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Primary membranous nephropathy (MN) is an important cause of nephrotic syndrome and chronic kidney disease (CKD) in the adult population. Although the discovery of different autoantibodies against glomerular/podocytic antigens have highlighted the role of B cells in the pathogenesis of MN, suboptimal response or even resistance to B cell-directed therapies occurs, suggesting that other pathophysiological mechanisms are involved in mediating podocyte injury. The complement system plays an important role in the innate immune response to infection, and dysregulation of the complement system has been observed in various kidney diseases. There is compelling evidence of complement cascade activation in primary MN, with the mannose-binding lectin (MBL) and alternative pathways particularly implicated. With appropriate validation, assays of complements and associated activation products could hold promise as adjunctive tools for non-invasive disease monitoring and prognostication. While there is growing interest to target the complement system in MN, there is concern regarding the risk of infection due to encapsulated organisms and high treatment costs, highlighting the need for clinical trials to identify patients most likely to benefit from complement-directed therapies.

The neuromuscular junction (NMJ) mediates neural control of skeletal muscle fibers. Neurotrophic signaling, specifically brain derived neurotrophic factor (BDNF) acting through its high-affinity tropomyosin related kinase B (TrkB) receptor is known to improve neuromuscular transmission. BDNF/TrkB signaling also maintains the integrity of antero- and retrograde communication between the motor neuron soma, its distal axons and pre-synaptic terminals and influences neuromuscular transmission. In this study, we employed a novel rat chemogenetic mutation (TrkBF616), in which a 1-naphthylmethyl phosphoprotein phosphatase 1 (1NMPP1) sensitive knock-in allele allowed specific, rapid and sustained inhibition of TrkB kinase activity. In adult female and male TrkBF616 rats, treatment with either 1NMPP1 (TrkB kinase inhibition) or DMSO (vehicle) was administered in drinking water for 14 days. To assess the extent of neuromuscular transmission failure (NMTF), diaphragm muscle isometric force evoked by nerve stimulation at 40 Hz (330 ms duration trains repeated each s) was compared to isometric forces evoked by superimposed direct muscle stimulation (every 15 s). Chronic TrkB kinase inhibition (1NMPP1 group) markedly worsened NMTF compared to vehicle controls. Acute BDNF treatment did not rescue NMTF in the 1NMPP1 group. Chronic TrkB kinase inhibition did not affect the apposition of pre-synaptic terminals (labeled with synaptophysin) and post-synaptic endplates (labeled with α-Bungarotoxin) at diaphragm NMJs. We conclude that inhibition of BDNF/TrkB signaling in TrkBF616 rats disrupts diaphragm neuromuscular transmission in a similar manner to TrkBF616A mice, likely via a pre-synaptic mechanism independent of axonal branch point failure.

A new process is reported for the incorporation of a fluoropolymer into a solid perovskite film. Poly(trifluoroethyl methacrylate) [CH2C(CH3)(CO2CH2CF3)]n was delivered to methylammonium lead iodide (CH3NH3PbI3) perovskite films by crystallizing the film in supercritical carbon dioxide/ethanol containing the dissolved fluoropolymer. The surface was characterized before and after fluoropolymer exposure using scanning electron microscopy, Raman spectroscopy, and contact angle measurements. The results indicate that the fluoropolymer was incorporated into the perovskite film during the supercritical fluid crystallization process. The incorporation of a hydrophobic fluoropolymer into perovskite has the potential to improve resistance to environmental degradation.

A study has been made of the effect of heat-treatment on the microstructures of commercial quality AISI4340 steel after austenitizing at 1128 K and austempering at temperatures ranging from 561 K to 644 K. The morphologies of the bainite structure were observed after etching using optical microscopy. The “Avrami” equation was used to determine the relationship between the transformed fraction and different austempering temperature. The activation energy was determined by using the “Arrhenius” equation. The results show the bainite sheaves and bainite width grow as the austempering temperature increases. High temperature results in fast bainite transformation and the bainite activation energy is 5.302 × 103 J/mol. The bainite microstructures highly enhanced tribological performance as compared to tempered martensite microstructures at the same hardness.

Abstract We recently documented that cardiopulmonary resuscitation (CPR) generates the same level of cardiac output (CO) and mean arterial pressure (MAP) during both normothermia (38 °C) and hypothermia (27 °C). Furthermore, continuous CPR at 27 °C provides O2 delivery (ḊO2) to support aerobic metabolism throughout a 3-h period. The aim of the present study was to investigate the effects of extracorporeal membrane oxygenation (ECMO) rewarming to restore ḊO2 and organ blood flow after prolonged hypothermic cardiac arrest. Eight male pigs were anesthetized and immersion cooled to 27 °C. After induction of hypothermic cardiac arrest, CPR was started and continued for a 3-h period. Thereafter, the animals were rewarmed with ECMO. Organ blood flow was measured using microspheres. After cooling with spontaneous circulation to 27 °C, MAP and CO were initially reduced to 66 and 44% of baseline, respectively. By 15 min after the onset of CPR, there was a further reduction in MAP and CO to 42 and 25% of baseline, respectively, which remained unchanged throughout the rest of 3-h CPR. During CPR, ḊO2 and O2 uptake (V̇O2) fell to critical low levels, but the simultaneous small increase in lactate and a modest reduction in pH, indicated the presence of maintained aerobic metabolism. Rewarming with ECMO restored MAP, CO, ḊO2, and blood flow to the heart and to parts of the brain, whereas flow to kidneys, stomach, liver and spleen remained significantly reduced. CPR for 3-h at 27 °C with sustained lower levels of CO and MAP maintained aerobic metabolism sufficient to support ḊO2. Rewarming with ECMO restores blood flow to the heart and brain, and creates a “shockable” cardiac rhythm. Thus, like continuous CPR, ECMO rewarming plays a crucial role in “the chain of survival” when resuscitating victims of hypothermic cardiac arrest.

Introduction: Using a porcine model of accidental immersion hypothermia and hypothermic cardiac arrest (HCA), the aim of the present study was to compare effects of different rewarming strategies on CPB on need for vascular fluid supply, level of cardiac restitution, and cerebral metabolism and pressures.Materials and Methods: Totally sixteen healthy, anesthetized castrated male pigs were immersion cooled to 20°C to induce HCA, maintained for 75 min and then randomized into two groups: 1) animals receiving CPB rewarming to 30°C followed by immersion rewarming to 36°C (CPB30, n = 8), or 2) animals receiving CPB rewarming to 36°C (CPB36, n = 8). Measurements of cerebral metabolism were collected using a microdialysis catheter. After rewarming to 36°C, surviving animals in both groups were further warmed by immersion to 38°C and observed for 2 h.Results: Survival rate at 2 h after rewarming was 5 out of 8 animals in the CPB30 group, and 8 out of 8 in the CPB36 group. All surviving animals displayed significant acute cardiac dysfunction irrespective of rewarming method. Differences between groups in CPB exposure time or rewarming rate created no differences in need for vascular volume supply, in variables of cerebral metabolism, or in cerebral pressures and blood flow.Conclusion: As 3 out of 8 animals did not survive weaning from CPB at 30°C, early weaning gave no advantages over weaning at 36°C. Further, in surviving animals, the results showed no differences between groups in the need for vascular volume replacement, nor any differences in cerebral blood flow or pressures. Most prominent, after weaning from CPB, was the existence of acute cardiac failure which was responsible for the inability to create an adequate perfusion irrespective of rewarming strategy.

Excessive dietary cholesterol is preferentially stored in the liver, favoring the development of nonalcoholic steatohepatitis (NASH), characterized by progressive hepatic inflammation and fibrosis. Emerging evidence indicates a critical contribution of hepatic macrophages to NASH severity. However, the impact of cholesterol on these cells in the setting of NASH remains elusive. Here, we demonstrate that the dietary cholesterol content directly affects hepatic macrophage global gene expression. Our findings suggest that the modifications triggered by prolonged high cholesterol intake induce long-lasting hepatic damage and support the expansion of a dysfunctional pro-fibrotic restorative macrophage population even after cholesterol reduction. The present work expands the understanding of the modulatory effects of cholesterol on innate immune cell transcriptome and may help identify novel therapeutic targets for NASH intervention.

There are few studies that investigate the effect of neutering bitches before or after puberty. The majority of current literature examining the impact of the timing of neutering on health and behaviour has used age rather than the onset of puberty as the key variable. The aim of this prospective cohort study was to investigate the effects of timing of neutering in relation to puberty on behaviour in female dogs reared and trained in an assistance dog programme. The study examined data for bitches neutered before or after puberty to compare scores for six behavioural factors (training and obedience, aggression, fear and anxiety, excitability, attachment and attention-seeking, and social behaviour) measured at 1 and 3 years of age. Labrador and Golden Retriever crossbreed bitches were neutered before (n = 155) or after (n = 151) puberty. Neutering before or after puberty had no impact on mean scores for the six behavioural factors at 1 or 3 years of age. When examining the change in behavioural factor scores between 1 and 3 years of age, only aggression behavioural factor scores were influenced by neutering before or after puberty. Bitches neutered after puberty were less likely to have aggression factor scores that increased between 1 and 3 years of age (OR = 0.959, 90% CI = 0.924 to 0.995, p = 0.06). However, the majority of bitches scored “0” for aggression at both time points (indicating no aggression behaviours were observed), and the number of bitches for which scores increased between 1 and 3 years of age was low (before puberty = 20, after puberty = 9). This is consistent with very mild aggressive behaviours being observed in a small number of animals and is, therefore, of questionable concern. The results suggest that, for Labrador and Golden Retriever crossbreed bitches, neutering before or after puberty has little to no effect on future behaviour. It is recommended that decisions about the timing of neutering are not informed solely by impacts on behaviour, but that they also consider evidence relating to the impacts on bitch health and well-being.

Background: Limb salvage procedures have become more prevalent in orthopedic oncology. Endoprostheses have been used successfully to reconstruct large skeletal deficits. The aim was to review intermediate to long-term follow-up of distal femoral replacements in the setting of neoplastic disease about the knee. Methods: This was a single-center retrospective cohort study from 1997 to 2018 in a national referral center for oncology. The secondary objectives were to describe morbidity and mortality in this cohort. We recorded the modes of failure using Henderson classification system, complications, revisions, and all further operations. Results: Seventy-two distal femoral replacements were performed. Osteosarcoma was the most common indication (55 patients). Other indications included chondrosarcoma (7 patients), giant cell tumor (5 patients), Ewing’s sarcoma (2 patients), metastatic spread (2 patients), and leiomyosarcoma (1 patient). One-year mortality was 1.38% with an overall mortality of 13.8%, at the end of the study period. The 1-year revision rate was 4.2%, 30.5% for 10 years, and 38.8% for more than 15 years. The overall implant survival rate was 63.8%. The most common reasons for failure included aseptic loosening (16.6%), infection (16.6%), and local recurrence (9.7%) with an amputation rate of 6.9% in the cohort. Conclusion: Neoplastic disease of the lower limb is associated with significant morbidity. Aseptic loosening (16.6%) and infection (16.6%) were the most common reasons for failure in this cohort.

Abstract In humans and dogs, a temporal decline in semen quality and increased incidence of testicular cancer is hypothesised to be associated with exposure to anthropogenic chemicals, particularly during fetal development. Human studies suggest that differential exposures to environmental chemicals may be associated with geographical differences in male reproductive health. Here we investigate testicular chemical profiles and pathologies in dogs residing in the UK [West Midlands (WM), East Midlands (EM), South East (SE)], Denmark (Copenhagen) and Finland (Vantaa). Testes, surplus from routine castrations, contained region specific differences in relative concentrations of diethylhexyl phthalate (DEHP), polybrominated diphenyl ethers (PBDE) and polychlorinated biphenyls (PCB). Relative to UK regions, testes from dogs living in Finland and Denmark had higher concentrations of PBDE and lower concentrations of DEHP and PCBs. Regional differences in the UK in PCB concentrations were also observed. Dog testes from Finland had fewer pathologies, reduced testicular area stained for Sertoli and germ cells and evidence of reduced cellular proliferation. Since the geographical differences in testis pathologies in dogs parallel reports of regional differences in human testicular cancer, we postulate that this may reflect chemical effects within the testis and that this may be related to environmental influences on male reproductive function.

No previous large prospective cohort studies have been identified that have investigated the impact of the surgical neutering of bitches before or after known puberty on their growth and physical development. This study was designed to examine the data on physical development, vulval size, and conformation for bitches neutered by ovariohysterectomy before puberty (PPN, n = 155) or after puberty (control, n = 151) using a prospective cohort study design. Data were gathered at six- and 17-months of age using bespoke physical assessment forms and digital images of the vulva. PPN bitches had greater changes in height measurements (mean difference = 2.039, SEM = 0.334, 91% CI = 1.471 to 2.608, p < 0.001) and smaller changes in the measurements of vulval length (mean difference = −0.377, SEM = 0.079, 91% CI = −0.511 to −0.243, p < 0.001) and width (mean difference = −0.221, SEM = 0.063, 91% CI = −0.328 to −0.113, p < 0.001) between six- and 17-months of age than for the control bitches. Although not significant, the PPN bitches were taller (mean 58.5 vs. 56.6 cm) and heavier (mean 28.3 vs. 27.3 kg) with smaller vulval size measurements (mean vulval length 2.8 vs. 3.2 cm, mean vulval width 1.7 vs. 2.1 cm) at 17-months of age. At 17-months of age, significantly more PPN bitches had vulvas that appeared juvenile (Yates’ Chi-square = 14.834, D.F. = 1, p < 0.001) and recessed (Yates’ Chi-square = 7.792, D.F. = 1, p = 0.005) at the physical assessment, and significantly more PPN bitches had vulvas that appeared ‘recessed/inverted’ on the examination of digital images (Chi-square = 9.902, D.F. = 1, p = 0.002). The results from this study suggest no contraindications to prepubertal ovariohysterectomy for large breed bitches. However, any longer-term health implications of these differences in physical development need to be investigated and better understood prior to recommendations being made.

The recently described deep-sea pennatulacean genus Porcupinella was previously known only by the type species, Porcupinella profunda from the equatorial eastern Atlantic to the eastern North Atlantic Ocean. New data is provided on morphology, distribution, bathymetry, and related taxa. A second species is added here as well – a new species is described from the Tasman Sea in the southwestern Pacific. The new species, Porcupinella tasmanica, is distinguished from P. profunda by its distinctive hook-shaped growth form, laterally compressed dorsal keel, and differing regions that are occupied by siphonozooids. A key to the species of the deep-sea pennatulacean family Chunellidae is included based on comparative morphology.

Introduction: Victims of accidental hypothermia in hypothermic cardiac arrest (HCA) may survive with favorable neurologic outcome if early and continuous prehospital cardiopulmonary resuscitation (CPR) is started and continued during evacuation and transport. The efficacy of cerebral autoregulation during hypothermic CPR is largely unknown and is aim of the present experiment.Methods: Anesthetized pigs (n = 8) were surface cooled to HCA at 27°C before 3 h continuous CPR. Central hemodynamics, cerebral O2 delivery (DO2) and uptake (VO2), cerebral blood flow (CBF), and cerebral perfusion pressure (CPP) were determined before cooling, at 32°C and at 27°C, then at 15 min after the start of CPR, and hourly thereafter. To estimate cerebral autoregulation, the static autoregulatory index (sARI), and the CBF/VO2 ratio were determined.Results: After the initial 15-min period of CPR at 27°C, cardiac output (CO) and mean arterial pressure (MAP) were reduced significantly when compared to corresponding values during spontaneous circulation at 27°C (−66.7% and −44.4%, respectively), and remained reduced during the subsequent 3-h period of CPR. During the first 2-h period of CPR at 27°C, blood flow in five different brain areas remained unchanged when compared to the level during spontaneous circulation at 27°C, but after 3 h of CPR blood flow in 2 of the 5 areas was significantly reduced. Cooling to 27°C reduced cerebral DO2 by 67.3% and VO2 by 84.4%. Cerebral VO2 was significantly reduced first after 3 h of CPR. Cerebral DO2 remained unaltered compared to corresponding levels measured during spontaneous circulation at 27°C. Cerebral autoregulation was preserved (sARI > 0.4), at least during the first 2 h of CPR. Interestingly, the CBF/VO2 ratio during spontaneous circulation at 27°C indicated the presence of an affluent cerebral DO2, whereas after CPR, the CBF/VO2 ratio returned to the level of spontaneous circulation at 38°C.Conclusion: Despite a reduced CO, continuous CPR for 3 h at 27°C provided sufficient cerebral DO2 to maintain aerobic metabolism and to preserve cerebral autoregulation during the first 2-h period of CPR. This new information supports early start and continued CPR in accidental hypothermia patients during rescue and transportation for in hospital rewarming.

Acute regulation of CO2 and pH homeostasis requires sensory feedback from peripheral (carotid body) and central (central) CO2/pH sensitive cells – so called respiratory chemoreceptors. Subsets of brainstem serotonin (5-HT) neurons in the medullary raphe are CO2 sensitive or insensitive based on differences in embryonic origin, suggesting these functionally distinct subpopulations may have unique transcriptional profiles. Here, we used Patch-to-Seq to determine if the CO2 responses in brainstem 5-HT neurons could be correlated to unique transcriptional profiles and/or unique molecular markers and pathways. First, firing rate changes with hypercapnic acidosis were measured in fluorescently labeled 5-HT neurons in acute brainstem slices from transgenic, Dahl SS (SSMcwi) rats expressing T2/ePet-eGFP transgene in Pet-1 expressing (serotonin) neurons (SSePet1–eGFP rats). Subsequently, the transcriptomic and pathway profiles of CO2 sensitive and insensitive 5-HT neurons were determined and compared by single cell RNA (scRNAseq) and bioinformatic analyses. Low baseline firing rates were a distinguishing feature of CO2 sensitive 5-HT neurons. scRNAseq of these recorded neurons revealed 166 differentially expressed genes among CO2 sensitive and insensitive 5-HT neurons. Pathway analyses yielded novel predicted upstream regulators, including the transcription factor Egr2 and Leptin. Additional bioinformatic analyses identified 6 candidate gene markers of CO2 sensitive 5-HT neurons, and 2 selected candidate genes (CD46 and Iba57) were both expressed in 5-HT neurons determined via in situ mRNA hybridization. Together, these data provide novel insights into the transcriptional control of cellular chemoreception and provide unbiased candidate gene markers of CO2 sensitive 5-HT neurons. Methodologically, these data highlight the utility of the patch-to-seq technique in enabling the linkage of gene expression to specific functions, like CO2 chemoreception, in a single cell to identify potential mechanisms underlying functional differences in otherwise similar cell types.

Abstract The genus Phyllachora contains numerous obligate fungal parasites that produce raised, melanized structures called stromata on their plant hosts referred to as tar spot. Members of this genus are known to infect many grass species but generally do not cause significant damage or defoliation, with the exception of P. maydis which has emerged as an important pathogen of maize throughout the Americas, but the origin of this pathogen remains unknown. To date, species designations for Phyllachora have been based on host associations and morphology, and most species are assumed to be host specific. We assessed the sequence diversity of 186 single stroma isolates collected from 16 hosts representing 15 countries. Samples included both herbarium and contemporary strains that covered a temporal range from 1905 to 2019. These 186 isolates were grouped into five distinct species with strong bootstrap support. We found three closely related, but genetically distinct groups of Phyllachora are capable of infecting maize in the United States, we refer to these as the P. maydis species complex. Based on herbarium specimens, we hypothesize that these three groups in the P. maydis species complex originated from Central America, Mexico, and the Caribbean. Although two of these groups were only found on maize, the third and largest group contained contemporary strains found on maize and other grass hosts, as well as herbarium specimens from maize and other grasses that include 10 species of Phyllachora. The herbarium specimens were previously identified based on morphology and host association. This work represents the first attempt at molecular characterization of Phyllachora species infecting grass hosts and indicates some Phyllachora species can infect a broad range of host species and there may be significant synonymy in the Phyllachora genus.

Introduction: Due to functional alterations of blood platelets and coagulation enzymes at low temperatures, excessive bleeding is a well-recognized complication in victims of accidental hypothermia and may present a great clinical challenge. Still, it remains largely unknown if hemostatic function normalizes upon rewarming. The aim of this study was to investigate effects of hypothermia and rewarming on blood coagulation in an intact porcine model.Methods: The animals were randomized to cooling and rewarming (n = 10), or to serve as normothermic, time-matched controls (n = 3). Animals in the hypothermic group were immersion cooled in ice water to 25°C, maintained at 25°C for 1 h, and rewarmed to 38°C (normal temperature in pigs) using warm water. Clotting time was assessed indirectly at different temperatures during cooling and rewarming using a whole blood coagulometer, which measures clotting time at 38°C.Results: Cooling to 25°C led to a significant increase in hemoglobin, hematocrit and red blood cell count, which persisted throughout rewarming. Cooling also caused a transiently decreased white blood cell count that returned to baseline levels upon rewarming. After rewarming from hypothermia, clotting time was significantly shortened compared to pre-hypothermic baseline values. In addition, platelet count was significantly increased.Discussion/Conclusion: We found that clotting time was significantly reduced after rewarming from hypothermia. This may indicate that rewarming from severe hypothermia induces a hypercoagulable state, in which thrombus formation is more likely to occur.

The speartooth shark Glyphis glyphis is a Critically Endangered whaler shark known from a few tropical river systems in northern Australia and Papua New Guinea. There is limited genetic exchange in populations residing in northern Australian rivers that are greater than 100 km apart. In Queensland, the species is only found in the Wenlock and Ducie River that flow into Port Musgrave. Juveniles are confined to upstream reaches of these rivers with seasonal downstream movement related to freshwater influx. This region also supports commercial and recreational fisheries including crab pot and gillnet fisheries. Being obligate ram-ventilators, entrapment in crab pots results in mortality of bycaught speartooth sharks after a few hours. Following anecdotal reports of juvenile speartooth sharks being captured in crab pots, we investigated catch rates in crab pots experimentally and examined commercial fishing effort in the Wenlock and Ducie River from logbook data. Twenty four juvenile (55–80 cm TL) speartooth sharks were captured in experimental crab pots in the Ducie River and Tentpole Creek (a tributary of the Wenlock River) with catch rates high; up to 0.82 (±1.86 SD) sharks pot–1 day–1. Experimental catch rates in crab pots varied between rivers and with distance upstream and were highest in areas of highest shark density based on detection of acoustically tagged sharks over 7 years and line fishing catch per unit effort data. Although commercial crab effort varies spatially and temporally in relation to current catch rates and market demands, consistent monthly overlap with juvenile speartooth shark core distribution occurred throughout the year. Using CPUE data multiplied by fishing effort in Tentpole Creek, we estimate that in November alone, between 51 and 279 speartooth sharks are potentially captured in years with high fishing effort. Bycatch of juvenile speartooth sharks in commercial and recreational crab pots poses a significant threat to this genetically isolated and small population. Urgent management intervention to drastically reduce bycatch mortality either through gear modifications or spatial closures are required to ensure the viability of this population.

Recent increases in frequency and intensity of warm water anomalies and marine heatwaves have led to shifts in species ranges and assemblages. Genomic tools can be instrumental in detecting such shifts. In the early stages of a project assessing population genetic structure in Pacific Sardine (Sardinops sagax), we detected the presence of Japanese Sardine (Sardinops melanosticta) along the west coast of North America for the first time. We assembled a high quality, chromosome-scale reference genome of the Pacific Sardine and generated low coverage, whole genome sequence (lcWGS) data for 345 sardine collected in the California Current Large Marine Ecosystem (CCLME) in 2021 and 2022. Fifty individuals sampled in 2022 were identified as Japanese Sardine based on strong differentiation observed in lcWGS SNP and full mitogenome data. Although we detected a single case of mitochondrial introgression, we did not observe evidence for recent hybridization events. These findings change our understanding of Sardinops spp. distribution and dispersal in the Pacific and highlight the importance of long-term monitoring programs.

Abstract Delimiting intraspecific genetic variation in harvested species is crucial to the assessment of population status for natural resource management and conservation purposes. Here, we evaluated genetic population structure in lingcod (Ophiodon elongatus), a commercially and recreationally important fishery species along the west coast of North America. We used 16,749 restriction site‐associated DNA sequencing (RADseq) markers, in 611 individuals collected from across the bulk of the species range from Southeast Alaska to Baja California, Mexico. In contrast to previous population genetic work on this species, we found strong evidence for two distinct genetic clusters. These groups separated latitudinally with a break near Point Reyes off Northern California, and there was a high frequency of admixed individuals in close proximity to the break. F‐statistics corroborate this genetic break between northern and southern sampling sites, although most loci are characterized by low FST values, suggesting high gene flow throughout most of the genome. Outlier analyses identified 182 loci putatively under divergent selection, most of which mapped to a single genomic region. When individuals were grouped by cluster assignment (northern, southern, and admixed), 71 loci were fixed between the northern and southern cluster, all of which were identified in the outlier scans. All individuals identified as admixed exhibited near 50:50 assignment to northern and southern clusters and were heterozygous for most fixed loci. Alignments of RADseq loci to a draft lingcod genome assembly and three other teleost genomes with chromosome‐level assemblies suggest that outlier and fixed loci are concentrated on a single chromosome. Similar genomic patterns have been attributed to chromosomal inversions in diverse taxonomic groups. Regardless of the evolutionary mechanism, these results represent novel observations of genetic structure in lingcod and designate clear evolutionary units that could be used to inform fisheries management.

This research presents an experimental study on the tribological behavior and plastic deformation layer response of quenched-tempered AISI 6150 steel and austempered AISI 6150 steel under sliding with a ball-on-disk type apparatus. Worn surfaces were analyzed by micro-hardness, 3D profilometer, microscopy and scanning electron microscope (SEM). The results showed that the disk surfaces were hardened after tribo-tests due to fresh-martensite formation caused by frictional heating/self-quenching during the sliding tests. The wear loss of the disk specimens was due to smearing plastic deformation resulting in material pile-up along the wear track and debris inside the wear track. The quenched-tempered disk specimens generated more debris than the austempered specimens. The greater amount of wear debris in the quench-tempered samples led to more severe contact stresses between the ball and disk samples which accelerated the smearing of material. As the tempering temperature increases, more cracks were observed for all quenched-tempered disk specimens. More voids and cracks was developed in the near surface region of tempered martensite leading to accelerated material loss through smearing and delamination. Also, more plate-like wear particles were observed on the disks of tempered martensite due to greater surface and subsurface crack fomation and propagation.

This study describes the laser surface hardening process effect on microstructures produced and their wear behavior. Ductile iron samples were austempered at three different austempering temperatures: 232 °C/288 °C/398 °C respectively. Then, the laser surface hardening process was applied on each sample. Different laser gaps were designed: 1.5mm/3mm/4 mm. The microstructures were observed using optical microscopy and tribo-tests were run using a UMT-3 tribo tester. A Rockwell hardness tester was used to measure the hardness after heat-treatment. Optical microscopy and SEM were used to observe the different microstructures and their distribution on the worn surface. The results showed that the laser processing generated ledeburite, martensite, or tempered bainite microstructures. Vickers hardness tests were carried out on these microstructures. The original needle-like microstructures were observed on the samples with 4 mm laser gap but not with 1.5 mm or 3 mm laser gap. This is because part of the 4 mm laser gap is beyond the laser heat effected zone. Generally, severe ploughing wear and smearing wear were observed on the tempered bainite zone but not the bainite zone. Debris was generated during the tribo-tests and led to three body abrasive wear which not only resulted in higher wear loss, but also polished the worn surface.

The current research focused on the tribological properties of flake-like WS2 particles dispersed into PAO4 base oil with oleic acid as surfactant. Various concentrations of 0.2 mass%, 1 mass% and 3 mass% were applied in the preparation of WS2-OA lubricant. The wear tests were carried out using a ball-on-plate reciprocating sliding test configuration. It was found that the highest COF of 0.578 was obtained using PAO4 base oil with significant fluctuations. The COF could be reduced to approximately 0.34 and stabilized after adding the OA. When introducing the WS2 articles, the COF was around 0.158 under 0.2 mass%, 0.143 under 1 mass% and 0.145 under 3 mass%, and became almost constant after 4 min. In addition, the highest wear rate in width of 61.5 µm/m and in depth of 2.2 µm/m was found using PAO4 base oil. The wear rate can be reduced to 51.6 µm/m in width (16.1%) and 0.9 µm/m (59.1%) in depth under 3 mass% OA. While using the WS2 particles, the wear rate in width could be further reduced to 45.2 µm/m using 1 mass% but with slightly higher wear rate in depth than that of OA. Based on the analysis in SEM and EDX, the abrasive grooves became less after introducing the OA, some dark spots composed of carbon acted as tribo-films on the worn area. While using WS2 particles, it could be found that WS2 flakes were adhered on the surfaces to reduce the friction and wear.

Austempered ductile iron has been considered as a substitution to replace conventional steel castings, steel forgings and even aluminum in many applications. Its excellent mechanical properties are mainly attributed to its unique ausferritic structure containing acicular ferrite and carbon saturated austenite. Some ADI components such as camshaft and engine valve commonly experience surface contact and relative motion under external load and pressure. Outstanding wear resistance of ADI is required to ensure the satisfactory working performance and service life of these key components. In order to meet the advanced requirements of mechanical properties and wear behavior of ADI, a dual-step austempering process and additional surface hardening treatments are suggested to be utilized. In this review, conventional single-step austempering process and corresponding ausferritic structure are introduced. Second, the positive effects of a novel dual-step austempering process on microstructure and mechanical properties of ADI are provided. Next, wear behavior of single-step and dual-step ADIs and wear mechanisms are discussed. Then, studies regarding the applications of surface hardening treatments on wear resistance of ADI are reviewed. Finally, a summary and expectations are discussed. The information presented in this paper would be beneficial to future studies and applications for any grade of ADI.

The present research studied the combined effects of quench-tempering and laser surface hardening treatments on wear behavior of gray cast iron, and compared results with conventional austempered gray cast iron. Four tempering temperatures of 316 °C (600 °F), 399 °C (750 °F), 482 °C (900 °F) or 552 °C (1025 °F) with a constant holding time of 60 min and four austempering temperatures of 232 °C (450 °F), 288 °C (550 °F), 343 °C (650 °F) or 399 °C (750 °F) with a constant holding time of 120 min were utilized in the heat treatment design. The wear tests were carried out on a universal mechanical tribometer with a reciprocating ball-on-plate sliding configuration. Also, the microstructure, micro-hardness profiles and worn tracks were examined. Through this work, it was found that three zones existed under the laser hardened surface. Zone 1 was the laser hardened zone containing ledeburite with hardness of approximately 68HRC. Zone 2 was the heat affected zone containing the martensite with hardness of approximately 66HRC. Zone 3 was the substrate with hardness ranging from 42.1 to 24.8HRC. In the sliding wear tests, the quench-tempering treatment only resulted in higher wear resistance of gray cast iron when compared with untreated specimens, but lower wear resistance than that of austempered gray cast iron under similar macro-hardness. The wear performance of the quench-tempered gray cast iron was enhanced after receiving the laser surface hardening treatment. Finally, the laser hardened and quench-tempered gray cast iron with tempering temperature of 552 °C showed similar mass loss due to wear as austempered gray cast iron with an austempering temperature of 232 °C. By observing the worn surfaces, the laser hardened regions could effectively inhibit the formation and propagation of cracks developed within the substrate regions. In addition, the substrate with low hardness in laser hardened and quench-tempered gray cast iron may provide enhanced ductility and toughness for gray cast iron engineering components. The results obtained in this research have significant value in selecting the optimum heat treatment process for laser hardened gray cast iron components.

The Automatic Identification System (AIS) provides situational awareness for vessels at sea. AIS has a number of known security vulnerabilities that can lead to a several types of attacks on AIS, including the ability to create ghost vessels, false warning or meteorological messages, or bogus virtual aids-to-navigation (AtoN). A number of methods, with varying levels of complexity, have been proposed to better secure AIS and, indeed, emerging AIS protocols will implement some of these mechanisms. Nevertheless, little has been done to secure the current standards, which will remain in use for some time. This paper presents Protected AIS (pAIS), a demonstration of capability implementation using public-key cryptography methods to address several AIS security vulnerabilities, maintain backward compatibility, and be able to interoperate with non-pAIS devices.

Abstract Genetically encoded Förster Resonance Energy Transfer (FRET)-based biosensors are powerful tools to illuminate spatiotemporal regulation of cell signaling in living cells, but the utility of the red spectrum for biosensing was limited due to a lack of bright and stable red fluorescent proteins. Here, we rationally improve the photophysical characteristics of the coral-derived fluorescent protein TagRFP-T. We show that a new single-residue mutant, super-TagRFP (stagRFP) has nearly twice the molecular brightness of TagRFP-T and negligible photoactivation. stagRFP facilitates significant improvements on multiple green-red biosensors as a FRET acceptor and is an efficient FRET donor that supports red/far-red FRET biosensing. Capitalizing on the ability of stagRFP to couple with multiple FRET partners, we develop a novel multiplex method to examine the confluence of signaling activities from three kinases simultaneously in single living cells, providing evidence for a role of Src family kinases in regulating growth factor induced Akt and ERK activities.

The present study mainly investigated the phase transformation and wear performance of laser hardened austempered gray cast iron specimens. Ball-on-Plate reciprocating sliding wear tests with PAO4 base oil were carried out on untreated, quench-tempered, austempered, laser hardened austempered gray cast iron specimens. Micro hardness profiles and worn surfaces were analyzed for specific wear mechanisms. It was found that four different zones were formed beneath the laser hardened surface including laser hardened zone (Ledeburite, ≈67HRC), upper heat affected zone (Martensite, ≈69HRC), lower heat affected zone (Tempered Ausferrite, ≈36HRC) and substrate (Ausferrite, ≈39HRC). In the sliding wear tests, the laser hardened austempered gray cast iron specimens showed higher wear resistance than others, which could be associated with the benefits of ausferritic structure with high fracture toughness and laser hardened regions with high hardness. By observing the worn surface, grooves and micro-sized material removal occurred within the substrate. The surface of the substrate ploughed by the asperities of the ball and hard wear debris stopped on the edge of the laser hardened regions since ledeburite and martensite had high hardness and abrasive wear resistance. However, some micro-cracks and spalls were developed within the laser hardened zone. The results obtained from this study could be used as reference in future research and applications of laser hardened austempered gray cast iron. Keywords: Gray cast iron, Austempering, Laser hardening, Sliding wear resistance

This research studies the kinetic transformation and austempering temperature effect on the morphologies of bainite for AISI 6150 steel. A minimum of 10 different holding times for each austempering temperature were utilized. All the AISI 6150 steel samples with original spheroidal pearlite were austenized at 855 °C for 20 min, followed by a lower temperature salt bath for austempering at various holding times. The hardness for each austempered temperature and holding time was measured, and the microstructures were observed by optical microscopy. The kinetic energy for needle like lower bainite and granular like upper bainite was analyzed by using kinetic transformation equations. The aim of this research was to study the transformation of bainite, in particular lower bainite, to obtain improved mechanical properties and higher ductility of AISI 6150 steel, and then apply AISI 6150 steel to more applications. Keywords: Bainite morphologies, Austempering process, Microstructures, Transformation kinetics, Phase activation energy

Austempered ductile iron (ADI) is a type of graphite cast iron produced by an isothermal heat treatment process. It is an alternative to traditional steel castings and forgings and even aluminum due to the exceptional mechanical properties such as high strength, good toughness and excellent machinability. In the matrix, the unique ausferritic structure consists of graphite nodules uniformly surrounded by acicular ferrite and carbon saturated austenite. In the automotive industry, ADI has been commonly applied in the manufacturing of camshafts, crankshafts, gears and engine valves. These components are frequently subjected to surface contact with relative motion and external load. Therefore, it is necessary to understand the wear behavior of ADI in order to solve the tribological issues in existing ADI applications and utilize ADI into future designs appropriately. This paper was aimed at reviewing the fabrication processes of single-step and dual-step ADIs. The corresponding microstructure and mechanical properties were also briefly discussed. The studies on wear performance of ADI and potential mechanisms have been systemically reviewed. Keywords: Austempered ductile iron, Single-step austempering, Dual-step austempering, Stress-induced transformation, Wear resistance

Hurricanes and tropical storms can significantly alter forested and non-forested areas, creating unique hazards and considerations for wildland firefighters and prescribed burners. Prior to responding to wildfires and planning prescribed fires, fire managers should anticipate how these changes will affect fire behavior, smoke, hazards, and access to the fire.

Background: Studies have suggested that dietary nitrate could lower blood pressure levels whereas ambient particulate matter (PM) may increase risk of hypertension. However, it is unknown if these exposures may modify each other. Objectives: We collected information on dietary nitrate intake and vegetables consumption and estimated long-term exposures to ambient PM for women in the Nurses’ Health Study. Methods: Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for risk of hypertension were calculated using Cox proportional hazards models with adjustment for potential demographic, lifestyle and dietary confounders. Interactions were assessed with multiplicative interaction terms and stratified models. Results: Increases in dietary nitrate intake (per 150 mg/d) and green leafy vegetables consumption (per serving/day) were both significantly associated with decreases in hypertension risk (both multivariable-adjusted HRs were 0.97, 95% CI: 0.94, 0.99). Long-term exposure to ambient PM with an aerodynamic diameter ≤ 2.5 µm (PM2.5) was associated with an increased risk of hypertension, with a multivariable-adjusted HR of hypertension of 1.06 (95% CI: 1.02, 1.11) per 10 µg/m3 increase in PM2.5. Ambient PM2.5 significantly modified the associations of dietary nitrate intake (Pinteraction = 0.02) and green leafy vegetables consumption (Pinteraction = 0.004). The associations with dietary factors were gradually weakened with increasing PM2.5: the fully-adjusted HRs for risk of hypertension were 0.94 (95% CI: 0.89, 0.99) and 0.94 (95% CI: 0.90, 0.99) for per 150 mg/d increase in nitrate intake and per serving/d increase in green leafy vegetables consumption, respectively, in the lowest PM2.5 quartile, and 1.00 (95% CI: 0.94, 1.06) and 1.02 (95% CI: 0.97, 1.08), respectively, in the highest PM2.5 quartile. Conclusion: Our research highlights a potentially protective effect of dietary nitrate intake in the prevention of hypertension and suggests that these benefits are attenuated by increasing exposure to ambient PM2.5.

IntroductionCooling by cardiopulmonary bypass (CPB) to deep hypothermic cardiac arrest (HCA) for cardiac surgical interventions, followed by CPB-rewarming is performed on a routine basis with relatively low mortality. In contrast, victims of deep accidental hypothermia rewarmed with CPB generally have a much worse prognosis. Thus, we have developed an intact pig model to compare effects on perfusion pressures and global oxygen delivery (DO2) during immersion cooling versus cooling by CPB. Further, we compared the effects of CPB-rewarming between groups, to restitute cardiovascular function, brain blood flow, and brain metabolism.Materials and MethodsTotal sixteen healthy, anesthetized juvenile (2–3 months) castrated male pigs were randomized in a prospective, open placebo-controlled experimental study to immersion cooling (IMMc, n = 8), or cooling by CPB (CPBc, n = 8). After 75 minutes of deep HCA in both groups, pigs were rewarmed by CPB. After weaning from CPB surviving animals were observed for 2 h before euthanasia.ResultsSurvival rates at 2 h after completed rewarming were 4 out of 8 in the IMMc group, and 8 out of 8 in the CPBc group. Compared with the CPBc-group, IMMc animals showed significant reduction in DO2, mean arterial pressure (MAP), cerebral perfusion pressure, and blood flow during cooling below 25°C as well as after weaning from CPB after rewarming. After rewarming, brain blood flow returned to control in CPBc animals only, and brain micro dialysate-data showed a significantly increase in the lactate/pyruvate ratio in IMMc vs. CPBc animals.ConclusionOur data indicate that, although global O2 consumption was independent of DO2, regional ischemic damage may have taken place during cooling in the brain of IMMc animals below 25°C. The need for prolonged extracorporeal membrane oxygenation (ECMO) should be considered in all victims of accidental hypothermic arrest that cannot be weaned from CPB immediately after rewarming.

Cardiovascular disease represents the leading cause of death in the United States, and metabolic diseases such as obesity represent the primary impediment to improving cardiovascular health. Rodent (mouse and rat) models are widely used to model cardiometabolic disease, and as a result, there is increasing interest in the development of accurate and precise methodologies with sufficiently high resolution to dissect mechanisms controlling cardiometabolic physiology in these small organisms. Further, there is great utility in the development of centralized core facilities furnished with high-throughput equipment configurations and staffed with professional content experts to guide investigators and ensure the rigor and reproducibility of experimental endeavors. Here, we outline the array of specialized equipment and approaches that are employed within the Comprehensive Rodent Metabolic Phenotyping Core (CRMPC) and our collaborating laboratories within the Departments of Physiology, Pediatrics, Microbiology & Immunology, and Biomedical Engineering at the Medical College of Wisconsin (MCW), for the detailed mechanistic dissection of cardiometabolic function in mice and rats. We highlight selected methods for the analysis of body composition and fluid compartmentalization, electrolyte accumulation and flux, energy accumulation and flux, physical activity, ingestive behaviors, ventilatory function, blood pressure, heart rate, autonomic function, and assessment and manipulation of the gut microbiota. Further, we include discussion of the advantages and disadvantages of these approaches for their use with rodent models, and considerations for experimental designs using these methods.

BackgroundMental health services are advocated to move from specialized care to more integrated and accessible primary care settings. The integration of mental health into primary health services is expanding in Ethiopia. However, there is a lack of research on the perspectives of health professionals on mental health services in Ethiopia. This study aimed to explore the perspectives, views, and experiences of health professionals regarding mental health services and the help-seeking behavior of people with mental illness in Northwest Ethiopia.MethodsThis qualitative study included sixteen health professionals. The participants were interviewed using a semi-structured interview guide. Interviews were conducted in Amharic and translated into English. We analyzed the data using reflexive thematic analysis.ResultsFive key themes were generated from the interview data: (1) Avoidance of mental healthcare; (2) Low literacy about mental illness; (3) Stigma as a hindrance to accessing mental health services; (4) The role of culture and religion in mental health services; and (5) Lack of government concern about mental health services.ConclusionThis study identified important factors related to mental health services in Northwest Ethiopia, from the perspectives of health professionals. Our findings highlighted that the government health agenda needs to prioritize mental health services. The role of religious and cultural healing places in the help-seeking pathway should be given due consideration to ensure success in mental health services provision and utilization.

Background Unplanned intensive care unit (ICU) readmission—ICU bounce back (ICUbb)—is associated with worse outcomes. Patients not requiring organ system support or intensive nursing are deemed ‘ICU discharge ready’ and transfer orders are placed. However, actual transfer only occurs when an appropriate, non-ICU bed is available. This is dependent on inherent system inefficiencies resulting in a naturally controlled experiment between when patients actually transfer: Early (24 hours) transfers, after order placement. This study leverages that natural experiment to determine if additional ICU time is protective against ICUbb. We hypothesize that Delayed transfer is protective against ICUbb.Methods Using a retrospective, cohort design, we queried a trauma research repository and electronic medical record during a 10-year period to capture traumatized patients admitted to the ICU. Patients were categorized into Early (24 hours) groups based on actual transfer time after order placement. Patient characteristics (age, Charlson Comorbidity Index (CCI)) and Injury Severity Score (ISS) were analyzed. Univariate and multivariate analyses were performed to compare ICUbb rates among Early and Unintended-Delayed groups.Results Of the 2004 patients who met the criteria, 1690 fell into the Early group, and 314 fell into the Delayed. The Early group was younger (mean age 52±23 vs. 55±22 years), had fewer comorbidities (median CCI score 1 (0, 3) vs. 2 (1, 3)), and was less injured (median ISS 17 (10–22) vs. 17 (13–25)), all p

As we near a complete catalog of mammalian cell types, the capability to engineer specific cell types on demand would transform biomedical research and regenerative medicine. However, the current pace of discovering new cell types far outstrips our ability to engineer them. One attractive strategy for cellular engineering is direct reprogramming, where induction of specific transcription factor (TF) cocktails orchestrates cell state transitions. Here, we review the foundational studies of TF-mediated reprogramming in the context of a general framework for cell fate engineering, which consists of: discovering new reprogramming cocktails, assessing engineered cells, and revealing molecular mechanisms. Traditional bulk reprogramming methods established a strong foundation for TF-mediated reprogramming, but were limited by their small scale and difficulty resolving cellular heterogeneity. Recently, single-cell technologies have overcome these challenges to rapidly accelerate progress in cell fate engineering. In the next decade, we anticipate that these tools will enable unprecedented control of cell state.

Aims: Rewarming from accidental hypothermia and therapeutic temperature management could be complicated by cardiac dysfunction. Although pharmacologic support is often applied when rewarming these patients, updated treatment recommendations are lacking. There is an underlying deficiency of clinical and experimental data to support such interventions and this prevents the development of clinical guidelines. Accordingly, we explored the clinical effects of epinephrine during hypothermic conditions.Materials and methods: Anesthetized pigs were immersion cooled to 32°C. Predetermined variables were compared at temperature/time-point baseline, after receiving 30 ng/kg/min and 90 ng/kg/min epinephrine infusions: (1) before and during hypothermia at 32°C, and after rewarming to 38°C (n = 7) and (2) a time-matched (5 h) normothermic control group (n = 5).Results: At 32°C, both stroke volume and cardiac output were elevated after 30 ng/kg/min administration, while systemic vascular resistance was reduced after 90 ng/kg/min. Epinephrine infusion did not alter blood flow in observed organs, except small intestine flow, and global O2 extraction rate was significantly reduced in response to 90 ng/kg/min infusion. Electrocardiographic measurements were unaffected by epinephrine infusion.Conclusion: Administration of both 30 ng/kg/min and 90 ng/kg/min at 32°C had a positive inotropic effect and reduced afterload. We found no evidence of increased pro-arrhythmic activity after epinephrine infusion in hypothermic pigs. Our experiment therefore suggests that β₁-receptor stimulation with epinephrine could be a favorable strategy for providing cardiovascular support in hypothermic patients, at core temperatures >32°C.

Background: Holistic processing is defined as the perceptual integration of facial features, and plays an important role in face recognition. While researchers recognize the crucial role played by holistic processing in face perception, a complete delineation of the underlying mechanisms is impending. Very few studies have examined the effects of perceptual discrimination and spatial perception on holistic processing. Hence, the present study aimed to examine the influence of perceptual discrimination and spatial perception on face recognition.Methods: We conducted two experiments by manipulating the perceptual discriminability of the target (the top-half faces) and non-target face (the bottom-half faces) parts in the composite-face task and examined how perceptual discriminability may affect holistic processing of faces.Results: The results of Experiment 1 illustrated that holistic processing was modulated by the perceptual discriminability of the face. Furthermore, differential patterns of perceptual discriminability with the target and non-target parts suggested that different mechanisms may be responsible for the influence of target and non-target parts on face perception. The results of Experiment 2 illustrated that holistic processing was modulated by spatial distance between two faces, implicating that feature-by-feature strategy might decrease the magnitude of holistic processing.Conclusion: The results of the present study suggest that holistic processing may lead to augmented perception effect exaggerating the differences between the two faces and may also be affected by the feature-by-feature strategy.

Sarcopenia is characterized by muscle fiber atrophy and weakness, which may be associated with mitochondrial fragmentation and dysfunction. Mitochondrial remodeling and biogenesis in muscle fibers occurs in response to exercise and increased muscle activity. However, the adaptability mitochondria may decrease with age. The diaphragm muscle (DIAm) sustains breathing, via recruitment of fatigue-resistant type I and IIa fibers. More fatigable, type IIx/IIb DIAm fibers are infrequently recruited during airway protective and expulsive behaviors. DIAm sarcopenia is restricted to the atrophy of type IIx/IIb fibers, which impairs higher force airway protective and expulsive behaviors. The aerobic capacity to generate ATP within muscle fibers depends on the volume and intrinsic respiratory capacity of mitochondria. In the present study, mitochondria in type-identified DIAm fibers were labeled using MitoTracker Green and imaged in 3-D using confocal microscopy. Mitochondrial volume density was higher in type I and IIa DIAm fibers compared with type IIx/IIb fibers. Mitochondrial volume density did not change with age in type I and IIa fibers but was reduced in type IIx/IIb fibers in 24-month rats. Furthermore, mitochondria were more fragmented in type IIx/IIb compared with type I and IIa fibers, and worsened in 24-month rats. The maximum respiratory capacity of mitochondria in DIAm fibers was determined using a quantitative histochemical technique to measure the maximum velocity of the succinate dehydrogenase reaction (SDHmax). SDHmax per fiber volume was higher in type I and IIa DIAm fibers and did not change with age. In contrast, SDHmax per fiber volume decreased with age in type IIx/IIb DIAm fibers. There were two distinct clusters for SDHmax per fiber volume and mitochondrial volume density, one comprising type I and IIa fibers and the second comprising type IIx/IIb fibers. The separation of these clusters increased with aging. There was also a clear relation between SDHmax per mitochondrial volume and the extent of mitochondrial fragmentation. The results show that DIAm sarcopenia is restricted to type IIx/IIb DIAm fibers and related to reduced mitochondrial volume, mitochondrial fragmentation and reduced SDHmax per fiber volume.

Introduction: Previously, we showed that the cardiopulmonary resuscitation (CPR) for hypothermic cardiac arrest (HCA) maintained cardiac output (CO) and mean arterial pressure (MAP) to the same reduced level during normothermia (38°C) vs. hypothermia (27°C). In addition, at 27°C, the CPR for 3-h provided global O2 delivery (DO2) to support aerobic metabolism. The present study investigated if rewarming with closed thoracic lavage induces a perfusing rhythm after 3-h continuous CPR at 27°C.Materials and Methods: Eight male pigs were anesthetized, and immersion-cooled. At 27°C, HCA was electrically induced, CPR was started and continued for a 3-h period. Thereafter, the animals were rewarmed by combining closed thoracic lavage and continued CPR. Organ blood flow was measured using microspheres.Results: After cooling with spontaneous circulation to 27°C, MAP and CO were initially reduced by 37 and 58% from baseline, respectively. By 15 min after the onset of CPR, MAP, and CO were further reduced by 58 and 77% from baseline, respectively, which remained unchanged throughout the rest of the 3-h period of CPR. During CPR at 27°C, DO2 and O2 extraction rate (VO2) fell to critically low levels, but the simultaneous small increase in lactate and a modest reduction in pH, indicated the presence of maintained aerobic metabolism. During rewarming with closed thoracic lavage, all animals displayed ventricular fibrillation, but only one animal could be electro-converted to restore a short-lived perfusing rhythm. Rewarming ended in circulatory collapse in all the animals at 38°C.Conclusion: The CPR for 3-h at 27°C managed to sustain lower levels of CO and MAP sufficient to support global DO2. Rewarming accidental hypothermia patients following prolonged CPR for HCA with closed thoracic lavage is not an alternative to rewarming by extra-corporeal life support as these patients are often in need of massive cardio-pulmonary support during as well as after rewarming.

Abstract Serotonin (5‐HT) influences brain development and has predominantly excitatory neuromodulatory effects on the neural respiratory control circuitry. Infants that succumb to sudden infant death syndrome (SIDS) have reduced brainstem 5‐HT levels and Tryptophan hydroxylase 2 (Tph2). Furthermore, there are age‐ and sex‐dependent risk factors associated with SIDS. Here we utilized our established Dark Agouti transgenic rat lacking central serotonin KO to test the hypotheses that CNS 5‐HT deficiency leads to: (1) high mortality in a sex‐independent manner, (2) age‐dependent alterations in other CNS aminergic systems, and (3) age‐dependent impairment of chemoreflexes during post‐natal development. KO rat pups showed high neonatal mortality but not in a sex‐dependent manner and did not show altered hypoxic or hypercapnic ventilatory chemoreflexes. However, KO rat pups had increased apnea‐related metrics during a specific developmental age (P12–16), which were preceded by transient increases in dopaminergic system activity (P7–8). These results support and extend the concept that 5‐HT per se is a critical factor in supporting respiratory control during post‐natal development.

Abstract Many of the major stem rust resistance genes deployed in commercial wheat (Triticum spp.) cultivars and breeding lines become ineffective over time because of the continuous emergence of virulent races. A genome‐wide association study (GWAS) was conducted using 26,439 single nucleotide polymorphism (SNP) markers and 280 durum wheat [Triticum turgidum L. subsp. Durum (Desf.) Husnot] lines from CIMMYT to identify genomic regions associated with seedling resistance to races TTKSK, TKTTF, JRCQC, and TTRTF and field resistance to TKTTF and JRCQC. The phenotypic data analysis across environments revealed 61–91 and 59–77% of phenotypic variation was explained by the genotypic component for seedling and adult plant response of lines, respectively. For seedling resistance, mixed linear model (MLM) identified eight novel and nine previously reported quantitative trait loci (QTL) while a fixed and random model circulating probability unification (FarmCPU) detected 12 novel and eight previously reported QTL. For field resistance, MLM identified 12 novel and seven previously reported loci while FarmCPU identified seven novel and nine previously reported loci. The regions of Sr7a, Sr8155B1, Sr11, alleles of Sr13, Sr17, Sr22/Sr25, and Sr49 were identified. Novel loci on chromosomes 3B, 4A, 6A, 6B, 7A, and 7B could be used as sources of resistance to the races virulent on durum wheat. Two large‐effect markers on chromosome 6A could potentially be used to differentiate resistant haplotypes of Sr13 (R1 and R3). Allelism tests for Sr13, breaking the deleterious effect associated with Sr22/Sr25 and retaining the resistance allele at the Sr49 locus, are needed to protect future varieties from emerging races.

Previously, we reported that in airway smooth muscle (ASM), the cytosolic Ca2+ ([Ca2+]cyt) and force response induced by acetyl choline (ACh) are increased by exposure to the pro-inflammatory cytokine tumor necrosis factor α (TNFα). The increase in ASM force induced by TNFα was not associated with an increase in regulatory myosin light chain (rMLC20) phosphorylation but was associated with an increase in contractile protein (actin and myosin) concentration and an enhancement of Ca2+ dependent actin polymerization. The sensitivity of ASM force generation to elevated [Ca2+]cyt (Ca2+ sensitivity) is dynamic involving both the shorter-term canonical calmodulin-myosin light chain kinase (MLCK) signaling cascade that regulates rMLC20 phosphorylation and cross-bridge recruitment as well as the longer-term regulation of actin polymerization that regulates contractile unit recruitment and actin tethering to the cortical cytoskeleton. In this study, we simultaneously measured [Ca2+]cyt and force responses to ACh and explored the impact of 24-h TNFα on the dynamic relationship between [Ca2+]cyt and force responses. The temporal delay between the onset of [Ca2+]cyt and force responses was not affected by TNFα. Similarly, the rates of rise of [Ca2+]cyt and force responses were not affected by TNFα. The absence of an impact of TNFα on the short delay relationships between [Ca2+]cyt and force was consistent with the absence of an effect of [Ca2+]cyt and force on rMLC20 phosphorylation. However, the integral of the phase-loop plot of [Ca2+]cyt and force increased with TNFα, consistent with an impact on actin polymerization and, contractile unit recruitment and actin tethering to the cortical cytoskeleton.

Objectives: The urinary excretion of organic and inorganic substances and their concentrations have attracted extensive attention for their role in the pathogenesis of urinary stone disease. The urinary excretion of specific factors associates with sex and age and seems to have a hereditary component, but the precise genomic determinants remain ill-defined. Methods: Genome-wide association studies previously conducted in 3 cohorts (Genetic Epidemiology Network of Arteriopathy study, January 1, 2006, through December 31, 2012; the combined Nurses’ Health Study (NHS), NHS II, and Health Professionals Follow-up Study, January 1, 1994, through December 31, 2003; and the Prevention of Renal and Vascular End-stage Disease study, January 1, 1997, through December 31, 1998) were combined into meta-analyses to evaluate genetic associations with available urinary phenotypes relevant to stone pathogenesis (calcium, magnesium, and uric acid excretion; total urine volume). Results: One region on chromosome 9q21.13 showed strong evidence of an association with urinary magnesium excretion. The strongest signal in this region was near TRPM6, whose protein product mediates magnesium transport in the colon and kidney, and C9orf40, C9orf41, NMRK1, and OSTF1 (rs1176815; P=1.70×10–14, with each copy of the A allele corresponding to a daily 5.29-mg decrease in magnesium excretion). The single nucleotide polymorphism (SNP) that achieved genome-wide significance for calcium excretion (rs17216707 on chromosome 20; P=1.12×10–8) was previously associated with fibroblast growth factor 23 levels, which regulate phosphorus and vitamin D metabolism. Urine volume and uric acid excretion did not have any genome-wide significant SNPs. Conclusion: Common variants near genes important for magnesium metabolism and bone health associate with urinary magnesium and calcium excretion.

The objective of this research was to investigate the bainitic formation in austempered SAE 52100 steel. The original microstructure of SAE 52100 steel consisted of spheroidized pearlite. In the formation of bainite, SAE 52100 steel samples were austenitized at a temperature of 849 °C for 20 min, and then quickly quenched to the isothermal temperatures between 232 °C and 427 °C for various holding times from 20 s to 120 min. The hardness and microstructure of austempered SAE 52100 samples were analyzed using a Rockwell C hardness tester and metallurgical optical microscope. In addition, the bainitic formation in SAE 52100 steel was characterized using the theory of kinetic phase transformation. The activation energies of lower bainite and upper bainite microstructure were found to be 4.72 × 104 J/mol and 6.07 × 104 J/mol with frequency factors of 23.03 (1/s) and 273.65 (1/s), respectively. Keywords: SAE 52100 steel, Austempering, Bainite, Rockwell hardness, Transformation kinetics

Science is humanity's best insurance against threats from nature, but it is a fragile enterprise that must be nourished and protected. The preponderance of scientific evidence indicates a natural origin for SARS-CoV-2. Yet, the theory that SARS-CoV-2 was engineered in and escaped from a lab dominates media attention, even in the absence of strong evidence. We discuss how the resulting anti-science movement puts the research community, scientific research, and pandemic preparedness at risk.

Personal protective equipment (PPE) is crucially important to the safety of both patients and medical personnel, particularly in the event of an infectious pandemic. As the incidence of Coronavirus Disease 2019 (COVID-19) increases exponentially in the United States and many parts of the world, healthcare provider demand for these necessities is currently outpacing supply. In the midst of the current pandemic, there has been a concerted effort to identify viable ways to conserve PPE, including decontamination after use. In this study, we outline a procedure by which PPE may be decontaminated using ultraviolet (UV) radiation in biosafety cabinets (BSCs), a common element of many academic, public health, and hospital laboratories. According to the literature, effective decontamination of N95 respirator masks or surgical masks requires UV-C doses of greater than 1 Jcm-2, which was achieved after 4.3 hours per side when placing the N95 at the bottom of the BSCs tested in this study. We then demonstrated complete inactivation of the human coronavirus NL63 on N95 mask material after 15 minutes of UV-C exposure at 61 cm (232 μWcm-2). Our results provide support to healthcare organizations looking for methods to extend their reserves of PPE.