Snow crab (Chionoecetes opilio) hemocytes and hepatopancreas transcriptomes: identification, validation, and application of immune-relevant biomarkers of exposure to noise

The snow crab (Chionoecetes opilio) fishery off the east coast of Newfoundland and Labrador, Canada, has been impacted by annual seismic oil and gas surveying in recent decades, and commercial crab harvesters are concerned that it could potentially affect this resource. A laboratory study was performed to investigate the effects of chronic noise exposure on the transcriptomes of snow crab hemocytes and hepatopancreas, which are important in immunity, metabolism and response to environmental stress. Snow crab were held in replicate control or experimental tanks; on alternating days, the experimental tanks were exposed to noise from an underwater speaker which played a recording of a seismic airgun firing every 10 sec in a continuous loop for ~ 22 weeks (chronic noise). RNA sequencing was used to identify candidate noise-responsive molecular biomarkers in both hemocytes and hepatopancreas. The quantified transcripts of individuals (i.e. n=10 from each of the four groups) were compared using DESeq2, identifying over 300 noise-responsive transcripts in each cell/tissue type. Real-time quantitative polymerase chain reaction (qPCR) assays were designed and run for 61 of these transcripts with significant BLASTx hits. One transcript (rgs2) was significantly (p < 0.05) higher expressed in both hemocytes and hepatopancreas in response to noise; five and seven other transcripts were either significant or showed a non-significant trend of differential expression (0.05 < p ≤ 0.1) in hemocytes (e.g. cfb upregulated, sacs and myof downregulated) and hepatopancreas (e.g. gpx3 and atf3 upregulated, sult1c4 downregulated), respectively. To further investigate the performance and utility of these candidate biomarkers in the field, expression levels of 25 selected transcripts were then examined in the hepatopancreas of snow crab that had been subjected to 2D and 3D seismic surveying using both qPCR and multivariate statistical analyses. Overall, few of these biomarkers showed consistent results in field-collected snow crab, highlighting the need to combine lab and field-based studies to fully evaluate the utility of biomarkers. Nonetheless, our study still identified noise-responsive biomarkers in both settings (including stress and immune relevant genes), providing valuable information for understanding the impact of ocean noise on snow crab physiology and health

Depressed mood in pregnancy: Prevalence and correlates in two Cape Town peri-urban settlements

<p>Abstract</p> <p>Background</p> <p>The disability associated with depression and its impact on maternal and child health has important implications for public health policy. While the prevalence of postnatal depression is high, there are no prevalence data on antenatal depression in South Africa. The purpose of this study was to determine the prevalence and correlates of depressed mood in pregnancy in Cape Town peri-urban settlements.</p> <p>Methods</p> <p>This study reports on baseline data collected from the Philani Mentor Mothers Project (PMMP), a community-based, cluster-randomized controlled trial on the outskirts of Cape Town, South Africa. The PMMP aims to evaluate the effectiveness of a home-based intervention for preventing and managing illnesses related to HIV, TB, alcohol use and malnutrition in pregnant mothers and their infants. Participants were 1062 pregnant women from Khayelitsha and Mfuleni, Cape Town. Measures included the Edinburgh Postnatal Depression Scale (EPDS), the Derived AUDIT-C, indices for social support with regards to partner and parents, and questions concerning socio-demographics, intimate partner violence, and the current pregnancy. Data were analysed using bivariate analyses followed by logistic regression.</p> <p>Results</p> <p>Depressed mood in pregnancy was reported by 39% of mothers. The strongest predictors of depressed mood were lack of partner support, intimate partner violence, having a household income below R2000 per month, and younger age.</p> <p>Conclusions</p> <p>The high prevalence of depressed mood in pregnancy necessitates early screening and intervention in primary health care and antenatal settings for depression. The effectiveness and scalability of community-based interventions for maternal depression must be developed for pregnant women in peri-urban settlements.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00972699">NCT00972699</a>.</p

Do International Health Partnerships contribute to reverse innovation? a mixed methods study of THET-supported partnerships in the UK

Background International health partnerships (IHPs) are changing, with an increased emphasis on mutual accountability and joint agenda setting for both the high- and the low- or middle-income country (LMIC) partners. There is now an important focus on the bi-directionality of learning however for the UK partners, this typically focuses on learning at the individual level, through personal and professional development. We sought to evaluate whether this learning also takes the shape of ‘Reverse Innovation’ –when an idea conceived in a low-income country is subsequently adopted in a higher-income country. Methods This mixed methods study used an initial scoping survey of all the UK-leads of the Tropical Health Education Trust (THET)-supported International Health Partnerships (n = 114) to ascertain the extent to which the IHPs are or have been vehicles for Reverse Innovation. The survey formed the sampling frame for further deep-dive interviews to focus on volunteers’ experiences and attitudes to learning from LMICs. Interviews of IHP leads (n = 12) were audio-recorded and transcribed verbatim. Survey data was analysed descriptively. Interview transcripts were coded thematically, using an inductive approach. Results Survey response rate was 27% (n = 34). The majority (70%) strongly agreed that supporting LMIC partners best described the mission of the partnership but only 13% of respondents strongly agreed that learning about new innovations and models was a primary mission of their partnership. Although more than half of respondents reported having observed innovative practice in the LMIC, only one IHP respondent indicated that this has led to Reverse Innovation. Interviews with a sample of survey respondents revealed themes primarily around how learning is conceptualised, but also a central power imbalance between the UK and LMIC partners. Paternalistic notions of knowledge could be traced to partnership power dynamics and latent attitudes to LMICs. Conclusions Given the global flow of innovation, if High-income countries (HICs) are to benefit from LMIC practices, it is paramount to keep an open mind about where such learning can come from. Making the potential for learning more explicit and facilitating innovation dissemination upon return will ultimately underpin the success of adoption

A Redescription of the Bulla, Antennae, and Mouth Parts of Female Clavella sp. (Copepoda: Siphonostomatoida: Lernaeopodidae) Infesting Wild Gadus morhua Using Scanning Electron Microscopy (SEM)

Many members of the Copepod family Lernaeopodidae are well-known parasites of gadids. This study reports on the occurrence of a lernaeopodid infestation of wild-sourced Gadus morhua sampled from separate inshore (Gilbert Bay, NL) and offshore (Virgin Rocks, NL) populations from Newfoundland, Canada. The majority of the parasites were observed to be associated with the buccal cavity, gill filaments, gill arch, and occasionally near the outer edge of the operculum. Anatomical analysis and detailed redescriptions of the parasite’s functional anatomy (mouth parts, antennae, and bulla complex) using high-resolution SEM indicated that the parasite was most likely of the genus Clavella. New morphological details of the second antennae ornamentation, first maxillae, bulla complex, and the oral cone are provided and discussed with regard to their potential in taxonomic applications

Notch1 Is Required for Kras-Induced Lung Adenocarcinoma and Controls Tumor Cell Survival via p53

The Notch pathway has been implicated in a number of malignancies with different roles that are cell- and tissue-type dependent. Notch1 is a putative oncogene in non-small cell lung cancer (NSCLC) and activation of the pathway represents a negative prognostic factor. To establish the role of Notch1 in lung adenocarcinoma, we directly assessed its requirement in Kras-induced tumorigenesis in vivo using an autochthonous model of lung adenocarcinoma with concomitant expression of oncogenic Kras and deletion of Notch1. We found that Notch1 function is required for tumor initiation via suppression of p53-mediated apoptosis through the regulation of p53 stability. These findings implicate Notch1 as a critical effector in Kras-driven lung adenocarcinoma and as a regulator of p53 at a posttranslational level. Moreover, our study provides new insights to explain, at a molecular level, the correlation between Notch1 activity and poor prognosis in patients with NSCLC carrying wild-type p53. This information is critical for design and implementation of new therapeutic strategies in this cohort of patients representing 50% of NSCLC cases. (C) 2013 AACR

Notch1 Functions as a Tumor Suppressor in a Model of K-ras-Induced Pancreatic Ductal Adenocarcinoma

K-ras is the most commonly mutated oncogene in pancreatic cancer and its activation in murine models is sufficient to recapitulate the spectrum of lesions seen in human pancreatic ductal adenocarcinoma (PDAC). Recent studies suggest that Notch receptor signaling becomes reactivated in a subset of PDACs, leading to the hypothesis that Notch1 functions as an oncogene in this setting. To determine whether Notch1 is required for K-ras-induced tumorigenesis, we used a mouse model in which an oncogenic allele of K-ras is activated and Notch1 is deleted simultaneously in the pancreas. Unexpectedly, the loss of Notch1 in this model resulted in increased tumor incidence and progression, implying that Notch1 can function as a tumor suppressor gene in PDAC. Cancer Res; 70(11); 4280-6. (C) 2010 AACR

Pharmacotherapy in Older Adults with Cardiovascular Disease: Report from an American College of Cardiology, American Geriatrics Society, and National Institute on Aging Workshop.

ObjectivesTo identify the top priority areas for research to optimize pharmacotherapy in older adults with cardiovascular disease (CVD).DesignConsensus meeting.SettingMultidisciplinary workshop supported by the National Institute on Aging, the American College of Cardiology, and the American Geriatrics Society, February 6-7, 2017.ParticipantsLeaders in the Cardiology and Geriatrics communities, (officers in professional societies, journal editors, clinical trialists, Division chiefs), representatives from the NIA; National Heart, Lung, and Blood Institute; Food and Drug Administration; Centers for Medicare and Medicaid Services, Alliance for Academic Internal Medicine, Patient-Centered Outcomes Research Institute, Agency for Healthcare Research and Quality, pharmaceutical industry, and trainees and early career faculty with interests in geriatric cardiology.MeasurementsSummary of workshop proceedings and recommendations.ResultsTo better align older adults' healthcare preferences with their care, research is needed to improve skills in patient engagement and communication. Similarly, to coordinate and meet the needs of older adults with multiple comorbidities encountering multiple healthcare providers and systems, systems and disciplines must be integrated. The lack of data from efficacy trials of CVD medications relevant to the majority of older adults creates uncertainty in determining the risks and benefits of many CVD therapies; thus, developing evidence-based guidelines for older adults with CVD is a top research priority. Polypharmacy and medication nonadherence lead to poor outcomes in older people, making research on appropriate prescribing and deprescribing to reduce polypharmacy and methods to improve adherence to beneficial therapies a priority.ConclusionThe needs and circumstances of older adults with CVD differ from those that the current medical system has been designed to meet. Optimizing pharmacotherapy in older adults will require new data from traditional and pragmatic research to determine optimal CVD therapy, reduce polypharmacy, increase adherence, and meet person-centered goals. Better integration of the multiple systems and disciplines involved in the care of older adults will be essential to implement and disseminate best practices. J Am Geriatr Soc 67:371-380, 2019