No Evidence for Biased Attention Towards Emotional Scenes in Bornean Orangutans (Pongo pygmaeus).

Attention may be swiftly and automatically tuned to emotional expressions in social primates, as has been demonstrated in humans, bonobos, and macaques, and with mixed evidence in chimpanzees, where rapid detection of emotional expressions is thought to aid in navigating their social environment. Compared to the other great apes, orangutans are considered semi-solitary, but still form temporary social parties in which sensitivity to others' emotional expressions may be beneficial. The current study investigated whether implicit emotion-biased attention is also present in orangutans (Pongo pygmaeus). We trained six orangutans on the dot-probe paradigm: an established paradigm used in comparative studies which measures reaction time in response to a probe replacing emotional and neutral stimuli. Emotional stimuli consisted of scenes depicting conspecifics having sex, playing, grooming, yawning, or displaying aggression. These scenes were contrasted with neutral scenes showing conspecifics with a neutral face and body posture. Using Bayesian mixed modeling, we found no evidence for an overall emotion bias in this species. When looking at emotion categories separately, we also did not find substantial biases. We discuss the absence of an implicit attention bias for emotional expressions in orangutans in relation to the existing primate literature, and the methodological limitations of the task. Furthermore, we reconsider the emotional stimuli used in this study and their biological relevance. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-022-00158-x.

Materials Imaging and Dynamics (MID) instrument at the European X-ray Free-Electron Laser Facility.

The Materials Imaging and Dynamics (MID) instrument at the European X-ray Free-Electron Laser (EuXFEL) facility is described. EuXFEL is the first hard X-ray free-electron laser operating in the MHz repetition range which provides novel science opportunities. The aim of MID is to enable studies of nano-structured materials, liquids, and soft- and hard-condensed matter using the bright X-ray beams generated by EuXFEL. Particular emphasis is on studies of structure and dynamics in materials by coherent scattering and imaging using hard X-rays. Commission of MID started at the end of 2018 and first experiments were performed in 2019.

Anti-Müllerian hormone in managed African and Asian rhino species.

Serum collected across the lifespan of four managed rhino species: black (Diceros bicornis, n = 16), white (Ceratotherium simum simum, n = 19), greater one-horned (GOH, Rhinoceros unicornis, n = 11) and Sumatran (Dicerorhinus sumatrensis, n = 6) were validated and analyzed in an anti-Müllerian hormone (AMH) enzyme- linked immunoassay. Concentrations of AMH were examined over time, between sexes and throughout different reproductive states which included n = 3 female white rhinos immunocontracepted with porcine zona pellucida (pZP). Across species, males produced higher AMH concentrations compared to females. Among males, AMH concentrations varied by species aside from comparable values secreted between black and white rhinos. The GOH and Sumatran rhino secreted the highest and lowest male AMH concentrations, respectively. However, within each species, AMH concentrations were similar across male age categories. Preliminary insight into male AMH changes from birth to sexual maturity suggest its potential as a marker for onset of testicular maturation. Female black, GOH and Sumatran rhinos secreted comparable AMH concentrations which were higher than those in white rhino. Within each species, inter-individual variation in AMH secretion occurred among females of similar age. While AMH secretion did not differ across the ages sampled for female white (4->26 yr) and GOH (4-26 yr) rhinos, black and Sumatran rhinos >26 and <4 yr, respectively secreted lower AMH compared to conspecific females 7-26 yr of age. Two idiopathic infertility cases corresponded to low (outside species range) AMH values. The establishment of normative AMH concentrations in managed African and Asian rhinos provides an additional metric beyond traditional sex steroids to assess gonadal function. Further work is needed to determine if AMH can predict fertility potential in rhinos.

Efficacy of piperacillin in combination with novel ß-lactamase inhibitor IID572 against ß-lactamase-producing strains of Enterobacteriaceae and Staphylococcus aureus in murine neutropenic thigh infection models.

OBJECTIVES: The neutropenic murine thigh infection model was used to assess the effectiveness of IID572, a novel ß-lactamase inhibitor, in rescuing piperacillin activity against bacterial strains expressing various ß-lactamase enzymes. METHODS: Mice (n = 4/group) were inoculated with Enterobacteriaceae or Staphylococcus aureus bacterial strains expressing a range of ß-lactamases via intramuscular injection. Two hours after bacterial inoculation, subcutaneous treatment with piperacillin/IID572 or piperacillin/tazobactam every 3 h was initiated. Animals were euthanized via CO2 24 h after the start of therapy and bacterial cfu (log10 cfu) per thigh was determined, and the static dose was calculated. RESULTS: In a dose-dependent manner, piperacillin/IID572 reduced the thigh bacterial burden in models established with Enterobacteriaceae producing class A, C and D ß-lactamases (e.g. ESBLs, KPC, CMY-2 and OXA-48). Piperacillin/IID572 was also efficacious against MSSA strains, including one producing ß-lactamase. Static doses of piperacillin/IID572 were calculable from animals infected with all strains tested and the calculated static doses ranged from 195 to 4612 mg/kg/day piperacillin, the active component in the combination. Of the 13 strains investigated, a 1 log10 bacterial reduction was achieved for 9 isolates and a 2 log10 reduction was achieved for 3 isolates; piperacillin/tazobactam was not efficacious against 6 of the 13 isolates tested. CONCLUSIONS: In contrast to tazobactam, IID572 was able to rescue piperacillin efficacy in murine thigh infection models established with ß-lactamase-producing strains of Enterobacteriaceae and S. aureus, including those expressing ESBLs or serine carbapenemases.

Pharmacokinetics and pharmacodynamics of the novel monobactam LYS228 in a neutropenic murine thigh model of infection.

Objectives: The neutropenic murine thigh infection model and a dose-fractionation approach were used to determine the pharmacokinetic/pharmacodynamic (PK/PD) relationship of LYS228, a novel monobactam antibiotic with activity against Enterobacteriaceae including carbapenem-resistant strains. Methods: Mice (n = 4 per group) were inoculated with Enterobacteriaceae strains via intramuscular injection. Two hours post-bacterial inoculation, treatment with LYS228 was initiated. Animals were euthanized with CO2 24 h after the start of therapy and bacterial counts (log10 cfu) per thigh were determined. PK parameters were calculated using free (f) plasma drug levels. Results: Following a dose-fractionation study, non-linear regression analysis determined that the predominant PK/PD parameter associated with antibacterial efficacy of LYS228 was the percentage of the dosing interval that free drug concentrations remained above the MIC (%fT>MIC). In a dose-dependent manner, LYS228 reduced the thigh bacterial burden in models established with Enterobacteriaceae producing ß-lactamase enzymes of all classes (e.g. ESBLs, NDM-1, KPC, CMY-2 and OXA-48). The range of the calculated static dose was 86-649 mg/kg/day for the isolates tested, and the magnitude of the driver of efficacy was 37-83 %fT>MIC. %fT>MIC was confirmed as the parameter predominantly driving efficacy as evidenced by a strong coefficient of determination (r2 = 0.68). Neutrophils had minimal impact on the effect of LYS228 in the murine thigh infection model. Conclusions: LYS228 is efficacious in murine thigh infection models using ß-lactamase-producing strains of Enterobacteriaceae, including those expressing metallo-ß-lactamases, ESBLs and serine carbapenemases, with the PK/PD driver of efficacy identified as %T>MIC.

Internal medicine fellowship directors' perspectives on the quality and utility of letters conforming to residency program director letter of recommendation guidelines.

Background: In May 2017, the Alliance for Academic Internal Medicine (AAIM) published guidelines intending to standardize and improve internal medicine residency program director (PD) letters of recommendation (LORs) for fellowship applicants. Objectives: This study aimed to examine fellowship PDs impressions of the new guidelines, letter writers' adherence to the guidelines, and the impact of LORs that conformed to guidelines compared to non-standardized letters. Methods: The authors anonymously surveyed fellowship PDs from January to March 2018 to gather input about LORs submitted to their programs during the 2017 fellowship application cycle. Results: A total of 78% of survey respondents were satisfied with letters that followed the AAIM guidelines, whereas 48% of respondents were satisfied with letters that did not. Fellowship PDs felt that letters that followed the AAIM guidelines were more helpful than letters that did not, especially for differentiating between applicants from the same institution and for understanding residents' performance across the six core competency domains. Fellowship PDs provided several suggestions for residency PDs to make the LORs even more helpful. Conclusion: Fellowship PD respondents indicated that LORs that followed the new AAIM guidelines were more helpful than letters that did not.

How representative are insomnia clinical trials?

OBJECTIVES: To address the question of how representative subjects studied in hypnotic clinical trials are of the broader insomnia population, this study assessed initial contact rates and reasons for inclusion and exclusion during recruitment to an efficacy trial and to a safety trial of Food & Drug Administration (FDA) approved hypnotics. METHODS: Otherwise heathy persons meeting Diagnostic Statistical Manual, Fourth Edition, Revised (DSM-IVR) criteria for insomnia were recruited. In one study, persons 32-65 yrs, were invited to a 12 month trial of nightly use of zolpidem or placebo. In the other, persons 21-64 yrs with driver's licenses were recruited to test the effects of a hypnotic on live on-the-road driving ability. In both studies screening was conducted through an initial telephone interview followed by a clinic visit. RESULTS: In the United States (US) study 13% (n = 410) of 3180 initial contacts and in the Netherlands (NL) study 67% (n = 53) of the 79 initial contacts proceeded to the clinic visit. Of those at clinic 25% of US and 37% of NL participants failed to meet additional insomnia criteria. Mental health exclusions accounted for 24% of US and 23% of NL participants and medical problems accounted for 23% of US and 9% NL exclusions. Finally 20% of US and 26% of NL participants were excluded for drug use/abuse histories. After all screening 4% of the initial US contacts and 0% of the NL contacts entered the study. CONCLUSIONS: These data suggest persons entering insomnia hypnotic clinical trials are a highly selected sample that is unlikely to be representative of the broad insomnia population or the population of potential medication users.

Development of a hard X-ray split-and-delay line and performance simulations for two-color pump-probe experiments at the European XFEL.

A hard X-ray Split-and-Delay Line (SDL) under construction for the Materials Imaging and Dynamics station at the European X-Ray Free-Electron Laser (XFEL) is presented. This device aims at providing pairs of X-ray pulses with a variable time delay ranging from -10 ps to 800 ps in a photon energy range from 5 to 10 keV for photon correlation and X-ray pump-probe experiments. A custom designed mechanical motion system including active feedback control ensures that the high demands for stability and accuracy can be met and the design goals achieved. Using special radiation configurations of the European XFEL's SASE-2 undulator (SASE: Self-Amplified Spontaneous Emission), two-color hard x-ray pump-probe schemes with varying photon energy separations have been proposed. Simulations indicate that more than 109 photons on the sample per pulse-pair and up to about 10% photon energy separation can be achieved in the hard X-ray region using the SDL.

Epigenetic mechanisms in alcohol- and adversity-induced developmental origins of neurobehavioral functioning.

The long-term effects of developmental alcohol and stress exposure are well documented in both humans and non-human animal models. Damage to the brain and attendant life-long impairments in cognition and increased risk for psychiatric disorders are debilitating consequences of developmental exposure to alcohol and/or psychological stress. Here we discuss evidence for a role of epigenetic mechanisms in mediating these consequences. While we highlight some of the common ways in which stress or alcohol impact the epigenome, we point out that little is understood of the epigenome's response to experiencing both stress and alcohol exposure, though stress is a contributing factor as to why women drink during pregnancy. Advancing our understanding of this relationship is of critical concern not just for the health and well-being of individuals directly exposed to these teratogens, but for generations to come.

Sex Differences in Early Postnatal Microglial Colonization of the Developing Rat Hippocampus Following a Single-Day Alcohol Exposure.

Microglia are involved in various homeostatic processes in the brain, including phagocytosis, apoptosis, and synaptic pruning. Sex differences in microglia colonization of the developing brain have been reported, but have not been established following alcohol insult. Developmental alcohol exposure represents a neuroimmune challenge that may contribute to cognitive dysfunction prevalent in humans with Fetal Alcohol Spectrum Disorders (FASD) and in rodent models of FASD. Most studies have investigated neuroimmune activation following adult alcohol exposure or following multiple exposures. The current study uses a single day binge alcohol exposure model (postnatal day [PD] 4) to examine sex differences in the neuroimmune response in the developing rat hippocampus on PD5 and 8. The neuroimmune response was evaluated through measurement of microglial number and cytokine gene expression at both time points. Male pups had higher microglial number compared to females in many hippocampal subregions on PD5, but this difference disappeared by PD8, unless exposed to alcohol. Expression of pro-inflammatory marker CD11b was higher on PD5 in alcohol-exposed (AE) females compared to AE males. After alcohol exposure, C-C motif chemokine ligand 4 (CCL4) was significantly increased in female AE pups on PD5 and PD8. Tumor necrosis factor-α (TNF-α) levels were also upregulated by AE in males on PD8. The results demonstrate a clear difference between the male and female neuroimmune response to an AE challenge, which also occurs in a time-dependent manner. These findings are significant as they add to our knowledge of specific sex-dependent effects of alcohol exposure on microglia within the developing brain.

Monitoring and controlling ovarian function in the rhinoceros.

Despite their size and potentially dangerous demeanor, the rhinoceros has been a preferred subject of wildlife reproductive scientists. Several factors contribute to this taxon's popularity including the ability to utilize insightful tools like non-invasive hormone metabolite monitoring and transrectal ultrasonography, the necessity for mate introductions to coincide with the female's estrus when breeding certain species or individuals, and the desire to develop assisted reproductive technologies to facilitate the genetic management and ultimate sustainability of small, managed populations in human care. The resulting profusion of rhinoceros reproductive studies has revealed significant species-specific characteristics and exposed the prevalence of aberrant reproductive activity within this taxon. Of equal importance, it has guided necessary intervention and enhanced our success in overcoming challenges associated with breeding rhinoceroses.

[Interdisciplinary management in geriatric trauma surgery : Results of a survey in Austria]. / Interdisziplinäres Management in der Alterstraumatologie : Ergebnisse einer österreichweiten Umfrage.

BACKGROUND: The treatment of geriatric patients in the field of trauma surgery is increasingly gaining importance. To provide optimized treatment to these mostly multimorbid patients, interdisciplinary treatment concepts between trauma surgeons and geriatricians have been designed and implemented successfully. OBJECTIVES: The aim of this survey was to evaluate the current state of interdisciplinary management in the treatment of geriatric patients on trauma surgery wards throughout Austria. MATERIAL AND METHODS: The directors of 64 Austrian trauma surgery wards were surveyed using an online-questionnaire regarding the current interdisciplinary treatment of geriatric patients. RESULTS: A total of 39 (61 %) questionnaires were analyzed. Of the participating wards, 20 % distinguished between geriatric and non-geriatric patients. There were various criteria to classify the patients. The average percentage of patients older than 70 years was 43 %. Of the participating wards, 26 % had established a periodical cooperation between trauma surgeons and geriatricians and 8 % of the participants stated that there is no interdisciplinary cooperation. The establishment of an interdisciplinary treatment concept in the near future was planned in 28 %. The most commonly mentioned obstacle that prevented trauma surgery wards from establishing an interdisciplinary management model was the lack of personnel resources (59 %) - especially the lack of geriatricians (62 %). CONCLUSION: The survey's results underline the geriatric trauma surgery's great importance especially regarding the high percentage of geriatric patients, as well as the fact that the significance of the interdisciplinary cooperation between trauma surgeons and geriatricians is not yet perceived by the majority of Austrian trauma surgery wards.

Impact of exercise and a complex environment on hippocampal dendritic morphology, Bdnf gene expression, and DNA methylation in male rat pups neonatally exposed to alcohol.

Alcohol exposure in utero can result in Fetal Alcohol Spectrums Disorders (FASD). Measures of hippocampal neuroplasticity, including long-term potentiation, synaptic and dendritic organization, and adult neurogenesis, are consistently disrupted in rodent models of FASD. The current study investigated whether third trimester-equivalent binge-like alcohol exposure (AE) [postnatal days (PD) 4-9] affects dendritic morphology of immature dentate gyrus granule cells, and brain-derived neurotrophic factor (Bdnf) gene expression and DNA methylation in hippocampal tissue in adult male rats. To understand immediate impact of alcohol, DNA methylation was measured in the PD10 hippocampus. In addition, two behavioral interventions, wheel running (WR) and environmental complexity (EC), were utilized as rehabilitative therapies for alcohol-induced deficits. AE significantly decreased dendritic complexity of the immature neurons, demonstrating the long-lasting impact of neonatal alcohol exposure on dendritic morphology of immature neurons in the hippocampus. Both housing conditions robustly enhanced dendritic complexity in the AE animals. While Bdnf exon I DNA methylation was lower in the AE and sham-intubated animals compared with suckle controls on PD10, alterations to Bdnf DNA methylation and gene expression levels were not present at PD72. In control animals, exercise, but not exercise followed by housing in EC, resulted in higher levels of hippocampal Bdnf gene expression and lower DNA methylation. These studies demonstrate the long-lasting negative impact of developmental alcohol exposure on hippocampal dendritic morphology and support the implementation of exercise and complex environments as therapeutic interventions for individuals with FASD. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 708-725, 2017.

Hyperarousal in insomnia and hypnotic dose escalation.

BACKGROUND: Given concerns about the abuse liability of hypnotics, this study assessed hyperarousal in people with insomnia and its relation to hypnotic self-administration over 12 months of nightly hypnotic use. METHODS: Ninety-five subjects with insomnia (age 32-64 years) underwent screening nocturnal polysomnogram (NPSG) and Multiple Sleep Latency Test (MSLT) the following day and, then, were randomized to receive zolpidem 10 mg or placebo nightly for 12 months. NPSGs and MSLTs were conducted and urine was collected (0700-1500 h) and analyzed for norepinephrine (NE) levels during months one and eight on study medication. A subset (n = 54) underwent hypnotic self-administration assessments in months one, four, and 12. RESULTS: Mean daily sleep latency on screening MSLT was distributed across the full range of MSLT latencies (2-20 min). The highest screening MSLT latencies were detected in subjects with higher NE levels, compared to those with the lowest MSLT latencies. In the subset undergoing self-administration assessment, those with the highest MSLT latencies chose more capsules (placebo and zolpidem) and increased the number of capsules chosen in months four relative to month one, compared to those with the lowest MSLT latencies. CONCLUSIONS: These data show that some insomniacs are hyperaroused with high MSLT/NE levels and, compared to low MSLT/NE insomniacs, they increase the number of capsules (zolpidem and placebo) self-administered on months four and 12 relative to Month one.

Orthogeriatric co-management improves the outcome of long-term care residents with fragility fractures.

BACKGROUND: Fragility fractures are a major health care problem worldwide. Both hip and non-hip fractures are associated with excess mortality in the years following the fracture. Residents of long-term nursing homes represent a special high-risk group for poor outcomes. Orthogeriatric co-management models of care have shown in multiple studies to have medical as well as economic advantages, but their impact on this high-risk group has not been well studied. OBJECTIVE: We studied the outcome of long-term care residents with hip and non-hip fractures admitted to a geriatric fracture center. METHODS: The study design is a single center, prospective cohort study at a level-I trauma center in Austria running a geriatric fracture center. The cohort included all fragility fracture patients aged over 70 admitted from a long-term care residence from May 2009 to November 2011. The data set consisted of 265 patients; the mean age was 86.8 ± 6.7 years, and 80 % were female. The mean follow-up after the index fracture was 789 days, with a range from 1 to 1842 days. Basic clinical and demographic data were collected at hospital admission. Functional status and mobility were assessed during follow-up at 3, 6, and 12 months. Additional outcome data regarding readmissions for new fractures were obtained from the hospital information database; mortality was crosschecked with the death registry from the governmental institute of epidemiology. RESULTS: 187 (70.6 %) patients died during the follow-up period, with 78 patients (29.4 %) dying in the first year. The mean life expectancy after the index fracture was 527 (±431) days. Differences in mortality rates between hip and non-hip fracture patients were not statistically significant. Compared to reported mortality rates in the literature, hip fracture patients in this orthogeriatric-comanaged cohort had a significantly reduced one-year mortality [OR of 0.57 (95 % CI 0.31-0.85)]. After adjustment for confounders, only older age (OR 1.091; p = 0.013; CI 1.019-1.169) and a lower Parker Mobility Scale (PMS) (OR 0.737; p = 0.022; CI 0.568-0.957) remained as independent predictors. During follow-up, 62 patients (23.4 %) sustained at least one subsequent fracture, and 10 patients (3.4 %) experienced multiple fractures; 29 patients (10.9 %) experienced an additional fracture within the first year. Nearly, half (47.1 %) regained their pre-fracture mobility based on the PMS. CONCLUSION: Despite the generally poor outcomes for fragility fracture patients residing in long-term care facilities, orthogeriatric co-management appears to improve the outcome of high-risk fragility fracture patients. One-year mortality was 29.4 % in this cohort, significantly lower than in comparable trials. Orthogeriatric co-management may also have positive impacts on both functional outcome and the risk of subsequent fractures.

Age-related changes in Egr1 transcription and DNA methylation within the hippocampus.

Aged animals show functional alterations in hippocampal neurons that lead to deficits in synaptic plasticity and changes in cognitive function. Transcription of immediate-early genes (IEGs), including Egr1, is necessary for processes such as long-term potentiation and memory consolidation. Here, we show an age-related reduction in the transcription of Egr1 in the dentate gyrus following spatial behavior, whereas in the area CA1, Egr1 is reduced at rest, but its transcription can be effectively driven by spatial behavior to levels equivalent to those observed in adult animals. One mechanism possibly contributing to these aging-related changes is an age-associated, CpG site-specific change in methylation in DNA associated with the promoter region of the Egr1 gene. Our results add to a growing body of work demonstrating that complex transcriptional and epigenetic changes in the hippocampus significantly contribute to brain and cognitive aging. © 2016 Wiley Periodicals, Inc.