Paralogous translation factors target distinct mRNAs to differentially regulate tolerance to oxidative stress in yeast.

Translation initiation factor 4G (eIF4G) is an integral component of the eIF4F complex which is key to translation initiation for most eukaryotic mRNAs. Many eIF4G isoforms have been described in diverse eukaryotic organisms but we currently have a poor understanding of their functional roles and whether they regulate translation in an mRNA specific manner. The yeast Saccharomyces cerevisiae expresses two eIF4G isoforms, eIF4G1 and eIF4G2, that have previously been considered as functionally redundant with any phenotypic differences arising due to alteration in eIF4G expression levels. Using homogenic strains that express eIF4G1 or eIF4G2 as the sole eIF4G isoforms at comparable expression levels to total eIF4G, we show that eIF4G1 is specifically required to mediate the translational response to oxidative stress. eIF4G1 binds the mRNA cap and remains associated with actively translating ribosomes during oxidative stress conditions and we use quantitative proteomics to show that eIF4G1 promotes oxidative stress-specific proteome changes. eIF4G1, but not eIF4G2, binds the Slf1 LARP protein which appears to mediate the eIF4G1-dependent translational response to oxidative stress. We show similar isoform specific roles for eIF4G in human cells suggesting convergent evolution of multiple eIF4G isoforms offers significant advantages especially where translation must continue under stress conditions.

QTL Determining Diel Flight Activity in Male Culex pipiens Mosquitoes.

Members of the Culex pipiens complex differ in physiological traits that facilitate their survival in diverse environments. Assortative mating within the complex occurs in some regions where autogenous (the ability to lay a batch of eggs without a blood meal) and anautogenous populations are sympatric, and differences in mating behaviors may be involved. For example, anautogenous populations mate in flight/swarms, while autogenous populations often mate at rest. Here, we characterized flight activity of males and found that anautogenous strain males were crepuscular, while autogenous strain males were crepuscular and nocturnal, with earlier activity onset times. We conducted quantitative trait locus (QTL) mapping to explore the genetic basis of circadian chronotype (crepuscular vs. crepuscular and nocturnal) and time of activity onset. One major-effect QTL was identified for chronotype, while 3 QTLs were identified for activity onset. The highest logarithm of the odds (LOD) score for the chronotype QTL coincides with a chromosome 3 marker that contains a 15-nucleotide indel within the coding region of the canonical clock gene, cryptochrome 2. Sequencing of this locus in 7 different strains showed that the C-terminus of CRY2 in the autogenous forms contain deletions not found in the anautogenous forms. Consequently, we monitored activity in constant darkness and found males from the anautogenous strain exhibited free running periods of ~24 h while those from the autogenous strain were ~22 h. This study provides novel insights into the genetic basis of flight behaviors that likely reflect adaptation to their distinct ecological niches.

DNA Barcoding Analysis of Trinidad Haemagogus Mosquitoes Reveals Evidence for Putative New Species.

Background: Haemagogus janthinomys is a primary sylvan vector of yellow fever virus and the emerging Mayaro virus. However, despite its medical importance, there is a dearth of data on the molecular taxonomy of this mosquito species. Methods: In this study, DNA barcoding analysis was performed on 64 adult female mosquitoes from Trinidad morphologically identified as Hg. janthinomys. The mitochondrial cytochrome c oxidase I (COI) gene and ribosomal DNA internal transcribed spacer 2 (ITS2) region of the mosquitoes were PCR amplified and sequenced, and molecular phylogenies inferred. Results: The BLASTN analysis showed that only 20% (n = 13/66) of COI sequences had high similarity (>99% identity) to Hg. janthinomys and the remaining sequences had low similarity (<90% identity) to reference GenBank sequences. Phylogenetic analysis of COI sequences revealed the presence of four strongly supported groups, with one distinct clade that did not align with any reference sequences. Corresponding ITS2 sequences for samples in this distinct COI group clustered into three clades. Conclusions: These molecular findings suggest the existence of a putative new Haemagogus mosquito species and underscore the need for further, more in-depth investigations into the taxonomy and classification of the Haemagogus genus.

Does on-site adequacy assessment by cytotechnologists improve results of EUS guided FNA of solid pancreaticobiliary lesions?

CONTEXT: Rapid onsite adequacy assessment is stated to improve the diagnostic performance of EUS-FNA. OBJECTIVES: The aim of this study was to establish if the introduction of adequacy assessment performed by a biomedical scientist (cytotechnologist) to an established EUS service improved the diagnostic accuracy of EUS guided FNA of solid pancreaticobiliary lesions. DESIGN AND PATIENTS: This retrospective study includes all patients with solid pancreaticobiliary lesions who underwent EUS-FNA from April 2009 to September 2010. An in room cytotechnologist was present for 2 out of the 4 weekly EUS lists and therefore there were two groups identified: Group 1, cytotechnologist absent; and Group 2, cytotechnologist present. RESULTS: There were 82 patients in Group 1 and 97 patients in Group 2. There was no statistically significant difference in the number of passes (4.1 vs. 4.3), the inadequate aspirate rate (7.3% vs. 5.1%) or the mean size of the lesions (34.7 vs. 32.6 mm) between the groups. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value in Group 1 were 89%, 88%, 100%, 100% and 50% respectively. The results in Group 2 were 91%, 90%, 100%, 100% and 69% respectively. There was no statistically significant difference between the two groups. CONCLUSIONS: In this study the adequacy assessment performed by a cytotechnologist did not improve the diagnostic accuracy of EUS-FNA. In an established EUS-FNA service with low inadequate aspirate rates, onsite adequacy assessment may not improve results of the test.

Mating Competitiveness of Transgenic Aedes aegypti (Diptera: Culicidae) Males Against Wild-Type Males Reared Under Simulated Field Conditions.

Efforts directed at genetic modification of mosquitoes for population control or replacement are highly dependent on the initial mating success of transgenic male mosquitoes following their release into natural populations. Adult mosquito phenotypes are influenced by the environmental conditions experienced as larvae. Semifield studies conducted to date have not taken that under consideration when testing male mating fitness, and have compared mating success of males reared under identical environmental conditions. We performed pairwise mating challenges between males from a genetically modified laboratory strain (BF2) versus males from a recent Trinidad field isolate of Aedes aegypti (L.), a major vector of multiple arboviruses. We utilized larval density and nutrition to simulate environmental stress experienced by the Trinidad males and females. Our results indicated that environmental stress during larval development negatively influenced the competitiveness and reproductive success of males from the Trinidad population when paired with optimum reared BF2 males. Small (0.027 m3) and large (0.216 m3) trials were conducted wherein stressed or optimum Trinidad males competed with optimum BF2 males for mating with stressed Trinidad females. When competing with stress reared Trinidad males, optimum reared BF2 males were predominant in matings with stress reared Trinidad females, and large proportions of these females mated with males of both strains. When competing with optimum reared Trinidad males, no difference in mating success was observed between them and BF2 males, and frequencies of multiple matings were low. Our results indicate that future mating competition studies should incorporate appropriate environmental conditions when designing mating fitness trials of genetically modified males.

Identification of Host Blood Meals of Mosquitoes (Diptera: Culicidae) Collected at the Aripo Savannas Scientific Reserve in Trinidad, West Indies.

Surveillance for blood-fed female mosquitoes was performed between August 2015 and February 2016 at sites along the periphery of the Aripo Savannas Environmentally Reserve (ASSR) located in northeastern Trinidad, West Indies. We collected engorged female mosquitoes representing 13 species. DNA extractions from dissected abdomens were subjected to PCR amplification with three primer pairs targeting the mitochondrial cytochrome oxidase I and cytochrome b gene sequences. High-quality sequence information and host identification were obtained for 42 specimens representing eight mosquito species with at least one primer combination. A broad range of vertebrates including humans were identified, but the majority were nonhuman mammals, both domestic and wild. Domestic dogs were the most common host and may represent potential sentinel species for monitoring local enzootic arbovirus activity in Trinidad. Culex declarator Dyer and Knab and Culex nigripalpus Theobald were the most common blood-fed mosquito species comprising 79.1% of the total number identified. These species obtained blood meals from birds, nonhuman mammals, and human hosts, and therefore pose significant risks as potential bridge vectors for epizootic arbovirus transmission in the ASSR area as well as other sylvan areas in Trinidad. These data represent the first such results for Trinidad.

Emergency stomas; should non-colorectal surgeons be doing it?

AIM: The aim of this study was to compare general and stoma specific short term complications in patients having stoma surgery in either an emergency or elective setting during their index hospital stay. It also compares the complications specific to a stoma carried out by surgeons with or without a specialist interest in colorectal surgery. BACKGROUND: The stoma created in emergency surgery has a high short and long term complication rate. Emergency stomas where the site has not been marked preoperatively by a stoma therapist are more prone to complications. These complications may severely affect a patient's quality of life. METHODS: We retrospectively analysed data for all non-urological stomas created over the last three years in our institute. This covered the period from January 2014 to January 2017. The stoma care department kept a full database record of all patients. Besides demography we analysed the type of stoma i.e. colostomy or ileostomy, indications for the stoma, most common operation, length of stay (LOS) and short term complications based on the Clavien-Dindo classification. We also analysed the perioperative stoma related complications within the emergency cohort. RESULTS: A total of 199 patients had new ostomies created during the three-year period. Four patients died during the inpatient stay and were excluded from the analysis. The total number of stomas created in the emergency cohort was 60 and 135 stomas were elective procedures. The male to female ratio was 1:1.01. The average age for the emergency cohort was 6 years older than for the elective cohort. There was a statistically significant difference in length of stay between the two cohorts (T Test P Value =.02). There was a higher number of elective patients discharged in the first week compared to the emergency surgery patients. The rate of grade 3 or 4 complications was higher in the emergency cohort of patients. The rate of grade 3 or 4 complications was also much higher in patients operated by surgeons who did not have a specialist interest in colorectal surgery. The majority of grade 3 complications seen in the emergency surgery cohort and operated on by non-colorectal specialists (NCS) were stoma related, i.e retraction, necrosis and prolapse. CONCLUSION: Emergency surgery procedures are frequently bowel related. Emergency stoma surgery should not be taken as trivial procedure, non-colorectal surgeons should take advice and assistance from specialist colorectal surgeons for bowel related cases, particularly when a stoma is involved.

Origin of a High-Latitude Population of Aedes aegypti in Washington, DC.

An overwintering population of Aedes aegypti has been documented in the Capitol Hill neighborhood of Washington, DC, since 2011. Mitochondrial cytochrome oxidase I (mtCOI) sequence data presented in a previous study traced the origin to the New World. Here, we use microsatellite and 14,071 single nucleotide polymorphisms along with mitochondrial DNA (mtDNA) sequences on Washington Ae. aegypti samples and samples from potential sources to further narrow the origin of this population. Genetically, Washington Ae. aegypti are closest to populations in Florida, meaning this is the most likely source. Florida experienced the first mosquito-borne transmission of dengue in the United States after decades of absence of this disease, as well as local transmission of chikungunya and Zika in recent years. This suggests that the Capitol Hill, Washington, DC population of Ae. aegypti is capable of transmitting viruses such as dengue, chikungunya, and Zika in modern US city environments.

A transcriptomic survey of the impact of environmental stress on response to dengue virus in the mosquito, Aedes aegypti.

Populations of Aedes aegypti naturally exhibit variable susceptibility to dengue viruses. This natural variation can be impacted by nutritional stress resulting from larval-stage crowding, indicating the influence of environment components on the adult mosquito immune response. In particular, larval crowding was previously shown to reduce the susceptibility of adult females of a Trinidad field isolate of A. aegypti to the dengue serotype 2 (JAM1409) virus. Here, we present the first whole transcriptome study to address the impact of environmental stress on A. aegypti response to dengue virus. We examined expression profiles of adult females resulting from crowded and optimum reared larvae from the same Trinidad isolate at two critical early time points-3 and 18 hours post dengue virus infected blood meal. We exposed specimens to either a dengue or naïve blood meal, and then characterized the response in ten gene co-expression modules based on their transcriptional associations with environmental stress and time. We further analyzed the top 30 hub or master regulatory genes in each of the modules, and validated our results via qRT-PCR. These hub genes reveal which functions are critical to the mechanisms that confer dengue virus refractoriness or susceptibility to stress conditioned A. aegypti, as well as the time points at which they are most important.

Matching services to patients' beliefs about depression in Dublin, Ireland.

OBJECTIVES: This study explored tensions between biomedical and psychosocial illness models and between the public health goal of stigma reduction and patients' perceptions of helplessness. Patients' etiological beliefs and use of language are considered as possible pathways to improved care. METHODS: Qualitative and quantitative data were obtained from 18 adults attending a mood disorders support group in Dublin, Ireland. RESULTS: Respondents reported feelings of helplessness concerning the occurrence of depressive episodes. When describing episodes of wellness and depression, respondents used a "light switch" metaphor to indicate this lack of control. For several respondents, acceptance of biomedical causality was linked to helplessness. In contrast, spiritual beliefs offered hope. CONCLUSIONS: Alleviating patients' sense of responsibility may reduce their guilt, but patients' perceptions of illness uncontrollability may diminish their sense of agency, reinforce depressive attributional styles, and undermine overall treatment outcomes. Communication and the patients' involvement in decisions are vital to treatment.

Larval stress alters dengue virus susceptibility in Aedes aegypti (L.) adult females.

In addition to genetic history, environmental conditions during larval stages are critical to the development, success and phenotypic fate of the Aedes aegypti mosquito. In particular, previous studies have shown a strong genotype-by-environment component to adult mosquito body size in response to optimal vs stressed larval conditions. Here, we expand upon those results by investigating the effects of larval-stage crowding and nutritional limitation on the susceptibility of a recent field isolate of Aedes aegypti to dengue virus serotype-2. Interestingly, female mosquitoes from larvae subjected to a stressed regime exhibited significantly reduced susceptibility to disseminated dengue infection 14days post infection compared to those subjected to optimal regimes. Short term survivorship post-infected blood feeding was not significantly different. As with body size, dengue virus susceptibility of a mosquito population is determined by a combination of genetic and environmental factors and is likely maintained by balancing selection. Here, we provide evidence that under different environmental conditions, the innate immune response of field-reared mosquitoes exhibits a large range of phenotypic variability with regard to dengue virus susceptibility. Further, as with body size, our results suggest that mosquitoes reared under optimal laboratory conditions, as employed in all mosquito-pathogen studies to date, may not always be realistic proxies for natural populations.

Managing clinical education through understanding key principles.

BACKGROUND: Traditionally, a practicum facilitated the integration of on-campus learning and practical workplace training. Over the past 3 decades, an educative practicum has evolved that promotes clinical reasoning, including analytical and evaluative abilities, through reflective practice. Anecdotal evidence indicates that the delivery of clinical education within medical radiation science entry-level programs continues to vacillate between traditional practicums and the new reflective practicums. PURPOSE: To review the literature about clinical education within the medical radiation sciences and identify key principles for practitioners seeking to reflect upon and improve their approach to teaching and supporting students in the clinical environment. METHODS: A search of 3 major journal databases, Internet searches, and hand searches of reference lists were conducted to identify literature about clinical education in the medical radiation sciences from January 1, 2000, to December 31, 2012. Twenty-two studies were included in this review. RESULTS: The 5 key elements associated with clinical education include the clinical support model and quality, overcoming the theory-practice gap, learning outcomes and reliable and valid assessment, preparing and supporting students, and accommodating differing teaching and learning needs. DISCUSSION: Many factors influence the quality of clinical education, including the culture of the clinical environment and clinical leadership roles. Several approaches can help students bridge the theory-practice gap, including simulators, role-playing activities, and reflective journals. In addition, clinical educators should use assessment strategies that objectively measure student progress, and they should be positive role models for their students. CONCLUSION: The successful clinical education of students in the medical radiation sciences depends upon the systems, structures, and people in the clinical environment. Clinical education is accomplished through the collaborative efforts of the clinical practitioner, the academic, and the student. Universities should include introductory material on clinical learning and teaching in their radiologic science curriculum.

A Qualitative Study of Gender-Based Pathways to Problem Drinking in Dublin, Ireland.

OBJECTIVE: High rates of alcohol-related harm have been reported in the European Union, including Ireland, for more than 20 years. This article's goal is to contextualise such rates by examining gender-based pathways to alcohol use disorders from the perspective of those self-identifying as in recovery using data collected midway through this 20-year trend. METHODS: Sixteen informants (nine men and seven women) were interviewed between 1998 and 1999 in Dublin, Ireland. Using qualitative methods, informants were asked to reflect upon their experiences of problem drinking and recovery. RESULTS: Drinking expectancies, pub-based socialising, social anxiety and perceived social expectations to drink were cited as common pathways to problem drinking by informants, highlighting contradictions in drinking practices and the symbolic functions of alcohol. Drinking contexts identified by informants were public pub-based drinking for men and home-based drinking for women. Primary barriers to problem acceptance centered on pub-based socialising norms and gender-based shame. Benefits of support group membership included establishing new social networks and learning alternative ways to cope with negative emotions. CONCLUSION: Consideration of drinking expectancies, the social contexts in which problematic drinking occurs, gender ideologies, the cultural meanings of drinking behaviours, and attention to feelings of isolation or loneliness experienced by those exhibiting problematic consumption behaviours might further understandings of potentially harmful drinking, especially in periods of economic uncertainty.

Radiation Oncology Safety Information System (ROSIS)--profiles of participants and the first 1074 incident reports.

BACKGROUND AND PURPOSE: The Radiation Oncology Safety Information System (ROSIS) was established in 2001. The aim of ROSIS is to collate and share information on incidents and near-incidents in radiotherapy, and to learn from these incidents in the context of departmental infrastructure and procedures. MATERIALS AND METHODS: A voluntary web-based cross-organisational and international reporting and learning system was developed (cf. the www.rosis.info website). Data is collected via online Department Description and Incident Report Forms. A total of 101 departments, and 1074 incident reports are reviewed. RESULTS: The ROSIS departments represent about 150,000 patients, 343 megavoltage (MV) units, and 114 brachytherapy units. On average, there are 437 patients per MV unit, 281 per radiation oncologist, 387 per physicist and 353 per radiation therapy technologist (RT/RTT). Only 14 departments have a completely networked system of electronic data transfer, while 10 departments have no electronic data transfer. On average seven quality assurance (QA) or quality control (QC) methods are used at each department. A total of 1074 ROSIS reports are analysed; 97.7% relate to external beam radiation treatment and 50% resulted in incorrect irradiation. Many incidents arise during pre-treatment but are not detected until later in the treatment process. Where an incident is not detected prior to treatment, an average of 22% of the prescribed treatment fractions were delivered incorrectly. The most commonly reported detection methods were "found at time of patient treatment" and during "chart-check". CONCLUSION: While the majority of the incidents that reported to this international cross-organisational reporting system are of minor dosimetric consequence, they affect on average more than 20% of the patient's treatment fractions. Nonetheless, defence-in-depth is apparent in departments registered with ROSIS. This indicates a need for further evaluation of the effectiveness of quality controls.

Update on research and treatment of premenstrual dysphoric disorder.

Many women in their reproductive years experience some mood, behavioral. or physical symptoms in the week prior to menses. Variability exists in the level of symptom burden in that some women experience mild symptoms, whereas a small minority experience severe and debilitating symptoms. For an estimated 5%-8% of premenopausal women, work or social functioning are affected by severe premenstrual syndrome. Many women in this group meet diagnostic criteria for premenstrual dysphoric disorder (PMDD). Among women who suffer from PMDD, mood and behavioral symptoms such as irritability, depressed mood, tension, and labile mood dominate. Somatic complaints, including breast tenderness and bloating, also can prove disruptive to women's overall functioning and quality of life. Recent evidence suggests that individual sensitivity to cyclical variations in levels of gonadal hormones may predispose certain women to experience these mood, behavioral, and somatic symptoms. Treatments include: antidepressants of the serotonin reuptake inhibitor class, taken intermittently or throughout the menstrual cycle; medications that suppress ovarian cyclicity; and newer oral contraceptives with novel progestins.