Disrupted Maturation of the Microbiota and Metabolome among Extremely Preterm Infants with Postnatal Growth Failure

Growth failure during infancy is a major global problem that has adverse effects on long-term health and neurodevelopment. Preterm infants are disproportionately affected by growth failure and its effects. Herein we found that extremely preterm infants with postnatal growth failure have disrupted maturation of the intestinal microbiota, characterized by persistently low diversity, dominance of pathogenic bacteria within the Enterobacteriaceae family, and a paucity of strictly anaerobic taxa including Veillonella relative to infants with appropriate postnatal growth. Metabolomic profiling of infants with growth failure demonstrated elevated serum acylcarnitines, fatty acids, and other byproducts of lipolysis and fatty acid oxidation. Machine learning algorithms for normal maturation of the microbiota and metabolome among infants with appropriate growth revealed a pattern of delayed maturation of the microbiota and metabolome among infants with growth failure. Collectively, we identified novel microbial and metabolic features of growth failure in preterm infants and potentially modifiable targets for intervention

Hypothyroidism and the risk of lower extremity arterial disease

Background: Although an independent association between hypothyroidism and coronary artery disease has been demonstrated, few studies have examined the association between hypo-thyroidism and peripheral arterial disease. In the current study, we test the hypothesis that there is an independent association between hypothyroidism and lower extremity arterial disease. Methods: We retrospectively compared the prevalence of hypothyroidism in patients who had infra-inguinal arterial bypass surgery over a 6-year period with that of a control group of surgical patients who had pure cardiac valve surgery during the same time period. Both unadjusted and adjusted odds ratios were calculated to estimate the association between hypothyroidism and lower extremity arterial disease. Results: A total of 614 cases and 529 control subjects had surgery during the study period. When comparing all subjects, there was no association between hypothyroidism and lower extremity arterial disease (unadjusted odds ratio 0.88; 95% confidence intervals [CI]: 0.61-1.28). However, gender was found to be a significant effect modifier (P \u3c 0.001), and gender-stratified analyses were subsequently performed. In men, there was a positive independent association between hypothyroidism and lower extremity arterial disease (adjusted odds ratio 2.65; 95% CI: 1.19-5.89), whereas in women there was a negative independent association (adjusted odds ratio 0.22; 95% CI: 0.11-0.46). Conclusions: Gender is a significant effect modifier for the association between hypothyroidism and lower extremity arterial disease. The association is positive in men and negative in women. Future prospective studies that evaluate hypothyroidism as a risk factor for peripheral arterial disease should consider gender stratification in order to corroborate this finding. © 2010 Mazzeffi et al, publisher and licensee Dove Medical Press Ltd

Inertial Imaging with Nanomechanical Systems

Mass sensing with nanoelectromechanical systems has advanced significantly during the last decade. With nanoelectromechanical systems sensors it is now possible to carry out ultrasensitive detection of gaseous analytes, to achieve atomic-scale mass resolution and to perform mass spectrometry on single proteins. Here, we demonstrate that the spatial distribution of mass within an individual analyte can be imaged—in real time and at the molecular scale—when it adsorbs onto a nanomechanical resonator. Each single-molecule adsorption event induces discrete, time-correlated perturbations to all modal frequencies of the device. We show that by continuously monitoring a multiplicity of vibrational modes, the spatial moments of mass distribution can be deduced for individual analytes, one-by-one, as they adsorb. We validate this method for inertial imaging, using both experimental measurements of multimode frequency shifts and numerical simulations, to analyse the inertial mass, position of adsorption and the size and shape of individual analytes. Unlike conventional imaging, the minimum analyte size detectable through nanomechanical inertial imaging is not limited by wavelength-dependent diffraction phenomena. Instead, frequency fluctuation processes determine the ultimate attainable resolution. Advanced nanoelectromechanical devices appear capable of resolving molecular-scale analytes

Web-based technologies to support carers of people living with dementia:a protocol for a mixed methods stepped-wedge cluster randomized controlled trial

BACKGROUND: Informal carers play a significant role in supporting people living with dementia; however, carers in rural areas are often isolated, with limited access to support services. Although dementia-friendly communities provide valued support for carers, access to them is limited as they are few and geographically dispersed. OBJECTIVE: This study’s aim was to increase support and services for rural informal carers of people living with dementia by using information and communication technologies accessed through an integrated website and mobile app—the Verily Connect app. The objective of this protocol is to detail the research design used in a complex study that was situated in a challenging real-world setting integrating web-based and on-ground technology and communication. Therefore, it is anticipated that this protocol will strengthen the research of others exploring similar complex concepts. METHODS: A stepped-wedge, open-cohort cluster randomized controlled trial was conducted to implement Verily Connect across 12 rural Australian communities. The Verily Connect intervention delivered web-based, curated information about dementia, a localized directory of dementia services and support, group and individual chat forums, and peer support through videoconference. During the implementation phase of 32 weeks, Verily Connect was progressively implemented in four 8-weekly waves of 3 communities per wave. Usual care, used as a comparator, was available to carers throughout the study period. Participants and researchers were unblinded to the intervention. There were 3 cohorts of participants: carers, volunteers, and staff; participants were recruited from their communities. The primary outcome measure was perceived carer social support measured using the Medical Outcomes Study-Social Support Survey. Volunteers and staff provided feedback on their participation in Verily Connect as qualitative data. Qualitative data were collected from all cohorts of participants through interviews and focus groups. Process evaluation data were collected through interviews and memos written by research staff. Data on the costs of implementing Verily Connect were collected by the research team members and evaluated by a health economist. RESULTS: Between August 2018 and September 2019, a total of 113 participants were recruited. There were 37 (32.7%) carers, 39 (34.5%) volunteers, and 37 (32.7%) health service staff. The study was complex because of the involvement of multiple and varied communities of carers, volunteers, health service staff, and research team members originating from 5 universities. Web-based technologies were used as intervention strategies to support carers and facilitate the process of undertaking the study. CONCLUSIONS: The Verily Connect trial enabled the testing and further development of a web-based approach to increasing support for carers of people living with dementia across a diverse rural landscape in Australia. This protocol provides an example of how to conduct a pragmatic evaluation of a complex and co-designed intervention involving multiple stakeholders. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618001213235; https://tinyurl.com/4rjvrasf INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/3302

Reciprocal Interactions of Pit1 and GATA2 Mediate Signaling Gradient–Induced Determination of Pituitary Cell Types

AbstractThe mechanisms by which transient gradients of signaling molecules lead to emergence of specific cell types remain a central question in mammalian organogenesis. Here, we demonstrate that the appearance of four ventral pituitary cell types is mediated via the reciprocal interactions of two transcription factors, Pit1 and GATA2, which are epistatic to the remainder of the cell type–specific transcription programs and serve as the molecular memory of the transient signaling events. Unexpectedly, this program includes a DNA binding–independent function of Pit1, suppressing the ventral GATA2-dependent gonadotrope program by inhibiting GATA2 binding to gonadotrope- but not thyrotrope-specific genes, indicating that both DNA binding–dependent and –independent actions of abundant determining factors contribute to generate distinct cell phenotypes

Exploring wearable sensors as an alternative to marker-based motion capture in the pitching delivery

Background Improvements in data processing, increased understanding of the biomechanical background behind kinetics and kinematics, and technological advancements in inertial measurement unit (IMU) sensors have enabled high precision in the measurement of joint angles and acceleration on human subjects. This has resulted in new devices that reportedly measure joint angles, arm speed, and stresses to the pitching arms of baseball players. This study seeks to validate one such sensor, the MotusBASEBALL unit, with a marker-based motion capture laboratory. Hypothesis We hypothesize that the joint angle measurements (“arm slot” and “shoulder rotation”) of the MotusBASEBALL device will hold a statistically significant level of reliability and accuracy, but that the “arm speed” and “stress” metrics will not be accurate due to limitations in IMU technology. Methods A total of 10 healthy subjects threw five to seven fastballs followed by five to seven breaking pitches (slider or curveball) in the motion capture lab. Subjects wore retroreflective markers and the MotusBASEBALL sensor simultaneously. Results It was found that the arm slot (R = 0.975, P < 0.001), shoulder rotation (R = 0.749, P < 0.001), and stress (R = 0.667, P = 0.001 when compared to elbow torque; R = 0.653, P = 0.002 when compared to shoulder torque) measurements were all significantly correlated with the results from the motion capture lab. Arm speed showed significant correlations to shoulder internal rotation speed (R = 0.668, P = 0.001) and shoulder velocity magnitude (R = 0.659, P = 0.002). For the entire sample, arm slot and shoulder rotation measurements were on a similar scale, or within 5–15% in absolute value, of magnitude to measurements from the motion capture test, averaging eight degrees less (12.9% relative differences) and nine degrees (5.4%) less, respectively. Arm speed had a much larger difference, averaging 3,745 deg/s (80.2%) lower than shoulder internal rotation velocity, and 3,891 deg/s (80.8%) less than the shoulder velocity magnitude. The stress metric was found to be 41 Newton meter (Nm; 38.7%) less when compared to elbow torque, and 42 Nm (39.3%) less when compared to shoulder torque. Despite the differences in magnitude, the correlations were extremely strong, indicating that the MotusBASEBALL sensor had high reliability for casual use. Conclusion This study attempts to validate the use of the MotusBASEBALL for future studies that look at the arm slot, shoulder rotation, arm speed, and stress measurements from the MotusBASEBALL sensor. Excepting elbow extension velocity, all metrics from the MotusBASEBALL unit showed significant correlations to their corresponding metrics from motion capture and while some magnitudes differ substantially and therefore fall short in validity, the link between the metrics is strong enough to indicate reliable casual use. Further research should be done to further investigate the validity and reliability of the arm speed metric

A baseline for the genetic stock identification of Atlantic herring, Clupea harengus, in ICES Divisions 6.a, 7.b-c

Atlantic herring in International Council for Exploration of the Sea (ICES) Divisions 6.a, 7.b-c comprises at least three populations, distinguished by temporal and spatial differences in spawning, which have until recently been managed as two stocks defined by geographical delineators. Outside of spawning the populations form mixed aggregations, which are the subject of acoustic surveys. The inability to distinguish the populations has prevented the development of separate survey indices and separate stock assessments. A panel of 45 single-nucleotide polymorphisms, derived from whole-genome sequencing, were used to genotype 3480 baseline spawning samples (2014-2021). A temporally stable baseline comprising 2316 herring from populations known to inhabit Division 6.a was used to develop a genetic assignment method, with a self-assignment accuracy greater than 90%. The long-term temporal stability of the assignment model was validated by assigning archive (2003-2004) baseline samples (270 individuals) with a high level of accuracy. Assignment of non-baseline samples (1514 individuals) from Divisions 6.a, 7.b-c indicated previously unrecognized levels of mixing of populations outside of the spawning season. The genetic markers and assignment models presented constitute a 'toolbox' that can be used for the assignment of herring caught in mixed survey and commercial catches in Division 6.a into their population of origin with a high level of accuracy

Eph-Dependent Tyrosine Phosphorylation of Ephexin1 Modulates Growth Cone Collapse

SummaryEphs regulate growth cone repulsion, a process controlled by the actin cytoskeleton. The guanine nucleotide exchange factor (GEF) ephexin1 interacts with EphA4 and has been suggested to mediate the effect of EphA on the activity of Rho GTPases, key regulators of the cytoskeleton and axon guidance. Using cultured ephexin1−/− mouse neurons and RNA interference in the chick, we report that ephexin1 is required for normal axon outgrowth and ephrin-dependent axon repulsion. Ephexin1 becomes tyrosine phosphorylated in response to EphA signaling in neurons, and this phosphorylation event is required for growth cone collapse. Tyrosine phosphorylation of ephexin1 enhances ephexin1’s GEF activity toward RhoA while not altering its activity toward Rac1 or Cdc42, thus changing the balance of GTPase activities. These findings reveal that ephexin1 plays a role in axon guidance and is regulated by a switch mechanism that is specifically tailored to control Eph-mediated growth cone collapse

Using H-alpha Morphology and Surface Brightness Fluctuations to Age-Date Star Clusters in M83

We use new WFC3 observations of the nearby grand design spiral galaxy M83 to develop two independent methods for estimating the ages of young star clusters. The first method uses the physical extent and morphology of Halpha emission to estimate the ages of clusters younger than tau ~10 Myr. It is based on the simple premise that the gas in very young (tau < few Myr) clusters is largely coincident with the cluster stars, is in a small, ring-like structure surrounding the stars in slightly older clusters (e.g., tau ~5 Myr), and is in a larger ring-like bubble for still older clusters (i.e., ~5-10 Myr). The second method is based on an observed relation between pixel-to-pixel flux variations within clusters and their ages. This method relies on the fact that the brightest individual stars in a cluster are most prominent at ages around 10 Myr, and fall below the detection limit (i.e., M_V < -3.5) for ages older than about 100 Myr. These two methods are the basis for a new morphological classification system which can be used to estimate the ages of star clusters based on their appearance. We compare previous age estimates of clusters in M83 determined from fitting UBVI Halpha measurements using predictions from stellar evolutionary models with our new morphological categories and find good agreement at the ~95% level. The scatter within categories is ~0.1 dex in log tau for young clusters (10 Myr) clusters. A by-product of this study is the identification of 22 "single-star" HII regions in M83, with central stars having ages ~4 Myr.Comment: 33 pages, 10 figures, 3 tables; published in March Ap

Ultraviolet Signposts of Resonant Dynamics in the Starburst-Ringed Sab Galaxy, M94 (NGC 4736)

M94 (NGC 4736) is investigated using images from the Ultraviolet Imaging Telescope (FUV-band), Hubble Space Telescope (NUV-band), Kitt Peak 0.9-m telescope (H-alpha, R, and I bands), and Palomar 5-m telescope (B-band), along with spectra from the International Ultraviolet Explorer and Lick 1-m telescopes. The wide-field UIT image shows FUV emission from (a) an elongated nucleus, (b) a diffuse inner disk, where H-alpha is observed in absorption, (c) a bright inner ring of H II regions at the perimeter of the inner disk (R = 48 arcsec. = 1.1 kpc), and (d) two 500-pc size knots of hot stars exterior to the ring on diametrically opposite sides of the nucleus (R= 130 arcsec. = 2.9 kpc). The HST/FOC image resolves the NUV emission from the nuclear region into a bright core and a faint 20 arcsec. long ``mini-bar'' at a position angle of 30 deg. Optical and IUE spectroscopy of the nucleus and diffuse inner disk indicates an approximately 10^7 or 10^8 yr-old stellar population from low-level starbirth activity blended with some LINER activity. Analysis of the H-alpha, FUV, NUV, B, R, and I-band emission along with other observed tracers of stars and gas in M94 indicates that most of the star formation is being orchestrated via ring-bar dynamics involving the nuclear mini-bar, inner ring, oval disk, and outer ring. The inner starburst ring and bi-symmetric knots at intermediate radius, in particular, argue for bar-mediated resonances as the primary drivers of evolution in M94 at the present epoch. Similar processes may be governing the evolution of the ``core-dominated'' galaxies that have been observed at high redshift. The gravitationally-lensed ``Pretzel Galaxy'' (0024+1654) at a redshift of approximately 1.5 provides an important precedent in this regard.Comment: revised figure 1 (corrected coordinate labels on declination axis); 19 pages of text + 19 figures (jpg files); accepted for publication in A