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Animal-assisted interventions (AAI) are increasingly used in clinical and school settings to promote psychological and social-emotional well-being among youth. However, the precise role of youth-animal relationships in shaping developmental trajectories is understudied. Research is needed to expand human-centric models of child development, specifically to examine how youth relationships with animals may be ecological assets and identify potential processes of change underlying these relationships. This study analyzed interviews from 30 students attending a school for special education and mental health services that incorporates AAI. Results indicated that youth perceived their relationships with animals as contributing to enhanced social connection, which was perceived as leading to self-esteem and confidence, enjoyment, and self-regulation. Youth reported positive sensory experiences with animals as supporting self-regulation. These findings suggest that AAI may need to be structured to prioritize youths' ability to form positive social connections with animals and incorporate positive sensory experiences while limiting negative ones.

Abstract Hepatitis E virus (HEV) genotype 3 infections in Germany are mainly transmitted zoonotically through the consumption of swine meat. Furthermore, there is evidence that pets might come into contact with HEV, but the relevance of companion animals as possible sources of HEV transmission in Germany still needs to be defined. A monitoring study was therefore carried out on dogs, cats, and horses from Germany. In total 365 serum samples from pets (124 dogs, 119 cats, and 122 horses) were tested for HEV by PCR and for anti-HEV antibodies by a commercial ELISA. The HEV seroprevalence determined by the sero-assay varied significantly between dogs (10%), cats (6%), and horses (2%). Liver injury-related enzymes, alanine transaminase (ALT), and aspartate transaminase (AST) showed no differences between HEV-positive or negative animals. None of the pet serum samples tested positive for PCR. This serological study suggests that dogs and cats are significantly exposed to HEV in Germany, while horses are of minor relevance.

Concrete tub crossings are at-grade railroad crossings used primarily on low-speed and low-tonnage rail lines. Concerns have been raised about the stiffness differential present between the track structure and crossing that could cause a localized shear strain increase. Due to this concern, much of the industry has limited speed of trains through these crossings to 40 kph (25 mph). This investigation evaluates a concrete tub crossing that experiences higher speeds and higher tonnage than typical. Visual observations and field performance indicate satisfactory performance of the crossing with little maintenance. Strain gauges mounted on the rail web were used to measure shear strains of trains at differing speeds. Results show little difference in maximum shear strain for train speeds up to 97 kph (60 mph). Concrete tub crossing shear demands are below shear capacity and independent of train speed, suggesting crossings can safely handle heavy railway traffic at greater speeds.

Abstract Adolescence is a key developmental period for the onset of social anxiety, as it is a time of social transitions and stressors. Therefore, it is important to identify protective factors within the environment that can prevent and/or reduce the effects of social anxiety in addition to existing evidence-based treatments. The presence of a supportive pet dog may be one way of reducing the effects of acute social stressors for youth, but these effects have not been tested robustly in real-world settings. This study aimed to assess the feasibility of using ecological momentary assessment (EMA) to assess physiological responses to pet interactions in real-life scenarios among adolescents with social anxiety (n = 37). Results indicated that this protocol was perceived as feasible by youth participants and allowed for integration across different data streams. Participant use of a wearable sensor to collect electrodermal activity was generally successful, with an average of 12 h of data collected per participant. However, the use of a timestamp button on the sensor was not an effective strategy for data collection. These findings suggest that EMA using self-report activity diary data combined with continuous psychophysiological measurement using wearable sensors is generally a feasible person-centered approach for measuring adolescent-dog interactions in a way that maintains ecological validity.

Abstract An elevated risk of myeloma precursor disease, monoclonal gammopathy of undetermined significance (MGUS), was identified among Fire Department of the City of New York (FDNY) World Trade Center (WTC)-exposed firefighters. Further investigation was needed to determine if these findings were reproducible in a more heterogeneous WTC-exposed rescue/recovery workers cohort, the Stony Brook University-General Responder Cohort GRC (SBU-GRC). MGUS risk was compared between the cohorts and to published general population estimates from Olmsted County, MN, USA. In this observational seroprevalence study, odds ratios (OR) and age-standardized risk ratios (RR) of MGUS (M-spike and light-chain-MGUS combined), M-spike, and light-chain-MGUS were estimated using logistic regression. Age-standardized prevalences were calculated for white males aged 50–79; RRs were estimated by comparing risk in the WTC-exposed cohort with the Olmsted County screened cohort. SBU-GRC had elevated odds of MGUS compared with FDNY (OR = 1.38; 95%CI = 1.00–1.89). The age-standardized prevalence of MGUS was 9.0/100 persons (95%CI = 7.5–10.6), over two-fold higher than the general population (RR = 2.08; 95%CI = 1.72–2.51); the age-standardized prevalence of light-chain-MGUS was 3.5-fold higher (RR = 3.54; 95%CI = 2.52–4.97). This study adds to mounting evidence supporting an association between WTC/environmental exposures and MGUS among rescue/recovery workers. Access to MGUS screenings for the entire WTC-exposed cohort could allow for treatment interventions that improve survival.

IntroductionThe objective of this study was to determine whether postoperative additive systemic steroid administration in chronic rhinosinusitis with nasal polyps (CRSwNP) impacted selected endoscopic, subjective and objective outcome measures.MethodsThis was a prospective, randomized, double-blind, placebo-controlled, noninferiority multicenter trial of n=106 patients with CRSwNP. All patients underwent primary functional endoscopic sinus surgery (FESS) followed by topical nasal steroids. Patients were randomized to a systemic steroid or placebo for 1 month. Patients were followed up for 2 years over 9 time points. The primary outcome measures were the differences between groups with respect to the nasal polyp score (NPS) and sinonasal quality of life (SNQoL). Secondary outcome measures included interactions with respect to the Lund-Kennedy score (LKS), sinonasal symptoms, general quality of life (GQoL), 16-item odor identification test scores, recurrence rates, need for revision surgery and mucus biomarker levels.Results106 patients were randomized to either the placebo or the systemic steroid group (n=53 per group). Postoperative systemic steroids were not superior to placebo with respect to all primary (p= 0.077) and secondary outcome measures (p>0.05 for all). Reported adverse events were similar between the two groups.ConclusionIn conclusion, the addition of postoperative systemic steroids after primary FESS did not confer a benefit over topical steroid nasal spray alone with respect to NPS, SNQOL, LKS, GQOL, sinonasal symptoms, smell scores, recurrence rates, the need for revision surgery or biomarkers over a short-term follow-up of up to 9 months and a long-term follow-up of up to 24 months in CRSwNP patients. Functional endoscopic surgery did, however, show a strong effect on all outcome measures, which remained relatively stable up to the endpoint at 2 years.

Abstract During the COVID-19 pandemic, a significant number of healthcare workers have been infected with SARS-CoV-2. However, there remains little knowledge regarding large droplet dissemination during airway management procedures in real life settings. 12 different airway management procedures were investigated during routine clinical care. A high-speed video camera (1000 frames/second) was for imaging. Quantitative droplet characteristics as size, distance traveled, and velocity were computed. Droplets were detected in 8/12 procedures. The droplet trajectories could be divided into two distinctive patterns (type 1/2). Type 1 represented a ballistic trajectory with higher speed large droplets whereas type 2 represented a random trajectory of slower particles that persisted longer in air. The use of tracheal cannula filters reduced the amount of droplets. Respiratory droplet patterns generated during airway management procedures follow two distinctive trajectories based on the influence of aerodynamic forces. Speaking and coughing produce more droplets than non-invasive ventilation therapy confirming these behaviors as exposure risks. Even large droplets may exhibit patterns resembling the fluid dynamics smaller airborne aerosols that follow the airflow convectively and may place the healthcare provider at risk.

As city governments take steps towards establishing emissions reduction targets, the atmospheric research community is increasingly able to assist in tracking emissions reductions. Researchers have established systems for observing atmospheric greenhouse gases in urban areas with the aim of attributing greenhouse gas concentration enhancements (and thus emissions) to the region in question. However, to attribute enhancements to a particular region, one must isolate the component of the observed concentration attributable to fluxes inside the region by removing the background, which is the component due to fluxes outside. In this study, we demonstrate methods to construct several versions of a background for our carbon dioxide and methane observing network in the Washington, DC, and Baltimore, MD, metropolitan region. Some of these versions rely on transport and flux models, while others are based on observations upwind of the domain. First, we evaluate the backgrounds in a synthetic data framework, and then we evaluate against real observations from our urban network. We find that backgrounds based on upwind observations capture the variability better than model-based backgrounds, although care must be taken to avoid bias from biospheric carbon dioxide fluxes near background stations in summer. Model-based backgrounds also perform well when upwind fluxes can be modeled accurately. Our study evaluates different background methods and provides guidance in determining background methodology that can impact the design of urban monitoring networks.

Objective: Companion animals are an important feature of the family system, and human-animal interaction is increasingly being recognized as an important social determinant of health. However, there is a need for more nuanced assessment of not only who owns pets, but how pet ownership is related to various health outcomes, and which sociodemographic and contextual factors moderate these associations. Design: Secondary analysis of cross-sectional data collected from an online, probability-based panel to generate a nationally representative sample of adults in the United States (n = 1267). Data were analyzed using hierarchical and logistic regression models. Results: Results suggested that pet owners are systematically different from non-pet owners on a number of key demographic and contextual characteristics, and these differences vary somewhat when looking at dog owners and cat owners. When controlling for individual and family-level covariates, pet ownership was not associated with overall health status or Body Mass Index, but dog ownership was associated with higher levels of physical activity. Pet ownership was associated with higher odds of having an anxiety disorder with gender moderating this relationship, but this association was not present for dog or cat owners, suggesting this relationship is limited to other types of pets. Higher odds of depression were associated with pet ownership (for both dog and cat owners), with employment status significantly moderating the relationship between dog ownership status and depression. Conclusions: These findings suggest that pet ownership is a complex and context specific phenomenon. Future research should carefully consider and control for sociodemographic predictors and use measurement and analysis approaches sensitive to the variations in human-animal relationships to fully understand how pets contribute to individual and family health and well-being.

Abstract Objective Repair of cerebrospinal fluid (CSF) leaks of the lateral recess of the sphenoid (LRS) sinus can be challenging to accomplish via an endoscopic transphenoidal approach. The endoscopic transpterygoid approach can improve surgical access to the lateral recess but requires more extensive surgical dissection. We review our experience with LRS CSF leak repair via both techniques to determine whether preoperative radiologic data can help predict the most appropriate surgical approach. Methods Electronic medical records of patients with LRS CSF leaks were retrospectively reviewed at a single tertiary referral center. Radiographic measurements from preoperative computed tomography images were reviewed. Results Twenty‐two LRS CSF leaks were identified. The transphenoidal and transpterygoid approach were used in 6 (27.3%) and 16 (72.7%) cases, respectively. The mean vidian canal to foramen rotundum angle of the repairs accessed transphenoidally as compared to the transptyergoid approach were not significantly different (41.93° ±10.91, 40.72° ±19.49, respectively; P = .63). However, the mean volume of the LRS accessed by the transpterygoid approach was significantly greater compared to those accessed through the transphenoidal approach (0.97 cm3 ± 0.48, 0.39 cm3 ± 0.40, respectively; P = .04). A LRS volume of 0.400 cm3 or greater predicted the use of the transpterygoid approach with 93.3% sensitivity and 60.0% specificity. Conclusion This study demonstrated that LRS CSF leaks that necessitated repair by the transpterygoid approach, rather than transphenoidal approach, were in the context of significantly larger lateral recess. Assessment of the LRS volume is a quantifiable parameter to aid in preoperative surgical planning. Level of Evidence Level 4.

Non-invasive biomarker analysis has made repetitive and painless sampling over time possible. Exosomes are being released from a parent cell and their cargo mirrors the cell micromilieu of the parent cell. Therefore, exosomes are promising surrogates for their parent cells. That is also why exosomes provide an improved signal-to-noise ratio. Current studies have identified valid non-invasive biomarkers that may be able to monitor disease severity. Exosomes are suggested to play an important role in interepithelial communication and are suggested to play a role in the initiation and maintenance of inflammation in CRS. They are, however, also involved simultaneously in several immunological processes including immune protection and immunosuppression. As the isolation of exosomes is time-consuming their value in everyday routine diagnostics has yet to be determined.

Human-animal-environment interaction (HAEI) is increasingly used in special education. While most research of HAEIs has identified effects that broadly support positive special education outcomes, further research of HAEI-based interventions in these environments is needed. Semi-structured interviews were conducted with 18 teaching staff at a special education school that utilizes a range of HAEIs. The teachers are responsible for implementing evidence-based interventions to facilitate social-emotional learning (SEL), so assessing their unique perspectives on the impacts of HAEIs on student SEL outcomes is imperative. Phenomenological coding of the interviews identified 9 major themes that represented positive impacts as well as barriers and challenges experienced by students during HAEIs.

If the 1950's became known to California rice growers as the years in which broadleaf weeds were finally controlled, then the 1960's appear to be the years in which grassy weeds—especially watergrass or barnyard grass—might also be brought under control with the use of selective chemicals. Preliminary tests and observations described in this report indicate that propanil, applied as a postemergence spray, and Ordram, a granular material applied at the preflood stage, may offer good control of watergrass in California rice fields which are continuously flooded during the growing season.

Despite higher annual installation costs, benefits from use of plastic levees for rice production can result in earnings of about one and a half times the extra cost, as compared with soil levees. Increased yields per acre result from production on land otherwise taken up by soil levees. Savings in time, labor and machinery are possible in tillage and harvesting operations. Plastic levees also permit a more rapid harvest so that problems with early fall rains are minimized. Photo to left shows completed plastic rice levee with upper check flooded.

A fly stem borer–Melanagromyza virens (Loew)–of wide tastes, showed 100% infestation of late-planted experimentally grown safflower at Davis during 1958.

Repulsive guidance molecule A (RGMa) is a potent inhibitor of axonal growth and a regulator of neuronal cell death. It is up-regulated following neuronal injury and accumulates in chronic neurodegenerative diseases. Neutralizing RGMa has the potential to promote neuroregeneration and neuroprotection. Previously we reported that a rat anti-N terminal RGMa (N-RGMa) antibody r5F9 and its humanized version h5F9 (ABT-207) promote neuroprotection and neuroregeneration in preclinical neurodegenerative disease models. However, due to its cross-reactivity to RGMc/hemojuvelin, ABT-207 causes iron accumulation in vivo, which could present a safety liability. Here we report the generation and characterization of a novel RGMa-selective anti-N-RGMa antibody elezanumab, which is currently under Phase 2 clinical evaluation in multiple disease indications. Elezanumab, a human monoclonal antibody generated by in vitro PROfusion mRNA display technology, competes with ABT-207 in binding to N-RGMa but lacks RGMc cross-reactivity with no impact on iron metabolism. It neutralizes repulsive activity of soluble RGMa in vitro and blocks membrane RGMa mediated BMP signaling. In the optic nerve crush and optic neuritis models, elezanumab promotes axonal regeneration and prevents retinal nerve fiber layer degeneration. In the spinal targeted experimental autoimmune encephalomyelitis (EAE) model, elezanumab promotes axonal regeneration and remyelination, decreases inflammatory lesion area and improves functional recovery. Finally, in the mouse cuprizone model, elezanumab reduces demyelination, which is consistent with its inhibitory effect on BMP signaling. Taken together, these preclinical data demonstrate that elezanumab has neuroregenerative and neuroprotective activities without impact on iron metabolism, thus providing a compelling rationale for its clinical development in neurodegenerative diseases.

For families with children during the COVID-19 pandemic, it is crucial to explore how both youth and parents view their roles with regard to the shared caretaking of pets. While most human–animal interaction studies examine adult or early childhood samples, our focus was on adolescent development. We present findings from a U.S. based mixed-method study of adolescent surveys and parent interviews regarding pet care responsibility. As part of an ongoing longitudinal study, we analyzed survey data from 567 pet-owning adolescents and a subset of 356 dog owning adolescents aged 10–17 as well as 31 in-depth interviews with parents of adolescents from the same study. Higher reported pet caretaking responsibilities was significantly associated with a preference for spending time with pets when stressed and improved family relationships during the COVID-19 pandemic for both pet owners and dog owners. For dog owners only, increased levels of responsibility for the pet was significantly associated with a higher likelihood of identifying as a pet owner. Qualitative findings showcase the range of parental expectations and adolescent initiative around pet caretaking. Our study highlights the continued importance of pet companionship during the adolescent years as they develop their identities as responsible pet owners.

Spinal cord injury (SCI) is a devastating condition characterized by loss of function, secondary to damaged spinal neurons, disrupted axonal connections, and myelin loss. Spontaneous recovery is limited, and there are no approved pharmaceutical treatments to reduce ongoing damage or promote repair. Repulsive guidance molecule A (RGMa) is upregulated following injury to the central nervous system (CNS), where it is believed to induce neuronal apoptosis and inhibit axonal growth and remyelination. We evaluated elezanumab, a human anti-RGMa monoclonal antibody, in a novel, newly characterized non-human primate (NHP) hemicompression model of thoracic SCI. Systemic intravenous (IV) administration of elezanumab over 6 months was well tolerated and associated with significant improvements in locomotor function. Treatment of animals for 16 weeks with a continuous intrathecal infusion of elezanumab below the lesion was not efficacious. IV elezanumab improved microstructural integrity of extralesional tissue as reflected by higher fractional anisotropy and magnetization transfer ratios in treated vs. untreated animals. IV elezanumab also reduced SCI-induced increases in soluble RGMa in cerebrospinal fluid, and membrane bound RGMa rostral and caudal to the lesion. Anterograde tracing of the corticospinal tract (CST) from the contralesional motor cortex following 20 weeks of IV elezanumab revealed a significant increase in the density of CST fibers emerging from the ipsilesional CST into the medial/ventral gray matter. There was a significant sprouting of serotonergic (5-HT) fibers rostral to the injury and in the ventral horn of lower thoracic regions. These data demonstrate that 6 months of intermittent IV administration of elezanumab, beginning within 24 h after a thoracic SCI, promotes neuroprotection and neuroplasticity of key descending pathways involved in locomotion. These findings emphasize the mechanisms leading to improved recovery of neuromotor functions with elezanumab in acute SCI in NHPs.

Background: Buruli ulcer (BU) is a cutaneous infectious disease caused by Mycobacterium ulcerans. In this prospective study, we aim to clarify the main histopathological features of cutaneous BU based on 4-mm skin punch biopsies and to evaluate the diagnostic value of this method. Methods: Between 2011 and 2013, a prospective study was conducted in Cameroon. Dry swabs from ulcerative lesions and fine-needle aspirates of nonulcerative lesions were examined for Ziehl-Neelsen (ZN) staining, followed by PCR targeting IS2404 and culture. Two 4-mm punch biopsies were performed in the center and in the periphery of each lesion. Results: The 364 patients included in the study had 422 lesions (381 were ulcerative and 357 lesions were biopsied). Among the 99 ulcerated lesions with a final diagnosis of BU, histological features for BU were fulfilled in 32 lesions. 32/32 showed subcutaneous necrosis with a neutrophilic inflammatory infiltrate. 26/32 presented alcohol-resistant bacilli confirmed by ZN stain on histology. Conclusion: Punch biopsies help in establishing the correct diagnosis of BU and also in the differential diagnosis of chronic ulcers. The main histological feature for BU is diffuse coagulative necrosis of subcutaneous tissue, with acid-fast bacilli detected by ZN stain.

Abstract Background Caregiver burden is present in many clients managing illness in a companion animal, but current assessment tools are time‐consuming and lack normative reference values. Objectives Statistical reduction of items in a measure of caregiver burden to create an abbreviated version, validation of the abbreviated version, and calculation of reference values. Animals None. Methods This study was conducted using observational methods. Owners of an ill cat or dog were recruited through social media (n = 429). Veterinary clients with an ill (n = 459) or healthy (n = 961) cat or dog were recruited through a general veterinary and an academic hospital with multiple specialties. The study was conducted in 3 stages: (a) reduction of the Zarit Burden Interview (ZBI) adapted for use in pets via factor and item analyses, (b) psychometric validation of the abbreviated instrument, and (c) standardization of the abbreviated (7 items) and full (18 items) measures. Results A 7‐item measure showed high correlations with the full measure (r = 0.88‐0.93) and good internal consistency (α = .71‐.75) across samples of veterinary clients with an ill cat or dog. This abbreviated measure correlated significantly (P

Greenhouse gas emissions mitigation requires understanding the dominant processes controlling fluxes of these trace gases at increasingly finer spatial and temporal scales. Trace gas fluxes can be estimated using a variety of approaches that translate observed atmospheric species mole fractions into fluxes or emission rates, often identifying the spatial and temporal characteristics of the emission sources as well. Meteorological models are commonly combined with tracer dispersion models to estimate fluxes using an inverse approach that optimizes emissions to best fit the trace gas mole fraction observations. One way to evaluate the accuracy of atmospheric flux estimation methods is to compare results from independent methods, including approaches in which different meteorological and tracer dispersion models are used. In this work, we use a rich data set of atmospheric methane observations collected during an intensive airborne campaign to compare different methane emissions estimates from the Barnett Shale oil and natural gas production basin in Texas, USA. We estimate emissions based on a variety of different meteorological and dispersion models. Previous estimates of methane emissions from this region relied on a simple model (a mass balance analysis) as well as on ground-based measurements and statistical data analysis (an inventory). We find that in addition to meteorological model choice, the choice of tracer dispersion model also has a significant impact on the predicted downwind methane concentrations given the same emissions field. The dispersion models tested often underpredicted the observed methane enhancements with significant variability (up to a factor of 3) between different models and between different days. We examine possible causes for this result and find that the models differ in their simulation of vertical dispersion, indicating that additional work is needed to evaluate and improve vertical mixing in the tracer dispersion models commonly used in regional trace gas flux inversions.

Acinic cell carcinoma (AciCC) is a rare salivary gland carcinoma that is poorly understood. Here the authors perform genomic, transcriptomic and epigenomic profiling of AciCC and find highly recurrent and specific rearrangements [t(4;9)(q13;q31)], which lead to enhancer hijacking that activates oncogenic transcription factor NR4A3.

Understanding the risk of infection by routine medical examination is important for the protection of the medical personnel. In this study we investigated respiratory particles emitted by patients during routine otolaryngologic procedures and assessed the risks for the performing physician. We developed two experimental setups to measure aerosol and droplet emission during rigid/flexible laryngoscopy, rhinoscopy, pharyngoscopy, otoscopy, sonography and patient interview for subjects with and without masks. A high-speed-camera setup was used to detect ballistic droplets (approx. > 100 µm) and an aerosol-particle-sizer was used to detect aerosol particles in the range of 0.3 µm to 10 µm. Aerosol particle counts were highly increased for coughing and slightly increased for heavy breathing in subjects without masks. The highest aerosol particle counts occurred during rigid laryngoscopy. During laryngoscopy and rhinoscopy, the examiner was exposed to increased particle emission due to close proximity to the patient’s face and provoked events such as coughing. However, even during sonography or otoscopy without a mask, aerosol particles were expelled close to the examiner. The physician’s exposure to respiratory particles can be reduced by deliberate choice of examination technique depending on medical indication and the use of appropriate equipment for the examiners and the patients (e.g., FFP2 masks for both).

The pathophysiological role of neural autoantibodies in acute psychotic disorders is receiving increased attention. However, there is still an ongoing debate, whether predominantly psychotic manifestations of autoimmune encephalitides exist that may remain undetected and, thus, untreated. Furthermore, it is discussed if such conditions can be diagnosed based on serum antibody results or if a reliable diagnosis requires additional cerebrospinal fluids (CSF) results. In this study, we screened pairs of serum and CSF samples from antipsychotic-naïve individuals with first-episode schizophrenic psychosis (FEP, n = 103), clinical high risk for psychosis (CHR, n = 47), and healthy volunteers (HV, n = 40) for eight different antibodies against various antigens that have been shown to be associated with autoimmune encephalitides: N-methyl-D-aspartate receptor (NMDAR, NR1 subunits only), glutamic acid decarboxylase (GAD65), leucine-rich glioma inactivated protein 1 (LGI1), contactin-associated protein-like 2 protein (CASPR2), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit 1, AMPAR subunit 2, γ-aminobutyric acid-B receptors (GABABR), and glycine receptors. All patients were within the norm with regards to a careful neurological examination, a magnetic resonance imaging (MRI) of the brain, an electroencephalogram (EEG), and routine blood pathology. All CSF samples were autoantibody-negative. In three serum samples of individuals with FEP, we detected low-titer CASPR2 immunoglobulin (Ig) G antibodies (≤1:160, n = 2) and non-IgG antibodies against NMDAR (n = 1) (overall serum-autoantibody prevalence in FEP: 2.91%). However, the IgG titers were below the laboratory cut-off defined for positivity, and non-IgG antibodies are of no clinical relevance. This suggests that there were no cases of autoimmune encephalitis in our cohort. Our results highlight the importance and the high specificity of CSF analysis to reliably detect autoantibodies. They confirm the hypothesis that pure psychotic manifestations of antibody-associated autoimmune encephalitides without any additional neuropsychiatric findings are very rare. However, special attention must be paid to those presenting with atypical mental illnesses with additional neurological symptoms, evidence of clinically-significant cognitive involvement, profound sleep-wake perturbations, seizures, electroencephalographic, or magnetic resonance imaging pathologies to be able to identify cases with autoimmune-mediated psychiatric syndromes.

Summary: Mutations in presenilin 1 (PSEN1) or presenilin 2 (PSEN2), the catalytic subunit of γ-secretase, cause familial Alzheimer’s disease (fAD). We hypothesized that mutations in PSEN1 reduce Notch signaling and alter neurogenesis. Expression data from developmental and adult neurogenesis show relative enrichment of Notch and γ-secretase expression in stem cells, whereas expression of APP and β-secretase is enriched in neurons. We observe premature neurogenesis in fAD iPSCs harboring PSEN1 mutations using two orthogonal systems: cortical differentiation in 2D and cerebral organoid generation in 3D. This is partly driven by reduced Notch signaling. We extend these studies to adult hippocampal neurogenesis in mutation-confirmed postmortem tissue. fAD cases show mutation-specific effects and a trend toward reduced abundance of newborn neurons, supporting a premature aging phenotype. Altogether, these results support altered neurogenesis as a result of fAD mutations and suggest that neural stem cell biology is affected in aging and disease.

Adolescence is a prime developmental period to explore human–pet relationships, particularly given that teens are often relying less on their families, and more on other attachment figures such as peers and pets. However, most research on pet companionship is conducted with adults and young children. Moreover, lived experiences around having pets in households with adolescents are underexplored, particularly from parents’ perspectives. This qualitative interview study of 31 parents/guardians in the Northeast U.S. explored perceptions of the benefits and challenges of having pets for their adolescent’s well-being as well as how adolescents affected their pet’s well-being. Our three main themes for perceived benefits of pets included social (e.g., reducing anxiety), physical (e.g., screen time companionship), and emotional (e.g., regulation of difficult emotions such as anger, loneliness). Challenges to adolescent well-being included such social topics as family tension around unevenly shared responsibilities, physical themes such as problematic animal behaviors, and emotional themes related to grieving the passing of pets. We offer a developmental systems approach to understanding pets within adolescent families, noting future directions for developing family interventions to improve pet–adolescent interactions given the demands of child and pet upbringing during adolescence.

The two main phytocannabinoids—delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)—have been extensively studied, and it has been shown that THC can induce transient psychosis. At the same time, CBD appears to have no psychotomimetic potential. On the contrary, emerging evidence for CBD's antipsychotic properties suggests that it may attenuate effects induced by THC. Thus, we investigated and compared the effects of THC and CBD administration on emotion, cognition, and attention as well as the impact of CBD pre-treatment on THC effects in healthy volunteers. We performed a placebo-controlled, double-blind, experimental trial (GEI-TCP II; ClinicalTrials.gov identifier: NCT02487381) with 60 healthy volunteers randomly allocated to four parallel intervention groups, receiving either placebo, 800 mg CBD, 20 mg THC, or both cannabinoids. Subjects underwent neuropsychological tests assessing working memory (Letter Number Sequencing test), cognitive processing speed (Digit Symbol Coding task), attention (d2 Test of Attention), and emotional state (adjective mood rating scale [EWL]). Administration of CBD alone did not influence the emotional state, cognitive performance, and attention. At the same time, THC affected two of six emotional categories—more precisely, the performance-related activity and extraversion—, reduced the cognitive processing speed and impaired the performance on the d2 Test of Attention. Interestingly, pre-treatment with CBD did not attenuate the effects induced by THC. These findings show that the acute intake of CBD itself has no effect per se in healthy volunteers and that a single dose of CBD prior to THC administration was insufficient to mitigate the detrimental impact of THC in the given setting. This is in support of a complex interaction between CBD and THC whose effects are not counterbalanced by CBD under all circumstances.

Spinal cord injury (SCI) often results in permanent functional loss due to a series of degenerative events including cell death, axonal damage, and the upregulation of inhibitory proteins that impede regeneration. Repulsive Guidance Molecule A (RGMa) is a potent inhibitor of axonal growth that is rapidly upregulated following injury in both the rodent and human central nervous system (CNS). Previously, we showed that monoclonal antibodies that specifically block inhibitory RGMa signaling promote neuroprotective and regenerative effects when administered acutely in a clinically relevant rat model of thoracic SCI. However, it is unknown whether systemic administration of RGMa blocking antibodies are effective for SCI after delayed administration. Here, we administered elezanumab, a human monoclonal antibody targeting RGMa, intravenously either acutely or at 3 h or 24 h following thoracic clip impact-compression SCI. Rats treated with elezanumab acutely and at 3 h post-injury showed improvements in overground locomotion and fine motor function and gait. Rats treated 24 h post-SCI trended towards better recovery demonstrating significantly greater stride length and swing speed. Treated rats also showed greater tissue preservation with reduced lesion areas. As seen with acute treatment, delayed administration of elezanumab at 3 h post-SCI also increased perilesional neuronal sparing and serotonergic and corticospinal axonal plasticity. In addition, all elezanumab treated rats showed earlier spontaneous voiding ability and less post-trauma bladder wall hypertrophy. Together, our data demonstrate the therapeutic efficacy of delayed systemic administration of elezanumab in a rat model of SCI, and uncovers a new role for RGMa inhibition in bladder recovery following SCI.

Objective: To describe perceptions of maternal discrimination and to begin to understand patterns around timing of starting families, infertility, and post-partum depression among veterinary mothers.Design: Cross-sectional questionnaire with closed and open-ended questions posted to a social media platform “Moms with a DVM.”Sample: 1,082 veterinary mothers in the United States.Procedures: An online questionnaire was administered regarding perceived discrimination, inequities in the work-place due to pregnant or maternal status, desired accommodations, timing of pregnancy(ies), fertility issues, and postpartum experiences.Results: At least one form of perceived discrimination was reported by 819 (75.7%) respondents (M = 2.6, SD = 2.1, range 0–10). Specifically, 789 (72.9%) reported maternal discrimination. Over half of the sample (n = 632, 58.4%) reported at least one instance of perceived inequity in the workplace due to status as a mother (M = 1.23, SD = 1.4, range 0–5). A majority (906, 83.7%) reported that their career had “definitely” or “maybe” affected the timing of their children. One hundred eighty-nine respondents (17.5%) experienced at least one miscarriage, and 192 (17.6%) used fertility treatment due to difficulty conceiving. Postpartum depression was diagnosed in 181 respondents (16.7%), and 353 (32.6%) reported symptoms consistent with postpartum depression but did not seek medical care. Of 953 participants who needed accommodations for breastfeeding and/or pumping while at work, 130 (13.6%) reported excellent accommodations, 454 (47.6%) adequate, 258 (27.1%) inadequate, and 111 (11.6%) had no accommodations provided.Conclusions and Clinical Relevance: Participants reported experiences of perceived maternal discrimination, as well as inequities and lack of support services due to status as a mother. These results highlight the need for attention and changes to ensure veterinarians have supportive and sustainable career options.

Solid phase peptide synthesis (SPPS) provides the possibility to chemically synthesize peptides and proteins. Applying the method on hydrophilic structures is usually without major drawbacks but faces extreme complications when it comes to “difficult sequences.” These includes the vitally important, ubiquitously present and structurally demanding membrane proteins and their functional parts, such as ion channels, G-protein receptors, and other pore-forming structures. Standard synthetic and ligation protocols are not enough for a successful synthesis of these challenging sequences. In this review we highlight, summarize and evaluate the possibilities for synthetic production of “difficult sequences” by SPPS, native chemical ligation (NCL) and follow-up protocols.

The objective of this manuscripts to review current knowledge regarding exosomes as they relate to the physiology and pathology of the human nose as well as their role as biomarkers of chronic rhinosinusitis with nasal polyps (CRSwNP).Exosomes are 30–150 nm membrane-bound vesicles secreted by virtually all cell types. Exosomes contribute to the rapid inter-epithelial transfer of proteins and mediate innate immunosurveillance and defense mechanisms in the human nasal cavity. Exosomes also protect their cell specific cargo from degradation by nucleases and proteases and mirrorCRS related tissue protein perturbations more effectively than whole mucus. Thus, exosomal isolation and analysis may be used to non-invasively monitor disease severity, prognosis, and potentially even treatment response.Recent studies of exosomes in CRS suggest they can be used to study the immunopathology of chronic sinonasal inflammation. Furthermore, their relative accessibility suggests that exosomal proteomescan be used as non-invasive, serial, and quantitative biosignatures for rhinosinusitis that can be sampled in clinic in order to predict disease severity, prognosis, and treatment response. Exosomal research has also led to important revelations regarding their physiologic function as they seem to play an important role in innate immunosurveillance and defense. However, exosomal research is still nascent and cost-effectiveness as well as feasibility of implementation in the routine workup for CRS have to be further explored.

The numerical modeling of tsunami inundation that incorporates the built environment of coastal communities is challenging for both 2-D and 3-D depth-integrated models, not only in modeling the flow but also in predicting forces on coastal structures. For depth-integrated 2-D models, inundation and flooding in this region can be very complex with variation in the vertical direction caused by wave breaking on shore and interactions with the built environment, and the model may not be able to produce enough detail. For 3-D models, a very fine mesh is required to properly capture the physics, dramatically increasing the computational cost and rendering impractical the modeling of some problems. In this paper, comparisons are made between GeoClaw, a depth-integrated 2-D model based on the nonlinear shallow-water equations (NSWEs), and OpenFOAM, a 3-D model based on Reynolds-averaged Navier–Stokes (RANS) equation for tsunami inundation modeling. The two models were first validated against existing experimental data of a bore impinging onto a single square column. Then they were used to simulate tsunami inundation of a physical model of Seaside, Oregon. The resulting flow parameters from the models are compared and discussed, and these results are used to extrapolate tsunami-induced force predictions. It was found that the 2-D model did not accurately capture the important details of the flow near initial impact due to the transiency and large vertical variation of the flow. Tuning the drag coefficient of the 2-D model worked well to predict tsunami forces on structures in simple cases, but this approach was not always reliable in complicated cases. The 3-D model was able to capture transient characteristic of the flow, but at a much higher computational cost; it was found this cost can be alleviated by subdividing the region into reasonably sized subdomains without loss of accuracy in critical regions.

Abstract Background Transcranial focused ultrasound (tFUS) is a new non-invasive neuromodulation technique that uses mechanical energy to modulate neuronal excitability with high spatial precision. tFUS has been shown to be capable of modulating EEG brain activity in humans that is spatially restricted, and here, we use 7T MRI to extend these findings. We test the effect of tFUS on 7T BOLD fMRI signals from individual finger representations in the human primary motor cortex (M1) and connected cortical motor regions. Participants (N = 5) performed a cued finger tapping task in a 7T MRI scanner with their thumb, index, and middle fingers to produce a BOLD signal for individual M1 finger representations during either tFUS or sham neuromodulation to the thumb representation. Results Results demonstrated a statistically significant increase in activation volume of the M1 thumb representation for the tFUS condition as compared to sham. No differences in percent BOLD changes were found. This effect was spatially confined as the index and middle finger M1 finger representations did not show similar significant changes in either percent change or activation volume. No effects were seen during tFUS to M1 in the supplementary motor area or the dorsal premotor cortex. Conclusions Single element tFUS can be paired with high field MRI that does not induce significant artifact. tFUS increases activation volumes of the targeted finger representation that is spatially restricted within M1 but does not extend to functionally connected motor regions. Trial registration ClinicalTrials.gov NCT03634631 08/14/18

Abstract Background We focused on human-animal interaction (HAI) as an important aspect of social functioning at the individual level, framing this emerging field from a public health perspective. Methods Using data from the Health and Retirement Study (HRS) 2012 HAI module, we describe the characteristics of pet ownership in a population of older adults, and examine the relation between pet ownership and multiple mental and physical health indicators such as health status, depression, and physical activity. Results Of the 1657 participants in our subsample, approximately half (51.5%) reported being pet owners; the majority owned dogs or cats, and most had only one pet. Pet ownership was significantly associated with a higher likelihood of ever having had depression, with pet owners being 1.89 times more likely to have experienced depression. However, pet ownership was not associated with having experienced depression within the last week. Conclusions The findings from this study could indicate a relationship between pet ownership and depression, but it is impossible to determine the directionality of that relationship. It is possible that owning a pet may put a person at an increased risk of developing depression, or individuals who are at risk, or who have already developed depression, may acquire a pet as a way of managing their depressive symptoms. The findings of this study provide an initial step in contributing to our understanding of the relationship between companion animals and the social, physical, and mental well-being of the HRS study population. Future research should include measures of HAI in longitudinal, population-based surveys.

Abstract Background Geriatric syndromes are rarely detected in family medicine. Within the AGE program (active geriatric evaluation), a brief assessment tool (BAT) designed for family physicians (FP) was developed and its diagnostic performance estimated by comparison to a comprehensive geriatric assessment. Methods This prospective diagnostic study was conducted in four primary care sites in Switzerland. Participants were aged at least 70 years and attending a routine appointment with their physician, without previous documented geriatric assessment. Participants were assessed by their family physicians using the BAT, and by a geriatriciant who performed a comprehensive geriatric assessment within the following two-month period (reference standard). Both the BAT and the full assessment targeted eight geriatric syndromes: cognitive impairment, mood impairment, urinary incontinence, visual impairment, hearing loss, undernutrition, osteoporosis and gait and balance impairment. Diagnostic accuracy of the BAT was estimated in terms of sensitivity, specificity, and predictive values; secondary outcomes were measures of feasibility, in terms of added consultation time and comprehensiveness in applying the BAT items. Results Prevalence of the geriatric syndromes in participants (N=85, 46 (54.1%) women, mean age 78 years (SD 6))ranged from 30.0% (malnutrition and cognitive impairment) to 71.0% (visual impairment), with a median number of 3 syndromes (IQR 2 to 4) per participant. Sensitivity of the BAT ranged from 25.0% for undernutrition (95%CI 9.8% - 46.7%) to 82.1% for hearing impairment (95%CI 66.5% - 92.5%), while specificity ranged from 45.8% for visual impairment (95%CI 25.6–67.2) to 87.7% for undernutrition (76.3% to 94.9%). Finally, most negative predictive values (NPV) were between 73.5% and 84.1%, excluding visual impairment with a NPV of 50.0%. Family physicians reported BAT use as per instructions for 76.7% of the syndromes assessed. Conclusions Although the BAT does not replace a comprehensive geriatric assessment, it is a useful and appropriate tool for the FP to screen elderly patients for most geriatric syndromes. Trial registration The study was registered on ClinicalTrials.gov on February 20, 2013 (NCT01816087).

The pandemic associated with the emergence of the novel coronavirus (COVID-19) is an unprecedented historical event with the potential to significantly impact adolescent loneliness. This study aimed to explore the role of companion animals and attachment to pets in the context of the pandemic. We used longitudinal quantitative survey data collected prior to and during the pandemic to assess the role of pets in predicting adolescent loneliness. Pet ownership was not a significant predictor of loneliness before the pandemic, but did predict higher levels of loneliness during COVID-19 as well as higher increases in loneliness from before to during the pandemic. Dog ownership predicted lower levels of loneliness prior to, but not during the pandemic, and dog owners were significantly more attached to their pets than non-dog pet owners. Adolescents with pets reported spending more time with their pets during the pandemic, and frequently reported pet interactions as a strategy for coping with stress. Overall, the results from this study did not support the presence of a buffering effect of companion animals on loneliness for adolescents and indicate complexity in the relationships between pet ownership, attachment, loneliness, and coping with stress. These results suggest a need for additional research further assessing how features of the relationship such as species and relationship quality might contribute to adolescent mental health outcomes.