Genomic characterisation of bioaerosols within livestock facilities: A systematic review.

Livestock facilities are widely regarded as reservoirs of infectious disease, owing to their abundance in particulate matter (PM) and microbial bioaerosols. Over the past decade, bioaerosol studies have increasingly utilised high throughput sequencing (HTS) to achieve superior throughput, taxonomic resolution, and the detection of unculturable organisms. However, the prevailing focus on amplicon sequencing has limited the identification of viruses and microbial taxa at the species-level. Herein, a literature search was conducted to identify methods capable of overcoming the aforementioned limitations. Screening 1531 international publications resulted in 29 eligible for review. Metagenomics capable of providing rich insights were identified in only three instances. Notably, long-read sequencing was not utilised for metagenomics. This review also identified that sample collection methods lack a uniform approach, highlighted by the differences in sampling equipment, flow rates and durations. Further heterogeneity was introduced by the unique sampling conditions, which makes it challenging to ground new findings within the established literature. For instance, winter was associated with increased microbial abundance and antimicrobial resistance, yet less alpha diversity. Researchers implementing metagenomics into the livestock environment should consider season, the microclimate, and livestock growth stage as influential upon their findings. Considering the increasing accessibility of long-read sequencing, future research should explore its viability within a novel uniform testing protocol for bioaerosol emissions.

Heterogeneity in Systematic Reviews of Medical Imaging Diagnostic Test Accuracy Studies: A Systematic Review.

Importance: Systematic reviews of medical imaging diagnostic test accuracy (DTA) studies are affected by between-study heterogeneity due to a range of factors. Failure to appropriately assess the extent and causes of heterogeneity compromises the interpretability of systematic review findings. Objective: To assess how heterogeneity has been examined in medical imaging DTA studies. Evidence Review: The PubMed database was searched for systematic reviews of medical imaging DTA studies that performed a meta-analysis. The search was limited to the 40 journals with highest impact factor in the radiology, nuclear medicine, and medical imaging category in the InCites Journal Citation Reports of 2021 to reach a sample size of 200 to 300 included studies. Descriptive analysis was performed to characterize the imaging modality, target condition, type of meta-analysis model used, strategies for evaluating heterogeneity, and sources of heterogeneity identified. Multivariable logistic regression was performed to assess whether any factors were associated with at least 1 source of heterogeneity being identified in the included meta-analyses. Methodological quality evaluation was not performed. Data analysis occurred from October to December 2022. Findings: A total of 242 meta-analyses involving a median (range) of 987 (119-441 510) patients across a diverse range of disease categories and imaging modalities were included. The extent of heterogeneity was adequately described (ie, whether it was absent, low, moderate, or high) in 220 studies (91%) and was most commonly assessed using the I2 statistic (185 studies [76%]) and forest plots (181 studies [75%]). Heterogeneity was rated as moderate to high in 191 studies (79%). Of all included meta-analyses, 122 (50%) performed subgroup analysis and 87 (36%) performed meta-regression. Of the 242 studies assessed, 189 (78%) included 10 or more primary studies. Of these 189 studies, 60 (32%) did not perform meta-regression or subgroup analysis. Reasons for being unable to investigate sources of heterogeneity included inadequate reporting of primary study characteristics and a low number of included primary studies. Use of meta-regression was associated with identification of at least 1 source of variability (odds ratio, 1.90; 95% CI, 1.11-3.23; P = .02). Conclusions and Relevance: In this systematic review of assessment of heterogeneity in medical imaging DTA meta-analyses, most meta-analyses were impacted by a moderate to high level of heterogeneity, presenting interpretive challenges. These findings suggest that, despite the development and availability of more rigorous statistical models, heterogeneity appeared to be incomplete, inconsistently evaluated, or methodologically questionable in many cases, which lessened the interpretability of the analyses performed; comprehensive heterogeneity assessment should be addressed at the author level by improving personal familiarity with appropriate statistical methodology for assessing heterogeneity and involving biostatisticians and epidemiologists in study design, as well as at the editorial level, by mandating adherence to methodologic standards in primary DTA studies and DTA meta-analyses.

The Craniofacial Collaboration UK: Developmental Outcomes in 7- and 10-Year-Old Children With Metopic Synostosis.

The Craniofacial Collaboration (CC-UK) is a shared initiative across the Psychology teams attached to 4 highly specialized craniofacial centers in the United Kingdom. The CC-UK aims to address key limitations in the existing craniofacial literature by analyzing data for homogenous samples of children with craniosynostosis. This article presents the fifth wave of CC-UK data collection, focused on 7- and 10-year olds who have undergone primary corrective surgery for metopic synostosis (MS). Data for children with sagittal synostosis and MS have previously been presented at 3 and 5 years. This paper continues to build on this with consideration to older age groups, presenting the first CC-UK analysis of cognitive assessment data using the Wechsler Abbreviated Scale of Intelligence-Second Edition. Results show that the majority of children with MS fall within the average ranges across behavioral and neurodevelopmental domains. However, several domains indicated a trend of heightened concern when compared with normative data, particularly for parent-reported outcomes, suggesting that there may be some subtle difficulties for children with MS. Consideration of how these findings compare with that of previous CC-UK analyses is explored. Further, implications for clinical practice and future research are considered, with the need for longitudinal analyses, as well as data from multiple perspectives (eg, school, parents, and self) at older age points to establish patterns over time. Through collaboration across the highly specialized craniofacial centers, the CC-UK hopes to work toward this goal moving forward.

Prevalence of Falciparum and non-Falciparum Malaria in the 2014-15 Rwanda Demographic Health Survey.

Background: Malaria remains a major cause of morbidity in sub-Saharan Africa. Undetected asymptomatic falciparum malaria results in a large transmission reservoir and there is evidence of increasing non-falciparum malaria as malaria is controlled in Africa, both resulting in challenges for malaria control programs. Methods: We performed quantitative real time PCR for 4 malaria species in 4,596 individuals from the 2014-2015 Rwanda Demographic Health Survey. Bivariate models were used to determine species-specific associations with risk factors. Results: Asymptomatic falciparum malaria, P. ovale spp., and P. malariae infection had broad spatial distribution across Rwanda. P. vivax infection was rare. Overall infection prevalence was 23.6% (95%CI [21.7%, 26.0%]), with falciparum and non-falciparum at 17.6% [15.9%, 19.0%] and 8.3% [7.0%, 10.0%], respectively. Parasitemias tended to be low and mixed species infections were common, especially where malaria transmission was the highest. Falciparum infection was associated with socio-econiomic status, rural residence and low altitude. Few risk factors were associated with non-falciparum malaria. Conclusions: Asymptomatic falciparum malaria and non-falciparum malaria are common and widely distributed across Rwanda. Continued molecular monitoring of Plasmodium spp. is needed to monitor these threats to malaria control in Africa.

Microarray molecular mapping of horses with severe asthma.

BACKGROUND: Severe asthma (SA) in horses, resembling human asthma, is a prevalent, debilitating allergic respiratory condition marked by elevated allergen-specific immunoglobulin E (IgE) against environmental proteins; however, research exploring the exposome's influence on IgE profiles is currently limited but holds paramount significance for diagnostic and therapeutic developments. ANIMALS: Thirty-five sports horses were analyzed, consisting of environmentally matched samples from France (5 SA; 6 control), the United States (6 SA; 6 control), and Canada (6 SEA; 6 control). METHODS: This intentional cross-sectional study investigated the sensitization profiles of SA-affected and healthy horses via serological antigen microarray profiling. Partial least square-discriminant analysis (PLS-DA) was used to identify and rank the importance of allergens for class separation (ie, affected/non-affected) as variable influence of projection (VIP), and allergen with commonality internationally established via frequency analysis. RESULTS: PLS-DA models showed high discriminatory power in predicting SA in horses from Canada (area under the curve [AUC] 0.995) and France (AUC 0.867) but poor discriminatory power in horses from the United States (AUC 0.38). Hev b 5.0101, Cyn D, Der p 2, and Rum cr were the only shared allergens across all geographical groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Microarray profiling can identify specific allergenic components associated with SA in horses, while mathematical modeling of this data can be used for disease classification, highlighting the variability of sensitization profiles between geographical locations and emphasizing the importance of local exposure to the prevalence of different allergens. Frequency scoring analysis can identify important variables that contribute to the classification of SA across different geographical regions.

Social Media and Website Use: The Experiences of Parents and Carers Accessing Care at the Oxford Craniofacial Unit.

INTRODUCTION: Historically, medical professionals have been the providers of specialist information about rare medical conditions. Now, increasingly, patients and the public are using the internet to access and generate information about medical diagnoses. The global nature of the internet allows patients to connect across geographical borders, and to obtain and share information that would have been previously inaccessible to them. This research investigated the use of website and social media by parents of children with craniosynostosis. METHODS: A cross-sectional survey-based design was employed. Participants were parents of children with craniosynostosis attending multidisciplinary craniofacial clinics within the Oxford Craniofacial Unit. A questionnaire was administered which assessed social media and website use adapted from the questionnaire created by Khouri and colleagues (2016) and Huggons and colleagues (2019). The surveys were administered over an 18-month period (November 2020 to May 2022). RESULTS: The final sample comprised 82 parents [70 mothers; 10 fathers; 1 sister/carer and 1 parent (mother/father unspecified)]. The children were aged 11 months-16 years of age (average age 6 y and 3 mo). Children had a variety of diagnoses: 31 sagittal, 19 metopic, 14 syndromic craniosynostosis, 8 unicoronal, 6 multisuture, 3 bicoronal, and 1 unilambdoid.Results showed that 93% (n=76/82) of parents used the internet to find out more about craniosynostosis, with 72% (n=59/82) of parents specifically using social media to find out more about craniosynostosis. The social media platforms used included: Facebook 64% (n=53/82), Instagram 24% (n=20/82), Blogs 12% (n=10/82), Twitter 4% (n= 4/82), Tik Tok 2% (n=2/82), and Snapchat 0.01% (n=1/82).Parents reported that Facebook was the most helpful source of information about craniosynostosis (52%; n=43/82). Parents indicated the key timepoints they used social media included: when their child received a diagnosis (70%; n=58/82), before their child's surgery (34%; n=28/82), before their first craniofacial clinic appointment (83%; n=25/30), and when child was older (17%; n=14/84). Forty percent (n=33/82) of parents said that a diagnosis of craniosynostosis made no difference to their social media use, whereas 34% (n=28/82) of parents used social media more, and 20% (n=16/82) used it less. CONCLUSION: Results highlight that parents use social media and other websites to access information relating to craniosynostosis. Future research should examine whether parental use of social media changes across their child's lifespan and evaluate the quality of this information.

Glitches in Rotating Supersolids.

Glitches, spin-up events in neutron stars, are of prime interest, as they reveal properties of nuclear matter at subnuclear densities. We numerically investigate the glitch mechanism due to vortex unpinning using analogies between neutron stars and dipolar supersolids. We explore the vortex and crystal dynamics during a glitch and its dependence on the supersolid quality, providing a tool to study glitches from different radial depths of a neutron star. Benchmarking our theory against neutron-star observations, our work will open a new avenue for the quantum simulation of stellar objects from Earth.

The clinical epidemiology, management, and outcomes of patients diagnosed with encephalitis in North Carolina, 2015-2020.

IMPORTANCE: Despite the relatively high mortality and the difficulty in diagnosis, nearly one-third of patients hospitalized with a documented diagnosis of encephalitis did not undergo a lumbar puncture (LP). When an LP was performed, pathogen-specific testing was greatly underutilized. Infectious etiologies were most common, but over 40% of cases were idiopathic at discharge. These findings suggest that there is a substantial opportunity to improve the quality of care through more accurate and timely diagnosis.

Nonbacterial Thrombotic Endocarditis of Bioprosthetic Aortic Valve Presenting as Cardioembolic Stroke in a Patient without Predisposing Systemic Disease.

Nonbacterial thrombotic endocarditis (NBTE) describes a cluster of noninfectious heart valve lesions and is histologically characterised by the presence of sterile platelet and fibrin-rich aggregates. Risk factors include hypercoagulable states such as active malignancy, autoimmune disorders, and prothrombotic haematological conditions. NBTE involving bioprosthetic heart valves is exceedingly rare. We present a case of a 73-year-old man with a bioprosthetic aortic valve and no NBTE risk factors who developed right-sided homonymous hemianopia during an admission for decompensated congestive cardiac failure. After detailed clinical work-up including brain MRI, the man was diagnosed with acute ischemic cardioembolic stroke involving the left posterior cerebral artery territory. He subsequently underwent successful bioprosthetic aortic valve replacement with histologic examination of the explant supporting diagnosis of NBTE. Evidence of new neurological deficit or disturbance in patients with prosthetic heart valves should prompt investigation for cardioembolic stroke. Whilst rare, NBTE should be considered as a differential diagnosis for cardioembolic stroke, even in patients without predisposing systemic disease.

Neuroimaging Findings in Axenfeld-Rieger Syndrome: A Case Series.

Axenfeld-Rieger syndrome is an autosomal dominant condition associated with multisystemic features including developmental anomalies of the anterior segment of the eye. Single nucleotide and copy number variants in the paired-like homeodomain transcription factor 2 (PITX2) and forkhead box C1 (FOXC1) genes are associated with Axenfeld-Rieger syndrome as well as other CNS malformations. We determined the association between Axenfeld-Rieger syndrome and specific brain MR imaging neuroradiologic anomalies in cases with or without a genetic diagnosis. This case series included 8 individuals with pathogenic variants in FOXC1; 2, in PITX2; and 2 without a genetic diagnosis. The most common observation was vertebrobasilar artery dolichoectasia, with 46% prevalence. Other prevalent abnormalities included WM hyperintensities, cerebellar hypoplasia, and ventriculomegaly. Vertebrobasilar artery dolichoectasia and absent/hypoplastic olfactory bulbs were reported in >50% of individuals with FOXC1 variants compared with 0% of PITX2 variants. Notwithstanding the small sample size, neuroimaging abnormalities were more prevalent in individuals with FOXC1 variants compared those with PITX2 variants.

Systematic review of adherence to the standards for reporting of diagnostic accuracy studies (STARD) 2015 reporting guideline in cerebral aneurysm imaging diagnostic accuracy studies.

BACKGROUND: Diagnostic neuroimaging plays an essential role in guiding clinical decision-making in the management of patients with cerebral aneurysms. Imaging technologies for investigating cerebral aneurysms constantly evolve, and clinicians rely on the published literature to remain up to date. Reporting guidelines have been developed to standardise and strengthen the reporting of clinical evidence. Therefore, it is essential that radiological diagnostic accuracy studies adhere to such guidelines to ensure completeness of reporting. Incomplete reporting hampers the reader's ability to detect bias, determine generalisability of study results or replicate investigation parameters, detracting from the credibility and reliability of studies. OBJECTIVE: The purpose of this systematic review was to evaluate adherence to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) 2015 reporting guideline amongst imaging diagnostic accuracy studies for cerebral aneurysms. METHODS: A systematic search for cerebral aneurysm imaging diagnostic accuracy studies was conducted. Journals were cross examined against the STARD 2015 checklist and their compliance with item numbers was recorded. RESULTS: The search yielded 66 articles. The mean number of STARD items reported was 24.2 ± 2.7 (71.2% ± 7.9%), with a range of 19 to 30 out of a maximum number of 34 items. CONCLUSION: Taken together, these results indicate that adherence to the STARD 2015 guideline in cerebral aneurysm imaging diagnostic accuracy studies was moderate. Measures to improve compliance include mandating STARD 2015 adherence in instructions to authors issued by journals.

Impact of malaria diagnostic choice on monitoring of Plasmodium falciparum prevalence estimates in the Democratic Republic of the Congo and relevance to control programs in high-burden countries.

Malaria programs rely upon a variety of diagnostic assays, including rapid diagnostic tests (RDTs), microscopy, polymerase chain reaction (PCR), and bead-based immunoassays (BBA), to monitor malaria prevalence and support control and elimination efforts. Data comparing these assays are limited, especially from high-burden countries like the Democratic Republic of the Congo (DRC). Using cross-sectional and routine data, we compared diagnostic performance and Plasmodium falciparum prevalence estimates across health areas of varying transmission intensity to illustrate the relevance of assay performance to malaria control programs. Data and samples were collected between March-June 2018 during a cross-sectional household survey across three health areas with low, moderate, and high transmission intensities within Kinshasa Province, DRC. Samples from 1,431 participants were evaluated using RDT, microscopy, PCR, and BBA. P. falciparum parasite prevalence varied between diagnostic methods across all health areas, with the highest prevalence estimates observed in Bu (57.4-72.4% across assays), followed by Kimpoko (32.6-53.2%), and Voix du Peuple (3.1-8.4%). Using latent class analysis to compare these diagnostic methods against an "alloyed gold standard," the most sensitive diagnostic method was BBA in Bu (high prevalence) and Voix du Peuple (low prevalence), while PCR diagnosis was most sensitive in Kimpoko (moderate prevalence). RDTs were consistently the most specific diagnostic method in all health areas. Among 9.0 million people residing in Kinshasa Province in 2018, the estimated P. falciparum prevalence by microscopy, PCR, and BBA were nearly double that of RDT. Comparison of malaria RDT, microscopy, PCR, and BBA results confirmed differences in sensitivity and specificity that varied by endemicity, with PCR and BBA performing best for detecting any P. falciparum infection. Prevalence estimates varied widely depending on assay type for parasite detection. Inherent differences in assay performance should be carefully considered when using community survey and surveillance data to guide policy decisions.

Developmental Outcomes for Children With Unoperated Metopic or Sagittal Craniosynostosis: Findings at 3 and 7 Years From the Craniofacial Collaboration UK.

The Craniofacial Collaboration UK (CC-UK) is a shared initiative with the aim of addressing key limitations in the existing literature and examining the development of homogenous samples of children with craniosynostosis. This article preliminarily describes developmental, behavioral, and cognitive outcomes for children with either metopic synostosis (MS) or sagittal synostosis (SS), who were unoperated and managed conservatively under the CC-UK protocol. A total of 112 patients were included, and assessments conducted at 3 and/or 7 years of age are presented. The majority of unoperated patients were assessed as having mild clinical severity. Findings are broadly consistent with previous work, indicating that the majority of unoperated patients perform within the average ranges across assessments. For unoperated MS patients, higher than expected rates of developmental concerns were seen at 3 years, particularly relating to gross and fine motor skills, and personal social skills. Slightly elevated rates of behavioral concerns relating to hyperactivity and prosocial behavior were also consistently shown. Few developmental issues were found for SS patients at 3 years. Some minor concerns with peer relationships and prosocial behavior at 3 years, and emotional problems at 7 years were shown, but these were inconsistent over time. Cognitive ability in both groups at 7 years seems to be close to average. Overall findings are positive, and future work should build on these findings by recruiting larger samples and examining longer-term outcomes in adolescence and adulthood, to better understand the developmental trajectory of patients with unoperated craniosynostosis.

A current assessment of the THOR 50M in rear impacts.

OBJECTIVE: This study presents a comparison of the Test Device for Human Occupant Restraint (THOR) 50M and Hybrid III (HIII) 50M anthropomorphic test device (ATD) geometries and rear impact head and neck biofidelity to each other and to postmortem human surrogate (PMHS) data to evaluate the usefulness of the THOR in rear impact testing. METHODS: Both ATDs were scanned in a seated position on a rigid bench seat. A series of rear impact sled tests with the rigid bench seat with no head restraint support were conducted with a HIII-50M at 16 and 24 kph. Tests at each speed were performed twice with the THOR-50M to allow an assessment of the repeatability of the THOR-50M. A comparison of the test results from THOR-50M testing were made to the results of a previous study that included PMHS. Rear impact sled tests with both ATDs in a modern seat were then conducted at 40 kph. RESULTS: The THOR-50M head was 48.4 mm rearward and 60.1 mm higher than the HIII-50M head when seated in the rigid bench seat. In the repeated rigid bench testing at 16 and 24 kph, the THOR-50M head longitudinal and vertical accelerations, upper neck moment, and overall kinematics showed good test-to-test repeatability. In the rigid bench tests, the THOR-50M neck experienced flexion prior to extension in the 16 kph tests, where the neck of the HIII only experienced extension. At 24 kph both ATDs only experienced extension. The THOR-50M head displaced more rearward at both test velocities. The rigid bench tests show that the THOR-50M neck allows for more extension motion or articulation than the HIII-50M neck. The rigid bench test also shows that the head longitudinal and vertical accelerations, angular head kinematics, and upper neck moments were reasonably comparable between the ATDs. The THOR-50M results were closer to the average of the PMHS results than the HIII-50-M results, with the exception of the upper neck. In the 40 kph tests, with a modern seat design, the THOR-50M resulted in more deformation of the seatback with greater head restraint loading than the HIII-50M. The THOR-50M head backset distance was less. CONCLUSION: This study provides insight into the differences and similarities between the THOR and the HIII-50M ATD geometries, instrumentation responses, and kinematics, as well as the repeatability of the THOR-50M in rear impacts testing. The overall geometries of the THOR-50M and the HIII-50M are similar. The seated head position of the THOR-50M is slightly further rearward and higher than the HIII-50M. The results indicate that the THOR-50M matches the PMHS results more closely than the HIII-50M and may have improved neck biofidelity in rear impact testing. The results indicate that the studied THOR-50M responses are repeatable within expected test-to-test variations in rear impacts. Early data suggest that the THOR-50M can be used in rear impact testing, though a more complete understanding of the THOR-50M differences to the HIII ATDs will allow for better correlation to the existing body of HIII rear impact testing.

Epigenetic and Genetic Population Structure is Coupled in a Marine Invertebrate.

Delineating the relative influence of genotype and the environment on DNA methylation is critical for characterizing the spectrum of organism fitness as driven by adaptation and phenotypic plasticity. In this study, we integrated genomic and DNA methylation data for two distinct Olympia oyster (Ostrea lurida) populations while controlling for within-generation environmental influences. In addition to providing the first characterization of genome-wide DNA methylation patterns in the oyster genus Ostrea, we identified 3,963 differentially methylated loci between populations. Our results show a clear coupling between genetic and epigenetic patterns of variation, with 27% of variation in interindividual methylation differences explained by genotype. Underlying this association are both direct genetic changes in CpGs (CpG-SNPs) and genetic variation with indirect influence on methylation (mQTLs). When comparing measures of genetic and epigenetic population divergence at specific genomic regions this relationship surprisingly breaks down, which has implications for the methods commonly used to study epigenetic and genetic coupling in marine invertebrates.

Protein microarray allergen profiling in bronchoalveolar lavage fluid and serum of horses with asthma.

BACKGROUND: The diagnostic value of allergen-specific immunoglobulin E (IgE) in horses with asthma is uncertain. A recently developed protein microarray detected abnormally high latex-specific IgE concentrations in the serum of horses with severe asthma. OBJECTIVES: The main objective was to characterize the IgE profiles of asthmatic horses in Switzerland using a protein microarray platform in serum and bronchoalveolar lavage fluid (BALF). The secondary objective was to determine whether serological and BALF allergen-specific IgE concentrations correlated. ANIMALS: Forty-four asthmatic and 39 control horses ≥5 years of age. METHODS: This prospective cross-sectional study investigated the sensitization profiles of horses with asthma compared with environmentally matched healthy controls. Both serum and BALF were analyzed using the protein microarray. Partial least square-discriminant analysis (PLS-DA) was used to identify and rank the importance of the allergens for class detection (ie, asthma vs control), with a variable influence on the projection (VIP) >1 considered significant. RESULTS: The allergens that best discriminated (VIP >1) asthmatic horses from controls were proteins derived from fungi (Aspergillus fumigatus), insects (Culicoides spp.), and latex (Hevea brasiliensis). The serological model predictive ability was markedly inferior (area under the curve [AUC] 0.585, 95% confidence interval [CI]: 0.454-0.747) to that of the BALF (AUC 0.751, 95% CI: 0.582-0.866). The two models shared nine allergens, of which eight showed significant weak to moderate correlations. CONCLUSION AND CLINICAL IMPORTANCE: The concentrations of several allergen-specific IgE were higher in asthmatic horses. The protein microarray performed better on BALF than serum for detection of asthma. Serological IgE concentrations do not closely correlate with BALF concentrations and should be interpreted with caution.

The effect of seatback deformation on out-of-position front-seat occupants in severe rear impacts.

OBJECTIVE: This study assesses the effects of seat deflection in severe oblique rear impacts with laterally out-of-position ATDs where the head is not supported by the head restraint. METHOD: Six high-speed rear sled tests were conducted at 48 km/h with a 195 degree PDOF. A lap-shoulder belted 50th percentile Hybrid III ATD was leaned inboard and seated in six different front passenger seats (A-F); five of the seats were selected from mid-sized sedans and one was a non-production rigidified Seat Integrated Restraint (SIR) seat. FRED-III pull tests resulted in seat stiffnesses that varied from 73 to 172 N/mm. Seat F had the greatest stiffness. The seat and ATD responses were assessed. The biomechanical responses were evaluated and compared to relevant IARVs. RESULTS: In all tests the ATD moved rearward and twisted the seat. There was limited differential motion of the torso relative to the seatback. The ATD position and PDOF prevented head restraint engagement allowing head and neck extension over the seatback. The seatback angle was measured on the inboard side. At maximum yield, it was greatest with Seat E, followed by Seat A and Seat D, at 71, 67 and 62 degrees, respectively. The duration of rearward deformation was also greatest with Seat A, Seat D and Seat E providing longer ride-down. The head, chest and upper neck responses were below IARVs. Lower-neck extension moments were above injury threshold with Seat B, C and F. Seat F had the highest lower-neck moment. CONCLUSION: Seats with greater deformation provided the greatest ride-down durations and the lowest overall biomechanical responses. The combination of high impact severity and lack of head support resulted in high lower-neck responses, highlighting the potential benefit of energy management from deforming seat structures.

Computational Investigation of Ligand Binding of Flavonoids in Cytochrome P450 Receptors.

AIM: The cytochrome P450 enzymes play a significant role in regulating cellular and physiological processes by activating endogenous compounds. They also play an essential role in the detoxification process of xenobiotics. Flavonoids belong to a class of polyphenols found in food, such as vegetables, red wine, beer, and fruits, which modulate biological functions in the body. METHODS: The inhibition of CYP1A1 and CYP1B1 using nutritional sources has been reported as a strategy for cancer prevention. This study investigated the interactions of selected flavonoids binding to the cytochrome P450 enzymes (CYP1A1 and CYP1B1) and their ADMET properties in silico. From docking studies, our findings showed flavonoids, isorhamnetin and pedalitin, to have the strongest binding energies in the crystal structures 6DWM and 6IQ5. RESULTS: The amino acid residues Asp 313 and Phe 224 in 6DWM interacted with all the ligands investigated, and Ala 330 in 6IQ5 interacted with all the ligands examined. The ligands did not violate any drug-likeness parameters. CONCLUSION: These data suggest roles for isorhamnetin and pedalitin as potential precursors for natural product- derived therapies.

Differential DNA methylation in Pacific oyster reproductive tissue in response to ocean acidification.

BACKGROUND: There is a need to investigate mechanisms of phenotypic plasticity in marine invertebrates as negative effects of climate change, like ocean acidification, are experienced by coastal ecosystems. Environmentally-induced changes to the methylome may regulate gene expression, but methylome responses can be species- and tissue-specific. Tissue-specificity has implications for gonad tissue, as gonad-specific methylation patterns may be inherited by offspring. We used the Pacific oyster (Crassostrea gigas) - a model for understanding pH impacts on bivalve molecular physiology due to its genomic resources and importance in global aquaculture- to assess how low pH could impact the gonad methylome. Oysters were exposed to either low pH (7.31 ± 0.02) or ambient pH (7.82 ± 0.02) conditions for 7 weeks. Whole genome bisulfite sequencing was used to identify methylated regions in female oyster gonad samples. C- > T single nucleotide polymorphisms were identified and removed to ensure accurate methylation characterization. RESULTS: Analysis of gonad methylomes revealed a total of 1284 differentially methylated loci (DML) found primarily in genes, with several genes containing multiple DML. Gene ontologies for genes containing DML were involved in development and stress response, suggesting methylation may promote gonad growth homeostasis in low pH conditions. Additionally, several of these genes were associated with cytoskeletal structure regulation, metabolism, and protein ubiquitination - commonly-observed responses to ocean acidification. Comparison of these DML with other Crassostrea spp. exposed to ocean acidification demonstrates that similar pathways, but not identical genes, are impacted by methylation. CONCLUSIONS: Our work suggests DNA methylation may have a regulatory role in gonad and larval development, which would shape adult and offspring responses to low pH stress. Combined with existing molluscan methylome research, our work further supports the need for tissue- and species-specific studies to understand the potential regulatory role of DNA methylation.