Risk of All-Cause Mortality in Alcohol-Dependent Individuals: A Systematic Literature Review and Meta-Analysis.

BACKGROUND: Alcohol dependence (AD) carries a high mortality burden, which may be mitigated by reduced alcohol consumption. We conducted a systematic literature review and meta-analysis investigating the risk of all-cause mortality in alcohol-dependent subjects. METHODS: MEDLINE, MEDLINE In-Process, Embase and PsycINFO were searched from database conception through 26th June 2014. Eligible studies reported all-cause mortality in both alcohol-dependent subjects and a comparator population of interest. Two individuals independently reviewed studies. Of 4540 records identified, 39 observational studies were included in meta-analyses. FINDINGS: We identified a significant increase in mortality for alcohol-dependent subjects compared with the general population (27 studies; relative risk [RR] = 3.45; 95% CI [2.96, 4.02]; p < 0.0001). The mortality increase was also significant compared to subjects qualifying for a diagnosis of alcohol abuse or subjects without alcohol use disorders (AUDs). Alcohol-dependent subjects continuing to drink heavily had significantly greater mortality than alcohol-dependent subjects who reduced alcohol intake, even if abstainers were excluded (p < 0.05). INTERPRETATION: AD was found to significantly increase an individual's risk of all-cause mortality. While abstinence in alcohol-dependent subjects led to greater mortality reduction than non-abstinence, this study suggests that alcohol-dependent subjects can significantly reduce their mortality risk by reducing alcohol consumption.

Impact of reclassifying noninvasive follicular variant of papillary thyroid carcinoma on the risk of malignancy in The Bethesda System for Reporting Thyroid Cytopathology.

BACKGROUND: Recent discussions have focused on redefining noninvasive follicular variant of papillary thyroid carcinoma (NI-FVPTC) as a neoplasm rather than a carcinoma. This study assesses the potential impact of such a reclassification on the implied risk of malignancy (ROM) for the diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). METHODS: The study consisted of consecutive fine-needle aspiration biopsy (FNAB) cases collected between January 1, 2013 and June 30, 2014 from 5 academic institutions. Demographic information, cytology diagnoses, and surgical pathology follow-up were recorded. The ROM was calculated with and without NI-FVPTC and was presented as a range: all cases (ie, overall risk of malignancy [OROM]) versus those with surgical follow-up only. RESULTS: The FNAB cohort consisted of 6943 thyroid nodules representing 5179 women and 1409 men with an average age of 54 years (range, 9-94 years). The combined average ROM and OROM for the diagnostic categories of TBSRTC were as follows: nondiagnostic, 4.4% to 25.3%; benign, 0.9% to 9.3%; atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 12.1% to 31.2%; follicular neoplasm (FN), 21.8% to 33.2%; suspicious for malignancy (SM), 62.1% to 82.6%; and malignant, 75.9% to 99.1%. The impact of reclassifying NI-FVPTC on the ROM and OROM was most pronounced and statistically significant in the 3 indeterminate categories: the AUS/FLUS category had a decrease of 5.2% to 13.6%, the FN category had a decrease of 9.9% to 15.1%, and the SM category had a decrease of 17.6% to 23.4% (P < .05), whereas the benign and malignant categories had decreases of 0.3% to 3.5% and 2.5% to 3.3%, respectfully. The trend of the effect on the ROM and OROM was similar for all 5 institutions. CONCLUSIONS: The results from this multi-institutional cohort indicate that the reclassification of NI-FVPTC will have a significant impact on the ROM for the 3 indeterminate categories of TBSRTC. Cancer Cytopathol 2016;124:181-187. © 2015 American Cancer Society.

Antibody levels against GLURP R2, MSP1 block 2 hybrid and AS202.11 and the risk of malaria in children living in hyperendemic (Burkina Faso) and hypo-endemic (Ghana) areas.

Differences in parasite transmission intensity influence the process of acquisition of host immunity to Plasmodium falciparum malaria and ultimately, the rate of malaria related morbidity and mortality. Potential vaccines being designed to complement current intervention efforts therefore need to be evaluated against different malaria endemicity backgrounds. The associations between antibody responses to the chimeric merozoite surface protein 1 block 2 hybrid (MSP1 hybrid), glutamate-rich protein region 2 (GLURP R2) and the peptide AS202.11, and the risk of malaria were assessed in children living in malaria hyperendemic (Burkina Faso, n = 354) and hypo-endemic (Ghana, n = 209) areas. Using the same reagent lots and standardized protocols for both study sites, immunoglobulin (Ig) M, IgG and IgG sub-class levels to each antigen were measured by ELISA in plasma from the children (aged 6-72 months). Associations between antibody levels and risk of malaria were assessed using Cox regression models adjusting for covariates. There was a significant association between GLURP R2 IgG3 and reduced risk of malaria after adjusting age of children in both the Burkinabe (hazard ratio 0.82; 95 % CI 0.74-0.91, p < 0.0001) and the Ghanaian (HR 0.48; 95 % CI 0.25-0.91, p = 0.02) cohorts. MSP1 hybrid IgM was associated (HR 0.85; 95 % CI 0.73-0.98, p = 0.02) with reduced risk of malaria in Burkina Faso cohort while IgG against AS202.11 in the Ghanaian children was associated with increased risk of malaria (HR 1.29; 95 % CI 1.01-1.65, p = 0.04). These findings support further development of GLURP R2 and MSP1 block 2 hybrid, perhaps as a fusion vaccine antigen targeting malaria blood stage that can be deployed in areas of varying transmission intensity.

Presence of Leishmania RNA Virus 1 in Leishmania guyanensis Increases the Risk of First-Line Treatment Failure and Symptomatic Relapse.

Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasis (TL). Such complications are seen frequently in Leishmania guyanensis infections, in which patients respond variously to first-line antileishmanials and are more prone to develop chronic cutaneous leishmaniasis. The factors underlying this pathology, however, are unknown. Recently, we reported that a double-stranded RNA virus, Leishmania RNA virus 1 (LRV1), nested within L. guyanensis parasites is able to exacerbate experimental murine leishmaniasis by inducing a hyperinflammatory response. This report investigates the prevalence of LRV1 in human L. guyanensis infection and its effect on treatment efficacy, as well as its correlation to symptomatic relapses after the completion of first-line treatment. In our cohort of 75 patients with a diagnosis of primary localized American TL, the prevalence of LRV1-positive L. guyanensis infection was elevated to 58%. All patients infected with LRV1-negative L. guyanensis were cured after 1 dose (22 of 31 [71%]) or 2 doses (31 of 31 [100%]) of pentamidine. In contrast, 12 of 44 LRV1-positive patients (27%) presented with persistent infection and symptomatic relapse that required extended therapy and the use of second-line drugs. Finally, LRV1 presence was associated with a significant increase in levels of intra-lesional inflammatory markers. In conclusion, LRV1 status in L. guyanensis infection is significantly predictive (P = .0009) of first-line treatment failure and symptomatic relapse and has the potential to guide therapeutic choices in American TL.

Will climate change increase the risk of plant invasions into mountains?

Mountain ecosystems have been less adversely affected by invasions of non-native plants than most other ecosystems, partially because most invasive plants in the lowlands are limited by climate and cannot grow under harsher high-elevation conditions. However, with ongoing climate change, invasive species may rapidly move upwards and threaten mid- then high-elevation mountain ecosystems. We evaluated this threat by predicting current and future potential distributions of 48 invasive plant species distributed in Switzerland (CH) and New South Wales (NSW), two areas where climate interacts differently with the elevation gradient. Using a species distribution modeling approach combining two scales, which builds on high-resolution data (< 250 m) but accounts for the global climatic niche of species, we found that different environmental drivers limit the elevation range of invasive species in the two regions, leading to region-specific species responses to climate change. Whereas the optimal suitability for plant invaders is predicted to markedly shift from the lowland to the montane or subalpine zone in CH, such an upward shift is far less pronounced in NSW where montane and subalpine elevations are currently already suitable. Non-native species able to invade the upper reaches of mountains in a future climate will be cold-tolerant in the Swiss Alps but preferring wet soils in the Australian Alps. Other plant traits were only marginally associated with elevation limits. These results demonstrate that a more systematic consideration of future distributions of invasive species is required in conservation plans of not yet invaded mountainous ecosystems.

Association of early repolarization with risk of cardiac mortality in the general population

Early repolarization, which is characterized by an elevation of the J-point on 12-lead electrocardiography, is a common finding that has been considered as benign for decades. However, in the last years, it has been related with vulnerability to idiopathic ventricular fibrillation and with cardiac mortality in the general population. Recently, 4 potential ECG predictors that could differentiate the benign from the malignant form of early repolarization have been suggested. Any previous study about early repolarization has been done in Spain. Aim. To ascertain whether the presence of early repolarization pattern in a resting electrocardiogram is associated with a major risk of cardiac death in a Spanish general population and to determine whether the presence of potential predictors of malignancy in a resting electrocardiogram increases the risk of cardiac mortality in patients with early repolarization pattern. Methods. We will analyse the presence of early repolarization and the occurrence of cardiac mortality in a retrospective cohort study of 4,279 participants aged 25 to 74 years in the province of Girona. This cohort has been followed during a mean of 9.8 years. Early repolarization will be stratified according to the degree of J-point elevation (≥0.1 mV or ≥0.2 mV), the morphology of the J-wave (slurring, notching or any of these two), the ST-segment pattern (ascending or descending) and the localization (inferior leads, lateral leads, or both). Association of early repolarization with cardiac death will be assessed by adjusted Cox-proportional hazards models

Risk of hypoglycemia in newborns from mothers with gestacional diabetes

There are not enough previous publications which are focused on mothers with well-controlled gestational diabetes mellitus (GDM) as a risk factor that determines the occurrence of neonatal hypoglycemia. In addition, approaches to blood glucose monitoring have been inconsistent and poorly defined. Our objective is to determine if being a newborn from a mother with well-controlled gestational diabetes (regardless insulin treatment) have a higher risk to develop hypoglycemia than a healthy newborn, using a defined and strict protocol. The project will take place in a regional hospital of Girona. We will recruit from 2014 to 2015 a cohort of 623 infants born in this center without any malformation or any perinatal pathology or complication, selected with a consecutive sampling. We will record sex, ethnicity and gestational age information. We will measure blood glucose levels and anthropometric measurements in newborns always taking into account the presence of well-controlled maternal gestational diabetes or not. Patients will be followed up during 24 hours to determine the incidence of hypoglycemia. We will analyze the contribution between exposure factors that we have studied and the incidence of the outcome using a multivariate analysis

Epithelial-to-mesenchymal transition mediates docetaxel resistance and high risk of relapse in prostate cancer

Molecular characterization of radical prostatectomy specimens after systemic therapy may identify a gene expression profile for resistance to therapy. This study assessed tumor cells from patients with prostate cancer participating in a phase II neoadjuvant docetaxel and androgen deprivation trial to identify mediators of resistance. Transcriptional level of 93 genes from a docetaxel-resistant prostate cancer cell lines microarray study was analyzed by TaqMan low-density arrays in tumors from patients with high-risk localized prostate cancer (36 surgically treated, 28 with neoadjuvant docetaxel þ androgen deprivation). Gene expression was compared between groups and correlated with clinical outcome. VIM, AR and RELA were validated by immunohistochemistry. CD44 and ZEB1 expression was tested by immunofluorescence in cells and tumor samples. Parental and docetaxel-resistant castration-resistant prostate cancer cell lines were tested for epithelial-to-mesenchymal transition (EMT) markers before and after docetaxel exposure. Reversion of EMT phenotype was investigated as a docetaxel resistance reversion strategy. Expression of 63 (67.7%) genes differed between groups (P < 0.05), including genes related to androgen receptor, NF-k B transcription factor, and EMT. Increased expression of EMT markers correlated with radiologic relapse. Docetaxel-resistant cells had increased EMT and stem-like cell markers expression. ZEB1 siRNA transfection reverted docetaxel resistance and reduced CD44 expression in DU-145R and PC-3R. Before docetaxel exposure, a selected CD44 þ subpopulation of PC-3 cells exhibited EMT phenotype and intrinsic docetaxel resistance; ZEB1/CD44 þ subpopulations were found in tumor cell lines and primary tumors; this correlated with aggressive clinical behavior. This study identifies genes potentially related to chemotherapy resistance and supports evi-dence of the EMT role in docetaxel resistance and adverse clinical behavior in early prostate cancer.

An analysis of the risk of cocoa moniliasis occurrence in Brazil as the result of climate change

The aim of this study was to evaluate the potential risk of moniliasis occurrence and the impacts of climate change on this disease in the coming decades, should this pathogen be introduced in Brazil. To this end, climate favorability maps were devised for the occurrence of moniliasis, both for the present and future time. The future scenarios (A2 and B2) focused on the decades of 2020, 2050 and 2080. These scenarios were obtained from six global climate models (GCMs) made available by the third assessment report of Intergovernmental Panel on Climate Change (IPCC). Currently, there are large areas with favorable climate conditions for moniliasis in Brazil, especially in regions at high risk of introduction of that pathogen. Considering the global warming scenarios provided by the IPCC, the potential risk of moniliasis occurrence in Brazil will be reduced. This decrease is predicted for both future scenarios, but will occur more sharply in scenario A2. However, there will still be areas with favorable climate conditions for the development of the disease, particularly in Brazil's main producing regions. Moreover, pathogen and host alike may undergo alterations due to climate change, which will affect the extent of their impacts on this pathosystem.

Identifying first graders at risk of reading and writing difficulties : creating a group-based screening tool in kiswahili in Tanzania

Early identification of beginning readers at risk of developing reading and writing difficulties plays an important role in the prevention and provision of appropriate intervention. In Tanzania, as in other countries, there are children in schools who are at risk of developing reading and writing difficulties. Many of these children complete school without being identified and without proper and relevant support. The main language in Tanzania is Kiswahili, a transparent language. Contextually relevant, reliable and valid instruments of identification are needed in Tanzanian schools. This study aimed at the construction and validation of a group-based screening instrument in the Kiswahili language for identifying beginning readers at risk of reading and writing difficulties. In studying the function of the test there was special interest in analyzing the explanatory power of certain contextual factors related to the home and school. Halfway through grade one, 337 children from four purposively selected primary schools in Morogoro municipality were screened with a group test consisting of 7 subscales measuring phonological awareness, word and letter knowledge and spelling. A questionnaire about background factors and the home and school environments related to literacy was also used. The schools were chosen based on performance status (i.e. high, good, average and low performing schools) in order to include variation. For validation, 64 children were chosen from the original sample to take an individual test measuring nonsense word reading, word reading, actual text reading, one-minute reading and writing. School marks from grade one and a follow-up test half way through grade two were also used for validation. The correlations between the results from the group test and the three measures used for validation were very high (.83-.95). Content validity of the group test was established by using items drawn from authorized text books for reading in grade one. Construct validity was analyzed through item analysis and principal component analysis. The difficulty level of most items in both the group test and the follow-up test was good. The items also discriminated well. Principal component analysis revealed one powerful latent dimension (initial literacy factor), accounting for 93% of the variance. This implies that it could be possible to use any set of the subtests of the group test for screening and prediction. The K-Means cluster analysis revealed four clusters: at-risk children, strugglers, readers and good readers. The main concern in this study was with the groups of at-risk children (24%) and strugglers (22%), who need the most assistance. The predictive validity of the group test was analyzed by correlating the measures from the two school years and by cross tabulating grade one and grade two clusters. All the correlations were positive and very high, and 94% of the at-risk children in grade two were already identified in the group test in grade one. The explanatory power of some of the home and school factors was very strong. The number of books at home accounted for 38% of the variance in reading and writing ability measured by the group test. Parents´ reading ability and the support children received at home for schoolwork were also influential factors. Among the studied school factors school attendance had the strongest explanatory power, accounting for 21% of the variance in reading and writing ability. Having been in nursery school was also of importance. Based on the findings in the study a short version of the group test was created. It is suggested for use in the screening processes in grade one aiming at identifying children at risk of reading and writing difficulties in the Tanzanian context. Suggestions for further research as well as for actions for improving the literacy skills of Tanzanian children are presented.

The effectiveness of short-term literacy skills intervention on children at risk of reading and writing difficulties in Tanzania : a study of grade one children with dynamic assessment approach

The aim of the study was to create and evaluate an intervention programme for Tanzanian children from a low-income area who are at risk of reading and writing difficulties. The learning difficulties, including reading and writing difficulties, are likely to be behind many of the common school problems in Tanzania, but they are not well understood, and research is needed. The design of the study included an identification and intervention phase with follow-up. A group based dynamic assessment approach was used in identifying children at risk of difficulties in reading and writing. The same approach was used in the intervention. The study was a randomized experiment with one experimental and two control groups. For the experimental and the control groups, a total of 96 (46 girls and 50 boys) children from grade one were screened out of 301 children from two schools in a low income urban area of Dar-es-Salaam. One third of the children, the experimental group, participated in an intensive training programme in literacy skills for five weeks, six hours per week, aimed at promoting reading and writing ability, while the children in the control groups had a mathematics and art programme. Follow-up was performed five months after the intervention. The intervention programme and the tests were based on the Zambian BASAT (Basic Skill Assessment Tool, Ketonen & Mulenga, 2003), but the content was drawn from the Kiswahili school curriculum in Tanzania. The main components of the training and testing programme were the same, only differing in content. The training process was different from traditional training in Tanzanian schools in that principles of teaching and training in dynamic assessment were followed. Feedback was the cornerstone of the training and the focus was on supporting the children in exploring knowledge and strategies in performing the tasks. The experimental group improved significantly more (p = .000) than the control groups during the intervention from pre-test to follow-up (repeated measures ANOVA). No differences between the control groups were noticed. The effect was significant on all the measures: phonological awareness, reading skills, writing skills and overall literacy skills. A transfer effect on school marks in Kiswahili and English was found. Following a discussion of the results, suggestions for further research and adaptation of the programme are presented.

Comparative study of the different degrees of risk of gastrointestinal stromal tumor

OBJECTIVE: To evaluate the applicability of the main categories of risk and morphological factors in the prognosis of gastrointestinal stromal tumors. METHODS: we retrospectively studied fifty-four cases of GIST, assessing the main prognostic factors of this neoplasis: risk levels, topography, size, mitotic index, necrosis, histological subtype and immunophenotype. We also verified their association and the reduction of overall survival. RESULTS: Univariate analysis showed that tumors with mitoses number greater than 5 per 50CGA (high-power fields), the presence of necrosis and a high risk for both the systems proposed by Fletcher and Miettinen had a significant association with reduced survival (p = 0.00001, 0.0056, 0.03 and 0.009, respectively). The remaining analyzed factors (size, histological subtype, topography and immunophenotype) had no such association. Multivariate analysis (Jacard index) showed that the Miettinen degree of risk was the one that best correlated with prognosis. CONCLUSION: the risk criteria of Fletcher and Miettinen are important in assessing the prognosis of patients with gastrointestinal stromal tumors, especially the latter, which adds to the mitotic index and the presence of tumor necrosis.