definition of more appropriate guidelines for testing chronic or sublethal effects of pesticides used in agriculture.

  20. Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees

    PubMed Central

    Di Prisco, Gennaro; Cavaliere, Valeria; Annoscia, Desiderato; Varricchio, Paola; Caprio, Emilio; Nazzi, Francesco; Gargiulo, Giuseppe; Pennacchio, Francesco

    2013-01-01

    Large-scale losses of honey bee colonies represent a poorly understood problem of global importance. Both biotic and abiotic factors are involved in this phenomenon that is often associated with high loads of parasites and pathogens. A stronger impact of pathogens in honey bees exposed to neonicotinoid insecticides has been reported, but the causal link between insecticide exposure and the possible immune alteration of honey bees remains elusive. Here, we demonstrate that the neonicotinoid insecticide clothianidin negatively modulates NF-κB immune signaling in insects and adversely affects honey bee antiviral defenses controlled by this transcription factor. We have identified in insects a negative modulator of NF-κB activation, which is a leucine-rich repeat protein. Exposure to clothianidin, by enhancing the transcription of the gene encoding this inhibitor, reduces immune defenses and promotes the replication of the deformed wing virus in honey bees bearing covert infections. This honey bee immunosuppression is similarly induced by a different neonicotinoid, imidacloprid, but not by the organophosphate chlorpyriphos, which does not affect NF-κB signaling. The occurrence at sublethal doses of this insecticide-induced viral proliferation suggests that the studied neonicotinoids might have a negative effect at the field level. Our experiments uncover a further level of regulation of the immune response in insects and set the stage for studies on neural modulation of immunity in animals. Furthermore, this study has implications for the conservation of bees, as it will contribute to the definition of more appropriate guidelines for testing chronic or sublethal effects of pesticides used in agriculture. PMID:24145453

  1. Does Herpes Virus Reactivation Affect Prognosis in Idiopathic Sudden Sensorineural Hearing Loss?

    PubMed Central

    Park, Sang Man; Han, Chun; Lee, Jae Woo; Kong, Tae Hoon; Seo, Young Joon

    2017-01-01

    Objectives Several etiologies have been proposed to underlie idiopathic sudden sensorineural hearing loss (ISSNHL), including viral infection, vascular disturbance, and immune-mediated mechanisms. However, none of these mechanisms are conclusive. Should ISSNHL be caused by reactivation of a viral infection, antiviral treatment would be an important option. Thus, in this study, we reported the prognosis according to serologic test results of herpes viruses in patients with ISSNHL. We also evaluated treatment response with acyclovir and corticosteroids versus corticosteroids alone in herpes simplex virus (HSV) seropositive ISSNHL patients. Methods We compared hematologic examinations and the results of audiometry testing in 232 patients with ISSNHL. Statistical analyses for initial hearing impairment, progression of hearing impairment, recovery of hearing loss, and laboratory results were performed in all patients. All statistical analyses were performed using SPSS software. Results The 232 ISSNHL patients were divided into two subgroups according to HSV immunoglobulin M (IgM) serologic results (seropositive or seronegative). When the seropositive group was compared to the seronegative group, age, gender, body mass index (BMI), white blood cell, absolute neutrophil count, absolute monocyte count, and platelet count were not significantly different. Initial hearing level, final recovery hearing level, and recovery time were also not significantly different between the two groups (P>0.05). Though there were no significant differences in age, gender, BMI, or viral HSV IgM titer, the two groups had similar initial hearing level, final recovery hearing level, and recovery time. The difference in hearing threshold before and after treatment was larger (18.7±37.1) in the group receiving antiviral medication than in the corticosteroids group (11.0±44.5), but this difference was not significant (P=0.619). Conclusion There was no significant difference of prognosis between

  2. Expression of the potential therapeutic target CXXC5 in primary acute myeloid leukemia cells - high expression is associated with adverse prognosis as well as altered intracellular signaling and transcriptional regulation

    PubMed Central

    Bruserud, Øystein; Reikvam, Håkon; Fredly, Hanne; Skavland, Jørn; Hagen, Karen-Marie; van Hoang, Tuyen Thy; Brenner, Annette K.; Kadi, Amir; Astori, Audrey; Gjertsen, Bjørn Tore; Pendino, Frederic

    2015-01-01

    The CXXC5 gene encodes a transcriptional activator with a zinc-finger domain, and high expression in human acute myeloid leukemia (AML) cells is associated with adverse prognosis. We now characterized the biological context of CXXC5 expression in primary human AML cells. The global gene expression profile of AML cells derived from 48 consecutive patients was analyzed; cells with high and low CXXC5 expression then showed major differences with regard to extracellular communication and intracellular signaling. We observed significant differences in the phosphorylation status of several intracellular signaling mediators (CREB, PDK1, SRC, STAT1, p38, STAT3, rpS6) that are important for PI3K-Akt-mTOR signaling and/or transcriptional regulation. High CXXC5 expression was also associated with high mRNA expression of several stem cell-associated transcriptional regulators, the strongest associations being with WT1, GATA2, RUNX1, LYL1, DNMT3, SPI1, and MYB. Finally, CXXC5 knockdown in human AML cell lines caused significantly increased expression of the potential tumor suppressor gene TSC22 and genes encoding the growth factor receptor KIT, the cytokine Angiopoietin 1 and the selenium-containing glycoprotein Selenoprotein P. Thus, high CXXC5 expression seems to affect several steps in human leukemogenesis, including intracellular events as well as extracellular communication. PMID:25605239

  3. Antioxidant-rich beetroot juice does not adversely affect acute neuromuscular adaptation following eccentric exercise.

    PubMed

    Clifford, Tom; Bell, Oliver; West, Daniel J; Howatson, Glyn; Stevenson, Emma J

    2017-04-01

    This study examined the effects of beetroot juice on the repeated bout effect (RBE) to eccentric exercise. Twenty-nine recreationally active males performed two bouts of 100-drop jumps, separated by 14-21 days. Using a double-blind, independent groups design, participants consumed either a higher dose beetroot juice (H-BT; 250 ml, n = 10), a lower dose beetroot juice (L-BT; 125 ml, n = 9) or an isocaloric placebo (PLA; 250 ml, n = 10) for 3 days after bout 1; no drinks were consumed after bout 2. Maximal isometric voluntary contraction (MIVC), countermovement jump (CMJ), pressure-pain threshold (PPT) and creatine kinase (CK) were measured pre, post, 24, 48 and 72 h following both bouts. In bout 2, CMJ and MIVC recovered quicker and CK activity was attenuated (versus bout 1) (P < 0.05) in all groups, demonstrating an RBE. At 24 h post bout 1, MIVC was 84.1 ± 16.1, 83.6 ± 11.6, 79.7 ± 15.1% relative to baseline values in the H-BT, L-BT and PLA groups, respectively; at 24 h post bout 2, MIVC recovered to 90.7 ± 13.7, 92.9 ± 6.9, 87.8 ± 6.9, in the H-BT, L-BT and PLA groups, respectively. These findings suggest that supplementation with antioxidant-rich beetroot juice does not adversely affect acute adaptations to a bout of eccentric exercise.

  4. Quality of life and functional capacity are adversely affected in osteoarthritis patients with neuropathic pain.

    PubMed

    Aşkın, Ayhan; Özkan, Ayten; Tosun, Aliye; Demirdal, Ümit Seçil; İsnaç, Fethi

    2017-03-01

    The aim of this study was to examine the neuropathic pain component of knee osteoarthritis (OA) patients and to investigate the relationship between neuropathic pain, disease stage, functional state, depression, anxiety, and quality of life. This study included 60 patients with knee OA. All demographic data and radiological results were recorded. Visual Analog Scale (VAS), Timed Up and Go Test, Chair Stand Test, Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), PainDETECT questionnaire, DN4 questionnaire, Short form-36 questionnaire, and Hospital Anxiety Depression Scale were performed for each patient. Neuropathic pain was detected in 66.7% of patients based on the PainDETECT scale and in 46.7% of patients based on DN4 scale. VAS-resting, OA grade, WOMAC scores, and SF-scores showed a significant difference in patients that detected neuropathic pain with PainDETECT (p<0.05). Based on the DN4 scale, patients with neuropathic pain had significantly higher WOMAC scores and significantly lower SF-36 scores (p<0.05). The PainDETECT questionnaire scores showed positive correlations with Timed Up-and-go Test, VAS-resting, WOMAC scores, Hospital Anxiety Depression Scale scores, and a negative correlation with all SF-36 scores (p<0.05). DN4 questionnaire scores showed a negative correlation with SF-36 scores and positive correlation with WOMAC scores (p<0.05). To conclude, it should be kept in mind that patients with knee OA who describe intense pain may have a neuropathic component involved in the clinical condition. Quality of life and functional capacity are adversely affected in patients with knee OA who have neuropathic pain. This should be taken into account while planning the treatment of these patients.

  5. Probabilities of adverse weather affecting transport in Europe: climatology and scenarios up to the 2050s

    NASA Astrophysics Data System (ADS)

    Vajda, A.; Tuomenvirta, H.; Jokinen, P.; Luomaranta, A.; Makkonen, L.; Tikanmäki, M.; Groenemeijer, P.; Saarikivi, P.; Michaelides, S.; Papadakis, M.; Tymvios, F.; Athanasatos, S.

    2012-04-01

    This paper provides the first comprehensive climatology of the adverse and extreme weather events affecting the European transport system by estimating the frequency (or probability) of phenomena for the present climate (1971-2000) and an overview of the projected changes in some of these extremes in the future climate until the 2050s. The research was carried out within the framework of the EWENT Project that addresses the European Union (EU) policies and strategies related to climate change, with a particular focus on extreme weather impacts on the EU transportation system. This project is funded by the Seventh Framework Programme (Transports, call ID FPT7-TPT-2008-RTD-1). The analyzed phenomena are wind, snow, blizzards, heavy precipitation, cold spells and heat waves. In addition, reduced visibility conditions determined by fog and dust events, small-scale phenomena affecting the transport system, such as thunderstorms, lightning, large hail and tornadoes and events damaging infrastructure of the transport system, have been considered. Frequency and probability analysis of past and present ex¬tremes were performed using observational and atmospheric reanalysis data. Future changes in the probability of severe events were assessed based on six regional climate model simulations produced in the FP6 ENSEMBLES project (http://www.ensembles-eu.org/). To facilitate the assessment of impacts and consequences of extreme phenomena on a continental level, the WP2 Deliverable introduces a regionalization of the European extreme phenomena, defining the climate zones with similarities in extreme phenomena. The projected changes as well as large natural variability in weather extremes on the transportation network will have impacts of both signs. The decline of extreme cold and snowfall over most of the continent implies a positive impact on road, rail, inland water and air transportation, e.g., by reducing snow removal. However, even with a general decreasing trend in

  6. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S... that are not likely to adversely affect listed species or critical habitat. 402.45 Section...

  7. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S... that are not likely to adversely affect listed species or critical habitat. 402.45 Section...

  8. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S... that are not likely to adversely affect listed species or critical habitat. 402.45 Section...

  9. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S... that are not likely to adversely affect listed species or critical habitat. 402.45 Section...

  10. 50 CFR 402.45 - Alternative consultation on FIFRA actions that are not likely to adversely affect listed species...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S... that are not likely to adversely affect listed species or critical habitat. 402.45 Section...

  11. Exposure to serotonin adversely affects oligodendrocyte development and myelination in vitro.

    PubMed

    Fan, Lir-Wan; Bhatt, Abhay; Tien, Lu-Tai; Zheng, Baoying; Simpson, Kimberly L; Lin, Rick C S; Cai, Zhengwei; Kumar, Praveen; Pang, Yi

    2015-05-01

    patterns of contactin-associated protein (Caspr) clustering were observed at the sites of Node of Ranvier, suggesting that 5-HT exposure may affect other axon-derived factors for myelination. In summary, this is the first study to demonstrate that manipulation of serotonin levels affects OL development and myelination, which may contribute to altered neural connectivity noted in SSRIs-treated animals. The current in vitro study demonstrated that exposure to high level of serotonin (5-HT) led to aberrant oligodendrocyte (OL) development, cell injury, and myelination deficit. We propose that elevated extracellular serotonin levels in the fetal brain, such as upon the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, may adversely affect OL development and/or myelination, thus contributing to altered neural connectivity seen in Autism Spectrum Disorders. OPC = oligodendrocyte progenitor cell.

  12. Telomere profiles and tumor-associated macrophages with different immune signatures affect prognosis in glioblastoma.

    PubMed

    Hung, Noelyn A; Eiholzer, Ramona A; Kirs, Stenar; Zhou, Jean; Ward-Hartstonge, Kirsten; Wiles, Anna K; Frampton, Chris M; Taha, Ahmad; Royds, Janice A; Slatter, Tania L

    2016-03-01

    Telomere maintenance is a hallmark of cancer and likely to be targeted in future treatments. In glioblastoma established methods of identifying telomerase and alternative lengthening of telomeres leave a significant proportion of tumors with no defined telomere maintenance mechanism. This study investigated the composition of these tumors using RNA-Seq. Glioblastomas with an indeterminate telomere maintenance mechanism had an increased immune signature compared with alternative lengthening of telomeres and telomerase-positive tumors. Immunohistochemistry for CD163 confirmed that the majority (80%) of tumors with an indeterminate telomere maintenance mechanism had a high presence of tumor-associated macrophages. The RNA-Seq and immunostaining data separated tumors with no defined telomere maintenance mechanism into three subgroups: alternative lengthening of telomeres like tumors with a high presence of tumor-associated macrophages and telomerase like tumors with a high presence of tumor-associated macrophages. The third subgroup had no increase in tumor-associated macrophages and may represent a distinct category. The presence of tumor-associated macrophages conferred a worse prognosis with reduced patient survival times (alternative lengthening of telomeres with and without macrophages P=0.0004, and telomerase with and without macrophages P=0.013). The immune signatures obtained from RNA-Seq were significantly different between telomere maintenance mechanisms. Alternative lengthening of telomeres like tumors with macrophages had increased expression of interferon-induced proteins with tetratricopeptide repeats (IFIT1-3). Telomerase-positive tumors with macrophages had increased expression of macrophage receptor with collagenous structure (MARCO), CXCL12 and sushi-repeat containing protein x-linked 2 (SRPX2). Telomerase-positive tumors with macrophages were also associated with a reduced frequency of total/near total resections (44% vs >76% for all other subtypes

  13. Severe Affective and Behavioural Dysregulation Is Associated with Significant Psychosocial Adversity and Impairment

    ERIC Educational Resources Information Center

    Jucksch, Viola; Salbach-Andrae, Harriet; Lenz, Klaus; Goth, Kirstin; Dopfner, Manfred; Poustka, Fritz; Freitag, Christine M.; Lehmkuhl, Gerd; Lehmkuhl, Ulrike; Holtmann, Martin

    2011-01-01

    Background: Recently, a highly heritable behavioral phenotype of simultaneous deviance on the Anxious/Depressed, Attention Problems, and Aggressive Behavior syndrome scales has been identified on the Child Behavior Checklist (CBCL-Dysregulation Profile, CBCL-DP). This study aims to investigate psychosocial adversity and impairment of the CBCL-DP.…

  14. 25 CFR 1000.317 - Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... AFA adversely affected by a reassumption action? 1000.317 Section 1000.317 Indians OFFICE OF THE....317 Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption... negotiate an AFA for programs not affected by the reassumption....

  15. 25 CFR 1000.317 - Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... AFA adversely affected by a reassumption action? 1000.317 Section 1000.317 Indians OFFICE OF THE....317 Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption... negotiate an AFA for programs not affected by the reassumption....

  16. 25 CFR 1000.317 - Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... AFA adversely affected by a reassumption action? 1000.317 Section 1000.317 Indians OFFICE OF THE....317 Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption... negotiate an AFA for programs not affected by the reassumption....

  17. 25 CFR 1000.317 - Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... AFA adversely affected by a reassumption action? 1000.317 Section 1000.317 Indians OFFICE OF THE....317 Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption... negotiate an AFA for programs not affected by the reassumption....

  18. 25 CFR 1000.317 - Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... AFA adversely affected by a reassumption action? 1000.317 Section 1000.317 Indians OFFICE OF THE....317 Is a Tribe's/Consortium's general right to negotiate an AFA adversely affected by a reassumption... negotiate an AFA for programs not affected by the reassumption....

  19. 30 CFR 585.816 - What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... conditions adversely affect a cable, pipeline, or facility? 585.816 Section 585.816 Mineral Resources BUREAU... affect a cable, pipeline, or facility? If environmental or other conditions adversely affect a cable, pipeline, or facility so as to endanger the safety or the environment, you must: (a) Submit a plan...

  20. 30 CFR 585.816 - What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... conditions adversely affect a cable, pipeline, or facility? 585.816 Section 585.816 Mineral Resources BUREAU... affect a cable, pipeline, or facility? If environmental or other conditions adversely affect a cable, pipeline, or facility so as to endanger the safety or the environment, you must: (a) Submit a plan...

  1. 30 CFR 585.816 - What must I do if environmental or other conditions adversely affect a cable, pipeline, or facility?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... conditions adversely affect a cable, pipeline, or facility? 585.816 Section 585.816 Mineral Resources BUREAU... affect a cable, pipeline, or facility? If environmental or other conditions adversely affect a cable, pipeline, or facility so as to endanger the safety or the environment, you must: (a) Submit a plan...

  2. Does Employment-Related Resilience Affect the Relationship between Childhood Adversity, Community Violence, and Depression?

    PubMed

    Welles, Seth L; Patel, Falguni; Chilton, Mariana

    2017-04-01

    Depression is a barrier to employment among low-income caregivers receiving Temporary Assistance for Needy Families (TANF), and adverse childhood experiences (ACEs) and exposure to community violence (ECV) are often associated with depression. Using baseline data of 103 TANF caregivers of young children of the Building Wealth and Health Network Randomized Controlled Trial Pilot, this study investigated associations of two forms of employment-related resilience-self-efficacy and employment hope-with exposure to adversity/violence and depression, measured by the Center for Epidemiologic Studies Depression (CES-D) short form. Using contingency table analysis and regression analysis, we identified associations between ACEs and depression [OR = 1.70 (1.25-2.32), p = 0.0008] and having high levels of ECV with a 6.9-fold increased risk for depression when compared with those without ECV [OR = 6.86 (1.43-33.01), p = 0.02]. While self-efficacy and employment hope were significantly associated with depression, neither resilience factor impacted the association of ACE level and depression, whereas self-efficacy and employment hope modestly reduced the associations between ECV and depression, 13 and 16%, respectively. Results suggest that self-efficacy and employment hope may not have an impact on the strong associations between adversity, violence, and depression.

  3. Folic acid supplementation can adversely affect murine neural tube closure and embryonic survival.

    PubMed

    Marean, Amber; Graf, Amanda; Zhang, Ying; Niswander, Lee

    2011-09-15

    Neural tube defects (NTDs), a common birth defect in humans, result from the failure of the embryonic neural tube (NT) to close properly. NT closure is a complex, poorly understood morphogenetic process influenced by genes and environment. The most effective environmental influence in decreasing the risk for NTDs is folic acid (FA) fortification and supplementation, and these findings led to the recommendation of periconceptual FA intake and mandatory fortification of the US grain supply in 1998. To explore the relationship between genetics and responsiveness to FA supplementation, we used five mouse NTDs models-Zic2, Shroom3, Frem2, Grhl2 (Grainyhead-like 2) and L3P (Line3P)-and a long-term generational FA supplementation scheme. Contrary to expectations, we find that three genetic mutants respond adversely to FA supplementation with increased incidence of NTDs in homozygous mutants, occurrence of NTDs in heterozygous embryos and embryonic lethality prior to NT closure. Because of these unexpected responses, we examined NTD risk after short-term FA supplementation. Our results indicate that, for the same genetic allele, NTD risk can depend on the length of FA exposure. Our data indicate that, depending on the gene mutation, FA supplementation may adversely influence embryonic development and NT closure.

  4. Does Maternal Prenatal Stress Adversely Affect the Child's Learning and Memory at Age Six?

    ERIC Educational Resources Information Center

    Gutteling, Barbara M.; de Weerth, Carolina; Zandbelt, Noortje; Mulder, Eduard J. H.; Visser, Gerard H. A.; Buitelaar, Jan K.

    2006-01-01

    Prenatal maternal stress has been shown to affect postnatal development in animals and humans. In animals, the morphology and function of the offspring's hippocampus is negatively affected by prenatal maternal stress. The present study prospectively investigated the influence of prenatal maternal stress on learning and memory of 112 children (50…

  5. Lead-induced oxidative stress adversely affects health of the occupational workers.

    PubMed

    Khan, D A; Qayyum, S; Saleem, S; Khan, F A

    2008-10-01

    Lead is a persistent toxic metal and associated with impairment of various body functions in occupational workers. The main objective was to determine the lead-induced oxidative stress and adverse health effects by biochemical markers in industrial workers. One hundred and forty-eight males consisting of 87 lead-exposed industrial workers and 61 controls were included. Blood lead level (BLL) was determined on a 3010B ESA lead analyzer. Blood complete counts were done on a hematology analyzer. Biochemical markers including serum uric acid, urea, creatinine, phosphate, alanine aminotransferase (ALT), and gamma glutamyltransferase (GGT) were measured on a Selectra E auto analyzer. Serum malondialdehyde (MDA) was measured spectrophotometrically and C-reactive protein (CRP) on Immulite-1000. Results revealed that lead-exposed workers had significantly high BLLs, median (range), 29.1 (9.0-61.1) microg/dL compared with controls, 8.3 (1.0-21.7) microg/dL. Oxidative stress (MDA, GGT) and inflammatory markers (high-sensitivity CRP) were significantly increased (P < or = 0.05). Blood pressure was raised, whereas hemoglobin was decreased in exposed group (P < or = 0.002). Serum urea, uric acid, phosphate, and ALT were significantly raised in lead-exposed workers (P < or = 0.001). Serum albumin, total proteins, and glomerular filtration rate (GFR) were decreased. Blood lead showed a significant positive correlation with serum GGT (r = 0.63), MDA (r = 0.71), CRP (r = 0.75), urea (r = 0.34), creatinine (r = 0.51), and uric acid (r = 0.29) (P < or = 0.01). It is concluded that lead exposure increases oxidative stress that correlates with adverse changes in hematological, renal, and hepatic function in the occupational workers. Elevated blood lead has positive correlation with oxidative stress, inflammatory and biochemical markers that might be used to detect impairment in the body function in lead exposed workers.

  6. Diagnosis of potential stressors adversely affecting benthic invertebrate communities in Greenwich Bay, Rhode Island, USA

    EPA Science Inventory

    Greenwich Bay is an urbanized embayment of Narragansett Bay potentially impacted by multiple stressors. The present study identified the important stressors affecting Greenwich Bay benthic fauna. First, existing data and information were used to confirm that the waterbody was imp...

  7. Can aircraft noise less than or equal 115 to dBA adversely affect reproductive outcome in USAF women?

    NASA Astrophysics Data System (ADS)

    Brubaker, P. A.

    1985-06-01

    It has been suggested, mainly through animal studies, that exposure to high noise levels may be associated with lower birth weight, reduced gestational length and other adverse reproductive outcomes. Few studies have been done on humans to show this association. The Air Force employs pregnant women in areas where there is a high potential for exposure to high noise levels. This study proposes a method to determine if there is an association between high frequency noise levels or = 115 dBA and adverse reproductive outcomes through a review of records and self-administered questionnaires in a case-comparison design. Prevelance rates will be calculated and a multiple logistic regression analysis computed for the independent variables that can affect reproduction.

  8. Elevated depressive affect is associated with adverse cardiovascular outcomes among African Americans with chronic kidney disease.

    PubMed

    Fischer, Michael J; Kimmel, Paul L; Greene, Tom; Gassman, Jennifer J; Wang, Xuelei; Brooks, Deborah H; Charleston, Jeanne; Dowie, Donna; Thornley-Brown, Denyse; Cooper, Lisa A; Bruce, Marino A; Kusek, John W; Norris, Keith C; Lash, James P

    2011-09-01

    This study was designed to examine the impact of elevated depressive affect on health outcomes among participants with hypertensive chronic kidney disease in the African-American Study of Kidney Disease and Hypertension (AASK) Cohort Study. Elevated depressive affect was defined by Beck Depression Inventory II (BDI-II) thresholds of 11 or more, above 14, and by 5-Unit increments in the score. Cox regression analyses were used to relate cardiovascular death/hospitalization, doubling of serum creatinine/end-stage renal disease, overall hospitalization, and all-cause death to depressive affect evaluated at baseline, the most recent annual visit (time-varying), or average from baseline to the most recent visit (cumulative). Among 628 participants at baseline, 42% had BDI-II scores of 11 or more and 26% had a score above 14. During a 5-year follow-up, the cumulative incidence of cardiovascular death/hospitalization was significantly greater for participants with baseline BDI-II scores of 11 or more compared with those with scores <11. The baseline, time-varying, and cumulative elevated depressive affect were each associated with a significant higher risk of cardiovascular death/hospitalization, especially with a time-varying BDI-II score over 14 (adjusted HR 1.63) but not with the other outcomes. Thus, elevated depressive affect is associated with unfavorable cardiovascular outcomes in African Americans with hypertensive chronic kidney disease.

  9. Adverse childhood experiences associate to reduced glutamate levels in the hippocampus of patients affected by mood disorders.

    PubMed

    Poletti, Sara; Locatelli, Clara; Falini, Andrea; Colombo, Cristina; Benedetti, Francesco

    2016-11-03

    Adverse childhood experiences (ACE) can possibly permanently alter the stress response system, affect the glutamatergic system and influence hippocampal volume in mood disorders. The aim of the study is to investigate the association between glutamate levels in the hippocampus, measured through single proton magnetic resonance spectroscopy (1H-MRS), and ACE in patients affected by mood disorders and healthy controls. Higher levels of early stress associate to reduced levels of Glx/Cr in the hippocampus in depressed patients but not in healthy controls. Exposure to stress during early life could lead to a hypofunctionality of the glutamatergic system in the hippocampus of depressed patients. Abnormalities of glutamatergic signaling could then possibly underpin the structural and functional abnormalities observed in patients affected by mood disorders.

  10. Exposure to zidovudine adversely affects mitochondrial turnover in primary T cells.

    PubMed

    Wallace, Zoë R; Sanderson, Sharon; Simon, Anna Katarina; Dorrell, Lucy

    2016-09-01

    Zidovudine (ZDV) is a widely used component of antiretroviral therapy (ART) in resource-limited settings, despite its known adverse effects, which include mitochondrial toxicity in muscle, liver and adipose tissue. It has also been associated with impaired immunological recovery. We hypothesised that ZDV might impair mitochondrial health and survival of primary T cells. We performed a cross-sectional analysis of mitochondrial function, mitophagy and susceptibility to apoptosis in healthy donor primary T cells after exposure to ZDV in vitro, together with T cells from patients who were virologically suppressed on ZDV-containing ART regimens for ≥1 year and age-matched subjects receiving non-ZDV ART regimens. The proportion of T cells expressing mitochondrial reactive oxygen species (mtROS) was significantly higher after in vitro (CD4(+) T cells and CD8(+) T cells) and in vivo (CD4(+) T cells) exposure to ZDV than other antiretroviral agents. We did not detect any effect of ZDV on mitophagy, as indicated by change in autophagic flux. However, spontaneous apoptosis, indicated by upregulation of caspase-3 was greater in ZDV-exposed T cells. In conclusion, ZDV exposure was associated with impaired mitochondrial turnover and increased susceptibility to apoptosis in T cells. These mechanisms could contribute to sub-optimal immune reconstitution.

  11. Coralline algal physiology is more adversely affected by elevated temperature than reduced pH

    PubMed Central

    Vásquez-Elizondo, Román Manuel; Enríquez, Susana

    2016-01-01

    In this study we analyzed the physiological responses of coralline algae to ocean acidification (OA) and global warming, by exposing algal thalli of three species with contrasting photobiology and growth-form to reduced pH and elevated temperature. The analysis aimed to discern between direct and combined effects, while elucidating the role of light and photosynthesis inhibition in this response. We demonstrate the high sensitivity of coralline algae to photodamage under elevated temperature and its severe consequences on thallus photosynthesis and calcification rates. Moderate levels of light-stress, however, were maintained under reduced pH, resulting in no impact on algal photosynthesis, although moderate adverse effects on calcification rates were still observed. Accordingly, our results support the conclusion that global warming is a stronger threat to algal performance than OA, in particular in highly illuminated habitats such as coral reefs. We provide in this study a quantitative physiological model for the estimation of the impact of thermal-stress on coralline carbonate production, useful to foresee the impact of global warming on coralline contribution to reef carbon budgets, reef cementation, coral recruitment and the maintenance of reef biodiversity. This model, however, cannot yet account for the moderate physiological impact of low pH on coralline calcification. PMID:26740396

  12. Maternal and young child nutrition adversely affected by external shocks such as increasing global food prices.

    PubMed

    Darnton-Hill, Ian; Cogill, Bruce

    2010-01-01

    Rising food prices, resulting from the ongoing global economic crisis, fuel price volatility, and climate change, have an adverse impact upon the poor, especially those in food-importing, resource-limited countries. The conventional approach by large organizations has been to advocate for increased staple crop yields of mainly cereals. High food prices are predicted to continue to at least 2015. Past shocks and their known impacts upon nutrition were reviewed. Price instability and increases have long been an existing global problem, which has been exacerbated by recent macroeconomic shocks such as acute emergencies due to war and civil strife, acute climatic events, increase in food prices, fuel price volatility, dysfunction of the global financial systems, long-term climate change, and the emergence of failed states. The FAO estimated that there were 815 million "hungry" people in 2006, with a now additional 75-135 million with increased vulnerability, and currently it is estimated that there are one billion people at risk of food insecurity. The shocks initially compromise maternal and child nutrition, mainly through a reduction in dietary quality and an increase in micronutrient deficiencies and concomitant increases in infectious disease morbidity and mortality. A further reduction in the quantity of diet may follow with greater underweight and wasting. Recent macroeconomic shocks have greatly increased the number of people who are vulnerable to hunger in developing countries. Nutritional surveillance systems need to be strengthened and expanded to inform policy decisions.

  13. Coralline algal physiology is more adversely affected by elevated temperature than reduced pH

    NASA Astrophysics Data System (ADS)

    Vásquez-Elizondo, Román Manuel; Enríquez, Susana

    2016-01-01

    In this study we analyzed the physiological responses of coralline algae to ocean acidification (OA) and global warming, by exposing algal thalli of three species with contrasting photobiology and growth-form to reduced pH and elevated temperature. The analysis aimed to discern between direct and combined effects, while elucidating the role of light and photosynthesis inhibition in this response. We demonstrate the high sensitivity of coralline algae to photodamage under elevated temperature and its severe consequences on thallus photosynthesis and calcification rates. Moderate levels of light-stress, however, were maintained under reduced pH, resulting in no impact on algal photosynthesis, although moderate adverse effects on calcification rates were still observed. Accordingly, our results support the conclusion that global warming is a stronger threat to algal performance than OA, in particular in highly illuminated habitats such as coral reefs. We provide in this study a quantitative physiological model for the estimation of the impact of thermal-stress on coralline carbonate production, useful to foresee the impact of global warming on coralline contribution to reef carbon budgets, reef cementation, coral recruitment and the maintenance of reef biodiversity. This model, however, cannot yet account for the moderate physiological impact of low pH on coralline calcification.

  14. Coralline algal physiology is more adversely affected by elevated temperature than reduced pH.

    PubMed

    Vásquez-Elizondo, Román Manuel; Enríquez, Susana

    2016-01-07

    In this study we analyzed the physiological responses of coralline algae to ocean acidification (OA) and global warming, by exposing algal thalli of three species with contrasting photobiology and growth-form to reduced pH and elevated temperature. The analysis aimed to discern between direct and combined effects, while elucidating the role of light and photosynthesis inhibition in this response. We demonstrate the high sensitivity of coralline algae to photodamage under elevated temperature and its severe consequences on thallus photosynthesis and calcification rates. Moderate levels of light-stress, however, were maintained under reduced pH, resulting in no impact on algal photosynthesis, although moderate adverse effects on calcification rates were still observed. Accordingly, our results support the conclusion that global warming is a stronger threat to algal performance than OA, in particular in highly illuminated habitats such as coral reefs. We provide in this study a quantitative physiological model for the estimation of the impact of thermal-stress on coralline carbonate production, useful to foresee the impact of global warming on coralline contribution to reef carbon budgets, reef cementation, coral recruitment and the maintenance of reef biodiversity. This model, however, cannot yet account for the moderate physiological impact of low pH on coralline calcification.

  15. Weight Reduction in Athletes May Adversely Affect the Phagocytic Function of Monocytes.

    ERIC Educational Resources Information Center

    Kono, Ichiro; And Others

    1988-01-01

    Study of the monocyte phagocytic function in nine competitive athletes before and after a two-week weight reduction (through calorie restriction) program revealed that their pre-program phagocytic activity was higher than in sedentary controls but decreased significantly after the program. This suggests calorie restriction may affect the human…

  16. Does maternal prenatal stress adversely affect the child's learning and memory at age six?

    PubMed

    Gutteling, Barbara M; de Weerth, Carolina; Zandbelt, Noortje; Mulder, Eduard J H; Visser, Gerard H A; Buitelaar, Jan K

    2006-12-01

    Prenatal maternal stress has been shown to affect postnatal development in animals and humans. In animals, the morphology and function of the offspring's hippocampus is negatively affected by prenatal maternal stress. The present study prospectively investigated the influence of prenatal maternal stress on learning and memory of 112 children (50 boys, 62 girls, Age: M=6.7 years, SD=8.4 months), with the Test of Memory and Learning (TOMAL). Maternal stress levels were determined three times during pregnancy by self-report questionnaires. Furthermore, maternal saliva cortisol samples were used as a measure of hypothalamus-pituitary-adrenal axis functioning. Results of hierarchical multivariate regression analyses showed that maternal life events measured during the first part of pregnancy were negatively associated with the child's attention/concentration index, while controlling for overall IQ, gender, and postnatal stress. No associations were found between prenatal maternal cortisol and the offspring's learning and memory.

  17. [Clinical usefulness of ondansetron hydrochloride for nausea and vomiting during repeated courses of chemotherapy for malignant lymphoma--impact of prognosis announcement on anti-emetic effect and evaluation of patient perception of chemotherapy-associated adverse events].

    PubMed

    Kodama, Fumio; Mohri, Hiroshi; Motomura, Shigeki; Fukawa, Hitoshi; Tanabe, Juichi; Koharasawa, Hideyuki; Kanamori, Heiwa; Hashimoto, Yoshimi; Harano, Hiroshi; Sakai, Rika; Tomita, Naoto; Fujimaki, Katsumichi; Takemura, Sachiya; Hattori, Michiko

    2002-02-01

    We evaluated the efficacy and safety of ondansetron hydrochloride (OND) on nausea and vomiting during repeated courses of CHOP or ACOMP-B therapy in patients with malignant lymphoma. The impact of the prognosis announcement on the anti-emetic effect and chemotherapy-associated adverse events was also investigated. Forty-two subjects with malignant lymphoma who underwent CHOP or ACOMP-B therapy including cyclophosphamide 600 mg/m2 and adriamycin 40 mg/m2 were investigated for a maximum of 6 courses. For acute nausea and vomiting, ondansetron was injected intravenously before the start of chemotherapy on the first day of each course of chemotherapy. For delayed emesis, ondansetron was administered orally for 4 days from the following day. The efficacy on acute nausea and vomiting was found to be 95.0% (1st course), 95.0% (2nd course), 90.9% (3rd course), 88.2% (4th course), 92.3% (5th course) and 91.7% (6th course), respectively. A high efficacy of > or = 85% was also obtained for delayed nausea and vomiting on each day. Though the adverse event of elevated GPT value developed in one subject. It was mild and resolved. No difference in efficacy was seen with or without announcement of prognosis to patients. Following the investigation on antiemetic effect, patient perception of chemotherapy-induced adverse events was evaluated. The most common event was hair loss, followed by taste abnormality and numbness and hyposthesia of the tips of the fingers. The incidence of nausea and vomiting was the 4th and 5th most common, which are less frequent than in the report of Coates in 1983. In conclusion, ondansetron is considered clinically useful with stable anti-emetic effect on both acute and delayed nausea and vomiting over repeated courses of chemotherapy, without any significant safety problem.

  18. Early-life adversity accelerates cellular ageing and affects adult inflammation: Experimental evidence from the European starling

    PubMed Central

    Nettle, Daniel; Andrews, Clare; Reichert, Sophie; Bedford, Tom; Kolenda, Claire; Parker, Craig; Martin-Ruiz, Carmen; Monaghan, Pat; Bateson, Melissa

    2017-01-01

    Early-life adversity is associated with accelerated cellular ageing during development and increased inflammation during adulthood. However, human studies can only establish correlation, not causation, and existing experimental animal approaches alter multiple components of early-life adversity simultaneously. We developed a novel hand-rearing paradigm in European starling nestlings (Sturnus vulgaris), in which we separately manipulated nutritional shortfall and begging effort for a period of 10 days. The experimental treatments accelerated erythrocyte telomere attrition and increased DNA damage measured in the juvenile period. For telomere attrition, amount of food and begging effort exerted additive effects. Only the combination of low food amount and high begging effort increased DNA damage. We then measured two markers of inflammation, high-sensitivity C-reactive protein and interleukin-6, when the birds were adults. The experimental treatments affected both inflammatory markers, though the patterns were complex and different for each marker. The effect of the experimental treatments on adult interleukin-6 was partially mediated by increased juvenile DNA damage. Our results show that both nutritional input and begging effort in the nestling period affect cellular ageing and adult inflammation in the starling. However, the pattern of effects is different for different biomarkers measured at different time points. PMID:28094324

  19. Altered glycometabolism affects both clinical features and prognosis of triple-negative and neoadjuvant chemotherapy-treated breast cancer.

    PubMed

    Dong, Tieying; Kang, Xinmei; Liu, Zhaoliang; Zhao, Shu; Ma, Wenjie; Xuan, Qijia; Liu, Hang; Wang, Zhipeng; Zhang, Qingyuan

    2016-06-01

    Glycometabolism is a distinctive aspect of energy metabolism in breast cancer, and key glycometabolism enzymes/pathways (glycolysis, hexosamine biosynthetic pathway, and pentose phosphate pathway) may directly or indirectly affect the clinical features. In this study, we analyzed the particular correlation between the altered glycometabolism and clinical features of breast cancer to instruct research and clinical treatment. Tissue microarrays containing 189 hollow needle aspiration samples and 295 triple-negative breast cancer tissues were used to test the expression of M2 isoform of pyruvate kinase (PKM2), glutamine-fructose-6-phosphate transaminase 1 (GFPT1), glucose-6-phosphate dehydrogenase (G6PD), and p53 by immunohistochemistry and the intensity of these glycometabolism-related protein was evaluated. Chi-square test, Kaplan-Meier estimates, and Cox proportional hazards model were used to analyze the relationship between the expression of these factors and major clinical features. PKM2, GFPT1, and G6PD affect the pathologic complete response rate of neoadjuvant chemotherapy patients in different ways; pyruvate kinase muscle isozyme 2 (PKM2) and G6PD are closely associated with the molecular subtypes, whereas GFPT1 is correlated with cancer size. All these three factors as well as p53 have impacts on the progression-free survival and overall survival of triple-negative breast cancer patients. Cancer size shows significant association with PKM2 and GFPT1 expression, while the pN stage and grade are associated with PKM2 and G6PD expression. Our study support that clinical characteristics are reflections of specific glycometabolism pathways, so their relationships may shed light on the orientation of research or clinical treatment. The expression of PKM2, GFPT1, and G6PD are hazardous factors for prognosis: high expression of these proteins predict worse progression-free survival and overall survival in triple-negative breast cancer, as well as worse pathologic

  20. Long-Term Outcome and Factors Affecting Prognosis of Extracorporeal Shockwave Therapy for Chronic Refractory Achilles Tendinopathy

    PubMed Central

    2017-01-01

    Objective To investigate the factors affecting prognosis of extracorporeal shockwave therapy (ESWT) for chronic refractory Achilles tendinopathy (AT). Methods Thirty-six patients (48 consecutive feet) with chronic AT (>6 months) and who underwent ESWT for ‘poor’ or ‘fair’ grade in Roles-Maudsley Score (RMS) after unsuccessful conservative treatment were included in the present study. A maximum of 12 sessions of ESWT were conducted until treatment success: RMS reached ‘good’ or ‘excellent’. Termination of ESWT for no response, or ‘poor’ or ‘fair’ grade was regarded as treatment failure. Immediate outcome, long-term outcome (telephone interview after mean 26 months), and factors affecting treatment success were analyzed. Results Numeric Rating Scale was significantly decreased at immediate and long-term follow-up. Success rate was 71.1% and 90.3%, respectively. Univariate logistic regression identified that immediate treatment success was associated with retrocalcaneal enthesophyte on X-ray (odds ratio [OR], 0.06; 95% confidence interval [CI], 0.01–0.28), pretreatment abnormal ultrasonography echogenicity within Achilles tendon (OR, 18.89; 95% CI, 2.08–171.96), mean duration of ‘post-treatment soreness’ (OR, 0.55; 95% CI, 0.33–0.94), and duration of ‘post-treatment soreness after first ESWT’ (OR, 0.06; 95% CI, 0.01–0.34). The duration of ‘post-treatment soreness after first ESWT’ was found to be the only factor associated with long-term success (OR, 0.32; 95% CI, 0.10–0.99). Conclusion ESWT appears to be effective in achieving long-term success in chronic refractory AT. Immediate success was associated with absence of retrocalcaneal enthesophyte on X-ray, presence of pretreatment abnormal ultrasonography echogenicity, shorter mean duration of ‘post-treatment soreness’, and shorter duration of ‘post-treatment soreness after first ESWT’. The shorter duration of ‘post-treatment soreness after first ESWT’ was

  1. Alkaline decontamination of sputum specimens adversely affects stability of mycobacterial mRNA.

    PubMed Central

    Desjardin, L E; Perkins, M D; Teixeira, L; Cave, M D; Eisenach, K D

    1996-01-01

    Reverse transcriptase PCR (RT-PCR) is an important tool for Mycobacterium tuberculosis research and diagnostics. A standard procedure using N-acetyl-L-cysteine (NALC) and NaOH has been widely adopted for digestion and decontamination of sputum specimens for mycobacterial culture. The objective of this study was to determine the compatibility of this method with the recovery of RNA for RT-PCR assays. Nineteen sputum specimens were collected from smear-positive, pretreatment tuberculosis patients. After homogenization with NALC and glass beads, specimens were further processed by the addition of either NaOH, as per the standard decontamination protocol, or phosphate buffer. RNA was prepared by using a modified guanidine-phenol extraction method developed specifically for sputum sediments. DNA was isolated from the same specimens. Reverse transcriptions of alpha antigen (85B protein) mRNA and 16S rRNA were performed together, and aliquots were removed for separate PCRs. In all specimens, the 85B mRNA target was greatly diminished by treatment with NaOH; however, the 16S rRNA target remained unaffected. Storing sputum specimens for 48 h at 4 degrees C before processing did not seem to affect the integrity or yield of RNA; however, some degradation occurred by 72 h. Data suggest that the NaOH-NALC method for processing sputum samples is not suitable for detecting mRNA targets in RT-PCR assays. PMID:8880495

  2. Fibrinolysis inhibitors adversely affect remodeling of tissues sealed with fibrin glue.

    PubMed

    Krishnan, Lissy K; Vijayan Lal, Arthur; Uma Shankar, P R; Mohanty, Mira

    2003-01-01

    Experiments have been carried out to determine if aprotinin and epsilon -amino caproic acid increases the quality of Fibrin glue. A rat model was used for tissues such as liver and skin while rabbits were used for application of glue in dura mater. Apposition of all the tissues, glued with fibrin was found to be good and remnants of the polymerized fibrin were seen even on the seventh day of application, though inhibitors were not incorporated with the glue. In skin, excessive amounts of fibrin remained as a result of addition of aprotinin and epsilon -amino caproic acid, as compared to the glue applied without any inhibitor. After dural sealing, the wound repair and new bone formation at craniotomy site progressed well in the fibrin glue applied area as compared to the commercially available glue that contained aprotinin. The adhesive strength of the glue without or with fibrinolysis inhibitors was found to be similar, after 1h grafts on rat back. The observations from this study suggests that the use of aprotinin with fibrin glue may not be required because, even liver tissue that is known to have high fibrinolytic activity was sealed and repaired well in the absence of plasminogen inhibitors. On the other hand, it was found that if inhibitors were added, nondegraded matrix remained in the tissue even after 15 days and affected migration of repair cells. Thus, the inhibition of fibrinolysis after fibrin glue application is found detrimental to wound healing.

  3. Combining S-cone and luminance signals adversely affects discrimination of objects within backgrounds

    PubMed Central

    Jennings, Ben J.; Tsattalios, Konstantinos; Chakravarthi, Ramakrishna; Martinovic, Jasna

    2016-01-01

    The visual system processes objects embedded in complex scenes that vary in both luminance and colour. In such scenes, colour contributes to the segmentation of objects from backgrounds, but does it also affect perceptual organisation of object contours which are already defined by luminance signals, or are these processes unaffected by colour’s presence? We investigated if luminance and chromatic signals comparably sustain processing of objects embedded in backgrounds, by varying contrast along the luminance dimension and along the two cone-opponent colour directions. In the first experiment thresholds for object/non-object discrimination of Gaborised shapes were obtained in the presence and absence of background clutter. Contrast of the component Gabors was modulated along single colour/luminance dimensions or co-modulated along multiple dimensions simultaneously. Background clutter elevated discrimination thresholds only for combined S-(L + M) and L + M signals. The second experiment replicated and extended this finding by demonstrating that the effect was dependent on the presence of relatively high S-(L + M) contrast. These results indicate that S-(L + M) signals impair spatial vision when combined with luminance. Since S-(L + M) signals are characterised by relatively large receptive fields, this is likely to be due to an increase in the size of the integration field over which contour-defining information is summed. PMID:26856308

  4. Glyphosate Adversely Affects Danio rerio Males: Acetylcholinesterase Modulation and Oxidative Stress.

    PubMed

    Lopes, Fernanda Moreira; Caldas, Sergiane Souza; Primel, Ednei Gilberto; da Rosa, Carlos Eduardo

    2017-04-01

    It has been demonstrated that glyphosate-based herbicides are toxic to animals. In the present study, reactive oxygen species (ROS) generation, antioxidant capacity against peroxyl radicals (ACAP), and lipid peroxidation (LPO), as well as the activity and expression of the acetylcholinesterase (AChE) enzyme, were evaluated in Danio rerio males exposed to 5 or 10 mg/L of glyphosate for 24 and 96 h. An increase in ACAP in gills after 24 h was observed in the animals exposed to 5 mg/L of glyphosate. A decrease in LPO was observed in brain tissue of animals exposed to 10 mg/L after 24 h, while an increase was observed in muscle after 96 h. No significant alterations were observed in ROS generation. AChE activity was not altered in muscles or brains of animals exposed to either glyphosate concentration for 24 or 96 h. However, gene expression of this enzyme in the brain was reduced after 24 h and was enhanced in both brain and muscle tissues after 96 h. Thus, contrary to previous findings that had attributed the imbalance in the oxidative state of animals exposed to glyphosate-based herbicides to surfactants and other inert compounds, the present study demonstrated that glyphosate per se promotes this same effect in zebrafish males. Although glyphosate concentrations did not alter AChE activity, this study demonstrated for the first time that this molecule affects ache expression in male zebrafish D. rerio.

  5. Does MRI-detected cranial nerve involvement affect the prognosis of locally advanced nasopharyngeal carcinoma treated with intensity modulated radiotherapy?

    PubMed

    Zong, Jingfeng; Lin, Shaojun; Chen, Yunbin; Wang, Bingyi; Xiao, Youping; Lin, Jin; Li, Rui; Pan, Jianji

    2014-01-01

    Nasopharyngeal carcinoma (NPC) is one of the common cancers in South China. It can easily invade into cranial nerves, especially in patients with local advanced disease. Despite the fact that the magnetic resonance imaging (MRI) findings are not always consistent with the symptoms of CN palsy, MRI is recommended for the detection of CN involvement (CNI). However, the prognostic impact of MRI-detected CNI in NPC patients is still controversial. To investigate the prognostic value of MRI detected CNI, we performed a retrospective analysis on the clinical data of 375 patients with NPC who were initially diagnosed by MRI. All patients had T3-4 disease and received radical intensity modulated radiation therapy (IMRT) as their primary treatment. The incidence of MRI-detected CNI was 60.8%. A higher incidence of MRI-detected CNI was observed in T4 disease compared with T3 disease (96.8% vs. 42.8%, P<0.001), and a higher incidence was also found in patients with Stage IV disease compared with those with Stage III disease (91.5% vs. 42.3%; P<0.001). The local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) of patients with T3 disease, with or without MRI-detected CNI, was superior to that of patients with T4 disease (P<0.05). No significant differences in LRFS, DMFS or OS were observed between T3 patients with or without MRI-detected CNI. The survival of Stage III patients with or without MRI-detected CNI was significantly superior to that of Stage IV patients (P<0.01), but there was no significant difference between Stage III patients with or without MRI-detected CNI for all endpoints. Therefore, when treated with IMRT, MRI-detected CNI in patients with NPC does not appear to affect the prognosis. In patients with clinical T3 disease, the presence of MRI-detected CNI is not sufficient evidence for defining T4 disease.

  6. Analysis of the predictive efficiency of S100P on adverse prognosis and the pathogenesis of S100P-mediated invasion and metastasis of colon adenocarcinoma.

    PubMed

    Shen, Zhi-Yong; Fang, Yuan; Zhen, Li; Zhu, Xian-Jun; Chen, Hao; Liu, Hao; Jiang, Bo; Li, Guo-Xin; Deng, Hai-Jun

    2016-04-01

    Elevated expression of S100P has been detected in several tumor types. To analyze the potential use of S100P for the prediction of colorectal cancer (CRC) metastasis and prognosis, S100P expression was detected in 125 patients with colon adenocarcinoma by immunohistochemistry, followed by correlation and survival analysis. High S100P expression was correlated with metastasis, as demonstrated by clinically relevant data, and predicted poor survival more effectively than preoperative serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels in colon adenocarcinoma. Stable S100P knockdown CRC cell lines were established to elucidate the relationship between S100P expression and tumor progression in vitro and in vivo. S100P knockdown resulted in reductions in the invasiveness and metastasis of CRC cells. Xenograft growth in nude mice also demonstrated that down-regulated S100P dramatically inhibited peritoneal metastasis of CRC cells. S100P promoted the invasion and metastasis of CRC by activating RAGE/ERK signaling and promoting the epithelial-mesenchymal transition (EMT). RAGE was found to be crucial for S100P-mediated EMT in colon cancer. Knockdown of RAGE in S100P-overexpressing colon cancer cells dramatically suppressed EMT process. Our results indicate that overexpression of S100P is related with an invasive and metastatic phenotype of CRC which is EMT-involved and RAGE dependent.

  7. Loss of ALCAM expression is linked to adverse phenotype and poor prognosis in breast cancer: a TMA-based immunohistochemical study on 2,197 breast cancer patients.

    PubMed

    Burandt, Eike; Bari Noubar, Tanaz; Lebeau, Annette; Minner, Sarah; Burdelski, Christoph; Jänicke, Fritz; Müller, Vollkmar; Terracciano, Luigi; Simon, Ronald; Sauter, Guido; Wilczak, Waldemar; Lebok, Patrick

    2014-12-01

    Activated leukocyte cell adhesion molecule (ALCAM) is a membranous cell adhesion protein that is often expressed in breast cancer. Data on the prognostic impact of ALCAM expression is highly controversial in this cancer. To evaluate the clinical impact of ALCAM expression in a sufficiently large patient cohort, we utilized a tissue microarray (TMA) containing more than 2,100 primary breast cancers with clinical follow-up data by immunohistochemistry. TMA spots containing normal breast epithelium showed moderate to strong membranous ALCAM staining. ALCAM staining was strong in 66.2%, moderate in 10.9%, weak in 11.1% and absent in 11.8% of 1,778 (80.9%) interpretable breast cancer tissue spots. Decreased ALCAM expression was significantly associated with advanced tumor size (p=0.0017), unfavorable tumor grade (p<0.0001), negative ER and PR status (p<0.0001 each) as well as high Ki67 labeling index (p<0.0001). Cancers with ACLAM expression loss had a significantly poorer overall (p<0.0001) and disease-specific survival (p=0.0088). This association also held true in the subset of nodal positive cancers (p<0.0001). In conclusion, these data demonstrate that ALCAM is generally expressed in normal and cancerous breast epithelium and that a marked reduction of ALCAM expression characterizes a subset of breast cancer patients with adverse tumor characteristics and unfavorable clinical outcome.

  8. The cultivation of Bt corn producing Cry1Ac toxins does not adversely affect non-target arthropods.

    PubMed

    Guo, Yanyan; Feng, Yanjie; Ge, Yang; Tetreau, Guillaume; Chen, Xiaowen; Dong, Xuehui; Shi, Wangpeng

    2014-01-01

    Transgenic corn producing Cry1Ac toxins from Bacillus thuringiensis (Bt) provides effective control of Asian corn borer, Ostrinia furnacalis (Guenée), and thus reduces insecticide applications. However, whether Bt corn exerts undesirable effects on non-target arthropods (NTAs) is still controversial. We conducted a 2-yr study in Shangzhuang Agricultural Experiment Station to assess the potential impact of Bt corn on field population density, biodiversity, community composition and structure of NTAs. On each sampling date, the total abundance, Shannon's diversity index, Pielou's evenness index and Simpson's diversity index were not significantly affected by Bt corn as compared to non-Bt corn. The "sampling dates" had a significant effect on these indices, but no clear tendencies related to "Bt corn" or "sampling dates X corn variety" interaction were recorded. Principal response curve analysis of variance indicated that Bt corn did not alter the distribution of NTAs communities. Bray-Curtis dissimilarity and distance analysis showed that Cry1Ac toxin exposure did not increase community dissimilarities between Bt and non-Bt corn plots and that the evolution of non-target arthropod community was similar on the two corn varieties. The cultivation of Bt corn failed to show any detrimental evidence on the density of non-target herbivores, predators and parasitoids. The composition of herbivores, predators and parasitoids was identical in Bt and non-Bt corn plots. Taken together, results from the present work support that Bt corn producing Cry1Ac toxins does not adversely affect NTAs.

  9. A genetic polymorphism affects the risk and prognosis of renal cell carcinoma: association with follistatin-like protein 1 expression

    PubMed Central

    Liu, Yan; Han, Xue; Yu, Yongwei; Ding, Yibo; Ni, Chong; Liu, Wenbin; Hou, Xiaomei; Li, Zixiong; Hou, Jianguo; Shen, Dan; Yin, Jianhua; Zhang, Hongwei; Thompson, Timothy C.; Tan, Xiaojie; Cao, Guangwen

    2016-01-01

    Few single nucleotide polymorphisms (SNPs) associated with the risk of renal cell carcinoma (RCC) have been identified, yet genetic predisposition contributes significantly to this malignancy. We previously showed that follistatin-like 1 (FSTL1) was significantly down-regulated in clear cell RCC (ccRCC), in particular metastatic ccRCC. In the present study, we systemically investigated the associations of the 6 SNPs within FSTL1-coding genomic region with RCC risk and postoperative prognosis. Age- and gender-matched case-control study (417 vs 855) indicated that rs1259293 variant genotype CC was significantly associated with an increased risk of RCC, with an odds ratio of 2.004 (95% confidence internal [CI] = 1.190–3.375). Multivariate Cox regression analysis in 309 of 417 cases showed that rs1259293 genotype (CC vs TT + CT) independently predicted an unfavorable prognosis, with a hazard ratio of 2.531 (95% CI = 1.052–6.086). Expression of FSTL1 was significantly higher in adjacent renal tissues than in tumors, and significantly higher in the tissues with rs1259293 TT genotype than in those with rs1259293 TC+CC genotypes. rs1259293 C allele might generate a CTCF binding site that blocks trans-activation of FSTL1 expression. Our results indicate that rs1259293 is associated with an increased risk and unfavorable postoperative prognosis of RCC, possibly by down-regulating FSTL1 expression in renal tissues. PMID:27225192

  10. The Cultivation of Bt Corn Producing Cry1Ac Toxins Does Not Adversely Affect Non-Target Arthropods

    PubMed Central

    Guo, Yanyan; Feng, Yanjie; Ge, Yang; Tetreau, Guillaume; Chen, Xiaowen; Dong, Xuehui; Shi, Wangpeng

    2014-01-01

    Transgenic corn producing Cry1Ac toxins from Bacillus thuringiensis (Bt) provides effective control of Asian corn borer, Ostrinia furnacalis (Guenée), and thus reduces insecticide applications. However, whether Bt corn exerts undesirable effects on non-target arthropods (NTAs) is still controversial. We conducted a 2-yr study in Shangzhuang Agricultural Experiment Station to assess the potential impact of Bt corn on field population density, biodiversity, community composition and structure of NTAs. On each sampling date, the total abundance, Shannon's diversity index, Pielou's evenness index and Simpson's diversity index were not significantly affected by Bt corn as compared to non-Bt corn. The “sampling dates” had a significant effect on these indices, but no clear tendencies related to “Bt corn” or “sampling dates X corn variety” interaction were recorded. Principal response curve analysis of variance indicated that Bt corn did not alter the distribution of NTAs communities. Bray-Curtis dissimilarity and distance analysis showed that Cry1Ac toxin exposure did not increase community dissimilarities between Bt and non-Bt corn plots and that the evolution of non-target arthropod community was similar on the two corn varieties. The cultivation of Bt corn failed to show any detrimental evidence on the density of non-target herbivores, predators and parasitoids. The composition of herbivores, predators and parasitoids was identical in Bt and non-Bt corn plots. Taken together, results from the present work support that Bt corn producing Cry1Ac toxins does not adversely affect NTAs. PMID:25437213

  11. Up-regulation of a HOXA-PBX3 homeobox-gene signature following down-regulation of miR-181 is associated with adverse prognosis in patients with cytogenetically abnormal AML.

    PubMed

    Li, Zejuan; Huang, Hao; Li, Yuanyuan; Jiang, Xi; Chen, Ping; Arnovitz, Stephen; Radmacher, Michael D; Maharry, Kati; Elkahloun, Abdel; Yang, Xinan; He, Chunjiang; He, Miao; Zhang, Zhiyu; Dohner, Konstanze; Neilly, Mary Beth; Price, Colles; Lussier, Yves A; Zhang, Yanming; Larson, Richard A; Le Beau, Michelle M; Caligiuri, Michael A; Bullinger, Lars; Valk, Peter J M; Delwel, Ruud; Lowenberg, Bob; Liu, Paul P; Marcucci, Guido; Bloomfield, Clara D; Rowley, Janet D; Chen, Jianjun

    2012-03-08

    Increased expression levels of miR-181 family members have been shown to be associated with favorable outcome in patients with cytogenetically normal acute myeloid leukemia. Here we show that increased expression of miR-181a and miR-181b is also significantly (P < .05; Cox regression) associated with favorable overall survival in cytogenetically abnormal AML (CA-AML) patients. We further show that up-regulation of a gene signature composed of 4 potential miR-181 targets (including HOXA7, HOXA9, HOXA11, and PBX3), associated with down-regulation of miR-181 family members, is an independent predictor of adverse overall survival on multivariable testing in analysis of 183 CA-AML patients. The independent prognostic impact of this 4-homeobox-gene signature was confirmed in a validation set of 271 CA-AML patients. Furthermore, our in vitro and in vivo studies indicated that ectopic expression of miR-181b significantly promoted apoptosis and inhibited viability/proliferation of leukemic cells and delayed leukemogenesis; such effects could be reversed by forced expression of PBX3. Thus, the up-regulation of the 4 homeobox genes resulting from the down-regulation of miR-181 family members probably contribute to the poor prognosis of patients with nonfavorable CA-AML. Restoring expression of miR-181b and/or targeting the HOXA/PBX3 pathways may provide new strategies to improve survival substantially.

  12. Extreme Air Pollution Conditions Adversely Affect Blood Pressure and Insulin Resistance: The Air Pollution and Cardiometabolic Disease Study.

    PubMed

    Brook, Robert D; Sun, Zhichao; Brook, Jeffrey R; Zhao, Xiaoyi; Ruan, Yanping; Yan, Jianhua; Mukherjee, Bhramar; Rao, Xiaoquan; Duan, Fengkui; Sun, Lixian; Liang, Ruijuan; Lian, Hui; Zhang, Shuyang; Fang, Quan; Gu, Dongfeng; Sun, Qinghua; Fan, Zhongjie; Rajagopalan, Sanjay

    2016-01-01

    Mounting evidence supports that fine particulate matter adversely affects cardiometabolic diseases particularly in susceptible individuals; however, health effects induced by the extreme concentrations within megacities in Asia are not well described. We enrolled 65 nonsmoking adults with metabolic syndrome and insulin resistance in the Beijing metropolitan area into a panel study of 4 repeated visits across 4 seasons since 2012. Daily ambient fine particulate matter and personal black carbon levels ranged from 9.0 to 552.5 µg/m(3) and 0.2 to 24.5 µg/m(3), respectively, with extreme levels observed during January 2013. Cumulative fine particulate matter exposure windows across the prior 1 to 7 days were significantly associated with systolic blood pressure elevations ranging from 2.0 (95% confidence interval, 0.3-3.7) to 2.7 (0.6-4.8) mm Hg per SD increase (67.2 µg/m(3)), whereas cumulative black carbon exposure during the previous 2 to 5 days were significantly associated with ranges in elevations in diastolic blood pressure from 1.3 (0.0-2.5) to 1.7 (0.3-3.2) mm Hg per SD increase (3.6 µg/m(3)). Both black carbon and fine particulate matter were significantly associated with worsening insulin resistance (0.18 [0.01-0.36] and 0.22 [0.04-0.39] unit increase per SD increase of personal-level black carbon and 0.18 [0.02-0.34] and 0.22 [0.08-0.36] unit increase per SD increase of ambient fine particulate matter on lag days 4 and 5). These results provide important global public health warnings that air pollution may pose a risk to cardiometabolic health even at the extremely high concentrations faced by billions of people in the developing world today.

  13. In chronic kidney disease staging the use of the chronicity criterion affects prognosis and the rate of progression.

    PubMed

    Eriksen, B O; Ingebretsen, O C

    2007-11-01

    The Kidney Disease Outcomes Quality Initiative definition and staging of chronic kidney disease (CKD) have been adopted by most nephrologists but include a criterion of chronicity that has not been investigated. This criterion specifies that renal structural damage and/or reduction in glomerular filtration rate (GFR) should be present for periods lasting longer than 3 months. We examined the effects of changing this criterion to 6, 9, or 12 months on the prognosis and the rate of progression in population-based cohorts with CKD stages 3 and 4. A 12-month chronicity criterion significantly reduced the number of CKD patients relative to the 3-month criterion for both stages 3 and 4. For both stages, there were statistically significant differences in 5-year mortality between the 6- and 9-month cohorts. For stage 4, the 5-year cumulative incidence of renal failure significantly increased from 6 to 9 months, and the rate of change in GFR significantly decreased between the same two cohorts. The 5-year cumulative incidence of improvement in GFR lasting 1 year or more was significantly higher for the 3-month cohort than for the 12-month cohort in the stage 3 group. Hence, we suggest that the chronicity criterion is an important determinant of the characteristics of the population of patients with CKD stages 3 and 4. This may have practical consequences in both research and clinical work.

  14. HPV-16/18 detection does not affect the prognosis of head and neck squamous cell carcinoma in younger and older patients

    PubMed Central

    Marques-Silva, Luciano; Farias, Lucyana Conceição; Fraga, Carlos Alberto de Carvalho; de Oliveira, Marcos Vinícius Macedo; Cardos, Cláudio Marcelo; Fonseca-Silva, Thiago; Gomes, Carolina Cavalieri; De-Paula, Alfredo Maurício Batista; Gomez, Ricardo Santiago

    2012-01-01

    Recently, high-risk human papillomavirus (HPV) has emerged as a possible agent associated with head and neck squamous cell carcinoma (HNSCC) in younger patients. Therefore, the purpose of the present study was to assess the effect of age on the distribution of HPV-16/18 in HNSCC, together with the impact of the virus on patient prognosis. A longitudinal prospective study was used adjusted for age, gender, TNM staging, smoking status and alcohol consumption. HPV was detected by PCR with consensus primers. Results showed there was no difference in the frequency of HPV-16/18 positivity when younger patients were compared to the older patients. No association was found among high-risk HPV positivity, gender, smoking habit and anatomical site. High-risk HPV was associated with advanced TNM in bivariate analyses; however, it did not impact on survival. Only TNM staging was associated with risk of mortality. Our study supports the theory that age does not affect the presence of HPV-16/18 in HNSCC and has no impact on patient prognosis. The incidence of HNSCC among patients under the age of 45 years is reportedly on the increase worldwide. The factors associated with HNSCC in younger adults are not well established. Findings of this study indicate that HPV-16/18 may not play a role in HNSCC patients under the age of 45 years. PMID:22741024

  15. Factors That Negatively Affect the Prognosis of Pediatric Community-Acquired Pneumonia in District Hospital in Tanzania

    PubMed Central

    Caggiano, Serena; Ullmann, Nicola; De Vitis, Elisa; Trivelli, Marzia; Mariani, Chiara; Podagrosi, Maria; Ursitti, Fabiana; Bertolaso, Chiara; Putotto, Carolina; Unolt, Marta; Pietravalle, Andrea; Pansa, Paola; Mphayokulela, Kajoro; Lemmo, Maria Incoronata; Mkwambe, Michael; Kazaura, Joseph; Duse, Marzia; Nieddu, Francesco; Azzari, Chiara; Cutrera, Renato

    2017-01-01

    Community-acquired pneumonia (CAP) is still the most important cause of death in countries with scarce resources. All children (33 months ± 35 DS) discharged from the Pediatric Unit of Itigi Hospital, Tanzania, with a diagnosis of CAP from August 2014 to April 2015 were enrolled. Clinical data were gathered. Dried blood spot (DBS) samples for quantitative real-time polymerase chain reaction (PCR) for bacterial detection were collected in all 100 children included. Twenty-four percent of patients were identified with severe CAP and 11% died. Surprisingly, 54% of patients were admitted with a wrong diagnosis, which increased complications, the need for antibiotics and chest X-rays, and the length of hospitalization. Comorbidity, found in 32% of children, significantly increased severity, complications, deaths, need for chest X-rays, and oxygen therapy. Malnourished children (29%) required more antibiotics. Microbiologically, Streptococcus pneumonia (S. p.), Haemophilus influenza type b (Hib) and Staphylococcus aureus (S. a.) were the bacteria more frequently isolated. Seventy-five percent of patients had mono-infection. Etiology was not correlated with severity, complications, deaths, oxygen demand, or duration of hospitalization. Our study highlights that difficult diagnoses and comorbidities negatively affect clinical evolution. S. p. and Hib still play a large role; thus, implementation of current vaccine strategies is needed. DBS is a simple and efficient diagnostic method for bacterial identification in countries with scarce resources. PMID:28335406

  16. Pre-operative psychological distress does not adversely affect functional or mental health gain after primary total hip arthroplasty.

    PubMed

    Hossain, Munier; Parfitt, Daniel J; Beard, David J; Darrah, Clare; Nolan, John; Murray, David W; Andrew, John G

    2011-01-01

    Preoperative psychological distress has been reported to predict poor outcome and patient dissatisfaction after total hip arthroplasty (THA). The purpose of this study was to investigate if pre-operative psychological distress was associated with adverse functional outcome after primary THR. We analysed the database of a prospective multi-centre study undertaken between January 1999 and January 2002. We recorded the Oxford Hip Score (OHS) and SF36 score preoperatively and up to five years after surgery for 1055 patients. We dichotomised the patients into the mentally distressed (Mental Health Scale score - MHS =56) and the not mentally distressed (MHS >56) groups based on their pre-operative MHS of the SF36. 762 (72.22%). Patients (595 not distressed and 167 distressed) were followed up at 5 years. Both pre and post-operative OHS and SF-36 scores were significantly worse in the distressed group (both p<0.001). However, both groups experienced statistically significant improvement in OHS and MHS, which was maximal at 1 year after surgery and was maintained over the follow up (p=0.00). There was a substantial improvement in mental distress in patients who reported mental distress prior to surgery. The results suggest that pre-operative psychological distress did not adversely compromise functional outcome gain after THA. Despite having worse absolute values both pre and post operatively, patients with mental distress did not have any less functional gain from THA as measured by improvement in OHS.

  17. Factors affecting the development of adverse drug reactions to β-blockers in hospitalized cardiac patient population.

    PubMed

    Mugoša, Snežana; Djordjević, Nataša; Djukanović, Nina; Protić, Dragana; Bukumirić, Zoran; Radosavljević, Ivan; Bošković, Aneta; Todorović, Zoran

    2016-01-01

    The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6) poor metabolizer alleles (*3, *4, *5, and *6) on a Montenegrin population and its impact on developing adverse drug reactions (ADRs) of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients' medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9%) patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (P<0.001), with ADRs' occurrence significantly correlating with slower CYP2D6 metabolism. Our study showed that the adverse reactions to β-blockers could be predicted by the length of hospitalization, CYP2D6 poor metabolizer phenotype, and the concomitant use of other CYP2D6-metabolizing drugs. Therefore, in hospitalized patients with polypharmacy CYP2D6 genotyping might be useful in detecting those at risk of ADRs.

  18. Factors affecting the development of adverse drug reactions to β-blockers in hospitalized cardiac patient population

    PubMed Central

    Mugoša, Snežana; Djordjević, Nataša; Djukanović, Nina; Protić, Dragana; Bukumirić, Zoran; Radosavljević, Ivan; Bošković, Aneta; Todorović, Zoran

    2016-01-01

    The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6) poor metabolizer alleles (*3, *4, *5, and *6) on a Montenegrin population and its impact on developing adverse drug reactions (ADRs) of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients’ medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9%) patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (P<0.001), with ADRs’ occurrence significantly correlating with slower CYP2D6 metabolism. Our study showed that the adverse reactions to β-blockers could be predicted by the length of hospitalization, CYP2D6 poor metabolizer phenotype, and the concomitant use of other CYP2D6-metabolizing drugs. Therefore, in hospitalized patients with polypharmacy CYP2D6 genotyping might be useful in detecting those at risk of ADRs. PMID:27536078

  19. A Computational Study on the Effects of Dynamic Roughness Application to Separated Transitional Flows Affected by Adverse Pressure Gradient

    NASA Astrophysics Data System (ADS)

    Campitelli, Gennaro

    The study of transitional flows is considered crucial for many practical engineering applications. In fact, a comprehensive understanding of the laminar-turbulent transition phenomenon often helps to improve the overall performance of apparatuses such as airfoils, wind turbines, hulls and turbomachinery blades. In addition to understanding and prediction of transitional flows, active research continues in the area of boundary layer control, which includes control of phenomena such as flow separation and transition. For instance, optimum geometrical shaping may be followed by the adoption on the wall-surface of riblets to adjust pressure gradient and reduce drag. Further "flow control" may also be acquired by introducing active devices able to modify the flow field in order to accomplish a desired aerodynamic task. Such flow manipulation is often achieved by using time-dependent forcing mechanisms which promote natural instabilities amplifying the control effectiveness. Localized energy inputs such as Lorentz-force actuator, piezoelectric flaps and synthetic jets all produce a consistent boundary layer mixing enhancement with lift increase and drag abatement. The current numerical study attempts to demonstrate the efficacy of dynamic roughness (DR) on altering separated-reattached transitional flows under adverse pressure gradient. It has already been proven how DR, acting on the boundary sublayer perturbation, is able to suppress (partially or completely) the typical leading edge separation for an airfoil at different angles of attack. This makes DR particularly suitable for separated flow control applications where the shear layer reattaches presenting the characteristic laminar separation bubble. A numerical sensitivity study has been conducted with an efficient orthogonal design taking into account four different control parameters on three levels (actuation frequency, humps height, rows displacement, synchronization) to provide an optimum DR setup which limits

  20. Lactate adversely affects the in vitro formation of endothelial cell tubular structures through the action of TGF-{beta}1

    SciTech Connect

    Schmid, Stephan A. . E-mail: leoni.kunz-schughart@oncoray.de; Gaumann, Andreas; Wondrak, Marit; Eckermann, Christoph; Schulte, Stephanie; Mueller-Klieser, Wolfgang; Wheatley, Denys N.; Kunz-Schughart, Leoni A.

    2007-07-15

    When lactate accumulation in a tumor microenvironment reaches an average concentration of 10-20 mM, it tends to reflect a high degree of malignancy. However, the hypothesis that tumor-derived lactate has a number of partially adverse biological effects on malignant and tumor-associated host cells requires further evidence. The present study attempted to evaluate the impact of lactate on the process of angiogenesis, in particular on the formation of tubular structures. The endothelial cell (EC) network in desmoplastic breast tumors is primarily located in areas of reactive fibroblastic stroma. We employed a fibroblast-endothelial cell co-culture model as in vitro angiogenesis system normally producing florid in vitro tubule formation to analyze this situation. In contrast to previous studies, we found that lactate significantly reduces EC network formation in a dose-dependent manner as quantified by semi-automated morphometric analyses following immunohistochemical staining. The decrease in CD31-positive tubular structures and the number of intersections was independent of VEGF supplementation and became more pronounced in the presence of protons. The number of cells, primarily of the fibroblast population, was reduced but cell loss could not be attributed to a decrease in proliferative activity or pronounced apoptotic cell death. Treatment with 10 mM lactate was accompanied by enhanced mRNA expression and release of TGF-{beta}1, which also shows anti-angiogenic activity in the model. Both TGF-{beta}1 and lactate induced myofibroblastic differentiation adjacent to the EC tubular structures. The lactate response on the EC network was diminished by TGF-{beta}1 neutralization, indicating a causal relationship between lactate and TGF-{beta}1 in the finely tuned processes of vessel formation and maturation which may also occur in vivo within tumor tissue.

  1. When the serotonin transporter gene meets adversity: the contribution of animal models to understanding epigenetic mechanisms in affective disorders and resilience.

    PubMed

    Lesch, Klaus-Peter

    2011-01-01

    Although converging epidemiological evidence links exposure to stressful life events with increased risk for affective spectrum disorders, there is extraordinary interindividual variability in vulnerability to adversity. The environmentally moderated penetrance of genetic variation is thought to play a major role in determining who will either develop disease or remain resilient. Research on genetic factors in the aetiology of disorders of emotion regulation has, nevertheless, been complicated by a mysterious discrepancy between high heritability estimates and a scarcity of replicable gene-disorder associations. One explanation for this incongruity is that at least some specific gene effects are conditional on environmental cues, i.e. gene-by-environment interaction (G × E) is present. For example, a remarkable number of studies reported an association of variation in the human serotonin (5-HT) transporter gene (SLC6A4, 5-HTT, SERT) with emotional and cognitive traits as well as increased risk for depression in interaction with psychosocial adversity. The results from investigations in non-human primate and mouse support the occurrence of G × E interaction by showing that variation of 5-HTT function is associated with a vulnerability to adversity across the lifespan leading to unfavourable outcomes resembling various neuropsychiatric disorders. The neural and molecular mechanisms by which environmental adversity in early life increases disease risk in adulthood are not known but may include epigenetic programming of gene expression during development. Epigenetic mechanisms, such as DNA methylation and chromatin modification, are dynamic and reversible and may also provide targets for intervention strategies (see Bountra et al., Curr Top Behav Neurosci, 2011). Animal models amenable to genetic manipulation are useful in the identification of molecular mechanisms underlying epigenetic programming by adverse environments and individual differences in

  2. The skin tissue is adversely affected by TNF-alpha blockers in patients with chronic inflammatory arthritis: a 5-year prospective analysis

    PubMed Central

    Machado, Natalia P.; dos Reis Neto, Edgard Torres; Soares, Maria Roberta M. P.; Freitas, Daniele S.; Porro, Adriana; Ciconelli, Rozana M.; Pinheiro, Marcelo M.

    2013-01-01

    OBJECTIVE: We evaluated the incidence of and the main risk factors associated with cutaneous adverse events in patients with chronic inflammatory arthritis following anti-TNF-α therapy. METHODS: A total of 257 patients with active arthritis who were taking TNF-α blockers, including 158 patients with rheumatoid arthritis, 87 with ankylosing spondylitis and 12 with psoriatic arthritis, were enrolled in a 5-year prospective analysis. Patients with overlapping or other rheumatic diseases were excluded. Anthropometric, socioeconomic, demographic and clinical data were evaluated, including the Disease Activity Score-28, Bath Ankylosing Spondylitis Disease Activity Index and Psoriasis Area Severity Index. Skin conditions were evaluated by two dermatology experts, and in doubtful cases, skin lesion biopsies were performed. Associations between adverse cutaneous events and clinical, demographic and epidemiological variables were determined using the chi-square test, and logistic regression analyses were performed to identify risk factors. The significance level was set at p<0.05. RESULTS: After 60 months of follow-up, 71 adverse events (73.85/1000 patient-years) were observed, of which allergic and immune-mediated phenomena were the most frequent events, followed by infectious conditions involving bacterial (47.1%), parasitic (23.5%), fungal (20.6%) and viral (8.8%) agents. CONCLUSION: The skin is significantly affected by adverse reactions resulting from the use of TNF-α blockers, and the main risk factors for cutaneous events were advanced age, female sex, a diagnosis of rheumatoid arthritis, disease activity and the use of infliximab. PMID:24141833

  3. Protein-enriched meal replacements do not adversely affect liver, kidney or bone density: an outpatient randomized controlled trial

    PubMed Central

    2010-01-01

    0.19 g/cm2, p = 0.210; SP -0.03 ± 0.17 g/cm2, p = 0.320) in either group over one year. Conclusions These studies demonstrate that protein-enriched meals replacements as compared to standard meal replacements recommended for weight management do not have adverse effects on routine measures of liver function, renal function or bone density at one year. Clinicaltrial.gov: NCT01030354. PMID:21194471

  4. Exposure to perfluorooctane sulfonic acid (PFOS) adversely affects the life-cycle of the damselfly Enallagma cyathigerum.

    PubMed

    Bots, Jessica; De Bruyn, Luc; Snijkers, Tom; Van den Branden, Bert; Van Gossum, Hans

    2010-03-01

    We evaluated whether life-time exposure to PFOS affects egg development, hatching, larval development, survival, metamorphosis and body mass of Enallagma cyathigerum (Insecta: Odonata). Eggs and larvae were exposed to five concentrations ranging from 0 to 10000 microg/L. Our results show reduced egg hatching success, slower larval development, greater larval mortality, and decreased metamorphosis success with increasing PFOS concentration. PFOS had no effect on egg developmental time and hatching or on mass of adults. Eggs were the least sensitive stage (NOEC=10000 microg/L). Larval NOEC values were 1000 times smaller (10 microg/L). Successful metamorphosis was the most sensitive response trait studied (NOEC<10 microg/L). The NOEC value suggests that E. cyathigerum is amongst the most sensitive freshwater organisms tested. NOEC for metamorphosis is less than 10-times greater than the ordinary reported environmental concentrations in freshwater, but is more than 200-times smaller than the greatest concentrations measured after accidental releases.

  5. Human Cytomegalovirus Infant Infection Adversely Affects Growth and Development in Maternally HIV-Exposed and Unexposed Infants in Zambia

    PubMed Central

    Larke, N.; Sanz-Ramos, M.; Bates, M.; Musonda, K.; Manno, D.; Siame, J.; Monze, M.; Filteau, S.

    2012-01-01

    Background. Human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV) coinfections have been shown to increase infant morbidity, mortality, and AIDS progression. In HIV-endemic regions, maternal HIV-exposed but HIV-uninfected infants, which is the majority of children affected by HIV, also show poor growth and increased morbidity. Although nutrition has been examined, the effects of HCMV infection have not been evaluated. We studied the effects of HCMV infection on the growth, development, and health of maternally HIV-exposed and unexposed infants in Zambia. Methods. Infants were examined in a cohort recruited to a trial of micronutrient-fortified complementary foods. HIV-infected mothers and infants had received perinatal antiretroviral therapy to prevent mother-to-child HIV transmission. Growth, development, and morbidity were analyzed by linear regression analyses in relation to maternal HIV exposure and HCMV infection, as screened by sera DNA for viremia at 6 months of age and by antibody for infection at 18 months. Results. All HCMV-seropositive infants had decreased length-for-age by 18 months compared with seronegative infants (standard deviation [z]-score difference: −0.44 [95% confidence interval {CI}, −.72 to −.17]; P = .002). In HIV-exposed infants, those who were HCMV positive compared with those who were negative, also had reduced head size (mean z-score difference: −0.72 [95% CI, −1.23 to −.22]; P = .01) and lower psychomotor development (Bayley test score difference: −4.1 [95% CI, −7.8 to −.5]; P = .03). HIV-exposed, HCMV-viremic infants were more commonly referred for hospital treatment than HCMV-negative infants. The effects of HCMV were unaffected by micronutrient fortification. Conclusion. HCMV affects child growth, development, and morbidity of African infants, particularly in those maternally exposed to HIV. HCMV is therefore a risk factor for child health in this region. PMID:22247303

  6. Mutation increasing β-carotene concentrations does not adversely affect concentrations of essential mineral elements in pepper fruit

    PubMed Central

    Thompson, Jacqueline A.; Penchev, Emil A.; Nielen, Stephan

    2017-01-01

    Vitamin and mineral deficiencies are prevalent in human populations throughout the world. Vitamin A deficiency affects hundreds of millions of pre-school age children in low income countries. Fruits of pepper (Capsicum annuum L.) can be a major dietary source of precursors to Vitamin A biosynthesis, such as β-carotene. Recently, pepper breeding programs have introduced the orange-fruited (of) trait of the mutant variety Oranzheva kapiya, which is associated with high fruit β-carotene concentrations, to the mutant variety Albena. In this manuscript, concentrations of β-carotene and mineral elements (magnesium, phosphorus, sulphur, potassium, zinc, calcium, manganese, iron and copper) were compared in fruit from P31, a red-fruited genotype derived from the variety Albena, and M38, a genotype developed by transferring the orange-fruited mutation (of) into Albena. It was observed that fruit from M38 plants had greater β-carotene concentration at both commercial and botanical maturity (4.9 and 52.7 mg / kg fresh weight, respectively) than fruit from P31 plants (2.3 and 30.1 mg / kg fresh weight, respectively). The mutation producing high β-carotene concentrations in pepper fruits had no detrimental effect on the concentrations of mineral elements required for human nutrition. PMID:28207797

  7. Mutation increasing β-carotene concentrations does not adversely affect concentrations of essential mineral elements in pepper fruit.

    PubMed

    Tomlekova, Nasya B; White, Philip J; Thompson, Jacqueline A; Penchev, Emil A; Nielen, Stephan

    2017-01-01

    Vitamin and mineral deficiencies are prevalent in human populations throughout the world. Vitamin A deficiency affects hundreds of millions of pre-school age children in low income countries. Fruits of pepper (Capsicum annuum L.) can be a major dietary source of precursors to Vitamin A biosynthesis, such as β-carotene. Recently, pepper breeding programs have introduced the orange-fruited (of) trait of the mutant variety Oranzheva kapiya, which is associated with high fruit β-carotene concentrations, to the mutant variety Albena. In this manuscript, concentrations of β-carotene and mineral elements (magnesium, phosphorus, sulphur, potassium, zinc, calcium, manganese, iron and copper) were compared in fruit from P31, a red-fruited genotype derived from the variety Albena, and M38, a genotype developed by transferring the orange-fruited mutation (of) into Albena. It was observed that fruit from M38 plants had greater β-carotene concentration at both commercial and botanical maturity (4.9 and 52.7 mg / kg fresh weight, respectively) than fruit from P31 plants (2.3 and 30.1 mg / kg fresh weight, respectively). The mutation producing high β-carotene concentrations in pepper fruits had no detrimental effect on the concentrations of mineral elements required for human nutrition.

  8. Unbalanced international collaboration affects adversely the usefulness of countries' scientific output as well as their technological and social impact.

    PubMed

    Zanotto, Sonia R; Haeffner, Cristina; Guimarães, Jorge A

    2016-01-01

    The unbalanced international scientific collaboration as cause of misleading information on the country's contribution to the scientific world output was analyzed. ESI Data Base (Thomson Reuters' InCites), covering the scientific production of 217 active countries in the period 2010-2014 was used. International collaboration implicates in a high percentage (33.1 %) of double-counted world articles, thus impacting qualitative data as citations, impact and impact relative to word. The countries were divided into three groups, according to their individual contribution to the world publications: Group I (24 countries, at least 1 %) representing 83.9 % of the total double-counted world articles. Group II (40 countries, 0.1-0.99 % each). Group III, 153 countries (70.5 %) with <0.1 % and altogether 1.9 % of the world. Qualitative characteristics of each group were also analyzed: percentage of the country's GNP applied in R&D, proportion of Scientists and Engineers per million inhabitants and Human Development Index. Average international collaboration were: Group I, 43.0 %; Group II, 55.8 % and Group III, 85.2 %. We concluded that very high and unbalanced international collaboration, as presented by many countries, misrepresent the importance of their scientific production, technological and social outputs. Furthermore, it jeopardizes qualitative outputs of the countries themselves, artificially increasing their scientific impact, affecting all fields and therefore, the whole world. The data confirm that when dealing with the qualitative contribution of countries, it is necessary to take in consideration the level of international cooperation because, as seen here, it can and in fact it does create false impression of the real contribution of countries.

  9. Single layer centrifugation of stallion spermatozoa through Androcoll™-E does not adversely affect their capacitation-like status, as measured by CTC staining.

    PubMed

    Bergqvist, A-S; Johannisson, A; Bäckgren, L; Dalin, A-M; Rodriguez-Martinez, H; Morrell, J M

    2011-02-01

    This study was designed to evaluate the effect of single layer centrifugation (SLC) and subsequent cold storage on stallion sperm capacitation-like status and acrosome reaction. Three stallions were included in the study, with three ejaculates per stallion. The samples were examined 4, 24 and 72 h after collection, extension and SLC, with storage at 6°C. Sperm capacitation-like status was investigated using the fluorescent dye chlortetracycline (CTC). There was no difference in capacitation-like status between colloid-selected and non-selected spermatozoa. Sperm motility decreased significantly during cold storage, whereas the proportion of apparently capacitated spermatozoa increased. There was no change in the proportion of acrosome-reacted spermatozoa. In conclusion, SLC through Androcoll™-E does not adversely affect the capacitation-like status of stallion spermatozoa, although it did increase with time during cold storage.

  10. Mapping patterns of depression-related brain regions with cytochrome oxidase histochemistry: relevance of animal affective systems to human disorders, with a focus on resilience to adverse events.

    PubMed

    Harro, Jaanus; Kanarik, Margus; Matrov, Denis; Panksepp, Jaak

    2011-10-01

    The search for novel antidepressants may be facilitated by pre-clinical animal models that relay on specific neural circuit and related neurochemical endpoint measures, which are anchored in concrete neuro-anatomical and functional neural-network analyzes. One of the most important initial considerations must be which regions of the brain are candidates for the maladaptive response to depressogenic challenges. Consideration of persistent differences or changes in the activity of cerebral networks can be achieved by mapping oxidative metabolism in ethologically or pathogenetically relevant animal models. Cytochrome oxidase histochemistry is a technique suitable to detect regional long-term brain activity changes relative to control conditions and has been used in a variety of animal models. This work is summarized and indicates that major changes occur mainly in subcortical areas, highlighting specific brain regions where some alterations in regional oxidative metabolism may represent adaptive changes to depressogenic adverse life events, while others may reflect failures of adaptation. Many of these changes in oxidative metabolism may depend upon the integrity of serotonergic neurotransmission, and occur in several brain regions shown by other techniques to be involved in endogenous affective circuits that control emotional behaviors as well as related higher brain regions that integrate learning and cognitive information processing. These brain regions appear as primary targets for further identification of endophenotypes specific to affective disorders.

  11. CYP1B1 G199T Polymorphism Affects Prognosis of NSCLC Patients with the Potential to Be an Indicator and Target for Precise Drug Intervention

    PubMed Central

    Zhang, Shaofeng; Zhang, Qi; Zhao, Shilei

    2017-01-01

    CYP1B1 gene single nucleotide polymorphisms G119T, C432G, and A453G were tested among 164 NSCLC patients treated by Video-Assisted Thoracoscopic Surgery. After a follow-up period of 5 years, it was found that CYP1B1 G119T mutant genotypes were related to a higher risk of tumor recurrence and death after surgical resection. However, C432G and A453G genotypes had no influence on long-term prognosis of the study cohort. Thus, G199T alleles are supposed to be an auxiliary predictor for prognosis of NSCLC patients and a potential target for precise drug intervention, as well as a candidate for further anticancer drug research. PMID:28377924

  12. Risk and prognosis of adult primary immune thrombocytopenia.

    PubMed

    Frederiksen, Henrik; Christiansen, Christian Fynbo; Nørgaard, Mette

    2012-04-01

    Adult immune thrombocytopenia was previously considered a benign disease affecting young people and with a low risk of severe bleeding. This view was challenged by studies published during the past decade, as the median age of adult immune thrombocytopenia patients has been found to be 55-60 years and the incidence increases with age. Recent studies reported that mortality and morbidity are increased compared with the general population. In this review, we describe patient-specific factors associated with the outcome of disease, the clinical course of immune thrombocytopenia including the potential adverse impact of some treatments and finally the overall prognosis.

  13. Characteristics, prevalence, and prognosis of postmyocardial infarction syndrome.

    PubMed Central

    Welin, L; Vedin, A; Wilhelmsson, C

    1983-01-01

    Among 1809 patients with myocardial infarction, 60 (3.3%) later developed a postmyocardial infarction syndrome. These 60 patients were compared with controls with myocardial infarction but without postmyocardial infarction syndrome. Cases with postmyocardial infarction syndrome had larger and more complicated infarcts than control subjects. Five year cumulative mortality was higher among cases (26%) than among control subjects (18%) but this difference was not statistically significant. Corticosteroid treatment did not adversely affect the prognosis of the postmyocardial infarction syndrome, which we conclude is mainly determined by the severity of the underlying coronary heart disease. PMID:6882603

  14. Venous Thromboembolism and Prognosis in Cancer

    PubMed Central

    Khorana, Alok A.

    2010-01-01

    Venous thromboembolism (VTE) is a frequent complication of malignancy, and its incidence has increased markedly in recent years. VTE itself can directly lead to patient mortality, and is the second leading cause of death in patients with cancer. Furthermore, emerging data suggest that activation of coagulation in malignancy is integrally linked with tumor biology, particularly with angiogenesis. The development of the clinical hypercoagulable state is also linked with adverse prognosis in patients with cancer, including patients receiving systemic chemotherapy. This review focuses on the clinical evidence documenting a link between VTE and adverse short-term and long-term prognosis in patients with cancer. PMID:20097409

  15. Down-regulation of muscarinic acetylcholine receptor M2 adversely affects the expression of Alzheimer's disease-relevant genes and proteins.

    PubMed

    Zuchner, Thole; Schliebs, Reinhard; Perez-Polo, J Regino

    2005-10-01

    Beta-amyloid peptides play a major role in the pathogenesis of Alzheimer's disease (AD). Therefore, preventing beta-amyloid formation by inhibition of the beta site amyloid precursor protein-cleaving enzyme (BACE) 1 is considered as a potential strategy to treat AD. Cholinergic mechanisms have been shown to control amyloid precursor protein processing and the number of muscarinic M2-acetylcholine receptors is decreased in brain regions of patients with AD enriched with senile plaques. Therefore, the present study investigates the effect of this M2 muscarinic receptor down-regulation by siRNA on total gene expression and on regulation of BACE1 in particular in SK-SH-SY5Y cells. This model system was used for microarray analysis after carbachol stimulation of siRNA-treated cells compared with carbachol stimulated, non-siRNA-treated cells. The same model system was used to elucidate changes at the protein level by using two-dimensional gels followed by Matrix Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF) analysis. Taken together, the results indicate that the M2 acetylcholine receptor down-regulation in brains of patients with AD has important effects on the expression of several genes and proteins with major functions in the pathology of AD. This includes beta-secretase BACE1 as well as several modulators of the tau protein and other AD-relevant genes and proteins. Moreover, most of these genes and proteins are adversely affected against the background of AD.

  16. High fat diet enriched with saturated, but not monounsaturated fatty acids adversely affects femur, and both diets increase calcium absorption in older female mice.

    PubMed

    Wang, Yang; Dellatore, Peter; Douard, Veronique; Qin, Ling; Watford, Malcolm; Ferraris, Ronaldo P; Lin, Tiao; Shapses, Sue A

    2016-07-01

    Diet induced obesity has been shown to reduce bone mineral density (BMD) and Ca absorption. However, previous experiments have not examined the effect of high fat diet (HFD) in the absence of obesity or addressed the type of dietary fatty acids. The primary objective of this study was to determine the effects of different types of high fat feeding, without obesity, on fractional calcium absorption (FCA) and bone health. It was hypothesized that dietary fat would increase FCA and reduce BMD. Mature 8-month-old female C57BL/6J mice were fed one of three diets: a HFD (45% fat) enriched either with monounsaturated fatty acids (MUFAs) or with saturated fatty acids (SFAs), and a normal fat diet (NFD; 10% fat). Food consumption was controlled to achieve a similar body weight gain in all groups. After 8wk, total body bone mineral content and BMD as well as femur total and cortical volumetric BMD were lower in SFA compared with NFD groups (P<.05). In contrast, femoral trabecular bone was not affected by the SFAs, whereas MUFAs increased trabecular volume fraction and thickness. The rise over time in FCA was greater in mice fed HFD than NFD and final FCA was higher with HFD (P<.05). Intestinal calbindin-D9k gene and hepatic cytochrome P450 2r1 protein levels were higher with the MUFA than the NFD diet (P<.05). In conclusion, HFDs elevated FCA overtime; however, an adverse effect of HFD on bone was only observed in the SFA group, while MUFAs show neutral or beneficial effects.

  17. Maternal fish oil supplementation during lactation may adversely affect long-term blood pressure, energy intake, and physical activity of 7-year-old boys.

    PubMed

    Asserhøj, Marie; Nehammer, Sofie; Matthiessen, Jeppe; Michaelsen, Kim F; Lauritzen, Lotte

    2009-02-01

    Early nutrition may program obesity and cardiovascular risk later in life, and one of the potential agents is (n-3) long-chain PUFA (LCPUFA). In this study, our objective was to examine whether fish oil (FO) supplementation during lactation affects blood pressure and body composition of children. Danish mothers (n = 122) were randomized to FO [1.5 g/d (n-3) LCPUFA] or olive oil (OO) supplementations during the first 4 mo of lactation. The trial also included a high-fish intake reference group (n = 53). Ninety-eight children were followed-up with blood pressure and anthropometry measurements at 7 y. Diet and physical activity level (PAL) were assessed by 4-d weighed dietary records and ActiReg. The PAL value was 4% lower (P = 0.048) and energy intake (EI) of the boys was 1.1 +/- 0.4 MJ/d higher (P = 0.014) in the FO group than in the OO group. Starch intake was 15 +/- 6 g/d higher (P = 0.012) in the FO group, but there were no other differences in diet. Body composition did not differ between the randomized groups with or without adjustment for starch intake, EI, and PAL. FO boys had 6 mm Hg higher diastolic and mean arterial blood pressure than OO boys (P < 0.01), but girls did not differ. Within the randomized groups, blood pressure was not correlated with maternal RBC (n-3) LCPUFA after the intervention, but PAL values were (r = -0.277; P = 0.038). We previously found higher BMI at 2.5 y in the FO group, but the difference did not persist. The differences in blood pressure, EI, and PAL, particularly among boys, suggest that early (n-3) LCPUFA intake may have adverse effects, which should be investigated in future studies.

  18. DELAY OF 2 OR 6 WEEKS ADVERSELY AFFECTS THE FUNCTIONAL OUTCOME OF AUGMENTED PRIMARY REPAIR OF THE PORCINE ANTERIOR CRUCIATE LIGAMENT

    PubMed Central

    Magarian, Elise M.; Fleming, Braden C.; Harrison, Sophia L.; Mastrangelo, Ashley N.; Badger, Gary J.; Murray, Martha M.

    2010-01-01

    BACKGROUND Enhanced primary ACL repair, in which suture repair is performed in conjunction with a collagen-platelet composite to stimulate healing, is a potential new treatment option for ACL injuries. Previous studies have evaluated this approach at the time of ACL disruption. HYPOTHESIS In this study, we hypothesized that delaying surgery by 2 or 6 weeks would have a significant effect on the functional outcome of the repair. STUDY DESIGN Controlled Laboratory Study METHODS Sixteen female Yorkshire pigs underwent staged, bilateral surgical ACL transections. ACL transection was initially performed on one knee and the knee closed. Two or six weeks later, enhanced primary repair was performed in that knee while the contralateral knee had an ACL transection and immediate repair. Biomechanical parameters were measured after 15 weeks in vivo to determine the effect of delay time relative to immediate repair on the healing response. RESULTS Yield load of the repairs at 15 weeks was decreased by 40% and 60% in the groups where repair was delayed for 2 and 6 weeks respectively (p=0.01). Maximum load showed similar results (55% and 60% decrease in the 2 and 6 week delay groups respectively, p=0.011). Linear stiffness also was adversely affected by delay (50% decrease compared to immediate repair after either a 2 or 6 week delay, p=0.011). AP laxity after 15 weeks of healing was 40% higher in knees repaired after a 2 week delay, and 10% higher in those repaired after a six week delay (p=0.012) when tested at 30 degrees of flexion, but was not significantly affected by delay when tested at 60 or 90 degrees (p=0.21). CONCLUSIONS A delay between ACL injury and enhanced primary repair has a significant negative effect on the functional performance of the repair. CLINICAL RELEVANCE As future investigations assess new techniques of ACL repair, the timing of the repair should be considered in the design and the interpretation of experimental studies. PMID:20855556

  19. Is detection of adverse events affected by record review methodology? an evaluation of the “Harvard Medical Practice Study” method and the “Global Trigger Tool”

    PubMed Central

    2013-01-01

    Background There has been a theoretical debate as to which retrospective record review method is the most valid, reliable, cost efficient and feasible for detecting adverse events. The aim of the present study was to evaluate the feasibility and capability of two common retrospective record review methods, the “Harvard Medical Practice Study” method and the “Global Trigger Tool” in detecting adverse events in adult orthopaedic inpatients. Methods We performed a three-stage structured retrospective record review process in a random sample of 350 orthopaedic admissions during 2009 at a Swedish university hospital. Two teams comprised each of a registered nurse and two physicians were assigned, one to each method. All records were primarily reviewed by registered nurses. Records containing a potential adverse event were forwarded to physicians for review in stage 2. Physicians made an independent review regarding, for example, healthcare causation, preventability and severity. In the third review stage all adverse events that were found with the two methods together were compared and all discrepancies after review stage 2 were analysed. Events that had not been identified by one of the methods in the first two review stages were reviewed by the respective physicians. Results Altogether, 160 different adverse events were identified in 105 (30.0%) of the 350 records with both methods combined. The “Harvard Medical Practice Study” method identified 155 of the 160 (96.9%, 95% CI: 92.9-99.0) adverse events in 104 (29.7%) records compared with 137 (85.6%, 95% CI: 79.2-90.7) adverse events in 98 (28.0%) records using the “Global Trigger Tool”. Adverse events “causing harm without permanent disability” accounted for most of the observed difference. The overall positive predictive value for criteria and triggers using the “Harvard Medical Practice Study” method and the “Global Trigger Tool” was 40.3% and 30.4%, respectively. Conclusions More adverse

  20. Factors Affecting Adverse Drug Reaction Reporting of Healthcare Professionals and Their Knowledge, Attitude, and Practice towards ADR Reporting in Nekemte Town, West Ethiopia

    PubMed Central

    Gurmesa, Lense Temesgen

    2016-01-01

    Background. Adverse drug reactions are global problems of major concern. Adverse drug reaction reporting helps the drug monitoring system to detect the unwanted effects of those drugs which are already in the market. Aims. To assess the knowledge, attitude, and practice of health care professionals working in Nekemte town towards adverse drug reaction reporting. Methods and Materials. A cross-sectional study design was conducted on a total of 133 health care professionals by interview to assess their knowledge, attitude, and practice using structured questionnaire. Results. Of the total respondents, only 64 (48.2%), 56 (42.1%), and 13 (9.8%) health care professionals have correctly answered the knowledge, attitude, and practice assessment questions, respectively. Lack of awareness and knowledge on what, when, and to whom to report adverse drug reactions and lack of commitments of health care professionals were identified as the major discouraging factors against adverse drug reaction reporting. Conclusion. This study has revealed that the knowledge, attitude, and practice of the health care professionals working in Nekemte town towards spontaneous adverse drug reaction reporting were low that we would like to recommend the concerned bodies to strive on the improvement of the knowledge, attitude, and practice status of health care professionals. PMID:28042569

  1. Understanding Your Cancer Prognosis

    Cancer.gov

    Understanding Your Cancer Prognosis is the main video in the NCI Prognosis Video Series, which offers the perspectives of three cancer patients and their doctor, an oncologist who is also a national expert in doctor-patient communication.

  2. Dipeptidyl Peptidase IV Inhibition Does Not Adversely Affect Immune or Virological Status in HIV Infected Men And Women: A Pilot Safety Study

    PubMed Central

    Goodwin, Scott R.; Reeds, Dominic N.; Royal, Michael; Struthers, Heidi; Laciny, Erin

    2013-01-01

    Context: People infected with HIV have a higher risk for developing insulin resistance, diabetes, and cardiovascular disease than the general population. Dipeptidyl peptidase IV (DPP4) inhibitors are glucose-lowering medications with pleiotropic actions that may particularly benefit people with HIV, but the immune and virological safety of DPP4 inhibition in HIV is unknown. Objective: DPP4 inhibition will not reduce CD4+ T lymphocyte number or increase HIV viremia in HIV-positive adults. Design: This was a randomized, placebo-controlled, double-blind safety trial of sitagliptin in HIV-positive adults. Setting: The study was conducted at an academic medical center. Participants: Twenty nondiabetic HIV-positive men and women (9.8 ± 5.5 years of known HIV) taking antiretroviral therapy and with stable immune (625 ± 134 CD4+ T cells per microliter) and virological (<48 copies HIV RNA per milliliter) status. Intervention: The intervention included sitagliptin (100 mg/d) vs matching placebo for up to 24 weeks. Main Outcome Measures: CD4+ T cell number and plasma HIV RNA were measured every 4 weeks; fasting serum regulated upon activation normal T-cell expressed and secreted (RANTES), stromal derived factor (SDF)-1α, Soluble TNF receptor II, and oral glucose tolerance were measured at baseline, week 8, and the end of study. ANOVA was used for between-group comparisons; P < .05 was considered significant. Results: Compared with placebo, sitagliptin did not reduce CD4+ T cell count, plasma HIV RNA remained less than 48 copies/mL, RANTES and soluble TNF receptor II concentrations did not increase. SDF1α concentrations declined (P < .0002) in the sitagliptin group. The oral glucose tolerance levels improved in the sitagliptin group at week 8. Conclusions: Despite lowering SDF1α levels, sitagliptin did not adversely affect immune or virological status, or increase immune activation, but did improve glycemia in healthy, nondiabetic HIV-positive adults. These safety data

  3. Analysis of Preoperative Metabolic Risk Factors Affecting the Prognosis of Patients with Esophageal Squamous Cell Carcinoma: The Fujian Prospective Investigation of Cancer (FIESTA) Study.

    PubMed

    Peng, Feng; Hu, Dan; Lin, Xiandong; Chen, Gang; Liang, Binying; Zhang, Hejun; Dong, Xiaoqun; Lin, Jinxiu; Zheng, Xiongwei; Niu, Wenquan

    2017-02-01

    Some metabolic factors have been shown to be associated with an increased risk of esophageal cancer; however the association with its prognosis is rarely reported. Here, we assessed the prediction of preoperative metabolic syndrome and its single components for esophageal cancer mortality by analyzing a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. Between 2000 and 2010, patients who underwent three-field lymphadenectomy were eligible for inclusion. Blood/tissue specimens, demographic and clinicopathologic data were collected at baseline. Metabolic syndrome is defined by the criteria proposed by Chinese Diabetes Society. In this study, analysis was restricted to esophageal squamous cell carcinoma (ESCC) due to the limited number of other histological types. The median follow-up in 2396 ESCC patients (males/females: 1822/574) was 38.2months (range, 0.5-180months). The multivariate-adjusted hazard ratio (HR) of metabolic syndrome for ESCC mortality was statistically significant in males (HR, 95% confidence interval, P: 1.45, 1.14-1.83, 0.002), but not in females (1.46, 0.92-2.31, 0.107). For single metabolic components, the multivariate-adjusted HRs were significant for hyperglycemia (1.98, 1.68-2.33, <0.001) and dyslipidemia (1.41, 1.20-1.65, <0.001) in males and for hyperglycemia (1.76, 1.23-2.51, <0.001) in females, independent of clinicopathologic characteristics and obesity. In tree-structured survival analysis, the top splitting factor in both genders was tumor-node-metastasis stage, followed by regional lymph node metastasis. Taken together, our findings demonstrate that preoperative metabolic syndrome was a significant independent predictor of ESCC mortality in males, and this effect was largely mediated by glyeolipid metabolism disorder.

  4. Vaccenic acid and trans fatty acid isomers from partially hydrogenated oil both adversely affect LDL cholesterol: a double-blind, randomized controlled trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Evidence of the adverse effects of industrially-produced trans fatty acids (iTFA) on risk of cardiovascular disease is consistent and well documented in the scientific literature; however, the cardiovascular effects of naturally-occurring TFA synthesized in ruminant animals (rTFA), such as vaccenic ...

  5. National Institutes of Health chronic graft-versus-host disease staging in severely affected patients: organ and global scoring correlate with established indicators of disease severity and prognosis.

    PubMed

    Baird, Kristin; Steinberg, Seth M; Grkovic, Lana; Pulanic, Drazen; Cowen, Edward W; Mitchell, Sandra A; Williams, Kirsten M; Datiles, Manuel B; Bishop, Rachel; Bassim, Carol W; Mays, Jacqueline W; Edwards, Dean; Cole, Kristen; Avila, Daniele N; Taylor, Tiffany; Urban, Amanda; Joe, Galen O; Comis, Leora E; Berger, Ann; Stratton, Pamela; Zhang, Dan; Shelhamer, James H; Gea-Banacloche, Juan C; Sportes, Claude; Fowler, Daniel H; Gress, Ronald E; Pavletic, Steven Z

    2013-04-01

    Between 2004 and 2010, 189 adult patients were enrolled on the National Cancer Institute's cross-sectional chronic graft-versus-host disease (cGVHD) natural history study. Patients were evaluated by multiple disease scales and outcome measures, including the 2005 National Institutes of Health (NIH) Consensus Project cGVHD severity scores. The purpose of this study was to assess the validity of the NIH scoring variables as determinants of disease severity in severely affected patients in efforts to standardize clinician evaluation and staging of cGVHD. Out of 189 patients enrolled, 125 met the criteria for severe cGVHD on the NIH global score, 62 of whom had moderate disease, with a median of 4 (range, 1-8) involved organs. Clinician-assigned average NIH organ score and the corresponding organ scores assigned by subspecialists were highly correlated (r = 0.64). NIH global severity scores showed significant associations with nearly all functional and quality of life outcome measures, including the Lee Symptom Scale, Short Form-36 Physical Component Scale, 2-minute walk, grip strength, range of motion, and Human Activity Profile. Joint/fascia, skin, and lung involvement affected function and quality of life most significantly and showed the greatest correlation with outcome measures. The final Cox model with factors jointly predictive for survival included the time from cGVHD diagnosis (>49 versus ≤49 months, hazard ratio [HR] = 0.23; P = .0011), absolute eosinophil count at the time of NIH evaluation (0-0.5 versus >0.5 cells/μL, HR = 3.95; P = .0006), and NIH lung score (3 versus 0-2, HR = 11.02; P < .0001). These results demonstrate that NIH organs and global severity scores are reliable measures of cGVHD disease burden. The strong association with subspecialist evaluation suggests that NIH organ and global severity scores are appropriate for clinical and research assessments, and may serve as a surrogate for more complex subspecialist examinations. In this

  6. MCM10 overexpression implicates adverse prognosis in urothelial carcinoma

    PubMed Central

    Li, Wei-Ming; Huang, Chun-Nung; Ke, Hung-Lung; Li, Ching-Chia; Wei, Yu-Ching; Yeh, Hsin-Chih; Chang, Lin-Li; Huang, Chun-Hsiung; Liang, Peir-In; Yeh, Bi-Wen; Chan, Ti-Chun; Li, Chien-Feng; Wu, Wen-Jeng

    2016-01-01

    Urothelial carcinoma (UC) occurs in the upper urinary tract (UTUC) and the urinary bladder (UBUC). The molecular pathogenesis of UC has not been fully elucidated. Through data mining of a published transcriptome of UBUC (GSE31684), we identified Minichromosome Maintenance Complex Component 2 (MCM2) and MCM10 as the two most significantly upregulated genes in UC progression among the MCM gene family, the key factors for the initiation of DNA replication. To validate the clinical significance of MCM2 and MCM10, immunohistochemistry, evaluated by H-score, was used in a pilot study of 50 UTUC and 50 UBUC samples. Only a high expression level of MCM10 predicted worse disease-specific survival (DSS) and inferior metastasis-free survival (MeFS) for both UTUC and UBUC. Correspondingly, evaluation of MCM10 mRNA expression in 36 UTUCs and 30 UBUCs showed significantly upregulated levels in high stage UC, suggesting its role in tumor progression. Evaluation of 340 UTUC and 296 UBUC tissue samples, respectively, demonstrated that high MCM10 immunoexpression was significantly associated with advanced primary tumors, nodal status, and the presence of vascular invasion in both groups of UCs. In multivariate Cox regression analyses, adjusted for standard clinicopathological features, MCM10 overexpression was independently associated with DSS (UTUC hazard ratio [HR]=2.401, P = 0.013; UBUC HR=4.323, P=0.001) and with MeFS (UTUC HR=3.294, P<0.001; UBUC HR=1.972, P=0.015). In vitro, knockdown of MCM10 gene significantly suppressed cell proliferation in both J82 and TCCSUP cells. In conclusion, MCM10 overexpression was associated with unfavorable clinicopathological characteristics and independent negative prognostic effects, justifying its potential theranostic value in UC. PMID:27780919

  7. Migration, Neighborhoods, and Networks: Approaches to Understanding How Urban Environmental Conditions Affect Syndemic Adverse Health Outcomes Among Gay, Bisexual and Other Men Who Have Sex with Men

    PubMed Central

    Egan, James E.; Kurtz, Steven P.; Latkin, Carl; Chen, Minxing; Tobin, Karin; Yang, Cui; Koblin, Beryl A.

    2011-01-01

    Adopting socioecological, intersectionality, and lifecourse theoretical frameworks may enhance our understanding of the production of syndemic adverse health outcomes among gay, bisexual and other men who have sex with men (MSM). From this perspective, we present preliminary data from three related studies that suggest ways in which social contexts may influence the health of MSM. The first study, using cross-sectional data, looked at migration of MSM to the gay resort area of South Florida, and found that amount of time lived in the area was associated with risk behaviors and HIV infection. The second study, using qualitative interviews, observed complex interactions between neighborhood-level social environments and individual-level racial and sexual identity among MSM in New York City. The third study, using egocentric network analysis with a sample of African American MSM in Baltimore, found that sexual partners were more likely to be found through face-to-face means than the Internet. They also observed that those who co-resided with a sex partner had larger networks of people to depend on for social and financial support, but had the same size sexual networks as those who did not live with a partner. Overall, these findings suggest the need for further investigation into the role of macro-level social forces on the emotional, behavioral, and physical health of urban MSM. PMID:21369730

  8. Synthetic progestins medroxyprogesterone acetate and dydrogesterone and their binary mixtures adversely affect reproduction and lead to histological and transcriptional alterations in zebrafish (Danio rerio).

    PubMed

    Zhao, Yanbin; Castiglioni, Sara; Fent, Karl

    2015-04-07

    Medroxyprogesterone acetate (MPA) and dydrogesterone (DDG) are synthetic progestins widely used in human and veterinary medicine. Although aquatic organisms are exposed to them through wastewater and animal farm runoff, very little is known about their effects in the environment. Here we provide a comprehensive analysis of the responses of zebrafish (Danio rerio) to MPA, DDG, and their binary mixtures at measured concentrations between 4.5 and 1663 ng/L. DDG and both mixtures impaired reproductive capacities (egg production) of breeding pairs and led to histological alterations of ovaries and testes and increased gonadosomatic index. Transcriptional analysis of up to 28 genes belonging to different pathways demonstrated alterations in steroid hormone receptors, steroidogenesis enzymes, and specifically, the circadian rhythm genes, in different organs of adult zebrafish and eleuthero-embryos. Alterations occurred even at environmentally relevant concentrations of 4.5-4.8 ng/L MPA, DDG and the mixture in eleuthero-embryos and at 43-89 ng/L in adult zebrafish. Additionally, the mixtures displayed additive effects in most but not all parameters in adults and eleuthero-embryos, suggesting concentration addition. Our data suggest that MPA and DDG and their mixtures induce multiple transcriptional responses at environmentally relevant concentrations and adverse effects on reproduction and gonad histology at higher levels.

  9. Rock Glacier Outflows May Adversely Affect Lakes: Lessons from the Past and Present of Two Neighboring Water Bodies in a Crystalline-Rock Watershed

    PubMed Central

    2014-01-01

    Despite the fact that rock glaciers are one of the most common geomorphological expressions of mountain permafrost, the impacts of their solute fluxes on lakes still remain largely obscure. We examined water and sediment chemistry, and biota of two neighboring water bodies with and without a rock glacier in their catchments in the European Alps. Paleolimnological techniques were applied to track long-term temporal trends in the ecotoxicological state of the water bodies and to establish their baseline conditions. We show that the active rock glacier in the mineralized catchment of Lake Rasass (RAS) represents a potent source of acid rock drainage that results in enormous concentrations of metals in water, sediment, and biota of RAS. The incidence of morphological abnormalities in the RAS population of Pseudodiamesa nivosa, a chironomid midge, is as high as that recorded in chironomid populations inhabiting sites heavily contaminated by trace metals of anthropogenic origin. The incidence of morphological deformities in P. nivosa of ∼70% persisted in RAS during the last 2.5 millennia and was ∼40% in the early Holocene. The formation of RAS at the toe of the rock glacier most probably began at the onset of acidic drainage in the freshly deglaciated area. The present adverse conditions are not unprecedented in the lake’s history and cannot be associated exclusively with enhanced thawing of the rock glacier in recent years. PMID:24804777

  10. Rock glacier outflows may adversely affect lakes: lessons from the past and present of two neighboring water bodies in a crystalline-rock watershed.

    PubMed

    Ilyashuk, Boris P; Ilyashuk, Elena A; Psenner, Roland; Tessadri, Richard; Koinig, Karin A

    2014-06-03

    Despite the fact that rock glaciers are one of the most common geomorphological expressions of mountain permafrost, the impacts of their solute fluxes on lakes still remain largely obscure. We examined water and sediment chemistry, and biota of two neighboring water bodies with and without a rock glacier in their catchments in the European Alps. Paleolimnological techniques were applied to track long-term temporal trends in the ecotoxicological state of the water bodies and to establish their baseline conditions. We show that the active rock glacier in the mineralized catchment of Lake Rasass (RAS) represents a potent source of acid rock drainage that results in enormous concentrations of metals in water, sediment, and biota of RAS. The incidence of morphological abnormalities in the RAS population of Pseudodiamesa nivosa, a chironomid midge, is as high as that recorded in chironomid populations inhabiting sites heavily contaminated by trace metals of anthropogenic origin. The incidence of morphological deformities in P. nivosa of ∼70% persisted in RAS during the last 2.5 millennia and was ∼40% in the early Holocene. The formation of RAS at the toe of the rock glacier most probably began at the onset of acidic drainage in the freshly deglaciated area. The present adverse conditions are not unprecedented in the lake's history and cannot be associated exclusively with enhanced thawing of the rock glacier in recent years.

  11. 2.45-GHz microwave irradiation adversely affects reproductive function in male mouse, Mus musculus by inducing oxidative and nitrosative stress.

    PubMed

    Shahin, S; Mishra, V; Singh, S P; Chaturvedi, C M

    2014-05-01

    Electromagnetic radiations are reported to produce long-term and short-term biological effects, which are of great concern to human health due to increasing use of devices emitting EMR especially microwave (MW) radiation in our daily life. In view of the unavoidable use of MW emitting devices (microwaves oven, mobile phones, Wi-Fi, etc.) and their harmful effects on biological system, it was thought worthwhile to investigate the long-term effects of low-level MW irradiation on the reproductive function of male Swiss strain mice and its mechanism of action. Twelve-week-old mice were exposed to non-thermal low-level 2.45-GHz MW radiation (CW for 2 h/day for 30 days, power density = 0.029812 mW/cm(2) and SAR = 0.018 W/Kg). Sperm count and sperm viability test were done as well as vital organs were processed to study different stress parameters. Plasma was used for testosterone and testis for 3β HSD assay. Immunohistochemistry of 3β HSD and nitric oxide synthase (i-NOS) was also performed in testis. We observed that MW irradiation induced a significant decrease in sperm count and sperm viability along with the decrease in seminiferous tubule diameter and degeneration of seminiferous tubules. Reduction in testicular 3β HSD activity and plasma testosterone levels was also noted in the exposed group of mice. Increased expression of testicular i-NOS was observed in the MW-irradiated group of mice. Further, these adverse reproductive effects suggest that chronic exposure to nonionizing MW radiation may lead to infertility via free radical species-mediated pathway.

  12. Early life adversity and serotonin transporter gene variation interact at the level of the adrenal gland to affect the adult hypothalamo-pituitary-adrenal axis.

    PubMed

    van der Doelen, R H A; Deschamps, W; D'Annibale, C; Peeters, D; Wevers, R A; Zelena, D; Homberg, J R; Kozicz, T

    2014-07-08

    The short allelic variant of the serotonin transporter (5-HTT) promoter-linked polymorphic region (5-HTTLPR) has been associated with the etiology of major depression by interaction with early life stress (ELS). Furthermore, 5-HTTLPR has been associated with abnormal functioning of the stress-responsive hypothalamo-pituitary-adrenal (HPA) axis. Here, we examined if, and at what level, the HPA-axis is affected in an animal model for ELS × 5-HTTLPR interactions. Heterozygous and homozygous 5-HTT knockout rats and their wild-type littermates were exposed daily at postnatal days 2-14 to 3 h of maternal separation. When grown to adulthood, plasma levels of adrenocorticotropic hormone (ACTH), and the major rat glucocorticoid, corticosterone (CORT), were measured. Furthermore, the gene expression of key HPA-axis players at the level of the hypothalamus, pituitary and adrenal glands was assessed. No 5-HTT genotype × ELS interaction effects on gene expression were observed at the level of the hypothalamus or pituitary. However, we found significant 5-HTT genotype × ELS interaction effects for plasma CORT levels and adrenal mRNA levels of the ACTH receptor, such that 5-HTT deficiency was associated under control conditions with increased, but after ELS with decreased basal HPA-axis activity. With the use of an in vitro adrenal assay, naïve 5-HTT knockout rats were furthermore shown to display increased adrenal ACTH sensitivity. Therefore, we conclude that basal HPA-axis activity is affected by the interaction of 5-HTT genotype and ELS, and is programmed, within the axis itself, predominantly at the level of the adrenal gland. This study therefore emphasizes the importance of the adrenal gland for HPA-related psychiatric disorders.

  13. Uveal melanoma: estimating prognosis.

    PubMed

    Kaliki, Swathi; Shields, Carol L; Shields, Jerry A

    2015-02-01

    Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms "uvea," "iris," "ciliary body," "choroid," "melanoma," "uveal melanoma" and "prognosis," "metastasis," "genetic testing," "gene expression profiling." Relevant English language articles were extracted, reviewed, and referenced appropriately.

  14. Early life adversity and serotonin transporter gene variation interact to affect DNA methylation of the corticotropin-releasing factor gene promoter region in the adult rat brain.

    PubMed

    van der Doelen, Rick H A; Arnoldussen, Ilse A; Ghareh, Hussein; van Och, Liselot; Homberg, Judith R; Kozicz, Tamás

    2015-02-01

    The interaction between childhood maltreatment and the serotonin transporter (5-HTT) gene linked polymorphic region has been associated with increased risk to develop major depression. This Gene × Environment interaction has furthermore been linked with increased levels of anxiety and glucocorticoid release upon exposure to stress. Both endophenotypes are regulated by the neuropeptide corticotropin-releasing factor (CRF) or hormone, which is expressed by the paraventricular nucleus of the hypothalamus, the bed nucleus of the stria terminalis, and the central amygdala (CeA). Therefore, we hypothesized that altered regulation of the expression of CRF in these areas represents a major neurobiological mechanism underlying the interaction of early life stress and 5-HTT gene variation. The programming of gene transcription by Gene × Environment interactions has been proposed to involve epigenetic mechanisms such as DNA methylation. In this study, we report that early life stress and 5-HTT genotype interact to affect DNA methylation of the Crf gene promoter in the CeA of adult male rats. Furthermore, we found that DNA methylation of a specific site in the Crf promoter significantly correlated with CRF mRNA levels in the CeA. Moreover, CeA CRF mRNA levels correlated with stress coping behavior in a learned helplessness paradigm. Together, our findings warrant further investigation of the link of Crf promoter methylation and CRF expression in the CeA with behavioral changes that are relevant for psychopathology.

  15. Offering a forage crop at pasture did not adversely affect voluntary cow traffic or milking visits in a pasture-based automatic milking system.

    PubMed

    Scott, V E; Kerrisk, K L; Garcia, S C

    2016-03-01

    Feed is a strong incentive for encouraging cows in automatic milking systems (AMS) to voluntarily move around the farm and achieve milkings distributed across the 24 h day. It has been reported that cows show preferences for some forages over others, and it is possible that offering preferred forages may increase cow traffic. A preliminary investigation was conducted to determine the effect of offering a forage crop for grazing on premilking voluntary waiting times in a pasture-based robotic rotary system. Cows were offered one of two treatments (SOYBEAN or GRASS) in a cross-over design. A restricted maximum likelihood procedure was used to model voluntary waiting times. Mean voluntary waiting time was 45.5±6.0 min, with no difference detected between treatments. High and mid-production cows spent 55 min/milking for low-production cows, whereas waiting time increased as queue length increased. Voluntary waiting time was 23% and 80% longer when cows were fetched from the paddock or had a period of forced waiting before volunteering for milking, respectively. The time it took cows to return to the dairy since last exiting was not affected by treatment, with a mean return time of 13.7±0.6 h. Although offering SOYBEAN did not encourage cows to traffic more readily through the premilking yard, the concept of incorporating forage crops in AMS still remains encouraging if the aim is to increase the volume or quantity of home-grown feed rather than improving cow traffic.

  16. Uveal melanoma: Estimating prognosis

    PubMed Central

    Kaliki, Swathi; Shields, Carol L; Shields, Jerry A

    2015-01-01

    Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms “uvea,” “iris,” “ciliary body,” “choroid,” “melanoma,” “uveal melanoma” and “prognosis,” “metastasis,” “genetic testing,” “gene expression profiling.” Relevant English language articles were extracted, reviewed, and referenced appropriately. PMID:25827538

  17. Adverse ocular reactions to drugs.

    PubMed Central

    Spiteri, M. A.; James, D. G.

    1983-01-01

    Drugs acting on various parts of the body may also affect the eye insidiously. Increased awareness of such drug toxicity by the prescribing doctor should encourage him to consider effects on the cornea, lens, retina, optic nerve and elsewhere when checking the patient's progress. The following review concerns adverse ocular effects of systemic drug administration. PMID:6356101

  18. Vaccine Adverse Events

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  19. [Adverse reaction to not iodinated contrast].

    PubMed

    Palma-Gómez, Samuel; González-Díaz, Sandra Nora; Arias-Cruz, Alfredo; Macías-Weinmann, Alejandra; Amaro-Vivian, Laura Elizabeth; Pérez-Vanzzini, Rafael; Gutiérrez-Mujica, José Julio; Yong-Rodríguez, Adrián

    2014-01-01

    Adverse reactions to drugs are relatively frequent in clinical practice, and some of them can be life threatening. Reactions to contrast material (CM) represent an important percentage of these adverse reactions. It has been found that 70% of reactions to contrast material happen within the first five minutes of their administration. Despite the fact that hypersensitivity reactions are traditionally classified as non-allergic, in recent years investigators have reported positive skin prick tests in patients with immediate and late reactions to contrast material. This paper reports the case of a female patient with non-Hodgkin lymphoma that has presented on two distinct occasions adverse reactions to contrast material. We discuss on the type of reaction, severity, suggested prophylaxis, prognosis and recommendations, keeping in mind the underlying disease and the need to have further image studies performed.

  20. Adverse events related to blood transfusion.

    PubMed

    Sahu, Sandeep; Hemlata; Verma, Anupam

    2014-09-01

    The acute blood transfusion reactions are responsible for causing most serious adverse events. Awareness about various clinical features of acute and delayed transfusion reactions with an ability to assess the serious reactions on time can lead to a better prognosis. Evidence-based medicine has changed today's scenario of clinical practice to decrease adverse transfusion reactions. New evidence-based algorithms of transfusion and improved haemovigilance lead to avoidance of unnecessary transfusions perioperatively. The recognition of adverse events under anaesthesia is always challenging. The unnecessary blood transfusions can be avoided with better blood conservation techniques during surgery and with anaesthesia techniques that reduce blood loss. Better and newer blood screening methods have decreased the infectious complications to almost negligible levels. With universal leukoreduction of red blood cells (RBCs), selection of potential donors such as use of male donors only plasma and restriction of RBC storage, most of the non-infectious complications can be avoided.

  1. [Prognosis in ankylosing spondylitis].

    PubMed

    Diethelm, U; Schüler, G

    1991-05-21

    Based on the literature we describe the prognosis and natural history of ankylosing spondylitis. The data on mortality are controversial and it seems that only a small group of patient show a decreased survival. It is a chronic disease with most prominent features of pain and increasing stiffness during the first decade. After a course of 40 years 90% of patients have none or only mild disability. Generally quality of life is slightly reduced. Most patients remain engaged in full-time employment, but job adaptations are often unavoidable and vocational counseling seems to be worthwhile.

  2. B-cell depletion inhibits arthritis in a collagen-induced arthritis (CIA) model, but does not adversely affect humoral responses in a respiratory syncytial virus (RSV) vaccination model.

    PubMed

    Dunussi-Joannopoulos, Kyri; Hancock, Gerald E; Kunz, Arthur; Hegen, Martin; Zhou, Xiaochuan X; Sheppard, Barbara J; Lamothe, Jennifer; Li, Evelyn; Ma, Hak-Ling; Hamann, Philip R; Damle, Nitin K; Collins, Mary

    2005-10-01

    We report the development of a mouse B cell-depleting immunoconjugate (anti-CD22 monoclonal antibody [mAb] conjugated to calicheamicin) and its in vivo use to characterize the kinetics of CD22+ B-cell depletion and reconstitution in murine primary and secondary lymphoid tissues. The effect of B-cell depletion was further studied in a murine collagen-induced arthritis (CIA) model and a respiratory syncytial virus (RSV) vaccination model. Our results show that (1) the immunoconjugate has B-cell-specific in vitro and in vivo cytotoxicity; (2) B-cell reconstitution starts in the bone marrow and spleen around day 30 after depletion and is completed in all tissues tested by day 50; (3) B-cell depletion inhibits the development of clinical and histologic arthritis in the CIA model; (4) depletion of type II collagen antibody levels is not necessary for clinical and histologic prevention of CIA; and (5) B-cell depletion does not adversely affect memory antibody responses after challenge nor clearance of infectious virus from lungs in the RSV vaccination model. These results demonstrate for the first time that only B-cell reduction but not type II collagen antibody levels correlate with the prevention of arthritis and represent key insights into the role of CD22-targeted B-cell depletion in mouse autoimmunity and vaccination models.

  3. Prognosis in critical care.

    PubMed

    Ohno-Machado, Lucila; Resnic, Frederic S; Matheny, Michael E

    2006-01-01

    Prognostic risk prediction models have been employed in the intensive care unit (ICU) setting since the 1980s and provide health care providers with important information to help inform decisions related to treatment and prognosis, as well as to compare outcomes across institutions. Prognostic models for critical care are among the most widely utilized and tested predictive models in healthcare. In this article, we review and compare mortality prediction models, including the APACHE (1981), SAPS (1984), APACHE-II (1985), MPM (1987), APACHE-III (1991), SAPS-II (1993), and MPM-II (1993). We emphasize the importance of model calibration in this domain. In addition, we present a brief review of the statistical methodology, multiple logistic regression, which underlies most of the models currently used in critical care.

  4. Urbanicity, social adversity and psychosis

    PubMed Central

    Heinz, Andreas; Deserno, Lorenz; Reininghaus, Ulrich

    2013-01-01

    In recent years, there has been increasing interest in research on geographical variation in the incidence of schizophrenia and other psychoses. In this paper, we review the evidence on variation in incidence of schizophrenia and other psychoses in terms of place, as well as the individual- and area-level factors that account for this variation. We further review findings on potential mechanisms that link adverse urban environment and psychosis. There is evidence from earlier and more recent studies that urbanicity is associated with an increased incidence of schizophrenia and non-affective psychosis. In addition, considerable variation in incidence across neighbourhoods has been observed for these disorders. Findings suggest it is unlikely that social drift alone can fully account for geographical variation in incidence. Evidence further suggests that the impact of adverse social contexts – indexed by area-level exposures such as population density, social fragmentation and deprivation – on risk of psychosis is explained (confounding) or modified (interaction) by environmental exposures at the individual level (i.e., cannabis use, social adversity, exclusion and discrimination). On a neurobiological level, several studies suggest a close link between social adversity, isolation and stress on the one hand, and monoamine dysfunction on the other, which resembles findings in schizophrenia patients. However, studies directly assessing correlations between urban stress or discrimination and neurobiological alterations in schizophrenia are lacking to date. PMID:24096775

  5. Effects of muscular strength on cardiovascular risk factors and prognosis.

    PubMed

    Artero, Enrique G; Lee, Duck-chul; Lavie, Carl J; España-Romero, Vanesa; Sui, Xuemei; Church, Timothy S; Blair, Steven N

    2012-01-01

    Physical fitness is one of the strongest predictors of individual future health status. Together with cardiorespiratory fitness (CRF), muscular strength has been increasingly recognized in the pathogenesis and prevention of chronic disease. We review the most recent literature on the effect of muscular strength in the development of cardiovascular disease, with special interest in elucidating its specific benefits beyond those from CRF and body composition. Muscular strength has shown an independent protective effect on all-cause and cancer mortality in healthy middle-aged men, as well as in men with hypertension and patients with heart failure. It has also been inversely associated with age-related weight and adiposity gains, risk of hypertension, and prevalence and incidence of the metabolic syndrome. In children and adolescents, higher levels of muscular fitness have been inversely associated with insulin resistance, clustered cardiometabolic risk, and inflammatory proteins. Generally, the influence of muscular fitness was weakened but remained protective after considering CRF. Also, interestingly, higher levels of muscular fitness seems to some extent counteract the adverse cardiovascular profile of overweight and obese individuals. As many of the investigations have been conducted with non-Hispanic white men, it is important to examine how race/ethnicity and gender may affect these relationships. To conclude, most important effects of resistance training are also summarized, to better understand how higher levels of muscular fitness may result in a better cardiovascular prognosis and survival.

  6. [Vestibular neuritis: treatment and prognosis].

    PubMed

    Reinhard, A; Maire, R

    2013-10-02

    Vestibular neuritis is a sudden unilateral peripheral vestibular deficit of unknown origin without associated hearing loss. It is the second cause of peripheral vertigo after Benign Paroxysmal Positional Vertigo (BPPV). The etiology remains unclear and some treatments are still controversial. The prognosis is good. The differential diagnosis of the disease mainly includes an acute vertigo of central origin. This article summarizes the management and prognosis of vestibular neuritis.

  7. 7 CFR 1900.55 - Adverse action procedures.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS... REGULATIONS GENERAL Adverse Decisions and Administrative Appeals § 1900.55 Adverse action procedures. (a) If an applicant, guaranteed lender, a holder, borrower or grantee is adversely affected by a...

  8. The prognosis of primary intracerebral tumours presenting with epilepsy: the outcome of medical and surgical management.

    PubMed Central

    Smith, D F; Hutton, J L; Sandemann, D; Foy, P M; Shaw, M D; Williams, I R; Chadwick, D W

    1991-01-01

    It is not known whether conservative or early aggressive (resective surgery with or without radiotherapy) management is better for tumours presenting with epilepsy. The prognosis of 560 patients with a clinical and CT diagnosis of intrinsic supratentorial tumour was examined retrospectively. Epilepsy was the first symptom in 164 patients. Histological confirmation of diagnosis was available in 391 (70%) of cases. Median survival was 37 months in the group presenting with epilepsy and six months in those presenting with other symptoms (p less than 0.0001). Patients presenting with epilepsy were more likely to have a normal clinical examination, a non-enhancing low density lesion on CT scan and a low grade tumour. From Cox's stepwise proportional hazards model, significant independent variables adversely affecting prognosis were increasing age, focal neurological signs and enhancing CT lesions at diagnosis, non-resective surgery and male sex. Of those presenting with epilepsy 80 patients had surgical treatment within two months of CT diagnosis. The Cox's model failed to identify any beneficial effects for either early resective surgery or radiotherapy. In primary intracerebral tumours with presentations other than epilepsy, resective surgery and radiotherapy were amongst the important factors associated with prolonged survival. Primary intracerebral tumours presenting with epilepsy are relatively benign and their outcome appears to be chiefly determined by clinical factors. PMID:1744647

  9. Scientists Trace Adversity's Toll

    ERIC Educational Resources Information Center

    Sparks, Sarah D.

    2012-01-01

    The stress of a spelling bee or a challenging science project can enhance a student's focus and promote learning. But the stress of a dysfunctional or unstable home life can poison a child's cognitive ability for a lifetime, according to new research. Those studies show that stress forms the link between childhood adversity and poor academic…

  10. An update on predictive biomarkers for major adverse cardiovascular events in patients undergoing vascular surgery.

    PubMed

    Patelis, Nikolaos; Kouvelos, George N; Koutsoumpelis, Andreas; Moris, Demetrios; Matsagkas, Miltiadis I; Arnaoutoglou, Eleni

    2016-09-01

    Cardiovascular complications signify a major cause of morbidity and mortality in patients undergoing vascular surgery adversely affecting both short- and long-term prognosis. During the last decade, unmet needs for a distinct cardiovascular risk assessment have led to an intensive research for establishment of biomarkers with sufficient predictive value. This literature review aims in examining the value of several biomarkers in predicting the incidence of major adverse cardiac events in vascular surgery patients. We reviewed the English language literature and analyzed the biomarkers as independent predictors or in correlation with other factors. We found several biomarkers showing a significant predictive value for a major adverse cardiovascular event in patients undergoing vascular surgery. These biomarkers can be used in clinical practice as outcome predictors, although sensitivity and specificity varies. Detection of subclinical cardiovascular damage may improve total risk estimation and facilitate clinical assessment of patients at risk for future cardiovascular events. The wide variety of sensitivity and specificity in predicting a MACE of these biomarkers exert the need for future trials in which these markers will be tested as adjunctive tools of cardiovascular risk estimation scoring systems.

  11. Prognosis of ependymoma.

    PubMed

    Schiffer, D; Giordana, M T

    1998-08-01

    Ependymoma is a rare tumor entity. It affects children and adults and has four preferential locations: supra- and infra-tentorial, spinal, and conus-cauda-filum. For statistical reasons, therefore, it is difficult to identify prognostic factors in series from single institutions because of the limited number of cases. The problem is complicated by the existence of some variants and by the difficulty in recognizing the anaplastic variant, because the common criteria used for recognizing malignancy in gliomas are not completely reliable in ependymomas. Apart from age and location, many parameters have been considered for prognostic purposes, including extension of surgical removal and radiotherapy. Among histological factors, the number of mitoses, labelling indices of proliferation markers, and cell density turned out to be good parameters for prognostic purposes. An overview is given of the contributions in the literature, including our own, on this problem.

  12. Adverse drug reactions.

    PubMed

    O'Reilly-Foley, Georgina

    2017-04-05

    What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The CPD article defined the different types of adverse drug reactions (ADRs) and explored when they can occur. It emphasised the importance of being knowledgeable about medications, considering patient safety when patients are taking medications, being alert to the possibility of ADRs, and recognising and responding to suspected ADRs.

  13. Early Adverse Experiences and the Developing Brain

    PubMed Central

    Bick, Johanna; Nelson, Charles A

    2016-01-01

    Children exposed to various forms of adversity early in life are at increased risk for a broad range of developmental difficulties, affecting both cognitive and emotional adjustment. We review a growing body of evidence suggesting that exposure to adverse circumstances affects the developing brain in ways that increase risk for a myriad of problems. We focus on two forms of adversity, one in which children are exposed to childhood maltreatment in family environments, and another in which children are exposed to extreme psychosocial deprivation in contexts of institutional rearing. We discuss ways in which each of these experiences represent violations of species-expected caregiving conditions, thereby imposing challenges to the developing brain. We also review emerging data pointing to the effectiveness of early intervention in remediating neurodevelopmental consequences associated with maltreatment or institutional rearing. We conclude by discussing implications of this work for public health efforts and highlight important directions for the field. PMID:26334107

  14. Risk factors and prognosis for salivary gland adenoid cystic carcinoma in southern china

    PubMed Central

    Ouyang, Dai-qiao; Liang, Li-zhong; Zheng, Guang-sen; Ke, Zun-fu; Weng, De-sheng; Yang, Wei-fa; Su, Yu-xiong; Liao, Gui-qing

    2017-01-01

    Abstract Adenoid cystic carcinoma (ACC) is characterized by slow growth, frequent local recurrences, and high incidence of distant metastasis (DM). The aim of this study was to evaluate predictive factors for local-regional (LR) recurrence, DM, and survival in ACC. A retrospective review of the medical records for patients with salivary glands ACC from 1990 to 2015 was performed. The clinical parameters were assessed to identify correlations with the development of LR recurrence, DM, and survival of these patients. Among 228 patients who underwent surgery as definitive treatment, 210 (92.1%) were followed up in the study. DM was detected in 64 (30.5%) patients, LR recurrence was detected in 58 (27.6%) patients. The estimated 5, 10, and 15-year overall survival rates were 84.7%, 70.8%, and 34.0%, respectively. Multivariate analysis revealed that the presence of lymphovascular invasion and a high T classification were very strong adverse factors, which independently influenced LR recurrence, DM, and survival of ACC patients. Positive/close margin and N+ status were independent risk factors for DM and LR recurrence, respectively. Survival of ACC patents was also affected by tumor location. Presence of lymphovascular invasion and a high T classification were very strong adverse factors and independent predictors for ACC patients’ prognosis, which influenced LR control, DM control, and survival. PMID:28151884

  15. Adverse effects of cannabis.

    PubMed

    2011-01-01

    Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to

  16. Adverse reactions to vaccines.

    PubMed

    Martin, Bryan L; Nelson, Michael R; Hershey, Joyce N; Engler, Renata J M

    2003-06-01

    (The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.) Immunization healthcare is becoming increasingly complex as the number and types of vaccines have continued to expand. Like all prescription drugs, vaccines may be associated with adverse events. The majority of these reactions are self-limited and not associated with prolonged disability. The media, Internet and public advocacy groups have focused on potentially serious vaccine-associated adverse events with questions raised about causal linkages to increasing frequencies of diseases such as autism and asthma. Despite a lack of evidence of a causal relationship to a variety of vaccine safety concerns, including extensive reviews by the Institute of Medicine, questions regarding vaccine safety continue to threaten the success of immunization programs. Risk communication arid individual risk assessment is further challenged by the public health success of vaccine programs creating the perception that certain vaccines are no longer necessary or justified because of the rare reaction risk. There is a need for improved understanding of true vaccine contraindications and precautions as well as host factors and disease threat in order to develop a patient specific balanced risk communication intervention. When they occur, vaccine related adverse events must be treated, documented and reported through the VAERS system. The increasing complexity of vaccination health care has led the Center of Disease Control and Prevention (CDC) to identify Vaccine Safety Assessment and Evaluation as a potential new specialty.

  17. Revisiting determinants of prognosis in cutaneous melanoma.

    PubMed

    Weiss, Sarah A; Hanniford, Douglas; Hernando, Eva; Osman, Iman

    2015-12-01

    The American Joint Committee on Cancer staging system for cutaneous melanoma is based on primary tumor thickness and the presence of ulceration, mitoses, lymph node spread, and distant metastases as determinants of prognosis. Although this cutaneous melanoma staging system has evolved over time to more accurately reflect patient prognosis, improvements are still needed, because current understanding of the particular factors (genetic mutation, expression alteration, host response, etc) that are critical for predicting patient outcomes is incomplete. Given the clinical and biologic heterogeneity of primary melanomas, new prognostic tools are needed to more precisely identify patients who are most likely to develop advanced disease. Such tools would affect clinical surveillance strategies and aid in patient selection for adjuvant therapy. The authors reviewed the literature on prognostic molecular and immunologic markers in primary cutaneous melanoma, their associations with clinicopathologic and survival outcomes, and their potential for incorporation into current staging models. Overall, the studies considered in this review did not define prognostic markers that could be readily incorporated into the current staging system. Therefore, efforts should be continued in these and other directions to maximize the likelihood of identifying clinically useful prognostic biomarkers for cutaneous melanoma.

  18. The Need for Biomarkers in Diagnosis and Prognosis of Drug-Induced Liver Disease: Does Metabolomics Have Any Role?

    PubMed Central

    Iruzubieta, Paula; Arias-Loste, Maria Teresa; Barbier-Torres, Lucía; Martinez-Chantar, Maria Luz; Crespo, Javier

    2015-01-01

    Drug-induced liver injury (DILI) is a potentially fatal adverse event and the leading cause of acute liver failure in the US and in the majority of Europe. The liver can be affected directly, in a dose-dependent manner, or idiosyncratically, independently of the dose, and therefore unpredictably. Currently, DILI is a diagnosis of exclusion that physicians should suspect in patients with unexplained elevated liver enzymes. Therefore, new diagnostic and prognostic biomarkers are necessary to achieve an early and reliable diagnosis of DILI and thus improve the prognosis. Although several DILI biomarkers have been found through analytical and genetic tests and pharmacokinetic approaches, none of them have been able to display enough specificity and sensitivity, so new approaches are needed. In this sense, metabolomics is a strongly and promising emerging field that, from biofluids collected through minimally invasive procedures, can obtain early biomarkers of toxicity, which may constitute specific indicators of liver damage. PMID:26824035

  19. Assessment of prognosis of cirrhosis.

    PubMed

    Durand, François; Valla, Dominique

    2008-02-01

    Once patients with cirrhosis experience decompensation, early mortality risk increases sharply. Liver transplantation has transformed the prognosis of decompensated cirrhosis. Child-Pugh score has been the reference for many years for assessing the prognosis of cirrhosis. However, Child-Pugh score has important limitations among which is subjective interpretation of some of its variables, making it difficult to categorize patients according to their own disease severity. The model for end-stage liver disease (MELD) score, which was originally designed for assessing the prognosis of cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt (TIPS), is a continuous score relying on three objective variables. Along with TIPS, MELD score proved to be a robust marker of early mortality across a wide spectrum of causes of cirrhosis, even though 10 to 20% of patients are still misclassified. MELD is especially useful for prioritizing candidates for transplantation according to a "sickest first" policy. However, MELD is not a universal prognostic marker of cirrhosis and several MELD exceptions require more specific approaches.

  20. [Cutaneous adverse drug reactions].

    PubMed

    Lebrun-Vignes, B; Valeyrie-Allanore, L

    2015-04-01

    Cutaneous adverse drug reactions (CADR) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Exanthematous eruptions, urticaria and vasculitis are the most common forms of CADR. Fixed eruption is uncommon in western countries. Serious reactions (fatal outcome, sequelae) represent 2% of CADR: bullous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), DRESS (drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome) and acute generalized exanthematous pustulosis (AGEP). These forms must be quickly diagnosed to guide their management. The main risk factors are immunosuppression, autoimmunity and some HLA alleles in bullous reactions and DRESS. Most systemic drugs may induce cutaneous adverse reactions, especially antibiotics, anticonvulsivants, antineoplastic drugs, non-steroidal anti-inflammatory drugs, allopurinol and contrast media. Pathogenesis includes immediate or delayed immunologic mechanism, usually not related to dose, and pharmacologic/toxic mechanism, commonly dose-dependent or time-dependent. In case of immunologic mechanism, allergologic exploration is possible to clarify drug causality, with a variable sensitivity according to the drug and to the CADR type. It includes epicutaneous patch testing, prick test and intradermal test. However, no in vivo or in vitro test can confirm the drug causality. To determine the cause of the eruption, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis is required, completed with a literature search. A reporting to pharmacovigilance network is essential in case of a serious CADR whatever the suspected drug and in any case if the involved drug is a newly marketed one or unusually related to cutaneous reactions.

  1. The prognosis of cyclical vomiting syndrome

    PubMed Central

    Dignan, F; Symon, D; AbuArafeh, I; Russell, G

    2001-01-01

    AIMS—The medium term prognosis of cyclical vomiting syndrome (CVS) was studied to determine the proportion of affected individuals who had gone on to develop headaches fulfilling the International Headache Society criteria for migraine.
METHODS—Twenty six (76%) of 34 CVS sufferers identified from the authors' clinical records were traced, and all agreed to participate. Each child was matched to a control, and telephone interviews were conducted using a standardised questionnaire.
RESULTS—Thirteen (50%) of the subjects had continuing CVS and/or migraine headaches while the remainder were currently asymptomatic. The prevalence of past or present migraine headaches in subjects (46%) was significantly higher than in the control population (12%).
CONCLUSION—Results support the concept that CVS is closely related to migraine.

 PMID:11124785

  2. The B-3 Ethylene Response Factor MtERF1-1 Mediates Resistance to a Subset of Root Pathogens in Medicago truncatula without Adversely Affecting Symbiosis with Rhizobia1[W][OA

    PubMed Central

    Anderson, Jonathan P.; Lichtenzveig, Judith; Gleason, Cynthia; Oliver, Richard P.; Singh, Karam B.

    2010-01-01

    The fungal necrotrophic pathogen Rhizoctonia solani is a significant constraint to a range of crops as diverse as cereals, canola, and legumes. Despite wide-ranging germplasm screens in many of these crops, no strong genetic resistance has been identified, suggesting that alternative strategies to improve resistance are required. In this study, we characterize moderate resistance to R. solani anastomosis group 8 identified in Medicago truncatula. The activity of the ethylene- and jasmonate-responsive GCC box promoter element was associated with moderate resistance, as was the induction of the B-3 subgroup of ethylene response transcription factors (ERFs). Genes of the B-1 subgroup showed no significant response to R. solani infection. Overexpression of a B-3 ERF, MtERF1-1, in Medicago roots increased resistance to R. solani as well as an oomycete root pathogen, Phytophthora medicaginis, but not root knot nematode. These results indicate that targeting specific regulators of ethylene defense may enhance resistance to an important subset of root pathogens. We also demonstrate that overexpression of MtERF1-1 enhances disease resistance without apparent impact on nodulation in the A17 background, while overexpression in sickle reduced the hypernodulation phenotype. This suggests that under normal regulation of nodulation, enhanced resistance to root diseases can be uncoupled from symbiotic plant-microbe interactions in the same tissue and that ethylene/ERF regulation of nodule number is distinct from the defenses regulated by B-3 ERFs. Furthermore, unlike the stunted phenotype previously described for Arabidopsis (Arabidopsis thaliana) ubiquitously overexpressing B-3 ERFs, overexpression of MtERF1-1 in M. truncatula roots did not show adverse effects on plant development. PMID:20713618

  3. Great Toe Necrosis Predicts an Unfavorable Limb Salvage Prognosis

    PubMed Central

    Ichioka, Shigeru

    2014-01-01

    Summary: The initial location of necrosis may affect the limb salvage rate. This study of 130 patients with chronic toe ulcers or gangrene was performed to assess whether the location of initial necrosis in the toes affected limb salvage prognosis. The patients were divided into 2 groups according to whether the initial necrosis was in the great toe or in other toes. Limb salvage prognosis was determined retrospectively. In the great toe group, the rates of total toe loss and major amputation were 50.0% and 24.4%, respectively. When the initial necrosis was in other toes, these rates were 27.3% and 9.3%, respectively. Great toe necrosis is associated with significantly higher rates of total toe loss (odds ratio = 3.10; P = 0.003; 95% confidence interval, 1.43−6.68) and major amputation (odds ratio = 3.66; P = 0.007; 95% confidence interval, 1.37−9.79). The great toe is supplied by 3 source arteries, whereas the lesser toes are fed by 1 or 2 arteries. Therefore, necrosis initiating from the great toe may reflect the presence of severe vascular disorders. The great toe is also anatomically connected to much of the foot via the tendons. Infection is more likely to spread along these tendons, which may reduce limb prognosis. Thus, the initial location of necrosis may be predictive of limb prognosis. PMID:25426399

  4. Adverse cutaneous drug reaction.

    PubMed

    Nayak, Surajit; Acharjya, Basanti

    2008-01-01

    In everyday clinical practice, almost all physicians come across many instances of suspected adverse cutaneous drug reactions (ACDR) in different forms. Although such cutaneous reactions are common, comprehensive information regarding their incidence, severity and ultimate health effects are often not available as many cases go unreported. It is also a fact that in the present world, almost everyday a new drug enters market; therefore, a chance of a new drug reaction manifesting somewhere in some form in any corner of world is unknown or unreported. Although many a times, presentation is too trivial and benign, the early identification of the condition and identifying the culprit drug and omit it at earliest holds the keystone in management and prevention of a more severe drug rash. Therefore, not only the dermatologists, but all practicing physicians should be familiar with these conditions to diagnose them early and to be prepared to handle them adequately. However, we all know it is most challenging and practically difficult when patient is on multiple medicines because of myriad clinical symptoms, poorly understood multiple mechanisms of drug-host interaction, relative paucity of laboratory testing that is available for any definitive and confirmatory drug-specific testing. Therefore, in practice, the diagnosis of ACDR is purely based on clinical judgment. In this discussion, we will be primarily focusing on pathomechanism and approach to reach a diagnosis, which is the vital pillar to manage any case of ACDR.

  5. Adverse childhood experiences and health anxiety in adulthood.

    PubMed

    Reiser, Sarah J; McMillan, Katherine A; Wright, Kristi D; Asmundson, Gordon J G

    2014-03-01

    Childhood experiences are thought to predispose a person to the development of health anxiety later in life. However, there is a lack of research investigating the influence of specific adverse experiences (e.g., childhood abuse, household dysfunction) on this condition. The current study examined the cumulative influence of multiple types of childhood adversities on health anxiety in adulthood. Adults 18-59 years of age (N=264) completed a battery of measures to assess adverse childhood experiences, health anxiety, and associated constructs (i.e., negative affect and trait anxiety). Significant associations were observed between adverse childhood experiences, health anxiety, and associated constructs. Hierarchical multiple regression analysis indicted that adverse childhood experiences were predictive of health anxiety in adulthood; however, the unique contribution of these experience were no longer significant following the inclusion of the other variables of interest. Subsequently, mediation analyses indicated that both negative affect and trait anxiety independently mediated the relationship between adverse childhood experiences and health anxiety in adulthood. Increased exposure to adverse childhood experiences is associated with higher levels of health anxiety in adulthood; this relationship is mediated through negative affect and trait anxiety. Findings support the long-term negative impact of cumulative adverse childhood experiences and emphasize the importance of addressing negative affect and trait anxiety in efforts to prevent and treat health anxiety.

  6. Major new developments affecting treatment and prognosis in hypertension.

    PubMed

    Gubner, R S

    1990-01-01

    Joint studies of the ALIMDA and Society of Actuaries, notably those of 1935, 1959 and 1979, established that there is a progressive rise in cardiovascular mortality with successive increments in blood pressure. This has provided the basis of underwriting. The converse is not true, or at least has not been true until very recently. Drugs that effectively reduce blood pressure have been available for several decades, but reduction and maintenance of blood pressure is still accomplished in only a minority of hypertensives. Long-term trials employing a combination of drugs, i.e., diuretics, vasodilators and reserpine and subsequently beta-blockers, almost without fail have not shown that treatment with these agents significantly reduces heart disease mortality and sudden death. This has been attributed, perhaps without basis, to an unfavorable countering effect of increased lipid levels, aggravating this risk factor, and other undesirable metabolic effect of diuretics, such as hypokalemia and depletion of body magnesium, increasing the propensity to ventricular arrhythmias, hyperglycemia, worsening diabetes, and hyperuricemia. A survey of 674 persons with hypertension seen personally during the period 1985-89, who were under the care of approximately that many physicians, reveals striking changes in drug prescription and use during this brief period that portend a major change in the outlook of hypertension. Two classes of drugs have increased rapidly in popularity: these are the angiotensin-converting enzyme inhibitors (ACE inhibitors) and the calcium blockers. Both classes of drugs effectively lower blood pressure and have minimal side effects with good compliance. They act not only to reduce peripheral vascular resistance, but also locally in the heart muscle to directly cause left ventricular hypertrophy to regress, an effect of great consequence. The drugs used in former trials such as the vasodilators and diuretics have no effect on left ventricular hypertrophy, unlike the ACE inhibitors and calcium antagonists. Left ventricular hypertrophy is the key lesion in hypertension and is only in part due to increased work load imposed by elevated pressure. It is associated with elevated blood pressure, but not closely and occurs independently; ventricular myocytes as well as myocytes of the vasculature being stimulated to growth by angiotensin and calcium, potentiating the effect of norepinephrine. Left ventricular hypertrophy greatly increases the propensity to ventricular arrhythmias and sudden death, and is a prime cause of cardiac mortality and sudden death not only in hypertension, but also in obesity, aging and diabetes, in which conditions left ventricular hypertrophy also is very common.(ABSTRACT TRUNCATED AT 400 WORDS)

  7. Does Cardiac Rehabilitation After Myocardial Infarction Favorably Affect Prognosis?

    ERIC Educational Resources Information Center

    Shephard, Roy J.

    1988-01-01

    This article discusses the limitations of 14 randomized controlled trials of exercise rehabilitation for patients who sustained myocardial infarction. The difficulty of sampling patients and controlling the sample size is discussed and the benefits of pooled statistical evidence are considered. (JL)

  8. Discovery of Genomic Breakpoints Affecting Breast Cancer Progression and Prognosis

    DTIC Science & Technology

    2009-10-01

    that binds other family member homologs such as RAD51D and Xrcc3 (Miller et al. 2004), possibly disrupting formation of the complex responsible for...doi: 10.1371/journal.pone.0000380. Liu, Y., Tarsounas, M., O’Regan, P., and West, S.C. 2007. Role of RAD51C and XRCC3 in genetic recombination and DNA

  9. Discovery of Genomic Breakpoints Affecting Breast Cancer Progression and Prognosis

    DTIC Science & Technology

    2010-10-01

    transcripts. By RT-PCR we determined that 4 showed a fusion mRNA. In the case of the ARFGEF2/SULF2, a non-functional Sulfatase 2 might be created. To give...suppressor Sulfatase 2. Another fusion, RAD51C/ATXN7 results in the truncation RAD51C, involved in double stranded break repair. We detected chimeric mRNA...the ARFGEF2/SULF2, and RAD51C/ATXN7. By the creation of the ARFGEF2/SULF2 fusion, the Sulfatase 2 (SULF2) protein loses its targeting peptide for

  10. Telithromycin: review of adverse effects.

    PubMed

    2014-11-01

    Telithromycin is a macrolide antibiotic that has been marketed since the early 2000s. It has not been shown to be more effective against any bacteria than other macrolide antibiotics. Its antibacterial activity is in no way remarkable. In early 2014, we reviewed its adverse effect profile using data from periodic safety update reports, drug regulatory agencies, and detailed published case reports. In addition to the adverse effect profile telithromycin shares with the other macrolides, it provokes several specific adverse effects: visual disturbances due to impaired accommodation; taste and smell disorders; severe liver damage; worsening of myasthenia gravis; rhabdomyolysis; and loss of consciousness. Prolongation of the QT interval with standard oral doses is a worrisome adverse effect. In practice, it is better not to use telithromycin as it exposes patients to disproportionate, serious adverse effects. When treatment with a macrolide antibiotic appears necessary, it is prudent to choose a different macrolide, such as spiramycin or azithromycin, which have fewer adverse effects.

  11. Impact of Body Weight and Body Composition on Ovarian Cancer Prognosis.

    PubMed

    Purcell, Sarah A; Elliott, Sarah A; Kroenke, Candyce H; Sawyer, Michael B; Prado, Carla M

    2016-02-01

    Measures of body weight and anthropometrics such as body mass index (BMI) are commonly used to assess nutritional status in clinical conditions including cancer. Extensive research has evaluated associations between body weight and prognosis in ovarian cancer patients, yet little is known about the potential impact of body composition (fat mass (FM) and fat-free mass (FFM)) in these patients. Thus, the purpose of this publication was to review the literature (using PubMed and EMBASE) evaluating the impact of body weight and particularly body composition on surgical complications, morbidity, chemotherapy dosing and toxicity (as predictors of prognosis), and survival in ovarian cancer patients. Body weight is rarely associated with intra-operative complications, but obesity predicts higher rates of venous thromboembolism and wound complications post-operatively in ovarian cancer patients. Low levels of FM and FFM are superior predictors of length of hospital stay compared to measures of body weight alone, but the role of body composition on other surgical morbidities is unknown. Obesity complicates chemotherapy dosing due to altered pharmacokinetics, imprecise dosing strategies, and wide variability in FM and FFM. Measurement of body composition has the potential to reduce toxicity if the results are incorporated into chemotherapy dosing calculations. Some findings suggest that excess body weight adversely affects survival, while others find no such association. Limited studies indicate that FM is a better predictor of survival than body weight in ovarian cancer patients, but the direction of this relationship has not been determined. In conclusion, body composition as an indicator of nutritional status is a better prognostic tool than body weight or BMI alone in ovarian cancer patients.

  12. The Neurobiology of Intervention and Prevention in Early Adversity.

    PubMed

    Fisher, Philip A; Beauchamp, Kate G; Roos, Leslie E; Noll, Laura K; Flannery, Jessica; Delker, Brianna C

    2016-01-01

    Early adverse experiences are well understood to affect development and well-being, placing individuals at risk for negative physical and mental health outcomes. A growing literature documents the effects of adversity on developing neurobiological systems. Fewer studies have examined stress neurobiology to understand how to mitigate the effects of early adversity. This review summarizes the research on three neurobiological systems relevant to interventions for populations experiencing high levels of early adversity: the hypothalamic-adrenal-pituitary axis, the prefrontal cortex regions involved in executive functioning, and the system involved in threat detection and response, particularly the amygdala. Also discussed is the emerging field of epigenetics and related interventions to mitigate early adversity. Further emphasized is the need for intervention research to integrate knowledge about the neurobiological effects of prenatal stressors (e.g., drug use, alcohol exposure) and early adversity. The review concludes with a discussion of the implications of this research topic for clinical psychology practice and public policy.

  13. The adverse health effects of chronic cannabis use.

    PubMed

    Hall, Wayne; Degenhardt, Louisa

    2014-01-01

    This paper summarizes the most probable of the adverse health effects of regular cannabis use sustained over years, as indicated by epidemiological studies that have established an association between cannabis use and adverse outcomes; ruled out reverse causation; and controlled for plausible alternative explanations. We have also focused on adverse outcomes for which there is good evidence of biological plausibility. The focus is on those adverse health effects of greatest potential public health significance--those that are most likely to occur and to affect a substantial proportion of regular cannabis users. These most probable adverse effects of regular use include a dependence syndrome, impaired respiratory function, cardiovascular disease, adverse effects on adolescent psychosocial development and mental health, and residual cognitive impairment.

  14. 25 CFR 170.110 - How can State and local governments prevent discrimination or adverse impacts?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and adverse effects on tribes and Native American populations. (b) Examples of adverse effects include... excessive access to culturally or religiously sensitive areas; (3) Negatively affecting natural resources, trust resources, tribal businesses, religious, and cultural sites; (4) Harming indigenous plants...

  15. Mechanical Failure Prognosis Through Oil Debris Monitoring

    DTIC Science & Technology

    1975-01-01

    AD/A-006 19U MECHANICAL FAILURE PROGNOSIS THROUGH OIL DEBRIS MONITORING Alan Beex"bower Exxon Research and Engineering Company Prepared...PERIOD COVERED Final Report 18 June 1973 to 1 August 197A 4. TITLE (•«id Subl/rl«) MECHANICAL FAILURE PROGNOSIS THROUGH OIL DEBRIS ...Company project entitled "Mechanical Failure Prognosis through Debris Analysis." This study was conducted for the Eustis Directorate, U.S. Army Air

  16. Acute Optic Neuritis: Prognosis for the Development of Multiple Sclerosis.

    DTIC Science & Technology

    1979-12-01

    The literature was reviewed in regard to acute optic neuritis: prognosis for the development of multiple sclerosis , with specific reference to our...series, was preselected and not prospective, causing a higher incidence of later multiple sclerosis . The second factor was the definition of multiple ...development of multiple sclerosis in patients affected with acute optic neuritis. This finding leads us to conclude that an incidence of 13% to 17

  17. Clinical presentation, diagnosis, and prognosis of chronic laminitis.

    PubMed

    Herthel, D; Hood, D M

    1999-08-01

    This article focuses on the initial assessment of the horse affected with chronic laminitis. Variations in the clinical presentation and primary considerations in making a differential diagnosis are included. The elements of a clinical history essential to sound, therapeutic management, and prognosis are summarized. The physical and radiographic assessment of the digital lesions and diagnostic approaches to the common systemic aspects of the disease are presented and discussed.

  18. Clinical presentation, diagnosis, and prognosis of chronic laminitis in Europe.

    PubMed

    Eustace, Robert A

    2010-08-01

    The terminology relating to laminitis is confusing. This article describes how equine veterinarians, by using their eyes and fingers alone, can diagnose and evaluate a case of chronic laminitis. This evaluation will enable veterinarians to give a statistically significant prognosis that can be further refined by measurements taken from plain, weight-bearing lateromedial radiographs of the affected hooves. Should invasive techniques such as digital venography also be used, the results of both techniques are complementary.

  19. The Use of Fish Oil with Warfarin Does Not Significantly Affect either the International Normalised Ratio or Incidence of Adverse Events in Patients with Atrial Fibrillation and Deep Vein Thrombosis: A Retrospective Study

    PubMed Central

    Pryce, Rebecca; Bernaitis, Nijole; Davey, Andrew K.; Badrick, Tony; Anoopkumar-Dukie, Shailendra

    2016-01-01

    Background: Warfarin is a leading anticoagulant in the management of atrial fibrillation (AF) and deep vein thrombosis (DVT). Drug interactions influence the safety of warfarin use and while extensive literature exists regarding the effect on warfarin control and bleeding incidence with many medicines, there is little evidence on the influence of complementary medicines. The aim of this study was to assess the influence of fish and krill oil supplementation on warfarin control and bleeding incidence in AF and DVT patients. Methods: A retrospective analysis was conducted utilising patient information from a large private pathology clinic. AF and DVT patients receiving long-term warfarin therapy (>30 days) at the clinic and taking fish and krill oil supplements were eligible for study inclusion. Results: Of the 2081 patients assessed, a total of 573 warfarin users met the inclusion criteria with 145 patients in the fish and krill oil group (supplement group) and 428 patients in the control group. Overall, it was found that fish and krill oils did not significantly alter warfarin time in therapeutic range (TTR) or bleeding incidence, even when compared by gender. Conclusion: Omega-3 supplementation with fish and krill oil does not significantly affect long-term warfarin control and bleeding and thromboembolic events when consumed concurrently in patients managed at an anticoagulation clinic. PMID:27657121

  20. Adverse Reactions to Hallucinogenic Drugs.

    ERIC Educational Resources Information Center

    Meyer, Roger E. , Ed.

    This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different…

  1. The Pringle manoeuvre should be avoided in hepatectomy for cancer patients due to its side effects on tumor recurrence and worse prognosis.

    PubMed

    Xiaobin, Feng; Zipei, Liu; Shuguo, Zheng; Jiahong, Dong; Xiaowu, Li

    2009-04-01

    Curative hepatectomy is still the best therapeutic strategy for liver cancer treatment up to now. The Pringle manoeuvre has been commonly used to avoid massive blood loss during operation since its advent, which greatly accelerates the advance of liver surgery and oncological surgery. In the past century, more attentions have been paid to different effects of ischemia-reperfusion injury elicited by Pringle manoeuvre. Theses include its impacts on complex metabolic, immunological, and microvascular changes, which altogether might contribute to hepatocellular damage and dysfunction, and contribute to haemodynamic instability. Despite these adverse impacts, the short-term outcome of affected patients under hepatectomy was greatly improved with the advances of surgical techniques and perioperative management in recent years. While the long-term prognosis remains unsatisfactory due to a high incidence of intra/extrahepatic recurrence. The reason for it was not totally elucidated. Furthermore, the effect of the Pringle manoeuvre on the prognosis of oncologic patients and behavior of the tumor cell was not deliberately mentioned. This point was put forward to the front-desk by the specific phenomenon from recent animal studies. It is showed that ischemia-reperfusion injury of the liver remnant may be a significant factor to promote the tumor recurrence and metastasis. If it is a truth in human, there must be a big challenge to the Pringle manoeuvre. So we hypothesized that the long-term prognosis of cancer patients could be worsened by the ischemia-reperfusion injury elicited by Pringle manoeuvre during the hepatectomy and it should be revised, or even, avoided in future hepatectomy for oncologic patients. The less surgical stress including ischemia-reperfusion injury in the hepatic resection without Pringle manoeuvre might contribute to a better prognosis. To get a deeper understanding, prospective randomized clinical trials need to be done. It is surely supposed to

  2. The MKK7 p.Glu116Lys Rare Variant Serves as a Predictor for Lung Cancer Risk and Prognosis in Chinese

    PubMed Central

    Lu, Xiaoxiao; Chen, Jiansong; Wu, Di; Wei, Yongfang; Nong, Qingqing; Zhang, Lisha; Fang, Wenxiang; Chen, Xiaoliang; Ling, Xiaoxuan; Yang, Binyao; Zhang, Xin; Zhou, Yifeng; Lu, Jiachun

    2016-01-01

    Accumulated evidence indicates that rare variants exert a vital role on predisposition and progression of human diseases, which provides neoteric insights into disease etiology. In the current study, based on three independently retrospective studies of 5,016 lung cancer patients and 5,181 controls, we analyzed the associations between five rare polymorphisms (i.e., p.Glu116Lys, p.Asn118Ser, p.Arg138Cys, p.Ala195Thr and p.Leu259Phe) in MKK7 and lung cancer risk and prognosis. To decipher the precise mechanisms of MKK7 rare variants on lung cancer, a series of biological experiments was further performed. We found that the MKK7 p.Glu116Lys rare polymorphism was significantly associated with lung cancer risk, progression and prognosis. Compared with Glu/Glu common genotype, the 116Lys rare variants (Lys/Glu/+ Lys/Lys) presented an adverse effect on lung cancer susceptibility (odds ratio [OR] = 3.29, 95% confidence interval [CI] = 2.70–4.01). These rare variants strengthened patients’ clinical progression that patients with 116Lys variants had a significantly higher metastasis rate and advanced N, M stages at diagnosis. In addition, the patients with 116Lys variants also contributed to worse cancer prognosis than those carriers with Glu/Glu genotype (hazard ratio [HR] = 1.53, 95% CI = 1.32–1.78). Functional experiments further verified that the MKK7 p.116Lys variants altered the expression of several cancer-related genes and thus affected lung cancer cells proliferation, tumor growth and metastasis in vivo and in vitro. Taken together, our findings proposed that the MKK7 p.Glu116Lys rare polymorphism incurred a pernicious impact on lung cancer risk and prognosis through modulating expressions of a serial of cancer-related genes. PMID:27028764

  3. Low-dose exposure to alkylphenols adversely affects the sexual development of Atlantic cod (Gadus morhua): acceleration of the onset of puberty and delayed seasonal gonad development in mature female cod.

    PubMed

    Meier, Sonnich; Morton, H Craig; Andersson, Eva; Geffen, Audrey J; Taranger, Geir Lasse; Larsen, Marita; Petersen, Marianne; Djurhuus, Rune; Klungsøyr, Jarle; Svardal, Asbjørn

    2011-09-01

    Produced water (PW), a by-product of the oil-production process, contains large amount of alkylphenols (APs) and other harmful oil compounds. In the last 20 years, there have been increasing concerns regarding the environmental impact of large increases in the amounts of PW released into the North Sea. We have previously shown that low levels of APs can induce disruption of the endocrine and reproductive systems of Atlantic cod (Gadus morhua). The aims of this follow-up study were to: (i) identify the lowest observable effect concentration of APs; (ii) study the effects of exposure to real PW, obtained from a North Sea oil-production platform; and (iii) study the biological mechanism of endocrine disruption in female cod. Fish were fed with feed paste containing several concentrations of four different APs (4-tert-butylphenol, 4-n-pentylphenol, 4-n-hexylphenol and 4-n-heptylphenol) or real PW for 20 weeks throughout the normal period of vitellogenesis in Atlantic cod from October to January. Male and female cod, exposed to AP and PW, were compared to unexposed fish and to fish fed paste containing 17β-oestradiol (E(2)). Approximately 60% of the females and 96% of the males in the unexposed groups were mature at the end of the experiment. Our results show that exposure to APs and E(2) have different effects depending on the developmental stage of the fish. We observed that juvenile females are advanced into puberty and maturation, while gonad development was delayed in both maturing females and males. The AP-exposed groups contained increased numbers of mature females, and significant differences between the untreated group and the AP-treated groups were seen down to a dose of 4 μg AP/kg body weight. In the high-dose AP and the E(2) exposed groups, all females matured and no juveniles were seen. These results suggest that AP-exposure can affect the timing of the onset of puberty in fish even at extremely low concentrations. Importantly, similar effects were not

  4. [Body weight, nutritional factors and physical activity--their influence on prognosis after breast cancer diagnosis].

    PubMed

    Weitzen, Rony; Tichler, Thomas; Kaufman, Bella; Catane, Raphael; Shpatz, Yael

    2006-11-01

    Numerous studies have examined the association between body weight, nutritional factors, physical activity and the risk for primary breast cancer. Relatively few studies, however, have examined the associations between these issues and the recurrence of the disease and cure of the primary tumor. Today, three areas of focus are actively being researched for breast cancer survivors: body weight, diet composition and physical activity with specific emphasis on the risk for recurrence, survival and quality of life. Increased body weight or BMI (Body Mass Index) at diagnosis was found to be a significant risk factor for recurrent disease, decreased survival, or both. Overall obesity has been shown to adversely affect prognosis. Appropriate weight control may be particularly beneficial for breast cancer survivors. Breast cancer survivors should be encouraged to achieve and maintain a healthy weight. Limiting fat intake can reduce the risk of breast cancer recurrence. Increasing consumption of vegetables and fruits seems to have possible beneficial effects during and after treatments. To date physical activity after breast cancer diagnosis has been found to reduce the risk of death. The greatest benefit occurred in women who performed the equivalent of walking 3-5 hours per week at an average pace. Safe weight loss via increased physical activity and healthful food choices should be encouraged for normal, overweight or obese breast cancer survivors in order to improve survival and life quality.

  5. Cutaneous adverse reactions to lenalidomide.

    PubMed

    Imbesi, S; Allegra, A; Calapai, G; Musolino, C; Gangemi, S

    2015-01-01

    Lenalidomide is an immunomodulatory drug (IMiD) used principally in the treatment of multiple myeloma (MM), myelodysplastic syndromes (MS) and amyloidosis. Adverse reactions related to lenalidomide include myelosuppression (mainly neutropenia but also thrombocytopenia), gastrointestinal problems, skin eruption, atrial fibrillation and asthenia, decreased peripheral blood stem cell yield during stem cell collection, venous thromboembolism, and secondary malignances. In this review we focused our attention on the cutaneous adverse reactions to lenalidomide.

  6. Syncope: epidemiology, etiology, and prognosis

    PubMed Central

    da Silva, Rose M. F. L.

    2014-01-01

    Syncope is a common medical problem, with a frequency between 15% and 39%. In the general population, the annual number episodes are 18.1–39.7 per 1000 patients, with similar incidence between genders. The first report of the incidence of syncope is 6.2 per 1000 person-years. However, there is a significant increase in the incidence of syncope after 70 years of age with rate annual 19.5 per thousand individuals after 80 years. It presents a recurrence rate of 35% and 29% of physical injury. Among the causes of syncope, the mediated neural reflex, known as neurocardiogenic or vasovagal syncope, is the most frequent. The others are of cardiac origin, orthostatic hypotension, carotid sinus hypersensitivity, neurological and endocrinological causes and psychiatric disorders. The diagnosis of syncope can be made by clinical method associated with the electrocardiogram in up 50% of patients. Its prognosis is determined by the underlying etiology specifically the presence and severity of cardiac disease. The annual mortality can reach between 18 and 33% if cardiac cause, and between 0 and 12% if the non-cardiac cause. Thus, it is imperative to identify its cause and risk stratification for positive impact in reducing morbidity and mortality. PMID:25538626

  7. Reverse Engineering Adverse Outcome Pathways

    SciTech Connect

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  8. Resiliency in the Face of Adversity: A Short Longitudinal Test of the Trait Hypothesis.

    PubMed

    Karaırmak, Özlem; Figley, Charles

    2017-01-01

    Resilience represents coping with adversity and is in line with a more positive paradigm for viewing responses to adversity. Most research has focused on resilience as coping-a state-based response to adversity. However, a competing hypothesis views resilience or resiliency as a trait that exists across time and types of adversity. We tested undergraduates enrolled in social work classes at a large southern university at two time periods during a single semester using measures of adversity, positive and negative affect, and trait-based resiliency. Consistent with the trait-based resiliency, and in contrast to state-based resilience, resiliency scores were not strongly correlated with adversity at both testing points but were with positive affect, and resiliency scores remained the same over time despite adversity variations. There was no gender or ethnic group difference in resilience scores. Black/African Americans reported significantly less negative affect and more positive affect than White/Caucasians.

  9. Recent perspectives of breast cancer prognosis and predictive factors

    PubMed Central

    Cao, Su-Sheng; Lu, Cun-Tao

    2016-01-01

    Breast cancer is the most common type of cancer affecting women worldwide. Although there have been great improvements in treating the disease and at present between 80 and 90% of the women survive ≥5-years after their primary diagnosis. However, due to the high incidence of the disease >450,000 women succumb to breast cancer annually worldwide. The majority of improvements in breast cancer survival may be explained through better knowledge of the development and progression of the disease. Consequently, the treatments employed have become more effective. Furthermore, continuous efforts are being made for the identification of novel and efficient biomarkers for the timely prognosis of breast cancer. The present review aims to examine recent perspectives of breast cancer prognosis and the predictive factors involved. PMID:27900052

  10. Adverse health effects of non-medical cannabis use.

    PubMed

    Hall, Wayne; Degenhardt, Louisa

    2009-10-17

    For over two decades, cannabis, commonly known as marijuana, has been the most widely used illicit drug by young people in high-income countries, and has recently become popular on a global scale. Epidemiological research during the past 10 years suggests that regular use of cannabis during adolescence and into adulthood can have adverse effects. Epidemiological, clinical, and laboratory studies have established an association between cannabis use and adverse outcomes. We focus on adverse health effects of greatest potential public health interest-that is, those that are most likely to occur and to affect a large number of cannabis users. The most probable adverse effects include a dependence syndrome, increased risk of motor vehicle crashes, impaired respiratory function, cardiovascular disease, and adverse effects of regular use on adolescent psychosocial development and mental health.

  11. Exposure to organic solvents. Does it adversely affect pregnancy?

    PubMed Central

    McMartin, K. I.; Koren, G.

    1999-01-01

    QUESTION: One of my patients is a laboratory technician who routinely handles organic solvents. She has just learned that she is pregnant, and she depends very much on this job because her husband is unemployed. What is the risk to her unborn baby? ANSWER: Available epidemiologic data indicate your patient's fetus might be at increased risk for malformations. We recommend that she minimize her occupational exposure to organic solvents by routinely using ventilation systems and protective equipment. This is most important during the first trimester of pregnancy. PMID:10424263

  12. Does prolonged breastfeeding adversely affect a child's nutritional status?

    PubMed

    Brakohiapa, L A; Yartey, J; Bille, A; Harrison, E; Quansah, E; Armar, M A; Kishi, K; Yamamoto, S

    1988-08-20

    In 202 children who visited a children's hospital in the city of Accra, Ghana, breastfeeding beyond the age of 19 months was found to be associated with malnutrition. The effect of weaning on food intake was then studied in 15 breastfed malnourished children in a rural community. Before weaning (complete cessation of breast-feeding) protein and energy intakes of all the malnourished children were about half those of 5 normal children. 10 of the malnourished children were weaned, and their intakes rose to the levels of the normal children; the 5 who continued breastfeeding maintained their low intakes. These results indicate that prolonged breastfeeding can reduce total food intake and thus predispose to malnutrition. They also suggest that in Ghana and other developing countries the proper weaning age may be about 18 months.

  13. Depression induces poor prognosis associates with the down-regulation brain derived neurotrophic factor of serum in advanced small cell lung cancer

    PubMed Central

    Wu, Yufeng; Si, Ruirui; Yang, Sen; Xia, Suhua; He, Zelai; Wang, Lili; He, Zhen; Wang, Qiming; Tang, Hong

    2016-01-01

    Patients with lung cancer often experience a state of depression, and these conditions may severely affect their quality of life (QoL) and prescription compliance. The current study was conducted to delineate the complex links between depression and the prognosis of patients with small cell lung cancer (SCLC) and the underlying mechanism was also explored. 186 patients who received platinum-based chemotherapy for newly diagnosed stage III or stage IV SCLC were enrolled. The Self-Rating Depression Scale (SDS) questionnaire was completed the day before the start of chemotherapy to assess the depression status of the patients. Patients with stage IV SCLC or lower BMI have higher depression scores. In terms of the adverse effects of chemotherapy, depression severely decreases patient tolerance to chemotherapy and their QoL score (R2 = 0.2385) and is also associated with severe vomiting (P < 0.001), leukopenia (R2 = 0.2332), and prolonged hospital stay (R2 = 0.1961). More importantly, severe depression reduces the PFS (R2 = 0.1943) and OS (P < 0.01) of the patients. We found that patients with severe depression displayed a downregulated level of serum BDNF and that the level of serum BDNF was highly correlated with the OS of the patients (R2 = 0.2292). Using the MTT cell viability assay in vitro, we observed that cotreatment with BDNF clearly enhanced the chemosensitivity of NCI-H69 tumor cells to Cisplatin and induced the downregulation of ABCG2. Based on this evidence, it appears that a relationship does exist between depression and prognosis in SCLC and that the mechanism by which depression affects prognosis is achieved via the downregulation of BDNF expression. PMID:27852063

  14. Azacitidine. Poor-prognosis myelodysplasia: promising, but more data needed.

    PubMed

    2011-02-01

    Some myelodysplastic syndromes carry a poor prognosis. This is also the case for chronic myelomonocytic leukaemia (related to myelodysplastic syndromes), and acute myeloblastic leukaemia, a frequent complication of myelodysplasia. The only treatment capable of providing long-term remission (in about 1 in 2 patients on average) is haematopoietic stem cell transplantation, but this burdensome treatment can only be used in a minority of cases. Azacitidine (Vidaza, Celgene), an agent that blocks DNA synthesis, is the first drug to receive EU marketing authorisation in these settings. Its clinical evaluation is based on an unblinded trial that included 358 patients comparable to those discussed in the marketing authorisation. In addition to individually tailored symptomatic care, they were randomised to receive either azacitidine or conventional care regimens chosen by their physician (no treatment, low-dose cytarabine, or an anthracycline plus cytarabine). The median overall survival time was significantly longer with azacitidine (24.5 versus 15 months), and transfusion requirements were also reduced. Another comparative trial versus symptomatic treatment alone in 191 patients with various prognoses also showed an increase in survival time with azacitidine, but this study suffered from methodological flaws. The main adverse effects of azacitidine are potentially severe toxicity for various blood cells, gastrointestinal disorders, and reactions at the injection site. In practice, when haematopoietic stem cell transplantation is not feasible for poor-prognosis patients with myelodysplastic syndromes or related disorders, azacitidine can be used instead of disappointing standard treatments, even though more clinical evaluation is needed.

  15. Divergent effects of various diabetes drugs on cardiovascular prognosis.

    PubMed

    Bell, David S H; Patil, Harshal R; O'Keefe, James H

    2013-01-01

    This review discusses the current data on various antidiabetic medications and their effects on major adverse cardiovascular events (MACE). Diabetes mellitus is a potent independent risk factor for MACE, and this risk increases in proportion to the elevation of hemoglobin A1c. Available data suggest that tight glycemic control in patients with diabetes reduces microvascular complications, but has limited effect or may even increase the risk of MACE and other macrovascular complications. For individuals with type 2 diabetes mellitus (T2DM) drugs that reduce postprandial glucose (α-glucosidase inhibitors, incretin mimetics, quick-acting bromocriptine, dipeptidyl peptidase-4 inhibitors, and colesevelam) are associated with a decrease in MACE. Drugs that directly reduce insulin resistance (pioglitazone and metformin) are also associated with lesser but still significant decreases in MACE. Insulin, rosiglitazone (but not pioglitazone), and sulfonylureas (especially with glyburide and particularly the glyburide + metformin combination) are associated with increases in MACE. In summary, drugs that reduce postprandial glucose and improve insulin resistance without predisposing patients to hypoglycemia appear to both control hyperglycemia and improve cardiovascular prognosis. However, many of the traditional agents used for treating T2DM, such as insulin and sulfonylureas, do not improve cardiovascular prognosis despite improving hyperglycemia.

  16. Neuropsychiatric Adverse Effects of Amphetamine and Methamphetamine.

    PubMed

    Harro, Jaanus

    2015-01-01

    Administration of amphetamine and methamphetamine can elicit psychiatric adverse effects at acute administration, binge use, withdrawal, and chronic use. Most troublesome of these are psychotic states and aggressive behavior, but a large variety of undesirable changes in cognition and affect can be induced. Adverse effects occur more frequently with higher dosages and long-term use. They can subside over time but some persist long-term. Multiple alterations in the gray and white matter of the brain assessed as changes in tissue volume or metabolism, or at molecular level, have been associated with amphetamine and methamphetamine use and the psychiatric adverse effects, but further studies are required to clarify their causal role, specificity, and relationship with preceding states and traits and comorbidities. The latter include other substance use disorders, mood and anxiety disorders, attention deficit hyperactivity disorder, and antisocial personality disorder. Amphetamine- and methamphetamine-related psychosis is similar to schizophrenia in terms of symptomatology and pathogenesis, and these two disorders share predisposing genetic factors.

  17. Combating adverse selection in secondary PC markets.

    PubMed

    Hickey, Stewart W; Fitzpatrick, Colin

    2008-04-15

    Adverse selection is a significant contributor to market failure in secondary personal computer (PC) markets. Signaling can act as a potential solution to adverse selection and facilitate superior remarketing of second-hand PCs. Signaling is a means whereby usage information can be utilized to enhance consumer perception of both value and utility of used PCs and, therefore, promote lifetime extension for these systems. This can help mitigate a large portion of the environmental impact associated with PC system manufacture. In this paper, the computer buying and selling behavior of consumers is characterized via a survey of 270 Irish residential users. Results confirm the existence of adverse selection in the Irish market with 76% of potential buyers being unwilling to purchase and 45% of potential vendors being unwilling to sell a used PC. The so-called "closet affect" is also apparent with 78% of users storing their PC after use has ceased. Results also indicate that consumers place a higher emphasis on specifications when considering a second-hand purchase. This contradicts their application needs which are predominantly Internet and word-processing/spreadsheet/presentation applications, 88% and 60% respectively. Finally, a market solution utilizing self monitoring and reporting technology (SMART) sensors for the purpose of real time usage monitoring is proposed, that can change consumer attitudes with regard to second-hand computer equipment.

  18. Novel Biomarker for Prognosis, Treatment Response

    Cancer.gov

    An NCI Cancer Currents blog about a study of a new type of cancer biomarker that measures the extent of chromosomal instability as a way to potentially predict patient prognosis and help guide cancer treatment choices.

  19. Endocrinological disorders affecting neurosurgical patients: An intensivists perspective

    PubMed Central

    Bajwa, Sukhminder Jit Singh; Haldar, Rudrashish

    2014-01-01

    Management of critically ill neurosurgical patients is often complicated by the presence or development of endocrinological ailments which complicate the clinical scenario and adversely affect the prognosis of these patients. The anatomical proximity to the vital centers regulating the endocrinological physiology and alteration in the neurotransmitter release causes disturbances in the hormonal homeostasis. This paves the way for development of diverse disorders where single or multiple hormones may be involved which can have deleterious effect on the different organ system. Understanding and awareness of these disorders is important for the treating intensivist to recognize these changes early in their course, so that appropriate and timely therapeutic measures can be initiated along with the treatment of the primary malady. PMID:25364671

  20. Scoring system for prediction of metastatic spine tumor prognosis

    PubMed Central

    Tokuhashi, Yasuaki; Uei, Hiroshi; Oshima, Masashi; Ajiro, Yasumitsu

    2014-01-01

    Assessing the prognosis before treatment for metastatic spine tumor is extremely important in therapy selection. Therefore, we review some prognostic scoring systems and their outcomes. Articles with combinations of two keywords among “metastatic spine tumor” and “prognosis”, “score”, “scoring system”, “predicting”, or “life expectancy” were searched for in PubMed. As a result, 236 articles were extracted. Those referring to representative scoring systems about predicting the survival of patients with metastatic spine tumors were used. The significance and limits of these scoring systems, and the future perspectives were described. Tokuhashi score, Tomita score, Baur score, Linden score, Rades score, and Katagiri score were introduced. They are all scoring systems prepared by combining factors that affect prognosis. The primary site of cancer and visceral metastasis were common factors in all of these scoring systems. Other factors selected to influence the prognosis varied. They were useful to roughly predict the survival period, such as, “more than one year or not” or “more than six months or not”. In particular, they were utilized for decision-making about operative indications and avoidance of excessive medical treatment. Because the function depended on the survival period in the patients with metastatic spine tumor, it was also utilized in assessing functional prognosis. However, no scoring system had more than 90% consistency between the predicted and actual survival periods. Future perspectives should adopt more oncological viewpoints with adjustment of the process of treatment for metastatic spine tumor. PMID:25035829

  1. Adverse Childhood Experiences and Hallucinations

    ERIC Educational Resources Information Center

    Whitfield, C.L.; Dube, S.R.; Felitti, V.J.; Anda, R.F.

    2005-01-01

    Objective:: Little information is available about the contribution of multiple adverse childhood experiences (ACEs) to the likelihood of reporting hallucinations. We used data from the ACE study to assess this relationship. Methods:: We conducted a survey about childhood abuse and household dysfunction while growing up, with questions about health…

  2. Reverse engineering adverse outcome pathways.

    PubMed

    Perkins, Edward J; Chipman, J Kevin; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-01

    The toxicological effects of many stressors are mediated through unknown, or incompletely characterized, mechanisms of action. The application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) can be used to overcome these limitations. This approach was used to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows (FHM, Pimephales promelas). Gene expression changes in FHM ovaries in response to seven different chemicals, over different times, doses, and in vivo versus in vitro conditions, were captured in a large data set of 868 arrays. Potential AOPs of the antiandrogen flutamide were examined using two mutual information-based methods to infer gene regulatory networks and potential AOPs. Representative networks from these studies were used to predict network paths from stressor to adverse outcome as candidate AOPs. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment, thus leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biological processes, biomarkers, or alternative endpoints that can be used to monitor an AOP. Finally, the unique challenges facing the application of this approach in ecotoxicology were identified and a road map for the utilization of these tools presented.

  3. [Prognosis and progression of cognitive impairment. Preventive measures].

    PubMed

    López Mongil, Rosa; López Trigo, José Antonio

    2016-06-01

    Because of the substantial increase in population ageing, age-related processes, such as dementia and Alzheimer disease (AD), are becoming highly prevalent. The course of this disease, including preprodromic phases, lasts at least 20 years. The presence of comorbidities, especially those of vascular origin, can trigger and aggravate disease progression. On the other hand, cognitive reserve, the absence or control of comorbid factors and healthy lifestyles can protect or modify -in the sense of slow down- disease progression. Knowledge of the phases of AD and their functional impact on affected individuals helps to identify the average prognosis and, in particular, to establish and predict care plans based on the individual's needs.

  4. Adverse effects of isolation in hospitalised patients: a systematic review.

    PubMed

    Abad, C; Fearday, A; Safdar, N

    2010-10-01

    The use of transmission precautions such as contact isolation in patients known to be colonised or infected with multidrug-resistant organisms is recommended in healthcare institutions. Although essential for infection control, contact isolation has recently been associated with adverse effects in patients. We undertook a systematic review to determine whether contact isolation leads to psychological or physical problems for patients. Studies were included if (1) hospitalised patients were placed under isolation precautions for an underlying medical indication, and (2) any adverse events related to the isolation were evaluated. We found 16 studies that reported data regarding the impact of isolation on patient mental well-being, patient satisfaction, patient safety or time spent by healthcare workers in direct patient care. The majority showed a negative impact on patient mental well-being and behaviour, including higher scores for depression, anxiety and anger among isolated patients. A few studies also found that healthcare workers spent less time with patients in isolation. Patient satisfaction was adversely affected by isolation if patients were kept uninformed of their healthcare. Patient safety was also negatively affected, leading to an eight-fold increase in adverse events related to supportive care failures. We found that contact isolation may negatively impact several dimensions of patient care. Well-validated tools are necessary to investigate these results further. Large studies examining a number of safety indicators to assess the adverse effects of isolation are needed. Patient education may be an important step to mitigate the adverse psychological effects of isolation and is recommended.

  5. Combined Diffusion and Perfusion MR Imaging as Biomarkers of Prognosis in Immunocompetent Patients with Primary Central Nervous System Lymphoma

    PubMed Central

    Valles, F.E.; Perez-Valles, C.L.; Regalado, S.; Barajas, R.F.; Rubenstein, J.L.; Cha, S.

    2014-01-01

    BACKGROUND AND PURPOSE ADC derived from DWI has been shown to correlate with PFS and OS in immunocompetent patients with PCNSL. The purpose of our study was to confirm the validity of ADC measurements as a prognostic biomarker and to determine whether rCBV measurements derived from DSC perfusion MR imaging provide prognostic information. MATERIALS AND METHODS Pretherapy baseline DWI and DSC perfusion MR imaging in 25 patients with PCNSL was analyzed before methotrexate-based induction chemotherapy. Contrast-enhancing tumor was segmented and coregistered with ADC and rCBV maps, and mean and minimum values were measured. Patients were separated into high or low ADC groups on the basis of previously published threshold values of ADCmin < 384 × 10−6 mm2/s. High and low rCBV groups were defined on the basis of receiver operating curve analysis. High and low ADC and rCBV groups were analyzed independently and in combination. Multivariate Cox survival analysis was performed. RESULTS Patients with ADCmin values < 384 × 10−6 mm2/s or rCBVmean values < 1.43 had worse PFS and OS. The patient cohort with combined low ADCmin–low rCBVmean had the worst prognosis. No other variables besides ADC and rCBV significantly affected survival. CONCLUSIONS Our study reinforces the validity of ADC values as a prognostic biomarker and provides the first evidence of low tumor rCBV as a novel risk factor for adverse prognosis in immunocompetent patients with PCNSL. PMID:22936096

  6. Activation of TREK-1 by morphine results in analgesia without adverse side effects.

    PubMed

    Devilliers, Maïly; Busserolles, Jérôme; Lolignier, Stéphane; Deval, Emmanuel; Pereira, Vanessa; Alloui, Abdelkrim; Christin, Marine; Mazet, Bruno; Delmas, Patrick; Noel, Jacques; Lazdunski, Michel; Eschalier, Alain

    2013-01-01

    Morphine is the gold-standard pain reliever for severe acute or chronic pain but it also produces adverse side effects that can alter the quality of life of patients and, in some rare cases, jeopardize the vital prognosis. Morphine elicits both therapeutic and adverse effects primarily through the same μ opioid receptor subtype, which makes it difficult to separate the two types of effects. Here we show that beneficial and deleterious effects of morphine are mediated through different signalling pathways downstream from μ opioid receptor. We demonstrate that the TREK-1 K(+) channel is a crucial contributor of morphine-induced analgesia in mice, while it is not involved in morphine-induced constipation, respiratory depression and dependence-three main adverse effects of opioid analgesic therapy. These observations suggest that direct activation of the TREK-1 K(+) channel, acting downstream from the μ opioid receptor, might have strong analgesic effects without opioid-like adverse effects.

  7. Adverse drug reactions: part II.

    PubMed

    Wooten, James M

    2010-11-01

    Pharmacovigilance is the process of identifying, monitoring, and effectively reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important consideration when assessing a patient's health. The proliferation of new pharmaceuticals means that the incidence of ADRs is increasing. The goal for all health care providers must be to minimize the risk of ADRs as much as possible. Steps to achieve this include understanding the pharmacology for all drugs prescribed and proactively assessing and monitoring those patients at greatest risk for developing an ADR. Groups at greatest risk for developing ADRs include the elderly, children, and pregnant patients, as well as others. Pharmacovigilance must be effectively practiced by all health care providers in order to avoid ADRs.

  8. Adverse drug reactions: Part I.

    PubMed

    Wooten, James M

    2010-10-01

    Pharmacovigilance is the process of identifying, monitoring, and effectively reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important consideration when assessing a patient's health. The proliferation of new pharmaceuticals means that the incidence of ADRs is increasing. The goal for all health care providers must be to minimize the risk of ADRs as much as possible. Steps to achieve this include understanding the pharmacology for all drugs prescribed and proactively assessing and monitoring those patients at greatest risk for developing an ADR. Groups at greatest risk for developing ADRs include the elderly, children, and pregnant patients, as well as others. Pharmacovigilance must effectively be practiced by all health providers in order to avoid ADRs.

  9. [Finasteride adverse effects: An update].

    PubMed

    Carreño-Orellana, Néstor; Moll-Manzur, Catherina; Carrasco-Zuber, Juan Eduardo; Álvarez-Véliz, Sergio; Berroeta-Mauriziano, Daniela; Porras-Kusmanic, Ninoska

    2016-12-01

    Finasteride is a 5-α reductase inhibitor that is widely used in the management of benign prostate hyperplasia and male pattern hair loss. It is well known that these agents improve the quality of life in men suffering from these conditions. However, they are associated with some transient and even permanent adverse effects. The aim of this article is to clarify the controversies about the safety of finasteride by analyzing the evidence available in the literature.

  10. [Pain as adverse drug reaction].

    PubMed

    Böhmdorfer, Birgit; Schaffarzick, Daniel; Nagano, Marietta; Janowitz, Susanne Melitta; Schweitzer, Ekkehard

    2012-09-01

    We present a multidisciplinary (anaesthesiology--clinical pharmacy--bioinformatics) analysis of pain as possible adverse drug reaction taking different manifestations of pain, indication groups, relevance to the Austrian drug market and possible mechanistic influence of drugs on development and apprehension of pain into consideration.We designed an overview that shows how transmitters that play a part in nociception and antinociception can be influenced by drugs. This allows conclusions to the dolorigene potential of therapeutics.

  11. Thiocolchicoside: review of adverse effects.

    PubMed

    2016-02-01

    Thiocolchicoside has long been used as a muscle relaxant, despite a lack of proven efficacy beyond the placebo effect. Its chemical structure consists of colchicine, a sugar (ose) and a sulphur-containing radical (thio), and its adverse effects are therefore likely to be similar to those of colchicine. Using the standard Prescrire methodology, we reviewed the available data on the adverse effects of thiocolchicoside. Liver injury, pancreatitis, seizures, blood cell disorders, severe cutaneous disorders, rhabdomyolysis and reproductive disorders have all been recorded in the French and European pharmacovigilance databases and in the periodic updates that the companies concerned submit to regulatory agencies. These data do not specify the frequency of the disorders nor do they identify the most susceptible patient populations. Thiocolchicoside is teratogenic in experimental animals and also damages chromosomes. Human data are limited to a follow-up of about 30 pregnant women (no major malformations) and reports of altered spermatogenesis, including cases of azoospermia. In practice, there is no justification for exposing patients to the adverse effects of thiocolchicoside. It is better to use an effective, well-known analgesic for patients complaining of muscle pain, starting with paracetamol.

  12. Adverse food-drug interactions.

    PubMed

    de Boer, Alie; van Hunsel, Florence; Bast, Aalt

    2015-12-01

    Food supplements and herbal products are increasingly popular amongst consumers. This leads to increased risks of interactions between prescribed drugs and these products containing bioactive ingredients. From 1991 up to 2014, 55 cases of suspected adverse drug reactions due to concomitant intake of health-enhancing products and drugs were reported to Lareb, the Netherlands Pharmacovigilance Centre. An overview of these suspected interactions is presented and their potential mechanisms of action are described. Mainly during the metabolism of xenobiotics and due to the pharmacodynamics effects interactions seem to occur, which may result in adverse drug reactions. Where legislation is seen to distinct food and medicine, legislation concerning these different bioactive products is less clear-cut. This can only be resolved by increasing the molecular knowledge on bioactive substances and their potential interactions. Thereby potential interactions can be better understood and prevented on an individual level. By considering the dietary pattern and use of bioactive substances with prescribed medication, both health professionals and consumers will be increasingly aware of interactions and these interactive adverse effects can be prevented.

  13. Six-year trajectories of post-traumatic stress and severe psychological distress symptoms and associations with timing of trauma exposure, ongoing adversity and sense of injustice: a latent transition analysis of a community cohort in conflict-affected Timor-Leste

    PubMed Central

    Rees, S; Steel, Z; Tam, N; Soares, Z; Soares, C; Silove, DM

    2016-01-01

    Objectives To identify the 6-year trajectories of post-traumatic stress symptoms (PTSS) and psychological distress symptoms, and examine for associations with timing of trauma exposure, ongoing adversity and with the sense of injustice in conflict-affected Timor-Leste. Setting A whole-of-household survey was conducted in 2004 and 2010 in Dili, the capital of Timor-Leste. Participants 1022 adults were followed up over 6 years (retention rate 84.5%). Interviews were conducted by field workers applying measures of traumatic events (TEs), ongoing adversity, a sense of injustice, PTS symptoms and psychological distress. Results Latent transition analysis supported a 3-class longitudinal model (psychological distress, comorbid symptoms and low symptoms). We derived 4 composite trajectories comprising recovery (20.8%), a persisting morbidity trajectory (7.2%), an incident trajectory (37.2%) and a low-symptom trajectory (34.7%). Compared with the low-symptom trajectory, the persistent and incident trajectories reported greater stress arising from poverty and family conflict, higher TE exposure for 2 historical periods, and a sense of injustice for 2 historical periods. The persistent trajectory was unique in reporting greater TE exposure in the Indonesian occupation, whereas the incident trajectory reported greater TE exposure during the later internal conflict that occurred between baseline and follow-up. Compared with the low-symptom trajectory, the incident trajectory reported a greater sense of injustice relating to the periods of the Indonesian occupation and independence. The persistent trajectory was characterised by a sense of injustice relating to the internal conflict and contemporary times. The recovery trajectory was characterised by the absence of these risk factors, the only difference from the low-symptom trajectory being that the former reported a sense of injustice for the period surrounding independence. Conclusions Our findings suggest that the timing

  14. Epidemiology, prognosis, and risk factors in mastocytosis.

    PubMed

    Brockow, Knut

    2014-05-01

    This article updates current knowledge about epidemiology, prognosis, and risk factors for major complications in mastocytosis. A prevalence of mastocytosis of 1 in 10000 inhabitants has been reported, but underdiagnosis is assumed. The prognosis for cutaneous and indolent systemic mastocytosis is excellent. For more advanced forms of disease, prognostic parameters have been identified. A high extent of skin involvement, increased basal serum tryptase values, and extensive blistering are risk factors for severe mast cell activation episodes in children, whereas these associations seem to be less strong or nonexistent for anaphylaxis and osteoporosis in adult patients with indolent systemic mastocytosis.

  15. Comorbidities impacting on prognosis after lung transplant.

    PubMed

    Vaquero Barrios, José Manuel; Redel Montero, Javier; Santos Luna, Francisco

    2014-01-01

    The aim of this review is to give an overview of the clinical circumstances presenting before lung transplant that may have negative repercussions on the long and short-term prognosis of the transplant. Methods for screening and diagnosis of common comorbidities with negative impact on the prognosis of the transplant are proposed, both for pulmonary and extrapulmonary diseases, and measures aimed at correcting these factors are discussed. Coordination and information exchange between referral centers and transplant centers would allow these comorbidities to be detected and corrected, with the aim of minimizing the risks and improving the life expectancy of transplant receivers.

  16. [Syncope : epidemiology, definition, classification, pathophysiology and prognosis].

    PubMed

    Heeger, C-H; Rillig, A; Ouyang, F; Kuck, K-H; Tilz, R R

    2014-06-01

    Syncope is a common clinical issue. Around 40 % of the total population experience syncope during their lifetime. Serious injuries and reduced quality of life are often observed after syncope. Furthermore, in some cases syncope can be associated with an unfavorable prognosis. Due to the complex etiology and pathophysiology, syncope provides challenges for doctors both in private and in clinical practices. This review is based on the latest European guidelines for syncope which were formulated by internists, neurologists, emergency physicians and cardiologists and gives an overview of the current epidemiology, definition, classification, pathophysiology and prognosis of syncope.

  17. Prognosis--the dilemma of modern periodontics.

    PubMed

    Pearlman, B

    2000-10-01

    As periodontics has progressed towards an understanding of the influences of risk factors such as genetics, smoking and stress in the occurrence and severity of periodontal disease, the question of prognosis, so essential to treatment planning, has become even more perplexing to the clinician. A survey of long term clinical practice gives insight into the outcome of therapy relative to initial severity, and modern concepts of bacteria versus host relationships provide directions for greater predictability. However, it is only with observation over time that a more accurate assessment of prognosis can be made, as response to initial therapeutic measures can be determined.

  18. Remaining Useful Life Estimation in Prognosis: An Uncertainty Propagation Problem

    NASA Technical Reports Server (NTRS)

    Sankararaman, Shankar; Goebel, Kai

    2013-01-01

    The estimation of remaining useful life is significant in the context of prognostics and health monitoring, and the prediction of remaining useful life is essential for online operations and decision-making. However, it is challenging to accurately predict the remaining useful life in practical aerospace applications due to the presence of various uncertainties that affect prognostic calculations, and in turn, render the remaining useful life prediction uncertain. It is challenging to identify and characterize the various sources of uncertainty in prognosis, understand how each of these sources of uncertainty affect the uncertainty in the remaining useful life prediction, and thereby compute the overall uncertainty in the remaining useful life prediction. In order to achieve these goals, this paper proposes that the task of estimating the remaining useful life must be approached as an uncertainty propagation problem. In this context, uncertainty propagation methods which are available in the literature are reviewed, and their applicability to prognostics and health monitoring are discussed.

  19. Adverse responses to local anaesthetics.

    PubMed

    Fisher, M M; Graham, R

    1984-11-01

    Progressive challenge was used to investigate twenty-seven patients with a history of an adverse response to local anaesthesia. True allergy was detected in only one patient. The method does not exclude reactions to additives and preservatives in local anaesthetics. If preservative-free local anaesthetics are used for subsequent exposure in patients with no response to progressive challenge, subsequent exposure is safe. The possibility that some of these patients may be reacting to preservatives in the solutions cannot be excluded by such testing. Where possible preservative-free local anaesthetic preparations should be used for subsequent anaesthesia.

  20. Adverse Outcomes in Group Psychotherapy

    PubMed Central

    Roback, Howard B.

    2000-01-01

    Group forms of therapy have been growing at a rapid rate, in part because of their documented effectiveness and economic considerations such as managed care. It is therefore becoming increasingly important to assess the psychological risks of these interventions. The author provides an overview of the published literature and conference presentations on negative effects in adult outpatient groups. Although much of the literature on adverse outcomes in group therapy focuses on single risk factors (e.g., negative leader, group process, or patient characteristics), the author argues that an interactional model should be encouraged. Means of reducing casualties are also discussed, as well as methodological issues and research directions. PMID:10896735

  1. The Natural History and Prognosis of Primary Biliary Cirrhosis with Clinical Features of Autoimmune Hepatitis.

    PubMed

    Yang, Fan; Wang, Qixia; Wang, Zhaoyue; Miao, Qi; Xiao, Xiao; Tang, Ruqi; Chen, Xiaoyu; Bian, Zhaolian; Zhang, Haiyan; Yang, Yue; Sheng, Li; Fang, Jingyuan; Qiu, Dekai; Krawitt, Edward L; Gershwin, M Eric; Ma, Xiong

    2016-02-01

    Although a variant of primary biliary cirrhosis (PBC) characterized by features of autoimmune hepatitis (AIH) has been recognized for many years, few studies with ample numbers of patients have focused on its natural history. This study aimed to clarify the natural history, prognosis, and response to therapy in a cohort of patients with PBC with AIH features. We retrospectively analyzed 277 PBC patients without AIH features and 46 PBC patients with AIH features seen between September 2004 and April 2014. The 5-year adverse outcome-free survival of PBC patients with AIH features was 58% compared to 81% in PBC patients without AIH features. Multivariate analysis in the patients with AIH features indicated that total bilirubin ≥ 2.70× the upper limit of normal predicted a poor prognosis (p = 0.008, relative risk 8.39, 95% confidence interval (CI) 1.73, 40.73). Combination therapy with ursodeoxycholic acid (UDCA) and immunosuppression provided better short-term responses in PBC patients with AIH features, defined by multiple criteria. Higher aspartate aminotransferase (AST) level at accession suggested better prognosis for PBC patients with AIH features while worse prognosis for PBC patients without AIH features. PBC patients with AIH features differ from those without AIH features in terms of natural history, prognostic indicators, and response to therapy.

  2. "Adversative Conjunction": The Poetics of Linguistic Opposition.

    ERIC Educational Resources Information Center

    Wallerstein, Nicholas

    1992-01-01

    The general use of adversative conjunction in (primarily) English and U.S. poetry is outlined. The contention is that the adversative is not merely a grammatical convenience but sometimes a highly functional tool of rhetorical strategy. (36 references) (LB)

  3. The international serious adverse events consortium.

    PubMed

    Holden, Arthur L; Contreras, Jorge L; John, Sally; Nelson, Matthew R

    2014-11-01

    The International Serious Adverse Events Consortium is generating novel insights into the genetics and biology of drug-induced serious adverse events, and thereby improving pharmaceutical product development and decision-making.

  4. Adverse drug reactions in neonates: could we be documenting more?

    PubMed

    Hawcutt, Daniel B; O'Connor, Olya; Turner, Mark A

    2014-11-01

    Neonates are vulnerable to adverse drug reactions but reports of these events are relatively infrequent. Reporting can be increased by adapting a number of standard techniques to the unique features of neonatal care and pathology. However, clinicians and parents will be reluctant to report information about harms in the absence of mechanisms to ensure that reports affect clinical practice. Improved reporting will depend on education and cultural change that are informed by research about pharmacovigilance in neonatal settings. The efficient use of neonatal adverse drug reaction reports will require harmonization of terminology and interoperable databases.

  5. Weight-of-evidence evaluation of an adverse outcome ...

    EPA Pesticide Factsheets

    Ongoing honey bee colony losses are of significant international concern because of the essential role these insects play in pollinating staple food crops. Chemical and non-chemical stressors both have been implicated as possible contributors to colony failure, however, the potential role of commonly-used neonicotinoid insecticides has emerged as particularly concerning. Neonicotinoids act on the nicotinic acetylcholine receptor (nAChR) to eliminate target pest insects, however, mounting evidence indicates that these chemicals may adversely affect beneficial pollinators, such as the honey bee, via impacts on learning and memory thereby affecting foraging success. However, the mechanisms linking activation of the nAChR to adverse effects on learning and memory are uncertain. Additionally, clear connections between observed impacts on individual bees and colony level effects are lacking. Therefore, the objective of this work was to develop adverse outcome pathways (AOPs) as a means to evaluate the biological plausibility and empirical evidence supporting (or refuting) the linkage between the nAChR and colony level impacts. Development of these AOPs has led to the identification of research gaps which, for example, may be of high priority in understanding how perturbation of pathways involved in neurotransmission can adversely affect honey bee health, causing colony instability and further failure. From this effort, an AOP network also was developed, laying the f

  6. Adverse reactions to drug additives.

    PubMed

    Simon, R A

    1984-10-01

    There is a long list of additives used by the pharmaceutical industry. Most of the agents used have not been implicated in hypersensitivity reactions. Among those that have, only reactions to parabens and sulfites have been well established. Parabens have been shown to be responsible for rare immunoglobulin E-mediated reactions that occur after the use of local anesthetics. Sulfites, which are present in many drugs, including agents commonly used to treat asthma, have been shown to provoke severe asthmatic attacks in sensitive individuals. Recent studies indicate that additives do not play a significant role in "hyperactivity." The role of additives in urticaria is not well established and therefore the incidence of adverse reactions in this patient population is simply not known. In double-blind, placebo-controlled studies, reactions to tartrazine or additives other than sulfites, if they occur at all, are indeed quite rare for the asthmatic population, even for the aspirin-sensitive subpopulation.

  7. Hyperglycemia in Critically Ill Patients: Management and Prognosis

    PubMed Central

    Godinjak, Amina; Iglica, Amer; Burekovic, Azra; Jusufovic, Selma; Ajanovic, Anes; Tancica, Ira; Kukuljac, Adis

    2015-01-01

    Introduction: Hyperglycemia is a common complication of critical illness. Patients in intensive care unit with stress hyperglycemia have significantly higher mortality (31%) compared to patients with previously confirmed diabetes (10%) or normoglycemia (11.3%). Stress hyperglycemia is associated with increased risk of critical illness polyneuropathy (CIP) and prolonged mechanical ventilation. Intensive monitoring and insulin therapy according to the protocol are an important part of the treatment of critically ill patients. Objective: To evaluate the incidence of stress hyperglycemia, complications and outcome in critically ill patients in our Medical intensive care unit. Materials and methods: This study included 100 patients hospitalized in Medical intensive care unit during the period January 2014–March 2015 which were divided into three groups: Diabetes mellitus, stress-hyperglycemia and normoglycemia. During the retrospective-prospective observational clinical investigation the following data was obtained: age, gender, SAPS, admission diagnosis, average daily blood glucose, highest blood glucose level, glycemic variability, vasopressor and corticosteroid therapy, days on mechanical ventilation, total days of hospitalization in Medical intensive care unit, and outcome. Results: Patients with DM treated with a continuous insulin infusion did not have significantly more complications than patients with normoglycemia, unlike patients with stress hyperglycemia, which had more severe prognosis. There was a significant difference between the maximum level of blood glucose in recovered and patients with adverse outcome (p = 0.0277). Glycemic variability (difference between max. and min. blood glucose) was the strongest predictor of adverse outcome. The difference in glycemic variability between the stress-hyperglycemia and normoglycemic group was statistically significant (p = 0.0066). There was no statistically significant difference in duration of mechanical

  8. Do Holocaust survivors show increased vulnerability or resilience to post-Holocaust cumulative adversity?

    PubMed

    Shrira, Amit; Palgi, Yuval; Ben-Ezra, Menachem; Shmotkin, Dov

    2010-06-01

    Prior trauma can hinder coping with additional adversity or inoculate against the effect of recurrent adversity. The present study further addressed this issue by examining whether a subsample of Holocaust survivors and comparison groups, drawn from the Israeli component of the Survey of Health, Ageing, and Retirement in Europe, were differentially affected by post-Holocaust cumulative adversity. Post-Holocaust cumulative adversity had a stronger effect on the lifetime depression of Holocaust survivors than on that of comparisons. However, comparisons were more negatively affected by post-Holocaust cumulative adversity when examining markers of physical and cognitive functioning. Our findings suggest that previous trauma can both sensitize and immunize, as Holocaust survivors show general resilience intertwined with specific vulnerability when confronted with additional cumulative adversity.

  9. Long-term Prognosis of Left Ventricular Lead

    PubMed Central

    Park, Seung-Jung; Oh, Il-Young; Yoon, Chang-Hwan; Park, Hyo-Eun; Choi, Eue-Keun; Nam, Gi-Byoung; Choi, Kee-June; Kim, You-Ho; Choi, Yun-Shik

    2010-01-01

    Transvenous left ventricular (LV) lead implantation is on the increase due to cardiac resynchronization therapy (CRT). However, there has been paucity of data on the prognosis of LV lead. Consecutive 32 patients with LV lead for CRT (n=22) or pacemaker (n=10) were subjected. Serial changes in pacing threshold and impedance along with lead-related complications were evaluated. Over 2 yr follow-up, there was no significant change in relative threshold voltage to the initial value (100%, 110%, 89.6%, and 79.6% at baseline, 1, 6, and 24 months respectively, P=0.62) as well as lead impedance (816±272, 650±178, 647±191, and 590±185 ohm at baseline, 1, 6, and 24 months respectively, P=0.80). The threshold change was not affected by lead position, lead polarity, and indication of lead implantation. The cumulative rates of lead revision were 6.3% (n=2) and 9.4% (n=3) in 6 month and 2 yr follow-up, respectively. One case of phrenic nerve capture at left lateral decubitus position was detected 1 month after the implantation. However, there were no serious complications over 2 yr period. In conclusion, transvenous LV lead implantation showed favorable long-term prognosis. Pacing parameters remained stable without significant changes over 2 yr follow-up. PMID:20890427

  10. Regionality of disease progression predicts prognosis in amyotrophic lateral sclerosis.

    PubMed

    van der Kleij, Lisa A; Jones, Ashley R; Steen, I Nick; Young, Carolyn A; Shaw, Pamela J; Shaw, Christopher E; Leigh, P Nigel; Turner, Martin R; Al-Chalabi, Ammar

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating neurological syndrome in which motor neurons degenerate relentlessly. Although the site of onset and the rate of spread have been studied extensively, little is known about whether focal as opposed to diffuse disease affects prognosis. We therefore tested the hypothesis that regionality of disease burden is a prognostic factor in ALS. We analysed clinical data from two large multicentre, longitudinal trials. Regionality was defined as the difference in progression rates in three domains as measured by the revised ALS Functional Rating Scale, omitting the respiratory domain from analysis. We used death by trial end as the outcome variable and tested this by logistic regression against predictor variables including regionality and overall rate of disease progression. There were 561 patients. Regionality of disease was independently associated with significantly higher chance of death by study end (odds ratio most diffuse against most focal category 0.354 (0.191, 0.657), p = 0.001), with a direct relationship between degree of regionality and odds of death. We have shown using clinical trial data that focal disease is associated with a worse prognosis in ALS. Measures of regionality warrant further independent consideration in the development of future prognostic models.

  11. Serious adverse events associated with yellow fever vaccine.

    PubMed

    de Menezes Martins, Reinaldo; Fernandes Leal, Maria da Luz; Homma, Akira

    2015-01-01

    Yellow fever vaccine was considered one of the safest vaccines, but in recent years it was found that it could rarely cause invasive and disseminated disease in some otherwise healthy individuals, with high lethality. After extensive studies, although some risk factors have been identified, the real cause of causes of this serious adverse event are largely unknown, but findings point to individual host factors. Meningoencephalitis, once considered to happen only in children less than 6 months of age, has also been identified in older children and adults, but with good prognosis. Efforts are being made to develop a safer yellow fever vaccine, and an inactivated vaccine or a vaccine prepared with the vaccine virus envelope produced in plants are being tested. Even with serious and rare adverse events, yellow fever vaccine is the best way to avoid yellow fever, a disease of high lethality and should be used routinely in endemic areas, and on people from non-endemic areas that could be exposed, according to a careful risk-benefit analysis.

  12. Early life adversity: Lasting consequences for emotional learning.

    PubMed

    Krugers, Harm J; Arp, J Marit; Xiong, Hui; Kanatsou, Sofia; Lesuis, Sylvie L; Korosi, Aniko; Joels, Marian; Lucassen, Paul J

    2017-02-01

    The early postnatal period is a highly sensitive time period for the developing brain, both in humans and rodents. During this time window, exposure to adverse experiences can lastingly impact cognitive and emotional development. In this review, we briefly discuss human and rodent studies investigating how exposure to adverse early life conditions - mainly related to quality of parental care - affects brain activity, brain structure, cognition and emotional responses later in life. We discuss the evidence that early life adversity hampers later hippocampal and prefrontal cortex functions, while increasing amygdala activity, and the sensitivity to stressors and emotional behavior later in life. Exposure to early life stress may thus on the one hand promote behavioral adaptation to potentially threatening conditions later in life -at the cost of contextual memory formation in less threatening situations- but may on the other hand also increase the sensitivity to develop stress-related and anxiety disorders in vulnerable individuals.

  13. ICOS is associated with poor prognosis in breast cancer as it promotes the amplification of immunosuppressive CD4(+) T cells by plasmacytoid dendritic cells.

    PubMed

    Faget, Julien; Sisirak, Vanja; Blay, Jean-Yves; Caux, Christophe; Bendriss-Vermare, Nathalie; Ménétrier-Caux, Christine

    2013-03-01

    Regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) that infiltrate primary breast tumors impair patient survival. The ICOS-mediated interaction between tumor-infiltrating CD4(+) T cells and pDCs leads to the amplification of Tregs and interleukin-10 secretion. Importantly, ICOS(+) cell infiltration correlates with adverse patient prognosis, identifying ICOS as a new target for cancer immunotherapy.

  14. Prognosis of Lung Cancer: Heredity or Environment

    DTIC Science & Technology

    2015-06-01

    diagnosed at distant stage than whites (57 versus 45%; p = 0.03). In multivariable analyses adjusted for pack-years of smoking, age, body mass index, health ...cancer in under- served populations,14 understanding lung cancer prognosis in these populations is necessary for targeted public health interventions...Division of Epidemiology, Department of Medicine, ‡Institute for Medicine and Public Health , Department of Medicine, Vanderbilt University Medical

  15. Validation of Biomarkers for Prostate Cancer Prognosis

    DTIC Science & Technology

    2014-12-01

    pathologists. In the end, the pathologists have resorted to scoring the slides either by directly reading the images scanned from the Leica scanner...stains. Regardless, the reading of 5304 cores requires a single pathologist on average approximately 70 hours to look at and score all of the cores...addition, we have proposed testing a series of biomarkers of prognosis and a set of biomarkers that correlate with Gleason Score . We have made

  16. Holographic data processing methods for medical prognosis

    NASA Astrophysics Data System (ADS)

    Antonov, V. A.; Grosmann, M. H.; Kartavenko, V. I.; Larkin, A. I.; Trukhanov, K. A.

    2015-10-01

    The various methods of laser coherent photonic implementations of multiparametric classification are discussed in this paper. The holographic and optical data processing methods for medical application are considered. Inverse two-phase coding and analysis of light distribution in the correlation plane enables us to realize a number of algorithms: search for a precedent, Hamming distance measurement, Bayes probability algorithm, deterministic and ‘correspondence’ algorithms. The experimental holographic results for medicine prognosis are shown.

  17. Adverse events in healthcare: learning from mistakes.

    PubMed

    Rafter, N; Hickey, A; Condell, S; Conroy, R; O'Connor, P; Vaughan, D; Williams, D

    2015-04-01

    Large national reviews of patient charts estimate that approximately 10% of hospital admissions are associated with an adverse event (defined as an injury resulting in prolonged hospitalization, disability or death, caused by healthcare management). Apart from having a significant impact on patient morbidity and mortality, adverse events also result in increased healthcare costs due to longer hospital stays. Furthermore, a substantial proportion of adverse events are preventable. Through identifying the nature and rate of adverse events, initiatives to improve care can be developed. A variety of methods exist to gather adverse event data both retrospectively and prospectively but these do not necessarily capture the same events and there is variability in the definition of an adverse event. For example, hospital incident reporting collects only a very small fraction of the adverse events found in retrospective chart reviews. Until there are systematic methods to identify adverse events, progress in patient safety cannot be reliably measured. This review aims to discuss the need for a safety culture that can learn from adverse events, describe ways to measure adverse events, and comment on why current adverse event monitoring is unable to demonstrate trends in patient safety.

  18. Cervical carcinoma: prognosis in younger patients.

    PubMed Central

    Russell, J M; Blair, V; Hunter, R D

    1987-01-01

    Retrospective analysis of 2870 patients with invasive carcinoma of the cervix treated by radiotherapy from 1971 to 1978 showed that the prognosis for younger patients (defined as either under 35 or under 40) was better than that for older age groups, but young patients presented with earlier disease. When the effect of stage on prognosis was also considered the improved survival of patients under 35 was confirmed, although the result was of only borderline significance. The better survival of younger patients was particularly noticeable for stage IB disease, the corrected five year survival of those under 35 being 93% compared with 79% for those over 35. On the basis of this analysis and a review of previous reports it is concluded that age alone is a poor indicator of prognosis and should not be used as an indication for adjuvant treatment. There is no evidence in this series of an aggressive form of cervical carcinoma in younger patients during the 1970s. PMID:3115418

  19. Severe Cutaneous Adverse Drug Reactions: A Clinicoepidemiological Study

    PubMed Central

    Sasidharanpillai, Sarita; Riyaz, Najeeba; Khader, Anza; Rajan, Uma; Binitha, Manikoth P; Sureshan, Deepthi N

    2015-01-01

    Background: Drug eruptions range from transient erythema to the life threatening severe cutaneous adverse reactions (SCAR) that encompass Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms complex (DRESS). Aims and Objectives: To study the clinical and epidemiological aspects of cutaneous adverse drug reactions (CADR). Materials and Methods: Ethical clearance was obtained from the institutional ethics committee. All patients admitted in the Dermatology ward of our tertiary care hospital with CADR (those who fit in the category of probable or possible drug reaction as per WHO casuality assessment) from first September 2011 to 31st August 2012 were included in this cross sectional study after obtaining written informed consent. The drug reaction patterns observed in the study population were determined and the common offending drugs were identified. Results: In the study, population of males outnumbered females and the majority were between 46 and 60 years of age. The commonest reaction pattern observed was SJS- TEN spectrum of illness and aromatic anticonvulsants were the common offending drugs. Prompt withdrawal of the culprit drug and administration of systemic steroids with or without I/V Ig reverted the adverse reaction in all except one. Conclusion: Severe drug reactions predominated as the study population was comprised of inpatients of a tertiary referral centre. Though; previous authors had reported a mortality rate of up to 20% in DRESS, all our patients with this reaction pattern, responded well to treatment. The mortality rate among TEN cases was much lower than the previous reports. Early diagnosis, prompt withdrawal of the suspected drug, careful monitoring for development of complications and immediate intervention can improve the prognosis of CADR. PMID:25657416

  20. Adverse effects of antihypertensive drugs.

    PubMed

    Husserl, F E; Messerli, F H

    1981-09-01

    Early essential hypertension is asymptomatic and should remain so throughout treatment. In view of the increasing number of available antihypertensive agents, clinicians need to become familiar with the potential side effects of these drugs. By placing more emphasis on non-pharmacological treatment (sodium restriction, weight loss, exercise) and thoroughly evaluating each case in particular, the pharmacological regimen can be optimally tailored to the patient's needs. Potential side effects should be predicted and can often be avoided; if they become clinically significant they should be rapidly recognised and corrected. These side effects can be easily remembered in most instances, as they fall into 3 broad categories: (a) those caused by an exaggerated therapeutic effect; (b) those due to a non-therapeutic pharmacological effect; and (c) those caused by a non-therapeutic, non-pharmacological effect probably representing idiosyncratic reactions. This review focuses mainly on adverse effects of the second and third kind. Each group of drugs in general shares the common side effects of the first two categories, while each individual drug has its own idiosyncratic side effects.

  1. Rethinking the Measurement of Adversity.

    PubMed

    Mersky, Joshua P; Janczewski, Colleen E; Topitzes, James

    2017-02-01

    Research on adverse childhood experiences (ACEs) has unified the study of interrelated risks and generated insights into the origins of disorder and disease. Ten indicators of child maltreatment and household dysfunction are widely accepted as ACEs, but further progress requires a more systematic approach to conceptualizing and measuring ACEs. Using data from a diverse, low-income sample of women who received home visiting services in Wisconsin ( N = 1,241), this study assessed the prevalence of and interrelations among 10 conventional ACEs and 7 potential ACEs: family financial problems, food insecurity, homelessness, parental absence, parent/sibling death, bullying, and violent crime. Associations between ACEs and two outcomes, perceived stress and smoking, were examined. The factor structure and test-retest reliability of ACEs was also explored. As expected, prevalence rates were high compared to studies of more representative samples. Except for parent/sibling death, all ACEs were intercorrelated and associated at the bivariate level with perceived stress and smoking. Exploratory factor analysis confirmed that conventional ACEs loaded on two factors, child maltreatment and household dysfunction, though a more complex four-factor solution emerged once new ACEs were introduced. All ACEs demonstrated acceptable test-retest reliability. Implications and future directions toward a second generation of ACE research are discussed.

  2. Life adversity is associated with smoking relapse after a quit attempt.

    PubMed

    Lemieux, Andrine; Olson, Leif; Nakajima, Motohiro; Schulberg, Lauren; al'Absi, Mustafa

    2016-09-01

    Multiple cross-sectional studies have linked adverse childhood events and adult adversities to current smoking, lifetime smoking, and former smoking. To date, however, there have been no direct observational studies assessing the influence of adversities on smoking relapse. We prospectively followed 123 participants, 86 of whom were habitual smokers, from pre-quit ad libitum smoking to four weeks post-quit. Thirty-seven non-smokers were also tested in parallel as a comparison group. Subjects provided biological samples for confirmation of abstinence status and self-report history of adversities such as abuse, neglect, family dysfunction, incarceration, and child-parent separation. They also completed mood and smoking withdrawal symptom measures. The results indicated that within non-smokers and smokers who relapsed within the first month of a quit attempt, but not abstainers, females had significantly higher adversity scores than males. Cigarette craving, which was independent from depressive affect, increased for low adversity participants, but not those with no adversity nor high adversity. These results demonstrate that sex and relapse status interact to predict adversity and that craving for nicotine may be an important additional mediator of relapse. These results add further support to the previous cross-sectional evidence of an adversity and smoking relationship. Further studies to clarify how adversity complicates smoking cessation and impacts smoking behaviors are warranted.

  3. Minimizing AED adverse effects: improving quality of life in the interictal state in epilepsy care.

    PubMed

    St Louis, Erik K; Louis, Erik K

    2009-06-01

    The goals of epilepsy therapy are to achieve seizure freedom while minimizing adverse effects of treatment. However, producing seizure-freedom is often overemphasized, at the expense of inducing adverse effects of treatment. All antiepileptic drugs (AEDs) have the potential to cause dose-related, "neurotoxic" adverse effects (i.e., drowsiness, fatigue, dizziness, blurry vision, and incoordination). Such adverse effects are common, especially when initiating AED therapy and with polytherapy. Dose-related adverse effects may be obviated in most patients by dose reduction of monotherapy, reduction or elimination of polytherapy, or substituting for a better tolerated AED. Additionally, all older and several newer AEDs have idiosyncratic adverse effects which usually require withdrawal in an affected patient, including serious rash (i.e., Stevens-Johnson Syndrome, toxic epidermal necrolysis), hematologic dyscrasias, hepatotoxicity, teratogenesis in women of child bearing potential, bone density loss, neuropathy, and severe gingival hyperplasia. Unfortunately, occurrence of idiosyncratic AED adverse effects cannot be predicted or, in most cases, prevented in susceptible patients. This article reviews a practical approach for the definition and identification of adverse effects of epilepsy therapies, and reviews the literature demonstrating that adverse effects result in detrimental quality of life in epilepsy patients. Strategies for minimizing AED adverse effects by reduction or elimination of AED polytherapy, appropriately employing drug-sparing therapies, and optimally administering AEDs are outlined, including tenets of AED selection, titration, therapeutic AED laboratory monitoring, and avoidance of chronic idiosyncratic adverse effects.

  4. OAE: The Ontology of Adverse Events

    PubMed Central

    2014-01-01

    Background A medical intervention is a medical procedure or application intended to relieve or prevent illness or injury. Examples of medical interventions include vaccination and drug administration. After a medical intervention, adverse events (AEs) may occur which lie outside the intended consequences of the intervention. The representation and analysis of AEs are critical to the improvement of public health. Description The Ontology of Adverse Events (OAE), previously named Adverse Event Ontology (AEO), is a community-driven ontology developed to standardize and integrate data relating to AEs arising subsequent to medical interventions, as well as to support computer-assisted reasoning. OAE has over 3,000 terms with unique identifiers, including terms imported from existing ontologies and more than 1,800 OAE-specific terms. In OAE, the term ‘adverse event’ denotes a pathological bodily process in a patient that occurs after a medical intervention. Causal adverse events are defined by OAE as those events that are causal consequences of a medical intervention. OAE represents various adverse events based on patient anatomic regions and clinical outcomes, including symptoms, signs, and abnormal processes. OAE has been used in the analysis of several different sorts of vaccine and drug adverse event data. For example, using the data extracted from the Vaccine Adverse Event Reporting System (VAERS), OAE was used to analyse vaccine adverse events associated with the administrations of different types of influenza vaccines. OAE has also been used to represent and classify the vaccine adverse events cited in package inserts of FDA-licensed human vaccines in the USA. Conclusion OAE is a biomedical ontology that logically defines and classifies various adverse events occurring after medical interventions. OAE has successfully been applied in several adverse event studies. The OAE ontological framework provides a platform for systematic representation and analysis of

  5. Changing Medicine and Building Community: Maine’s Adverse Childhood Experiences Momentum

    PubMed Central

    Forstadt, Leslie; Cooper, Sally; Andrews, Sue Mackey

    2015-01-01

    Physicians are instrumental in community education, prevention, and intervention for adverse childhood experiences. In Maine, a statewide effort is focusing on education about adverse childhood experiences and ways that communities and physicians can approach childhood adversity. This article describes how education about adversity and resilience can positively change the practice of medicine and related fields. The Maine Resilience Building Network brings together ongoing programs, supports new ventures, and builds on existing resources to increase its impact. It exemplifies the collective impact model by increasing community knowledge, affecting medical practice, and improving lives. PMID:25902346

  6. Hospital deaths and adverse events in Brazil

    PubMed Central

    2011-01-01

    Background Adverse events are considered a major international problem related to the performance of health systems. Evaluating the occurrence of adverse events involves, as any other outcome measure, determining the extent to which the observed differences can be attributed to the patient's risk factors or to variations in the treatment process, and this in turn highlights the importance of measuring differences in the severity of the cases. The current study aims to evaluate the association between deaths and adverse events, adjusted according to patient risk factors. Methods The study is based on a random sample of 1103 patient charts from hospitalizations in the year 2003 in 3 teaching hospitals in the state of Rio de Janeiro, Brazil. The methodology involved a retrospective review of patient charts in two stages - screening phase and evaluation phase. Logistic regression was used to evaluate the relationship between hospital deaths and adverse events. Results The overall mortality rate was 8.5%, while the rate related to the occurrence of an adverse event was 2.9% (32/1103) and that related to preventable adverse events was 2.3% (25/1103). Among the 94 deaths analyzed, 34% were related to cases involving adverse events, and 26.6% of deaths occurred in cases whose adverse events were considered preventable. The models tested showed good discriminatory capacity. The unadjusted odds ratio (OR 11.43) and the odds ratio adjusted for patient risk factors (OR 8.23) between death and preventable adverse event were high. Conclusions Despite discussions in the literature regarding the limitations of evaluating preventable adverse events based on peer review, the results presented here emphasize that adverse events are not only prevalent, but are associated with serious harm and even death. These results also highlight the importance of risk adjustment and multivariate models in the study of adverse events. PMID:21929810

  7. Influencing factor on the prognosis of arthrocentesis

    PubMed Central

    Kim, Yoon Ho; Jeong, Tae Min; Pang, Kang Mi

    2014-01-01

    Objectives The purpose of this article is to evaluate factors influencing prognosis of arthrocentesis in patients with temporomandibular joint (TMJ) disorder. Materials and Methods The subjects included 145 patients treated with arthrocentesis at the Dental Center of Ajou University Hospital from 2011 to 2013 for the purpose of recovering mouth opening limitation (MOL) and pain relief. Prognosis of arthrocentesis was evaluated 1 month after the operation. Improvement on MOL was defined as an increase from below 30 mm (MOL ≤30 mm) to above 40 mm (MOL ≥40 mm), and pain relief was defined as when a group with TMJ pain with a visual analog scale (VAS) score of 4 or more (VAS ≥4) decreased to a score of 3 or more. The success of arthrocentesis was determined when either mouth opening improved or pain relief was fulfilled. To determine the factors influencing the success of arthrocentesis, the patients were classified by age, gender, diagnosis group (the anterior disc displacement without reduction group, the anterior disc displacement with reduction group, or other TMJ disorders group), time of onset and oral habits (clenching, bruxism) to investigate the correlations between these factors and prognosis. Results One hundred twenty out of 145 patients who underwent arthrocentesis (83.4%) were found to be successful. Among the influencing factors mentioned above, age, diagnosis and time of onset had no statistically significant correlation with the success of arthrocentesis. However, a group of patients in their fifties showed a lower success rate (ANOVA P=0.053) and the success rate of the group with oral habits was 71% (Pearson's chi-square test P=0.035). Conclusion From this study, we find that factors influencing the success of arthrocentesis include age and oral habits. We also conclude that arthrocentesis is effective in treating mouth opening symptoms and for pain relief. PMID:25247144

  8. Characterizing "Adversity" of Pathology Findings in ...

    EPA Pesticide Factsheets

    The identification of adverse health effects has a central role in the development and risk/safety assessment of chemical entities and pharmaceuticals. There is currently a need for better alignment in the toxicologic pathology community regarding how nonclinical adversity is determined and characterized. The European Society of Toxicologic Pathology (ESTP) therefore coordinated a workshop in June 2015 to review available definitions of adversity, weigh determining and qualifying factors of adversity based on case examples, and recommend a practical approach to define and characterize adversity in toxicology reports. The international group of expert pathologists and toxicologists emphasized that a holistic, weight-of-evidence, case-specific approach should be followed for each adversity assessment. It was recommended that nonclinical adversity should typically be determined at a morphological level (most often the organ) in the pathology report and should refer specifically to the test species. Final adversity calls, integration of target pharmacology/pathway information, and consideration of human translation should generally be made in toxicology overview reports. Differences in interpretation and implications of adversity calls between (agro)chemical and pharmaceutical industries and among world regions were highlighted. The results of this workshop should serve a valuable prerequisite for future organ- or lesion-specific workshops planned by the ESTP. This

  9. [Laron syndrome: Presentation, treatment and prognosis].

    PubMed

    Latrech, Hanane; Polak, Michel

    2016-01-01

    Laron syndrome is a rare cause of short stature due to an abnormality of growth hormone receptor (GHR). It is characterized by poor phenotype-genotype correlation and geographic predilection essentially in the Mediterranean rim, the Middle East and Indian subcontinent. This syndrome corresponds to an endogenous and exogenous complete insensitivity of GH and manifests by early hypoglycemia, an extremely severe short stature and dysmorphic features contrasting with high levels of circulating GH. To date, treatment with recombinant IGF1 is the only treatment option that has improved the terrible prognosis in these patients but does not actually realize the conditions for genuine replacement therapy.

  10. [Diagnosis and prognosis of preterm labor: physical examination and ultrasonography].

    PubMed

    Goffinet, F; Kayem, G

    2002-11-01

    Diagnosis. Preterm labor is defined by cervical changes associated with regular painful uterine contractions (UC) between 22 and 36 weeks + 6 days. Tocometry does not improve diagnosis or prognosis, despite the identification of more UC (NP 4). Electromyography and cervical distensibility (cervicotonometer) are promising techniques but are still in the research field. Clinical markers for prognosis. Clinical markers associated with clinical cervical examination tested in scoring systems are not validated and can't be recommended in clinical practise (NP 4). Ultrasonographic examination of the cervix. Technical evaluation of ultrasonographic examination of the cervix is satisfactory (NP 3); the transvaginal technical have to be used (NP 3). This method has a better accuracy and reproducibility than clinical examination provided a good apprenticeship (NP 3). Three ultrasound abnormal criteria are defined: a short length, a large internal cervical os and the presence of a funnel in the cervical canal. The best cut-off of cervical length to predict preterm delivery lies between 18 and 30 mm (NP 3). The choice of the cutt-off level depends on the prectitioner: high sensitivity but with many false-positives (cut-off close to 30 mm) or lower sensitivity with few false-positives (close to 20 mm). Cervical length seems to be more accurate that internal os or presence of a funnel which should be used with caution in clinical decisions (NP 3). There is no comparative study about the use of ultrasonographic examination of the cervix in women with preterm labor to evaluate benefits and adverse effects in clinical practice. However, ultrasonographic examination of the cervix supply a progress identifying women at risk of preterm delivery and this technique has a better predictive value than clinical cervical examination (NP 3). It seems reasonable to recommend utilisation of ultrasonographic examination of the cervic in preterm labor. It would not seem reasonable to replace the

  11. Loss of Bad expression confers poor prognosis in non-small cell lung cancer.

    PubMed

    Huang, Yi; Liu, Dan; Chen, Bojiang; Zeng, Jing; Wang, Lei; Zhang, Shangfu; Mo, Xianming; Li, Weimin

    2012-09-01

    Proapoptotic BH-3-only protein Bad (Bcl-Xl/Bcl-2-associated death promoter homolog, Bad) initiates apoptosis in human cells, and contributes to tumorigenesis and chemotherapy resistant in malignancies. This study explored association between the Bad expression level and prognosis in patients with non-small cell lung cancer (NSCLC). In our study, a cohort of 88 resected primary NSCLC cases were collected and analyzed. Bad expression level was determined via immunohistochemical staining assay. The prognostic significances of Bad expression were evaluated with univariate and multivariate survival analysis. The results showed that compared with normal lung tissues, Bad expression level significantly decreased in NSCLC (P < 0.05). Bad expression was associated with adjuvant therapy status. Loss of Bad independently predicted poor prognosis in whole NSCLC cohort and early stage subjects (T1 + T2 and N0 + N1) (all P < 0.05). Overall survival time was also drastically shortened for Bad negative phenotype in NSCLC patients with smoking history, especially lung squamous cell carcinoma (all P < 0.05). In conclusion, this study provided clinical evidence that loss of Bad is an independent and powerful predictor of adverse prognosis in NSCLC. Bad protein could be a new biomarker for selecting individual therapy strategies and predicting therapeutic response in subjects with NSCLC.

  12. Prognosis of synchronous bilateral breast cancer: a review and meta-analysis of observational studies.

    PubMed

    Holm, Marianne; Tjønneland, Anne; Balslev, Eva; Kroman, Niels

    2014-08-01

    Currently, no consistent evidence-based guidelines for the management of synchronous bilateral breast cancer (SBBC) exist and it is uncertain how presenting with SBBC affects patients' prognosis. We conducted a review of studies analyzing the association between SBBC and prognosis. The studies that reported adjusted effect measures were included in meta-analyses of effect of bilaterality on breast cancer mortality. From 57 initially identified records 17 studies from 11 different countries including 8,050 SBBC patients were included. The quality of the studies varied but was generally low with small sample sizes, and lack of consistent, detailed histo-pathological information. When doing meta-analysis on the subgroup of studies that provided adjusted effect estimates on breast cancer mortality (nine studies including 3,631 SBBC cases), we found that bilaterality in itself had a negative impact on prognosis after adjustment for known prognostic factors (pooled HR 1.37, 95 % CI 1.24-1.50, p < 0.0001). Multiple sensitivity analyses indicated robustness of the overall estimate. This review summarizes the current evidence of the association between SBBC and prognosis. The previously accepted convention that appropriate adjuvant treatment can be determined by considering the higher risk cancer was not confirmed in this review; rather it seems that being diagnosed with two tumors simultaneously entails a worse prognosis above and beyond that of the unilateral cancers of the same stage. To determine the true association between SBBC and breast cancer prognosis, studies of large and updated samples of SBBC should be done and include thorough histo-pathologic information.

  13. Effects of Timing of Adversity on Adolescent and Young Adult Adjustment.

    PubMed

    Kiff, Cara J; Cortes, Rebecca; Lengua, Lilana; Kosterman, Rick; Hawkins, J David; Mason, W Alex

    2012-06-01

    Effects of Timing of Adversity on Adolescent and Young Adult Adjustment Abstract Exposure to adversity during childhood and adolescence predicts adjustment across development. Further, adolescent adjustment problems persist into young adulthood. This study examined relations of contextual adversity with concurrent adolescent adjustment and prospective mental health and health outcomes in young adulthood. A longitudinal sample (N = 808) was followed from age 10 through 27. Perceptions of neighborhood in childhood predicted depression, alcohol use disorders, and HIV risk in young adulthood. Further, the timing of adversity was important in determining the type of problem experienced in adulthood. Youth adjustment predicted adult outcomes, and in some cases, mediated the relation between adversity and outcomes. These findings support the importance of adversity in predicting adjustment and elucidate factors that affect outcomes into young adulthood.

  14. Dietary flavonoids, lignans and colorectal cancer prognosis

    PubMed Central

    Zamora-Ros, Raul; Guinó, Elisabeth; Henar Alonso, M.; Vidal, Carmen; Barenys, Mercè; Soriano, Antonio; Moreno, Victor

    2015-01-01

    Flavonoids and lignans are polyphenol classes with anticarcinogenic activities against colorectal cancer (CRC). However, very limited epidemiological evidence exists on their effects on CRC prognosis. This study aimed to evaluate the association between flavonoid and lignan intakes with the risk of CRC recurrence and overall survival in CRC patients. The study followed incident histologically confirmed CRC cases in Barcelona (Spain). Validated dietary questionnaires and lifestyle information were collected at recruitment. An ad hoc food composition database on flavonoids and lignans was compiled by using data from the US Department of Agriculture and Phenol-Explorer databases. Adjusted hazards ratios (HR) and 95% confidence intervals (CIs) were estimated using multivariable Cox models. After 8.6 years of mean follow-up, 133 of 409 (32.5%) participants died and 77 of 319 (24.1%) had a CRC recurrence. Total flavonoids were associated neither with CRC recurrence (HR comparing extreme tertiles 1.13, 95% CI 0.64–2.02; P-trend 0.67) nor with overall survival (HRT3vsT1 1.06, 95% CI 0.69–1.65; P-trend 0.78) in the multivariable models. No associations were also observed with either total lignans or any flavonoid subclass intake. In conclusion, the results of the current study do not support a role of flavonoid and lignan intake in the CRC prognosis. PMID:26369380

  15. Fatigue damage prognosis using affine arithmetic

    NASA Astrophysics Data System (ADS)

    Gbaguidi, Audrey; Kim, Daewon

    2014-02-01

    Among the essential steps to be taken in structural health monitoring systems, damage prognosis would be the field that is least investigated due to the complexity of the uncertainties. This paper presents the possibility of using Affine Arithmetic for uncertainty propagation of crack damage in damage prognosis. The structures examined are thin rectangular plates made of titanium alloys with central mode I cracks and a composite plate with an internal delamination caused by mixed mode I and II fracture modes, under a harmonic uniaxial loading condition. The model-based method for crack growth rates are considered using the Paris Erdogan law model for the isotropic plates and the delamination growth law model proposed by Kardomateas for the composite plate. The parameters for both models are randomly taken and their uncertainties are considered as defined by an interval instead of a probability distribution. A Monte Carlo method is also applied to check whether Affine Arithmetic (AA) leads to tight bounds on the lifetime of the structure.

  16. [Clinical characteristics and prognosis of mediastinal fibrosis].

    PubMed

    Liao, J P; Hu, Y; Qiu, J X; Jin, Z; Zhang, H; Ma, J; Wang, G F

    2017-03-12

    Objective: To investigate the clinical characteristics and prognosis of mediastinal fibrosis. Methods: Twelve patients with mediastinal fibrosis diagnosed between 2008 and 2015 in our hospital were studied retrospectively. Clinical manifestations, radiological characteristics, endoscopic features, treatment and prognosis were analyzed. Results: There were 3 males and 9 females, with a mean age of 68.8 years.Six patients had previous tuberculosis infection. The most common clinical symptoms were dyspnea on exertion (11 cases), cough (7 cases), and wheezing (6 cases). Chest CT scans revealed an infiltrative mediastinal process, with a discrete mass, enlargement of mediastinal lymph nodes, mediastinal lymph node calcification (9 case). Twelve patients had bronchial and pulmonary artery compression at lobar or segmental levels, 7 cases had localized pulmonary edema, and 6 cases had pulmonary atelectasis. The principal findings of bronchoscopy were distortion of bronchus with stenosis, multiple pigmentation of bronchial mucosa, and bronchial mucosal edema. Pulmonary hypertension (PH) was the main severe complication. One patients suffered from sudden death after bronchoscopy. Eleven patients were followed for 3 month to 7 years, and 5 patients got progression. Anti-tuberculosis therapy with or without corticosteroid was not beneficial. Conclusion: Tuberculosis was the leading cause of mediastinal fibrosis in our study, which was characterized with diffuse bronchial and pulmonary artery compression at lobar or segmental levels, and multiple pigmentation of bronchial mucosa.Anti-tuberculosis therapy with or without corticosteroids was not beneficial.

  17. Understanding adverse events: human factors.

    PubMed Central

    Reason, J

    1995-01-01

    (1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional "capture" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with

  18. Strategic approaches to adverse outcome pathway development

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are conceptual frameworks for organizing biological and toxicological knowledge in a manner that supports extrapolation of data pertaining to the initiation or early progression of toxicity to an apical adverse outcome that occurs at a level of org...

  19. Patient management scenario: a framework for clinical decision and prognosis.

    PubMed

    Gospodarowicz, Mary; O'Sullivan, Brian

    2003-01-01

    The depiction of prognosis is one of the main activities and a mainstay in medical practice. In cancer, as in other diseases, the prognosis differs for a variety of situations and evolves with time and with medical interventions. Although most commonly described at diagnosis, prognosis may be defined at any time during the course of the disease and for any endpoint including response to therapy, failure of treatment, survival, or preservation of function, and so forth. To facilitate the accurate portrayal of the future, the prognosis should be defined within a specific setting, referred to as a 'management scenario'. In the concept of a management scenario, the prognosis is defined using systematically considered prognostic factors, interventions and the outcome of interest. A deliberate and careful determination of prognosis is essential to clinical decision making and patient care. We illustrate the use of the concept of management scenario in several clinical examples.

  20. A probabilistic approach for prognosis of battery pack aging

    NASA Astrophysics Data System (ADS)

    Chang, Chin-Yao; Tulpule, Punit; Rizzoni, Giorgio; Zhang, Wei; Du, Xinyu

    2017-04-01

    A probabilistic framework is developed for the prognosis of battery packs. It is demonstrated using aging campaign data, that aging models alone may not be sufficient for aging prognosis, and aging model parameter estimation may further improve the accuracy of prognosis. A systematic framework that extends the aging models to battery pack aging and prognosis still remains challenging. We propose a framework that bridges the gap in cell and pack aging prognosis in a probabilistic sense, and further improves the prognosis by estimating the aging model parameters for the pack. The framework is versatile for various applications because it is not restricted to a specific cell chemistry, or a type of aging model. In addition, the proposed framework could distinguish more aged cells as compared to other cells in the pack. Numerical examples are provided to demonstrate the effectiveness of the proposed framework.

  1. High LEF1 expression predicts adverse prognosis in chronic lymphocytic leukemia and may be targeted by ethacrynic acid.

    PubMed

    Wu, Wei; Zhu, Huayuan; Fu, Yuan; Shen, Wenyi; Miao, Kourong; Hong, Min; Xu, Wei; Fan, Lei; Young, Ken H; Liu, Peng; Li, Jianyong

    2016-04-19

    Aberrant activation of lymphoid enhancer-binding factor-1 (LEF1) has been identified in several cancers, including chronic lymphocytic leukemia (CLL). As a key transcription factor of the Wnt/β-catenin pathway, LEF1 helps to regulate important genes involved in tumor cell death mechanisms. In this study, we determined LEF1 gene expression levels in CLL (n = 197) and monoclonal B-cell lymphocytosis (MBL) (n = 6) patients through real-time RT-PCR. LEF1 was significantly up-regulated in both MBL and CLL patients compared with normal B cells. Treatment-free survival (TFS) time and overall survival (OS) time were much longer in CLL patients with low LEF1 expression than in those with high LEF1 levels. Furthermore, Wnt inhibitor ethacrynic acid (EA) induced both apoptosis and necroptosis in primary CLL cells. EA also enhanced the cytotoxicity of both fludarabine and cyclophosphamide against CLL cells in vitro. Finally, we demonstrated that EA functions by inhibiting the recruitment of LEF1 to DNA promoters and restoring cylindromatosis (CYLD) expression in CLL cells. Our results showed, for the first time, that high LEF1 expression is associated with poor survival for CLL patients. Combined with other chemotherapeutic drugs, EA may be a promising therapeutic agent for CLL.

  2. High LEF1 expression predicts adverse prognosis in chronic lymphocytic leukemia and may be targeted by ethacrynic acid

    PubMed Central

    Wu, Wei; Zhu, Huayuan; Fu, Yuan; Shen, Wenyi; Miao, Kourong; Hong, Min; Xu, Wei; Fan, Lei; Young, Ken H.; Liu, Peng; Li, Jianyong

    2016-01-01

    Aberrant activation of lymphoid enhancer-binding factor-1 (LEF1) has been identified in several cancers, including chronic lymphocytic leukemia (CLL). As a key transcription factor of the Wnt/β-catenin pathway, LEF1 helps to regulate important genes involved in tumor cell death mechanisms. In this study, we determined LEF1 gene expression levels in CLL (n = 197) and monoclonal B-cell lymphocytosis (MBL) (n = 6) patients through real-time RT-PCR. LEF1 was significantly up-regulated in both MBL and CLL patients compared with normal B cells. Treatment-free survival (TFS) time and overall survival (OS) time were much longer in CLL patients with low LEF1 expression than in those with high LEF1 levels. Furthermore, Wnt inhibitor ethacrynic acid (EA) induced both apoptosis and necroptosis in primary CLL cells. EA also enhanced the cytotoxicity of both fludarabine and cyclophosphamide against CLL cells in vitro. Finally, we demonstrated that EA functions by inhibiting the recruitment of LEF1 to DNA promoters and restoring cylindromatosis (CYLD) expression in CLL cells. Our results showed, for the first time, that high LEF1 expression is associated with poor survival for CLL patients. Combined with other chemotherapeutic drugs, EA may be a promising therapeutic agent for CLL. PMID:26950276

  3. Rosai-Dorfman Disease Involving Multiple Organs: An Unusual Case with Poor Prognosis

    PubMed Central

    Ranaivo, Irina Mamisoa; Andrianarison, Malalaniaina; Razanakoto, Naina Harinjara; Ramarozatovo, Lala Soavina

    2016-01-01

    Rosai-Dorfman disease is a rare, benign histiocytic proliferative disorder that usually affects the lymph nodes. Although extranodal involvement has been reported in diverse sites, manifestation in the cardiovascular system is extremely rare. Specifically, cardiac involvement in Rosai-Dorfman disease is an extraordinarily infrequent event. We describe a case of a 36-year-old female who presented Rosai-Dorfman disease of multiple organs including the heart, with poor prognosis. PMID:27872644

  4. Effect of ALDH1 on prognosis and chemoresistance by breast cancer subtype.

    PubMed

    Kida, Kumiko; Ishikawa, Takashi; Yamada, Akimitsu; Shimada, Kazuhiro; Narui, Kazutaka; Sugae, Sadatoshi; Shimizu, Daisuke; Tanabe, Mikiko; Sasaki, Takeshi; Ichikawa, Yasushi; Endo, Itaru

    2016-04-01

    Aldehyde dehydrogenase 1 (ALDH1) has been identified as a breast cancer stem cell marker, but its value as a predictor of prognosis and chemoresistance is controversial. This study investigated the effect of ALDH1 on prognosis and chemoresponse by breast cancer subtype. We immunohistochemically analyzed 653 invasive breast cancer specimens and evaluated correlations among clinicopathological factors, survival status, response to neoadjuvant chemotherapy, and ALDH1 expression. Of 653 specimens, 139 (21.3 %) expressed ALDH1 in tumor cells. ALDH1 expression was correlated significantly with larger tumor size, node metastasis, higher nuclear grade, and with HER2(+) and progesterone/estrogen receptor (HR)(-) subtypes. ALDH1 expression was significantly observed in HER2 type and triple-negative breast cancer (TNBC). Patients with ALDH1(+) cancers had significantly shorter disease-free survival (P < 0001) and overall survival (P = 0.044). ALDH1 expression significantly affected prognosis of luminal types, but not TNBC and HER2-enriched types. For the 234 patients treated with neoadjuvant chemotherapy, pathological complete response (pCR) rate was significantly lower in ALDH1(+) cases (13.5 vs. 30.3 %, P = 0.003). pCR and ALDH1 expression were significantly correlated in TNBC patients (P = 0.003). ALDH1(+) breast cancers tended to be aggressive, with poor prognoses. Although ALDH1(+) TNBC showed higher chemoresistance, ALDH1 had significant impact on prognosis in the luminal type but not in TNBC.

  5. Synergistic childhood adversities and complex adult psychopathology.

    PubMed

    Putnam, Karen T; Harris, William W; Putnam, Frank W

    2013-08-01

    Numerous studies find a cumulative effect of different types of childhood adversities on increasing risk for serious adult mental and medical outcomes. This study uses the National Comorbidity Survey-Replication sample to investigate the cumulative impact of 8 childhood adversities on complex adult psychopathology as indexed by (a) number of lifetime diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM-IV; American Psychiatric Association, 1994); (b) number of 4 DSM-IV disorder categories (mood, anxiety, impulse control, and substance abuse disorders); and (c) coexistence of internalizing and externalizing disorders. Seven of the 8 childhood adversities were significantly associated with complex adult psychopathology. Individuals with 4 or more childhood adversities had an odds ratio of 7.3, 95% confidence interval [4.7, 11.7] for 4 disorder categories. Additive and multiplicative synergistic effects increasing adult psychopathology were found for specific pairwise combinations of childhood adversities. Synergistic patterns differed by gender suggesting that women are more impacted by sexual abuse and men by economic hardship. The absence of childhood adversities was protective, in that it significantly decreased an individual's risk for subsequent adult mental illness. The results support the clinical impression that increased childhood adversity is associated with more complex adult psychopathology.

  6. Idiopathic Pulmonary Fibrosis: Treatment and Prognosis

    PubMed Central

    Fujimoto, Hajime; Kobayashi, Tetsu; Azuma, Arata

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with a prognosis that can be worse than for many cancers. The initial stages of the condition were thought to mainly involve chronic inflammation; therefore, corticosteroids and other drugs that have anti-inflammatory and immunosuppressive actions were used. However, recently, agents targeting persistent fibrosis resulting from aberrant repair of alveolar epithelial injury have been in the spotlight. There has also been an increase in the number of available antifibrotic treatment options, starting with pirfenidone and nintedanib. These drugs prevent deterioration but do not improve IPF. Therefore, nonpharmacologic approaches such as long-term oxygen therapy, pulmonary rehabilitation, and lung transplantation must be considered as additional treatment modalities. PMID:27980445

  7. Adverse Effects of Wheat Gluten.

    PubMed

    Koning, Frits

    2015-01-01

    Man began to consume cereals approximately 10,000 years ago when hunter-gatherers settled in the fertile golden crescent in the Middle East. Gluten has been an integral part of the Western type of diet ever since, and wheat consumption is also common in the Middle East, parts of India and China as well as Australia and Africa. In fact, the food supply in the world heavily depends on the availability of cereal-based food products, with wheat being one of the largest crops in the world. Part of this is due to the unique properties of wheat gluten, which has a high nutritional value and is crucial for the preparation of high-quality dough. In the last 10 years, however, wheat and gluten have received much negative attention. Many believe that it is inherently bad for our health and try to avoid consumption of gluten-containing cereals; a gluten-low lifestyle so to speak. This is fueled by a series of popular publications like Wheat Belly; Lose the Wheat, Lose the Weight, and Find Your Path Back to Health. However, in reality, there is only one condition where gluten is definitively the culprit: celiac disease (CD), affecting approximately 1% of the population in the Western world. Here, I describe the complexity of the cereals from which gluten is derived, the special properties of gluten which make it so widely used in the food industry, the basis for its toxicity in CD patients and the potential for the development of safe gluten and alternatives to the gluten-free diet.

  8. Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament.

    PubMed

    Kuhn, Manuel; Scharfenort, Robert; Schümann, Dirk; Schiele, Miriam A; Münsterkötter, Anna L; Deckert, Jürgen; Domschke, Katharina; Haaker, Jan; Kalisch, Raffael; Pauli, Paul; Reif, Andreas; Romanos, Marcel; Zwanzger, Peter; Lonsdorf, Tina B

    2016-04-01

    Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences.

  9. Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament

    PubMed Central

    Kuhn, Manuel; Scharfenort, Robert; Schümann, Dirk; Schiele, Miriam A.; Münsterkötter, Anna L.; Deckert, Jürgen; Domschke, Katharina; Haaker, Jan; Kalisch, Raffael; Pauli, Paul; Reif, Andreas; Romanos, Marcel; Zwanzger, Peter

    2016-01-01

    Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences. PMID:26568620

  10. Uncertainty Comparison of Visual Sensing in Adverse Weather Conditions†

    PubMed Central

    Lo, Shi-Wei; Wu, Jyh-Horng; Chen, Lun-Chi; Tseng, Chien-Hao; Lin, Fang-Pang; Hsu, Ching-Han

    2016-01-01

    This paper focuses on flood-region detection using monitoring images. However, adverse weather affects the outcome of image segmentation methods. In this paper, we present an experimental comparison of an outdoor visual sensing system using region-growing methods with two different growing rules—namely, GrowCut and RegGro. For each growing rule, several tests on adverse weather and lens-stained scenes were performed, taking into account and analyzing different weather conditions with the outdoor visual sensing system. The influence of several weather conditions was analyzed, highlighting their effect on the outdoor visual sensing system with different growing rules. Furthermore, experimental errors and uncertainties obtained with the growing rules were compared. The segmentation accuracy of flood regions yielded by the GrowCut, RegGro, and hybrid methods was 75%, 85%, and 87.7%, respectively. PMID:27447642

  11. Mechanisms and assessment of statin-related muscular adverse effects.

    PubMed

    Moßhammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mörike, Klaus

    2014-09-01

    Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers.

  12. Chemical research on red pigments after adverse reactions to tattoo.

    PubMed

    Tammaro, A; Toniolo, C; Giulianelli, V; Serafini, M; Persechino, S

    2016-03-01

    Currently, the incidence of tattooing is on the rise compared to the past, especially among adolescents, and it leads to the urgency of monitoring the security status of tattooing centers, as well as to inform people about the risks of tattoo practice. In our clinical experience, 20% of tattooed patients presented adverse reactions, like allergic contact dermatitis, psoriasis with Koebner's phenomena and granulomatous reactions, with the latter most prevalent and most often related to red pigment. Adverse reactions to tattoo pigments, especially the red one, are well known and described in literature. Great attention has to be focused on the pigments used, especially for the presence of new substances, often not well known. For this reason, we decided to perform a study on 12 samples of red tattoo ink, obtained by patients affected by different cutaneous reactions in the site of tattoo, to analyze their chemical composition.

  13. Antiepileptic drugs and adverse skin reactions: An update.

    PubMed

    Błaszczyk, Barbara; Lasoń, Władysław; Czuczwar, Stanisław Jerzy

    2015-06-01

    This paper summarizes current views on clinical manifestation, pathogenesis, prognosis and management of antiepileptic drug (AED)-induced adverse skin reactions. Cochrane Central Register of Controlled Trials, MEDLINE (PubMed) and ISI Web of Knowledge were searched. The recent classification, among drug-induced skin injuries, points to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis and hypersensitivity syndrome (HSS), which may be also recognized as a drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS). The use of aromatic AEDs, e.g. phenytoin, carbamazepine, oxcarbazepine, phenobarbital, primidone, zonisamide, and lamotrigine is more frequently associated with cutaneous eruption and other signs or symptoms of drug hypersensitivity. There is a high degree of cross-reactivity (40-80%) in patients with hypersensitivity or allergic reactions to AEDs. Pharmacogenetic variations in drug biotransformation may also play a role in inducing these undesired effects. It is suggested that avoidance of specific AEDs in populations at special risk, cautious dose titration and careful monitoring of clinical response and, if applicable, laboratory parameters can minimize the serious consequences of idiosyncratic reactions.

  14. [Cardiovascular pharmacotherapy. Risks and adverse effects].

    PubMed

    Voigt, N; Heijman, J; Dobrev, D

    2014-03-01

    Adverse side effects of drugs are a significantly underestimated problem in modern medicine. In this review article, we summarize common adverse side effects of cardiovascular drugs. In particular, we highlight the factors promoting these adverse side effects in patients, including reduced hepatic or renal clearance in elderly patients that often requires dosage adjustment. Pharmacodynamic and pharmacokinetic interactions between drugs (e.g. through the cytochrome P450 system or P-glycoproteins) can modify the plasma concentration of many compounds, thereby also increasing the likelihood of unwanted side effects. The most prominent cardiac side effects include arrhythmias, e.g. atrioventricular (AV) block, drug-induced long-QT syndrome and torsade de pointes and altered inotropy. Non-cardiac side effects are subsequently discussed grouped by drug class. A better understanding of the risks and side effects of cardiovascular drugs is expected to reduce the mortality and morbidity associated with adverse side effects.

  15. Childhood adversities and psychosis: evidence, challenges, implications

    PubMed Central

    Morgan, Craig; Gayer‐Anderson, Charlotte

    2016-01-01

    There is a substantial body of research reporting evidence of associations between various forms of childhood adversity and psychosis, across the spectrum from experiences to disorder. This has been extended, more recently, to include studies of cumulative effects, of interactions with other factors, of specific effects, and of putative biological and psychological mechanisms. In this paper we evaluate this research and highlight the remaining methodological issues and gaps that temper, but do not dismiss, conclusions about the causal role of childhood adversity. We also consider the emerging work on cumulative, synergistic, and specific effects and on mechanisms; and discuss the broader implications of this line of research for our understanding of psychosis. We conclude that the current balance of evidence is that childhood adversities – particularly exposure to multiple adversities involving hostility and threat – do, in some people, contribute to the onset of psychotic experiences and psychotic disorders. PMID:27265690

  16. Childhood adversity: a review of measurement instruments.

    PubMed

    Burgermeister, Diane

    2007-01-01

    Measurement instruments are needed to stimulate research on the long-term outcomes of childhood adversity. Therefore, the purpose of this review was to locate, describe, and assess instruments to measure retrospective perceptions of childhood adversity. An electronic search of instruments was conducted using a combination of keywords that included child maltreatment, child trauma, and childhood stressful events. Nine instruments were located and described according to format, definition of childhood adversity as measured by the instrument, characteristics of the sample used in development and testing, reliability and validity evidence, and feasibility for use. Six out of the nine instruments were suitable for investigators who require a comprehensive measure of childhood adversity. Corroboration with independent sources and use of randomized samples are needed to improve upon reports of validity.

  17. RACIAL RESIDENTIAL SEGREGATION AND ADVERSE BIRTH OUTCOMES

    EPA Science Inventory

    INTRODUCTION. The disparity between black and white women's adverse birth outcomes has been subject to much investigation, yet the factors underlying its persistence remain elusive, which has encouraged research on neighborhood-level influences, including racial residential segr...

  18. Adverse Outcome Pathways: From Definition to Application

    EPA Science Inventory

    A challenge for both human health and ecological toxicologists is the transparent application of mechanistic (e.g., molecular, biochemical, histological) data to risk assessments. The adverse outcome pathway (AOP) is a conceptual framework designed to meet this need. Specifical...

  19. Design of Adverse Drug Events-Scorecards.

    PubMed

    Marcilly, Romaric; Chazard, Emmanuel; Beuscart-Zéphir, Marie-Catherine; Hackl, Werner; Băceanu, Adrian; Kushniruk, Andre; Borycki, Elizabeth M

    2011-01-01

    This paper presents the design of Adverse Drug Event-Scorecards. The scorecards described are innovative and novel, not having previously been reported in the literature. The Scorecards provide organizations (e.g. hospitals) with summary information about Adverse Drug Events (ADEs) using a Web-based platform. The data used in the Scorecards are routinely updated and report on ADEs detected through data mining processes. The development of the ADE Scorecards is ongoing and they are currently undergoing clinical testing.

  20. [Allergies and adverse events associated with fluoroquinolones].

    PubMed

    Muller, Y; Andrey, D; Emonet, S; Harr, T; Spoerl, D

    2015-04-08

    The prescription ot fluoroquinolones has been constantly increasing over the past decade. consequently, an increasing number of hyper-sensitivity reactions and adverse events have been reported. The aim of the review is to discuss the incidence of hypersensitivity reactions either IgE (immediate) or T cells mediated (delayed). We will make an overview ofthe diagnostic tools available to detect such hypersensitivity reactions. Finally, the specific adverse events associated with fluoroquinolones, including tendinopathy, chondrotoxicity, peripheral neuropathy or retinal detachment will be discussed.

  1. Childhood adversity and frequent medical consultations.

    PubMed

    Fiddler, Maggie; Jackson, Judy; Kapur, Navneet; Wells, Adrian; Creed, Francis

    2004-01-01

    We assessed possible psychological mediators of the relationship between childhood adversity and frequent medical consultations among new outpatients at neurology, cardiology, and gastroenterology clinics. We assessed whether these differed in patients with and without organic disease that explained their symptoms. At first clinic visit we recorded Hospital Anxiety and Depression scale (HADS--anxiety and depression subscale scores), Illness Perception Questionnaire (IPQ--four subscales: consequences, cure, identity, timeline), Health Anxiety Questionnaire (total score), and Symptom Amplification Scale (total score). Subjects were divided into two groups according to whether they had experienced any type of childhood adversity using the Childhood Experience of Care and Abuse Schedule. Outcome was the (log) number of medical consultations for 12 months before and 6 months after the index clinic visits. Multiple regression analysis was used to determine mediators; this was performed separately for patients with symptoms explained and not explained by organic disease. One-hundred and twenty-nine patients (61% response) were interviewed. Fifty-two (40.3%) had experienced childhood adversity; they made a median of 16 doctor visits compared with 10 for those without adversity (adjusted P=.026). IPQ identity score (number of symptoms attributed to the illness) and HAD depression scores were significantly associated with both childhood adversity and number of medical consultations and these variables acted as mediators between childhood adversity and frequency of consultation in the multiple regression analyses. This association was limited to patients with medically unexplained symptoms and was mediated by IPQ Identity Score (number of symptoms attributed to the patient's illness) and HAD depression score. Sexual abuse and overt neglect were the adversities most closely associated with frequent consultations. In patients with medically unexplained symptoms the association

  2. Adverse drug reactions in hospitalized Colombian children

    PubMed Central

    Díaz-Agudelo, Daniela; Burgos-Flórez, Francisco Javier; Vaca, Claudia; Serrano-Meriño, Dolores Vanessa

    2016-01-01

    Introduction: The occurrence of adverse drug reactions is an important issue due to the lack of drug safety data in children. Objective: To describe the Adverse Drug Reactions in inpatient children under 6 years of age in two general pediatrics wards located in Barranquilla, Colombia. Methods: A prospective cohort study based on intensive pharmacovigilance was conducted during six months in order to monitor the emergence of Adverse Drug Reactions in inpatients children under 6 years of age with at least one medication prescribed. The study was conducted in two pediatric wards of two hospitals located in Barranquilla, Colombia. Naranjo´s Algorithm was used to evaluate imputability, the modified Hartwig and Siegel assessment scale to establish severity and the Schumock and Thornton criteria to determine preventability. Results: Of a total of 772 monitored patients, 156 Adverse Drug Reactions were detected on 147 children. The cumulative incidence of Adverse Drug Reactions was 19.0% (147/772); the incidence density was 37.6 Adverse Drug Reactions per 1,000 patients-days (147/3,913). The frequency was higher in children under 2 years of age (12.7%). Emergence of Adverse Drug Reactions was higher in male patients (RR= 1.66; 95% CI= 1.22-2.22, p= 0.001) and in those who used systemic antibiotics (RR= 1.82; 95% CI= 1.17-2.82, p= 0.005). Conclusions: Adverse Drug Reactions are common among hospitalized children and represent an additional burden of morbidity and risk, particularly in those who used several medicines, including antibiotics. PMID:27821893

  3. Recognizing and reporting adverse drug reactions.

    PubMed Central

    Lucas, L. M.; Colley, C. A.

    1992-01-01

    Although physicians in practice are most likely to see patients with adverse drug reactions, they may fail to recognize an adverse effect or to attribute it to a drug effect and, when recognized, they may fail to report serious reactions to the US Food and Drug Administration (FDA). To recognize and attribute an adverse event to a drug effect, physicians should review the patient's clinical course, looking at patient risk factors, the known adverse reactions to the suspected drug, and the likelihood of a causal relationship between the drug and the adverse event-based on the temporal relationship, response to stopping or restarting the drug, and whether other factors could explain the reaction. Once an adverse drug reaction has been identified, the patient should be informed and appropriate documentation made in the patient's medical record. Serious known reactions and all reactions to newly released drugs or those not previously known to occur (even if the certainty is low) should be reported to the FDA. PMID:1536067

  4. Adverse selection with a multiple choice among health insurance plans: a simulation analysis.

    PubMed

    Marquis, M S

    1992-08-01

    This study uses simulation methods to quantify the effects of adverse selection. The data used to develop the model provide information about whether families can accurately forecast their risk and whether this forecast affects the purchase of insurance coverage--key conditions for adverse selection to matter. The results suggest that adverse selection is sufficient to eliminate high-option benefit plans in multiple choice markets if insurers charge a single, experience-rated premium. Adverse selection is substantially reduced if premiums are varied according to demographic factors. Adverse selection is also restricted in supplementary insurance markets. In this market, supplementary policies are underpriced because a part of the additional benefits that purchasers can expect is a cost to the base plan and is not reflected in the supplementary premium. As a result, full supplementary coverage is attractive to both low and high risks.

  5. New Nuclear Emergency Prognosis system in Korea

    NASA Astrophysics Data System (ADS)

    Lee, Hyun-Ha; Jeong, Seung-Young; Park, Sang-Hyun; Lee, Kwan-Hee

    2016-04-01

    This paper reviews the status of assessment and prognosis system for nuclear emergency response in Korea, especially atmospheric dispersion model. The Korea Institute of Nuclear Safety (KINS) performs the regulation and radiological emergency preparedness of the nuclear facilities and radiation utilizations. Also, KINS has set up the "Radiological Emergency Technical Advisory Plan" and the associated procedures such as an emergency response manual in consideration of the IAEA Safety Standards GS-R-2, GS-G-2.0, and GS-G-2.1. The Radiological Emergency Technical Advisory Center (RETAC) organized in an emergency situation provides the technical advice on radiological emergency response. The "Atomic Computerized Technical Advisory System for nuclear emergency" (AtomCARE) has been developed to implement assessment and prognosis by RETAC. KINS developed Accident Dose Assessment and Monitoring (ADAMO) system in 2015 to reflect the lessons learned from Fukushima accident. It incorporates (1) the dose assessment on the entire Korean peninsula, Asia region, and global region, (2) multi-units accident assessment (3) applying new methodology of dose rate assessment and the source term estimation with inverse modeling, (4) dose assessment and monitoring with the environmental measurements result. The ADAMO is the renovated version of current FADAS of AtomCARE. The ADAMO increases the accuracy of the radioactive material dispersion with applying the LDAPS(Local Data Assimilation Prediction System, Spatial resolution: 1.5 km) and RDAPS(Regional Data Assimilation Prediction System, Spatial resolution: 12km) of weather prediction data, and performing the data assimilation of automatic weather system (AWS) data from Korea Meteorological Administration (KMA) and data from the weather observation tower at NPP site. The prediction model of the radiological material dispersion is based on the set of the Lagrangian Particle model and Lagrangian Puff model. The dose estimation methodology

  6. Developing robust crop plants for sustaining growth and yield under adverse climatic changes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agricultural production and quality are expected to suffer from adverse changes in climatic conditions, including global warming, and this will affect worldwide human and animal food security. Global warming has been shown to negatively impact crop yield and therefore will affect sustainability of a...

  7. Adverse effects of common medications on male fertility.

    PubMed

    Samplaski, Mary K; Nangia, Ajay K

    2015-07-01

    An increasing number of patients require long-term medication regimens at a young age, but the adverse effects of medications on male reproduction are often inadequately considered, recognized and investigated. Medications can affect male reproduction through central hormonal effects, direct gonadotoxic effects, effects on sperm function or on sexual function. For example, exogenous testosterone inhibits spermatogenesis through central suppression of the hypothalamic-pituitary-gonadal hormonal axis. 5α-reductase inhibitors can impair sexual function, decrease semen volume and negatively affect sperm parameters, depending on dose and treatment duration. α-Blockers might decrease seminal emission and cause retrograde ejaculation, depending on the receptor specificity and dose of the agent. Phosphodiesterase inhibitors seem to have variable effects based on the isoform inhibited and evidence is conflicting. Antihypertensive and psychotropic agents can affect sperm, sexual function and hormonal parameters. For antibiotics, the literature on effects on sperm and sperm function is limited and dated. Many chemotherapeutic agents have a direct gonadotoxic effect, depending on agents used, dosing and number of treatment cycles. Overall, many medications commonly used in urology can have effects on male fertility (mostly reversible) but conclusive evidence in humans is often limited. Men should be counselled appropriately about potential drug-related adverse effects on their fertility.

  8. Tumor Volumes and Prognosis in Laryngeal Cancer

    PubMed Central

    Issa, Mohamad R.; Samuels, Stuart E.; Bellile, Emily; Shalabi, Firas L.; Eisbruch, Avraham; Wolf, Gregory

    2015-01-01

    Tumor staging systems for laryngeal cancer (LC) have been developed to assist in estimating prognosis after treatment and comparing treatment results across institutions. While the laryngeal TNM system has been shown to have prognostic information, varying cure rates in the literature have suggested concern about the accuracy and effectiveness of the T-classification in particular. To test the hypothesis that tumor volumes are more useful than T classification, we conducted a retrospective review of 78 patients with laryngeal cancer treated with radiation therapy at our institution. Using multivariable analysis, we demonstrate the significant prognostic value of anatomic volumes in patients with previously untreated laryngeal cancer. In this cohort, primary tumor volume (GTVP), composite nodal volumes (GTVN) and composite total volume (GTVP + GTVN = GTVC) had prognostic value in both univariate and multivariate cox model analysis. Interestingly, when anatomic volumes were measured from CT scans after a single cycle of induction chemotherapy, all significant prognosticating value for measured anatomic volumes was lost. Given the literature findings and the results of this study, the authors advocate the use of tumor anatomic volumes calculated from pretreatment scans to supplement the TNM staging system in subjects with untreated laryngeal cancer. The study found that tumor volume assessment after induction chemotherapy is not of prognostic significance. PMID:26569309

  9. Liver Cirrhosis: Evaluation, Nutritional Status, and Prognosis.

    PubMed

    Nishikawa, Hiroki; Osaki, Yukio

    2015-01-01

    The liver is the major organ for the metabolism of three major nutrients: protein, fat, and carbohydrate. Chronic hepatitis C virus infection is the major cause of chronic liver disease. Liver cirrhosis (LC) results from different mechanisms of liver injury that lead to necroinflammation and fibrosis. LC has been seen to be not a single disease entity but one that can be graded into distinct clinical stages related to clinical outcome. Several noninvasive methods have been developed for assessing liver fibrosis and these methods have been used for predicting prognosis in patients with LC. On the other hand, subjects with LC often have protein-energy malnutrition (PEM) and poor physical activity. These conditions often result in sarcopenia, which is the loss of skeletal muscle volume and increased muscle weakness. Recent studies have demonstrated that PEM and sarcopenia are predictive factors for poorer survival in patients with LC. Based on these backgrounds, several methods for evaluating nutritional status in patients with chronic liver disease have been developed and they have been preferably used in the clinical field practice. In this review, we will summarize the current knowledge in the field of LC from the viewpoints of diagnostic method, nutritional status, and clinical outcomes.

  10. Diagnosis and Prognosis of Weapon Systems

    NASA Technical Reports Server (NTRS)

    Nolan, Mary; Catania, Rebecca; deMare, Gregory

    2005-01-01

    The Prognostics Framework is a set of software tools with an open architecture that affords a capability to integrate various prognostic software mechanisms and to provide information for operational and battlefield decision-making and logistical planning pertaining to weapon systems. The Prognostics NASA Tech Briefs, February 2005 17 Framework is also a system-level health -management software system that (1) receives data from performance- monitoring and built-in-test sensors and from other prognostic software and (2) processes the received data to derive a diagnosis and a prognosis for a weapon system. This software relates the diagnostic and prognostic information to the overall health of the system, to the ability of the system to perform specific missions, and to needed maintenance actions and maintenance resources. In the development of the Prognostics Framework, effort was focused primarily on extending previously developed model-based diagnostic-reasoning software to add prognostic reasoning capabilities, including capabilities to perform statistical analyses and to utilize information pertaining to deterioration of parts, failure modes, time sensitivity of measured values, mission criticality, historical data, and trends in measurement data. As thus extended, the software offers an overall health-monitoring capability.

  11. Pathophysiology, presentation, prognosis, and management of intracranial arterial dolichoectasia.

    PubMed

    Pico, Fernando; Labreuche, Julien; Amarenco, Pierre

    2015-08-01

    Up to 12% of patients with stroke have intracranial arterial dolichoectasia (IADE) and the basilar artery is affected in 80% of these cases. Diagnostic criteria and prognosis studies of IADE are based on basilar artery diameter, which is a good quantitative marker for the severity of the disease. The pathophysiology is largely unknown, but IADE can be viewed as a common final pathway of arterial wall response or damage in the tunica media due to various mechanisms, such as matrix metalloproteinase dysfunction or muscle cell or elastic fibre injury. No randomised controlled trials have been undertaken in IADE and thus little high-level evidence is available on which to base treatment guidelines. IADE management depends on clinical presentation and disease severity, and includes blood pressure control, antithrombotic treatments, endovascular procedures, and surgery. Further studies are needed to better define IADE in the general population, to establish its prevalence and pathophysiology, to identify subgroups at risk of life-threatening complications, and to offer effective treatment options.

  12. Presentation and prognosis of shrinking lung syndrome in systemic lupus erythematosus: report of four cases.

    PubMed

    Calderaro, Débora Cerqueira; Ferreira, Gilda Aparecida

    2012-05-01

    Systemic lupus erythematosus is an autoimmune systemic disease that commonly affects the respiratory system. Shrinking lung syndrome is a rare respiratory complication associated with systemic lupus erythematosus. Patients present with dyspnea alone or associated with chest pain and orthopnea, lung volume reduction with no parenchymal abnormalities and a restrictive ventilatory defect on pulmonary function tests. The pathogenesis, treatment, and prognosis of shrinking lung syndrome remain controversial. This study describes the clinical features, investigations, and outcome of a series of four patients with systemic lupus erythematosus and shrinking lung syndrome regularly followed on Rheumatology Service of the Clinics Hospital of the Federal University of Minas Gerais, Brazil, with a brief review of literature. It emphasizes that, despite prognosis of shrinking lung syndrome has been reported as good, it may cause severe functional pulmonary abnormalities and must be treated promptly and aggressively in order to, at least, stabilize pulmonary function tests.

  13. Interventions designed to prevent adverse programming outcomes resulting from exposure to maternal obesity during development

    PubMed Central

    Nathanielsz, PW; Ford, SP; Long, NM; Vega, CC; Reyes-Castro, LA; Zambrano, E

    2013-01-01

    Maternal obesity is a global epidemic affecting the developed and developing world. Human and animal studies indicate that maternal obesity programs development predisposing offspring to later-life chronic diseases. Several mechanisms act together to produce these adverse health problems. There is a need for effective interventions that prevent these outcomes and guide management in human pregnancy. We report here dietary and exercise intervention studies in both altricial and precocial species, rats and sheep, designed to prevent adverse offspring outcomes. Both interventions present exciting opportunities to at least in part prevent adverse metabolic and other outcomes in mother and offspring. PMID:24147928

  14. Adverse events temporally associated with meningococcal vaccines.

    PubMed Central

    Yergeau, A; Alain, L; Pless, R; Robert, Y

    1996-01-01

    OBJECTIVE: To determine the incidence of severe adverse events temporally associated with meningococcal vaccines administered as part of a mass vaccination program. DESIGN: Retrospective descriptive study of events reported to a passive provincial surveillance system. SETTING: The province of Quebec. PARTICIPANTS: The 1,198,751 individuals aged 6 months to 20 years who were vaccinated against meningococcal disease between Dec. 27, 1992, and Mar. 31, 1993. OUTCOME MEASURES: Total numbers and rates of severe adverse events, including allergic reactions, anaphylactic reactions, neurological events (other than abnormal crying and screaming) and other serious or unusual events. RESULTS: A total of 118 reports of severe adverse events were selected from the surveillance system. The most frequent were allergic reactions (9.2 per 100,000 doses). Few anaphylactic or neurologic reactions were reported (0.1 and 0.5 per 100,000 doses respectively). There were no reports of sequelae or of encephalopathy, meningitis or encephalitis. CONCLUSION: Meningococcal vaccines seem to be associated with fewer adverse events than have previously been reported. Existing surveillance programs are useful for determining the incidence of adverse events temporally associated with vaccines. PMID:8630839

  15. Putative adverse outcome pathways relevant to neurotoxicity

    PubMed Central

    Bal-Price, Anna; Crofton, Kevin M.; Sachana, Magdalini; Shafer, Timothy J.; Behl, Mamta; Forsby, Anna; Hargreaves, Alan; Landesmann, Brigitte; Lein, Pamela J.; Louisse, Jochem; Monnet-Tschudi, Florianne; Paini, Alicia; Rolaki, Alexandra; Schrattenholz, André; Suñol, Cristina; van Thriel, Christoph; Whelan, Maurice; Fritsche, Ellen

    2016-01-01

    The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways. PMID:25605028

  16. The Complement System and Adverse Pregnancy Outcomes

    PubMed Central

    Regal, Jean F.; Gilbert, Jeffrey S.; Burwick, Richard M.

    2015-01-01

    Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the feta allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child. PMID:25802092

  17. Is It Adverse, Nonadverse, Adaptive, or Artifact?

    PubMed

    Pandiri, Arun R; Kerlin, Roy L; Mann, Peter C; Everds, Nancy E; Sharma, Alok K; Myers, L Peyton; Steinbach, Thomas J

    2017-01-01

    One of the principal challenges facing a toxicologic pathologist is to determine and differentiate a true adverse effect from a nonadverse or an adaptive response. Recent publications from the Society of Toxicologic Pathology (STP) and the European STP provide guidance for determining and communicating adversity in nonclinical toxicology studies. In order to provide a forum to inform and engage in a discussion on this important topic, a continuing education (CE) course was held during the 2016 STP Annual meeting in San Diego, CA. The lectures at this course provided guidance on determining and communicating adversity using case studies involving both clinical pathology and anatomic pathology. In addition, one talk also focused on data quality, study design, and interpretation of artifacts that could hinder the determination of adversity. The CE course ended with a talk on understanding adversity in preclinical studies and engaging the regulatory agencies in the decision-making process. This manuscript is designed to provide brief summaries of all the talks in this well-received CE course.

  18. Environmental adversity and uncertainty favour cooperation

    PubMed Central

    Andras, Peter; Lazarus, John; Roberts, Gilbert

    2007-01-01

    Background A major cornerstone of evolutionary biology theory is the explanation of the emergence of cooperation in communities of selfish individuals. There is an unexplained tendency in the plant and animal world – with examples from alpine plants, worms, fish, mole-rats, monkeys and humans – for cooperation to flourish where the environment is more adverse (harsher) or more unpredictable. Results Using mathematical arguments and computer simulations we show that in more adverse environments individuals perceive their resources to be more unpredictable, and that this unpredictability favours cooperation. First we show analytically that in a more adverse environment the individual experiences greater perceived uncertainty. Second we show through a simulation study that more perceived uncertainty implies higher level of cooperation in communities of selfish individuals. Conclusion This study captures the essential features of the natural examples: the positive impact of resource adversity or uncertainty on cooperation. These newly discovered connections between environmental adversity, uncertainty and cooperation help to explain the emergence and evolution of cooperation in animal and human societies. PMID:18053138

  19. Pharmacogenomics of statins: understanding susceptibility to adverse effects

    PubMed Central

    Kitzmiller, Joseph P; Mikulik, Eduard B; Dauki, Anees M; Murkherjee, Chandrama; Luzum, Jasmine A

    2016-01-01

    Statins are a cornerstone of the pharmacologic treatment and prevention of atherosclerotic cardiovascular disease. Atherosclerotic disease is a predominant cause of mortality and morbidity worldwide. Statins are among the most commonly prescribed classes of medications, and their prescribing indications and target patient populations have been significantly expanded in the official guidelines recently published by the American and European expert panels. Adverse effects of statin pharmacotherapy, however, result in significant cost and morbidity and can lead to nonadherence and discontinuation of therapy. Statin-associated muscle symptoms occur in ~10% of patients on statins and constitute the most commonly reported adverse effect associated with statin pharmacotherapy. Substantial clinical and nonclinical research effort has been dedicated to determining whether genetics can provide meaningful insight regarding an individual patient’s risk of statin adverse effects. This contemporary review of the relevant clinical research on polymorphisms in several key genes that affect statin pharmacokinetics (eg, transporters and metabolizing enzymes), statin efficacy (eg, drug targets and pathways), and end-organ toxicity (eg, myopathy pathways) highlights several promising pharmacogenomic candidates. However, SLCO1B1 521C is currently the only clinically relevant pharmacogenetic test regarding statin toxicity, and its relevance is limited to simvastatin myopathy. PMID:27757045

  20. Adverse Family Experiences during Childhood and Adolescent Obesity

    PubMed Central

    Heerman, William J.; Krishnaswami, Shanthi; Barkin, Shari L.; McPheeters, Melissa

    2015-01-01

    Objective To evaluate the association between adverse family experiences (AFEs) during childhood and adolescent obesity and to determine populations at highest risk for adverse family experiences. Methods Cross sectional analysis of the 2011-2012 National Survey of Children’s Health, including children ages 10-17. Weighted estimates of 31,258,575 children were based on interviews with 42,239 caregivers. Caregiver-report of 9 psychosocial risk factors measured AFEs during childhood. Adolescent overweight and obesity were derived by caregiver-report of child height and weight. Results Nearly one-third (30.5%) of children had experienced ≥2 AFEs, with geographic variation by state. The prevalence of obesity among children experiencing ≥2 AFEs was 20.4%, compared with 12.5% among children with 0 AFEs. Adjusted survey regression models controlled for child, parent, household, and neighborhood characteristics. Children with ≥ 2 AFEs in childhood were more likely to be obese (AOR 1.8; 95% CI 1.47, 2.17; p<0.001) than those with no AFEs, with Non-Hispanic, White children most affected. Conclusions Adolescents in this national sample who were exposed to greater numbers of adverse family experiences in childhood also had higher rates of overweight and obesity. Geographic variation and differential associations based on race/ethnicity identify children at greatest risk. PMID:26853526

  1. Adverse health consequences of the Iraq War.

    PubMed

    Levy, Barry S; Sidel, Victor W

    2013-03-16

    The adverse health consequences of the Iraq War (2003-11) were profound. We conclude that at least 116,903 Iraqi non-combatants and more than 4800 coalition military personnel died over the 8-year course. Many Iraqi civilians were injured or became ill because of damage to the health-supporting infrastructure of the country, and about 5 million were displaced. More than 31,000 US military personnel were injured and a substantial percentage of those deployed suffered post-traumatic stress disorder, traumatic brain injury, and other neuropsychological disorders and their concomitant psychosocial problems. Many family members of military personnel had psychological problems. Further review of the adverse health consequences of this war could help to minimise the adverse health consequences of, and help to prevent, future wars.

  2. Standardizing drug adverse event reporting data.

    PubMed

    Wang, Liwei; Jiang, Guoqian; Li, Dingcheng; Liu, Hongfang

    2013-01-01

    Normalizing data in the Adverse Event Reporting System (AERS), an FDA database, would improve the mining capacity of AERS for drug safety signal detection. In this study, we aim to normalize AERS and build a publicly available normalized Adverse drug events (ADE) data source.he drug information in AERS is normalized to RxNorm, a standard terminology source for medication. Drug class information is then obtained from the National Drug File - Reference Terminology (NDF-RT). Adverse drug events (ADE) are aggregated through mapping with the PT (Preferred Term) and SOC (System Organ Class) codes of MedDRA. Our study yields an aggregated knowledge-enhanced AERS data mining set (AERS-DM). The AERS-DM could provide more perspectives to mine AERS database for drug safety signal detection and could be used by research community in the data mining field.

  3. Adverse perinatal events associated with ART.

    PubMed

    Skora, Daniel; Frankfurter, David

    2012-04-01

    Since the advent of ART, much research has focused on the potential adverse for resultant harm. Prematurity, low birth-weight, PIH, congenital malformations, and CP are closely tied to multiple gestation. With the increase in elective single embryo transfer, there will be a reduction in adversity related to multiple birth. It is understood that underlying causes of infertility, including advanced maternal age, PCOS, thyroid disease, and uterine fibroids, predispose to adverse outcomes. However, imprinting abnormalities do not appear to stem from multiple births, and thus the need to consider the association between fertility treatment and methylation disorders remains essential. These, as well as risks of multi-fetal gestation, must be discussed with patients when considering using assisted reproduction.

  4. ICOS is associated with poor prognosis in breast cancer as it promotes the amplification of immunosuppressive CD4+ T cells by plasmacytoid dendritic cells

    PubMed Central

    Faget, Julien; Sisirak, Vanja; Blay, Jean-Yves; Caux, Christophe; Bendriss-Vermare, Nathalie; Ménétrier-Caux, Christine

    2013-01-01

    Regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) that infiltrate primary breast tumors impair patient survival. The ICOS-mediated interaction between tumor-infiltrating CD4+ T cells and pDCs leads to the amplification of Tregs and interleukin-10 secretion. Importantly, ICOS+ cell infiltration correlates with adverse patient prognosis, identifying ICOS as a new target for cancer immunotherapy. PMID:23802069

  5. Loneliness, eudaimonia, and the human conserved transcriptional response to adversity

    PubMed Central

    Cole, Steven W.; Levine, Morgan E.; Arevalo, Jesusa M. G.; Ma, Jeffrey; Weir, David R.; Crimmins, Eileen M.

    2015-01-01

    Background Chronic social adversity activates a conserved transcriptional response to adversity (CTRA) marked by increased expression of pro-inflammatory genes and decreased expression of antiviral- and antibody-related genes. Recent findings suggest that some psychological resilience factors may help buffer CTRA activation, but the relative impact of resilience and adversity factors remains poorly understood. Here we examined the relative strength of CTRA association for the two best-established psychological correlates of CTRA gene expression – the risk factor of perceived social isolation (loneliness) and the resilience factor of eudaimonic well-being (purpose and meaning in life). Methods Peripheral blood samples and validated measures of loneliness and eudaimonic well-being were analyzed in 108 community-dwelling older adults participating in the longitudinal US Health and Retirement Study (56% female, mean age 73). Mixed effect linear model analyses quantified the strength of association between CTRA gene expression and measures of loneliness and eudaimonic well-being in separate and joint analyses. Results As in previous studies, separate analyses found CTRA gene expression to be up-regulated in association with loneliness and down-regulated in association with eudaimonic well-being. In joint analyses, effects of loneliness were completely abrogated whereas eudaimonic well-being continued to associate with CTRA down-regulation. Similar eudaimonia-dominant effects were observed for positive and negative affect, optimism and pessimism, and anxiety symptoms. All results were independent of demographic and behavioral health risk factors. Conclusions Eudaimonic well-being may have the potential to compensate for the adverse impact of loneliness on CTRA gene expression. Findings suggest a novel approach to targeting the health risks associated with social isolation by promoting purpose and meaning in life. PMID:26246388

  6. Adrenocortical carcinoma (ACC): diagnosis, prognosis, and treatment

    PubMed Central

    Libé, Rossella

    2015-01-01

    Adrenocortical carticnoma (ACC) is a rare malignancy with an incidence of 0.7–2.0 cases/million habitants/year. The diagnosis of malignancy relies on careful investigations of clinical, biological, and imaging features before surgery and pathological examination after tumor removal. Most patients present with steroid hormone excess or abdominal mass effects, but 15% of patients with ACC is initially diagnosed incidentally. After the diagnosis, in order to assess the ACC prognosis and establish an adequate basis for treatment decisions different tools are proposed. The stage classification proposed by the European Network for the Study of Adrenal Tumors (ENSAT) is recommended. Pathology reports define the Weiss score, the resection status and the proliferative index, including the mitotic count and the Ki67 index. As far as the treatment is concerned, in case of tumor limited to the adrenal gland, the complete resection of the tumor is the first option. Most patients benefit from adjuvant mitotane treatment. In metastatic disease, mitotane is the cornerstone of initial treatment, and cytotoxic drugs should be added in case of progression. Recently, the First International Randomized (FIRM-ACT) Trial in metastatic ACC reported the association between mitotane and etoposide/doxorubicin/cisplatin (EDP) as the new standard in first line treatment of ACC. In last years, new targeted therapies, including the IGF-1 receptor inhibitors, have been investigated, but their efficacy remains limited. Thus, new treatment concepts are urgently needed. The ongoing “omic approaches” and next-generation sequencing will improve our understanding of the pathogenesis and hopefully will lead to better therapies. PMID:26191527

  7. Novel predictive biomarkers for cervical cancer prognosis

    PubMed Central

    Moreno-Acosta, Pablo; Carrillo, Schyrly; Gamboa, Oscar; Romero-Rojas, Alfredo; Acosta, Jinneth; Molano, Monica; Balart-Serra, Joseph; Cotes, Martha; Rancoule, Chloé; Magné, Nicolas

    2016-01-01

    High hypoxic, glycolytic and acidosis metabolisms characterize cervical cancer tumors and have been described to be involved in chemoradioresistance mechanisms. Based on these observations, the present study assessed four selected novel biomarkers on the prognosis of locally advanced cervical carcinoma. A total of 66 patients with stage IIB/IIIB cervical cancer were retrospectively included. The protein expression levels of glucose transporter 1 (GLUT1), carbonic anhydrase 9 (CAIX) and hexokinase 1 (HKII) were investigated by immunohistochemistry on tumor biopsies, hemoglobin was measured and the disease outcome was monitored. A total of 53 patients (80.3%) presented a complete response. For these patients, the protein expression levels of GLUT1, CAIX and HKII were overexpressed. A significant difference was observed (P=0.0127) for hemoglobin levels (≤11 g/dl) in responsive compared with non-responsive patients. The expression of GLUT1 is associated with a lower rate of both overall and disease-free survival, with a trend of decreased risk of 1.1x and 1.5x, respectively. Co-expression of GLUT1 and HKII is associated with a decreased trend risk of 1.6x for overall survival. Patients with hemoglobin levels ≤11 g/dl had a 4.3-fold risk (P=0.02) in decreasing both to the rate of overall and disease-free survival. The presence of anemic hypoxia (hemoglobin ≤11 g/dl) and the expression of GLUT1 and/or HKII influence treatment response and are associated with a lower overall and disease-free survival. The present results demonstrated that these biomarkers may be used as predictive markers and suggested that these metabolic pathways can be used as potential novel therapeutic targets. PMID:28101358

  8. Survival Prognosis in Very Old Adults

    PubMed Central

    Thinggaard, Mikael; McGue, Matt; Jeune, Bernard; Osler, Merete; Vaupel, James W.; Christensen, Kaare

    2016-01-01

    OBJECTIVES To determine whether simple functional indicators are predictors of survival prognosis in very old adults. DESIGN In-person survey conducted over a 3-month period in 1998; assessment of survival over a 15-year follow-up period. SETTING Denmark. PARTICIPANTS All 3,600 Danes born in 1905 and living in Denmark in 1998, were invited to participate regardless of residence and health; 2,262 (63%) participated in the survey: 1,814 (80.2%) in person and 448 (19.8%) through a proxy. MEASUREMENTS Socioeconomic factors, medications and diseases, activities of daily living, physical performance, cognition, depression symptomatology, self-rated health, and all-cause mortality, evaluated as average remaining lifespan and chance of surviving to 100 years. RESULTS Men aged 92 to 93 had an overall 6.0% chance of surviving to 100 years, whereas the chance for women was 11.4%. Being able to rise without use of hands increased the chance for men to 11.2% (95% confidence interval (CI) = 7.7–14.7) and for women to 22.0% (95% CI = 18.9–25.1). When combining this with a Mini-Mental State Examination (MMSE) scores from 28 to 30, the chances were 21.7% (95% CI = 11.5–31.9) for men and 34.2% (95% CI = 24.8–43.5) for women. CONCLUSION Chair stand score combined with MMSE score is a quick and easy way to estimate overall chance of survival in very old adults, which is particularly relevant when treatment with potential side effects for nonacute diseases is considered. J Am Geriatr Soc 64:81–88, 2016. PMID:26782855

  9. [Epidemiology and prognosis of heart failure].

    PubMed

    Edelmann, F

    2015-04-01

    Heart failure (HF) is a major and growing health problem in western communities. Recent data indicate that more than 50% of patients with the clinical syndrome of HF have a preserved left ventricular ejection fraction (HF with preserved ejection fraction, HFpEF). In contrast to the calculated expectations, the observed incidence of HF is rising. Despite the fact that the relative proportion of patients with preserved left ventricular function is also increasing, other factors, such as ageing of the population and the concomitant change of compound risk factors may also contribute to the actual rise in the incidence of HF. Patients with HF suffer from reduced exercise capacity, impaired quality of life and also from recurrent hospitalization due to HF. Over the past decades, an increase of recurrent HF events has been documented. In contrast to earlier reports in which HFpEF was considered to be more benign than HF with reduced ejection fraction (HFrEF), recent data suggest that once hospitalized for HF, patients with HFpEF and those with HFrEF have a comparable prognosis in terms of morbidity and mortality. Despite increasing clinical and economic relevance, no treatment has yet been shown to convincingly reduce mortality in HFpEF. In contrast, strategies for improving survival have now been established for HFrEF. The problem of HF will continue to be major challenge for the healthcare systems in western communities; therefore, consolidated clinical research is necessary to further improve therapeutic strategies for HFrEF and to generally establish treatment options for HFpEF.

  10. Repolarization Heterogeneity of Magnetocardiography Predicts Long-Term Prognosis in Patients with Acute Myocardial Infarction

    PubMed Central

    Bang, Woo-Dae; Kim, Kiwoong; Lee, Yong-Ho; Kwon, Hyukchan; Park, Yongki; Pak, Hui-Nam; Ko, Young-Guk; Lee, Moonhyoung

    2016-01-01

    Purpose Magnetocardiography (MCG) has been proposed as a noninvasive, diagnostic tool for risk-stratifying patients with acute myocardial infarction (AMI). This study evaluated whether MCG predicts long-term prognosis in AMI. Materials and Methods In 124 AMI patients (95 males, mean age 60±11 years), including 39 with ST-elevation myocardial infarction, a 64-channel MCG was performed within 2 days after AMI. During a mean follow-up period of 6.1 years, major adverse cardiac events (MACE) were evaluated. Results MACE occurred in 31 (25%) patients, including 20 revascularizations, 8 deaths, and 3 re-infarctions. Non-dipole patterns were observed at the end of the T wave in every patients. However, they were observed at T-peak in 77% (24/31) and 54% (50/93) of patients with and without MACE, respectively (p=0.03). Maximum current, field map angles, and distance dynamics were not different between groups. In the multivariate analysis, patients with non-dipole patterns at T-peak had increased age- and gender-adjusted hazard ratios for MACE (hazard ratio 2.89, 95% confidence interval 1.20–6.97, p=0.02) and lower cumulative MACE-free survival than those with dipole patterns (p=0.02). Conclusion Non-dipole patterns at T-peak were more frequently observed in patients with MACE and were related to poor long-term prognosis. Thus, repolarization heterogeneity measured by MCG may be a useful predictor for AMI prognosis. PMID:27593860

  11. Deregulation of COMMD1 Is Associated with Poor Prognosis in Diffuse Large B-cell Lymphoma

    PubMed Central

    Taskinen, Minna; Louhimo, Riku; Koivula, Satu; Chen, Ping; Rantanen, Ville; Holte, Harald; Delabie, Jan; Karjalainen-Lindsberg, Marja-Liisa; Björkholm, Magnus; Fluge, Øystein; Pedersen, Lars Møller; Fjordén, Karin; Jerkeman, Mats; Eriksson, Mikael; Hautaniemi, Sampsa; Leppä, Sirpa

    2014-01-01

    Background Despite improved survival for the patients with diffuse large B-cell lymphoma (DLBCL), the prognosis after relapse is poor. The aim was to identify molecular events that contribute to relapse and treatment resistance in DLBCL. Methods We analysed 51 prospectively collected pretreatment tumour samples from clinically high risk patients treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis with high resolution array comparative genomic hybridization (aCGH) and gene expression microarrays. Major finding was validated at the protein level immunohistochemically in a trial specific tissue microarray series of 70, and in an independent validation series of 146 patients. Results We identified 31 genes whose expression changes were strongly associated with copy number aberrations. In addition, gains of chromosomes 2p15 and 18q12.2 were associated with unfavourable survival. The 2p15 aberration harboured COMMD1 gene, whose expression had a significant adverse prognostic impact on survival. Immunohistochemical analysis of COMMD1 expression in two series confirmed the association of COMMD1 expression with poor prognosis. Conclusion COMMD1 is a potential novel prognostic factor in DLBCLs. The results highlight the value of integrated comprehensive analysis to identify prognostic markers and genetic driver events not previously implicated in DLBCL. Trial Registration ClinicalTrials.gov NCT01502982 PMID:24625556

  12. CD147/EMMPRIN overexpression and prognosis in cancer: A systematic review and meta-analysis

    PubMed Central

    Xin, Xiaoyan; Zeng, Xianqin; Gu, Huajian; Li, Min; Tan, Huaming; Jin, Zhishan; Hua, Teng; Shi, Rui; Wang, Hongbo

    2016-01-01

    CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) plays an important role in tumor progression and a number of studies have suggested that it is an indicator of tumor prognosis. This current meta-analysis systematically reevaluated the predictive potential of CD147/EMMPRIN in various cancers. We searched PubMed and Embase databases to screen the literature. Fixed-effect and random-effect meta-analytical techniques were used to correlate CD147 expression with outcome measures. A total of 53 studies that included 68 datasets were eligible for inclusion in the final analysis. We found a significant association between CD147/EMMPRIN overexpression and adverse tumor outcomes, such as overall survival, disease-specific survival, progression-free survival, metastasis-free survival or recurrence-free survival, irrespective of the model analysis. In addition, CD147/EMMPRIN overexpression predicted a high risk for chemotherapy drugs resistance. CD147/EMMPRIN is a central player in tumor progression and predicts a poor prognosis, including in patients who have received chemo-radiotherapy. Our results provide the evidence that CD147/EMMPRIN could be a potential therapeutic target for cancers. PMID:27608940

  13. Adverse Reactions Due to Directly Observed Treatment Strategy Therapy in Chinese Tuberculosis Patients: A Prospective Study

    PubMed Central

    Lv, Xiaozhen; Tang, Shaowen; Xia, Yinyin; Wang, Xiaomeng; Yuan, Yanli; Hu, Daiyu; Liu, Feiying; Wu, Shanshan; Zhang, Yuan; Yang, Zhirong; Tu, Dehua; Chen, Yixin; Deng, Peiyuan; Ma, Yu; Chen, Ru; Zhan, Siyan

    2013-01-01

    Background More than 1 million tuberculosis (TB) patients are receiving directly observed treatment strategy (DOTS) therapy in China every year. As to the profile of adverse drug reactions (ADRs) due to DOTS therapy, no consensus has been reached. There is no report regarding ADRs due to DOTS therapy with a large Chinese TB population. This study aimed to determine the incidence and prognosis of ADRs due to DOTS therapy, and to evaluate their impact on anti-TB treatment in China. Methods A prospective population-based cohort study was performed during 2007–2008. Sputum smear positive pulmonary TB patients who received DOTS therapy were included and followed up for six to nine months in 52 counties of four regions in China. The suspected ADRs were recorded and reviewed by Chinese State Food and Drug Administration. Results A total of 4304 TB patients were included in this study. 649 patients (15.08%) showed at least one ADR and 766 cases in total were detected. The incidence (count) of ADR based on affected organ was: liver dysfunction 6.34% (273), gastrointestinal disorders 3.74% (161), arthralgia 2.51% (108), allergic reactions 2.35% (101), neurological system disorders 2.04% (88), renal impairment 0.07% (3) and others 0.05% (2). Most cases of ADRs (95%) had a good clinical outcome, while two with hepatotoxicity and one with renal impairment died. Compared with patients without ADRs, patients with ADRs were more likely to have positive smear test results at the end of the intensive phase (adjusted OR, 2.00; 95%CI, 1.44–2.78) and unsuccessful anti-TB outcomes (adjusted OR, 2.58; 95%CI, 1.43–4.68). Conclusions The incidence of ADRs due to DOTS therapy was 15.08%. Those ADRs had a substantial impact on TB control in China. This highlighted the importance of developing strategies to ameliorate ADRs both to improve the quality of patient care and to control TB safely. PMID:23750225

  14. Enduring psychobiological effects of childhood adversity.

    PubMed

    Ehlert, Ulrike

    2013-09-01

    This mini-review refers to recent findings on psychobiological long-term consequences of childhood trauma and adverse living conditions. The continuum of trauma-provoked aftermath reaches from healthy adaptation with high resilience, to severe maladjustment with co-occurring psychiatric and physical pathologies in children, adolescents and adults. There is increasing evidence of a strong interconnectivity between genetic dispositions, epigenetic processes, stress-related hormonal systems and immune parameters in all forms of (mal)-adjustment to adverse living conditions. Unfavorable constellations of these dispositions and systems, such as low cortisol levels and elevated markers of inflammation in maltreated children, seem to promote the (co)-occurrence of psychiatric and physical pathologies such as posttraumatic stress disorder, obesity, or diabetes. Although findings from prospective study designs support a deepened understanding of causal relations between adverse living conditions, including traumatic experiences, during childhood and its psychobiological effects, so far, little is known about the temporal coincidence of stress-sensitive developmental stages during childhood and adolescence and trauma consequences. Taken together, childhood adversity is a severe risk factor for the onset of psychobiological (mal)-adjustment, which has to be explained under consideration of diverse physiological systems and developmental stages of childhood and adolescence.

  15. Reducing Adverse Impact: One City's Efforts.

    ERIC Educational Resources Information Center

    Prewitt, Jeff

    Following a workshop on "Innovations in Employment Testing that Improve Validity and Reduce Adverse Impact," the City of Louisville (Kentucky) implemented a strategy to develop a comprehensive testing and recruiting program for police recruits. To improve candidate expectations and preparation, the following activities were undertaken:…

  16. Educational Leadership: The Uses of Adversity

    ERIC Educational Resources Information Center

    Culbertson, Jack

    1976-01-01

    Skepticism about the power of education challenges the educational administrator to (1) attain a better understanding of the sources of dissatisfaction and their implications for change, (2) learn to cope with adversity and make constructive use of it, and (3) define the leadership requirements needed to address education's problems. (MB)

  17. The adverse outcome pathway knowledge base

    EPA Science Inventory

    The rapid advancement of the Adverse Outcome Pathway (AOP) framework has been paralleled by the development of tools to store, analyse, and explore AOPs. The AOP Knowledge Base (AOP-KB) project has brought three independently developed platforms (Effectopedia, AOP-Wiki, and AOP-X...

  18. Clinical spectrum of adverse reactions to tartrazine.

    PubMed

    Collins-Williams, C

    1985-01-01

    Tartrazine, a common additive in foods and drugs, often causes adverse reactions such as recurrent urticaria, angioedema, and asthma and is frequently implicated in hyperkinesis. This paper summarizes the recent literature on the subject and outlines a practical approach for the practicing physician to diagnose and treat these patients in an optimal manner.

  19. The Public Health Burden of Early Adversity

    ERIC Educational Resources Information Center

    Schlueter, Lisa J.; Watamura, Sarah Enos

    2017-01-01

    Severe and chronic stress in early childhood has enormous physical and mental health costs across an individual's lifespan. Unfortunately, exposure to early life adversity is common, and costs accrue to individuals and society. This article highlights several promising approaches to buffer children from the negative health consequences associated…

  20. [Analysis of Spontaneously Reported Adverse Events].

    PubMed

    Nakamura, Mitsuhiro

    2016-01-01

    Observational study is necessary for the evaluation of drug effectiveness in clinical practice. In recent years, the use of spontaneous reporting systems (SRS) for adverse drug reactions has increased and they have become an important resource for regulatory science. SRS, being the largest and most well-known databases worldwide, are one of the primary tools used for postmarketing surveillance and pharmacovigilance. To analyze SRS, the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report Database (JADER) are reviewed. Authorized pharmacovigilance algorithms were used for signal detection, including the reporting odds ratio. An SRS is a passive reporting database and is therefore subject to numerous sources of selection bias, including overreporting, underreporting, and a lack of a denominator. Despite the inherent limitations of spontaneous reporting, SRS databases are a rich resource and data mining index that provide powerful means of identifying potential associations between drugs and their adverse effects. Our results, which are based on the evaluation of SRS databases, provide essential knowledge that could improve our understanding of clinical issues.

  1. Adverse skin reactions following intravitreal bevacizumab injection

    PubMed Central

    Ameen, S; Entabi, M; Lee, N; Stavrakoglou, A

    2011-01-01

    The authors describe two separate cases of skin eruption following intravitreal bevacizumab injection with evidence to suggest that these were adverse drug reactions to bevacizumab. The authors also discuss how each case was treated and report on the final outcome. PMID:22715260

  2. Due Process in Adverse Personnel Action.

    ERIC Educational Resources Information Center

    Scriven, Michael

    1997-01-01

    A detailed checklist and timeline for ensuring due process are provided for adverse personnel actions, and the need to supplement this with expert, same-jurisdiction legal advice is stressed. This approach emphasizes the importance of treating due process as an ethical as well as a legal requirement. (SLD)

  3. Adverse outcome pathway (AOP) development and evaluation

    EPA Science Inventory

    The Adverse Outcome Pathway provides a construct for assembling mechanistic information at different levels of biological organization in a form designed to support regulatory decision making. In particular, it frames the link between molecular and cellular events that can be mea...

  4. [Laser trabeculoplasty: therapeutic options and adverse effects].

    PubMed

    Wacker, T; Eckert, S

    2010-01-01

    Laser trabeculoplasty is a simple method for treating glaucoma and ocular hypertension and has few adverse effects. There are different laser systems for reducing the intraocular pressure of patients with glaucoma and ocular hypertension. Complications include transient intraocular pressure elevation, iritis, and anterior synechiae.

  5. Resilience in the Face of Adversity.

    ERIC Educational Resources Information Center

    Patterson, Jerry

    2001-01-01

    "Resilience" is the capacity for moving ahead under adverse circumstances. School superintendents are advised to stay upbeat and mindful of "both-and" opportunities; stay focused on what they care about; remain flexible and tolerant of ambiguity; be proactive, not reactive; and apply resilience-conserving strategies during…

  6. Integrated analysis of multidimensional omics data on cutaneous melanoma prognosis.

    PubMed

    Jiang, Yu; Shi, Xingjie; Zhao, Qing; Krauthammer, Michael; Rothberg, Bonnie E Gould; Ma, Shuangge

    2016-06-01

    Multiple types of genetic, epigenetic, and genomic changes have been implicated in cutaneous melanoma prognosis. Many of the existing studies are limited in analyzing a single type of omics measurement and cannot comprehensively describe the biological processes underlying prognosis. As a result, the obtained prognostic models may be less satisfactory, and the identified prognostic markers may be less informative. The recently collected TCGA (The Cancer Genome Atlas) data have a high quality and comprehensive omics measurements, making it possible to more comprehensively and more accurately model prognosis. In this study, we first describe the statistical approaches that can integrate multiple types of omics measurements with the assistance of variable selection and dimension reduction techniques. Data analysis suggests that, for cutaneous melanoma, integrating multiple types of measurements leads to prognostic models with an improved prediction performance. Informative individual markers and pathways are identified, which can provide valuable insights into melanoma prognosis.

  7. [Testing the automobile driver in cases of uncertain qualification prognosis].

    PubMed

    Bode, H J

    1989-05-01

    The qualification of a person to drive a motor vehicle is the presupposition for the required permission. The prognosis on future human behaviour, which is indispensible for a judgement on such a qualification, is difficult. Only in a few of these cases a clear "good"-prognosis or "bad"-prognosis can be found out. Frequently only an "uncertain"-prognosis is to be justified as a matter of fact. It is only to be said by the regulations of law, whether in cases of uncertain qualification prognosis the driver's licence should be given or denied or whether a driver's licence already given should be withdrawn or not. Starting points for theory and dogmatics on prognosis-decisions due to law and orientated in the knowledge of empiric sciences are to be found in administrative law as well as in criminal law. For example: penal regulations which call for prognosis should be interpreted in the manner that as a sanction (only to be imposed in cases of "bad"-prognosis) the milder measure is to be used at first. Only after an unsuccessful attempt with this milder measure it is allowed to take a more incisive measure (Frisch). In planning law the dilemma with prognosis should be overcome by reflexive feedback within the scope of a new type of procedural law, which would make a process of learning and evaluation possible and enforcable. From these starting points common legal principles on a "test-method" can be developed, which may be used in cases of "uncertain"-prognosis. Such a test-method may help for example to decide on execution relaxations due to the Law on Execution of the Sentence (OLG Celle). The decree on driver's licences on probation (valid since 1.11.1986) contains the most extensive regulations concerning the application of test-methods within driver's licences law. The solution of the problem shown there should be extended: Not only the first driver's licence should only be given on probation but also a renewed one. Even motorists coming conspicuous after the

  8. Adverse events of intravenous immunoglobulin infusions: a ten-year retrospective study

    PubMed Central

    Kwong, Shirley L.; Padua, Florecita R.

    2013-01-01

    Background Intravenous immunoglobulin (IVIG) is a biological product with adverse effects that appears to vary considerably among different IVIG preparations. Objectives To describe the adverse events of patients given intravenous immunoglobulin infusions. Method Data was collected on all patients receiving IVIG infusion at a tertiary hospital from January 2001 to December 2010. Descriptive statistics was used. Results 77 patients (45 males, 32 females) received IVIG infusions. Thirty two percent (n = 25) experienced adverse reactions. The most common indication was Kawasaki disease (85.7%) followed by immunodeficiency disorders (7.8%). Majority of the patients were children, with the highest frequency of infusions among those aged 2 to 8 years old (52%). 36 infusions were associated with occurrence of adverse effects. Fever was the most common adverse event (n = 11, 30.6%), followed by rash (n = 8, 22.2%) and chills (n = 7, 19.4%). Other adverse events were cyanosis (n = 3, 8.3%), hypotension (n = 2, 5.6%), hypothermia (n = 2, 5.6%), irritability (n = 1, 2.8%), vomiting (n = 1, 2.8%), and chest pain (n = 1, 2.8%). Adverse events were observed to occur most frequently within 1 to 6 h from onset of IVIG infusion. Among the various IVIG preparations available locally (Gammagard, Kiovig, Gamimune, Veno-S & IV Globulin S), Gammagard was the brand frequently used (50.7%). It also has the most number of adverse events, with 17 out of 41 (41.5%) infusions resulting in adverse reactions. Most of the reactions occurred with fast infusion rates, and clinical manifestations subsided when the rate of infusion was reduced. Conclusion In this study, thirty two percent of patients given IVIG infusions experienced adverse events. Fever was the most common manifestation. Symptoms occurred within 1 to 6 h from onset of infusion, were affected by fast infusion rates, and managed by reducing the rate of infusion. PMID:24260730

  9. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  10. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  11. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  12. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  13. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  14. Data Requirements for Model-Based Cancer Prognosis Prediction

    PubMed Central

    Dalton, Lori A.; Yousefi, Mohammadmahdi R.

    2015-01-01

    Cancer prognosis prediction is typically carried out without integrating scientific knowledge available on genomic pathways, the effect of drugs on cell dynamics, or modeling mutations in the population. Recent work addresses some of these problems by formulating an uncertainty class of Boolean regulatory models for abnormal gene regulation, assigning prognosis scores to each network based on intervention outcomes, and partitioning networks in the uncertainty class into prognosis classes based on these scores. For a new patient, the probability distribution of the prognosis class was evaluated using optimal Bayesian classification, given patient data. It was assumed that (1) disease is the result of several mutations of a known healthy network and that these mutations and their probability distribution in the population are known and (2) only a single snapshot of the patient’s gene activity profile is observed. It was shown that, even in ideal settings where cancer in the population and the effect of a drug are fully modeled, a single static measurement is typically not sufficient. Here, we study what measurements are sufficient to predict prognosis. In particular, we relax assumption (1) by addressing how population data may be used to estimate network probabilities, and extend assumption (2) to include static and time-series measurements of both population and patient data. Furthermore, we extend the prediction of prognosis classes to optimal Bayesian regression of prognosis metrics. Even when time-series data is preferable to infer a stochastic dynamical network, we show that static data can be superior for prognosis prediction when constrained to small samples. Furthermore, although population data is helpful, performance is not sensitive to inaccuracies in the estimated network probabilities. PMID:27127404

  15. Factors predicting poor prognosis in ischemic colitis

    PubMed Central

    Añón, Ramón; Boscá, Marta Maia; Sanchiz, Vicente; Tosca, Joan; Almela, Pedro; Amorós, Cirilo; Benages, Adolfo

    2006-01-01

    ). Stenosis was the only endoscopic finding that appeared more frequently in seriously ill patients than in slightly ill patients (66.6% vs 17.3%, P = 0.017). CONCLUSION: The factors that can predict poor prognosis of IC are the absence of hematochezia, tachycardia and peritonism, anemia and hyponatremia and stenosis. PMID:16937472

  16. Determining prognosis in acute exacerbation of COPD

    PubMed Central

    Flattet, Yves; Garin, Nicolas; Serratrice, Jacques; Perrier, Arnaud; Stirnemann, Jérome; Carballo, Sebastian

    2017-01-01

    Background Acute exacerbations are the leading causes of hospitalization and mortality in patients with COPD. Prognostic tools for patients with chronic COPD exist, but there are scarce data regarding acute exacerbations. We aimed to identify the prognostic factors of death and readmission after exacerbation of COPD. Methods This was a retrospective study conducted in the Department of Internal Medicine of Geneva University Hospitals. All patients admitted to the hospital with a diagnosis of exacerbation of COPD between 2008 and 2011 were included. The studied variables included comorbidities, Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity classification, and biological and clinical parameters. The main outcome was death or readmission during a 5-year follow-up. The secondary outcome was death. Survival analysis was performed (log-rank and Cox). Results We identified a total of 359 patients (195 men and 164 women, average age 72 years). During 5-year follow-up, 242 patients died or were hospitalized for the exacerbation of COPD. In multivariate analysis, age (hazard ratio [HR] 1.03, 95% CI 1.02–1.05; P<0.0001), severity of airflow obstruction (forced expiratory volume in 1 s <30%; HR 4.65, 95% CI 1.42–15.1; P=0.01), diabetes (HR 1.47, 95% CI 1.003–2.16; P=0.048), cancer (HR 2.79, 95% CI 1.68–4.64; P<0.0001), creatinine (HR 1.003, 95% CI 1.0004–1.006; P=0.02), and respiratory rate (HR 1.03, 95% CI 1.003–1.05; P=0.028) on admission were significantly associated with the primary outcome. Age, cancer, and procalcitonin were significantly associated with the secondary outcome. Conclusion COPD remains of ominous prognosis, especially after exacerbation requiring hospitalization. Baseline pulmonary function remains the strongest predictor of mortality and new admission. Demographic factors, such as age and comorbidities and notably diabetes and cancer, are closely associated with the outcome of the patient. Respiratory rate at admission

  17. TP53 dysfunction in CLL: Implications for prognosis and treatment.

    PubMed

    Te Raa, Gera D; Kater, Arnon P

    2016-03-01

    Despite the availability of novel targeted agents, TP53 defects remain the most important adverse prognostic factor in chronic lymphocytic leukemia (CLL). Detection of deletion of TP53 locus (17p deletion) by fluorescent in situ hybridization (FISH) has become standard and performed prior to every line of treatment as the incidence dramatically increases as relapses occur. As monoallelic mutations of TP53 equally affect outcome, novel methods are being developed to improve detection of TP53 defects and include next-generation sequencing (NGS) and functional assays. TP53 defects highly affect outcome of immunochemotherapy but also alter response durations of tyrosine kinase inhibitors. Although BCR-targeting agents and Bcl-2-inhibitos have achieved durable responses in some patients with TP53 defects, long-term follow-up is currently lacking. In this review biological and clinical consequences of TP53 dysfunction as well as applicability of currently available methods to detect TP53 defects are described. In addition, proposed novel therapeutic strategies specifically for patients with TP53 dysfunction are discussed. In summary, the only curative treatment option for TP53-defective CLL is still allogeneic hematopoietic stem cell transplantation. Other treatment strategies such as rationale combinations of agents with different (TP53 independent) targets, including kinase inhibitors and inhibitors of anti-apoptotic molecules but also immunomodulatory agents need to be further explored.

  18. Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

    PubMed Central

    Torres, Carolina; Linares, Ana; Alejandre, Maria José; Palomino-Morales, Rogelio J.; Caba, Octavio; Prados, Jose; Aránega, Antonia; Delgado, Juan R.; Irigoyen, Antonio; Martínez-Galán, Joaquina; Ortuño, Francisco M.; Rojas, Ignacio; Perales, Sonia

    2015-01-01

    The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients' outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox's proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease. PMID:26346854

  19. Treatment and prognosis in peptic ulcer bleeding.

    PubMed

    Laursen, Stig Borbjerg

    2014-02-01

    Peptic ulcer bleeding is a frequent cause of admission. Despite several advances in treatment the 30-day mortality seems unchanged at a level around 11%. Use of risk scoring systems is shown to be advantageous in the primary assessment of patients presenting with symptoms of peptic ulcer bleeding. Studies performed outside Denmark have demonstrated that use of risk scoring systems facilitates identification of low-risk patients suitable for outpatient management. Nevertheless, these systems have not been implemented for routine use in Denmark. This is mainly explained by concerns about the external validity due to considerable inter-country variation in patients' characteristics. In recent years, transcatheter arterial embolization (TAE) has become increasingly used for achievement of haemostasis in patients with peptic ulcer bleeding not responding to endoscopic therapy. As rebleeding is associated with poor outcome TAE could, in theory, also be beneficial as a supplementary treatment in patients with ulcer bleeding responding to endoscopic therapy. This has not been examined previously. Several studies have concluded that peptic ulcer bleeding is associated with excess long-term mortality. These findings are, however, questioned as the studies were based on life-table analysis, unmatched control groups, or did not perform adequate adjustment for comorbidity. Treatment with blood transfusion is, among patients undergoing cardiac bypass surgery, shown to increase the long-term mortality. Despite frequent use of blood transfusion in treatment of peptic ulcer bleeding a possible adverse effect of on long-term survival has not been examined in these patients.

  20. Mental stress-induced left ventricular dysfunction and adverse outcome in ischemic heart disease patients.

    PubMed

    Sun, Julia L; Boyle, Stephen H; Samad, Zainab; Babyak, Michael A; Wilson, Jennifer L; Kuhn, Cynthia; Becker, Richard C; Ortel, Thomas L; Williams, Redford B; Rogers, Joseph G; O'Connor, Christopher M; Velazquez, Eric J; Jiang, Wei

    2017-04-01

    Aims Mental stress-induced myocardial ischemia (MSIMI) occurs in up to 70% of patients with clinically stable ischemic heart disease and is associated with increased risk of adverse prognosis. We aimed to examine the prognostic value of indices of MSIMI and exercise stress-induced myocardial ischemia (ESIMI) in a population of ischemic heart disease patients that was not confined by having a recent positive physical stress test. Methods and results The Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment (REMIT) study enrolled 310 subjects who underwent mental and exercise stress testing and were followed annually for a median of four years. Study endpoints included time to first and total rate of major adverse cardiovascular events, defined as all-cause mortality and hospitalizations for cardiovascular causes. Cox and negative binomial regression adjusting for age, sex, resting left ventricular ejection fraction, and heart failure status were used to examine associations of indices of MSIMI and ESIMI with study endpoints. The continuous variable of mental stress-induced left ventricular ejection fraction change was significantly associated with both endpoints (all p values < 0.05). For every reduction of 5% in left ventricular ejection fraction induced by mental stress, patients had a 5% increase in the probability of a major adverse cardiovascular event at the median follow-up time and a 20% increase in the number of major adverse cardiovascular events endured over the follow-up period of six years. Indices of ESIMI did not predict endpoints ( ps > 0.05). Conclusion In patients with stable ischemic heart disease, mental, but not exercise, stress-induced left ventricular ejection fraction change significantly predicts risk of future adverse cardiovascular events.

  1. Quinolones: review of psychiatric and neurological adverse reactions.

    PubMed

    Tomé, Ana M; Filipe, Augusto

    2011-06-01

    of reports, while for ofloxacin and pefloxacin, the number of reports may be over-representative. A total of 232 ADRs were identified from the selected articles, with 206 of these related to psychiatric and/or neurological ADRs. The other 26 were related to other body systems but were reported together with the reactions of interest. Mania, insomnia, acute psychosis and delirium were the most frequently reported psychiatric adverse events; grand mal convulsion, confusional state, convulsions and myoclonus were the most frequently reported neurological adverse events. Several aspects should be taken into account in the development of CNS adverse effects, such as the pharmacokinetics of quinolones, chemical structure and quinolone uptake in the brain. These events may affect not only susceptible patients but also 'healthy' patients.

  2. Close Friends' Psychopathology as a Pathway From Early Adversity to Young Adulthood Depressive Symptoms.

    PubMed

    Raposa, Elizabeth B; Hammen, Constance L; Brennan, Patricia A

    2015-01-01

    Past research has highlighted the negative impact of early adverse experiences on childhood social functioning, including friendship selection, and later mental health. The current study explored the long-term effects of early adversity on young adults' close friends' psychological symptoms and the impact of these close friendships on later depressive symptoms. A prospective longitudinal design was used to examine 816 youth from a large community-based sample, who were followed from birth through age 25. Participants' mothers provided contemporaneous information about adversity exposure up to age 5, and participants completed questionnaires about their own depressive symptoms at age 20 and in their early 20s. Youth also nominated a best friend to complete questionnaires about his or her own psychopathology at age 20. Individuals who experienced more early adversity by age 5 had best friends with higher rates of psychopathology at age 20. Moreover, best friends' psychopathology predicted target youth depressive symptoms 2 to 5 years later. Results indicate that early adversity continues to affect social functioning throughout young adulthood and that best friendships marked by elevated psychopathology in turn negatively affect mental health. Findings have implications for clinical interventions designed to prevent the development of depressive symptoms in youth who have been exposed to early adversity.

  3. Aberrant DNA methylation impacts gene expression and prognosis in breast cancer subtypes.

    PubMed

    Győrffy, Balázs; Bottai, Giulia; Fleischer, Thomas; Munkácsy, Gyöngyi; Budczies, Jan; Paladini, Laura; Børresen-Dale, Anne-Lise; Kristensen, Vessela N; Santarpia, Libero

    2016-01-01

    DNA methylation has a substantial impact on gene expression, affecting the prognosis of breast cancer (BC) patients dependent on molecular subtypes. In this study, we investigated the prognostic relevance of the expression of genes reported as aberrantly methylated, and the link between gene expression and DNA methylation in BC subtypes. The prognostic value of the expression of 144 aberrantly methylated genes was evaluated in ER+/HER2-, HER2+, and ER-/HER2- molecular BC subtypes, in a meta-analysis of two large transcriptomic cohorts of BC patients (n = 1,938 and n = 1,640). The correlation between gene expression and DNA methylation in distinct gene regions was also investigated in an independent dataset of 104 BCs. Survival and Pearson correlation analyses were computed for each gene separately. The expression of 48 genes was significantly associated with BC prognosis (p < 0.05), and 32 of these prognostic genes exhibited a direct expression-methylation correlation. The expression of several immune-related genes, including CD3D and HLA-A, was associated with both relapse-free survival (HR = 0.42, p = 3.5E-06; HR = 0.35, p = 1.7E-08) and overall survival (HR = 0.50, p = 5.5E-04; HR = 0.68, p = 4.5E-02) in ER-/HER2- BCs. On the overall, the distribution of both positive and negative expression-methylation correlation in distinct gene regions have different effects on gene expression and prognosis in BC subtypes. This large-scale meta-analysis allowed the identification of several genes consistently associated with prognosis, whose DNA methylation could represent a promising biomarker for prognostication and clinical stratification of patients with distinct BC subtypes.

  4. Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer

    PubMed Central

    Jorissen, Robert N; Christie, Michael; Mouradov, Dmitri; Sakthianandeswaren, Anuratha; Li, Shan; Love, Christopher; Xu, Zheng-Zhou; Molloy, Peter L; Jones, Ian T; McLaughlin, Stephen; Ward, Robyn L; Hawkins, Nicholas J; Ruszkiewicz, Andrew R; Moore, James; Burgess, Antony W; Busam, Dana; Zhao, Qi; Strausberg, Robert L; Lipton, Lara; Desai, Jayesh; Gibbs, Peter; Sieber, Oliver M

    2015-01-01

    Background: APC mutations (APC-mt) occur in ∼70% of colorectal cancers (CRCs), but their relationship to prognosis is unclear. Methods: APC prognostic value was evaluated in 746 stage I–IV CRC patients, stratifying for tumour location and microsatellite instability (MSI). Microarrays were used to identify a gene signature that could classify APC mutation status, and classifier ability to predict prognosis was examined in an independent cohort. Results: Wild-type APC microsatellite stable (APC-wt/MSS) tumours from the proximal colon showed poorer overall and recurrence-free survival (OS, RFS) than APC-mt/MSS proximal, APC-wt/MSS distal and APC-mt/MSS distal tumours (OS HR⩾1.79, P⩽0.015; RFS HR⩾1.88, P⩽0.026). APC was a stronger prognostic indicator than BRAF, KRAS, PIK3CA, TP53, CpG island methylator phenotype or chromosomal instability status (P⩽0.036). Microarray analysis similarly revealed poorer survival in MSS proximal cancers with an APC-wt-like signature (P=0.019). APC status did not affect outcomes in MSI tumours. In a validation on 206 patients with proximal colon cancer, APC-wt-like signature MSS cases showed poorer survival than APC-mt-like signature MSS or MSI cases (OS HR⩾2.50, P⩽0.010; RFS HR⩾2.14, P⩽0.025). Poor prognosis APC-wt/MSS proximal tumours exhibited features of the sessile serrated neoplasia pathway (P⩽0.016). Conclusions: APC-wt status is a marker of poor prognosis in MSS proximal colon cancer. PMID:26305864

  5. Short and long term prognosis in perinatal asphyxia: An update

    PubMed Central

    Ahearne, Caroline E; Boylan, Geraldine B; Murray, Deirdre M

    2016-01-01

    Interruption of blood flow and gas exchange to the fetus in the perinatal period, known as perinatal asphyxia, can, if significant, trigger a cascade of neuronal injury, leading on to neonatal encephalopathy (NE) and resultant long-term damage. While the majority of infants who are exposed to perinatal hypoxia-ischaemia will recover quickly and go on to have a completely normal survival, a proportion will suffer from an evolving clinical encephalopathy termed hypoxic-ischaemic encephalopathy (HIE) or NE if the diagnosis is unclear. Resultant complications of HIE/NE are wide-ranging and may affect the motor, sensory, cognitive and behavioural outcome of the child. The advent of therapeutic hypothermia as a neuroprotective treatment for those with moderate and severe encephalopathy has improved prognosis. Outcome prediction in these infants has changed, but is more important than ever, as hypothermia is a time sensitive intervention, with a very narrow therapeutic window. To identify those who will benefit from current and emerging neuroprotective therapies we must be able to establish the severity of their injury soon after birth. Currently available indicators such as blood biochemistry, clinical examination and electrophysiology are limited. Emerging biological and physiological markers have the potential to improve our ability to select those infants who will benefit most from intervention. Biomarkers identified from work in proteomics, metabolomics and transcriptomics as well as physiological markers such as heart rate variability, EEG analysis and radiological imaging when combined with neuroprotective measures have the potential to improve outcome in HIE/NE. The aim of this review is to give an overview of the literature in regards to short and long-term outcome following perinatal asphyxia, and to discuss the prediction of this outcome in the early hours after birth when intervention is most crucial; looking at both currently available tools and introducing

  6. Pars Planitis: Epidemiology, Clinical Characteristics, Management and Visual Prognosis

    PubMed Central

    Ozdal, Pinar Cakar; Berker, Nilufer; Tugal-Tutkun, Ilknur

    2015-01-01

    Pars planitis is an idiopathic chronic intermediate uveitis which predominantly affects children and adolescents, and accounts for 5-26.7% of pediatric uveitis. Although an autoimmune process with a genetic predisposition has been suggested, its etiology still remains unknown. The most common presenting symptoms are floaters and blurred vision. Diffuse vitreous cells, haze, snowballs and snowbanks are typical findings of pars planitis. Peripheral retinal vasculitis, optic disc edema and anterior segment inflammation are other well-known findings. Although pars planitis is known to be a benign form of uveitis in most cases, it may become a potentially blinding disease due to complications including cataract, cystoid macular edema, vitreous opacities and optic disc edema. Cystoid macular edema is the most common cause of visual morbidity. Band keratopathy, epiretinal membrane formation, vitreous condensation, neovascularizations, vitreous hemorrhage, retinal detachment, cyclitic membranes, glaucoma and amblyopia may develop as a consequence of the chronic course of the disease. Exclusion of infectious and non-infectious causes which may present with intermediate uveitis is of utmost importance before starting treatment. Treatment of pars planitis has been a controversial issue. There is no consensus specifically for treatment of cases with minimal inflammation and relatively good visual acuity. However, current experience shows that pars planitis may cause severe inflammation and needs an aggressive treatment. A stepladder approach including corticosteroids, immunosupressive agents, anti-tumor necrosis factor-alpha and pars plana vitrectomy and/or laser photocoagulation is the most commonly used method for treatment of pars planitis. Adequate control of inflammation and prompt detection of associated complications are crucial in order to improve the overall prognosis of the disease. PMID:27051493

  7. Standardized EEG interpretation accurately predicts prognosis after cardiac arrest

    PubMed Central

    Rossetti, Andrea O.; van Rootselaar, Anne-Fleur; Wesenberg Kjaer, Troels; Horn, Janneke; Ullén, Susann; Friberg, Hans; Nielsen, Niklas; Rosén, Ingmar; Åneman, Anders; Erlinge, David; Gasche, Yvan; Hassager, Christian; Hovdenes, Jan; Kjaergaard, Jesper; Kuiper, Michael; Pellis, Tommaso; Stammet, Pascal; Wanscher, Michael; Wetterslev, Jørn; Wise, Matt P.; Cronberg, Tobias

    2016-01-01

    Objective: To identify reliable predictors of outcome in comatose patients after cardiac arrest using a single routine EEG and standardized interpretation according to the terminology proposed by the American Clinical Neurophysiology Society. Methods: In this cohort study, 4 EEG specialists, blinded to outcome, evaluated prospectively recorded EEGs in the Target Temperature Management trial (TTM trial) that randomized patients to 33°C vs 36°C. Routine EEG was performed in patients still comatose after rewarming. EEGs were classified into highly malignant (suppression, suppression with periodic discharges, burst-suppression), malignant (periodic or rhythmic patterns, pathological or nonreactive background), and benign EEG (absence of malignant features). Poor outcome was defined as best Cerebral Performance Category score 3–5 until 180 days. Results: Eight TTM sites randomized 202 patients. EEGs were recorded in 103 patients at a median 77 hours after cardiac arrest; 37% had a highly malignant EEG and all had a poor outcome (specificity 100%, sensitivity 50%). Any malignant EEG feature had a low specificity to predict poor prognosis (48%) but if 2 malignant EEG features were present specificity increased to 96% (p < 0.001). Specificity and sensitivity were not significantly affected by targeted temperature or sedation. A benign EEG was found in 1% of the patients with a poor outcome. Conclusions: Highly malignant EEG after rewarming reliably predicted poor outcome in half of patients without false predictions. An isolated finding of a single malignant feature did not predict poor outcome whereas a benign EEG was highly predictive of a good outcome. PMID:26865516

  8. Adverse events following yellow fever immunization: Report and analysis of 67 neurological cases in Brazil.

    PubMed

    Martins, Reinaldo de Menezes; Pavão, Ana Luiza Braz; de Oliveira, Patrícia Mouta Nunes; dos Santos, Paulo Roberto Gomes; Carvalho, Sandra Maria D; Mohrdieck, Renate; Fernandes, Alexandre Ribeiro; Sato, Helena Keico; de Figueiredo, Patricia Mandali; von Doellinger, Vanessa Dos Reis; Leal, Maria da Luz Fernandes; Homma, Akira; Maia, Maria de Lourdes S

    2014-11-20

    Neurological adverse events following administration of the 17DD substrain of yellow fever vaccine (YEL-AND) in the Brazilian population are described and analyzed. Based on information obtained from the National Immunization Program through passive surveillance or intensified passive surveillance, from 2007 to 2012, descriptive analysis, national and regional rates of YFV associated neurotropic, neurological autoimmune disease, and reporting rate ratios with their respective 95% confidence intervals were calculated for first time vaccinees stratified on age and year. Sixty-seven neurological cases were found, with the highest rate of neurological adverse events in the age group from 5 to 9 years (2.66 per 100,000 vaccine doses in Rio Grande do Sul state, and 0.83 per 100,000 doses in national analysis). Two cases had a combination of neurotropic and autoimmune features. This is the largest sample of YEL-AND already analyzed. Rates are similar to other recent studies, but on this study the age group from 5 to 9 years of age had the highest risk. As neurological adverse events have in general a good prognosis, they should not contraindicate the use of yellow fever vaccine in face of risk of infection by yellow fever virus.

  9. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of...

  10. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of...

  11. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of...

  12. p53 exon 7 mutations as a predictor of poor prognosis in patients with colorectal cancer.

    PubMed

    Iniesta, P; Vega, F J; Caldés, T; Massa, M; de Juan, C; Cerdán, F J; Sánchez, A; López, J A; Torres, A J; Balibrea, J L; Benito, M

    1998-08-14

    We have studied 61 resected colorectal adenocarcinomas in order to investigate p53 mutations as a prognostic factor for this pathology. Mutations in exons 5-9 of the p53 gene were analyzed by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique followed by sequencing. Our data indicate that p53 exon 7 mutations were prevalent in the latest stages of colorectal carcinogenesis and patients bearing this alteration had the worst prognosis. Therefore, according to our results, mutations affecting exon 7 of the p53 gene could be considered as a useful marker of biological aggressiveness for colorectal cancer.

  13. Clinical utility of biomarkers of endothelial activation and coagulation for prognosis in HIV infection

    PubMed Central

    Graham, Susan M; Mwilu, Regina; Liles, W Conrad

    2013-01-01

    Introduction: HIV infection is associated with vascular dysfunction and adverse cardiovascular outcomes. Our objective was to review the evidence regarding the clinical utility of endothelial activation and coagulation biomarkers for the prognosis of HIV-infected patients. Methods: We searched PubMed and Embase for publications using the keywords “HIV” or “HIV infection” and “endothelium” or “coagulation”. We reviewed reference lists and hand-searched for additional relevant articles. All clinical studies that enrolled non-pregnant, HIV-infected adults, measured biomarkers reflecting endothelial activation or coagulation, and prospectively evaluated their associations with vascular dysfunction or clinical outcomes were included. Results: Seventeen studies were identified that fulfilled the inclusion criteria, of which 11 investigated endothelial activation biomarkers and 12 investigated coagulation biomarkers. Biomarkers and outcomes varied widely across studies. Overall, published studies support an association between P-selectin and venous thromboembolism in HIV-infected patients, an association between tissue-type plasminogen activator and death, and associations between D-dimer and several clinical outcomes, including venous thromboembolism, cardiovascular disease, and all-cause mortality. Conclusions: Several studies have demonstrated associations between biomarkers of endothelial activation and coagulation and clinically important outcomes in HIV-1 infection. Additional large-scale prospective investigations to determine the utility of endothelial activation and coagulation biomarkers for risk stratification and prediction of adverse outcomes are clearly warranted. PMID:23732995

  14. Recurrent adverse pregnancy outcome and antiphospholipid antibodies.

    PubMed

    Reece, E A; Gabrielli, S; Cullen, M T; Zheng, X Z; Hobbins, J C; Harris, E N

    1990-07-01

    Antiphospholipid antibodies, which include lupus-like anticoagulant and anticardiolipin antibody, have been linked to a number of adverse pregnancy outcomes, although their exact pathogenic mechanisms remain poorly defined. The relative risk of complications such as intrauterine growth retardation, spontaneous abortions, and stillbirth in patients with antiphospholipid antibodies also remains undetermined. Heightened attention has been focused on the association, leading to investigations into the pathogenesis. Uncontrolled studies have also explored therapeutic regimens such as aspirin, steroids, and heparin, and clinical trials have used various treatment protocols. Although knowledge into the association of antiphospholipid antibodies and recurrent adverse pregnancy outcome is limited and continues to evolve, this association provides new insights into the disease and offers promise for pharmacologic prophylaxis. In this article, current concepts on pathogenesis, diagnosis, and therapy are reviewed and recommendations are made for clinical care of these patients.

  15. An Ss Model with Adverse Selection.

    ERIC Educational Resources Information Center

    House, Christopher L.; Leahy, John V.

    2004-01-01

    We present a model of the market for a used durable in which agents face fixed costs of adjustment, the magnitude of which depends on the degree of adverse selection in the secondary market. We find that, unlike typical models, the sS bands in our model contract as the variance of the shock increases. We also analyze a dynamic version of the model…

  16. Childhood Adversities and Adult Cardiometabolic Health: Does the Quantity, Timing, and Type of Adversity Matter?

    PubMed Central

    Friedman, Esther M.; Montez, Jennifer Karas; Sheehan, Connor McDevitt; Guenewald, Tara L.; Seeman, Teresa E.

    2015-01-01

    Objective Adverse events in childhood can indelibly influence adult health. While evidence for this association has mounted, a fundamental set of questions about how to operationalize adverse events has been understudied. Method We used data from the National Survey of Midlife Development in the United States to examine how quantity, timing, and types of adverse events in childhood are associated with adult cardiometabolic health. Results The best-fitting specification of quantity of events was a linear measure reflecting a dose–response relationship. Timing of event mattered less than repeated exposure to events. Regarding the type of event, academic interruptions and sexual/physical abuse were most important. Adverse childhood events elevated the risk of diabetes and obesity similarly for men and women but had a greater impact on women’s risk of heart disease. Discussion Findings demonstrate the insights that can be gleaned about the early-life origins of adult health by examining operationalization of childhood exposures. PMID:25903978

  17. Prognosis of critical limb ischemia: Major vs. minor amputation comparison.

    PubMed

    Matsuzaki, Kyoichi; Hayashi, Ruka; Okabe, Keisuke; Aramaki-Hattori, Noriko; Kishi, Kazuo

    2015-09-01

    Healthcare providers treating wounds have difficulties assessing the prognosis of patients with critical limb ischemia who had been discharged after complete healing of major amputation wounds. The word "major" in "major amputation" gives the impression of "being more severe" than "minor amputation." Therefore, even if wounds are healed after major amputation, they imagine that prognosis after major amputation would be poorer than that after minor amputation. We investigated the prognosis of diabetic nephropathy patients 2 years after amputations. Those patients underwent dialysis as well as amputation following percutaneous transluminal angioplasty for their foot wounds. They were ambulatory prior to these surgeries. Among 56 cases of minor amputation, 45 were males and 11 were females, and mortality was 41.1%. The mortality of cases with and without a coronary intervention history was 53.1% and 25.0%, respectively (p = 0.034). Among 10 cases of major amputation, 9 were males and 1 was female, and mortality was 60%. The mortality of cases with and without a coronary intervention history was 75.0% and 0%, respectively. Although we predicted poor prognosis in cases with major amputation, there was no significant difference in mortality 2 years after amputations (p = 0.267). Thus far poor prognosis has been reported for major amputation. It might be due to inclusion of the following patients: patients with wounds proximal to ankle joints, patients with extensive gangrene spreading to the lower legs, patients with septicemia from wound infection and who died around the time of operation, and patients with malnutrition. The results of our present study showed that the outcomes at 2 years postoperatively were similar between patients with major amputations and those with minor amputations, if surgical wounds were able to heal. We should not estimate the prognosis by the level of amputation, rather we should consider the effect of coronary intervention history on

  18. Adverse Outcome Pathway (AOP) Network Development for ...

    EPA Pesticide Factsheets

    Adverse outcome pathways (AOPs) are descriptive biological sequences that start from a molecular initiating event (MIE) and end with an adverse health outcome. AOPs provide biological context for high throughput chemical testing and further prioritize environmental health risk research. According to the Organization for Economic Co-operation and Development guidelines, AOPs are pathways with one MIE anchored to an adverse outcome (AO) by key events (KEs) and key event relationships (KERs). However, this approach does not always capture the cumulative impacts of multiple MIEs on the AO. For example, hepatic lipid flux due to chemical-induced toxicity initiates from multiple ligand-activated receptors and signaling pathways that cascade across biology to converge upon a common fatty liver (FL, also known as steatosis) outcome. To capture this complexity, a top-down strategy was used to develop a FL AOP network (AOPnet). Literature was queried based on the terms steatosis, fatty liver, cirrhosis, and hepatocellular carcinoma. Search results were analyzed for physiological and pathophysiological organ level, cellular and molecular processes, as well as pathway intermediates, to identify potential KEs and MIEs that are key for hepatic lipid metabolism, maintenance, and dysregulation. The analysis identified four apical KE nodes (hepatic fatty acid uptake, de novo fatty acid and lipid synthesis, fatty acid oxidation, and lipid efflux) juxtaposed to the FL AO. The apic

  19. Serious Adverse Events After Cataract Surgery

    PubMed Central

    Stein, Joshua D.

    2013-01-01

    Purpose Over the past several decades there have been many advances in the equipment, instrumentation and techniques of performing cataract surgery. This review will address the impact of these advances on the safety profile of cataract surgery. Recent Findings Recent studies have demonstrated a decline in the risk of serious postoperative adverse events (endophthalmitis, suprachoroidal hemorrhage, retinal detachment) following cataract surgery. Factors that increase the risk of serious complications from cataract surgery include patient-related factors (male sex, concomitant diabetic retinopathy, same day cataract surgery combined with another intraocular surgery, tamsulosin use) and surgeon-related factors (low surgical volume, limited experience, operating on patients who are most prone to adverse events). Summary Cataract surgery continues to be a very safe surgical procedure with few patients experiencing serious sight-threatening adverse events. Studies in the literature have helped surgeons identify patients who are at high risk for surgical complications and to develop strategies to limit surgical complications when operating on these patients. As multifocal intraocular lenses, femtosecond laser technology, and other surgical innovations continue to gain popularity, it will be interesting in the coming years to determine whether there will be a continued reduction in complications of cataract surgery. PMID:22450221

  20. Statin-Associated Muscle Adverse Events

    PubMed Central

    Al-Mohaissen, Maha A.; Ignaszewski, Martha J.; Frohlich, Jiri; Ignaszewski, Andrew P.

    2016-01-01

    Statins are potent medications which reduce low-density lipoprotein cholesterol (LDL-C) levels. Their efficacy in cardiovascular risk reduction is well established and indications for their use are expanding. While statins are generally well tolerated and safe, adverse events are relatively common, particularly statin-associated muscle adverse events (SaMAEs), which are the most frequently encountered type of adverse event. Recent guidelines and guideline updates on SaMAEs and statin intolerance have included revised definitions of SaMAEs, incorporating new evidence on their pathogenesis and management. As SaMAEs emerge as a therapeutic challenge, it is important for physicians to be aware of updates on management strategies to ensure better patient outcomes. The majority of patients who are considered statin-intolerant can nevertheless tolerate some forms of statin therapy and successfully achieve optimal LDL-C levels. This review article discusses the recent classification of SaMAEs with emphasis on pathogenesis and management strategies. PMID:28003885

  1. Metabolic and adverse effects of diuretics.

    PubMed

    Wilcox, C S

    1999-11-01

    Diuretics are among the most frequently prescribed drugs. They enjoy a very high clinical reputation for safety and efficacy. However, more than 3 decades of clinical investigation have disclosed a number of abnormalities in fluid electrolyte handling, metabolism, and other adverse effects that can complicate therapy with diuretic drugs. Some of these complications are a direct extension of the wanted action of the drug. These include extracellular fluid volume depletion, associated orthostatic hypotension, and prerenal azotemia. Others are not a direct action of the diuretic, but can be explained as an intranephronal compensation to the diuretic action. These include hypokalemia, in part to increased potassium secretion secondary to the enhanced tubular fluid flow and aldosterone secretion induced by diuretic administration. Metabolic abnormalities are usually mild. Hyperglycemia and carbohydrate intolerance have been related to diuretic-induced hypokalemia, which inhibits insulin secretion by the beta cells, and reductions in extracellular fluid volume and cardiac output. This is compounded by increases in catecholamines from sympathetic nerve activity which decrease peripheral glucose utilization. A mild increase in serum cholesterol concentration is seen frequently during initiation of diuretic therapy, but during steady state therapy after 6 to 12 months, values usually return to baseline. Knowledge of the more common adverse effects induced by diuretics helps the physician in predicting patients at risk and taking effective steps to anticipate or treat adverse responses.

  2. Adverse effects of bisphenol A on male reproductive function.

    PubMed

    Manfo, Faustin Pascal Tsagué; Jubendradass, Rajamanickam; Nantia, Edouard Akono; Moundipa, Paul Fewou; Mathur, Premendu Prakash

    2014-01-01

    BPA is a ubiquitous environmental contaminant, resulting mainly from manufacturing,use or disposal of plastics of which it is a component, and the degradation of industrial plastic-related wastes. Growing evidence from research on laboratory animals, wildlife, and humans supports the view that BPA produces an endocrine disrupting effect and adversely affects male reproductive function. To better understand the adverse effects caused by exposure to BPA, we performed an up-to-date literature review on the topic, with particular emphasis on in utero exposure, and associated effects on spermatogenesis, steroidogenesis, and accessory organs.BPA studies on experimental animals show that effects are generally more detrimental during in utero exposure, a critical developmental stage for the embryo. BPA has been found to produce several defects in the embryo, such as feminization of male fetuses, atrophy of the testes and epididymides, increased prostate size, shortening of AGD, disruption of BTB, and alteration of adult sperm parameters (e.g.,sperm count, motility, and density). BPA also affects embryo thyroid development.During the postnatal and pubertal periods and adulthood, BPA affects the hypothalamic-pituitary-testicular axis by modulating hormone (e.g., LH and FSH,androgen and estrogen) synthesis, expression and function of respective receptors(ER, AR). These effects alter sperm parameters. BPA also induces oxidative stress in the testis and epididymis, by inhibiting antioxidant enzymes and stimulating lipid peroxidation. This suggests that employing antioxidants may be a promising strategy to relieve BPA-induced disturbances.Epidemiological studies have also provided data indicating that BPA alters male reproductive function in humans. These investigations revealed that men occupationally exposed to BPA had high blood/urinary BPA levels, and abnormal semen parameters. BPA-exposed men also showed reduced libido and erectile ejaculatory difficulties; moreover, the

  3. Adjuvant diet to improve hormonal and metabolic factors affecting breast cancer prognosis.

    PubMed

    Berrino, Franco; Villarini, Anna; De Petris, Michela; Raimondi, Milena; Pasanisi, Patrizia

    2006-11-01

    Western lifestyle, characterized by reduced physical activity and a diet rich in fat, refined carbohydrates, and animal protein is associated with high prevalence of overweight, metabolic syndrome, insulin resistance, and high plasma levels of several growth factors and sex hormones. Most of these factors are associated with breast cancer risk and, in breast cancer patients, with increased risk of recurrences. Recent trials have proven that such a metabolic and endocrine imbalance can be favorably modified through comprehensive dietary modification, shifting from Western to Mediterranean and macrobiotic diet.

  4. Prognosis in autism: do specialist treatments affect long-term outcome?

    PubMed

    Howlin, P

    1997-06-01

    Many different treatments have been claimed to have a dramatic impact on children with autism. This paper reviews what is known about the outcome in adult life and examines the limitations and advantages of a variety of intervention approaches. It concludes that there is little evidence of any "cure" for autism, but appropriately structured programmes for education and management in the early years can play a significant role in enhancing functioning in later life.

  5. Baseline characteristics, chromosomal alterations, and treatment affecting prognosis of deletion 17p in newly diagnosed myeloma.

    PubMed

    Merz, Maximilian; Hielscher, Thomas; Seckinger, Anja; Hose, Dirk; Mai, Elias K; Raab, Marc S; Goldschmidt, Hartmut; Jauch, Anna; Hillengass, Jens

    2016-11-01

    Deletion 17p13, del(17p), is associated with poor outcome in myeloma but some patients show long-term survival. With the current study we intended to identify factors impacting outcome of such high risk patients. We analyzed 110 newly diagnosed, symptomatic patients with del(17p) detected by fluorescence in situ hybridization (FISH) in CD138-purified myeloma cells to identify prognostic factors for survival. Age >65 years, ISS III, and elevated LDH negatively impacted survival. Patients with subclonal (10-60% of plasma cells) del(17p) had longer progression-free survival (PFS) than patients with del(17p) in >60% of plasma cells (26 vs. 19 months, P = 0.03). Additional gain of 1q21 was associated with shorter PFS (17 vs. 25 months, P = 0.01). Hyperdiploidy did not ameliorate impact of del(17p), but gain 19q13 predicted longer PFS (30 vs. 18 months, P = 0.01) and overall survival (50 vs. 29 months, P = 0.01). Multivariate analysis in transplant eligible patients (≤65 years) revealed better survival for patients treated with upfront autologous transplantation (hazard ratio, [95% confidence interval]: 0.15 [0.04, 0.58], P = 0.006). Application of maintenance therapy was associated with better survival in transplant-eligible patients (0.30 [0.09, 0.99], P = 0.05). We demonstrate heterogeneous outcome of patients with del(17p) according to baseline characteristics and treatment. 19q13 should be included in routine FISH panel, since gains were associated with better survival. Am. J. Hematol. 91:E473-E477, 2016. © 2016 Wiley Periodicals, Inc.

  6. Treatment and prognosis in peptic ulcer bleeding.

    PubMed

    Laursen, Stig Borbjerg

    2014-01-01

    Peptic ulcer bleeding is a frequent cause of admission. Despite several advances in treatment the 30-day mortality seems unchanged at a level around 11%. Use of risk scoring systems is shown to be advantageous in the primary assessment of patients presenting with symptoms of peptic ulcer bleeding. Studies performed outside Denmark have demonstrated that use of risk scoring systems facilitates identification of low-risk patients suitable for outpatient management. Nevertheless, these systems have not been implemented for routine use in Denmark. This is mainly explained by concerns about the external validity due to considerable inter-country variation in patients' characteristics. In recent years, transcatheter arterial embolization (TAE) has become increasingly used for achievement of hemostasis in patients with peptic ulcer bleeding not responding to endoscopic therapy. As rebleeding is associated with poor outcome TAE could, in theory, also be beneficial as a supplementary treatment in patients with ulcer bleeding responding to endoscopic therapy. This has not been examined previously. Several studies have concluded that peptic ulcer bleeding is associated with excess long-term mortality. These findings are, however, questioned as the studies were based on life-table analysis, unmatched control groups, or did not perform adequate adjustment for comorbidity. Treatment with blood transfusion is, among patients undergoing cardiac bypass surgery, shown to increase the long-term mortality. Despite frequent use of blood transfusion in treatment of peptic ulcer bleeding a possible adverse effect of on long-term survival has not been examined in these patients. The aims of the present thesis were: 1. To examine which risk scoring system is best at predicting need of hospital-based intervention, rebleeding, and mortality in patients presenting with upper gastrointestinal bleeding (Study I) 2. To evaluate if supplementary transcatheter arterial embolization (STAE) after

  7. [Differential diagnosis and prognosis of phobic disorders].

    PubMed

    Lakosina, N D; Kolupaev, G P

    1998-01-01

    The paper presents differential-diagnostic signs of phobic disorders of different etiology. Acute episodes of depersonalization preceding phobias and fears arising during the first age crisis are considered as some diagnostic signs of endogenous phobias. The significant criteria for diagnosis of psychogenic phobias are anxious suspiciousness, affective instability, susceptibility, spontaneity of reactivity and the presence of personally important psychic trauma. An autonomic paroxysm caused by alcoholic situation in exogenic organic pathology (alcoholism) was transformed quite fast into some senestopathias, which themselves maintained the of fear. The relationships of phobias and depressions in endogenous disorders was different: in slow-progredient variations of the disease depression resulted in a decrease of the manifestations of the phobias, and vice versa; in shift-like variations depression is an independent syndrome in the depressive-phobic complex. Depressions and phobias are closely connected in psychogenic phobias, they complicated and developed in parallel. In exogenic-organic phobias both affective disorders and phobias had a paroxysmal character and transformed into dysphorias.

  8. Congenital Aniridia: Clinic, Genetics, Therapeutics, and Prognosis

    PubMed Central

    Santos-Silva, R.; Falcão-Reis, F.; Rocha-Sousa, A.

    2014-01-01

    Congenital aniridia is a rare condition related to a deficiency in the PAX6 gene expression, which may occur as a result of a family inheritance or a sporadic occurrence. Additionally, this condition may occur as an isolated ocular phenotype or in association with a systemic syndrome. The most common abnormality is iris hypoplasia; however, a panocular disease which also affects the cornea, anterior chamber of the eye, lens, and the posterior segment with presence of optic nerve and foveal hypoplasia is also evident. The development of keratopathy, glaucoma, and cataract is frequent and its presence has implications in the patient's visual acuity. Managing aniridia is challenging since the focus is on treating the previously mentioned disorders, and the outcomes are often disappointing. In this paper, we shall review the epidemiology, pathophysiology, and clinical characteristics of patients with aniridia. We shall also make a review of the therapeutic options for the several conditions affecting this syndrome and consider the genetics and prognostic factors. PMID:27355034

  9. Lidar monitoring of infrared target detection ranges through adverse weather

    NASA Astrophysics Data System (ADS)

    Bissonnette, Luc R.; Roy, Gilles; Theriault, Jean-Marc

    1998-11-01

    Despite recent technical advances, adverse weather still constitutes an important decision factor in the efficient use of IR sensors. The presence of fog, clouds or precipitation affects both the IR transmission and background properties of the atmosphere. Taking these effects into account requires the knowledge of the optical parameters of fog, clouds or precipitation which, in general, fluctuate too much on a scale of a few kilometers to be predictable with acceptable accuracy. Therefore, systems performance calculations based on modeling alone cannot provide all the necessary information for real time, on-site decision making. A promising alternative is continuous monitoring of atmospheric aerosol properties with a lidar. The method use in this study is the multiple-field- of-view technique which takes advantage of the information contained in the multiple scattering contributions to solve for both the droplet concentration and effective diameter. We can then use these solutions to derive the atmospheric radiance and transmittance, and calculate from there the contrast-to-noise ratio of IR images of small targets. Using actual lidar probings, examples of performance curves of a generic surveillance sensor are obtained for two types of targets. Results show that performance can drastically change over an interval as short as one minute, which emphasizes the need for real time, on site monitoring in adverse weather.

  10. Adverse drug reactions in special populations – the elderly

    PubMed Central

    Davies, E A; O’Mahony, M S

    2015-01-01

    The International Conference on Harmonization considers older people a ‘special population’, as they differ from younger adults in terms of comorbidity, polypharmacy, pharmacokinetics and greater vulnerability to adverse drug reactions (ADRs). Medical practice is often based on single disease guidelines derived from clinical trials that have not included frail older people or those with multiple morbidities. This presents a challenge caring for older people, as drug doses in trials may not be achievable in real world patients and risks of ADRs are underestimated in clinical trial populations. The majority of ADRs in older people are Type A, potentially avoidable and associated with commonly prescribed medications. Several ADRs are particularly associated with major adverse consequences in the elderly and their reduction is therefore a clinical priority. Falls are strongly associated with benzodiazepines, neuroleptics, antidepressants and antihypertensives. There is good evidence for medication review as part of a multifactorial intervention to reduce falls risk in community dwelling elderly. Multiple medications also contribute to delirium, another multifactorial syndrome resulting in excess mortality particularly in frail older people. Clostridium difficile associated with use of broad spectrum antibiotics mainly affects frail older people and results in prolonged hospital stay with substantial morbidity and mortality. Antipsychotics increase the risk of stroke by more than three-fold in patients with dementia. Inappropriate prescribing can be reduced by adherence to prescribing guidelines, suitable monitoring and regular medication review. Given the heterogeneity within the older population, providing individualized care is pivotal to preventing ADRs. PMID:25619317

  11. Characterization and Long-Term Prognosis of Postmyocarditic Dilated Cardiomyopathy Compared With Idiopathic Dilated Cardiomyopathy.

    PubMed

    Merlo, Marco; Anzini, Marco; Bussani, Rossana; Artico, Jessica; Barbati, Giulia; Stolfo, Davide; Gigli, Marta; Muça, Matilda; Naso, Paola; Ramani, Federica; Di Lenarda, Andrea; Pinamonti, Bruno; Sinagra, Gianfranco

    2016-09-15

    Dilated cardiomyopathy (DC) is the final common pathway of different pathogenetic processes and presents a significant prognostic heterogeneity, possibly related to its etiologic variety. The characterization and long-term prognosis of postmyocarditic dilated cardiomyopathy (PM-DC) remain unknown. This study assesses the clinical-instrumental evolution and long-term prognosis of a large cohort of patients with PM-DC. We analyzed 175 patients affected with DC consecutively enrolled from 1993 to 2008 with endomyocardial biopsy (EMB) data available. PM-DC was defined in the presence of borderline myocarditis at EMB or persistent left ventricular dysfunction 1 year after diagnosis of active myocarditis at EMB. Other patients were defined as affected by idiopathic dilated cardiomyopathy (IDC). Analysis of follow-up evaluations was performed at 24, 60, and 120 months. We found 72 PM-DC of 175 enrolled patients (41%). Compared with IDC, patients with PM-DC were more frequently females and less frequently presented a familial history of DC. No other baseline significant differences were found. During the long-term follow-up (median 154, first to third interquartile range 78 to 220 months), patients with PM-DC showed a trend toward slower disease progression. Globally, 18 patients with PM-DC (25%) versus 49 with IDC (48%) experienced death/heart transplantation (p = 0.045). The prognostic advantage for patients with PM-DC became significant beyond 40 months of follow-up. At multivariable time-dependent Cox analysis, PM-DC was confirmed to have a global independent protective role (hazard ratio 0.53, 95% confidence interval 0.28 to 0.97, p = 0.04). In conclusion, PM-DC is characterized by better long-term prognosis compared with IDC. An exhaustive etiologic characterization appears relevant in the prognostic assessment of DC.

  12. Improved prognosis in soft-tissue sarcoma of extremity and trunk wall

    PubMed Central

    Sampo, Mika M; Klintrup, Katariina; Tukiainen, Erkki J; Böhling, Tom O; Blomqvist, Carl P

    2017-01-01

    Background and purpose — Soft-tissue sarcoma (STS) is rare, with challenging individualized treatment, so diagnostics and treatment should be centralized. Historical controls are sometimes used for investigation of whether new diagnostic or therapeutic tools affect patient outcome. However, as yet unknown factors may affect the outcome. We investigated prognostic factors and prognosis in 2 nationwide cohorts of patients diagnosed with a local STS during the periods 1998–2001 and 2005–2010, with special interest in finding factors lying behind possible improvement of prognosis. Patients and methods — 2 cohorts of patients with STS of the extremities or trunk diagnosed during the periods 1998–2001 and 2005–2010 were retrieved from the nationwide Finnish Cancer Registry. Detailed information was gathered from patient files. Results — Compared to first cohort, a larger proportion of patients with inadequate surgery in the second cohort received radiation therapy, and both the local control rate and the sarcoma-specific survival rate improved in the second cohort. For sarcoma-specific survival, cohort (HR =0.6, 95% CI: 0.5–0.9), age, depth, grade, and margin were significant factors in multivariate analysis. For local control, cohort (HR =0.6, 95% CI: 0.5–0.9), age, and margin were significant in multivariate analysis. Interpretation — Known prognostic factors including type of treatment did not entirely explain the secular trend of continuous improvement in prognosis in STS. This illustrates the danger of using historical controls for investigation of whether new diagnostic or therapeutic tools have an effect on patient outcome. PMID:27321676

  13. The College Student and Marijuana: Research Findings Concerning Adverse Biological and Psychological Effects.

    ERIC Educational Resources Information Center

    Nicholi, Armand M., Jr.

    1983-01-01

    This paper focuses on current knowledge about adverse biological and psychological affects of marijuana use, with special reference to risks for college students. Short-term effects on intellectual functioning and perceptual-motor coordination and long-term effects on reproduction and motivation are highlighted. (PP)

  14. Adverse effects of statins - myths and reality.

    PubMed

    Šimić, Iveta; Reiner, Željko

    2015-01-01

    Statins reduce cardiovascular mortality and morbidity as well as cardiovascular events in patients with a very high risk of cardiovascular disease (CVD) and also in subjects with high or moderate risk by reducing the levels of low-density lipoprotein cholesterol (LDL-C). Although they are considered to be drugs with a very good safety profile, because of their wide use there are many concerns that their adverse effects might compromise their proven beneficial effects. Therefore this article reviews all the data and provides an evidence- based insight what are the proven adverse effects of statins and what are the "myths" about them. The most important side effects include myopathy and rhabdomyolysis. Another side effect is increased activity of liver tests which occurs occasionally and is reversible. However, recent studies even suggest that statin therapy can improve hepatic steatosis. It is beyond any doubt that statins do slightly increase the incidence of type 2 diabetes mellitus in people with two or more components of metabolic syndrome but the cardiovascular benefits of such a treatment by far exceed this risk. Statin therapy has also been associated with some adverse renal effects, eg. acute renal failure, but recent data suggest even a possible protective effect of these drugs on renal dysfunction. Concerns that statins might increase cancer have not been proven. On the contrary, several studies have indicated a possible benefit of these drugs in patients with different types of cancer. Early concerns about cognitive dysfunction and memory loss associated with statins use could not be proven and most recent data even suggest a possible beneficial effect of statins in the prevention of dementia. Systematic reviews and clinical guidelines suggest that the cardiovascular benefits of statins by far out-weight non-cardiovascular harms in patients with cardiovascular risk.

  15. Determinants of Adverse Events in Vascular Surgery

    PubMed Central

    Hernandez-Boussard, Tina; McDonald, Kathryn; Morton, John; Dalman, Ron L; Bech, Fritz R

    2016-01-01

    Background Patient safety is a national priority. Patient Safety Indicators (PSIs) monitor potential adverse events during hospital stays. Surgical specialty PSI benchmarks do not exist, which are needed to account for differences in the range of procedures performed, reasons for the procedure, and differences in patient characteristics. A comprehensive profile of adverse events in vascular surgery was created. Study Design The Nationwide Inpatient Sample was queried for 8 vascular procedures using ICD-9-CM codes from 2005–2009. Factors associated with PSI development were evaluated in univariate and multivariate analyses. Results A total of 1,412,703 patients underwent a vascular procedure and 5.2% developed a PSI. PSIs were more frequent in female, non-white patients with public payers (p<.01). Patients at mid and low volume hospitals had greater odds of developing a PSI (Odds Ratio [OR], 1.17; 95% Confidence Interval [CI], 1.10–1.23 and OR, 1.69; CI, 1.53–1.87). Amputations had highest PSI risk-adjusted rate (RAR) and carotid endarterectomy and endovascular abdominal aortic aneurysm (AAA) repair had lower RAR (p<.0001). PSI RAR increased linearly by severity of patient indication: claudicants (OR, 0.40, CI, 0.35–0.46), rest pain patients (OR, 0.78, CI 0.69–0.90), ulcer (OR: 1.20, CI: 1.07–1.34) and gangrene patients (OR:1.85, CI: 1.66–2.06). Conclusions Patient safety events in vascular surgery were high and varied by procedure, with amputations and open AAA having substantially more potential adverse events. PSIs were associated with black race, public payer, and procedure indication. It is important to note the overall higher rates of PSIs occurring in vascular patients and appropriately adjust benchmarks for this surgical specialty. PMID:22425449

  16. The ellipsis of prognosis in modern medical thought.

    PubMed

    Christakis, N A

    1997-02-01

    Contemporary textbooks of internal medicine give scant attention to the prognosis of diseases. Has this always been the case? If not, when and why did prognosis come to be de-emphasized? Using a highly regarded, standard medical textbook initially authored by William Osler, The Principles and Practice of Medicine, I performed qualitative and quantitative content analysis of entries regarding lobar pneumonia in selected editions published between 1892 and 1988, with special attention to the period between 1892 and 1947. I chose lobar pneumonia because it was a leading cause of death throughout this period and because it is recognizable across time, thus making it possible to follow the evolution in clinical thinking about prognosis while holding constant the diagnosis. I argue that two powerful forces converged to lead to the ellipsis of prognosis: (1) the emergence of effective therapy, and (2) a fundamental change in the cognitive basis of medicine. With respect to the former, I show that there is a complementary, inverse relationship between the clinical acts of prognostication and therapy; as one increases in salience in the management of a disease, the other decreases. With respect to the latter, I argue that the particular clinical facts deemed to be important about a patient's case have shifted over time, and I explore changes in the clinical and cognitive foundations of physicians' estimation of patients' prognoses-in particular, "symptoms" and "complications." I conclude that, concurrent with a shift in clinical thought from an individual-based to a diagnosis-based conceptualization of disease, prognosis came to be seen as intrinsic to diagnosis and therapy, and explicit attention to prognosis consequently diminished.

  17. Agomelatine: a review of adverse effects.

    PubMed

    2013-03-01

    More pharmacovigilance data on agomelatine became available in 2012. The main sources of information were surveillance data from the French national monitoring system, EU periodic safety update reports (PSURs), and the European pharmacovigilance database. The principal adverse effects of agomelatine consist of hepatic, pancreatic, neuropsychiatric, muscular and cutaneous disorders. The harms associated with agomelatine, which has no proven efficacy in depression, clearly outweigh the benefits. Until regulatory agencies decide to withdraw agomelatine from the market, it is up to healthcare professionals to protect patients from this unnecessarily dangerous drug.

  18. Joint Commission suspends 'auto' adverse decision.

    PubMed

    2010-08-01

    The Joint Commission's revision of its policy on root cause analysis puts greater attention of something that, quite frankly, some ED managers might not have been aware of. The ED manager plays an important role when events occur in the department, such as: knowing who the main Joint Commission contact is in the hospital, and making them aware of a potential adverse or sentinel event that has occurred; participating in the root cause analysis to identify what ED processes might need improvement; making sure the remedial activities recommended can be measured, so The Joint Commission can see an active attempt is being made to improve.

  19. Environmental Perchlorate Exposure: Potential Adverse Thyroid Effects

    PubMed Central

    Leung, Angela M.; Pearce, Elizabeth N.; Braverman, Lewis E.

    2014-01-01

    Purpose of review This review will present a general overview of the sources, human studies, and proposed regulatory action regarding environmental perchlorate exposure. Recent findings Some recent studies have reported significant associations between urinary perchlorate concentrations, thyroid dysfunction, and decreased infant IQ in groups who would be particularly susceptible to perchlorate effects. An update regarding the recent proposed regulatory actions and potential costs surrounding amelioration of perchlorate contamination is provided. Summary The potential adverse thyroidal effects of environmental perchlorate exposure remain controversial, and further research is needed to further define its relationship to human health among pregnant and lactating women and their infants. PMID:25106002

  20. [Adverse drug effects in the community pharmacy].

    PubMed

    Arnet, Isabelle; Seidling, Hanna M; Hersberger, Kurt E

    2015-12-01

    Community pharmacists represent an important pillar for the identification and the reporting of adverse drug effects (ADE}. Thanks to their broad view on the pharmacotherapy, over-the-counter medication included, they contribute greatly to the improvement of drug safety. In principle, the community pharmacy will face three groups of ADE which require specific attention. This article deals with these specific ADE groups and presents some illustrative examples from daily practice. Furthermore, we suggest some solutions to identify potential relevant interactions - including herbal-drug interactions - and give tips for daily practice, along with some often overseen cutaneous ADE.

  1. Mitigation of adverse environmental and unavoidable impacts

    SciTech Connect

    1995-10-01

    This portion of the Energy Vision 2020 draft report is a broad scope discussion of the mitigation of adverse environmental and unavoidable impacts. TVA will mitigate site specific environmental impacts from the construction and operation of new power facilities through a combination of planning, pollution prevention, and environmental controls. However, one of the most important mitigative measures associated with Energy Vision 2020 is the multi-attribute tradeoff method used for the evaluation. This method allowed proposed strategies to be reformated in order to reduce potential impacts.

  2. Adverse environments and children's creativity development: transforming the notion of "success in adversity" in China.

    PubMed

    Cheng, Li; Tan, Mei; Liu, Zhengkui

    2015-01-01

    China has been undergoing great social change due to its new focus on urbanization and globalization. Such change has had a tremendous adverse impact on the living conditions of millions of young children, simultaneously generating new interest in children's creativity development. The intersection of these two issues has important implications for China's future as it brings together one of China's core cultural values-"success in adversity"-the importance of creativity, and very real social and economic needs. "Success in adversity" reflects the strongly held belief that individuals who suffer adverse environments can rise to excellence and success through persistence, effort, and creativity. In this article, we briefly explore the historical sources of this belief and how it is closely related to the Chinese conception of creativity. We then present some studies on the creativity of some of China's migrant children. Findings show that while migrant children as a group may not generally exhibit higher creativity than their urban peers as hypothesized, indications of resilience and creative potential suggest that the notion of success in adversity may contribute to the positive development of China's migrant children more substantially when it is informed by research and augmented by research-supported policy.

  3. Pancreatic endocrine neoplasms: Epidemiology and prognosis of pancreatic endocrine tumors

    PubMed Central

    Halfdanarson, Thorvardur R.; Rubin, Joseph; Farnell, Michael B.; Grant, Clive S.; Petersen, Gloria M.

    2009-01-01

    Pancreatic endocrine neoplasms (PETs) are uncommon tumors with an annual incidence less than 1 per 100,000 persons per year in the general population. PETs that produce hormones resulting in symptoms are designated as functional. The majority of PETs are nonfunctional. Of the functional tumors, insulinomas are the most common, followed by gastrinomas. The clinical course of patients with PETs is variable and depends on the extent of the disease and the treatment rendered. Patients with completely resected tumors generally have a good prognosis, and aggressive surgical therapy in patients with advanced disease may also prolong survival. The epidemiology, prognosis and established and novel prognostic markers of PETs are reviewed. PMID:18508996

  4. Adverse Effects of Psychotropic Medications: A Call to Action.

    PubMed

    Mago, Rajnish

    2016-09-01

    Adverse effects are common, bothersome, and a leading cause of discontinuation of treatment. The methodology for evaluating adverse effects of medications has been greatly neglected, however, especially in comparison to the methodology for assessment of efficacy of medications. Existing methods for assessment and reporting of adverse effects have important limitations leading to lack of much-needed data related to adverse effects. Lastly, there is little systematic research into management of most adverse effects. A series of recommendations are made in this article about how to improve identification, assessment, reporting, and management of adverse effects.

  5. Adversity in Preschool-Aged Children: Effects on Salivary Interleukin-1β

    PubMed Central

    Tyrka, Audrey R.; Parade, Stephanie H.; Valentine, Thomas R.; Eslinger, Nicole M.; Seifer, Ronald

    2016-01-01

    Exposure to early life adversity is linked to impaired affective, cognitive, and behavioral functioning and increases risk for various psychiatric and medical conditions. Stress-induced increases in pro-inflammatory cytokines may be a biological mechanism of these effects. Few studies have examined cytokine levels in children experiencing early life adversity, and very little research has investigated cytokines or other markers of inflammation in saliva. In the present study, we examined salivary IL-1β and C-reactive protein (CRP) levels in relation to stress exposure in 40 children aged 3 to 5 years who were enrolled in a larger study of early life adversity. Childhood maltreatment status was assessed via review of child welfare records, and contextual stress exposure, traumatic life event history, and symptoms of psychopathology were assessed via caregiver interviews at a home visit. In a subsequent visit, salivary IL-1β and CRP were obtained before and after participation in four emotion-eliciting tasks. Number of past month contextual stressors, lifetime contextual stressors, and traumatic life events each demonstrated a significant main effect on IL-1β. Baseline IL-1β was positively associated with each of the significant main-effect adversities. Post-challenge IL-1β displayed positive associations with each adversity variable, but were not significant. CRP was not significantly associated with any of the adversity variables. Given evidence suggesting involvement of IL-1β in the neuropathology of psychiatric conditions, these results may have important implications for developmental outcomes. PMID:25997772

  6. The Useage of Opioids and their Adverse Effects in Gastrointestinal Practice: A Review

    PubMed Central

    Khansari, MahmoudReza; Sohrabi, MasourReza; Zamani, Farhad

    2013-01-01

    Opium is one of the oldest herbal medicines currently used as an analgesic, sedative and antidiarrheal treatment. The effects of opium are principally mediated by the μ-, κ- and δ-opioid receptors. Opioid substances consist of all natural and synthetic alkaloids that are derived from opium. Most of their effects on gastrointestinal motility and secretion result from suppression of neural activity. Inhibition of gastric emptying, increase in sphincter tone, changes in motor patterns, and blockage of peristalsis result from opioid use. Common adverse effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, dependency and tolerance, and respiratory depression. The most common adverse effect of opioid use is constipation. Although stool softeners are frequently used to decrease opioid-induced bowel dysfunction, however they are not efficacious. Possibly, the use of specific opioid receptor antagonists is a more suitable approach. Opioid antagonists, both central and peripheral, could affect gastrointestinal function and visceromotor sensitivity, which suggests an important role for endogenous opioid peptides in the control of gastrointestinal physiology. Underlying diseases or medications known to influence the central nervous system (CNS) often accelerate the opioid’s adverse effects. However, changing the opioid and/or route of administration could also decrease their adverse effects. Appropriate patient selection, patient education and discussion regarding potential adverse effects may assist physicians in maximizing the effectiveness of opioids, while reducing the number and severity of adverse effects. PMID:24829664

  7. Familial risk and childhood adversity interplay in the onset of psychosis

    PubMed Central

    Trotta, Antonella; Di Forti, Marta; Iyegbe, Conrad; Green, Priscilla; Dazzan, Paola; Mondelli, Valeria; Morgan, Craig; Murray, Robin M.

    2015-01-01

    Background The association between childhood adversity and psychosis in adulthood is well established. However, genetic factors might confound or moderate this association. Aims Using a catchment-based case–control sample, we explored the main effects of, and interplay between, childhood adversity and family psychiatric history on the onset of psychosis. Method Childhood adversity (parental separation and death, physical and sexual abuse) was assessed retrospectively in 224 individuals with a first presentation of psychosis and 256 community controls from South London, UK. Occurrence of psychotic and affective disorders in first-degree relatives was ascertained with the Family Interview for Genetic Studies (FIGS). Results Parental history of psychosis did not confound the association between childhood adversity and psychotic disorder. There was no evidence that childhood adversity and familial liability combined synergistically to increase odds of psychosis beyond the effect of each individually. Conclusions Our results do not support the hypothesis that family psychiatric history amplifies the effect of childhood adversity on odds of psychosis. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) licence. PMID:27703716

  8. Association of hypothyroidism with adverse events in patients with heart failure receiving cardiac resynchronization therapy.

    PubMed

    Sharma, Ajay K; Vegh, Eszter; Orencole, Mary; Miller, Alexandra; Blendea, Dan; Moore, Stephanie; Lewis, Gregory D; Singh, Jagmeet P; Parks, Kimberly A; Heist, E Kevin

    2015-05-01

    Hypothyroidism is associated with an adverse prognosis in cardiac patients in general and in particular in patients with heart failure (HF). The aim of this study was to evaluate the impact of hypothyroidism on patients with HF receiving cardiac resynchronization therapy (CRT). Additionally, the impact of level of control of hypothyroidism on risk of adverse events after CRT implantation was also evaluated. We included consecutive patients in whom a CRT device was implanted from April 2004 to April 2010 at our institution with sufficient follow-up data available for analysis; 511 patients were included (age 68.5±12.4 years, women 20.4%); 84 patients with a clinical history of hypothyroidism, on treatment with thyroid hormone repletion or serum thyroid-stimulating hormone level≥5.00 μU/ml, were included in the hypothyroid group. The patients were followed for up to 3 years after implant for a composite end point of hospitalization for HF, left ventricular assist device placement, or heart transplant and cardiac death; 215 composite end point events were noted in this period. In a multivariate model, hypothyroidism (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.027 to 2.085, p=0.035), female gender (HR 0.64, 95% CI 0.428 to 0.963, p=0.032), and creatinine (HR 1.26, 95% CI 1.145 to 1.382, p<0.001) were significantly associated with occurrence of the composite end point; 53.6% of patients with hypothyroidism at baseline developed the composite end point compared with 39.8% of those with euthyroidism (p=0.02). In conclusion, hypothyroidism is associated with a worse prognosis after CRT implantation.

  9. Effect of CETP Polymorphism on Atorvastatin Lipid-Regulating Effect and Clinical Prognosis of Patients with Coronary Heart Disease

    PubMed Central

    Gu, Guo-Long; Xu, Xiao-Lin; Yang, Qing-You; Zeng, Ruo-Long

    2014-01-01

    Background The aim of this study was to investigate the influence of genetic polymorphism of cholesteryl ester transfer protein (CETP) gene polymorphism −629C/A on the therapeutic effect of atorvastatin and clinical outcome in Han Chinese patients with coronary heart disease (CHD). Material/Methods From October 2011 to December 2012, 348 patients with angiographically confirmed CHD were recruited. CETP gene polymorphism was determined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) method. Serum level of CETP was determined with enzyme-1inked immunosorbent assay (ELISA). Lipid 1evel in all patients was determined at baseline and after 12 months of treatment with 20 mg/d of atorvastatin. All the patients were followed-up at least 12 months. Major adverse cardiac events, including death, non-fatal infarction, revascularization, and stroke (MACE), were recorded. Results The frequency of the −629A allele was 0.412. Compared with CC or CA genotypes, individuals with AA genotype had lower CETP levels (P=0.026) and higher high-density lipoprotein cholesterol (HDL-C) levels (P=0.035). After 12 months of atorvastatin therapy, carriers with CC genotype had greater reduction of low-density lipoprotein cholesterol (LDL-C) (P<0.001), reduced LP (a) (P=0.005), and elevated HDL-C (P=0.045) compared with CA or AA genotypes. The incidence of MACE after a mean follow-up of 17.3±5.2 months was 8.8%. The cumulative MACE-free survival rates were 90.1%, 85.2%, and 71.1% for CC, CA, and AA genotypes, respectively. Conclusions Our results suggest that the AA variant of the −629A allele of CETP gene had higher HDL-C levels and reduced CETP levels, but patients with CC genotype appeared to have benefited more from statin therapy with reduction in LDL-C and LP (a) levels. Long-term clinical prognosis was, however, not affected by the 3 genotypes. PMID:25547030

  10. Adverse effects of outdoor pollution in the elderly.

    PubMed

    Simoni, Marzia; Baldacci, Sandra; Maio, Sara; Cerrai, Sonia; Sarno, Giuseppe; Viegi, Giovanni

    2015-01-01

    With fewer newborns and people living longer, older people are making up an increasing fraction of the total population. Epidemiological evidence shows that older-age-related health problems affect a wide and expanding proportion of the world population. One of the major epidemiological trends of this century is the rise of chronic diseases that affect more elderly than younger people. A total of 3.7 million premature deaths worldwide in 2012 are attributable to outdoor air pollution; the susceptibility to adverse effects of air pollution is expected to differ widely between people and within the same person, and also over time. Frailty history, a measure of multi-system decline, modifies cumulative associations between air pollution and lung function. Moreover, pre-existing diseases may determine susceptibility. In the elderly, due to comorbidity, exposure to air pollutants may even be fatal. Rapid and not-well-planned urbanization is associated with high level of ambient air pollution, mainly caused by vehicular exhausts. In general, there is sufficient evidence of the adverse effects related to short-term exposure, while fewer studies have addressed the longer-term health effects. Increased pollution exposures have been associated with increased mortality, hospital admissions/emergency-room visits, mainly due to exacerbations of chronic diseases or to respiratory tract infections (e.g., pneumonia). These effects may also be modulated by ambient temperature and many studies show that the elderly are mostly vulnerable to heat waves. The association between heat and mortality in the elderly is well-documented, while less is known regarding the associations with hospital admissions. Chronic exposure to elevated levels of air pollution has been related to the incidence of chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), asthma, and emphysema. There is also growing evidence suggesting adverse effects on lung function related to long-term exposure

  11. Adverse effects of outdoor pollution in the elderly

    PubMed Central

    Baldacci, Sandra; Maio, Sara; Cerrai, Sonia; Sarno, Giuseppe; Viegi, Giovanni

    2015-01-01

    With fewer newborns and people living longer, older people are making up an increasing fraction of the total population. Epidemiological evidence shows that older-age-related health problems affect a wide and expanding proportion of the world population. One of the major epidemiological trends of this century is the rise of chronic diseases that affect more elderly than younger people. A total of 3.7 million premature deaths worldwide in 2012 are attributable to outdoor air pollution; the susceptibility to adverse effects of air pollution is expected to differ widely between people and within the same person, and also over time. Frailty history, a measure of multi-system decline, modifies cumulative associations between air pollution and lung function. Moreover, pre-existing diseases may determine susceptibility. In the elderly, due to comorbidity, exposure to air pollutants may even be fatal. Rapid and not-well-planned urbanization is associated with high level of ambient air pollution, mainly caused by vehicular exhausts. In general, there is sufficient evidence of the adverse effects related to short-term exposure, while fewer studies have addressed the longer-term health effects. Increased pollution exposures have been associated with increased mortality, hospital admissions/emergency-room visits, mainly due to exacerbations of chronic diseases or to respiratory tract infections (e.g., pneumonia). These effects may also be modulated by ambient temperature and many studies show that the elderly are mostly vulnerable to heat waves. The association between heat and mortality in the elderly is well-documented, while less is known regarding the associations with hospital admissions. Chronic exposure to elevated levels of air pollution has been related to the incidence of chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), asthma, and emphysema. There is also growing evidence suggesting adverse effects on lung function related to long-term exposure

  12. Adverse outcome pathway development II: best practices.

    PubMed

    Villeneuve, Daniel L; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H; LaLone, Carlie A; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-12-01

    Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including those derived through high-throughput in vitro, high content omics and imaging, and biomarker approaches, in risk-based decision making. The previously ad hoc process of AOP development is being formalized through development of internationally harmonized guidance and principles. The goal of this article was to outline the information content desired for formal AOP description and some rules of thumb and best practices intended to facilitate reuse and connectivity of elements of an AOP description in a knowledgebase and network context. For example, key events (KEs) are measurements of change in biological state that are indicative of progression of a perturbation toward a specified adverse outcome. Best practices for KE description suggest that each KE should be defined as an independent measurement made at a particular level of biological organization. The concept of "functional equivalence" can help guide both decisions about how many KEs to include in an AOP and the specificity with which they are defined. Likewise, in describing both KEs and evidence that supports a causal linkage or statistical association between them (ie, a key event relationship; KER), best practice is to build from and contribute to existing KE or KER descriptions in the AOP knowledgebase rather than creating redundant descriptions. The best practices proposed address many of the challenges and uncertainties related to AOP development and help promote a consistent and reliable, yet flexible approach.

  13. Adverse outcome pathway (AOP) development and evaluation ...

    EPA Pesticide Factsheets

    The Adverse Outcome Pathway provides a construct for assembling mechanistic information at different levels of biological organization in a form designed to support regulatory decision making. In particular, it frames the link between molecular and cellular events that can be measured in high throughput toxicity testing and the organism or population-level events that are commonly relevant in defining risk. Recognizing the importance of this emerging framework, the Organisation for Economic Co-operation and Development (OECD) launched a program to support the development, documentation and consideration of AOPs by the international community in 2012 (http://www.oecd.org/chemicalsafety/testing/adverse-outcome-pathways-molecular-screening-and-toxicogenomics.htm). In 2014, a handbook (https://aopkb.org/common/AOP_Handbook.pdf) was developed to guide users in the documentation and evaluation of AOPs and their entry into an official knowledgebase. The handbook draws on longstanding experience in consideration of mechanistic data (e.g., mode of action analysis) to inform risk assessment. To further assist users, a training program was developed by members of the OECD Extended Advisory Group to teach users the basic principles of AOP development and the best practices as outlined in the OECD AOP handbook. Training sessions began in early 2015, and this course will provide training for interested SOT scientists. Following this course, all participants will be familiar w

  14. [Adverse events of immune checkpoint inhibitors].

    PubMed

    Foller, S; Oppel-Heuchel, H; Fetter, I; Winkler, Y; Grimm, M-O

    2017-04-01

    After immune checkpoint inhibitor therapy was approved for renal cell carcinoma last year, this new immune therapy has spread to urology. Further approvals (atezolizumab, nivolumab, pembrolizumab) are expected in 2017 for metastatic urothelial carcinoma that has progressed following treatment with platinum-based chemotherapy. With expanding use of immune checkpoint inhibitors, experience in diagnosing and managing immune-mediated adverse events increases. Although of low incidence, grade 3/4 toxicities play a central role. Organs most common for immune-mediated adverse events are skin, liver (hepatitis), kidneys (nephritis), gastrointestinal tract (diarrhea and colitis), lungs (pneumonitis), and endocrine organs (hyper-, hypothyroidism and hypophysitis). Diagnostic workup includes routine laboratory tests (including liver function tests) and may be supplemented with hormone values. In cases of pneumonitis or hypophysitis, imaging (high-resolution CT, MRI) can confirm diagnoses. Immune-mediated toxicities are treated with therapy interruption and administration of corticosteroids (and in individual cases additional immunosuppression). Dose modification is not intended!

  15. Adverse effects of new antiepileptic drugs.

    PubMed

    Onat, Filiz; Ozkara, Cigdem

    2004-04-01

    Starting with phenobarbital in the 1900s, it took almost 70-80 years to introduce old-generation agents for the treatment of epilepsy. Then, in eleven years, nine more new antiepileptic drugs were added to the armamentarium. These drugs produce a nearly 40-50% decrease in seizure incidence in refractory patients, but few patients have been able to achieve complete freedom from seizures. So the search for more effective drugs with minimal adverse effect profiles will continue. Although the new antiepileptic drugs do not demonstrate a superior efficacy compared to the older ones, they do offer some advantages in terms of tolerability, fewer drug interactions and simpler pharmacokinetics. However, our knowledge concerning their safety profiles can not yet be considered adequate due to the relatively short time these drugs have been on the market and to the limited number of patients exposed to them. The fact that the serious side effects of felbamate and vigabatrine appeared late after marketing should be taken as an important lesson because it implies the potential for unknown side effects at any time during treatment. Antiepileptic drug treatment should begin with diagnosis of the seizure and epileptic syndrome, followed by selection of the drug most appropriate for treatment of the individual patient, and continued with monitoring of not only the seizures but the adverse effect profile as well.

  16. Immunomodulatory drugs: Oral and systemic adverse effects

    PubMed Central

    Mattila, Riikka; Gomez-Font, Rafael; Meurman, Jukka H.

    2014-01-01

    Objectives: The main objectives are to present the different adverses effects of the immunomodulatory drugs that can impair the quality of life of the immunosupressed patients and study the impact of immunomodualtion on oral diseases. Immunomodulatory drugs have changed the treatment protocols of many diseases where immune functions play a central role, such as rheumatic diseases. Their effect on oral health has not been systematically investigated, however. Study Design: We review current data on the new immunomodulatory drugs from the oral health perspective based on open literature search of the topic. Results: These target specific drugs appear to have less drug interactions than earlier immunomodulating medicines but have nevertheless potential side effects such as activating latent infections. There are some data showing that the new immunomodulatory drugs may also have a role in the treatment of certain oral diseases such as lichen planus or ameliorating symptoms in Sjögren´s syndrome, but the results have not been overly promising. Conclusions: In general, data are sparse of the effect of these new drugs vs. oral diseases and there are no properly powered randomized controlled trials published on this topic. Key words:Immunomodulatory drugs, oral diseases, adverse effects, therapeutic action. PMID:23986016

  17. Development of a Pediatric Adverse Events Terminology

    PubMed Central

    Gipson, Debbie S.; Kirkendall, Eric S.; Gumbs-Petty, Brenda; Quinn, Theresa; Steen, A.; Hicks, Amanda; McMahon, Ann; Nicholas, Savian; Zhao-Wong, Anna; Taylor-Zapata, Perdita; Turner, Mark; Herreshoff, Emily; Jones, Charlotte; Davis, Jonathan M.; Haber, Margaret; Hirschfeld, Steven

    2017-01-01

    In 2009, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Pediatric Terminology Harmonization Initiative to establish a core library of terms to facilitate the acquisition and sharing of knowledge between pediatric clinical research, practice, and safety reporting. A coalition of partners established a Pediatric Terminology Adverse Event Working Group in 2013 to develop a specific terminology relevant to international pediatric adverse event (AE) reporting. Pediatric specialists with backgrounds in clinical care, research, safety reporting, or informatics, supported by biomedical terminology experts from the National Cancer Institute’s Enterprise Vocabulary Services participated. The multinational group developed a working definition of AEs and reviewed concepts (terms, synonyms, and definitions) from 16 pediatric clinical domains. The resulting AE terminology contains >1000 pediatric diseases, disorders, or clinical findings. The terms were tested for proof of concept use in 2 different settings: hospital readmissions and the NICU. The advantages of the AE terminology include ease of adoption due to integration with well-established and internationally accepted biomedical terminologies, a uniquely temporal focus on pediatric health and disease from conception through adolescence, and terms that could be used in both well- and underresourced environments. The AE terminology is available for use without restriction through the National Cancer Institute’s Enterprise Vocabulary Services and is fully compatible with, and represented in, the Medical Dictionary for Regulatory Activities. The terminology is intended to mature with use, user feedback, and optimization. PMID:28028203

  18. Development of a Pediatric Adverse Events Terminology.

    PubMed

    Gipson, Debbie S; Kirkendall, Eric S; Gumbs-Petty, Brenda; Quinn, Theresa; Steen, A; Hicks, Amanda; McMahon, Ann; Nicholas, Savian; Zhao-Wong, Anna; Taylor-Zapata, Perdita; Turner, Mark; Herreshoff, Emily; Jones, Charlotte; Davis, Jonathan M; Haber, Margaret; Hirschfeld, Steven

    2017-01-01

    In 2009, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Pediatric Terminology Harmonization Initiative to establish a core library of terms to facilitate the acquisition and sharing of knowledge between pediatric clinical research, practice, and safety reporting. A coalition of partners established a Pediatric Terminology Adverse Event Working Group in 2013 to develop a specific terminology relevant to international pediatric adverse event (AE) reporting. Pediatric specialists with backgrounds in clinical care, research, safety reporting, or informatics, supported by biomedical terminology experts from the National Cancer Institute's Enterprise Vocabulary Services participated. The multinational group developed a working definition of AEs and reviewed concepts (terms, synonyms, and definitions) from 16 pediatric clinical domains. The resulting AE terminology contains >1000 pediatric diseases, disorders, or clinical findings. The terms were tested for proof of concept use in 2 different settings: hospital readmissions and the NICU. The advantages of the AE terminology include ease of adoption due to integration with well-established and internationally accepted biomedical terminologies, a uniquely temporal focus on pediatric health and disease from conception through adolescence, and terms that could be used in both well- and underresourced environments. The AE terminology is available for use without restriction through the National Cancer Institute's Enterprise Vocabulary Services and is fully compatible with, and represented in, the Medical Dictionary for Regulatory Activities. The terminology is intended to mature with use, user feedback, and optimization.

  19. Consumer reporting of adverse events following immunization

    PubMed Central

    Clothier, Hazel J; Selvaraj, Gowri; Easton, Mee Lee; Lewis, Georgina; Crawford, Nigel W; Buttery, Jim P

    2014-01-01

    Surveillance of adverse events following immunisation (AEFI) is an essential component of vaccine safety monitoring. The most commonly utilized passive surveillance systems rely predominantly on reporting by health care providers (HCP). We reviewed adverse event reports received in Victoria, Australia since surveillance commencement in July 2007, to June 2013 (6 years) to ascertain the contribution of consumer (vaccinee or their parent/guardian) reporting to vaccine safety monitoring and to inform future surveillance system development directions. Categorical data included were: reporter type; serious and non-serious AEFI category; and, vaccinee age group. Chi-square test and 2-sample test of proportions were used to compare categories; trend changes were assessed using linear regression. Consumer reporting increased over the 6 years, reaching 21% of reports received in 2013 (P <0.001), most commonly for children aged less than 7 years. Consumer reports were 5% more likely to describe serious AEFI than HCP (P = 0.018) and 10% more likely to result in specialist clinic attendance (P <0.001). Although online reporting increased to 32% of all report since its introduction in 2010, 85% of consumers continued to report by phone. Consumer reporting of AEFI is a valuable component of vaccine safety surveillance in addition to HCP reporting. Changes are required to AEFI reporting systems to implement efficient consumer AEFI reporting, but may be justified for their potential impact on signal detection sensitivity. PMID:25483686

  20. Accelerating Adverse Outcome Pathway (AOP) development ...

    EPA Pesticide Factsheets

    The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. However, the conventional process for assembly of these AOPs is time and resource intensive, and has been a rate limiting step for AOP use and development. Therefore computational approaches to accelerate the process need to be developed. We previously developed a method for generating computationally predicted AOPs (cpAOPs) by association mining and integration of data from publicly available databases. In this work, a cpAOP network of ~21,000 associations was established between 105 phenotypes from TG-GATEs rat liver data from different time points (including microarray, pathological effects and clinical chemistry data), 994 REACTOME pathways, 688 High-throughput assays from ToxCast and 194 chemicals. A second network of 128,536 associations was generated by connecting 255 biological target genes from ToxCast to 4,980 diseases from CTD using either HT screening activity from ToxCast for 286 chemicals or CTD gene expression changes in response to 2,330 chemicals. Both networks were separately evaluated through manual extraction of disease-specific cpAOPs and comparison with expert curation of the relevant literature. By employing data integration strategies that involve the weighting of n

  1. PUTATIVE ADVERSE OUTCOME PATHWAY FOR INHIBITON ...

    EPA Pesticide Factsheets

    The adverse outcome pathway (AOP) provides a framework for organizing knowledge to define links between a molecular initiating event (MIE) and an adverse outcome (AO) occurring at a higher level of biological organization, such as the individual or population. The AOP framework proceeds from a general (e.g., not chemical specific) molecular mode of action, designated as a MIE, through stepwise changes in biological status, defined as key events (KEs), to a final AO that can be used in risk assessment. Because aromatase-inhibiting pharmaceuticals are widely used to treat breast cancer patients, we explored the unintended consequences that might occur in fish exposed to these chemicals through wastewater discharge into the aquatic environment. Unlike mammals, fish have two isoforms of aromatase, one that predominates in the ovary (cyp19a1a) and a second (cyp19a1b) that prevails in the brain. Aromatase activity in fish brain can be 100 to 1000 times that in mammals and is associated with reproduction. We have developed a putative AOP for inhibition of brain aromatase in fish leading to reproductive dysfunction based on review of relevant literature and reproductive experiments with the marine fish cunner (Tautogolabrus adspersus) exposed to aromatase-inhibiting pharmaceuticals in the laboratory. The first KE in this AOP is a decrease in brain aromatase activity due to exposure to an aromatase inhibitor. KEs then progress through subsequent steps including decreas

  2. The adverse effects profile of levetiracetam in epilepsy: a more detailed look.

    PubMed

    Mbizvo, Gashirai K; Dixon, Pete; Hutton, Jane L; Marson, Anthony G

    2014-09-01

    The adverse effects profile of levetiracetam in epilepsy is still being fully described. We recently published a Cochrane Review evaluating the effectiveness of levetiracetam, added on to usual care, in treating drug-resistant focal epilepsy. The five most common adverse effects were reported and analysed with no scope for reporting any less common adverse effects than those. Here, we report and analyse the remaining adverse effects (including the five most common). These were (in decreasing order of frequency) somnolence; headache; asthenia; accidental injury; dizziness; infection; pharyngitis; pain; rhinitis; abdominal pain; flu syndrome; vomiting; diarrhoea; convulsion; nausea; increased cough; anorexia; upper respiratory tract infection; hostility; personality disorder; urinary tract infection; nervousness; depression; aggression; back pain; agitation; emotional liability; psychomotor hyperactivity; pyrexia; rash; ECG abnormalities; decreased appetite; nasal congestion; irritability; abnormal behaviour; epistaxis; insomnia; altered mood; anxiety; bloody urine; diplopia; dissociation; memory impairment; pruritis; increased appetite; acne; and stomach discomfort. Only somnolence and infection were significantly associated with levetiracetam. When adverse effects pertaining to infection were combined, these affected 19.7% and 15.1% of participants on levetiracetam and placebo (relative risk 1.16, CI 0.89-1.50, Chi(2) heterogeneity p = 0.13). Somnolence and infection further retained significance in adults while no single adverse effect was significant in children. This review updates the adverse effects profile data on levetiracetam use by empirically reporting its common and uncommon adverse effects and analysing their relative importance statistically using data from a group of trials that possess low Risk of Bias and high Quality of Evidence GRADE scores.

  3. Adverse reactions to antituberculosis drugs in Manguinhos, Rio de Janeiro, Brazil

    PubMed Central

    Damasceno, Glauciene Santana; Guaraldo, Lusiele; Engstrom, Elyne Montenegro; Filha, Mariza Miranda Theme; Santos, Reinaldo Souza-; Vasconcelos, Ana Gloria Godoi; Rozenfeld, Suely

    2013-01-01

    OBJECTIVES: This study aimed to characterize and estimate the frequency of adverse reactions to antituberculosis drugs in the population treated at the Centro de Saúde Escola Germano Sinval Faria, a primary health care clinic in Manguinhos, Rio de Janeiro City, and to explore the relationship between adverse drug reactions and some of the patients' demographic and health characteristics. METHODS: This descriptive study was conducted via patient record review of incident cases between 2004 and 2008. RESULTS: Of the 176 patients studied, 41.5% developed one or more adverse reactions to antituberculosis drugs, totaling 126 occurrences. The rate of adverse reactions to antituberculosis drugs was higher among women, patients aged 50 years or older, those with four or more comorbidities, and those who used five or more drugs. Of the total reactions, 71.4% were mild. The organ systems most affected were as follows: the gastrointestinal tract (29.4%), the skin and appendages (21.4%), and the central and peripheral nervous systems (14.3%). Of the patients who experienced adverse reactions to antituberculosis drugs, 65.8% received no drug treatment for their adverse reactions, and 4.1% had one of the antituberculosis drugs suspended because of adverse reactions. “Probable reactions” (75%) predominated over “possible reactions” (24%). In the study sample, 64.3% of the reactions occurred during the first two months of treatment, and most (92.6%) of the reactions were ascribed to the combination of rifampicin + isoniazid + pyrazinamide (Regimen I). A high dropout rate from tuberculosis treatment (24.4%) was also observed. CONCLUSION: This study suggests a high rate of adverse reactions to antituberculosis drugs. PMID:23644852

  4. 19 CFR 181.116 - Petition regarding adverse marking decision.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... for NAFTA Review of Adverse Marking Decision” and shall be signed by the exporter, producer or his... other than the principal. (c) Content. The Petition for NAFTA Review of Adverse Marking Decision...

  5. 19 CFR 181.116 - Petition regarding adverse marking decision.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... for NAFTA Review of Adverse Marking Decision” and shall be signed by the exporter, producer or his... other than the principal. (c) Content. The Petition for NAFTA Review of Adverse Marking Decision...

  6. 19 CFR 181.116 - Petition regarding adverse marking decision.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... for NAFTA Review of Adverse Marking Decision” and shall be signed by the exporter, producer or his... other than the principal. (c) Content. The Petition for NAFTA Review of Adverse Marking Decision...

  7. 19 CFR 181.116 - Petition regarding adverse marking decision.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... for NAFTA Review of Adverse Marking Decision” and shall be signed by the exporter, producer or his... other than the principal. (c) Content. The Petition for NAFTA Review of Adverse Marking Decision...

  8. 19 CFR 181.116 - Petition regarding adverse marking decision.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... for NAFTA Review of Adverse Marking Decision” and shall be signed by the exporter, producer or his... other than the principal. (c) Content. The Petition for NAFTA Review of Adverse Marking Decision...

  9. Adverse Outcome Pathways – Tailoring Development to Support Use

    EPA Science Inventory

    Adverse Outcome Pathways (AOPs) represent an ideal framework for connecting high-throughput screening (HTS) data and other toxicity testing results to adverse outcomes of regulatory importance. The AOP Knowledgebase (AOP-KB) captures AOP information to facilitate the development,...

  10. Adverse outcome pathway (AOP) development I: Strategies and principles

    EPA Science Inventory

    An adverse outcome pathway (AOP) is a conceptual framework that organizes existing knowledge concerning biologically plausible, and empirically-supported, links between molecular-level perturbation of a biological system and an adverse outcome at a level of biological organizatio...

  11. Adverse Outcome Pathway (AOP) Network Development for Fatty Liver

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are descriptive biological sequences that start from a molecular initiating event (MIE) and end with an adverse health outcome. AOPs provide biological context for high throughput chemical testing and further prioritize environmental health risk re...

  12. Cerebro-costo-mandibular syndrome: prognosis and proposal for classification.

    PubMed

    Nagasawa, Hiroyuki; Yamamoto, Yutaka; Kohno, Yoshinori

    2010-09-01

    Cerebro-costo-mandibular syndrome (CCMS) is a very rare syndrome characterized by micrognathia and posterior rib gap, with a poor prognosis. To date, only 75 cases have been reported worldwide. The overall survival rate for patients with this disorder has not been reported, and a classification of the patients on the basis of the prognosis is not yet available. The present study analyzed the figures and prognoses of past patients and documented a new case of CCMS. Formerly published case reports and personal communications were used to reveal the prognosis and classification of CCMS. The occurrence ratios of rib gap defects and of missing ribs were examined. Patients were divided into the following three groups according to their life span: lethal type, where the patients died before 1 month; severe type, where the patients lived for 1-12 months; and mild type, where they survived for more than 1 year. A comparison was made of the number of rib gaps, missing ribs, and the rib gap ratio (defined as the number of rib gaps divided by the number of all existing ribs) among these three groups. A significant difference in the number of rib defects between the lethal type and other types was noted. Short life span of severe type patients, compared to mild type, was attributed to their subjection to severe respiratory infection. CCMS can be classified into three categories--lethal, severe, and mild--according to the severity of the symptoms and prognosis.

  13. Integrated Fatigue Damage Diagnosis and Prognosis Under Uncertainties

    DTIC Science & Technology

    2012-09-01

    length. Next, a Bayesian updating algorithm is implemented incorporating the damage diagnostic result for the fatigue crack growth prediction...proposed methodology is demonstrated using data from fatigue testing of realistic fuselage lap joints and the model predictions are validated using...damage prognosis process. Finally, the proposed methodology is demonstrated using data from fatigue testing of realistic fuselage lap joints and the model

  14. Movement Disorders Following Cerebrovascular Lesions: Etiology, Treatment Options and Prognosis

    PubMed Central

    Kwon, Do-Young

    2016-01-01

    Post-stroke movement disorders are uncommon, but comprise an important part of secondary movement disorders. These exert variable and heterogeneous clinical courses according to the stroke lesion and its temporal relationships. Moreover, the predominant stroke symptoms hinder a proper diagnosis in clinical practice. This article describes the etiology, treatment options and prognosis of post-stroke movement disorders. PMID:27240807

  15. [Tooth decay and its complication prognosis in smokers].

    PubMed

    Orekhova, L Iu; Osipova, M V

    2014-01-01

    The study focuses on complicated and non-complicated tooth decay course and prognosis in smokers. Oral status, prevention and treatment effectiveness was assessed in 330 non-smokers and 345 smoking patients. The results allowed concluding with guidelines for tooth decay prevention and treatment in smokers.

  16. Visual prognosis following treatment of acute central retinal artery obstruction.

    PubMed Central

    Augsburger, J J; Magargal, L E

    1980-01-01

    The authors report the visual outcome in 34 consecutive cases of treated acute central retinal artery obstruction. Visual acuity equal to or better than 6/30 was recovered in 35% of the cases. The presenting visual acuity and duration of visual impairment appear to correlate with visual prognosis. PMID:7448144

  17. Coping with Poor Prognosis in the Pediatric Intensive Care Unit.

    ERIC Educational Resources Information Center

    Waller, David A.; And Others

    1979-01-01

    The intensive care pediatrician who prophesies to parents that their child's illness is irreversible may encounter denial and hostility. Four cases are reported in which parents rejected their child's hopeless prognosis, counterprophesied miraculous cures, resolved to obtain exorcism, criticized the care, or accused nurses of neglect. Journal…

  18. [Pathogenesis and prognosis of pyoderma gangrenosum (dermatitis ulcerosa) (author's transl)].

    PubMed

    Odeh, F

    1981-12-15

    The diagnosis of p. g. is based on clinical appearance. P. g. is frequently associated with systemic disease. This paper presents 23 cases of p. g. associated with other sufferings and a review of the Literature in which pathogenesis, prognosis, age and sex of this cutaneous disorder are standing in foreground for a discussion.

  19. Factors related to prognosis of acquired aphasia in children.

    PubMed

    van Dongen, H R; Loonen, M C

    1977-06-01

    In a follow up study of 15 children with acquired aphasia, it was found that the persistent presence of concomitant neurological disorders was important for the final outcome. Prognosis seemed to be related to etiology, EEG disturbances and the severity of comprehension deficit at the onset of aphasia.

  20. Adverse weather impacts on arable cropping systems

    NASA Astrophysics Data System (ADS)

    Gobin, Anne

    2016-04-01

    Damages due to extreme or adverse weather strongly depend on crop type, crop stage, soil conditions and management. The impact is largest during the sensitive periods of the farming calendar, and requires a modelling approach to capture the interactions between the crop, its environment and the occurrence of the meteorological event. The hypothesis is that extreme and adverse weather events can be quantified and subsequently incorporated in current crop models. Since crop development is driven by thermal time and photoperiod, a regional crop model was used to examine the likely frequency, magnitude and impacts of frost, drought, heat stress and waterlogging in relation to the cropping season and crop sensitive stages. Risk profiles and associated return levels were obtained by fitting generalized extreme value distributions to block maxima for air humidity, water balance and temperature variables. The risk profiles were subsequently confronted with yields and yield losses for the major arable crops in Belgium, notably winter wheat, winter barley, winter oilseed rape, sugar beet, potato and maize at the field (farm records) to regional scale (statistics). The average daily vapour pressure deficit (VPD) and reference evapotranspiration (ET0) during the growing season is significantly lower (p < 0.001) and has a higher variability before 1988 than after 1988. Distribution patterns of VPD and ET0 have relevant impacts on crop yields. The response to rising temperatures depends on the crop's capability to condition its microenvironment. Crops short of water close their stomata, lose their evaporative cooling potential and ultimately become susceptible to heat stress. Effects of heat stress therefore have to be combined with moisture availability such as the precipitation deficit or the soil water balance. Risks of combined heat and moisture deficit stress appear during the summer. These risks are subsequently related to crop damage. The methodology of defining

  1. Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function

    PubMed Central

    Anacker, Christoph; O'Donnell, Kieran J.; Meaney, Michael J.

    2014-01-01

    We review studies with human and nonhuman species that examine the hypothesis that epigenetic mechanisms, particularly those affecting the expression of genes implicated in stress responses, mediate the association between early childhood adversity and later risk of depression. The resulting studies provide evidence consistent with the idea that social adversity, particularly that involving parent-offspring interactions, alters the epigenetic state and expression of a wide range of genes, the products of which regulate hypothalamic-pituitary-adrenal function. We also address the challenges for future studies, including that of the translation of epigenetic studies towards improvements in treatments. PMID:25364283

  2. Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function.

    PubMed

    Anacker, Christoph; O'Donnell, Kieran J; Meaney, Michael J

    2014-09-01

    We review studies with human and nonhuman species that examine the hypothesis that epigenetic mechanisms, particularly those affecting the expression of genes implicated in stress responses, mediate the association between early childhood adversity and later risk of depression. The resulting studies provide evidence consistent with the idea that social adversity, particularly that involving parent-offspring interactions, alters the epigenetic state and expression of a wide range of genes, the products of which regulate hypothalamic-pituitary-adrenal function. We also address the challenges for future studies, including that of the translation of epigenetic studies towards improvements in treatments.

  3. Transgenerational transmission of pregestational and prenatal experience: maternal adversity, enrichment, and underlying epigenetic and environmental mechanisms.

    PubMed

    Taouk, L; Schulkin, J

    2016-12-01

    Transgenerational transmission refers to positive and negative adaptations in brain function and behavior that affect following generations. In this paper, empirical findings regarding the transgenerational transmission of maternal adversity during three critical periods - childhood, pregestational adulthood and pregnancy - will be reviewed in terms of pregnancy outcomes, maternal care, offspring behavior and development, and physiological functioning. Research on the transgenerational transmission of enrichment and the implications for interventions to ameliorate the consequences of adversity will also be presented. In the final section, underlying epigenetic and environmental mechanisms that have been proposed to explain how experience is transferred across generations through transgenerational transmission will be reviewed. Directions for future research are suggested throughout.

  4. Patient stratification and identification of adverse event correlations in the space of 1190 drug related adverse events

    PubMed Central

    Roitmann, Eva; Eriksson, Robert; Brunak, Søren

    2014-01-01

    Purpose: New pharmacovigilance methods are needed as a consequence of the morbidity caused by drugs. We exploit fine-grained drug related adverse event information extracted by text mining from electronic medical records (EMRs) to stratify patients based on their adverse events and to determine adverse event co-occurrences. Methods: We analyzed the similarity of adverse event profiles of 2347 patients extracted from EMRs from a mental health center in Denmark. The patients were clustered based on their adverse event profiles and the similarities were presented as a network. The set of adverse events in each main patient cluster was evaluated. Co-occurrences of adverse events in patients (p-value < 0.01) were identified and presented as well. Results: We found that each cluster of patients typically had a most distinguishing adverse event. Examination of the co-occurrences of adverse events in patients led to the identification of potentially interesting adverse event correlations that may be further investigated as well as provide further patient stratification opportunities. Conclusions: We have demonstrated the feasibility of a novel approach in pharmacovigilance to stratify patients based on fine-grained adverse event profiles, which also makes it possible to identify adverse event correlations. Used on larger data sets, this data-driven method has the potential to reveal unknown patterns concerning adverse event occurrences. PMID:25249979

  5. Adversity and Resilience: A Synthesis of International Research

    ERIC Educational Resources Information Center

    Noltemeyer, Amity L.; Bush, Kevin R.

    2013-01-01

    Children and adolescents worldwide experience a variety of adversities that have the potential to disrupt typical development. However, some of these individuals exhibit resilience, evidencing normal development in the face of adversity. Here we review research on these constructs of risk, adversity, and resilience; synthesize international…

  6. 36 CFR 800.5 - Assessment of adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Assessment of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.5 Assessment of adverse effects. (a) Apply criteria of adverse effect. In consultation with the SHPO/THPO and any Indian tribe or Native...

  7. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. Link to an amendment published at 77 FR 18, Jan. 3, 2012. (a) Records shall be maintained of any reports of complaints of adverse reactions regarding each unit of blood or blood...

  8. 36 CFR 800.6 - Resolution of adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Resolution of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.6 Resolution of adverse effects. (a) Continue... the undertaking that could avoid, minimize, or mitigate adverse effects on historic properties....

  9. A genetic programming approach to oral cancer prognosis

    PubMed Central

    Tan, Mei Sze; Tan, Jing Wei; Yap, Hwa Jen; Abdul Kareem, Sameem; Zain, Rosnah Binti

    2016-01-01

    Background The potential of genetic programming (GP) on various fields has been attained in recent years. In bio-medical field, many researches in GP are focused on the recognition of cancerous cells and also on gene expression profiling data. In this research, the aim is to study the performance of GP on the survival prediction of a small sample size of oral cancer prognosis dataset, which is the first study in the field of oral cancer prognosis. Method GP is applied on an oral cancer dataset that contains 31 cases collected from the Malaysia Oral Cancer Database and Tissue Bank System (MOCDTBS). The feature subsets that is automatically selected through GP were noted and the influences of this subset on the results of GP were recorded. In addition, a comparison between the GP performance and that of the Support Vector Machine (SVM) and logistic regression (LR) are also done in order to verify the predictive capabilities of the GP. Result The result shows that GP performed the best (average accuracy of 83.87% and average AUROC of 0.8341) when the features selected are smoking, drinking, chewing, histological differentiation of SCC, and oncogene p63. In addition, based on the comparison results, we found that the GP outperformed the SVM and LR in oral cancer prognosis. Discussion Some of the features in the dataset are found to be statistically co-related. This is because the accuracy of the GP prediction drops when one of the feature in the best feature subset is excluded. Thus, GP provides an automatic feature selection function, which chooses features that are highly correlated to the prognosis of oral cancer. This makes GP an ideal prediction model for cancer clinical and genomic data that can be used to aid physicians in their decision making stage of diagnosis or prognosis. PMID:27688975

  10. Prognosis of glioblastoma multiforme using textural properties on MRI

    NASA Astrophysics Data System (ADS)

    Heydari, Maysam

    This thesis addresses the challenge of prognosis, in terms of survival prediction, for patients with Glioblastoma Multiforme brain tumors. Glioblastoma is the most malignant brain tumor, which has a median survival time of no more than a year. Accurate assessment of prognostic factors is critical in deciding amongst different treatment options and in designing stratified clinical trials. This thesis is motivated by two observations. Firstly, clinicians often refer to properties of glioblastoma tumors based on magnetic resonance images when assessing prognosis. However, clinical data, along with histological and most recently, molecular and gene expression data, have been more widely and systematically studied and used in prognosis assessment than image based information. Secondly, patient survival times are often used along with clinical data to conduct population studies on brain tumor patients. Recursive Partitioning Analysis is typically used in these population studies. However, researchers validate and assess the predictive power of these models by measuring the statistical association between survival groups and survival times. In this thesis, we propose a learning approach that uses historical training data to produce a system that predicts patient survival. We introduce a classification model for predicting patient survival class, which uses texture based features extracted from magnetic resonance images as well as other patient properties. Our prognosis approach is novel as it is the first to use image-extracted textural characteristics of glioblastoma scans, in a classification model whose accuracy can be reliably validated by cross validation. We show that our approach is a promising new direction for prognosis in brain tumor patients

  11. A mathematical prognosis model for pancreatic cancer patients receiving immunotherapy.

    PubMed

    Li, Xuefang; Xu, Jian-Xin

    2016-10-07

    Pancreatic cancer is one of the most deadly types of cancer since it typically spreads rapidly and can seldom be detected in its early stage. Pancreatic cancer therapy is thus a challenging task, and appropriate prognosis or assessment for pancreatic cancer therapy is of critical importance. In this work, based on available clinical data in Niu et al. (2013) we develop a mathematical prognosis model that can predict the overall survival of pancreatic cancer patients who receive immunotherapy. The mathematical model incorporates pancreatic cancer cells, pancreatic stellate cells, three major classes of immune effector cells CD8+ T cells, natural killer cells, helper T cells, and two major classes of cytokines interleukin-2 (IL-2) and interferon-γ (IFN-γ). The proposed model describes the dynamic interaction between tumor and immune cells. In order for the model to be able to generate appropriate prognostic results for disease progression, the distribution and stability properties of equilibria in the mathematical model are computed and analysed in absence of treatments. In addition, numerical simulations for disease progression with or without treatments are performed. It turns out that the median overall survival associated with CIK immunotherapy is prolonged from 7 to 13months compared with the survival without treatment, this is consistent with the clinical data observed in Niu et al. (2013). The validity of the proposed mathematical prognosis model is thus verified. Our study confirms that immunotherapy offers a better prognosis for pancreatic cancer patients. As a direct extension of this work, various new therapy methods that are under exploration and clinical trials could be assessed or evaluated using the newly developed mathematical prognosis model.

  12. Diabetes mellitus and prognosis in women with breast cancer

    PubMed Central

    Zhao, Xiao-Bo; Ren, Guo-Sheng

    2016-01-01

    Abstract Background: Diabetes mellitus is associated with an increased risk of breast cancer, but studies of the effects of diabetes on the prognosis of women with breast cancer have yielded inconsistent findings. The present meta-analysis aimed to investigate the impact of preexisting diabetes on the prognosis in terms of overall survival (OS), disease-free survival (DFS), and relapse-free period (RFP) in women with breast cancer. Methods: We searched the Embase and PubMed databases until June 2016 for cohort or case–control studies assessing the impact of diabetes on the prognosis of women with breast cancer. The pooled multivariate adjusted hazard ratio (HR) and their 95% confidence intervals (CIs) for OS, DFS, and RFP were used to analyze the impact of diabetes on the prognosis of breast cancer patients. Results: Seventeen studies involving 48,315 women with breast cancer met our predefined inclusion criteria. Meta-analysis showed that the pooled adjusted HR was 1.51 (95% CI 1.34–1.70) for OS and 1.28 (95% CI 1.09–1.50) for DFS in breast cancer patients with diabetes compared to those without diabetes. However, RFP did not differ significantly between patients with and without diabetes (HR 1.42; 95% CI 0.90–2.23). Conclusions: The present meta-analysis suggests that preexisting diabetes is independently associated with poor OS and DFS in female breast cancer patients. However, the impact of diabetes on RFP should be further verified. More prospective studies are warranted to investigate whether appropriate glycemic control with modification of antihyperglycemic agents can improve the prognosis of female breast cancer patients with diabetes. PMID:27930583

  13. Adverse effects of differential parental attention1

    PubMed Central

    Sajwaj, Thomas E.; Pinkston, Susan; Cordua, Glenn; Jackson, Carolyn; Herbert, Emily W.; Pinkston, Elsie M.; Hayden, M. Loeman

    1973-01-01

    In two independent parent training projects (Kansas and Mississippi), mothers of deviant young children were observed to follow almost all child behaviors with attention. The mothers were then trained to use differential attention procedures to increase their child's appropriate behaviors and to decrease deviant behaviors. Contrary to expectations, the differential attention procedure produced substantial increases in deviant behavior for four of the children. This adverse effect was maintained over many sessions and was replicated in single organism, reversal designs. A fifth child showed no change. A sixth child showed some improvement. However, this effect was not recovered in a second application of differential attention, and the child became worse. The results underline the importance of subject generality in applied behavior analysis and strongly suggest that service programs using operant techniques must carefully evaluate their effects on behavior. PMID:16795386

  14. D-Dimer elevation and adverse outcomes.

    PubMed

    Halaby, Rim; Popma, Christopher J; Cohen, Ander; Chi, Gerald; Zacarkim, Marcelo Rodrigues; Romero, Gonzalo; Goldhaber, Samuel Z; Hull, Russell; Hernandez, Adrian; Mentz, Robert; Harrington, Robert; Lip, Gregory; Peacock, Frank; Welker, James; Martin-Loeches, Ignacio; Daaboul, Yazan; Korjian, Serge; Gibson, C Michael

    2015-01-01

    D-Dimer is a biomarker of fibrin formation and degradation. While a D-dimer within normal limits is used to rule out the diagnosis of deep venous thrombosis and pulmonary embolism among patients with a low clinical probability of venous thromboembolism (VTE), the prognostic association of an elevated D-dimer with adverse outcomes has received far less emphasis. An elevated D-dimer is independently associated with an increased risk for incident VTE, recurrent VTE, and mortality. An elevated D-dimer is an independent correlate of increased mortality and subsequent VTE across a broad variety of disease states. Therefore, medically ill subjects in whom the D-dimer is elevated constitute a high risk subgroup in which the prospective evaluation of the efficacy and safety of antithrombotic therapy is warranted.

  15. Adverse reactions to the sulphite additives

    PubMed Central

    Misso, Neil LA

    2012-01-01

    Sulphites are widely used as preservative and antioxidant additives in the food and pharmaceutical industries. Exposure to sulphites has been reported to induce a range of adverse clinical effects in sensitive individuals, ranging from dermatitis, urticaria, flushing, hypotension, abdominal pain and diarrhoea to life-threatening anaphylactic and asthmatic reactions. Exposure to the sulphites arises mainly from the consumption of foods and drinks that contain these additives; however exposure may also occur through the use of pharmaceutical products, as well as in occupational settings. Most studies report a prevalence of sulphite sensitivity of 3 to 10% among asthmatic subjects who ingest these additives. However, the severity of these reactions varies, and steroid-dependent asthmatics, those with marked airway hyperresponsiveness, and children with chronic asthma, appear to be at greater risk. Although a number of potential mechanisms have been proposed, the precise mechanisms underlying sulphite sensitivity remain unclear. PMID:24834193

  16. Adverse Risks Associated With Proton Pump Inhibitors

    PubMed Central

    2009-01-01

    Proton pump inhibitors (PPIs) are among the most commonly utilized agents for treatment of symptomatic disorders of the upper gastrointestinal tract, accounting for a significant proportion of sales of both over-the-counter and prescription formulations. A systematic review of the literature was conducted via MEDLINE to evaluate the most rigorous studies linking the potential risk of PPI therapy with adverse events. Emerging data illustrate the potential risks associated with both short-and long-term PPI therapy, including Clostridium difficile–associated diarrhea, community-acquired pneumonia, osteoporotic fracture, vitamin B12 deficiency, and inhibition of antiplatelet therapy. Due to these associations, it is recommended that clinicians assess the continuing need for PPI therapy and use the lowest possible dose to achieve the desired therapeutic goals.

  17. Vaccine adverse events: separating myth from reality.

    PubMed

    Kimmel, Sanford R

    2002-12-01

    Vaccines have turned many childhood diseases into distant memories in industrialized countries. However, questions have been raised about the safety of some vaccines because of rare but serious adverse effects that have been attributed to them. Pain, swelling, and redness at the injection site are common local reactions to vaccines. Fever and irritability may occur after some immunizations. Currently, no substantial evidence links measles-mumps-rubella vaccine to autism, or hepatitis B vaccine to multiple sclerosis. Thimerosal is being eliminated from routine childhood vaccines because of concerns that multiple immunizations with vaccines containing this preservative could exceed recommended mercury exposures. Family physicians should be knowledgeable about vaccines so that they can inform their patients of the benefits of immunization and any proven risks. If immunization rates fall, the incidence of vaccine-preventable illnesses may rise.

  18. An Observational Study on Aberrant Methylation of Runx3 With the Prognosis in Chronic Atrophic Gastritis Patients.

    PubMed

    Zhao, Chunna; Li, Ping; Zhang, Lili; Wang, Bei; Xiao, Lili; Guo, Feng; Wei, Yueguang

    2016-05-01

    The aim of this study is to discuss whether the methylation levels of Runx3 could be used as the early biomarker for predicting the prognosis in chronic atrophic gastritis (CAG) patients. A total of 200 subjects including 60 controls without CAG (Group 1), 70 patients with mild CAG (Group 2), and 70 patients with moderate and severe CAG (Group 3) were recruited for this cross-sectional investigation in the Department of Gastroenterology in Daqing Oilfield General Hospital from July 2013 to May 2014. The MlALDI-TOF-MS was used to measure the methylation levels of Runx3 in all of the subjects. Real-time quantitative reverse transcription polymerase chain reaction and western blotting were chosen to determine the expression levels of Runx3. The correlations between methylation levels of Runx3 among these CAG patients and their prognosis were shown by logistic regression models. The results demonstrated that the methylation levels of CpG13, CpG14, and CpG15 in Runx3 were higher in Group 3 than those in Groups 1 and 2 (P <0.05), whereas the mRNA and protein expression levels of Runx3 were lower in Group 3 than those in Groups 1 and 2 (P <0.05). There were significantly negative correlations between the methylation levels of Runx3 with its expression and the healing prognosis of CAG patients. In brief, this study proved that the hypermethylation modifications of CpG13, CpG14, and CpG15 in the promoter region of Runx3 could result in the down regulation of Runx3 expression to affect the prognosis of CAG. So the methylation levels of these CpG sites in Runx3 in the peripheral blood can be used as the biomarker for predicting the healing prognosis of CAG patients.

  19. Adverse Environments and Children's Creativity Development: Transforming the Notion of "Success in Adversity" in China

    ERIC Educational Resources Information Center

    Cheng, Li; Tan, Mei; Liu, Zhengkui

    2015-01-01

    China has been undergoing great social change due to its new focus on urbanization and globalization. Such change has had a tremendous adverse impact on the living conditions of millions of young children, simultaneously generating new interest in children's creativity development. The intersection of these two issues has important implications…

  20. Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse Event Reporting System Database.

    PubMed

    Soukavong, Mick; Kim, Jungmee; Park, Kyounghoon; Yang, Bo Ram; Lee, Joongyub; Jin, Xue Mei; Park, Byung Joo

    2016-09-01

    We conducted pharmacovigilance data mining for a β-lactam antibiotics, amoxicillin, and compare the adverse events (AEs) with the drug labels of 9 countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a nationwide database of AE reports, between December 1988 and June 2014. Frequentist and Bayesian methods were used to calculate disproportionality distribution of drug-AE pairs. The AE which was detected by all the three indices of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) was defined as a signal. The KAERS database contained a total of 807,582 AE reports, among which 1,722 reports were attributed to amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin signals. Comparing the drug labels of 9 countries, 12 adverse events including ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth, gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal crying, induration, pulmonary carcinoma, and influenza-like symptoms were not listed on any of the labels of nine countries. In conclusion, we detected 12 new signals of amoxicillin which were not listed on the labels of 9 countries. Therefore, it should be followed by signal evaluation including causal association, clinical significance, and preventability.

  1. Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse Event Reporting System Database

    PubMed Central

    2016-01-01

    We conducted pharmacovigilance data mining for a β-lactam antibiotics, amoxicillin, and compare the adverse events (AEs) with the drug labels of 9 countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a nationwide database of AE reports, between December 1988 and June 2014. Frequentist and Bayesian methods were used to calculate disproportionality distribution of drug-AE pairs. The AE which was detected by all the three indices of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) was defined as a signal. The KAERS database contained a total of 807,582 AE reports, among which 1,722 reports were attributed to amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin signals. Comparing the drug labels of 9 countries, 12 adverse events including ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth, gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal crying, induration, pulmonary carcinoma, and influenza-like symptoms were not listed on any of the labels of nine countries. In conclusion, we detected 12 new signals of amoxicillin which were not listed on the labels of 9 countries. Therefore, it should be followed by signal evaluation including causal association, clinical significance, and preventability. PMID:27510377

  2. The NAS Perchlorate Review: Adverse Effects?

    SciTech Connect

    Johnston, Richard B.; Corley, Richard; Cowan, Linda; Utiger, Robert D.

    2005-11-01

    To the editor: Drs. Ginsberg and Rice argue that the reference dose for perchlorate of 0.0007 mg/kg per day recommended by the National Academies’ Committee to Assess the Health Implications of Perchlorate Ingestion is not adequately protective. As members of the committee, we disagree. Ginsberg and Rice base their conclusion on three points. The first involves the designation of the point of departure as a NOEL (no-observed-effect level) versus a LOAEL (lowest-observed-adverse- effect level). The committee chose as its point of departure a dose of perchlorate (0.007 mg/kg per day) that when given for 14 days to 7 normal subjects did not cause a significant decrease in the group mean thyroid iodide uptake (Greer et al. 2002). Accordingly, the committee considered it a NOEL. Ginsberg and Rice focus on the fact that only 7 subjects were given that dose, and they 1seem to say that attention should be paid only to the results in those subjects in whom there was a 1fall in thyroid iodide uptake, and that the results in those in whom there was no fall or an increase should be ignored. They consider the dose to be a LOAEL because of the fall in uptake in those few subjects. It is important to note that a statistically significant decrease of, for example, 5% or even 10%, would not be biologically important and, more important, would not be sustained. For example, in another study (Braverman et al. 2004), administration of 0.04 mg/kg per day to normal subjects for 6 months had no effect on thyroid iodide uptake when measured at 3 and 6 months, and no effect on serum thyroid hormone or thyrotropin concentrations measured monthly (inspection of Figure 5A in the paper by Greer et al. suggests that this dose would inhibit thyroid iodide uptake by about 25% if measured at 2 weeks). The second issue involves database uncertainty. In clinical studies, perchlorate has been administered prospectively to 68 normal subjects for 2 weeks to 6 months. In one study (Brabant et al. 1992

  3. Differences in perspective on prognosis and treatment of children with trisomy 18.

    PubMed

    Hurley, Edward H; Krishnan, Sankaran; Parton, Lance A; Dozor, Allen J

    2014-10-01

    Differences in perspective between physicians caring for children with trisomy 18 may be confusing and stressful for parents. The hypothesis of this study was that neonatologists and pediatric pulmonologists differ in their opinions regarding long-term prognosis and recommended interventions. Neonatologists and pediatric pulmonologists in New York State were surveyed. Respondents were asked to report their personal experience caring for affected children, opinions on prognosis, major influences on their opinions, and their likelihood of recommending specific medical or surgical interventions for two clinical vignettes. A total of 393 surveys were mailed, 327 to neonatologists and 66 to pediatric pulmonologists. Sixty-six (20%) neonatologists and 21 (32%) pediatric pulmonologists completed the survey. Neonatologists had cared for more patients with trisomy 18. Twenty-nine percent of pediatric pulmonologists had never cared for a patient with trisomy 18 compared to 2% of neonatologists, P < 0.001. Pediatric pulmonologists were more likely to recommend almost all interventions including antibiotics for pneumonia, mechanical ventilation, cardiac and orthopedic surgery, and "full code resuscitation." Neonatologists were more likely to recommend comfort care only or palliative care. Fifty-four percent of neonatologists and 5% of pediatric pulmonologists thought patients with trisomy 18 without significant congenital heart disease would die before age one despite aggressive medical care, P < 0.001. The major influences impacting these recommendations also varied. Pediatric pulmonologists are more optimistic about the prognosis for children than neonatologists and more likely to recommend medical and surgical interventions. Experience with the condition and perception of survivability may contribute to these differences in approach.

  4. [Affective disorders and eating disorders].

    PubMed

    Fakra, Eric; Belzeaux, R; Azorin, J M; Adida, M

    2014-12-01

    Epidemiologic studies show a frequent co-occurence of affective and eating disorders. The incidence of one disorder in patients suffering from the other disorder is well over the incidence in the general population. Several causes could explain this increased comorbidity. First, the iatrogenic origin is detailed. Indeed, psychotropic drugs, and particularly mood stabilizers, often lead to modification in eating behaviors, generally inducing weight gain. These drugs can increase desire for food, reduce baseline metabolism or decrease motor activity. Also, affective and eating disorders share several characteristics in semiology. These similarities can not only obscure the differential diagnosis but may also attest of conjoint pathophysiological bases in the two conditions. However, genetic and biological findings so far are too sparse to corroborate this last hypothesis. Nonetheless, it is noteworthy that comorbidity of affective and eating disorders worsens patients'prognosis and is associated with more severe forms of affective disorders characterized by an earlier age of onset in the disease, higher number of mood episodes and a higher suicidality. Lastly, psychotropic drugs used in affective disorders (lithium, antiepileptic mood stabilizers, atypical antipsychotics, antidepressants) are reviewed in order to weigh their efficacy in eating disorders. This could help establish the best therapeutic option when confronted to comorbidity.

  5. Adverse Drug Reactions and quality deviations monitored by spontaneous reports

    PubMed Central

    Visacri, Marília Berlofa; de Souza, Cinthia Madeira; Sato, Catarina Miyako Shibata; Granja, Silvia; de Marialva, Mécia; Mazzola, Priscila Gava; Moriel, Patricia

    2014-01-01

    Objectives The aim of this study was to determine the frequency and profile of spontaneous reports of Adverse Drug Reactions (ADRs) and quality deviations in a Brazilian teaching hospital and propose a consistent classification to study quality deviations. Methods This is a descriptive and retrospective study involving the analysis of spontaneous reports of ADRs and quality deviations in 2010. ADRs were classified according to the reaction mechanism, severity, and causality. The drugs were classified according to their therapeutic classes and symptoms according to the affected organ. The quality deviations were classified according to the type of deviation and type of medicine available in the Brazilian market. Results A total of 68 forms were examined; ADRs accounted for 39.7% of the notifications, while quality deviations accounted for 60.3%. ADRs occurred more frequently in men (51.9%) and adults (63.0%). The skin (28.0%) was the most affected organ, while anti-infectives (40.7%) were the therapeutic class that caused the most ADRs. The most common ADRs were type B (74.0%), moderates (37.0%), and probables (55.6%). In relation to quality deviations, the most frequent notifications were breaks, splits and leaks (20.9%) and related to generic drugs (43.9%). Conclusion The classification system to study quality deviations was clear and consistent. This study demonstrated that practices and public policies related to more effective pharmacovigilance need to be implemented so that the number of spontaneous reports increases. PMID:25972731

  6. Epigenetic programming of neurodegenerative diseases by an adverse environment.

    PubMed

    Babenko, Olena; Kovalchuk, Igor; Metz, Gerlinde A

    2012-03-20

    Experience and environment can critically influence the risk and progression of neurodegenerative disorders. Epigenetic mechanisms, such as miRNA expression, DNA methylation, and histone modifications, readily respond to experience and environmental factors. Here we propose that epigenetic regulation of gene expression and environmental modulation thereof may play a key role in the onset and course of common neurological conditions, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. For example, epigenetic mechanisms may mediate long-term responses to adverse experience, such as stress, to affect disease susceptibility and the course of neurodegenerative events. This review introduces the epigenetic components and their possible role in mediating neuropathological processes in response to stress. We argue that epigenetic modifications will affect neurodegenerative events through altered gene function. The study of epigenetic states in neurodegenerative diseases presents an opportunity to gain new insights into risk factors and pathogenic mechanisms. Moreover, research into epigenetic regulation of disease may revolutionize health care by opening new avenues of personalized, preventive and curative medicine.

  7. Adverse reactions triggered by dental local anesthetics: a clinical survey.

    PubMed Central

    Kaufman, E.; Goharian, S.; Katz, Y.

    2000-01-01

    One hundred and seventy-nine patients completed a questionnaire focusing on adverse reactions to dental local anesthetics as manifested by 16 signs and symptoms. Twenty-six percent of the participants reported having at least 1 adverse reaction. It was found that most of the adverse reactions occurred within the first 2 hours following the injection of local anesthetics. Pallor, palpitations, diaphoresis, and dizziness were the most common adverse reactions reported in the study. The results pointed to a significant relationship between anxiety, gender, injection technique, and procedure with a higher incidence of adverse reactions. PMID:11432179

  8. A prospective study of adverse drug reactions in hospitalized children

    PubMed Central

    Martínez-Mir, Inocencia; García-López, Mercedes; Palop, Vicente; Ferrer, José M; Rubio, Elena; Morales-Olivas, Francisco J

    1999-01-01

    Aims There are few publications of adverse drug reactions (ADRs) among paediatric patients, though ADR incidence is usually stated to be higher during the first year of life and in male patients. We have carried out a prospective study to assess the extent, pattern and profile risk for ADRs in hospitalized patients between 1 and 24 months of age. Methods An intensive events monitoring scheme was used. A total of 512 successive admissions to two medical paediatric wards (47 beds) were analysed. The hospital records were screened daily during two periods (summer, 105 days and winter, 99 days), and adverse clinical events observed were recorded. Results A total of 282 events were detected; of these, 112 were considered to be manifestations of ADRs. The cumulative incidence was 16.6%, no differences being observed between periods. Although there were no differences between patients under and over 12 months of age, risk was found to be significantly higher among girls compared with boys (RR = 1.66, 95% CI 1.03–2.52). The gastro-intestinal system was most frequently affected. The therapeutic group most commonly implicated was anti-infective drugs and vaccines (41.5%). The ADRs were mild or moderate in over 90% of cases. A consistent relationship was noted between the number of drugs administered and the incidence of ADRs. Conclusions Hospitalized patients exhibited an ADR risk profile that included female sex and the number of drugs administered. No particular age predisposition was observed. The most commonly prescribed drugs are those most often implicated in ADRs in paediatric patients. PMID:10383547

  9. Adverse testicular effects of Botox® in mature rats

    SciTech Connect

    Breikaa, Randa M.; Mosli, Hisham A.; Nagy, Ayman A.; Abdel-Naim, Ashraf B.

    2014-03-01

    testicular spasms. • This study outlines possible testicular adverse effects of these injections. • Botox® affected normal testicular function and physiology. • Infertility is a serious problem that Botox® injections could cause.

  10. Cumulative early life adversity predicts longevity in wild baboons

    PubMed Central

    Tung, Jenny; Archie, Elizabeth A.; Altmann, Jeanne; Alberts, Susan C.

    2016-01-01

    In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations. PMID:27091302

  11. Cumulative early life adversity predicts longevity in wild baboons.

    PubMed

    Tung, Jenny; Archie, Elizabeth A; Altmann, Jeanne; Alberts, Susan C

    2016-04-19

    In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations.

  12. Prior adversities predict posttraumatic stress reactions in adolescents following the Oslo Terror events 2011

    PubMed Central

    Nordanger, Dag Ø.; Breivik, Kyrre; Haugland, Bente Storm; Lehmann, Stine; Mæhle, Magne; Braarud, Hanne Cecilie; Hysing, Mari

    2014-01-01

    Background Former studies suggest that prior exposure to adverse experiences such as violence or sexual abuse increases vulnerability to posttraumatic stress reactions in victims of subsequent trauma. However, little is known about how such a history affects responses to terror in the general adolescent population. Objective To explore the role of prior exposure to adverse experiences as risk factors for posttraumatic stress reactions to the Oslo Terror events. Method We used data from 10,220 high school students in a large cross-sectional survey of adolescents in Norway that took place seven months after the Oslo Terror events. Prior exposure assessed was: direct exposure to violence, witnessing of violence, and unwanted sexual acts. We explored how these prior adversities interact with well-established risk factors such as proximity to the events, perceived life threat during the terror events, and gender. Results All types of prior exposure as well as the other risk factors were associated with terror-related posttraumatic stress reactions. The effects of prior adversities were, although small, independent of adolescents’ proximity to the terror events. Among prior adversities, only the effect of direct exposure to violence was moderated by perceived life threat. Exposure to prior adversities increased the risk of posttraumatic stress reactions equally for both genders, but proximity to the terror events and perceived life threat increased the risk more in females. Conclusions Terror events can have a more destabilizing impact on victims of prior adversities, independent of their level of exposure. The findings may be relevant to mental health workers and others providing post-trauma health care. PMID:24872862

  13. Future Directions in Childhood Adversity and Youth Psychopathology.

    PubMed

    McLaughlin, Katie A

    2016-01-01

    Despite long-standing interest in the influence of adverse early experiences on mental health, systematic scientific inquiry into childhood adversity and developmental outcomes has emerged only recently. Existing research has amply demonstrated that exposure to childhood adversity is associated with elevated risk for multiple forms of youth psychopathology. In contrast, knowledge of developmental mechanisms linking childhood adversity to the onset of psychopathology-and whether those mechanisms are general or specific to particular kinds of adversity-remains cursory. Greater understanding of these pathways and identification of protective factors that buffer children from developmental disruptions following exposure to adversity is essential to guide the development of interventions to prevent the onset of psychopathology following adverse childhood experiences. This article provides recommendations for future research in this area. In particular, use of a consistent definition of childhood adversity, integration of studies of typical development with those focused on childhood adversity, and identification of distinct dimensions of environmental experience that differentially influence development are required to uncover mechanisms that explain how childhood adversity is associated with numerous psychopathology outcomes (i.e., multifinality) and identify moderators that shape divergent trajectories following adverse childhood experiences. A transdiagnostic model that highlights disruptions in emotional processing and poor executive functioning as key mechanisms linking childhood adversity with multiple forms of psychopathology is presented as a starting point in this endeavour. Distinguishing between general and specific mechanisms linking childhood adversity with psychopathology is needed to generate empirically informed interventions to prevent the long-term consequences of adverse early environments on children's development.

  14. Clinical characteristics and prognosis of cerebral venous thrombosis in Chinese women during pregnancy and puerperium

    PubMed Central

    Liang, Zhu-Wei; Gao, Wan-Li; Feng, Li-Min

    2017-01-01

    Due to the specific physiology associated with pregnancy and puerperium, cerebral venous sinus thrombosis (CVT) may manifest different characteristics. This study aimed to identify the clinical manifestations and prognosis of pregnancy-associated CVT. A total of 43 pregnancy-associated CVT patients were enrolled. We analysed the clinical presentations of the disease and performed a multivariate logistic regression analysis to determine which variables were associated with prognosis. Our descriptive results showed the following: 1) the incidence was 202 per 100,000 deliveries, and the mortality rate was 11.63%; 2) the most frequent symptom was headache; 3) the most frequent abnormal laboratory findings were increased levels of fibrinogen and several serum lipoproteins (including triglyceride, cholesterol, high-density lipoprotein, low-density lipoprotein, apolipoprotein A1, and apolipoprotein B); and 4) the superior sagittal sinus and transverse sinus were the most frequently affected locations. Moreover, an increased modified Rankin Scale score was positively associated with infection, seizure, intracerebral haemorrhage (ICH) and hypertensive disorders of pregnancy (HDP). Comparably, the occurrence of death was positively and significantly associated with infection, seizure and ICH. Consequently, timely diagnosis and treatment of pregnancy-associated CVT patients with infection, seizure, ICH or HDP are needed. Patients with infection, seizure or ICH have a greater risk of death. PMID:28262755

  15. Prognosis of neonatal tetanus in the modern management era: an observational study in 107 Vietnamese infants

    PubMed Central

    Lam, Phung Khanh; Trieu, Huynh T.; Lubis, Inke Nadia D.; Loan, Huynh T.; Thuy, Tran Thi Diem; Wills, Bridget; Parry, Christopher M.; Day, Nicholas P.J.; Qui, Phan T.; Yen, Lam Minh; Thwaites, C. Louise

    2015-01-01

    Summary Objectives Most data regarding the prognosis in neonatal tetanus originate from regions where limited resources have historically impeded management. It is not known whether recent improvements in critical care facilities in many low- and middle-income countries have affected indicators of a poor prognosis in neonatal tetanus. We aimed to determine the factors associated with worse outcomes in a Vietnamese hospital with neonatal intensive care facilities. Methods Data were collected from 107 cases of neonatal tetanus. Clinical features on admission were analyzed against mortality and a combined endpoint of ‘death or prolonged hospital stay’. Results Multivariable analysis showed that only younger age (odds ratio (OR) for mortality 0.69, 95% confidence interval (CI) 0.48–0.98) and lower weight (OR for mortality 0.06, 95% CI 0.01–0.54) were significantly associated with both the combined endpoint and death. A shorter period of onset (OR 0.94, 95% CI 0.88–0.99), raised white cell count (OR 1.17, 95% CI 1.02–1.35), and time between first symptom and admission (OR 3.77, 95% CI 1.14–12.51) were also indicators of mortality. Conclusions Risk factors for a poor outcome in neonatal tetanus in a setting with critical care facilities include younger age, lower weight, delay in admission, and leukocytosis. PMID:25499039

  16. A three-gene signature for prognosis in patients with MGMT promoter-methylated glioblastoma.

    PubMed

    Wang, Wen; Zhang, Lu; Wang, Zheng; Yang, Fan; Wang, Haoyuan; Liang, Tingyu; Wu, Fan; Lan, Qing; Wang, Jiangfei; Zhao, Jizong

    2016-10-25

    Glioblastoma is the most malignant tumor and has high mortality rate. The methylated prompter of MGMT results in chemotherapy sensitivity for these patients. However, there are still other factors that affected the prognosis for the glioblastoma patients with similar MGMT methylation status. We developed a signature with three genes screened from the whole genome mRNA expression profile from Chinese Glioma Genome Atlas (CGGA) and RNAseq data from The Cancer Genome Atlas (TCGA). Patients with MGMT methylation in low risk group had longer survival than those in high risk group (median overall survival 1074 vs. 372 days; P = 0.0033). Moreover, the prognostic value of the signature was significant difference in cohorts stratified by MGMT methylation and chemotherapy (P=0.0473), while there is no significant difference between low and high risk group or unmethylated MGMT patients without chemotherapy. Multivariate analysis indicated that the risk score was an independent prognosis factor (P = 0.004). In conclusion, our results showed that the signature has prognostic value for patients with MGMT promoter-methylated glioblastomas based on bioinformatics analysis.

  17. A network medicine approach to build a comprehensive atlas for the prognosis of human cancer.

    PubMed

    Zhang, Fan; Ren, Chunyan; Lau, Kwun Kit; Zheng, Zihan; Lu, Geming; Yi, Zhengzi; Zhao, Yongzhong; Su, Fei; Zhang, Shaojun; Zhang, Bin; Sobie, Eric A; Zhang, Weijia; Walsh, Martin J

    2016-11-01

    The Cancer Genome Atlas project has generated multi-dimensional and highly integrated genomic data from a large number of patient samples with detailed clinical records across many cancer types, but it remains unclear how to best integrate the massive amount of genomic data into clinical practice. We report here our methodology to build a multi-dimensional subnetwork atlas for cancer prognosis to better investigate the potential impact of multiple genetic and epigenetic (gene expression, copy number variation, microRNA expression and DNA methylation) changes on the molecular states of networks that in turn affects complex cancer survivorship. We uncover an average of 38 novel subnetworks in the protein-protein interaction network that correlate with prognosis across four prominent cancer types. The clinical utility of these subnetwork biomarkers was further evaluated by prognostic impact evaluation, functional enrichment analysis, drug target annotation, tumor stratification and independent validation. Some pathways including the dynactin, cohesion and pyruvate dehydrogenase-related subnetworks are identified as promising new targets for therapy in specific cancer types. In conclusion, this integrative analysis of existing protein interactome and cancer genomics data allows us to systematically dissect the molecular mechanisms that underlie unexpected outcomes for cancer, which could be used to better understand and predict clinical outcomes, optimize treatment and to provide new opportunities for developing therapeutics related to the subnetworks identified.

  18. Chronic Activation of Innate Immunity Correlates With Poor Prognosis in Cancer Patients Treated With Oncolytic Adenovirus.

    PubMed

    Taipale, Kristian; Liikanen, Ilkka; Juhila, Juuso; Turkki, Riku; Tähtinen, Siri; Kankainen, Matti; Vassilev, Lotta; Ristimäki, Ari; Koski, Anniina; Kanerva, Anna; Diaconu, Iulia; Cerullo, Vincenzo; Vähä-Koskela, Markus; Oksanen, Minna; Linder, Nina; Joensuu, Timo; Lundin, Johan; Hemminki, Akseli

    2016-02-01

    Despite many clinical trials conducted with oncolytic viruses, the exact tumor-level mechanisms affecting therapeutic efficacy have not been established. Currently there are no biomarkers available that would predict the clinical outcome to any oncolytic virus. To assess the baseline immunological phenotype and find potential prognostic biomarkers, we monitored mRNA expression levels in 31 tumor biopsy or fluid samples from 27 patients treated with oncolytic adenovirus. Additionally, protein expression was studied from 19 biopsies using immunohistochemical staining. We found highly significant changes in several signaling pathways and genes associated with immune responses, such as B-cell receptor signaling (P < 0.001), granulocyte macrophage colony-stimulating factor (GM-CSF) signaling (P < 0.001), and leukocyte extravasation signaling (P < 0.001), in patients surviving a shorter time than their controls. In immunohistochemical analysis, markers CD4 and CD163 were significantly elevated (P = 0.020 and P = 0.016 respectively), in patients with shorter than expected survival. Interestingly, T-cell exhaustion marker TIM-3 was also found to be significantly upregulated (P = 0.006) in patients with poor prognosis. Collectively, these data suggest that activation of several functions of the innate immunity before treatment is associated with inferior survival in patients treated with oncolytic adenovirus. Conversely, lack of chronic innate inflammation at baseline may predict improved treatment outcome, as suggested by good overall prognosis.

  19. Human papillomavirus types 16 and 18 and the prognosis of patients with stage I cervical cancer

    PubMed Central

    de Araújo Catão Zampronha, Rossana; Freitas-Junior, Ruffo; Murta, Eddie Fernando Candido; Michelin, Márcia Antoniazi; Barbaresco, Aline Almeida; Adad, Sheila Jorge; de Oliveira, Amaurillo Monteiro; Rassi, Amanda B.; Oton, Glória Jabur Bittar

    2013-01-01

    OBJECTIVE: This study sought to evaluate the prevalence of human papillomavirus (HPV) types 16 and 18 in women with clinical stage IB cervical cancer treated by radical hysterectomy with pelvic lymphadenectomy as well as to establish a correlation between HPV type and cancer prognosis. METHODS: A single-center cohort study was conducted with 86 patients who had undergone radical hysterectomy for stage I cervical cancer. Prognostic factors and the presence of HPV 16 and 18 were analyzed using a polymerase chain reaction assay. A univariate analysis using Kaplan-Meier curves was conducted to estimate survival. RESULTS: The prevalence of HPV 16 in the study group was 65.3%, and the prevalence of HPV 18 was 33.3%. The prevalence of infection with both viruses was 26.9%. Overall survival at 5 years was 91% among women with HPV 18 and 96% among those without this virus type (p = 0.133). Among the women with HPV 16, the overall survival was 94%, whereas this rate was 96% among those without this virus type (p = 0.663). Disease-free survival was unaffected by the presence of HPV type 16 or 18. CONCLUSION: In the present study, despite the high prevalence of HPV types 16 and 18, the presence of these virus types did not affect the prognosis of patients with stage I cervical cancer who underwent radical hysterectomy. PMID:23778490

  20. Clinical significance of para-aortic lymph node dissection and prognosis in ovarian cancer.

    PubMed

    Li, Xianxian; Xing, Hui; Li, Lin; Huang, Yanli; Zhou, Min; Liu, Qiong; Qin, Xiaomin; He, Min

    2014-03-01

    Lymph node metastasis has an important effect on prognosis of patients with ovarian cancer. Moreover, the impact of para-aortic lymph node (PAN) removal on patient prognosis is still unclear. In this study, 80 patients were divided into groups A and B. Group A consisted of 30 patients who underwent PAN + pelvic lymph node (PLN) dissection, whereas group B consisted of 50 patients who only underwent PLN dissection. Analysis of the correlation between PAN clearance and prognosis in epithelial ovarian cancer was conducted. Nineteen cases of lymph node metastasis were found in group A, among whom seven cases were positive for PAN, three cases for PLN, and nine cases for both PAN and PLN. In group B, 13 cases were positive for lymph node metastasis. Our study suggested that the metastatic rate of lymph node is 40.0%. Lymph node metastasis was significantly correlated with FIGO stage, tumor differentiation, and histological type both in groups A and B (P < 0.05). In groups A and B, the three-year survival rates were 77.9% and 69.0%, and the five-year survival rates were 46.7% and 39.2%, respectively. However, the difference was not statistically significant (P > 0.05). The three-year survival rates of PLN metastasis in groups A and B were 68.5% and 41.4%, and the five-year survival rates were 49.7% and 26.4%, respectively. Furthermore, PLN-positive patients who cleared PAN had significantly higher survival rate (P = 0.044). In group A, the three-year survival rates of positive and negative lymph nodes were 43.5% and 72.7%, and the five-year survival rates were 27.2% and 58.5%, respectively. The difference was statistically significant (P = 0.048). Cox model analysis of single factor suggested that lymph node status affected the survival rate (P < 0.01), which was the death risk factor. Consequently, in ovarian carcinoma cytoreductive surgery, resection of the para-aortic lymph node, which has an important function in clinical treatment and prognosis of patients with

  1. Population Analysis of Adverse Events in Different Age Groups Using Big Clinical Trials Data

    PubMed Central

    Eldredge, Christina; Cho, Chi C; Cisler, Ron A

    2016-01-01

    Background Understanding adverse event patterns in clinical studies across populations is important for patient safety and protection in clinical trials as well as for developing appropriate drug therapies, procedures, and treatment plans. Objectives The objective of our study was to conduct a data-driven population-based analysis to estimate the incidence, diversity, and association patterns of adverse events by age of the clinical trials patients and participants. Methods Two aspects of adverse event patterns were measured: (1) the adverse event incidence rate in each of the patient age groups and (2) the diversity of adverse events defined as distinct types of adverse events categorized by organ system. Statistical analysis was done on the summarized clinical trial data. The incident rate and diversity level in each of the age groups were compared with the lowest group (reference group) using t tests. Cohort data was obtained from ClinicalTrials.gov, and 186,339 clinical studies were analyzed; data were extracted from the 17,853 clinical trials that reported clinical outcomes. The total number of clinical trial participants was 6,808,619, and total number of participants affected by adverse events in these trials was 1,840,432. The trial participants were divided into eight different age groups to support cross-age group comparison. Results In general, children and older patients are more susceptible to adverse events in clinical trial studies. Using the lowest incidence age group as the reference group (20-29 years), the incidence rate of the 0-9 years-old group was 31.41%, approximately 1.51 times higher (P=.04) than the young adult group (20-29 years) at 20.76%. The second-highest group is the 50-59 years-old group with an incidence rate of 30.09%, significantly higher (P<.001) when compared with the lowest incidence in the 20-29 years-old group. The adverse event diversity also increased with increase in patient age. Clinical studies that recruited older

  2. The adverse prognostic hallmarks in identical twins with Langerhans cell histiocytosis: a clinical report and literature review.

    PubMed

    Chai, Damin; Tao, Yisheng; Bao, Zhengqi; Yang, Li; Feng, Zhenzhong; Ma, Li; Liang, Limei; Zhou, Xinwen

    2013-01-01

    Langerhans cell histiocytosis (LCH) is characterized by uncontrolled proliferation of Langerhans cells accompanying eosinophils. It often attacks children under 10 years of age. LCH in identical twins is very rare and its prognosis is different. Here we report identical-twin sisters with LCH. Computed tomography (CT) revealed osteolytic change in each twin's skull, and the elder exhibited poor eyesight. There were massive histiocyte-like cells surrounded by eosinophils in pathologic specimen of the abnormal lesions, which is typical pathologic finding in LCH. These pathologic cells were positive for S-100 and the cell surface protein CD1 antigen (CD1α), the known markers of LCH. After treating them with surgery, no symptoms were seen in the younger until now. While the older was found another soft mass (about 2.0 cm in diameter) in the left temporal area 18 months later. The same treatment was given to the older after admission, and she is healthy to date. To explore the relationship between hallmarks and the prognosis of identical-twin patients with LCH, we retrieved the 16 literatures (16 identical-twin pairs, 31 patients) listed in PubMed during the past 60 years. The data revealed all those patients who have disseminated to the bone marrow, spleen and liver with symptoms of fever and hepatosplenomegaly exhibited worse prognosis (9 out of the 31 patients). The other identical-twin subjects without infiltration of those organs recovered well. In conclusion, this study reveals the adverse hallmarks of prognosis in identical-twin patients with LCH by reviewing relevant literatures.

  3. Impact of childhood adversities on the short-term course of illness in psychotic spectrum disorders.

    PubMed

    Schalinski, Inga; Fischer, Yolanda; Rockstroh, Brigitte

    2015-08-30

    Accumulating evidence indicates an impact of childhood adversities on the severity and course of mental disorders, whereas this impact on psychotic disorders remains to be specified. Effects of childhood adversities on comorbidity, on symptom severity of the Positive and Negative Syndrome Scale and global functioning across four months (upon admission, 1 and 4 months after initial assessment), as well as the course of illness (measured by the remission rate, number of re-hospitalizations and dropout rate) were evaluated in 62 inpatients with psychotic spectrum disorders. Adverse experiences (of at least 1 type) were reported by 73% of patients. Patients with higher overall level of childhood adversities (n=33) exhibited more co-morbid disorders, especially alcohol/substance abuse and dependency, and higher dropout rates than patients with a lower levels of adverse experiences (n=29), together with higher levels of positive symptoms and symptoms of excitement and disorganization. Emotional and physical neglect were particularly related to symptom severity. Results suggest that psychological stress in childhood affects the symptom severity and, additionally, a more unfavorable course of disorder in patients diagnosed with psychoses. This impact calls for its consideration in diagnostic assessment and psychiatric care.

  4. Lycopersicon esculentum (Tomato) Prevents Adverse Effects of Lead on Blood Constituents

    PubMed Central

    SALAWU, Emmanuel O

    2010-01-01

    Background: Lead is known for its adverse effects on various organs and systems. In this study, the ability of lead to adversely affect blood parameters was investigated, and Lycopersicon esculentum, or commonly known as tomato (a source of antioxidants), was administered orally in the form of tomato paste (TP) to reduce the adverse effects of lead. Methods: The study involved 56 Wistar rats divided equally into 4 groups of 14 rats each: Control, LAG, TPG, and LA+TPG. Control and TPG rats were given distilled water ad libitum, while LAG and LA+TPG rats were given 1% lead (II) acetate (LA) per day. TPG and LA+TPG rats were additionally treated with 1.5 ml of TP per day. All treatments lasted for 10 weeks, after which the rats were weighed and sacrificed, and haematological and biochemical parameters were measured. The independent samples t test was used to analyse the results. Results: Lead caused significant reductions in the following parameters: weight; packed cell volume; red blood cell and white blood cell counts; the percentages of lymphocytes and monocytes; total serum protein, albumin, and globulin levels; and plasma superoxide dismutase and catalase activities. In contrast, lead caused a significant increase in the percentage of neutrophils and the plasma malondialdehyde concentration. TP, however, significantly prevented the adverse effects of LA. Conclusion: The oral administration of TP prevents the adverse effects of lead on blood constituents. PMID:22135544

  5. Depression among Black bisexual men with early and later life adversities.

    PubMed

    Allen, Vincent C; Myers, Hector F; Williams, John K

    2014-01-01

    This study examined the role of adulthood adversities in the relationship between childhood adversities and depression in 117 HIV-positive Black men who have sex with men and women (MSMW) and who have histories of childhood sexual abuse (CSA). Men were participants in the Enhanced Sexual Health Intervention for Men, a 6-session health intervention, and, at baseline, reported their experiences of CSA, childhood adversities, perceived discrimination, chronic stress, social support, and depressive symptoms. The relationship between childhood adversities, including CSA, and depression was mediated by experiences with racial and HIV discrimination, R² = .25, F(3, 112) = 12.67, p < .001, and chronic stress, R² = .17, F(3, 112) = 7.41, p < .001. Social support moderated the mediated effects of both racial and HIV discrimination, b = -.154, t(111) = -2.82, p < .01, and chronic stress, b = -.019, t(111) = -3.759, p < .01. Men's early adverse experiences were predictive of depression in adulthood; however, this relationship was largely affected by adulthood experiences, specifically discrimination, high chronic stress, and low social support. These findings illustrate pathways by which Black MSMW's early vulnerability for depression is either exacerbated or attenuated by their experiences as adults.

  6. Assessment of the expectancy, seriousness and severity of adverse drug reactions reported for chronic obstructive pulmonary disease therapy

    PubMed Central

    Petrova, Guenka; Stoimenova, Assena; Dimitrova, Maria; Kamusheva, Maria; Petrova, Daniela; Georgiev, Ognian

    2017-01-01

    Introduction: Adverse drug reactions can cause increased morbidity and mortality, and therefore information needs to be studied systematically. Little is known about the adverse drug reactions for chronic obstructive pulmonary disease therapy. The goal of this study is to assess the expectedness, seriousness and severity of adverse drug reactions during chronic obstructive pulmonary disease therapy based on their reporting in the national pharmacovigilance system. Methods: This was a prospective, observational, 1-year, real-life study about the pharmacotherapy of a sample of 390 chronic obstructive pulmonary disease patients. Prescribed medicines were systematized and national pharmacovigilance databases were searched for reported adverse drug reactions. The expectedness was evaluated through the review of the summary of product characteristics, the seriousness was evaluated by the clinicians based on the life threatening nature of the adverse drug reactions, and the severity was evaluated through Hartwig’s Severity Assessment Scale. Descriptive statistics of the reported adverse drug reactions was performed and the relative risk of developing an adverse drug reaction with all international non-proprietary names included in the analysis was calculated. Results: Results confirm that the chronic obstructive pulmonary disease is a disease with high appearance of adverse drug reactions, and causes many additional costs to the healthcare system. Unexpected and severe adverse drug reactions are frequent. A total of 4.8% of adverse drug reactions were evaluated as life threatening. Majority of adverse drug reactions are classified in Levels 1 (32.6%), 2 (26.4%) and 3 (19%) according to Hartwig’s Severity Assessment Scale. Approximately 22% of reported adverse drug reactions affect people’s everyday life to a greater extent and require additional therapy which might further increase the risk. The relative risk of developing an adverse drug reaction was highest for

  7. Adverse events after manual therapy among patients seeking care for neck and/or back pain: a randomized controlled trial

    PubMed Central

    2014-01-01

    : 1.77-3.52)) compared to men. Conclusion Adverse events after manual therapy are common and transient. Excluding spinal manipulation or stretching do not affect the occurrence of adverse events. The most common adverse event is soreness in the muscles. Women reports more adverse events than men. Trial registration This trial was registered in a public registry (Current Controlled Trials) (ISRCTN92249294). PMID:24618345

  8. Sleep apnoea adversely affects the outcome in patients who undergo posterior lumbar fusion

    PubMed Central

    Stundner, O.; Chiu, Y-L.; Sun, X.; Ramachandran, S-K.; Gerner, P.; Vougioukas, V.; Mazumdar, M.; Memtsoudis, S. G.

    2014-01-01

    Despite the increasing prevalence of sleep apnoea, little information is available regarding its impact on the peri-operative outcome of patients undergoing posterior lumbar fusion. Using a national database, patients who underwent lumbar fusion between 2006 and 2010 were identified, sub-grouped by diagnosis of sleep apnoea and compared. The impact of sleep apnoea on various outcome measures was assessed by regression analysis. The records of 84 655 patients undergoing posterior lumbar fusion were identified and 7.28% also had a diagnostic code for sleep apnoea. Compared with patients without sleep apnoea, these patients were older, more frequently female, had a higher comorbidity burden and higher rates of peri-operative complications, post-operative mechanical ventilation, blood transfusion, and intensive care. Patients with sleep apnoea also had longer and more costly periods of hospitalisation. In the regression analysis, sleep apnoea emerged as an independent risk factor for the development of peri-operative complications (Odds Ratio (OR) 1.50, Confidence Interval (CI) 1.38;1.62), blood transfusions (OR 1.12, CI 1.03;1.23), mechanical ventilation (OR 6.97, CI 5.90;8.23), critical care services (OR 1.86, CI 1.71;2.03), prolonged hospitalisation and increased cost (OR 1.28, CI 1.19;1.37; OR 1.10, CI 1.03;1.18). Patients with sleep apnoea who undergo posterior lumbar fusion pose significant challenges to clinicians. PMID:24493191

  9. Diabetes distress may adversely affect the eating styles of women with type 1 diabetes

    PubMed Central

    Quinn, Laurie; Hacker, Eileen; Park, Hanjong; Kujath, Amber S.

    2015-01-01

    The aim of this study was to determine the relationships among diabetes distress, fear of hypoglycemia, and eating styles in women with type 1 diabetes (T1DM). Fifteen women (mean age 37 ± 13.5 years) with T1DM completed surveys measuring diabetes distress, fear of hypoglycemia (FOH), and eating style. Height, weight, and A1C were obtained, and open-ended comments regarding hypoglycemic concerns and experiences were recorded. Diabetes distress was positively associated with A1C (r = .655, p = .008). High levels of external (73 %), emotional (47 %), and restrained (53 %) eating styles were reported. Emotional and external eating styles were positively associated with diabetes distress (r = .575 and r = .622; p <.05). Those with poorer glycemic control (A1C ≥ 7 %; 53 mmol/mol) had higher levels of restrained eating behavior (F = 10.69, p = .006) and greater interpersonal distress (F = 5.916, p = .03) than those with better glycemic control (A1C < 7 %; 53 mmol/mol). A nonlinear relationship was identified between interpersonal distress and FOH (behavior subscale, p = .0383) indicating that fewer behavioral approaches were employed to avoid hypoglycemia at higher distress levels. The women in this sample were emotionally burdened by their disease. Distress was associated with eating styles linked with overeating and poor glycemic control. High levels of emotional and external eating styles may have important clinical implications for those with T1DM. PMID:24615054

  10. Urban cultivation in allotments maintains soil qualities adversely affected by conventional agriculture

    PubMed Central

    Edmondson, Jill L; Davies, Zoe G; Gaston, Kevin J; Leake, Jonathan R

    2014-01-01

    Modern agriculture, in seeking to maximize yields to meet growing global food demand, has caused loss of soil organic carbon (SOC) and compaction, impairing critical regulating and supporting ecosystem services upon which humans also depend. Own-growing makes an important contribution to food security in urban areas globally, but its effects on soil qualities that underpin ecosystem service provision are currently unknown. We compared the main indicators of soil quality; SOC storage, total nitrogen (TN), C : N ratio and bulk density (BD) in urban allotments to soils from the surrounding agricultural region, and between the allotments and other urban greenspaces in a typical UK city. A questionnaire was used to investigate allotment management practices that influence soil properties. Allotment soils had 32% higher SOC concentrations and 36% higher C : N ratios than pastures and arable fields and 25% higher TN and 10% lower BD than arable soils. There was no significant difference between SOC concentration in allotments and urban non-domestic greenspaces, but it was higher in domestic gardens beneath woody vegetation. Allotment soil C : N ratio exceeded that in non-domestic greenspaces, but was lower than that in garden soil. Three-quarters of surveyed allotment plot holders added manure, 95% composted biomass on-site, and many added organic-based fertilizers and commercial composts. This may explain the maintenance of SOC, C : N ratios, TN and low BD, which are positively associated with soil functioning. Synthesis and applications. Maintenance and protection of the quality of our soil resource is essential for sustainable food production and for regulating and supporting ecosystem services upon which we depend. Our study establishes, for the first time, that small-scale urban food production can occur without the penalty of soil degradation seen in conventional agriculture, and maintains the high soil quality seen in urban greenspaces. Given the involvement of over 800 million people in urban agriculture globally, and its important contribution to food security, our findings suggest that to better protect soil functions, local, national and international urban planning and policy making should promote more urban own-growing in preference to further intensification of conventional agriculture to meet increasing food demand. PMID:25641978

  11. Prenatal zinc supplementation of zinc-adequate rats adversely affects immunity in offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously showed that zinc (Zn) supplementation of Zn-adequate dams induced immunosuppressive effects that persist in the offspring after weaning. We investigated whether the immunosuppressive effects were due to in utero exposure and/or mediated via milk using a cross-fostering design. Pregnant...

  12. Estradiol and endocrine disrupting compounds adversely affect development of sea urchin embryos at environmentally relevant concentrations.

    PubMed

    Roepke, Troy A; Snyder, Mark J; Cherr, Gary N

    2005-01-26

    Environmental endocrine disrupting compounds (EDCs) are a wide variety of chemicals that typically exert effects, either directly or indirectly, through receptor-mediated processes, thus mimicking endogenous hormones and/or inhibiting normal hormone activities and metabolism. Little is known about the effects of EDCs on echinoderm physiology, reproduction and development. We exposed developing sea urchin embryos (Strongylocentrotus purpuratus and Lytechinus anamesus) to two known EDCs (4-octylphenol (OCT), bisphenol A (BisA)) and to natural and synthetic reproductive hormones (17beta-estradiol (E2), estrone (E1), estriol (E3), progesterone (P4) and 17alpha-ethynylestradiol (EE2)). In addition, we studied two non-estrogenic EDCs, tributyltin (TBT) and o,p-DDD. Successful development to the pluteus larval stage (96 h post-fertilization) was used to define EDC concentration-response relationships. The order of compound potency based on EC50 values for a reduction in normal development was as follows: TBT(L. anamesus)>OCT>TBT(S. purpuratus)>E2>EE2>DDD>BisA>P4>E1>E3. The effect of TBT was pronounced even at concentrations substantially lower than those commonly reported in heavily contaminated areas, but the response was significantly different in the two model species. Sea urchin embryos were generally more sensitive to estrogenic EDCs and TBT than most other invertebrate larvae. Stage-specific exposure experiments were conducted to determine the most sensitive developmental periods using blastula, gastrula and post-gastrula (pluteus) stages. The stage most sensitive to E2, OCT and TBT was the blastula stage with less overall sensitivity in the gastrula stage, regardless of concentration. Selective estrogen receptor modulators (SERMs) were added to the experiments individually and in combination with estrogenic EDCs to interfere with potential receptor-mediated actions. Tamoxifen, a partial ER agonist, alone inhibited development at concentrations as low as 0.02 ng/ml and was effective at this concentration in decreasing the sensitivities of the embryos to estradiol and estrogenic EDCs. The complete antagonist ICI 182,780 inhibited development at concentrations as low as 0.03 ng/ml but increased embryo sensitivity to estradiol and estrogenic EDCs. Estradiol and estrogenic EDCs all cause developmental toxicity in sea urchins through a TAM-sensitive but an ICI-insensitive mechanism. It remains to be demonstrated whether this mechanism involves an estrogen-responsive nuclear receptor (NR), a membrane receptor (NR or non-NR-related) or a completely different mechanism of toxicity. However, early embryo sensitivity and the differential response to SERM co-incubation further suggests more than one mode of EDC action in the developing sea urchin embryo.

  13. Children's health insurance program premiums adversely affect enrollment, especially among lower-income children.

    PubMed

    Abdus, Salam; Hudson, Julie; Hill, Steven C; Selden, Thomas M

    2014-08-01

    Both Medicaid and the Children's Health Insurance Program (CHIP), which are run by the states and funded by federal and state dollars, offer health insurance coverage for low-income children. Thirty-three states charged premiums for children at some income ranges in CHIP or Medicaid in 2013. Using data from the 1999-2010 Medical Expenditure Panel Surveys, we show that the relationship between premiums and coverage varies considerably by income level and by parental access to employer-sponsored insurance. Among children with family incomes above 150 percent of the federal poverty level, a $10 increase in monthly premiums is associated with a 1.6-percentage-point reduction in Medicaid or CHIP coverage. In this income range, the increase in uninsurance may be higher among those children whose parents lack an offer of employer-sponsored insurance than among those whose parents have such an offer. Among children with family incomes of 101-150 percent of poverty, a $10 increase in monthly premiums is associated with a 6.7-percentage-point reduction in Medicaid or CHIP coverage and a 3.3-percentage-point increase in uninsurance. In this income range, the increase in uninsurance is even larger among children whose parents lack offers of employer coverage.

  14. Cellular senescence induced by prolonged subculture adversely affects glutamate uptake in C6 lineage.

    PubMed

    Pereira, Mery Stéfani Leivas; Zenki, Kamila; Cavalheiro, Marcela Mendonça; Thomé, Chairini Cássia; Filippi-Chiela, Eduardo Cremonese; Lenz, Guido; de Souza, Diogo Onofre Gomes; de Oliveira, Diogo Losch

    2014-05-01

    Several researchers have recently used C6 cells to evaluate functional properties of high-affinity glutamate transporters. However, it has been demonstrated that this lineage suffers several morphological and biochemical alterations according to the number of passages in culture. Currently, there are no reports showing whether functional properties of high-affinity glutamate transporters comply with these sub culturing-dependent modifications. The present study aimed to compare the functional properties of high-affinity glutamate transporters expressed in early (EPC6) and late (LPC6) passage C6 cells through a detailed pharmacological and biochemical characterization. Between 60-180 min of L-[(3)H]glu incubation, LPC6 presented an intracellular [(3)H] 55% lower than EPC6. Both cultures showed a time-dependent increase of intracellular [(3)H] reaching maximal levels at 120 min. Cultures incubated with D-[(3)H]asp showed a time-dependent increase of [(3)H] until 180 min. Moreover, LPC6 have a D-[(3)H]asp-derived intracellular [(3)H] 30-45% lower than EPC6 until 120 min. Only EAAT3 was immunodetected in cultures and its total content was equal between them. PMA-stimulated EAAT3 trafficking to membrane increased 50% of L-[(3)H]glu-derived intracellular [(3)H] in EPC6 and had no effect in LPC6. LPC6 displayed characteristics that resemble senescence, such as high β-Gal staining, cell enlargement and increase of large and regular nuclei. Our results demonstrated that LPC6 exhibited glutamate uptake impairment, which may have occurred due to its inability to mobilize EAAT3 to cell membrane. This profile might be related to senescent process observed in this culture. Our results suggest that LPC6 cells are an inappropriate glial cellular model to investigate the functional properties of high-affinity glutamate transporters.

  15. To provide additional housing assistance for certain individuals and households adversely affected by a major disaster.

    THOMAS, 111th Congress

    Rep. Hinchey, Maurice D. [D-NY-22

    2009-06-26

    06/29/2009 Referred to the Subcommittee on Economic Development, Public Buildings and Emergency Management. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  16. Our Results-Driven, Testing Culture: How It Adversely Affects Students' Personal Experience

    ERIC Educational Resources Information Center

    Lesch, Lyn

    2007-01-01

    Author Lyn Lesch advocates that learning cannot be measured by empirical results like testing and grading. As the founder of Chicago's The Children's School, Lesch didn't give grades or submit students to standardized testing. Such conditions may seem blasphemous to most educators, but the results spoke for themselves. Without the high-stakes…

  17. Maternal mobile phone exposure adversely affects the electrophysiological properties of Purkinje neurons in rat offspring.

    PubMed

    Haghani, M; Shabani, M; Moazzami, K

    2013-10-10

    Electromagnetic field (EMF) radiations emitted from mobile phones may cause structural damage to neurons. With the increased usage of mobile phones worldwide, concerns about their possible effects on the nervous system are rising. In the present study, we aimed to elucidate the possible effects of prenatal EMF exposure on the cerebellum of offspring Wistar rats. Rats in the EMF group were exposed to 900-MHz pulse-EMF irradiation for 6h per day during all gestation period. Ten offspring per each group were evaluated for behavioral and electrophysiological evaluations. Cerebellum-related behavioral dysfunctions were analyzed using motor learning and cerebellum-dependent functional tasks (Accelerated Rotarod, Hanging and Open field tests). Whole-cell patch clamp recordings were used for electrophysiological evaluations. The results of the present study failed to show any behavioral abnormalities in rats exposed to chronic EMF radiation. However, whole-cell patch clamp recordings revealed decreased neuronal excitability of Purkinje cells in rats exposed to EMF. The most prominent changes included afterhyperpolarization amplitude, spike frequency, half width and first spike latency. In conclusion, the results of the present study show that prenatal EMF exposure results in altered electrophysiological properties of Purkinje neurons. However, these changes may not be severe enough to alter the cerebellum-dependent functional tasks.

  18. Urban-rural status affects associations between domains of environmental quality and adverse birth outcomes

    EPA Science Inventory

    The relationship between environmental conditions and human health varies by environmental domain and urbanicity. To account for multiple ambient environmental conditions, we constructed an Environmental Quality Index (EQI) for health research. We used U.S. county level data rep...

  19. Cognitive load imposed by ultrasound-facilitated teaching does not adversely affect gross anatomy learning outcomes.

    PubMed

    Jamniczky, Heather A; Cotton, Darrel; Paget, Michael; Ramji, Qahir; Lenz, Ryan; McLaughlin, Kevin; Coderre, Sylvain; Ma, Irene W Y

    2017-03-01

    Ultrasonography is increasingly used in medical education, but its impact on learning outcomes is unclear. Adding ultrasound may facilitate learning, but may also potentially overwhelm novice learners. Based upon the framework of cognitive load theory, this study seeks to evaluate the relationship between cognitive load associated with using ultrasound and learning outcomes. The use of ultrasound was hypothesized to facilitate learning in anatomy for 161 novice first-year medical students. Using linear regression analyses, the relationship between reported cognitive load on using ultrasound and learning outcomes as measured by anatomy laboratory examination scores four weeks after ultrasound-guided anatomy training was evaluated in consenting students. Second anatomy examination scores of students who were taught anatomy with ultrasound were compared with historical controls (those not taught with ultrasound). Ultrasound's perceived utility for learning was measured on a five-point scale. Cognitive load on using ultrasound was measured on a nine-point scale. Primary outcome was the laboratory examination score (60 questions). Learners found ultrasound useful for learning. Weighted factor score on "image interpretation" was negatively, but insignificantly, associated with examination scores [F (1,135) = 0.28, beta = -0.22; P = 0.61]. Weighted factor score on "basic knobology" was positively and insignificantly associated with scores; [F (1,138) = 0.27, beta = 0.42; P = 0.60]. Cohorts exposed to ultrasound had significantly higher scores than historical controls (82.4% ± SD 8.6% vs. 78.8% ± 8.5%, Cohen's d = 0.41, P < 0.001). Using ultrasound to teach anatomy does not negatively impact learning and may improve learning outcomes. Anat Sci Educ 10: 144-151. © 2016 American Association of Anatomists.

  20. Aggregation of adverse behaviors and its affecting factors among young military conscripts in Taiwan.

    PubMed

    Wu, Der-Min; Chu, Nain-Feng; Lin, Yaoh-Shiang; Lai, Hsiang-Ru

    2007-06-01

    The authors studied the prevalence of the aggregation in common lifestyle habits, namely, cigarette smoking, alcohol drinking, and betel-nut chewing and the demographic correlates of individual aggregation in these lifestyle behaviors among young military conscripts in Taiwan. Cross-sectional screening was conducted among conscripts in southern and eastern sections of Taiwan from Aug. 1st to Dec. 31st 2001. Totally, 3913 conscripts who had more than 1 month of service were included in this multistage sampling study. Information on smoking, drinking, and betel-nut chewing habits were ascertained as part of a self-administered questionnaire completed by examinees at the service unit. Aggregation in lifestyle habits was studied by comparing the observed and expected proportions (O/E ratio) with their 95% confidence intervals (CI) for zero, one, two, and three simultaneously occurring lifestyle habits. The study results showed a significant clustering of lifestyle habits studied; the number of subjects was greater than expected in groups with two (for cigarette smoking and betel-nut chewing, O/E ratio=1.17, 95%CI=1.06-1.28), and three (O/E ratio=5.63, 95%CI=5.06-6.20) lifestyle habits. Determinants for this clustering of lifestyle habits included lower educational levels and residential area in southern and eastern sections of Taiwan. There was a significant individual aggregation in lifestyle habits including cigarette smoking, alcohol drinking, and betel-nut chewing in the health survey among young military conscripts. In addition, young military conscripts with low educational levels and residential area in southern and eastern sections of Taiwan had an apparent tendency toward the aggregation in these lifestyle habits.

  1. Ageing Adversely Affects the Migration and Function of Marginal Zone B Cells.

    PubMed

    Turner, Vivian M; Mabbott, Neil A

    2017-04-02

    Marginal zone (MZ) B cells are positioned within the spleen to capture blood-borne Ag and immune complexes and deliver them to follicular dendritic cells in the B cell follicles. We show that within the spleens of aged mice antigen (Ag) capture by MZ B cells, and their ability to shuttle between the follicle and MZ were impaired. The ability of aged MZ B cells to migrate towards the MZ chemoattractant sphingosine 1-phosphate was increased, suggesting that aged MZ B cells had a greater propensity to be retained within the MZ. An extrinsic impairment in aged B cell migration towards the MZ was demonstrated using bone marrow chimeras. The follicular shuttling of MZ B cells derived from either young or aged bone marrow was similarly reduced in aged recipient spleens, showing that ageing effects on splenic stromal cells were responsible for the impaired follicular shuttling of MZ B cells. MZ B cells rapidly mount T cell-independent (TI) antibody-responses to microbial polysaccharide Ag. In aged mice the ability to produce immunoglobulins in response to the TI-type 1 Ag, TNP-LPS, was impaired. These ageing related changes to the MZ and MZ B cells have implications for the clearance of blood-borne pathogens. Indeed elderly people have increased susceptibility to Streptococcus pneumoniae, a TI Ag, and decreased responses to vaccination. A thorough analysis of the mechanisms that underpin the ageing-related decline in the status of the MZ and MZ B cells will help the design of novel treatments to improve immunity in the elderly. This article is protected by copyright. All rights reserved.

  2. Psychosocial problems of donor heart recipients adversely affecting quality of life.

    PubMed

    Bunzel, B; Wollenek, G; Grundböck, A

    1992-10-01

    Heart transplantation has become an accepted therapy for patients suffering from terminal heart disease for whom neither standard forms of medication nor the usual surgery are of any benefit. Although results regarding postoperative quantity and quality of life are encouraging, it must not be overlooked that the patient and his family face, and have to overcome, profound psychosocial problems. The main stressors were identified in interviews with 47 heart transplant patients. The main preoperative problems were: the way of being informed about the diagnosis, the waiting period for transplantation, anguishing doubts about the decision to have a transplant, being a body without heart ('zombie'), guilt and shame regarding the donor, the reactions of others. Postoperatively the patients have to cope with: re-entering social systems, reactions of friends, neighbours and colleagues, rejection episodes, death of a fellow patient, the need to redesign family life. All the problems reported by the patients interviewed are discussed regarding their psychosocial implications, and hints are given on how to minimize them.

  3. Navy Acquisition. SUBACS (Submarine Advanced Combat System) Problems May Adversely Affect Navy Attack Submarine Programs.

    DTIC Science & Technology

    1985-11-01

    also the combat system design for the proposed new attack submarine class, SSN 21. In December 1983, the Navy awarded the International Business Machines...VI: Comments From International Business 35 Machines Corporation Abbreviations DNSARC Department of the Navy Systems Acquisition Review Council DSARC...Defense Systems Acquisition Review Council GAO General Accounting Office IBM International Business Machines Corporation NAVsEA Naval Sea Systems

  4. Urban cultivation in allotments maintains soil qualities adversely affected by conventional agriculture.

    PubMed

    Edmondson, Jill L; Davies, Zoe G; Gaston, Kevin J; Leake, Jonathan R

    2014-08-01

    Modern agriculture, in seeking to maximize yields to meet growing global food demand, has caused loss of soil organic carbon (SOC) and compaction, impairing critical regulating and supporting ecosystem services upon which humans also depend. Own-growing makes an important contribution to food security in urban areas globally, but its effects on soil qualities that underpin ecosystem service provision are currently unknown. We compared the main indicators of soil quality; SOC storage, total nitrogen (TN), C : N ratio and bulk density (BD) in urban allotments to soils from the surrounding agricultural region, and between the allotments and other urban greenspaces in a typical UK city. A questionnaire was used to investigate allotment management practices that influence soil properties. Allotment soils had 32% higher SOC concentrations and 36% higher C : N ratios than pastures and arable fields and 25% higher TN and 10% lower BD than arable soils. There was no significant difference between SOC concentration in allotments and urban non-domestic greenspaces, but it was higher in domestic gardens beneath woody vegetation. Allotment soil C : N ratio exceeded that in non-domestic greenspaces, but was lower than that in garden soil. Three-quarters of surveyed allotment plot holders added manure, 95% composted biomass on-site, and many added organic-based fertilizers and commercial composts. This may explain the maintenance of SOC, C : N ratios, TN and low BD, which are positively associated with soil functioning. Synthesis and applications. Maintenance and protection of the quality of our soil resource is essential for sustainable food production and for regulating and supporting ecosystem services upon which we depend. Our study establishes, for the first time, that small-scale urban food production can occur without the penalty of soil degradation seen in conventional agriculture, and maintains the high soil quality seen in urban greenspaces. Given the involvement of over 800 million people in urban agriculture globally, and its important contribution to food security, our findings suggest that to better protect soil functions, local, national and international urban planning and policy making should promote more urban own-growing in preference to further intensification of conventional agriculture to meet increasing food demand.

  5. Inactivation of PPARβ/δ adversely affects satellite cells and reduces postnatal myogenesis.

    PubMed

    Chandrashekar, Preeti; Manickam, Ravikumar; Ge, Xiaojia; Bonala, Sabeera; McFarlane, Craig; Sharma, Mridula; Wahli, Walter; Kambadur, Ravi

    2015-07-15

    Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a ubiquitously expressed gene with higher levels observed in skeletal muscle. Recently, our laboratory showed (Bonala S, Lokireddy S, Arigela H, Teng S, Wahli W, Sharma M, McFarlane C, Kambadur R. J Biol Chem 287: 12935-12951, 2012) that PPARβ/δ modulates myostatin activity to induce myogenesis in skeletal muscle. In the present study, we show that PPARβ/δ-null mice display reduced body weight, skeletal muscle weight, and myofiber atrophy during postnatal development. In addition, a significant reduction in satellite cell number was observed in PPARβ/δ-null mice, suggesting a role for PPARβ/δ in muscle regeneration. To investigate this, tibialis anterior muscles were injured with notexin, and muscle regeneration was monitored on days 3, 5, 7, and 28 postinjury. Immunohistochemical analysis revealed an increased inflammatory response and reduced myoblast proliferation in regenerating muscle from PPARβ/δ-null mice. Histological analysis confirmed that the regenerated muscle fibers of PPARβ/δ-null mice maintained an atrophy phenotype with reduced numbers of centrally placed nuclei. Even though satellite cell numbers were reduced before injury, satellite cell self-renewal was found to be unaffected in PPARβ/δ-null mice after regeneration. Previously, our laboratory had showed (Bonala S, Lokireddy S, Arigela H, Teng S, Wahli W, Sharma M, McFarlane C, Kambadur R. J Biol Chem 287: 12935-12951, 2012) that inactivation of PPARβ/δ increases myostatin signaling and inhibits myogenesis. Our results here indeed confirm that inactivation of myostatin signaling rescues the atrophy phenotype and improves muscle fiber cross-sectional area in both uninjured and regenerated tibialis anterior muscle from PPARβ/δ-null mice. Taken together, these data suggest that absence of PPARβ/δ leads to loss of satellite cells, impaired skeletal muscle regeneration, and postnatal myogenesis. Furthermore, our results also demonstrate that functional antagonism of myostatin has utility in rescuing these effects.

  6. Mexico City air pollution adversely affects olfactory function and intranasal trigeminal sensitivity.

    PubMed

    Guarneros, Marco; Hummel, Thomas; Martínez-Gómez, Margaríta; Hudson, Robyn

    2009-11-01

    Surprisingly little is known about the effects of big-city air pollution on olfactory function and even less about its effects on the intranasal trigeminal system, which elicits sensations like burning, stinging, pungent, or fresh and contributes to the overall chemosensory experience. Using the Sniffin' Sticks olfactory test battery and an established test for intranasal trigeminal perception, we compared the olfactory performance and trigeminal sensitivity of residents of Mexico City, a region with high air pollution, with the performance of a control population from the Mexican state of Tlaxcala, a geographically comparable but less polluted region. We compared the ability of 30 young adults from each location to detect a rose-like odor (2-phenyl ethanol), to discriminate between different odorants, and to identify several other common odorants. The control subjects from Tlaxcala detected 2-phenyl ethanol at significantly lower concentrations than the Mexico City subjects, they could discriminate between odorants significantly better, and they performed significantly better in the test of trigeminal sensitivity. We conclude that Mexico City air pollution impairs olfactory function and intranasal trigeminal sensitivity, even in otherwise healthy young adults.

  7. Peripartum cocaine use and adverse pregnancy outcome.

    PubMed

    Little, Bertis B.; Snell, Laura M.; Trimmer, Kenneth J.; Ramin, Susan M.; Ghali, Fred; Blakely, Craig A.; Garret, Andrea

    1999-09-01

    The objective of the study was to analyze possible adverse effects of peripartum cocaine use on maternal and fetal outcomes. Informed consent was given by 720 (97%) of 740 women who delivered consecutively at a large urban public hospital to test an umbilical cord blood sample for the presence of non-medically administered drugs of abuse and alcohol and to be interviewed for the study. Samples were tested for the presence of a cocaine metabolite (benzoylecgonine-BZE) by radioimmunoassay. The presence of other substances of abuse (alcohol, methamphetamine, opiates) resulted in exclusion from the sample of 143 subjects. Thus, in this cohort analysis, drug-free controls (N = 469) were compared to those positive for cocaine only (N = 108). Peripartum exposure to cocaine only, and no other substances of abuse, was associated with an increased frequency of abruptio placentae (1.9% vs 0% for control, P < 0.004), thick meconium stained amniotic fluid (3.9% vs 0.7% for controls, P < 0.006), premature rupture of membranes (P < 0.02), genitourinary anomalies (OR = 3.6, P < 0.05), abdominal wall defects (OR = 4.4, P < 0.01) and increased frequency of low birth weight (OR = 2.0, P < 0.02). These are important findings because previous studies have been complicated by the confounding effects of other substances of abuse. Am. J. Hum. Biol. 11:598-602, 1999. Copyright 1999 Wiley-Liss, Inc.

  8. Constructing Adverse Outcome Pathways: a Demonstration of ...

    EPA Pesticide Factsheets

    Adverse outcome pathway (AOP) provides a conceptual framework to evaluate and integrate chemical toxicity and its effects across the levels of biological organization. As such, it is essential to develop a resource-efficient and effective approach to extend molecular initiating events (MIEs) of chemicals to their downstream phenotypes of a greater regulatory relevance. A number of ongoing public phenomics (high throughput phenotyping) efforts have been generating abundant phenotypic data annotated with ontology terms. These phenotypes can be analyzed semantically and linked to MIEs of interest, all in the context of a knowledge base integrated from a variety of ontologies for various species and knowledge domains. In such analyses, two phenotypic profiles (PPs; anchored by genes or diseases) each characterized by multiple ontology terms are compared for their semantic similarities within a common ontology graph, but across boundaries of species and knowledge domains. Taking advantage of publicly available ontologies and software tool kits, we have implemented an OS-Mapping (Ontology-based Semantics Mapping) approach as a Java application, and constructed a network of 19383 PPs as nodes with edges weighed by their pairwise semantic similarity scores. Individual PPs were assembled from public phenomics data. Out of possible 1.87×108 pairwise connections among these nodes, about 71% of them have similarity scores between 0.2 and the maximum possible of 1.0.

  9. Adapting biomarker technologies to adverse outcome ...

    EPA Pesticide Factsheets

    Adverse outcome pathways (AOP) research is a relatively new concept in human systems biology for assessing the molecular level linkage from an initiating (chemical) event that could lead to a disease state. Although most implementations of AOPs are based on liquids analyses, there are now new technologies being considered derived from the broad field of breath research, especially in applications of gas-phase analysis and instrumentation. The ultimate goal is to discover disease progressions in human or animal systems, identify them at the molecular or cellular level, and then choose analytes that can distinctly define the presence of a particular path (Ankley et al. 2010, Villeneuve et al. 2014). Once such in vivo pathways are identified, then in vitro assays can be developed for streamlined testing of chemical effects without additional human or animal based studies (Pleil et al. 2012). Recent work has focused on discovery analysis in breath, or other biological media, wherein as many as possible compounds are cataloged and then linked to their biochemical source as exogenous (external), endogenous (internal) or from the microbiome (Pleil et al. 2013a, de Lacy Costello 2014, Pleil et al. 2013b, Trefz et al. 2013, Pleil et al. 2014). Such research lays the groundwork for identifying compounds from systems biology that might be relevant for developing AOPs for in vitro research. The National Exposure Research Laboratory’s (NERL’s) Human Exposure and Atm

  10. [Management of adverse effects with antituberculosis chemotherapy].

    PubMed

    Tsuyuguchi, Kazunari; Wada, Masako

    2011-02-01

    Tuberculosis has now become a curable disease with chemotherapy. So it is natural that the present issues in tuberculosis management are focused on how to complete standard chemotherapy. In this context, management of adverse effects constitutes an essential part of antituberculosis chemotherapy, as well as directly observed therapy. In this symposium, discussions were held about three major subjects on this issue. First, hepatotoxicity develops frequently and has sometimes fatal outcome, which makes it the most problematic adverse effect. "Management of hepatotoxicity during antituberculosis chemotherapy" was published by the Japanese Society for Tuberculosis (JST) in 2006. Dr. Shinsho Yoshiba evaluated this recommendation and pointed out that the criteria for discontinuation of drug based on AST, ALT and bilirubin levels is too sensitive and the concept of predicting fulminant hepatic failure (FHF) is lacking. He stressed the importance of monitoring serum prothrombin time for predicting FHF. Next, allergic drug reaction such as fever or skin rash often causes distress, although rarely fatal. As isoniazid (INH) and rifampicin (RFP) are key drugs for the cure, readministration of these drugs is often attempted by desensitization therapy. "Recommendation about desensitization therapy of antituberculosis drugs" was also published by JST in 1997. Dr. Yoshihiro Kobashi reported high success rates of 79 percent for INH and 75 percent for RFP according to this recommendation. He also reported correlated factor with the success, such as the longer period from the discontinuation to the desensitization therapy and lower doses of drugs at starting desensitization. Finally, we sometimes experience transient worsening of radiographical findings and general symptoms during antituberculosis chemotherapy. This is presumed to be due to allergic reaction to dead bacilli without requiring discontinuation of the drug. Differential diagnosis includes drug-induced pneumonia requring

  11. Adverse health consequences of the Vietnam War.

    PubMed

    Levy, Barry S; Sidel, Victor W

    2015-01-01

    The 40th anniversary of the end of the Vietnam War is a useful time to review the adverse health consequences of that war and to identify and address serious problems related to armed conflict, such as the protection of noncombatant civilians. More than 58,000 U.S. servicemembers died during the war and more than 150,000 were wounded. Many suffered from posttraumatic stress disorders and other mental disorders and from the long-term consequences of physical injuries. However, morbidity and mortality, although difficult to determine precisely, was substantially higher among the Vietnamese people, with at least two million of them dying during the course of the war. In addition, more than one million Vietnamese were forced to migrate during the war and its aftermath, including many "boat people" who died at sea during attempts to flee. Wars continue to kill and injure large numbers of noncombatant civilians and continue to damage the health-supporting infrastructure of society, expose civilians to toxic chemicals, forcibly displace many people, and divert resources away from services to benefit noncombatant civilians. Health professionals can play important roles in promoting the protection of noncombatant civilians during war and helping to prevent war and create a culture of peace.

  12. Adverse immunologic effects of antithyroid drugs.

    PubMed Central

    Wing, S S; Fantus, I G

    1987-01-01

    Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described. A review of the literature revealed 53 similar cases over a 35-year period. Rash, fever, arthralgias and granulocytopenia were the most common manifestations. Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal. The clinical evidence suggests that an immunologic mechanism is involved. A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus. Thus, the reactions do not represent a true drug-induced lupus syndrome. Current hypotheses and experimental data regarding the cause of the reactions are reviewed. No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy. Cross-reactivity between the two antithyroid drugs can be expected. Except for minor symptoms (e.g., mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism. In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful. PMID:3539299

  13. Idiosyncratic Adverse Drug Reactions: Current Concepts

    PubMed Central

    Naisbitt, Dean J.

    2013-01-01

    Idiosyncratic drug reactions are a significant cause of morbidity and mortality for patients; they also markedly increase the uncertainty of drug development. The major targets are skin, liver, and bone marrow. Clinical characteristics suggest that IDRs are immune mediated, and there is substantive evidence that most, but not all, IDRs are caused by chemically reactive species. However, rigorous mechanistic studies are very difficult to perform, especially in the absence of valid animal models. Models to explain how drugs or reactive metabolites interact with the MHC/T-cell receptor complex include the hapten and P-I models, and most recently it was found that abacavir can interact reversibly with MHC to alter the endogenous peptides that are presented to T cells. The discovery of HLA molecules as important risk factors for some IDRs has also significantly contributed to our understanding of these adverse reactions, but it is not yet clear what fraction of IDRs have a strong HLA dependence. In addition, with the exception of abacavir, most patients who have the HLA that confers a higher IDR risk with a specific drug will not have an IDR when treated with that drug. Interindividual differences in T-cell receptors and other factors also presumably play a role in determining which patients will have an IDR. The immune response represents a delicate balance, and immune tolerance may be the dominant response to a drug that can cause IDRs. PMID:23476052

  14. Analyzing risks of adverse pregnancy outcomes.

    PubMed

    Kramer, Michael S; Zhang, Xun; Platt, Robert W

    2014-02-01

    Approaches for analyzing the risks of adverse pregnancy outcomes have been the source of much debate and many publications. Much of the problem, in our view, is the conflation of time at risk with gestational age at birth (or birth weight, a proxy for gestational age). We consider the causal questions underlying such analyses with the help of a generic directed acyclic graph. We discuss competing risks and populations at risk in the context of appropriate numerators and denominators, respectively. We summarize 3 different approaches to quantifying risks with respect to gestational age, each of which addresses a distinct etiological or prognostic question (i.e., cumulative risk, prospective risk, or instantaneous risk (hazard)) and suggest the appropriate denominators for each. We show how the gestational age-specific risk of perinatal death (PND) can be decomposed as the product of the gestational age-specific risk of birth and the risk of PND conditional on birth at a given gestational age. Finally, we demonstrate how failure to consider the first of these 2 risks leads to selection bias. This selection bias creates the well-known crossover paradox, thus obviating the need to posit common causes of early birth and PND other than the study exposure.

  15. Reporting vaccine-associated adverse events.

    PubMed Central

    Duclos, P.; Hockin, J.; Pless, R.; Lawlor, B.

    1997-01-01

    OBJECTIVE: To determine family physicians' awareness of the need to monitor and report vaccine-associated adverse events (VAAE) in Canada and to identify mechanisms that could facilitate reporting. DESIGN: Mailed survey. SETTING: Canadian family practices. PARTICIPANTS: Random sample of 747 family physicians. Overall response rate was 32% (226 of 717 eligible physicians). MAIN OUTCOME MEASURES: Access to education on VAAE; knowledge about VAAE monitoring systems, reporting criteria, and reporting forms; method of reporting VAAEs and reasons for not reporting them; and current experience with VAAEs. RESULTS: Of 226 respondents, 55% reported observing VAAEs, and 42% reported the event. Fewer than 50% were aware of a monitoring system for VAAE, and only 39% had had VAAE-related education during medical training. Only 28% knew the reporting criteria. Reporting was significantly associated with knowledge of VAAE monitoring systems and reporting criteria (P < 0.01). CONCLUSION: Physicians need more feedback and education on VAAE reporting and more information about the importance of reporting and about reporting criteria and methods. PMID:9303234

  16. Orthographic Resources Affect Reading Acquisition--If They Are Used.

    ERIC Educational Resources Information Center

    Gleitman, Lila R.

    1985-01-01

    The article replies to H. Stevenson (EC 162 649), who has interpreted his cross-linguistic studies as showing that differences in orthographies do not materially affect the reading-acquisition process or the prognosis for successful learning. The reply asserts that Stevenson's results derive from a faulty interpretation of comparisons among…

  17. Melanoma molecular classes and prognosis in the postgenomic era.

    PubMed

    Tremante, Elisa; Ginebri, Agnese; Lo Monaco, Elisa; Frascione, Pasquale; Di Filippo, Franco; Terrenato, Irene; Benevolo, Maria; Mottolese, Marcella; Pescarmona, Edoardo; Visca, Paolo; Natali, Pier Giorgio; Giacomini, Patrizio

    2012-05-01

    Gene expression profiling is a powerful method to classify human tumours on the basis of biological aggressiveness, response to therapy, and outcome for the patient, but its application in melanoma lags behind that of other cancers. From more than 100 articles available on the topic, we selected 14 focusing on patients' outcome. We review and briefly discuss salient findings, and list ten reasons why melanoma molecular classes are not yet used in clinical diagnosis and prognosis. The available evidence suggests that we are on the verge of creating a framework for the use of melanoma molecular classes in prognosis, but so far there is little consensus to put together informative diagnostic and prognostic gene sets.

  18. Prognosis Driven Rehabilitation After Rotator Cuff Repair Surgery

    PubMed Central

    Kokmeyer, Dirk; Dube, Eric; Millett,, Peter J.

    2016-01-01

    Background: Rehabilitation after rotator cuff repair surgery has been the focus of several clinical trials in the past decade. Many illuminate new evidence with regard to the prognosis of structural and functional success after surgery. Methods: A selective literature search was performed and personal physiotherapeutic and surgical experiences are reported. Results: Post-operative rehabilitation parameters, namely the decision to delay or allow early range of motion after surgery, play a large role in the overall success after surgery. Using a prognosis driven rehabilitation program offers clinicians a means of prescribing optimal rehabilitation parameters while ensuring structural and functional success. This commentary aims to synthesize the evidence in a spectrum of prognostic factors to guide post-operative rehabilitation. Conclusion: The optimal rehabilitation program after rotator cuff repair surgery is debatable; therefore, we suggest using a spectrum of prognostic factors to determine a rehabilitation program suited to ensure structural and functional success, quickly and safely. PMID:27708736

  19. [Prognosis-criteria after long-term imprisonment (author's transl)].

    PubMed

    Albrecht, P A

    1981-02-01

    This report shows a series of prognosis-data drawn from an examination of the social situation of all "lifers", who were released from prison in Lower Saxony between 1945 and 1973. The main point of the analysis is the high rate of over 90% of successful post-institutional legal behaviour. For most of the ex-convicts an increase in income and a higher job satisfaction (upward social mobility) were registered after release from prison; family integration is another explanation for the high rate of successful behaviour. On the other hand a long term of imprisonment destroys prisoners' ability to fit into society. The potentiality to social activity diminishes, family ties break down and the burden of the results of imprisonment -- a dangerous influence on the process of reintegration -- increases. Age and prison adjustment behaviour are mostly irrelevant as prognosis-criteria.

  20. Alcoholism: diagnosis, prognosis, epidemiology, and burden of the disease.

    PubMed

    Beresford, Thomas P; Wongngamnit, Narin; Temple, Benjamin A

    2014-01-01

    To the clinician, alcoholism can appear as an amorphous entity that is confusing with respect to diagnosis, treatment prognosis, and the role of the health professional, despite its high incidence and associated morbidities and mortality when unrecognized or untreated. This chapter focuses on the clinical application of current knowledge, with the aim of being useful to the practitioner in working directly with patients for whom alcoholism may or may not be an already identified problem. It briefly reviews large-scale studies and then focuses on diagnosis and prognosis assessment and decision making. Also considered are current controversies in nomenclature and the chapter ends with an economic perspective with respect to healthcare and cost to society. As the introductory chapter, the goal is to provide a context of the scope of alcoholism and attendant problems for the rest of the chapters.