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A suite of plasma diagnostics will be installed on the SPARC tokamak to allow for real-time plasma control, an investigation of high-field tokamak physics, and to de-risk the design of ARC, a compact fusion power plant with the aim to supply electricity to the grid. Among these diagnostics is the neutral gas diagnostics system (NTGS), a set of pressure sensors and gas analyzers used to monitor neutral pressure and gas composition for plasma control, optimization of wall conditioning, and helium ash removal, among other measurement functions linked to operational and scientific research needs. While reliable measurements of neutral pressure and gas composition have been fielded on existing magnetic-confinement fusion devices, SPARC represents a step increase in challenge due to its larger power density, higher field, high vacuum vessel bake temperatures, and higher neutron flux environment, as well as a step decrease in the accessibility for maintenance of in-vessel sensors. Multiple sensor types will be employed to have defense-in-depth and mitigate common failure modes. The NTGS system is currently progressing through final design, working to close out decisions using prototyping and analysis, and then moving on to procuring sensors for assembly and installation on SPARC. This paper outlines the current status of the system design and the diagnostic requirements that motivate neutral gas measurements on SPARC, as well as highlights the planned prototyping activities. [ABSTRACT FROM AUTHOR]

The SPARC tokamak will have scrape-off layer parallel heat fluxes on the order of GW/m2. Managing power exhaust of this magnitude will be mandatory for a reactor-scale device. To enable this mission, a thermal diagnostic suite will be deployed to measure the in-vessel structural temperatures to ensure they do not exceed their design limits and to determine the spatial distribution and magnitude of energy deposited onto the first wall. Thermocouples and fiber Bragg gratings have been selected for their environmental compatibility and proven useful on other fusion devices. High-density thermocouple arrays in the divertor will have two spring-loaded thermocouples per divertor target tile, which are being used as calorimeters, and will look to resolve the temperature distribution within the tile due to a swept or static strike point. All systems will need to survive the vacuum vessel bake, set at a minimum plasma facing surface temperature of 350 °C, which presents a particularly challenging environment for the fiber-based subsystem. Along with this temperature design requirement, all the materials in the primary vacuum need to be ultra-high vacuum compatible, able to handle the expected neutron and gamma radiation, as well as tritium exposure, all of which restrict material options. Finally, due to the expected activated environment in SPARC, there will be little chance to replace defective sensors, so system resilience is ensured through toroidal redundancy, probe material selection, and mitigating the impact of common-mode failures. Initial testing of sensors show that intershot structural measurements are sufficiently captured with the raw output, but intrashot measurements of the plasma facing material requires model-based interpretive tools. [ABSTRACT FROM AUTHOR]

To control and optimize the power of the SPARC tokamak, we require information on the total radiated power of the plasma and its 2D and 3D spatial distribution. The SPARC bolometry diagnostic is being designed and built to measure the radiated power for controlling power balance, investigating the dissipation capabilities of various divertor concepts, and measuring the efficacy of the disruption thermal load mitigation. Proven resistive bolometer sensor technology will be used, with 248 lines of sight integrated into pinhole cameras in 20 different locations. This diversity of views will allow the bolometers to view the core, divertor, and particularly X-points of the plasma with high resolution. 14 of these camera locations are dedicated to 2D equilibrium radiated power, while the remaining six locations are designed to measure 3D radiated energy during disruptions. The bolometer sensor holders, pinhole camera boxes, and cabling have been designed to survive the high neutron flux (but low fluence) and up to 400 °C temperatures seen during operation and vacuum bake. The resistive bolometer sensors use Au absorbers with an Al heat conduction layer and C anti-reflective layer. These sensor chips are wire-bonded to an AlN circuit board, both of which are held inside a custom AlN and stainless steel bolometer holder. Design and optimization of the pinhole camera lines of sight are performed using Cherab. This work details the current state of the design of the SPARC bolometry diagnostic and its interfaces, as well as ongoing work to validate the design. [ABSTRACT FROM AUTHOR]

An overview of physical oceanographic conditions in the Gulf of St. Lawrence (GSL) in 2021 is presented as part of the Atlantic Zone Monitoring Program (AZMP). AZMP data as well as data from regional monitoring programs are analyzed and presented in relation to long-term means. The annual average freshwater runoffs of the St. Lawrence River measured at Québec City and its combination with rivers flowing into the Estuary (RIVSUM II) were well below normal. The sea ice seasonal maximum volume was just shy of the series low record of 2010 and the January-April average was at a series record low. The winter mixed layer volume was second lowest of the 1996-2021 time series for waters colder than -1 °C and lowest for waters colder than 0 °C. The August cold intermediate layer (CIL) average minimum temperature was the highest of the 1985-2021 time series and the seasonally averaged minimum temperature index was the highest since 1980. On the Magdalen Shallows, the bottom area covered by waters cooler than 1 °C in August-September was at a record low. Sea surface temperatures (SST) averaged monthly over the Gulf were the highest of the satellite record (since 1981) in October and November. The May-November average SST for the Gulf was 3rd highest of the time series after 2006 and 2012. Deep water temperatures have been increasing overall in the Gulf since 2009, with inward advection from Cabot Strait. Gulf-wide average temperature has hit new series record highs (since 1915) of 4.1 °C at 150 m, 6.0 °C at 200 m, 6.7 °C at 250 m and 6.9 °C at 300 m. Bottom area covered by waters warmer than 6 °C was at a record high in all regions along the deep channels, with a notable increase in the Estuary. In the northeast Gulf, there was about the same bottom area between 6 °C and 7 °C as there was > 7 °C. [ABSTRACT FROM AUTHOR]

An overview of physical oceanographic conditions in the Gulf of St. Lawrence (GSL) in 2020 is presented as part of the Atlantic Zone Monitoring Program (AZMP). AZMP data as well as data from regional monitoring programs are analysed and presented in relation to long-term means, shifted from 1981-2010 to 1991-2020 in this edition of the report. The annual average freshwater runoffs of the St. Lawrence River measured at Québec City and its combination with rivers flowing into the Estuary (RIVSUM II) were above normal. Sea-ice maximum volume was below normal, but the winter mixed layer volume was near normal. The August cold intermediate layer (CIL) was warmer than normal but the seasonally averaged minimum temperature index was near normal. Surface water temperatures in the Estuary reached an unusual series record high in July; upwelling and mixing that occurs at the head of the Laurentian Channel usually keeps Estuary surface water cool, but North-easterly winds appear to have created a circulation that capped the mixing region with warmer waters. The overall seasonal average May-November SST for the Gulf was near normal in spite of an above normal seasonal August maximum (+0.7°C, +0.9 SD). Surface water temperatures were then at a record low in September in the Estuary and Northwest Gulf, caused by strong vertical wind mixing. This mixing warmed the bottom waters of the Magdalen Shallows such that the area covered by water with temperatures <1°C in September decreased to a near record low. Deep water temperatures have been increasing overall in the Gulf since 2009, with inward advection from Cabot Strait. Gulf-wide average temperature at 150 m was lower than the 2015 record highs but above normal at 3.7°C (+1.6 SD). New series record highs (since 1915) were set at 200, 250 and 300 m, at 5.7°C (+1.2°C, +1.9 SD), 6.6°C (+1.1°C, +2.5 SD) and 6.8°C (+1.1°C, +2.7 SD) respectively. Bottom area covered by waters warmer than 6°C was at a record high in the Northwest Gulf, the Northeast Gulf, and in Centre and Cabot Strait, and some 7-8°C habitat appeared for the first time in the Northeast Gulf. [ABSTRACT FROM AUTHOR]

Copyright of West Indian Medical Journal is the property of West Indian Medical Journal (WIMJ) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Describe the habits prevalent in Québec's chiropractic practice regarding the prescription of exercise. Methodology: Postal survey of chiropractors belonging to the Québec Order of Chiropractors completed on a voluntary, anonymous basis. Results: 403 Québec chiropractors (37.6%) returned the completed questionnaire. Stretching and strengthening exercises are prescribed more often than are posture or proprioception exercises. Moreover, they are used more frequently for clinical conditions in chronic phase than acute phase. Chiropractors resort more often to prescription of exercises for the cervical and lumbar anatomical regions than for the thoracic region and the extremities. The exercises are more often used for adults and the elderly than for children and adolescents. Conclusion: Prescription of exercises is perceived as an important element in chiropractic treatment and is used by a majority of those responding to the survey. Neither gender nor number of years of experience are factors that appear to influence Québec chiropractors' exercise prescription habits. The majority of chiropractors believe that a computer-based tool could facilitate the prescription of exercises in their clinic. [ABSTRACT FROM AUTHOR]

In 26 villages (1987 population 12,302), hyperendemic for savanna onchocerciasis in North Cameroon, ivermectin was distributed annually between 1987/89 and 1995. Each year until 1992, ophthalmologic examinations were performed before treatment. A final examination was made in 1995. The effects of ivermectin on ocular onchocerciasis were assessed by following (a) the ophthalmologic indices in three cohorts of males recruited before treatment in 1987, 1988 and 1989, who were treated and examined annually, and (b) the indices recorded yearly in the cross-section of males aged 15-19 years. The indices in 1995 from patients who had received up to eight doses were compared with those calculated before treatment in individuals of similar age. In the cohorts, the prevalences of microfilariae in the anterior chamber (MFAC) and of punctate keratitis (PK) recorded in 1995 were markedly reduced; there was a non-significant decrease in sclerosing keratitis (SK), and a significant worsening in the fundus indices in the cohorts. The cross-sectional analysis showed significant decreases in the prevalences of MFAC, PK and SK, and a significant increase in the mean visual acuity; there was no significant change in any fundus index. The findings suggest that repeated ivermectin treatment does not prevent the appearance of initial retinal lesions or the worsening of existing retinal lesions. [ABSTRACT FROM AUTHOR]

The SPARC tokamak is a high-field, Bt0 ∼12 T, medium-sized, R0 = 1.85 m, tokamak that is presently under construction in Devens, MA, led by Commonwealth Fusion Systems. It will be used to de-risk the high-field tokamak path to a fusion power plant and demonstrate the commercial viability of fusion energy. SPARC's first campaign plan is to achieve Qfus > 1 using an ICRF-heated, <10 MW, high current, Ip ∼ 8.5 MA, L-mode fueled by D-T gas injection, and its second campaign will investigate H-mode operations in D-D. To facilitate plasma control and scientific learning, a targeted set of ∼50 plasma diagnostics are being designed and built for operation during these campaigns. While nearly all diagnostics are based on established techniques, the pace of deployment, relative to the first plasma, and the harshness of the thermal, electromagnetic, and radiation environment are unprecedented for medium-sized tokamaks. An overview of the SPARC diagnostic set is given, providing context to further details communicated by the SPARC team in companion publications that are system-specific. The system engineering philosophy for SPARC diagnostics is outlined, and the design and engineering verification process for components inside and outside the primary vacuum boundary are described. Diagnostics are mounted directly to the vacuum vessel as well as housed within a series of eight midplane and 24 off-midplane replaceable port plugs. With limited exceptions, signal conditioning, digitization electronics and cameras as well as lasers and microwave sources are localized to a series of five Diagnostic Lab spaces, totaling ∼350 m2, located >15 m from the center of the tokamak, on the other side of a 2.4 m concrete shielding wall. A series of 31 large-scale penetrations have been included in the SPARC Tokamak Hall to facilitate integration of early campaign diagnostics and to provide upgradability., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/).)

In wounded Arabidopsis thaliana leaves, four 13 S -lipoxygenases (AtLOX2, AtLOX3, AtLOX4, AtLOX6) act in a hierarchical manner to contribute to the jasmonate burst. This leads to defense responses with LOX2 playing an important role in plant resistance against caterpillar herb-ivory. In this study, we sought to characterize the impact of AtLOX2 on wound-induced phytohormonal and transcriptional responses to foliar mechanical damage using wildtype (WT) and lox2 mutant plants. Compared with WT, the lox2 mutant had higher constitutive levels of the phytohormone salicylic acid (SA) and enhanced expression of SA-responsive genes. This suggests that AtLOX2 may be involved in the biosynthesis of jasmonates that are involved in the antagonism of SA biosynthesis. As expected, the jasmonate burst in response to wounding was dampened in lox2 plants. Generally, 1 h after wounding, genes linked to jasmonate biosynthesis, jasmonate signaling attenuation and abscisic acid-responsive genes, which are primarily involved in wound sealing and healing, were differentially regulated between WT and lox2 mutants. Twelve h after wounding, WT plants showed stronger expression of genes associated with plant protection against insect herbivory. This study highlights the dynamic nature of jasmonate-responsive gene expression and the contribution of AtLOX2 to this pathway and plant resistance against insects.

Many plant species, particularly legumes, protect themselves with saponins. Previously, a correlation was observed between levels of oleanolic acid-derived saponins, such as hederagenin-derived compounds, in the legume Medicago truncatula and caterpillar deterrence. Using concentrations that reflect the foliar levels of hederagenin-type saponins, the sapogenin hederagenin was not toxic to 4th instar caterpillars of the cabbage looper Trichoplusia ni nor did it act as a feeding deterrent. Female caterpillars consumed more diet than males, presumably to obtain the additional nutrients required for oogenesis, and are, thus, exposed to higher hederagenin levels. When fed the hederagenin diet, male caterpillars expressed genes encoding trypsin-like proteins (LOC113500509, LOC113501951, LOC113501953, LOC113501966, LOC113501965, LOC113499659, LOC113501950, LOC113501948, LOC113501957, LOC113501962, LOC113497819, LOC113501946, LOC113503910) as well as stress-responsive (LOC113503484, LOC113505107) proteins and cytochrome P 450 6B2-like (LOC113493761) at higher levels than females. In comparison, female caterpillars expressed higher levels of cytochrome P 450 6B7-like (LOC113492289). Bioinformatic tools predict that cytochrome P 450 s could catalyze the oxygenation of hederagenin which would increase the hydrophilicity of the compound. Expression of a Major Facilitator Subfamily (MFS) transporter (LOC113492899) showed a hederagenin dose-dependent increase in gene expression suggesting that this transporter may be involved in sapogenin efflux. These sex-related differences in feeding and detoxification should be taken into consideration in insecticide evaluations to minimize pesticide resistance., (© 2024. The Author(s).)

Background: The organochlorine dichlorodiphenyltrichloroethane (DDT) is banned worldwide owing to its negative health effects. It is exceptionally used as an insecticide for malaria control. Exposure occurs in regions where DDT is applied, as well as in the Arctic, where its endocrine disrupting metabolite, p , p ' - dichlorodiphenyldichloroethylene ( p , p ' - DDE) accumulates in marine mammals and fish. DDT and p , p ' - DDE exposures are linked to birth defects, infertility, cancer, and neurodevelopmental delays. Of particular concern is the potential of DDT use to impact the health of generations to come via the heritable sperm epigenome., Objectives: The objective of this study was to assess the sperm epigenome in relation to p , p ' - DDE serum levels between geographically diverse populations., Methods: In the Limpopo Province of South Africa, we recruited 247 VhaVenda South African men and selected 50 paired blood serum and semen samples, and 47 Greenlandic Inuit blood and semen paired samples were selected from a total of 193 samples from the biobank of the INUENDO cohort, an EU Fifth Framework Programme Research and Development project. Sample selection was based on obtaining a range of p , p ' -DDE serum levels ( mean = 870.734 ± 134.030  ng / mL ). We assessed the sperm epigenome in relation to serum p , p ' -DDE levels using MethylC-Capture-sequencing (MCC-seq) and chromatin immunoprecipitation followed by sequencing (ChIP-seq). We identified genomic regions with altered DNA methylation (DNAme) and differential enrichment of histone H3 lysine 4 trimethylation (H3K4me3) in sperm., Results: Differences in DNAme and H3K4me3 enrichment were identified at transposable elements and regulatory regions involved in fertility, disease, development, and neurofunction. A subset of regions with sperm DNAme and H3K4me3 that differed between exposure groups was predicted to persist in the preimplantation embryo and to be associated with embryonic gene expression., Discussion: These findings suggest that DDT and p , p ' - DDE exposure impacts the sperm epigenome in a dose-response-like manner and may negatively impact the health of future generations through epigenetic mechanisms. Confounding factors, such as other environmental exposures, genetic diversity, and selection bias, cannot be ruled out. https://doi.org/10.1289/EHP12013.

Coronavirus disease (COVID-19) has had a significant impact on global health since the start of the pandemic in 2019. As of June 2022, over 539 million cases have been confirmed worldwide with over 6.3 million deaths as a result. Artificial Intelligence (AI) solutions such as machine learning and deep learning have played a major part in this pandemic for the diagnosis and treatment of COVID-19. In this research, we review these modern tools deployed to solve a variety of complex problems. We explore research that focused on analyzing medical images using AI models for identification, classification, and tissue segmentation of the disease. We also explore prognostic models that were developed to predict health outcomes and optimize the allocation of scarce medical resources. Longitudinal studies were conducted to better understand COVID-19 and its effects on patients over a period of time. This comprehensive review of the different AI methods and modeling efforts will shed light on the role that AI has played and what path it intends to take in the fight against COVID-19.

Objective: Parental environmental exposures can strongly influence descendant risks for adult disease. How paternal obesity changes the sperm chromatin leading to the acquisition of metabolic disease in offspring remains controversial and ill-defined. The objective of this study was to assess (1) whether obesity induced by a high-fat diet alters sperm histone methylation; (2) whether paternal obesity can induce metabolic disturbances across generations; (3) whether there could be cumulative damage to the sperm epigenome leading to enhanced metabolic dysfunction in descendants; and (4) whether obesity-sensitive regions associate with embryonic epigenetic and transcriptomic profiles. Using a genetic mouse model of epigenetic inheritance, we investigated the role of histone H3 lysine 4 methylation (H3K4me3) in the paternal transmission of metabolic dysfunction. This transgenic mouse overexpresses the histone demethylase enzyme KDM1A in the developing germline and has an altered sperm epigenome at the level of histone H3K4 methylation. We hypothesized that challenging transgenic sires with a high-fat diet would further erode the sperm epigenome and lead to enhanced metabolic disturbances in the next generations., Methods: To assess whether paternal obesity can have inter- or transgenerational impacts, and if so to identify potential mechanisms of this non-genetic inheritance, we used wild-type C57BL/6NCrl and transgenic males with a pre-existing altered sperm epigenome. To induce obesity, sires were fed either a control or high-fat diet (10% or 60% kcal fat, respectively) for 10-12 weeks, then bred to wild-type C57BL/6NCrl females fed a regular diet. F 1 and F 2 descendants were characterized for metabolic phenotypes by examining the effects of paternal obesity by sex, on body weight, fat mass distribution, the liver transcriptome, intraperitoneal glucose, and insulin tolerance tests. To determine whether obesity altered the F 0 sperm chromatin, native chromatin immunoprecipitation-sequencing targeting H3K4me3 was performed. To gain insight into mechanisms of paternal transmission, we compared our sperm H3K4me3 profiles with embryonic and placental chromatin states, histone modification, and gene expression profiles., Results: Obesity-induced alterations in H3K4me3 occurred in genes implicated in metabolic, inflammatory, and developmental processes. These processes were associated with offspring metabolic dysfunction and corresponded to genes enriched for H3K4me3 in embryos and overlapped embryonic and placenta gene expression profiles. Transgenerational susceptibility to metabolic disease was only observed when obese F 0 had a pre-existing modified sperm epigenome. This coincided with increased H3K4me3 alterations in sperm and more severe phenotypes affecting their offspring., Conclusions: Our data suggest sperm H3K4me3 might serve as a metabolic sensor that connects paternal diet with offspring phenotypes via the placenta. This non-DNA-based knowledge of inheritance has the potential to improve our understanding of how environment shapes heritability and may lead to novel routes for the prevention of disease. This study highlights the need to further study the connection between the sperm epigenome, placental development, and children's health., Summary Sentence: Paternal obesity impacts sperm H3K4me3 and is associated with placenta, embryonic and metabolic outcomes in descendants., (Copyright © 2022. Published by Elsevier GmbH.)

In the field of epigenetic inheritance, delineating molecular mechanisms implicated in the transfer of paternal environmental conditions to descendants has been elusive. This protocol details how to track sperm chromatin intergenerationally. We describe mouse model design to probe chromatin states in single mouse sperm and techniques to assess pre-implantation embryo chromatin and gene expression. We place emphasis on how to obtain high-quality and quantifiable data sets in sperm and embryos, as well as highlight the limitations of working with low input. For complete details on the use and execution of this protocol, please refer to Lismer et al. (2021)., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

A father's lifestyle impacts offspring health; yet, the underlying molecular mechanisms remain elusive. We hypothesized that a diet that changes methyl donor availability will alter the sperm and embryo epigenomes to impact embryonic gene expression and development. Here, we demonstrate that a folate-deficient (FD) diet alters histone H3 lysine 4 trimethylation (H3K4me3) in sperm at developmental genes and putative enhancers. A subset of H3K4me3 alterations in sperm are retained in the pre-implantation embryo and associated with deregulated embryonic gene expression. Using a genetic mouse model in which sires have pre-existing altered H3K4me2/3 in sperm, we show that a FD diet exacerbates alterations in sperm H3K4me3 and embryonic gene expression, leading to an increase in developmental defect severity. These findings imply that paternal H3K4me3 is transmitted to the embryo and influences gene expression and development. It further suggests that epigenetic errors can accumulate in sperm to worsen offspring developmental outcomes., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Advancing the molecular knowledge surrounding fertility and inheritance has become critical given the halving of sperm counts in the last 40 years, and the rise in complex disease which cannot be explained by genetics alone. The connection between both these trends may lie in alterations to the sperm epigenome and occur through environmental exposures. Changes to the sperm epigenome are also associated with health risks across generations such as metabolic disorders and cancer. Thus, it is imperative to identify the epigenetic modifications that escape reprogramming during spermatogenesis and embryogenesis. Here, we aimed to identify the chromatin signature(s) involved in transgenerational phenotypes in our genetic mouse model of epigenetic inheritance that overexpresses the histone demethylase KDM1A in their germ cells. We used sperm-specific chromatin immunoprecipitation followed by in depth sequencing (ChIP-seq), and computational analysis to identify whether differential enrichment of histone H3 lysine 4 trimethylation (H3K4me3), and histone H3 lysine 27 trimethylation (H3K27me3) serve as mechanisms for transgenerational epigenetic inheritance through the paternal germline. Our analysis on the sperm of KDM1A transgenic males revealed specific changes in H3K4me3 enrichment that predominantly occurred independently from bivalent H3K4me3/H3K27me3 regions. Many regions with altered H3K4me3 enrichment in sperm were identified on the paternal allele of the pre-implantation embryo. These findings suggest that sperm H3K4me3 functions in the transmission of non-genetic phenotypes transgenerationally., (© ? The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Hibernators suppress physiological processes when expressing torpor, yet little is known about the effects of torpor on male reproductive physiology. Studies of hibernating mammals suggest that deep torpor negatively impacts spermatogenesis and that transitions between torpor and euthermic arousals increase cellular oxidative stress, with potentially damaging effects on sperm. Here, we hypothesize that variation in torpor expression affects the reproductive readiness of hibernators by impacting their sperm production. To test this, we examined the relationship between torpor expression and spermatogenesis in captive eastern chipmunks ( Tamias striatus ). We determined torpor depth with temperature data loggers and assessed its relationship with spermatogenesis by examining spermatogenic progression, cell division, sperm counts, sperm maturity, and DNA damage. We show that deep hibernators (high levels of torpor) largely halted spermatogenesis in late hibernation in comparison with shallow hibernators (low levels of torpor), where ongoing spermatogenesis was observed. Despite these differences in spermatogenic state during hibernation, spermatogenic progression, sperm numbers, and maturity did not differ in spring, potentially reflecting similar degrees of reproductive readiness. Interestingly, shallow hibernators exhibited higher rates of DNA damage in spermatogenic cells during hibernation, with this trend reversing in spring. Our results thus indicate that once heterothermy is terminated, deep hibernators resume spermatogenesis but are characterized by higher rates of DNA damage in spermatogenic cells at the seasonal stage when spring mating commences. Therefore, our study confirmed posthibernation recovery of sperm production but also a potential impact of deep torpor expression during winter on DNA damage in spring.

Background: Extracorporeal membrane oxygenation (ECMO) has frequent and sometimes lethal thrombotic complications. The role that activated platelets, leukocytes, and small (0.3-micron to 1-micron) extracellular vesicles (EVs) play in ECMO thrombosis is not well understood., Objectives: To test the effect of blood flow rate on the generation of activated platelets, leukocytes, and EVs in a simulated neonatal ECMO circuit using heparinized human whole blood., Methods: Simulated neonatal roller pump circuits circulated whole blood at low, nominal, and high flow rates (0.3, 0.5, and 0.7 L/min) for 6 h. Coagulopathy was defined by thromboelastography (TEG), STA ® -procoagulant phospholipid clot time (STA ®- Procoag-PPL), and calibrated automated thrombogram. High-resolution flow cytometry measured the cellular expression of prothrombotic phospholipids and proteins on platelets, leukocytes, and EV., Results: Despite heparinization, occlusive thrombosis halted flow in two of five circuits at 0.3 L/min and three of five circuits at 0.7 L/min. None of the five circuits at 0.5 L/min exhibited occlusive thrombosis. Phosphatidylserine (PS)-positive platelets and EVs increased at all flow rates more than blood under static conditions (P < .0002). Tissue factor (TF)-positive leukocytes and EVs increased only in low-flow and high-flow circuits (P < .0001). Tissue factor pathway inhibitor (TFPI), at 50 times more than the concentration in healthy adults, failed to suppress thrombin initiation in low-flow and high-flow circuits., Conclusions: This in vitro study informs ECMO specialists to avoid low and high blood flow that increases TF expression on leukocytes and EVs, which likely initiate clot formation. Interventions to decrease TF generated by ECMO may be an effective approach to decrease thrombosis., (© 2019 International Society on Thrombosis and Haemostasis.)

Environmental exposures can alter the long-term health and development of offspring. How this environmental information is transmitted via the germline remains unknown, but it is thought to involve epigenetic inheritance. We recently determined that genetic disruption of histone H3 di-methylation at lysine 4 (H3K4me2) in sperm alters gene expression in the embryo and negatively impacts development across generations. However, little is known regarding when in spermatogenesis H3K4me2 methylation is established, and whether specific regions bearing H3K4me2 resist the epigenome remodeling that occurs throughout spermatogenesis. Our objective was to determine what genomic regions bearing histone H3K4me2 in spermatogonia are also present in sperm. Methods: Using transgenic mice expressing Oct4-GFP, we isolated an enriched spermatogonia population and performed ChIP-seq for H3K4me2, followed by downstream bioinformatics analysis. Using our epigenomic data and existing datasets, we compared the genomic distribution of H3K4me2 between spermatogonia and sperm. We also assessed the expression level of genes enriched in H3K4me2 in spermatogenic cell types and at specific embryonic developmental time-points. We observed that many regions of the sperm epigenome bearing H3K4me2 are already present in spermatogonia, suggesting an early establishment of this histone mark in spermatogenesis. Subsets of genes with a high enrichment in H3K4me2 in sperm are strongly expressed in spermatogenesis and others are associated with high gene expression during embryo development. These findings suggest that if epimutations in H3K4me2 are induced in spermatogonia they have the possibility to persist throughout spermatogenesis and may influence fertility by altering gene expression in spermatogenesis and in the embryo., (© The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction.)

Background: Adolescents are especially vulnerable due to increased biological, social and economic risks associated with early pregnancy and childbirth, yet most pregnancy and childbirth-related complications are preventable through a combination of proven, cost-effective clinical interventions including timely antenatal care (ANC). The voices and specific needs of adolescents are currently underrepresented in the literature on antenatal and maternity care. Objectives were to a) increase our understanding of adolescents' experiences with, and perceptions of, ANC and b) explore how these perspectives might be applied towards future initiatives to enhance adolescent care-seeking behaviour., Methods: This cross-sectional qualitative study employed 14 focus group discussions with 112 adolescents aged 15-20 years in Singida Region in Tanzania and Volta and Eastern Regions in Ghana who had accessed ANC during their most recent pregnancy. We were particularly interested in what these young women valued and understood about their ANC experience, as this would provide insights into what factors motivated them to seek care. Transcripts were analyzed using conventional content analysis. Based on emergent themes and drawing on the Health Belief Model (HBM) as an analytical tool, a conceptual framework was developed to illustrate the myriad factors influencing adolescents' decision to attend ANC., Results: Interpreting results through an adapted HBM demonstrates that adolescent health-seeking behaviour can vary widely among individuals and within communities, is shaped by the opinions of family members and peers, and is intrinsically influenced by broader health systems-level factors., Conclusions: The results led to our development of an adapted theory-based framework to illustrate the complexity of adolescent care-seeking during pregnancy in resource-poor settings. We demonstrate that while an adolescent mother is capable of exercising her own agency, she is also developmentally vulnerable to external influences and must be supported in her ability to make autonomous decisions. While the model presented here focuses specifically on ANC utilization, it may have applications for understanding how adolescents engage with health services more broadly.

Mobile health (mHealth) applications have been developed for community health workers (CHW) to help simplify tasks, enhance service delivery and promote healthy behaviours. These strategies hold promise, particularly for support of pregnancy and childbirth in low-income countries (LIC), but their design and implementation must incorporate CHW clients' perspectives to be effective and sustainable. Few studies examine how mHealth influences client and supervisor perceptions of CHW performance and quality of care in LIC. This study was embedded within a larger cluster-randomized, community intervention trial in Singida, Tanzania. CHW in intervention areas were trained to use a smartphone application designed to improve data management, patient tracking and delivery of health messages during prenatal counselling visits with women clients. Qualitative data collected through focus groups and in-depth interviews illustrated mostly positive perceptions of smartphone-assisted counselling among clients and supervisors including: increased quality of care; and improved communication, efficiency and data management. Clients also associated smartphone-assisted counselling with overall health system improvements even though the functions of the smartphones were not well understood. Smartphones were thought to signify modern, up-to-date biomedical information deemed highly desirable during pregnancy and childbirth in this context. In this rural Tanzanian setting, mHealth tools positively influenced community perceptions of health system services and client expectations of health workers; policymakers and implementers must ensure these expectations are met. Such interventions must be deeply embedded into health systems to have long-term impacts on maternal and newborn health outcomes., (© The Author(s) 2019. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: About half of births in rural Tanzania are assisted by skilled providers. Point-of-care mobile phone applications hold promise in boosting job support for community health workers aiming to ensure safe motherhood through increased facility delivery awareness, access and uptake. We conducted a controlled comparison to evaluate a smartphone-based application designed to assist community health workers with data collection, education delivery, gestational danger sign identification, and referrals., Methods: Community health workers in 32 randomly selected villages were cluster-randomized to training on either smartphone (intervention) or paper-based (control) protocols for use during household visits with pregnant women. The primary outcome measure was postnatal report of delivery location by 572 women randomly selected to participate in a survey conducted by home visit. A mixed-effects model was used to account for clustering of subjects and other measured factors influencing facility delivery., Findings: The smartphone intervention was associated with significantly higher facility delivery: 74% of mothers in intervention areas delivered at or in transit to a health facility, versus 63% in control areas. The odds of facility delivery among women counseled by smartphone-assisted health workers were double the odds among women living in control villages (OR, 1.96; CI, 1.21-3.19; adjusted analyses). Women in intervention areas were more likely to receive two or more visits from a community health worker during pregnancy than women in the control group (72% vs. 60%; chi-square = 6.9; p < 0.01). Previous facility delivery, uptake of antenatal care, and distance to the nearest facility were also strong independent predictors of facility delivery., Interpretation: Community health worker use of smartphones increased facility delivery, likely through increased frequency of prenatal home visits. Smartphone-based job aids may enhance community health worker support and effectiveness as one component of intervention packages targeting safe motherhood., Trial Registration: NCT03161184., Competing Interests: The authors have declared that no competing interests exist.

A father's lifetime experiences can be transmitted to his offspring to affect health and development. However, the mechanisms underlying paternal epigenetic transmission are unclear. Unlike in somatic cells, there are few nucleosomes in sperm, and their function in epigenetic inheritance is unknown. We generated transgenic mice in which overexpression of the histone H3 lysine 4 (H3K4) demethylase KDM1A (also known as LSD1) during spermatogenesis reduced H3K4 dimethylation in sperm. KDM1A overexpression in one generation severely impaired development and survivability of offspring. These defects persisted transgenerationally in the absence of KDM1A germline expression and were associated with altered RNA profiles in sperm and offspring. We show that epigenetic inheritance of aberrant development can be initiated by histone demethylase activity in developing sperm, without changes to DNA methylation at CpG-rich regions., (Copyright © 2015, American Association for the Advancement of Science.)

Little is known of the fundamental processes governed by epigenetic mechanisms in the supplier cells of spermatogenesis, the spermatogonial stem cells (SSCs). The histone H3 lysine demethylase KDM1A is expressed in spermatogonia. We hypothesized that KDM1A serves in transcriptional regulation of SSCs and fertility. Using a conditional deletion of Kdm1a [conditional knockout (cKO)] in mouse spermatogonia, we determined that Kdm1a is essential for spermatogenesis as adult cKO males completely lack germ cells. Analysis of postnatal testis development revealed that undifferentiated and differentiating spermatogonial populations form in Kdm1a-cKO animals, yet the majority fail to enter meiosis. Loss of germ cells in the cKO was rapid with none remaining by postnatal day (PND) 21. To gain insight into the mechanistic implications of Kdm1a ablation, we isolated PND 6 spermatogonia enriched for SSCs and analyzed their transcriptome by RNA sequencing. Loss of Kdm1a was associated with altered transcription of 1206 genes. Importantly, differentially expressed genes between control and Kdm1a-cKO animals included those that are essential for SSC and progenitor maintenance and spermatogonial differentiation. The complete loss of fertility and failure to establish spermatogenesis indicate that Kdm1a is a master controller of gene transcription in spermatogonia and is required for SSC and progenitor maintenance and differentiation., (© FASEB.)

Impairments in pituitary FSH synthesis or action cause infertility. However, causes of FSH dysregulation are poorly described, in part because of our incomplete understanding of mechanisms controlling FSH synthesis. Previously, we discovered a critical role for forkhead protein L2 (FOXL2) in activin-stimulated FSH β-subunit (Fshb) transcription in immortalized cells in vitro. Here, we tested the hypothesis that FOXL2 is required for FSH synthesis in vivo. Using a Cre/lox approach, we selectively ablated Foxl2 in murine anterior pituitary gonadotrope cells. Conditional knockout (cKO) mice developed overtly normally but were subfertile in adulthood. Testis size and spermatogenesis were significantly impaired in cKO males. cKO females exhibited reduced ovarian weight and ovulated fewer oocytes in natural estrous cycles compared with controls. In contrast, ovaries of juvenile cKO females showed normal responses to exogenous gonadotropin stimulation. Both male and female cKO mice were FSH deficient, secondary to diminished pituitary Fshb mRNA production. Basal and activin-stimulated Fshb expression was similarly impaired in Foxl2 depleted primary pituitary cultures. Collectively, these data definitively establish FOXL2 as the first identified gonadotrope-restricted transcription factor required for selective FSH synthesis in vivo.

Healthcare workers (HCW) experience decisional conflict or uncertainty of the best alternative when deciding about influenza immunization. Despite free and easy access to influenza vaccine, and resource consuming campaigns, immunization rates among HCW remain unacceptably low. This is in part due to decisional conflict, which may be alleviated by a decision aid. To address this issue we developed the Ottawa Influenza Decision Aid (OIDA) to help HCW make an informed decision about influenza immunization. The OIDA was tested in a large acute care hospital during the influenza immunization campaign. We recruited HCWs from the Orthopaedic Ward and Logistical Services, using block randomization, to complete the OIDA and a feedback questionnaire. The majority (85%) of respondents that completed the OIDA felt that immunization was very important to avoid getting influenza and 95% were sure of the best choice for them. In response to the feedback questionnaire, 84% of respondents found the information clear and 77% concluded the OIDA helped them to recognize a decision. Results of this study support the OIDA as a useful tool for HCWs considering influenza immunization. This study is an important step towards evaluating the usefulness of the OIDA within prevention campaigns. Recommendations include evaluation of the OIDA by incorporating it into large-scale influenza immunization campaigns.

A three-year randomized, controlled, double-blind trial was conducted in Cameroon to determine whether ivermectin, given at three-monthly intervals and/or at high doses (800 microg/kg), had a greater effect on adult Onchocerca volvulus than standard doses (150 microg/kg annually). As several patients complained of transitory subjective visual problems after treatment, some of them being of an unexpected type, we organized two series of detailed ophthalmological examinations to evaluate whether they were associated with ocular lesions. Analysis showed that these complaints were significantly more frequent in the two groups treated with high doses of ivermectin than in the reference group. In the ophthalmological examinations, the only differences recorded between the groups were a lower prevalence and mean number of microfilariae in the anterior chamber in the groups treated three-monthly, and, at the first examination round, a higher prevalence of early lesions of the iris in the group treated at high doses annually. These findings do not allow us to explain the cause of the transitory ocular complaints, nor why they were more frequent in the groups treated at high doses. However, one may conclude that using doses of ivermectin higher than the standard one should be considered with caution.

The human leukocyte antigen DRB1 locus (HLA-DRB1) was typed in genomic DNA extracted from whole blood samples of 34 Mexican dengue hemorrhagic fever (DHF) patients and 47 dengue fever (DF) patients, by polymerase chain reaction-sequence-specific oligonucleotide reverse dot blot. HLA-DRB1*04 was negatively associated with risk of DHF (OR 0.31, 95% CI 0.11-0.85). HLA-DR4 homozygous individuals were 11.6 times less likely to develop DHF in comparison to DR4 negative persons (OR 0.08, 95% CI 0.01-0.75). After adjusting for gender and infection type by logistic regression, DR4 positive individuals were 3.6 times less likely to develop DHF than DR4 negative persons (OR 0.28, 95% CI 0.12-0.66). A secondary dengue virus infection was also positively linked with DHF risk (OR 2.89, 95% CI 0.92-9.07). This data suggests that genes of the major histocompatibility complex play a major role in the susceptibility and/or resistance to develop DHF. In Mexicans, HLA-DR4 may be a genetic factor that is protective against DHF. Because HLA-DR4 has been positively selected in Latin American populations, these results may apply also to other similar ethnic groups, particularly those with high percentages of admixture with indigenous Amerindian genes.