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The fine structure of the IsoVector Giant Dipole Resonance (IVGDR) in the doubly-magic nuclei 40,48Ca observed in inelastic proton scattering experiments under 0∘ is used to investigate the role of different mechanisms contributing to the IVGDR decay width. Characteristic energy scales are extracted from the fine structure by means of wavelet analysis. The experimental scales are compared to different theoretical approaches allowing for the inclusion of complex configurations beyond the mean-field level. Calculations are performed in the framework of RPA and beyond-RPA in a relativistic approach based on an effective meson-exchange interaction, with the UCOM effective interaction and, for the first time, with realistic two- plus three-nucleon interactions from chiral effective field theory employing the in-medium similarity renormalization group. All models highlight the role of Landau fragmentation for the damping of the IVGDR, while the differences in the coupling strength between one particle-one hole (1p-1h) and two particle-two hole (2p-2h) correlated (relativistic) and non-correlated (non-relativistic) configurations lead to very different pictures of the importance of the spreading width resulting in wavelet scales being a sensitive measure of their interplay. The relativistic approach with particle-vibration coupling, in particular, shows impressive agreement with the number and absolute values of the scales extracted from the experimental data.

Involvement in social media activities has become a significant aspect of adolescents’ lives. Participation in numerous social media challenges with a variety of goals is also common among youth across platforms. Recently, the new app called TikTok has resulted in an increased level and variety of social media activities among youth. This study examines the factors related to participation in TikTok challenges, their potential impacts on adolescents and young adults, and participant reflection after performing a challenge. We recruited 25 adolescents and young adults who were actively involved in TikTok challenges from several secondary schools and colleges in South India. We administered a semi-structured, retrospective interview after screening participants through an online survey. The interview assessed motivations for participation, content of social media posts, and perceived consequences of participation. Based on the integrated behavior model, we conducted a theoretically grounded thematic analysis of the data. Our thematic analysis revealed that the factors closely related to the integrated behavior model motivated participation, such as attitudes, norms, personal agency, knowledge and skill, environmental constraints, habits, and individual differences. Further, one of the most frequent reasons reported as a motivational factor was being affirmed by others or peer pressure. Participants typically reported enjoying these challenges and experiencing positive feelings after completing the challenge. Overall, the participants seemed to have positive views of TikTok challenges and enjoyed the views and likes that came from posting about their participation in the challenge. Irrespective of the type of challenge participated in, the participants commented that taking part in online challenges is enjoyable and makes them feel confident. In sum, these adolescents appear to spend large amounts of time on TikTok due to the lure of online challenges and associated emotional states.

Atrial septal defects (ASD) caused by traumatic events, specifically blunt cardiac trauma, are considered an infrequent occurrence, yet their true prevalence has been difficult to ascertain. The general lack of knowledge is likely due to the pathology being severely understudied. We present the case of a 21-year-old male who was diagnosed with ASD following a motor vehicle accident. Initial assessment utilizing the point-of-care ultrasound (POCUS) technique - focused assessment with sonography for trauma (FAST) was found to be negative for free intraperitoneal or pericardial fluid. Subsequent computed tomography displayed multiple injuries but agreed with the FAST exam findings of no fluid within the abdomen or pericardium. Later in the patient's care a dedicated POCUS transthoracic echocardiogram was performed which identified right sided heart dilatation. The patient was managed in the intensive care unit (ICU) for an extensive period but recovered sufficiently to be discharged. The plan was to repair the ASD on a non-emergent basis. This case highlights the importance and diagnostic utility of bedside POCUS. Categories: Emergency Medicine

Dyspnea is a common complaint in patients who present to the emergency department and can be due to numerous etiologies. This case report details a 90-year-old female with a history significant for hypertension, hyperlipidemia, and new diagnosis of ovarian malignancy whose symptoms increased over the past three days. Point-of-care Ultrasonography showed multiple B-lines, a plethoric IVC without respiratory variation, a markedly low EF and a lack of RV dilation. There was also no evidence of effusion which led the emergency medicine team to the diagnosis of acute decompensated heart failure. This quick diagnosis was possible due to using the standardized POCUS approach guided by the BEE FIRST algorithm. BEE FIRST can help physicians remember: B-lines are indicative of interstitial thickening, Effusion such as pericardial or pleural should be checked for, Ejection Fraction is useful in assessing for heart failure, IVC/Infection/Infarct correlates with central venous pressure, and can be used to assess volume status, check for enlargement, evidence of pneumonia, subpleural consolidation “shred sign”, hepatization of lung, and/or pulmonary infarction related to pulmonary embolism, Right Heart Strain can indicate pulmonary embolism or pulmonary hypertension, Sliding Lung can assess for pneumothorax and pleural characteristics, and lastly, Thrombosis/Tumor can assess for myxoma and interrogation of lower extremities for deep vein thrombosis can aid in dyspnea differentiation. In this report, we demonstrate how the framework BEE FIRST offers a standardized stepwise approach to the utilization of POCUS in a patient with acute dyspnea in the ED setting.

Syncope is a common emergency department (ED) chief complaint. Rarely, syncope can be the result of right ventricular outflow obstruction from an intracardiac tumor, such as an intracardiac extension of intravenous leiomyomatosis (IVL). Typically, this type of tumor is confined to the pelvic veins, but in very rare cases, it can extend through the inferior vena cava into the right atrium. Point-of-care ultrasound (POCUS) can be a crucial tool in the ED for identifying intracardiac tumors presenting as syncope and expediting clinical management.We present the case of a 39-year-old female with no prior medical history that presented to the ED having experienced dyspnea on exertion and two syncopal episodes prior to ED admission. POCUS use in the ED elucidated the presence of a right atrial mass and further imaging showed a mass on the patient's uterus. After surgical removal of a portion of the atrial mass, a subsequent biopsy revealed it had leiomyoma-like features; as such, the patient was diagnosed with IVL. This case illustrates the importance of using POCUS in the ED to help determine the etiology of syncope. Although intracardiac extensions of IVL are rare, it is important for emergency physicians to keep this diagnosis in the differential in patients with symptoms or risk factors suggestive of IVL with intracardiac extension.

Intrauterine devices (IUDs) are used worldwide. The 2 types that are used are the levonorgestrel IUD and a copper containing IUD. This is a case study of a 30-year-old female with a levonorgestrel IUD who was diagnosed with a ruptured ectopic pregnancy in the emergency department (ED). Point-of-care urine pregnancy test and point-of-care ultrasound (POCUS) were vital in making this diagnosis and should be utilized in patients assigned female at birth who present with abdominal pain.

Emergency physicians often rely on heuristics to facilitate clinical decisions due to the large volume of patients they see daily. Consequently, they are vulnerable to error and bias. We report the case of a 69-year-old male that presented to the emergency department (ED) with shortness of breath, productive cough, and dyspnea on exertion. One day prior to ED admission, he was diagnosed with bronchitis; however, point-of-care ultrasound (POCUS) in the ED identified acute pulmonary embolism. This case illustrates the potential dangers of anchoring bias and shows the benefits of using point-of-care ultrasound of the lungs and heart to assist in the diagnosis of acute pulmonary embolism.

The World Health Organization categorized coronavirus disease 2019 (COVID-19) as a pandemic due to its high contagion rate and widespread infectivity in February 2020. In the United States, one of the public health concerns is the adequacy of resources to treat infected cases. We describe a case of a previously well, 9-year-old obese boy who presented to the emergency department with shortness of breath, fever, abdominal pain, and cough with chest pain. He was diagnosed with COVID-19 through significant family contact, confirmed by polymerase chain reaction and found to be at high risk of venous thromboembolism due to abnormal d-dimer. Lung point-of-care ultrasound (POCUS) in the emergency department observed significant lung pathology, including pleural thickening, consolidation, and B lines. A chest X-ray found bilateral ground glass opacities and interstitial prominences consistent with viral pneumonia. Our case suggests that lung POCUS can provide adequate and rapid imaging to assess lung pathology of COVID-19 in a pediatric patient. As there is limited literature on use of lung POCUS in pediatric patients infected with SARS-CoV-2, our case emphasizes its function as a potentially efficient modality in bedside assessment.

The structure of exotic nuclei provides valuable tests for state-of-the-art nuclear theory. In particular electromagnetic transition rates are more sensitive to aspects of nuclear forces and many-body physics than excitation energies alone. We report the first lifetime measurement of excited states in 21O, finding τ1/2+=420−32+35(stat)−12+34(sys) ps. This result together with the deduced level scheme and branching ratio of several γ-ray decays are compared to both phenomenological shell-model and ab initio calculations based on two- and three-nucleon forces derived from chiral effective field theory. We find that the electric quadrupole reduced transition probability of B(E2;1/2+→5/2g.s.+)=0.71−0.06−0.06+0.07+0.02 e2fm4, derived from the lifetime of the 1/2+ state, is smaller than the phenomenological result where standard effective charges are employed, suggesting the need for modifications of the latter in neutron-rich oxygen isotopes. We compare this result to both large-space and valence-space ab initio calculations, and by using multiple input interactions we explore the sensitivity of this observable to underlying details of nuclear forces.

The microtubule-associated protein Tau is strongly implicated in Alzheimer's disease (AD) and aggregates into neurofibrillary tangles in AD. Genetic reduction of Tau is protective in several animal models of AD and cell culture models of amyloid-β (Aβ) toxicity, making it an exciting therapeutic target for treating AD. A variety of evidence indicates that Tau's interactions with Fyn kinase and other SH3 domain–containing proteins, which bind to PxxP motifs in Tau's proline-rich domain, may contribute to AD deficits and Aβ toxicity. Thus, we sought to determine if inhibiting Tau-SH3 interactions ameliorates Aβ toxicity. We developed a peptide inhibitor of Tau-SH3 interactions and a proximity ligation assay (PLA)-based target engagement assay. Then, we used membrane trafficking and neurite degeneration assays to determine if inhibiting Tau-SH3 interactions ameliorated Aβ oligomer (Aβo)-induced toxicity in primary hippocampal neurons from rats. We verified that Tau reduction ameliorated Aβo toxicity in neurons. Using PLA, we identified a peptide inhibitor that reduced Tau-SH3 interactions in HEK-293 cells and primary neurons. This peptide reduced Tau phosphorylation by Fyn without affecting Fyn's kinase activity state. In primary neurons, endogenous Tau-Fyn interaction was present primarily in neurites and was reduced by the peptide inhibitor, from which we inferred target engagement. Reducing Tau-SH3 interactions in neurons ameliorated Aβo toxicity by multiple outcome measures, namely Aβo-induced membrane trafficking abnormalities and neurite degeneration. Our results indicate that Tau-SH3 interactions are critical for Aβo toxicity and that inhibiting them is a promising therapeutic target for AD.

A Rayleigh–Schrödinger many-body perturbation theory (MBPT) approach is introduced by making use of a particle-number-breaking Bogoliubov reference state to tackle (near-)degenerate open-shell fermionic systems. By choosing a reference state that solves the Hartree–Fock–Bogoliubov variational problem, the approach reduces to the well-tested Møller–Plesset, i.e., Hartree–Fock based, MBPT when applied to closed-shell systems. Due to its algorithmic simplicity, the newly developed framework provides a computationally simple yet accurate alternative to state-of-the-art non-perturbative many-body approaches. At the price of working in the quasi-particle basis associated with a single-particle basis of sufficient size, the computational scaling of the method is independent of the particle number. This paper presents the first realistic applications of the method ranging from the oxygen to the nickel isotopic chains on the basis of a modern nuclear Hamiltonian derived from chiral effective field theory. Keywords: Perturbation theory, Many-body theory, Ab initio, Open-shell nuclei

As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950–Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra- and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium. While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.

The (J,T)=(1,1) parity doublet in 20Ne at 11.26 MeV is a good candidate to study parity violation in nuclei. However, its energy splitting is known with insufficient accuracy for quantitative estimates of parity violating effects. To improve on this unsatisfactory situation, nuclear resonance fluorescence experiments using linearly and circularly polarized γ-ray beams were used to determine the energy difference of the parity doublet ΔE=E(1−)−E(1+)=−3.2(±0.7)stat(−1.2+0.6)sys keV and the ratio of their integrated cross sections Is,0(+)/Is,0(−)=29(±3)stat(−7+14)sys. Shell-model calculations predict a parity-violating matrix element having a value in the range 0.46–0.83 eV for the parity doublet. The small energy difference of the parity doublet makes 20Ne an excellent candidate to study parity violation in nuclear excitations. Keywords: Parity doublet, Parity violation

We report ab initio calculations for neutron drops in a 10 MeV external harmonic-oscillator trap using chiral nucleon–nucleon plus three-nucleon interactions. We present total binding energies, internal energies, radii and odd–even energy differences for neutron numbers N=2–18 using the no-core shell model with and without importance truncation. Furthermore, we present total binding energies for N=8,16,20,28,40,50 obtained in a coupled-cluster approach. Comparisons with quantum Monte Carlo results, where available, using Argonne v8′ with three-nucleon interactions reveal important dependences on the chosen Hamiltonian. Keywords: Neutron drop, Ab initio, Chiral Hamiltonian, No-core shell model, Importance truncation, Coupled cluster

To elucidate the relationship between age and cognitive decline, it is important to consider structural brain changes such as white matter hyperintensities (WMHs), which are common in older age and may affect behavior. Therefore, we aimed to investigate if WMH load is a mediator of the relationship between age and cognitive decline. Healthy participants (N = 166, 20-80 years) completed the Montreal Cognitive Assessment (MoCA). WMHs were manually delineated on FLAIR scans. Mediation analysis was conducted to determine if WMH load mediates the relationship between age and cognition. Older age was associated with worse cognition (p < 0.001), but this was an indirect effect: older participants had more WMHs, and, in turn, increased WMH load was associated with worse MoCA scores. WMH load mediates the relationship between age and cognitive decline. Importantly, this relationship was not moderated by age (i.e., increased WMH severity is associated with poorer MoCA scores irrespective of age). Across all ages, high cholesterol was associated with increased WMH severity., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Premature age-related brain changes may be influenced by physical health factors. Lower socioeconomic status (SES) is often associated with poorer physical health. In this study, we aimed to investigate the relationship between SES and premature brain aging., Methods: Brain age was estimated from T1-weighted images using BrainAgeR in 217 participants from the ABC@UofSC Repository. The difference between brain and chronological age (BrainGAP) was calculated. Multiple regression models were used to predict BrainGAP with age, SES, body mass index, diabetes, hypertension, sex, race, and education as predictors. SES was calculated from size-adjusted household income and the cost of living., Results: Fifty-five participants (25.35%) had greater brain age than chronological age (premature brain aging). Multiple regression models revealed that age, sex, and SES were significant predictors of BrainGAP with lower SES associated with greater BrainGAP (premature brain aging)., Conclusions: This study demonstrates that lower SES is an independent contributor to premature brain aging. This may provide additional insight into the mechanisms associated with brain health, cognition, and resilience to neurological injury., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the feasibility of delivering a low-dose mindfulness-based stress reduction (MBSR) intervention among prediabetes/diabetes patients in a clinical setting., Design and Setting: This was a single-arm, mixed methods, feasibility study among prediabetes/diabetes patients at a healthcare center in United States., Intervention: The low-dose MBSR intervention was delivered in group format over 4 waves and each wave comprised 8-10 h of 8 sessions over 6-8 weeks., Main Outcome Measures: We evaluated recruitment, adherence, and attrition rates, participants' satisfaction, motivation and barriers of low-dose MBSR. Psychological, behavioral, and physical measures were compared between pre- and post-intervention., Results: We enrolled 19 participants of 34 eligible individuals with a recruitment rate of 55.9%. Among 19 enrolled participants, 4 dropped out after baseline data collection and did not attend any session and 1 attended one session but did not finish post-intervention data collection, resulting in an attrition rate of 26.3%. Among 15 participants attending at least one session, 46.7% attended all sessions and 80.0% attended at least 5 sessions. Qualitative analysis among 11 participants indicated that 90.9% had positive overall experience with the intervention. Compared to pre-intervention, there was a significant reduction in depression score (mean reduction = 5.04, SD = 7.66, p = 0.02), a higher proportion of engaging in flexibility exercises (42.86% vs. 85.71%, p = 0.01) and a lower level of glycosylated hemoglobin (HbA1c) (mean reduction = 1.43%, SD = 2.54%, p = 0.03) at post-intervention., Conclusions: Delivering a low-dose MBSR intervention to prediabetes/diabetes patients in a primary care setting is feasible. Future studies with randomized controlled design and larger sample are warranted., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lesion-based studies are among the most informative approaches to determine a critical relationship between a particular brain region and specific function. Importantly, brain lesions cause disconnection of other brain areas that appear to be intact and may cause functional deficits in these regions due to a lack of afferent projections. If only the location of necrosis and gliosis after the stroke is considered to be the lesion, the full spectrum of brain dysfunction is only partly assessed, and there is a high probability that incomplete region-to-function inferences are made. In this chapter we (1) outline how structural connectivity can be measured in individuals with stroke, and (2) provide an overview of the importance of disrupted structural connectivity in aphasia. We conclude that connection-based and region/voxel-based symptom mapping yield complementary information and together provide an in-depth picture of brain and function relationships., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The ability to string together words into a structured arrangement capable of conveying nuanced information is key to speech production. The assessment of the neural bases for structuring sentences has been challenged by the need of experts to delineate the aberrant morphosyntactic structures in aphasic speech. Most studies have relied on focused tasks with limited ecological validity. We characterized syntactic complexity during connected speech produced by patients with chronic post-stroke aphasia. We automated this process by employing Natural Language Processing (NLP). We conducted voxel-based and connectome-based lesion-symptom mapping to identify brain regions crucially associated with sentence production and syntactic complexity. Posterior-inferior aspects of left frontal and parietal lobes, as well as white matter tracts connecting these areas, were essential for syntactic complexity, particularly the posterior inferior frontal gyrus. These findings suggest that sentence structuring during word production depends on the integrity of Broca's area and the dorsal stream of language processing., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Feral and semi-feral donkeys are recognised as a problem in some world regions. The main problem associated with uncontrolled donkey populations is habitat degradation and competition for feed resources, especially in arid climes. Controlling population numbers would reduce the impact of donkeys and other species. While removal by various means is effective, it has been shown to stimulate reproductive rate. Probably the most effective and humane solution is reducing reproduction using minimally invasive methods including immunocontraception. This study tested the immunocontraceptive efficacy and safety of zona pellucida (ZP) vaccines, both recombinant (reZP; three treatments) and native porcine (pZP; two treatments) vaccines formulated with Freund's modified complete (primary) and Freund's incomplete (boosters) adjuvants in donkey jennies. Control jennies received adjuvants only (two treatments). Twenty-five non-pregnant jennies were randomly assigned to reZP (n = 9), pZP (n = 8) or control (n = 8) groups. Weekly monitoring of the reproductive tract and ovaries via transrectal palpation and ultrasound and inspection of injection sites was conducted and anti-pZP antibody titers were measured. Five weeks after last treatment, one donkey jack was introduced to each group and rotated every 21 days. By 232 days after last treatment the number pregnant and median days to pregnancy was 2/9 and 214 (reZP group), 1/8 and 196 (pZP group) and 8/8 and 77 (control group). Median time to ovarian shut-down was 77 (9/9) and 56 (7/8) days for reZP and pZP groups, respectively. This was observed in association with a distinct reduction in mean uterine diameter. The antibody response was equally good for both ZP-treated groups. Incorporation of Freund's adjuvants initially produced a high incidence of side effects from local swelling and intermittent lameness followed weeks later by sterile abscesses (reZP, 9/9; pZP, 7/8; control, 3/8). Both ZP vaccines effectively controlled reproduction in jennies, albeit with a high incidence of adjuvant-associated side effects., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Until today, the oral delivery of peptide drugs is hampered due to their instability in the gastrointestinal tract and low mucosal penetration. To overcome these hurdles, PLA (polylactide acid)-nanoparticles were coated with a cyclic, polyarginine-rich, cell penetrating peptide (cyclic R9-CPP). These surface-modified nanoparticles showed a size and polydispersity index comparable to standard PLA-nanoparticles. The zeta potential showed a significant increase indicating successful CPP-coupling to the surface of the nanoparticles. Cryo-EM micrographs confirmed the appropriate size and morphology of the modified nanoparticles. A high encapsulation efficiency of liraglutide could be achieved. In vitro tests using Caco-2 cells showed high viability indicating the tolerability of this novel formulation. A strongly enhanced mucosal binding and penetration was demonstrated by a Caco-2 binding and uptake assay. In Wistar rats, the novel nanoparticles showed a substantial, 4.5-fold increase in the oral bioavailability of liraglutide revealing great potential for the oral delivery of peptide drugs., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

The gene encoding for Epstein-Barr virus-induced G-protein-coupled receptor 2 (EBI2) is a risk gene for inflammatory bowel disease (IBD). Together with its oxysterol ligand 7α,25-dihydroxycholesterol, EBI2 mediates migration and differentiation of immune cells. However, the role of EBI2 in the colonic immune system remains insufficiently studied. We found increased mRNA expression of EBI2 and oxysterol-synthesizing enzymes (CH25H, CYP7B1) in the inflamed colon of patients with ulcerative colitis and mice with acute or chronic dextran sulfate sodium (DSS) colitis. Accordingly, we detected elevated levels of 25-hydroxylated oxysterols, including 7α,25-dihydroxycholesterol in mice with acute colonic inflammation. Knockout of EBI2 or CH25H did not affect severity of DSS colitis; however, inflammation was decreased in male EBI2 -/- mice in the IL-10 colitis model. The colonic immune system comprises mucosal lymphoid structures, which accumulate upon chronic inflammation in IL-10-deficient mice and in chronic DSS colitis. However, EBI2 -/- mice formed significantly less colonic lymphoid structures at baseline and showed defects in inflammation-induced accumulation of lymphoid structures. In summary, we report induction of the EBI2-7α,25-dihydroxycholesterol axis in colitis and a role of EBI2 for the accumulation of lymphoid tissue during homeostasis and inflammation. These data implicate the EBI2-7α,25-dihydroxycholesterol axis in IBD pathogenesis.

An important determinant in the selection of any contraceptive agent is the impact on ovarian function, both in the short and longer term. In this study, ovarian activity was monitored in mares immunised with one of the following vaccine formulations; native porcine zona pellucida (pZP), recombinant zona pellucida proteins ZP3 and ZP4 (reZP), pZP and reZP combined or a commercially available anti-GnRH vaccine. The ZP antigens were prepared in an adjuvant formulation consisting of 6% polymeric adjuvant (Montanide™ PetGel A, Seppic, France) and 500 μg polyinosinic-polycytidylic acid - TLR3-agonist (Poly(I:C) HMW VacciGrade™, Invivogen, USA). A vehicle-only control group was administered the adjuvant formulation without antigen. Ovarian activity was monitored using clinical observations (transrectal palpation and ultrasonography of the reproductive tract) in addition to blood sampling for serum progesterone and anti-Müllerian hormone (AMH) concentrations while employing a low sampling frequency. Treatments and measurements were initiated in December (southern hemisphere summer) and subsequent data collection was performed in January, February, March and May. Both reZP and anti-GnRH vaccination were associated with clinically evident ovarian suppression in the short term. Ovarian activity in mares administered a reZP or anti-GnRH vaccine was significantly different to adjuvant control and pZP treated mares. Serum AMH concentrations were different between pZP and anti-GnRH treated mares 3.5 months after the final vaccination. Serum AMH concentrations were significantly correlated with mare age, serum progesterone and ovarian volume., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Controversy remains as to whether Ki-67 labeling on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cell blocks (CBs) can be used to grade pancreatic neuroendocrine neoplasms (PanNENs) reliably and what would be the best methodology for doing so., Materials and Methods: A retrospective search identified cases with both EUS-FNA and correlating surgical pathology (SP) available. 58 CBs (>100 tumor cells) were identified. Ki-67 labeling on CB was counted using both manual count (MC) and digital image analysis (DIA, ImmunoRatio software). The grades determined on CB were compared with those on corresponding SP reports (kappa statistics). The correct grading rates between MC and DIA were compared (McNemar's test). Total tumor cell number (TTCN, cutoffs: 500 and 2000) was used as a stratification factor (chi-square tests for trend)., Results: Of 58 cases, the SP grade distribution was 31 grade 1, 23 grade 2, and 4 grade 3. Overall, the grading concordance of CB MC and SP was higher than that of CB DIA and SP (McNemar's P-value = 0.022). Compared with SP, CB MC correctly graded 69% (40 of 58) [κ = 0.44 (95% CI: 0.21, 0.66)]; CB DIA correctly graded 55% (32 of 58) [κ = 0.19 (95% CI: 0.04, 0.42)]. Grade 1 tumors had the highest concordance. Although the correct grading rate improved as TTCN increased, no statistical significance was found., Conclusion: Although Ki-67 labeling on CB can be used to grade PanNENs, limitation exists, particularly for grade 2 tumors. The method of counting makes a difference: MC is more accurate than DIA. The major reasons of discordance include non-tumor cell contamination and insufficient sampling., (Copyright © 2016 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Objective: The TEDDY Study is an international, multi-center prospective study designed to identify the environmental triggers of type 1 diabetes (T1D) in genetically at-risk children. This report investigates ethnic minority (EM) differences in patterns of enrollment and retention in the US centers., Methods: As of June 2009, 267,739 newborns had been screened at birth for high risk T1D genotypes. Data collected at the time of screening, enrollment and at the baseline visit were used. Descriptive and multiple-logistic regression analyses assessed differences between EM groups regarding exclusion, enrollment and early withdrawal., Results: Of the 10,975 eligible subjects, 6,912 (67%) were invited to participate. EM subjects were more likely to be excluded because of an inability to contact. Of those invited 3,265 (47%) enrolled by the age of 4.5 months. Adjusted analyses showed that except for those classified as other EM, the odds of enrolling were similar across groups. EM subjects had elevated early withdrawal rates. Adjusted models demonstrated that this was significantly more likely among Hispanic subjects., Conclusion: Understanding patterns associated with EM participation in research extends our ability to make more accurate inferences and permits assessment of strategies that promote inclusion of EM to better address health disparities., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Our objective was to identify characteristics of infants and their families who were enrolled, refused to enroll, or were excluded from The Environmental Determinants of Diabetes in the Young (TEDDY) study., Method: 16,435 infants screened at birth and identified as at increased genetic risk for type 1 diabetes (T1DM) were placed into one of three categories: enrolled, excluded, or refused to enroll. Enrollment, exclusion and refusal rates were compared across countries and between infants from the general population (GP) and infants with a first degree T1DM relative (FDR). A multivariate logistic model was used to identify factors associated with TEDDY enrollment., Results: TEDDY enrollment, exclusion, and refusal rates differed by country and by GP/FDR status but reasons for refusal to enroll were similar across countries and GP/FDR populations. Sweden had the highest enrollment rate, US had the highest exclusion rate, and Finland had the highest refusal rate. FDR infants were more likely to enroll than GP infants. Inability to re-contact the family was the most common reason for exclusion. Primary reasons for refusal to enroll included protocol factors (e.g. blood draws) or family factors (e.g., too busy). Study enrollment was associated with FDR status, European country of origin, older maternal age, a singleton birth, and having another child in TEDDY., Conclusions: Findings highlight the importance of country specific estimates for enrollment targets in longitudinal pediatric studies and suggest that enrollment estimates should be lowered when the study involves the general population, painful procedures, or makes multiple demands on families., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Acutely secreted von Willebrand factor (VWF) multimers adhere to endothelial cells, support platelet adhesion, and may induce microvascular thrombosis. Immunofluorescence microscopy of live human umbilical vein endothelial cells showed that VWF multimers rapidly formed strings several hundred micrometers long on the cell surface after stimulation with histamine. Unexpectedly, only a subset of VWF strings supported platelet binding, which depended on platelet glycoprotein Ib. Electron microscopy showed that VWF strings often consisted of bundles and networks of VWF multimers, and each string was tethered to the cell surface by a limited number of sites. Several approaches implicated P-selectin and integrin alpha(v)beta(3) in anchoring VWF strings. An RGDS peptide or a function-blocking antibody to integrin alpha(v)beta(3) reduced the number of VWF strings formed. In addition, integrin alpha(v) decorated the VWF strings by immunofluorescence microscopy. Furthermore, lentiviral transduction of shRNA against the alpha(v) subunit reduced the expression of cell-surface integrin alpha(v)beta(3) and impaired the ability of endothelial cells to retain VWF strings. Soluble P-selectin reduced the number of platelet-decorated VWF strings in the absence of Ca(2+) and Mg(2+) but had no effect in the presence of these cations. These results indicate that VWF strings bind specifically to integrin alpha(v)beta(3) on human endothelial cells.

Muscle wasting in chronic renal failure is associated with increased morbidity and mortality; however, resistance exercise is effective at increasing muscle mass while improving muscle strength and function. To study the mechanism by which this occurs, we compared uremic and control rats where work overload was surgically induced unilaterally in the plantaris muscle. We found that work overload increases muscle insulin-like growth factor-1 and mechano-growth factor expression. This in addition to direct mechanical activation of signaling was likely the cause of the observed increased in the protein levels and phosphorylation of the mediators of these growth factors, the insulin receptor substrate-1/phosphoinositide 3-kinase/Akt pathway. The mechanical enhancement of signal transduction appeared to be mediated in part by increased signal protein levels and decreased SOCS2 mRNA expression (suppressor of cytokine signaling-2). Despite impaired basal signaling, the work-induced signaling response was similar to that observed in nonuremic rats and produced changes consistent with decreased muscle protein degradation, increased protein synthetic capacity, and an increased number of multinucleated muscle cells. Our studies suggest that these work-induced changes account for the improved uremic muscle mass reaching levels comparable to those seen in normal rats.

The role of preoperative embolization should be evaluated for the surgical treatment of spinal and pelvic metastases. Selective embolization was performed in 32 patients (19 men, 13 women; mean age 63.4 years) before surgery by anterior resection of spinal metastases (n = 21) or pelvic metastases (n = 11). Evaluation parameters consisted of the intraoperative blood loss, the need for blood replacement, and the operating time. There was a significant difference in blood loss and transfusion requirements in the spinal group (P = 0.02) as well as in the pelvic group (P = 0.05) compared to a nonembolized control group of spinal (n = 20) and pelvic (n = 10) metastases. The operating time in the embolized group was shorter, but the difference was not significant. Surgical revision was required in two cases in the embolized spinal group owing to necrosis of the psoas muscle. No neurological deficit was observed that could be attributed to the embolization procedure. Preoperative embolization is thus a suitable method for reducing intraoperative blood loss and transfusion requirements in hypervascularized spinal and pelvic metastases.