Development of properly-polarized trophoblast stem cell-derived organoids to model early human pregnancy.

The development of human trophoblast stem cells (hTSC) and stem cell-derived trophoblast organoids has enabled investigation of placental physiology and disease and early maternal-fetal interactions during a stage of human pregnancy that previously had been severely restricted. A key shortcoming in existing trophoblast organoid methodologies is the non-physiologic position of the syncytiotrophoblast (STB) within the inner portion of the organoid, which neither recapitulates placental villous morphology in vivo nor allows for facile modeling of STB exposure to the endometrium or the contents of the intervillous space. Here we have successfully established properly-polarized human trophoblast stem cell (hTSC)-sourced organoids with STB forming on the surface of the organoid. These organoids can also be induced to give rise to the extravillous trophoblast (EVT) lineage with HLA-G + migratory cells that invade into an extracellular matrix-based hydrogel. Compared to previous hTSC organoid methods, organoids created by this method more closely mimic the architecture of the developing human placenta and provide a novel platform to study normal and abnormal human placental development and to model exposures to pharmaceuticals, pathogens and environmental insults. Motivation: Human placental organoids have been generated to mimic physiological cell-cell interactions. However, those published models derived from human trophoblast stem cells (hTSCs) or placental villi display a non-physiologic "inside-out" morphology. In vivo , the placental villi have an outer layer of syncytialized cells that are in direct contact with maternal blood, acting as a conduit for gas and nutrient exchange, and an inner layer of progenitor, single cytotrophoblast cells that fuse to create the syncytiotrophoblast layer. Existing "inside-out" models put the cytotrophoblast cells in contact with culture media and substrate, making physiologic interactions between syncytiotrophoblast and other cells/tissues and normal and pathogenic exposures coming from maternal blood difficult to model. The goal of this study was to develop an hTSC-derived 3-D human trophoblast organoid model that positions the syncytiotrophoblast layer on the outside of the multicellular organoid.

A pilot study to assess the impact of aboriginal and torres strait islander cultural humility webinars on australian medical school students.

BACKGROUND: The Aboriginal and Torres Strait Islander Health Curriculum Framework helps higher education providers to deliver safe and well-informed cultural humility education. However, there is currently a scarcity of evidence surrounding the efficacy and impact of cultural humility education. This study will use qualitative and quantitative research methods to evaluate learning outcomes from an Indigenous health educational webinar aimed at Australian medical students. METHODS: A pilot study was conducted following a group of Australian medical students who attended an educational Indigenous health (IH) culturally responsive webinar. Recruitment was conducted via the webinar hosts' social media pages. Quantitative methods involved sending one pre- and two post-webinar questionnaires to attendees. To assess participants' retention of information, one post-webinar survey was sent out immediately after the webinar and another three months after the webinar. These questionnaires were designed to reflect pre-determined learning objectives for the webinar. Qualitative methods involved a focus group discussion to identify common themes from participant feedback. RESULTS: Twenty-six participants were included in the final quantitative analysis. Most of the participants were clinical students between 18 and 24 years old who did not identify as Aboriginal and/or Torres Strait Islander. There was a significant increase (p = 0.007) between pre-intervention (M = 0.35, SD = 0.26) and post-webinar knowledge for the learning outcome exploring the links between health and education (M = 047, SD = 0.25). No results were obtained from the three months post-intervention questionnaire. The qualitative analysis synthesized feedback from three participants and identified presenter delivery style as an important mediator of webinar effectiveness. CONCLUSIONS: There was a significant increase in knowledge and understanding for the learning outcome that explored the links between health and education. We attribute this partly to the engaging and conversational delivery style of the webinar presenters. The importance of Indigenous facilitators that encourage reflective teaching should not be understated. Our results suggest that cultural humility webinars can have a positive impact on medical students' understanding of the Aboriginal and/or Torres Strait Islander health landscape. This pilot study warrants further research on a larger population.

Capnodynamic monitoring of lung volume and pulmonary blood flow during alveolar recruitment: a prospective observational study in postoperative cardiac patients.

Alveolar recruitment manoeuvres may mitigate ventilation and perfusion mismatch after cardiac surgery. Monitoring the efficacy of recruitment manoeuvres should provide concurrent information on pulmonary and cardiac changes. This study in postoperative cardiac patients applied capnodynamic monitoring of changes in end-expiratory lung volume and effective pulmonary blood flow. Alveolar recruitment was performed by incremental increases in positive end-expiratory pressure (PEEP) to a maximum of 15 cmH2O from a baseline of 5 cmH2O over 30 min. The change in systemic oxygen delivery index after the recruitment manoeuvre was used to identify responders (> 10% increase) with all other changes (≤ 10%) denoting non-responders. Mixed factor ANOVA using Bonferroni correction for multiple comparisons was used to denote significant changes (p < 0.05) reported as mean differences and 95% CI. Changes in end-expiratory lung volume and effective pulmonary blood flow were correlated using Pearson's regression. Twenty-seven (42%) of 64 patients were responders increasing oxygen delivery index by 172 (95% CI 61-2984) mL min-1 m-2 (p < 0.001). End-expiratory lung volume increased by 549 (95% CI 220-1116) mL (p = 0.042) in responders associated with an increase in effective pulmonary blood flow of 1140 (95% CI 435-2146) mL min-1 (p = 0.012) compared to non-responders. A positive correlation (r = 0.79, 95% CI 0.5-0.90, p < 0.001) between increased end-expiratory lung volume and effective pulmonary blood flow was only observed in responders. Changes in oxygen delivery index after lung recruitment were correlated to changes in end-expiratory lung volume (r = 0.39, 95% CI 0.16-0.59, p = 0.002) and effective pulmonary blood flow (r = 0.60, 95% CI 0.41-0.74, p < 0.001). Capnodynamic monitoring of end-expiratory lung volume and effective pulmonary blood flow early in postoperative cardiac patients identified a characteristic parallel increase in both lung volume and perfusion after the recruitment manoeuvre in patients with a significant increase in oxygen delivery.Trial registration This study was registered on ClinicalTrials.gov (NCT05082168, 18th of October 2021).

Modeling human peri-implantation placental development and function†.

It is very difficult to gain a better understanding of the events in human pregnancy that occur during and just after implantation because such pregnancies are not yet clinically detectable. Animal models of human placentation are inadequate. In vitro models that utilize immortalized cell lines and cells derived from trophoblast cancers have multiple limitations. Primary cell and tissue cultures often have limited lifespans and cannot be obtained from the peri-implantation period. We present here two contemporary models of human peri-implantation placental development: extended blastocyst culture and stem-cell derived trophoblast culture. We discuss current research efforts that employ these models and how such models might be used in the future to study the "black box" stage of human pregnancy.

Assessing marbling scores of beef at the 10th rib vs. 12th rib of longissimus thoracis in the slaughter line using camera grading technology in Germany.

Internationally, different Video Image Analysis Systems (VIAS) are established to enable categorization of beef carcasses according to a marbling score as determining part of trading categories. Different established standardized cutting positions of longissimus thoracis, among other reasons, hamper the use of VIAS in European countries. The objective of the study was to explore the potential of a VIAS-based grading system VBG 2000 for the estimation of marbling of carcasses cut according to German standards. The correlation coefficient between the camera assessed marbling scores (n = 354 halves of carcasses) at the 10th rib section at the left and right side achieved 0.89 (P < .01) and 0.80 (P < .01) for camera assessed marbling scores between the right 12th/13th and 10th/11th rib interface of longissmus thoracis. Thus, modification of the cut position towards the US standard provides comparable results, and assessing VIA based marbling scores at the 10th rib is correlated to the 12th rib.

Impact of health challenges on pig growth performance, carcass characteristics, and net returns under commercial conditions.

Understanding how disease affects commercial production is imperative for pig producers to quantify its full impact on pig performance, carcass quality, and net returns. The objective of this experiment was to assess the productivity and economic importance of naturally occurring health challenges (HC) under commercial conditions. Three 1,000 pig grow-finish facilities received 936 pigs each. The experimental period started approximately 34 d post placement at an average start BW of 13.1 ± 0.2 kg. Barns were characterized based on the relative HC, determined by diagnostic assessments as the main characterization tool, along with other health indicators. Barns were characterized as low challenge health (LCh), moderate challenge health (MCh), and high challenge health (HCh). All barns tested positive for porcine reproductive and respiratory syndrome virus infection prior to the start of the experiment. Additionally, the MCh and HCh barns experienced influenza type A virus of swine. Similar to commercial production conditions, the disease challenge was not imposed but rather occurred naturally. Reduced ADG, ADFI, and G:F were observed with an increased HC (P < 0.001). Similarly, mortality was increased when the HC increased (P < 0.001). Decreased ADG increased days to achieve harvest BW, by 10 and 15 d in the MCh and HCh treatments compared with LCh, respectively (P < 0.001). No differences were observed for percent lean, loin depth, or fat depth (P > 0.10). The economic impact of the HC was assessed by applying these growth performance data to two economic models encompassing the two main marketing methods used by U.S. pig producers: fixed-weight and fixed-time. Financial losses attributed to the variation in disease severity that occurred in the present study ranged from $8.49 and $26.10 U.S. dollars (USD)/pig marketed using a fixed-market weight model, or between $11.02 and $29.82 USD/pig using a fixed-time model, depending on feed costs and market hog prices. In conclusion, increasing severity of HC under commercial conditions reduced ADG by 8% and 14% and resulted in mortality as high as 19.9%. Losses of $8.49 to $29.82/pig marketed underscore the potential magnitude of the economic impact of mixed etiology concurrent diseases in pork production.

Temporal mapping of photochemical reactions and molecular excited states with carbon specificity.

Photochemical reactions are essential to a large number of important industrial and biological processes. A method for monitoring photochemical reaction kinetics and the dynamics of molecular excitations with spatial resolution within the active molecule would allow a rigorous exploration of the pathway and mechanism of photophysical and photochemical processes. Here we demonstrate that laser-excited muon pump-probe spin spectroscopy (photo-µSR) can temporally and spatially map these processes with a spatial resolution at the single-carbon level in a molecule with a pentacene backbone. The observed time-dependent light-induced changes of an avoided level crossing resonance demonstrate that the photochemical reactivity of a specific carbon atom is modified as a result of the presence of the excited state wavefunction. This demonstrates the sensitivity and potential of this technique in probing molecular excitations and photochemistry.

BEEF SPECIES SYMPOSIUM: Economic considerations related to U.S. beef herd expansion.

Significant attention perpetually surrounds possible changes in breeding herd inventories in the U.S. beef cattle industry. This article outlines economic considerations of U.S. herd expansion. Factors restricting expansion include land availability, increasing production efficiency, operator demographics, capital requirements, and commodity price volatility. Several offsetting factors support herd expansion including unprecedented cow-calf returns, ongoing global beef demand growth, and timing within the current cattle cycle. In addition to these industry-wide factors, several important variations in individual ranch considerations are outlined. The authors' expectations on future herd dynamics are provided, highlighting broader implications for individual operations, industry leaders, and the entire beef-cattle supply chain. The substantial economic impact and importance of the cow-calf sector warrants broader appreciation of these economic factors impacting herd expansion. The future size of the U.S. cattle industry is determined by the individual decisions of over 70,000 cattle owners, making this issue worthy of review by all industry stakeholders.

Increased prevalence of gastrointestinal viruses and diminished secretory immunoglobulin a levels in antibody deficiencies.

PURPOSE: Gastrointestinal disease occurs frequently in antibody deficiencies. This study aims to explore the relation between gastrointestinal infections and mucosal homeostasis in patients with antibody deficiencies. METHODS: We performed an observational study including 54 pediatric antibody deficient patients (48 % CVID, 41 % CVID-like, 11 % XLA) and 66 healthy controls. Clinical symptom scores and stool samples were collected prospectively. Stool samples were evaluated for bacteria, parasites, viruses, secretory IgA- and for calprotectin levels. Results were compared between patients and controls. RESULTS: 24 % of antibody deficient patients versus 9 % of healthy controls tested positive for gastrointestinal viruses (p = 0.028). Fecal calprotectin levels were significantly higher in virus positive patients compared to virus negative patients (p = 0.002). However, in controls, fecal calprotectin levels were similar between virus positive and virus negative controls. Moreover, gastrointestinal virus positive patients had low serum IgA levels in 13/14 cases (94 %) versus 40/62 (62 %) patients in the virus negative patient group (p = 0.04). The virus positive patient group also displayed significantly lower secretory IgA levels in stool (median 13 ug/ml) than patients without gastrointestinal viruses detected or healthy controls (median 155 ug/ml) (p = 0.046). CONCLUSION: We here report an increased prevalence of gastrointestinal viruses and gastrointestinal complaints in antibody deficient patients. Patients that tested positive for gastrointestinal viruses showed diminished serum- and secretory IgA levels, and only in patients, virus positivity was associated with signs of mucosal inflammation. These findings suggest that particularly patients with low IgA are at risk for longstanding replication of gastrointestinal viruses, which may eventually result in CVID-related enteropathy.

Importance of spin-orbit interaction for the electron spin relaxation in organic semiconductors.

Despite the great interest organic spintronics has recently attracted, there is only a partial understanding of the fundamental physics behind electron spin relaxation in organic semiconductors. Mechanisms based on hyperfine interaction have been demonstrated, but the role of the spin-orbit interaction remains elusive. Here, we report muon spin spectroscopy and time-resolved photoluminescence measurements on two series of molecular semiconductors in which the strength of the spin-orbit interaction has been systematically modified with a targeted chemical substitution of different atoms at a particular molecular site. We find that the spin-orbit interaction is a significant source of electron spin relaxation in these materials.

Comparison of extravillous trophoblast cells derived from human embryonic stem cells and from first trimester human placentas.

INTRODUCTION: Preeclampsia and other placental pathologies are characterized by a lack of spiral artery remodeling associated with insufficient invasion by extravillous trophoblast cells (EVT). Because trophoblast invasion occurs in early pregnancy when access to human placental tissue is limited, there is a need for model systems for the study of trophoblast differentiation and invasion. Human embryonic stem cells (hESC) treated with BMP4- differentiate to trophoblast, and express HLA-G, a marker of EVT. The goals of the present study were to further characterize the HLA-G(+) cells derived from BMP4-treated hESC, and determine their suitability as a model. METHODS: HESC were treated with BMP4 under 4% or 20% oxygen and tested in Matrigel invasion chambers. Both BMP4-treated hESC and primary human placental cells were separated into HLA-G(+) and HLA-G(-)/TACSTD2(+) populations with immunomagnetic beads and expression profiles analyzed by microarray. RESULTS: There was a 10-fold increase in invasion when hESC were BMP4-treated. There was also an independent, stimulatory effect of oxygen on this process. Invasive cells expressed trophoblast marker KRT7, and the majority were also HLA-G(+). Gene expression profiles revealed that HLA-G(+), BMP4-treated hESC were similar to, but distinct from, HLA-G(+) cells isolated from first trimester placentas. Whereas HLA-G(+) and HLA-G(-) cells from first trimester placentas had highly divergent gene expression profiles, HLA-G(+) and HLA-G(-) cells from BMP4-treated hESC had somewhat similar profiles, and both expressed genes characteristic of early trophoblast development. CONCLUSIONS: We conclude that hESC treated with BMP4 provide a model for studying transition to the EVT lineage.

Engineering spin propagation across a hybrid organic/inorganic interface using a polar layer.

Spintronics has shown a remarkable and rapid development, for example from the initial discovery of giant magnetoresistance in spin valves to their ubiquity in hard-disk read heads in a relatively short time. However, the ability to fully harness electron spin as another degree of freedom in semiconductor devices has been slower to take off. One future avenue that may expand the spintronic technology base is to take advantage of the flexibility intrinsic to organic semiconductors (OSCs), where it is possible to engineer and control their electronic properties and tailor them to obtain new device concepts. Here we show that we can control the spin polarization of extracted charge carriers from an OSC by the inclusion of a thin interfacial layer of polar material. The electric dipole moment brought about by this layer shifts the OSC highest occupied molecular orbital with respect to the Fermi energy of the ferromagnetic contact. This approach allows us full control of the spin band appropriate for charge-carrier extraction, opening up new spintronic device concepts for future exploitation.

The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the dog.

The dog is a common model for study of osteoarthritis (OA). Subjective histologic scoring systems have often served as the reference standard for presence and severity of OA. However, these scoring systems have perceived shortcomings. The system developed for this report attempts to address these shortcomings by providing a standardized methodology for global assessment of the joint, versatility and the potential for relative weighting of pathology, allowing for comparison among time points, studies, and centers, and critical analysis of the system's reliability. The proposed system for assessment of canine tissues appears to provide an effective method for global assessment of articular pathology in OA. The system is versatile, comprehensive, and reliable and appears to have advantages over conventional scoring systems.

Incommensurate magnetic order and dynamics induced by spinless impurities in YBa(2)Cu(3)O(6.6).

We report an inelastic-neutron-scattering and muon-spin-relaxation study of the effect of 2% spinless (Zn) impurities on the magnetic order and dynamics of YBa(2)Cu(3)O(6.6), an underdoped high-temperature superconductor that exhibits a prominent spin pseudogap in its normal state. Zn substitution induces static magnetic order at low temperatures and triggers a large-scale spectral-weight redistribution from the magnetic resonant mode at 38 meV into uniaxial, incommensurate spin excitations with energies well below the spin pseudogap. These observations indicate a competition between incommensurate magnetic order and superconductivity close to a quantum critical point. Comparison to prior data on La(2-x)Sr(x)CuO(4) suggests that this behavior is universal for the layered copper oxides and analogous to impurity-induced magnetic order in one-dimensional quantum magnets.

Coexistence and competition of magnetism and superconductivity on the nanometer scale in underdoped BaFe1.89Co0.11As2.

We report muon spin rotation (µSR) and infrared spectroscopy experiments on underdoped BaFe1.89Co0.11As2 which show that bulk magnetism and superconductivity (SC) coexist and compete on the nanometer length scale. Our combined data reveal a bulk magnetic order, likely due to an incommensurate spin density wave (SDW), which develops below T(mag)≈32 K and becomes reduced in magnitude (but not in volume) below Tc=21.7 K. A slowly fluctuating precursor of the SDW seems to develop already below the structural transition at T(s)≈50 K. The bulk nature of SC is established by the µSR data which show a bulk SC vortex lattice and the IR data which reveal that the majority of low-energy states is gapped and participates in the condensate at T≪T(c).

Elastic torsion effects in magnetic nanoparticle diblock-copolymer structures.

Magnetic properties of thin composite films, consisting of non-interacting polystyrene-coated γ-Fe(2)O(3) (maghemite) nanoparticles embedded into polystyrene-block-polyisoprene P(S-b-I) diblock-copolymer films are investigated. Different particle concentrations, ranging from 0.7 to 43 wt%, have been used. The magnetization measured as a function of external field and temperature shows typical features of anisotropic superparamagnets including a hysteresis at low temperatures and blocking phenomena. However, the data cannot be reconciled with the unmodified Stoner-Wohlfarth-Néel theory. Applying an appropriate generalization we find evidence for either an elastic torque being exerted on the nanoparticles by the field or a broad distribution of anisotropy constants.

Electronic phase separation in the slightly underdoped iron pnictide superconductor Ba1-xKxFe2As2.

Here we present a combined study of the slightly underdoped novel pnictide superconductor Ba1-xKxFe2As2 by means of x-ray powder diffraction, neutron scattering, muon-spin rotation (microSR), and magnetic force microscopy (MFM). Static antiferromagnetic order sets in below T{m} approximately 70 K as inferred from the neutron scattering and zero-field-microSR data. Transverse-field microSR below Tc shows a coexistence of magnetically ordered and nonmagnetic states, which is also confirmed by MFM imaging. We explain such coexistence by electronic phase separation into antiferromagnetic and superconducting- or normal-state regions on a lateral scale of several tens of nanometers. Our findings indicate that such mesoscopic phase separation can be considered an intrinsic property of some iron pnictide superconductors.

Ambiguous results of an attempt to withdraw barbiturates in epilepsy patients with intellectual disability.

Phenobarbital and primidone frequently have adverse effects on mental functions. Therefore, an attempt was made to taper barbiturates in 85 patients out of a resident population with epilepsy and intellectual disability who were selected according to clinical criteria. The objectives were to reduce the use of barbiturates, to improve the patients' cognitive and psychological state, and to reduce polypharmacy while avoiding seizure exacerbation. Four months after complete withdrawal changes in seizure frequency were assessed as well as changes in cognitive abilities, psychological state and behaviour (using the clinical global impression scale). In 13 patients the tapering failed due to complications (seizure increase in 11 patients). In 72 patients the barbiturate was completely withdrawn (mean duration of tapering: 393 days). Cognitive improvement was achieved in 17 patients (23.6%), 5 patients (6.9%) deteriorated. Seizure frequency remained unchanged in 33 patients (45.8%), in another 15 patients (20.8%) the seizure frequency decreased. Reduction in polypharmacy was obtained in 61 patients (84.7%). In an overall judgement (clinical global impression scale) of cognitive abilities AND seizure control, 25 patients (34.7%) were improved. 31 patients (43.1%) remained unchanged while 12 patients deteriorated (4 patients: impossible to judge). For statistical analysis three outcome groups were defined: the improved group (N=25), the unchanged group (N=31), and the deteriorated/failed group (N=25) consisting of the 12 deteriorated patients plus the 13 patients in whom tapering failed. Stepwise logistic regression revealed a history of an attempt to withdraw phenobarbital/primidone (p=0.017; OR 3.8), age (p=0.012) and seizure frequency (marginally significant: p=0.097) as outcome predictors. Older age was associated with better outcome. A high seizure frequency before tapering was related to good outcome, while seizure freedom and a history of failed withdrawal were associated with deterioration/failure. Outcome did not depend on duration of barbiturate therapy, dosage or serum concentration, co-medication, reduction rate, degree of intellectual disability, or epilepsy syndrome. In summary, the number of barbiturate medications has been considerably reduced, but the principal aim of the project, to relieve patients from assumed barbiturate side effects, has been achieved only in one out of four patients.

Effect of leptin on mouse trophoblast giant cells.

Leptin plays a role in both energy homeostasis and reproduction, and it is required in early pregnancy. It stimulates metalloproteinase activity in cultured human trophoblasts and invasiveness of cultured mouse trophoblasts. Our goal has been to examine mechanisms that underpin the ability of leptin to promote trophoblast invasiveness in primary cultures of mouse trophoblasts. Leptin stimulated the phosphorylation of MEK (MAP2K1) but not signal transducer and activator of transcription 3 (STAT3) in the cultures, increased the concentration of the suppressor of cytokine signaling 3 (SOCS3) protein, and upregulated metalloproteinase activity. Microarray analysis revealed that leptin stimulated select genes with roles in cell motility, including Stmn, a gene linked to invasiveness in other cell types. There was also an increase in activity of several genes associated with MAPK and RhoGTPase signaling. In addition, leptin muted expression of genes correlated with terminal differentiation of trophoblast giant cells, including ones associated with the TGFbeta signaling pathway and endoreduplication of DNA, and upregulated selected prolactin-related family members. Feulgen staining of leptin-treated cells revealed a loss of cells with low ploidy. The data suggest that leptin accelerates disappearance of non-giant cells while inhibiting terminal differentiation of committed giant cells, possibly by maintaining cells in an intermediate stage of differentiation.