Neutron Star Matter as a Dilute Solution of Protons in Neutrons.

Neutron stars contain neutron-rich matter with around 5% protons at nuclear saturation density. In this Letter, we consider equilibrium between bulk phases of matter based on asymmetric nuclear matter calculations using chiral effective field theory interactions rather than, as has been done in the past, by interpolation between the properties of symmetric nuclear matter and pure neutron matter. Neutron drip (coexistence of nuclear matter with pure neutrons) is well established, but from earlier work it is unclear whether proton drip (equilibrium between two phases, both of which contain protons and neutrons) is possible. We find that proton drip is a robust prediction of any physically reasonable equation of state, but that it occurs over a limited region of densities and proton fractions. An analytical model based on expanding the energy in powers of the proton density, rather than the neutron excess, is able to account for these features of the phase diagram.

Nuclear Equation of State for Arbitrary Proton Fraction and Temperature Based on Chiral Effective Field Theory and a Gaussian Process Emulator.

We calculate the equation of state of asymmetric nuclear matter at finite temperature based on chiral effective field theory interactions to next-to-next-to-next-to-leading order. Our results assess the theoretical uncertainties from the many-body calculation and the chiral expansion. Using a Gaussian process emulator for the free energy, we derive the thermodynamic properties of matter through consistent derivatives and use the Gaussian process to access arbitrary proton fraction and temperature. This enables a first nonparametric calculation of the equation of state in beta equilibrium, and of the speed of sound and the symmetry energy at finite temperature. Moreover, our results show that the thermal part of the pressure decreases with increasing densities.

Prior differences in previous trauma exposure primarily drive the observed racial/ethnic differences in posttrauma depression and anxiety following a recent trauma.

BACKGROUND: Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time. METHODS: As part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors. RESULTS: Racial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants. CONCLUSIONS: The present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories.

Conversion of unresponsiveness to immune checkpoint inhibition by fecal microbiota transplantation in patients with metastatic melanoma: study protocol for a randomized phase Ib/IIa trial.

BACKGROUND: The gut microbiome plays an important role in immune modulation. Specifically, presence or absence of certain gut bacterial taxa has been associated with better antitumor immune responses. Furthermore, in trials using fecal microbiota transplantation (FMT) to treat melanoma patients unresponsive to immune checkpoint inhibitors (ICI), complete responses (CR), partial responses (PR), and durable stable disease (SD) have been observed. However, the underlying mechanism determining which patients will or will not respond and what the optimal FMT composition is, has not been fully elucidated, and a discrepancy in microbial taxa associated with clinical response has been observed between studies. Furthermore, it is unknown whether a change in the microbiome itself, irrespective of its origin, or FMT from ICI responding donors, is required for reversion of ICI-unresponsiveness. To address this, we will transfer microbiota of either ICI responder or nonresponder metastatic melanoma patients via FMT. METHODS: In this randomized, double-blinded phase Ib/IIa trial, 24 anti-PD1-refractory patients with advanced stage cutaneous melanoma will receive an FMT from either an ICI responding or nonresponding donor, while continuing anti-PD-1 treatment. Donors will be selected from patients with metastatic melanoma treated with anti-PD-1 therapy. Two patients with a good response (≥ 30% decrease according to RECIST 1.1 within the past 24 months) and two patients with progression (≥ 20% increase according to RECIST 1.1 within the past 3 months) will be selected as ICI responding or nonresponding donors, respectively. The primary endpoint is clinical benefit (SD, PR or CR) at 12 weeks, confirmed on a CT scan at 16 weeks. The secondary endpoint is safety, defined as the occurrence of grade ≥ 3 toxicity. Exploratory endpoints are progression-free survival and changes in the gut microbiome, metabolome, and immune cells. DISCUSSION: Transplanting fecal microbiota to restore the patients' perturbed microbiome has proven successful in several indications. However, less is known about the potential role of FMT to improve antitumor immune response. In this trial, we aim to investigate whether administration of FMT can reverse resistance to anti-PD-1 treatment in patients with advanced stage melanoma, and whether the ICI-responsiveness of the feces donor is associated with its effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05251389 (registered 22-Feb-2022). Protocol V4.0 (08-02-2022).

mm-wave Rydberg-Rydberg transitions gauge intermolecular coupling in a molecular ultracold plasma.

Out-of-equilibrium, strong correlation in a many-body system can trigger emergent properties that act to constrain the natural dissipation of energy and matter. Signs of such self-organization appear in the avalanche, bifurcation, and quench of a state-selected Rydberg gas of nitric oxide to form an ultracold, strongly correlated ultracold plasma. Work reported here focuses on the initial stages of avalanche and quench and uses the mm-wave spectroscopy of an embedded quantum probe to characterize the intermolecular interaction dynamics associated with the evolution to plasma. Double-resonance excitation prepares a Rydberg gas of nitric oxide composed of a single selected state of principal quantum number, n0. Penning ionization, followed by an avalanche of electron-Rydberg collisions, forms a plasma of NO+ ions and weakly bound electrons, in which a residual population of n0 Rydberg molecules evolves to a state of high orbital angular momentum, ℓ. Predissociation depletes the plasma of low-ℓ molecules. Relaxation ceases and n0ℓ(2) molecules with ℓ ≥ 4 persist for very long times. At short times, varying excitation spectra of mm-wave Rydberg-Rydberg transitions mark the rate of electron-collisional ℓ-mixing. Deep depletion resonances that persist for long times signal energy redistribution in the basis of central-field Rydberg states. The widths and asymmetries of Fano line shapes witness the degree to which coupling in the arrested bath (i) broadens the allowed transition and (ii) mixes the local network of levels in the ensemble.

Novel KEL allele associated with loss of Kpb identified in a white blood donor.

The importance of identifying variant alleles among blood donors is significant to the safety of transfusion for recipients. Molecular methods have become more prominent in the routine process of antigen typing donor units. Some variant antigens cannot be detected using only serologic methods. Molecular testing allows the determination of nucleotide sequences that are used to predict a phenotype. Antigens of the Kell blood group system are known for being highly immunogenic and causing adverse reactions upon antibody formation. A female white blood donor who typed Kp(b-) using serologic methods on multiple donations since 2005 was the subject of a typing discrepancy investigation. Routine genotyping using a commercial genotyping kit (HemoID DQS Panel; Agena Bioscience, San Diego, CA) predicted the donor to type Kp(a+b+). Investigation of the discrepancy between these two results identified a rare single nucleotide variant in the KEL gene at nucleotide position c.948G>T that alters amino acid residue 316 from tryptophan (Trp) to cysteine (Cys). After discovery of the novel allele, adsorption and elution studies were performed to see if there was weakened Kpb expression. The elution studies yielded negative results, which indicated that Kpb is not expressed. The KEL transcripts expressed by the donor were determined using cDNA analysis, and the predicted amino acid sequence of the novel allele was modeled to investigate the impact of the amino acid sequence on the structure of the KEL polypeptide. Both SWISS-MODEL and Robetta software were used to evaluate the impact of the p.Trp316Cys on the three-dimensional protein structure. There was no conformational change noted with SWISS-MODEL, whereas the Robetta software showed a significant conformational change compared with the normal Kp(b+) reference sequence. Because the donor is homozygous for variants associated with k and Jsb expression, it was not possible to determine whether the novel allele is associated with loss of Kpb only or loss of all Kell antigens.

Clinical Application and Potential of Fecal Microbiota Transplantation.

Fecal microbiota transplantation (FMT) is a well-established treatment for recurrent Clostridioides difficile infection. FMT has become a more readily available and useful new treatment option as a result of stool banks. The current state of knowledge indicates that dysbiosis of the gut microbiota is implicated in several disorders in addition to C. difficile infection. Randomized controlled studies have shown FMT to be somewhat effective in treating ulcerative colitis, irritable bowel syndrome, and hepatic encephalopathy. In addition, FMT has been beneficial in treating several other conditions, such as the eradication of multidrug-resistant organisms and graft-versus-host disease. We expect that FMT will soon be implemented as a treatment strategy for several new indications, although further studies are needed.

Influence of pregnancy and non-fasting conditions on the plasma metabolome in a rat prenatal toxicity study.

The current parameters for determining maternal toxicity (e.g. clinical signs, food consumption, body weight development) lack specificity and may underestimate the extent of effects of test compounds on the dams. Previous reports have highlighted the use of plasma metabolomics for an improved and mechanism-based identification of maternal toxicity. To establish metabolite profiles of healthy pregnancies and evaluate the influence of food consumption as a confounding factor, metabolite profiling of rat plasma was performed by gas- and liquid-chromatography-tandem mass spectrometry techniques. Metabolite changes in response to pregnancy, food consumption prior to blood sampling (non-fasting) as well as the interaction of both conditions were studied. In dams, both conditions, non-fasting and pregnancy, had a marked influence on the plasma metabolome and resulted in distinct individual patterns of changed metabolites. Non-fasting was characterized by increased plasma concentrations of amino acids and diet related compounds and lower levels of ketone bodies. The metabolic profile of pregnant rats was characterized by lower amino acids and glucose levels and higher concentrations of plasma fatty acids, triglycerides and hormones, capturing the normal biochemical changes undergone during pregnancy. The establishment of metabolic profiles of pregnant non-fasted rats serves as a baseline to create metabolic fingerprints for prenatal and maternal toxicity studies.

Hygiene-Eliciting Brood Semiochemicals as a Tool for Assaying Honey Bee (Hymenoptera: Apidae) Colony Resistance to Varroa (Mesostigmata: Varroidae).

Despite numerous interventions, the ectoparasitic mite Varroa (Varroa destructor Anderson and Trueman [Mesostigmata: Varroidae]) and the pathogens it vectors remain a primary threat to honey bee (Apis mellifera Linnaeus [Hymenoptera: Apidae]) health. Hygienic behavior, the ability to detect, uncap, and remove unhealthy brood from the colony, has been bred for selectively for over two decades and continues to be a promising avenue for improved Varroa management. Although hygienic behavior is expressed more in Varroa-resistant colonies, hygiene does not always confer resistance to Varroa. Additionally, existing Varroa resistance selection methods trade efficacy for efficiency, because those achieving the highest levels of Varroa resistance can be time-consuming, and thus expensive and impractical for apicultural use. Here, we tested the hypothesis that hygienic response to a mixture of semiochemicals associated with Varroa-infested honey bee brood can serve as an improved tool for predicting colony-level Varroa resistance. In support of our hypothesis, we demonstrated that a mixture of the compounds (Z)-10-tritriacontene, (Z)-8-hentriacontene, (Z)-8-heptadecene, and (Z)-6-pentadecene triggers hygienic behavior in a two-hour assay, and that high-performing colonies (hygienic response to ≥60% of treated cells) have significantly lower Varroa infestations, remove significantly more introduced Varroa, and are significantly more likely to survive the winter compared to low-performing colonies (hygienic response to <60% of treated cells). We discuss the relative efficacy and efficiency of this assay for facilitating apiary management decisions and selection of Varroa-resistant honey bees, as well as the relevance of these findings to honey bee health, pollination services, and social insect communication.

DELLA family duplication events lead to different selective constraints in angiosperms.

Gibberellic acid (GA) is a major plant hormone involved in several biological processes from the flowering to the symbiosis with microorganisms. Thus, the GA regulation is crucial for plant biology. This regulation occurs via the DELLA proteins that belong to the GRAS transcription factor family. DELLA proteins are characterised by a DELLA N-terminal and a GRAS C-terminal domains. It is well known that DELLA activity appears after the bryophytes divergence and then evolved in the vascular plant lineages. Here we present the phylogeny of DELLA across 75 species belonging to various lineages from algae, liverworts and angiosperms. Our study confirmed two main duplication events, the first occurring before the angiosperms divergence and the other specific to the eudicots lineage. Comparative analysis of DELLA subclades in angiosperms revealed the loss in Poaceae and strong alteration in other species of the DELLA functional domain in the DELLA2 clade. In addition, molecular evolution analysis suggests that each of the clades (named DELLA1.1, DELLA1.2 and DELLA2) evolved differently but copies of each subclade are under strong purifying selection. This also suggests that, although the DELLA functional domain is altered in DELLA2, DELLA2 orthologs are still functional and operate in a different way compared to DELLA1 copies. In angiosperms, additional duplication events occurred and led to duplicate copies in species, genus or family such as in the Fabaceae subfamily Papilionoideae. This duplication led to the formation of additional paralogs in the DELLA1.2 subclade (DELLA1.2.1 and DELLA1.2.2). Interestingly, both copies appeared to be under relaxing selection revealing different evolutionary fate of the DELLA duplicated copies.

Systematic changes of the static upper body posture with a symmetric occlusion condition.

BACKGROUND: Temporary occlusal changes and their influence on the upper body statics are still controversially discussed. Furthermore, concrete statements on whether age- or gender-specific differences in neurophysiological reactions exist are missing. Therefore, it is the aim of this study to evaluate the immediate effects of a symmetrical occlusion blocking on the upper body posture. These effects shall be investigated for both genders and for a larger age range. METHODS: In this study, 800 (407f/393 m) subjects volunteered aged from 21 to 60 years. Both genders were divided into four age groups according to decades. The three-dimensional upper body posture was measured by using the rasterstereography (ABW-Bodymapper). The habitual static posture was measured in two dental occlusion conditions (a) in rest position and (b) symmetrical blocking in the bicuspid region by cotton rolls. RESULTS: A significant reduction of the trunk length (0.72 mm; p <  0.001), an increase of the lumbar (0.30°; p <  0.001) and the thoracic bending angle (0.14°; p = 0.001), a reduction of the spinal forward decline (0.16°; p <  0.001) and a reduction of the scapular distance (0.36 mm; p = 0.001) was found. Gender-specific reactions can only be recorded in scapular distance, in that regard men reduce this distance while over all age groups women did not show a significant change. DISCUSSION: Slight gender- and age-independent reactions due to a symmetric occlusion blockade are shown: A gender independent reaction of the spinal related variables in the sagittal plane (thoracic and lumbar flexion angle, trunk length, spinal forward decline). In addition, a gender specific change of the shoulder blade distance could be observed, where men reduced the distance while female did not show a change. However, since these reactions are of a minimum amount, it can be concluded that neurophysiological compensation mechanisms work equally well regardless of age and sex, and the upper body posture of healthy people changes only very slightly due to a temporarily symmetrical altered bite position.

HPA axis in major depression: cortisol, clinical symptomatology and genetic variation predict cognition.

The hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of a variety of mood and cognitive disorders. Neuroendocrine studies have demonstrated HPA axis overactivity in major depression, a relationship of HPA axis activity to cognitive performance and a potential role of HPA axis genetic variation in cognition. The present study investigated the simultaneous roles HPA axis activity, clinical symptomatology and HPA genetic variation play in cognitive performance. Patients with major depression with psychotic major depression (PMD) and with nonpsychotic major depression (NPMD) and healthy controls (HC) were studied. All participants underwent a diagnostic interview and psychiatric ratings, a comprehensive neuropsychological battery, overnight hourly blood sampling for cortisol and genetic assessment. Cognitive performance differed as a function of depression subtype. Across all subjects, cognitive performance was negatively correlated with higher cortisol, and PMD patients had higher cortisol than did NPMDs and HCs. Cortisol, clinical symptoms and variation in genes, NR3C1 (glucocorticoid receptor; GR) and NR3C2 (mineralocorticoid receptor; MR) that encode for GRs and MRs, predicted cognitive performance. Beyond the effects of cortisol, demographics and clinical symptoms, NR3C1 variation predicted attention and working memory, whereas NR3C2 polymorphisms predicted memory performance. These findings parallel the distribution of GR and MR in primate brain and their putative roles in specific cognitive tasks. HPA axis genetic variation and activity were important predictors of cognition across the entire sample of depressed subjects and HR. GR and MR genetic variation predicted unique cognitive functions, beyond the influence of cortisol and clinical symptoms. GR genetic variation was implicated in attention and working memory, whereas MR was implicated in verbal memory.

Implementation of the North Carolina HIV Bridge Counseling Program to Facilitate Linkage and Reengagement in Care for Individuals Infected with HIV/AIDS.

BACKGROUND Statewide interventions are critical to meeting the goals of the National HIV/AIDS Strategy in this country. In 2012, the North Carolina Division of Public Health developed the North Carolina State Bridge Counselor program to improve linkage to and reengagement in care for newly diagnosed persons and persons living with HIV who were out-of-care.METHODS We reviewed the planning process for the North Carolina State Bridge Counselor program, which involved a review of existing strengths-based counseling models for persons living with HIV, implementation of these models, and communication strategies with other providers. State bridge counselor responsibilities were delineated from the role of disease intervention specialists while retaining the fieldwork capability of disease intervention specialists to conduct outreach and provide services for persons living with HIV throughout the state.RESULTS Program implementation required extensive planning with stakeholders, incorporation of strengths-based counseling models, development of performance standards, and utilization of CAREWare, an HIV care software program to document referrals and data-sharing between state bridge counselors and clinics. By the end of 2014, state bridge counselor services were provided to approximately 60 of the 400 persons living with HIV (15%) who are diagnosed each quarter in North Carolina, with increasing utilization of the program.LIMITATIONS We assessed the development of this intervention specific to the North Carolina Division of Public Health, which may limit its generalizability. However, the State Bridge Counselor program was implemented in both urban and rural areas throughout the state, which increases its applicability to different public health programs throughout the country.CONCLUSION We demonstrated that a statewide State Bridge Counselor program for linkage and reengagement activities can be implemented by leveraging existing infrastructures, electronic medical records, HIV care networks, and fieldwork activities.

Treatment of recurrent and severe Clostridium difficile infection.

Clostridium difficile infection (CDI) is a serious complication of hospitalization and antibiotic use with a high mortality and very high costs. Despite appropriate treatment, a subset of patients develop chronic recurrent CDI. Some other patients develop severe and life-threatening colitis. The risk factors, pathogenesis, and treatment of recurrent CDI and severe CDI are discussed in this review. In particular, fecal microbiota transplantation (FMT) as a treatment strategy is outlined and a treatment algorithm incorporating FMT is described.

Impaired fracture healing with high non-union rates remains irreversible after traumatic brain injury in leptin-deficient mice.

Patients with traumatic brain injury (TBI) and long-bone fractures can show increased callus formation. This effect has already been reproduced in wild-type (wt) mice. However, the mechanisms remain poorly understood. Leptin is significantly increased following TBI, while its role in bone healing remains unclear. The aim of this study was to evaluate fracture healing in leptin-deficient ob/ob mice and to measure any possible impact of TBI on callus formation. 138 female, 12 weeks old, ob/ob mice were divided into four groups: Control, fracture, TBI and combined trauma. Osteotomies were stabilized with an external fixator; TBI was induced with Controlled Cortical Impact Injury. Callus bridging was weekly evaluated with in vivo micro-CT. Biomechanical testing was performed ex vivo. Micro-CT showed high non-union rates after three and four weeks in the fracture and combined trauma group. No differences were observed in callus volume, density and biomechanical properties at any time point. This study shows that bony bridging is impaired in the present leptin-deficient trauma model. Furthermore, the phenomenon of increased callus formation after TBI could not be reproduced in ob/ob mice, as in wt mice. Our findings suggest that the increased callus formation after TBI may be dependent on leptin signaling.

[Willingness of Patients with Obesity to Use New Media in Rehabilitation Aftercare]. / Die Nutzungsbereitschaft von Patienten mit Adipositas gegenüber neuen Medien in der Rehabilitationsnachsorge.

Digital media offer new possibilities in rehabilitation aftercare. This study investigates the rehabilitants' willingness to use new media (sms, internet, social networks) in rehabilitation aftercare and factors that are associated with the willingness to use media-based aftercare. 92 rehabilitants (patients with obesity) filled in a questionnaire on the willingness to use new media in rehabilitation aftercare. In order to identify influencing factors, binary logistic regression models were calculated. 3 quarters of the rehabilitants (76.1%) reported that they would be willing to use new media in rehabilitation aftercare. The binary logistic regression model yielded two factors that were associated with the willingness to use media-based aftercare: the possession of a smartphone and the willingness to receive telephone counseling for aftercare. The majority of the rehabilitants was willing to use new media in rehabilitation aftercare. The reasons for refusal of media-based aftercare need to be examined more closely.

[Fecal microbiota transplantation, a novel therapy for recurrent Clostridium difficile infection]. / Fecale microbiota transplantatie: een nieuwe behandeling voor recidiverende Clostridium difficile-infectie.

Clostridium difficile infection is caused by a disturbance of the gut microbiota, often resulting from the use of antibiotics. Among a sub group of patients with this disorder, treatment with antibiotics is not effective. They develop a chronic, recurrent infection. Such patients can be treated with a fecal microbiota transplantation (FMT), or fecal transplantation. The crucial steps for safe application of fecal transplantation are central donor selection and screening. To optimise safety and to guarantee the availability of donor feces for fecal transplantation, the Nederlandse Donor Feces Bank (Dutch Donor Feces Bank) was established. At this facility, ready-to-use, screened donor feces can be ordered for patients with (recurrent) Clostridium difficile infections, who can then be treated at their own hospital.