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Abstract A group of highly experienced pilots performed full-motion, simulated T-38 landings before and after extended missions aboard the International Space Station (ISS). On the day of return from the ISS pilots’ performance was degraded on the initial landing attempt, with difficulty maintaining altitude during banking turns and navigational errors, which affected touchdown parameters such as touchdown speed, height over runway threshold and touchdown distance from the runway threshold. A positive result was that all pilots successfully completed a second landing attempt on the same day, suggesting a rapid recovery of performance once exposed to the task at hand. These results are consistent with a previous study that demonstrated significant deficits in post-flight driving performance, and both the pilot and driver subjects’ performance recovered to pre-flight levels within four days of return from the ISS. We propose that the primary factors underlying the post-flight performance deficits were the inability to respond appropriately to gravitational and visual tilts and a reduction in multitasking ability.

This study explored measures of subjective and objective sleep health and the association with fall occurrence and falls risk for older adults. A longitudinal observational study was conducted with participants in residential aged care (n = 36) and community dwelling (n = 35) settings. At baseline, objective sleep data involved wearing wrist worn accelerometers and measuring falls risk by walking using the Quantitative timed up and go (QTUG) of a simple, cognitive, and motor task. Subjective sleep data was collected by completing sleep diaries using the Karolinska Sleepiness Scale and sleep quality scale, respectively. Longitudinal falls data were collected at baseline, 3, 6, and 9 months. Falls risk was calculated via QTUG. Responses to a fall questionnaire were used to quantify fall occurrence. Independent samples t -test examined differences in objective and subjective sleep variables between settings. Logistic regression explored whether objective or subjective sleep variables could predict an overall fall occurrence. Linear regression determined if a particular sleep variable could predict an overall falls risk. Multiple regression determined if sleep variables could predict falls risk. No significant differences were found between residential and community-dwelling adults in subjective or objective sleep measures. Logistic regression showed no significant associations between most sleep variables and falls risk, except for average awakening length, where each additional minute was associated with a 1.8% increase in fall likelihood (OR = 1.02, 95% CI [1.00-1.03], P = .037). Conversely, higher awakening frequency was associated with reduced falls risk in the simple timed up-and-go task ( R ² = .21, β = −.69, P = .009, 95% CI [−1.20 to −0.18]). Findings suggest no significant differences in sleep health or falls risk between residential and community-dwelling older adults, though specific sleep disruptions showed minor associations with falls risk.

Ultra-processed food consumption has increased worldwide, but associations with cancer risk remain unclear and potential underlying mechanisms are speculative. A robust, multidisciplinary, research agenda is needed to address current research limitations and gaps.

Abstract Background Filar cysts are frequently found on neonatal ultrasound and are physiologically involuting structures with natural resolution. Hence, there has been no previous histologic correlation. Ventriculus terminalis is a focal central canal dilation in the conus medullaris and usually not clinically significant. Extra-axial cyst at the conus–filum junction connected to ventriculus terminalis is extremely rare, especially when associated with tethered lipomatous filum terminale and with progressive cyst enlargement. Case presentation A Caucasian female neonate with abnormal gluteal cleft had ventriculus terminalis cyst with an extra-axial cyst at the conus–filar junction and taut lipomatous filum on ultrasound examination and magnetic resonance imaging. This persisted at 6-month follow up imaging. In light of the nonresolving extra-axial mass and thick taut lipomatous filum, the child underwent L1–L3 osteoplastic laminectomies. The extra-axial cyst expanded after bony decompression and furthermore on dural opening; visualized on ultrasound. It communicated with the central canal and was documented with intraoperative photomicrographs. It was excised and filum sectioned. Histological immunostaining of the cyst wall showed neuroglial and axonal elements. The child did well without deficits at 4-year follow up with normal urodynamics. Conclusion Progression dilation of ventriculus terminalis and extra-axial conofilar cyst with tethered lipomatous filum will likely progress to clinical significance and require surgical intervention. The embryologic basis for this pathology is discussed, with literature review.

Background: Exposures to perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), environmentally persistent chemicals detectable in the blood of most Americans, have been associated with several health outcomes. To offer insight into their possible biologic effects, we evaluated the metabolomic correlates of circulating PFOS and PFOA among 3,647 participants in eight nested case-control serum metabolomic profiling studies from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Methods: Metabolomic profiling was conducted by Metabolon Inc., using ultra high-performance liquid chromatography/tandem accurate mass spectrometry. We conducted study-specific multivariable linear regression analyses estimating the associations of metabolite levels with levels of PFOS or PFOA. For metabolites measured in at least 3 of 8 nested case-control studies, random effects meta-analysis was used to summarize study-specific results (1,038 metabolites in PFOS analyses and 1,100 in PFOA analyses). Results: The meta-analysis identified 51 and 38 metabolites associated with PFOS and PFOA, respectively, at a Bonferroni-corrected significance level (4.8x10-5 and 4.6x10-5, respectively). For both PFOS and PFOA, the most common types of associated metabolites were lipids (sphingolipids, fatty acid metabolites) and xenobiotics (xanthine metabolites, chemicals). Positive associations were commonly observed with lipid metabolites sphingomyelin (d18:1/18:0) (P = 2.0x10-10 and 2.0x10-8, respectively), 3-carboxy-4-methyl-5-pentyl-2-furanpropionate (P = 2.7x10-15, 1.1x10-17), and lignoceroylcarnitine (C24) (P = 2.6x10-8, 6.2x10-6). The strongest positive associations were observed for chemicals 3,5-dichloro-2,6-dihydroxybenzoic acid (P = 3.0x10-112 and 6.8x10-13, respectively) and 3-bromo-5-chloro-2,6-dihydroxybenzoic acid (P = 1.6x10-14, 2.3x10-6). Other metabolites positively associated with PFOS included D-glucose (carbohydrate), carotene diol (vitamin A metabolism), and L-alpha-aminobutyric acid (glutathione metabolism), while uric acid (purine metabolite) was positively associated with PFOA. PFOS associations were consistent even after adjusting for PFOA as a covariate, while PFOA associations were greatly attenuated with PFOS adjustment. Conclusions: In this large metabolomic study, we observed robust positive associations with PFOS for several molecules. Further investigation of these metabolites may offer insight into PFOS-related biologic effects.

Background: Health sciences libraries in medical schools, academic health centers, health care networks, and hospitals have established institutional repositories (IRs) to showcase their research achievements, increase visibility, expand the reach of institutional scholarship, and disseminate unique content. Newer roles for IRs include publishing open access journals, tracking researcher productivity, and serving as repositories for data sharing. Many repository managers oversee their IR with limited assistance from others at their institution. Therefore, IR practitioners find it valuable to network and learn from colleagues at other institutions. Case Presentation: This case report describes the genesis and implementation of a new initiative specifically designed for a health sciences audience: the Medical Institutional Repositories in Libraries (MIRL) Symposium. Six medical librarians from hospitals and academic institutions in the U.S. organized the inaugural symposium held virtually in November 2021. The goal was to fill a perceived gap in conference programming for IR practitioners in health settings. Themes of the 2021 and subsequent 2022 symposium included IR management, increasing readership and engagement, and platform migration. Post-symposium surveys were completed by 73/238 attendees (31%) in 2021 and by 62/180 (34%) in 2022. Feedback was overwhelmingly positive. Discussion: Participant responses in post-symposium surveys rated MIRL highly. The MIRL planning group intends to continue the symposium and hopes MIRL will steadily evolve, build community among IR practitioners in the health sciences, and expand the conversation around best practices for digital archiving of institutional content. The implementation design of MIRL serves as a blueprint for collaboratively bringing together a professional community of practice.

Abstract The descriptions of muscle pathology in dysferlinopathy patients have classically included an inflammatory infiltrate that can mimic inflammatory myopathies. Based on over 20 years of institutional experience in evaluating dystrophic and inflammatory myopathy muscle biopsies at the University of Iowa, we hypothesized the inflammatory histopathology of dysferlinopathy is more similar to limb-girdle pattern muscular dystrophies such as calpainopathy and Becker muscular dystrophy, and distinct from true inflammatory myopathies. Muscle biopsies from 32 dysferlinopathy, 30 calpainopathy, 30 Becker muscular dystrophy, and 30 inflammatory myopathies (15 each of dermatomyositis and inclusion body myositis) were analyzed through digital quantitation of CD3, CD4, CD8, CD20, and PU.1 immunostaining. The expression of MHC class I and deposition of complement C5b-9 was also evaluated. Dysferlinopathy, calpainopathy, and Becker muscular dystrophy muscle biopsies had similar numbers of inflammatory cell infiltrates and significantly fewer CD3+ T-lymphocytes than dermatomyositis (p = 0.05) and inclusion body myositis (p

Abstract The use of autonomous recordings of animal sounds to detect species is a popular conservation tool, constantly improving in fidelity as audio hardware and software evolves. Current classification algorithms utilise sound features extracted from the recording rather than the sound itself, with varying degrees of success. Neural networks that learn directly from the raw sound waveforms have been implemented in human speech recognition but the requirements of detailed labelled data have limited their use in bioacoustics. Here we test SincNet, an efficient neural network architecture that learns from the raw waveform using sinc-based filters. Results using an off-the-shelf implementation of SincNet on a publicly available bird sound dataset (NIPS4Bplus) show that the neural network rapidly converged reaching accuracies of over 65% with limited data. Their performance is comparable with traditional methods after hyperparameter tuning but they are more efficient. Learning directly from the raw waveform allows the algorithm to select automatically those elements of the sound that are best suited for the task, bypassing the onerous task of selecting feature extraction techniques and reducing possible biases. We use publicly released code and datasets to encourage others to replicate our results and to apply SincNet to their own datasets; and we review possible enhancements in the hope that algorithms that learn from the raw waveform will become useful bioacoustic tools.

Dominant mutations in serine palmitoyltransferase long chain base subunit 1 (SPTLC1), a known cause of hereditary sensory autonomic neuropathy type 1 (HSAN1), are a recently identified cause of juvenile amyotrophic lateral sclerosis (JALS) with slow progression. We present a case of SPTLC1-associated JALS followed for 30 years. She was initially evaluated at age 22 years for upper extremity weakness. She experienced gradual decline in muscle strength with development of weakness and hyperreflexia in lower extremities and diffuse fasciculations in the upper extremities at 26 years. She lost independent ambulation at age 45 years. Pulmonary function declined from a forced vital capacity of 94% predicted at 27 years to 49% predicted at 47 years, and she was hospitalized twice for respiratory failure. To our knowledge, this is the longest documented follow-up period of JALS caused by a de novo pathogenic variant in SPTLC1.

Barrier-to-autointegration factor (BAF) is an essential component of the nuclear lamina. Encoded by BANF1, this DNA binding protein contributes to the regulation of gene expression, cell cycle progression, and nuclear integrity. A rare recessive BAF variant, Ala12Thr, causes the premature aging syndrome, Néstor–Guillermo progeria syndrome (NGPS). Here, we report the first dominant pathogenic BAF variant, Gly16Arg, identified in a patient presenting with progressive neuromuscular weakness. Although disease variants carry nearby amino acid substitutions, cellular and biochemical properties are distinct. In contrast to NGPS, Gly16Arg patient fibroblasts show modest changes in nuclear lamina structure and increases in repressive marks associated with heterochromatin. Structural studies reveal that the Gly16Arg substitution introduces a salt bridge between BAF monomers, reducing the conformation ensemble available to BAF. We show that this structural change increases the double-stranded DNA binding affinity of BAF Gly16Arg. Together, our findings suggest that BAF Gly16Arg has an increased chromatin occupancy that leads to epigenetic changes and impacts nuclear functions. These observations provide a new example of how a missense mutation can change a protein conformational equilibrium to cause a dominant disease and extend our understanding of mechanisms by which BAF function impacts human health.

Televised public service announcements were one of the ways that the U.S. federal government distributed health information about the COVID-19 pandemic to Americans in 2020. However, little is known about the reach of these campaigns or the populations who might have been exposed to the information these ads conveyed. We conducted a descriptive analysis of federally-affiliated public service announcement airings to assess where they were aired and the market-level social and demographic characteristics associated with the airings. We found no correspondence between airings and COVID-19 incidence rates from March to December 2020, but we found a positive association between airings and the Democratic vote share of the market, adjusting for other market demographic characteristics. Our results suggest that PSAs may have contributed to divergent exposure to health information among the U.S. public during the first year of the COVID-19 pandemic.

Background: In the US in 2021, 76,080 kidney cancers are expected and >80% are renal cell carcinomas (RCCs). Along with excess fat, metabolic dysfunction is implicated in RCC etiology. To identify RCC-associated metabolites, we conducted a 1:1 matched case–control study nested within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Methods: We measured 522 serum metabolites in 267 cases/control pairs. Cases were followed for a median 7.1 years from blood draw to diagnosis. Using conditional logistic regression, we computed adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing risk between 90th and 10th percentiles of log metabolite intensity, with the significance threshold at a false discovery rate Results: Four metabolites were inversely associated with risk of RCC during follow-up—C38:4 PI, C34:0 PC, C14:0 SM, and C16:1 SM (ORs ranging from 0.33–0.44). Two were positively associated with RCC risk—C3-DC-CH3 carnitine and C5 carnitine (ORs = 2.84 and 2.83, respectively). These results were robust when further adjusted for metabolic risk factors (body mass index (BMI), physical activity, diabetes/hypertension history). Metabolites associated with RCC had weak correlations (|r| < 0.2) with risk factors of BMI, physical activity, smoking, alcohol, and diabetes/hypertension history. In mutually adjusted models, three metabolites (C38:4 PI, C14:0 SM, and C3-DC-CH3 carnitine) were independently associated with RCC risk. Conclusions: Serum concentrations of six metabolites were associated with RCC risk, and three of these had independent associations from the mutually adjusted model. These metabolites may point toward new biological pathways of relevance to this malignancy.

Abstract Background Metabolomics is emerging as an important tool for detecting differences between diseased and non-diseased individuals. However, prospective studies are limited. Methods We examined the detectability, reliability, and distribution of metabolites measured in pre-diagnostic plasma samples in a pilot study of women enrolled in the Northern California site of the Breast Cancer Family Registry. The study included 45 cases diagnosed with breast cancer at least one year after the blood draw, and 45 controls. Controls were matched on age (within 5 years), family status, BRCA status, and menopausal status. Duplicate samples were included for reliability assessment. We used a liquid chromatography/gas chromatography mass spectrometer platform to measure metabolites. We calculated intraclass correlations (ICCs) among duplicate samples, and coefficients of variation (CVs) across metabolites. Results Of the 661 named metabolites detected, 338 (51%) were found in all samples, and 490 (74%) in more than 80% of samples. The median ICC between duplicates was 0.96 (25th – 75th percentile: 0.82–0.99). We observed a greater than 20% case-control difference in 24 metabolites (p

Abstract Background Transport protein particle (TRAPP) is a supramolecular protein complex that functions in localizing proteins to the Golgi compartment. The TRAPPC11 subunit has been implicated in muscle disease by virtue of homozygous and compound heterozygous deleterious mutations being identified in individuals with limb girdle muscular dystrophy and congenital muscular dystrophy. It remains unclear how this protein leads to muscle disease. Furthermore, a role for this protein, or any other membrane trafficking protein, in the etiology of the dystroglycanopathy group of muscular dystrophies has yet to be found. Here, using a multidisciplinary approach including genetics, immunofluorescence, western blotting, and live cell analysis, we implicate both TRAPPC11 and another membrane trafficking protein, GOSR2, in α-dystroglycan hypoglycosylation. Case presentation Subject 1 presented with severe epileptic episodes and subsequent developmental deterioration. Upon clinical evaluation she was found to have brain, eye, and liver abnormalities. Her serum aminotransferases and creatine kinase were abnormally high. Subjects 2 and 3 are siblings from a family unrelated to subject 1. Both siblings displayed hypotonia, muscle weakness, low muscle bulk, and elevated creatine kinase levels. Subject 3 also developed a seizure disorder. Muscle biopsies from subjects 1 and 3 were severely dystrophic with abnormal immunofluorescence and western blotting indicative of α-dystroglycan hypoglycosylation. Compound heterozygous mutations in TRAPPC11 were identified in subject 1: c.851A>C and c.965+5G>T. Cellular biological analyses on fibroblasts confirmed abnormal membrane trafficking. Subject 3 was found to have compound heterozygous mutations in GOSR2: c.430G>T and c.2T>G. Cellular biological analyses on fibroblasts from subject 3 using two different model cargo proteins did not reveal defects in protein transport. No mutations were found in any of the genes currently known to cause dystroglycanopathy in either individual. Conclusion Recessive mutations in TRAPPC11 and GOSR2 are associated with congenital muscular dystrophy and hypoglycosylation of α-dystroglycan. This is the first report linking membrane trafficking proteins to dystroglycanopathy and suggests that these genes should be considered in the diagnostic evaluation of patients with congenital muscular dystrophy and dystroglycanopathy.

Self-sensing techniques for atomic force microscope (AFM) cantilevers have several advantageous characteristics compared to the optical beam deflection method. The possibility of down scaling, parallelization of cantilever arrays and the absence of optical interference associated imaging artifacts have led to an increased research interest in these methods. However, for multifrequency AFM, the optimization of the transducer layout on the cantilever for higher order modes has not been addressed. To fully utilize an integrated piezoelectric transducer, this work alters the layout of the piezoelectric layer to maximize both the deflection of the cantilever and measured piezoelectric charge response for a given mode with respect to the spatial distribution of the strain. On a prototype cantilever design, significant increases in actuator and sensor sensitivities were achieved for the first four modes without any substantial increase in sensor noise. The transduction mechanism is specifically targeted at multifrequency AFM and has the potential to provide higher resolution imaging on higher order modes.