Microvasculature of the suspensory ligament of the equine hind limb.

OBJECTIVE: To describe the microvascular anatomy of the equine hind limb suspensory ligament. ANIMALS: 18 hind limbs harvested from 9 adult horses euthanized for reasons unrelated to lameness. METHODS: A catheter was placed in the transected cranial tibial artery at the level of the mid-distal tibia for each hind limb and used to inject 120 to 150 mL of contrast medium (2 limbs) to identify principal vasculature using contrast-enhanced CT or India ink (11 limbs) to identify microvasculature using the Spalteholz tissue-clearing technique. Routine histologic evaluation was performed on transverse sections from 4 hind limbs. RESULTS: The hind limb suspensory ligament is principally supplied by branches of the medial and lateral plantar metatarsal arteries and, to a lesser extent, the medial and lateral plantar arteries as well as the associated proximal and distal deep plantar arches. A uniformly distributed intraligamentous microvascular supply was observed without relative deficiencies in vascularity between the proximal, midbody, and distal regions. Histologic examination supported these findings, demonstrating a network of connective tissue surrounding and entering the suspensory ligament containing cross-sections of branches of the principal vasculature. CLINICAL RELEVANCE: The equine hind limb suspensory ligament has a uniformly distributed and abundant microvascular supply throughout its length, with no evidence of relative deficiency of vascular supply in any region. A region of hypovascularity does not appear to be a viable explanation for the high rate of injury to and commonality of lameness associated with the proximal hind suspensory ligament in horses.

Semiautomated approach focused on new genomic information results in time and effort-efficient reannotation of negative exome data.

Most rare disease patients (75-50%) undergoing genomic sequencing remain unsolved, often due to lack of information about variants identified. Data review over time can leverage novel information regarding disease-causing variants and genes, increasing this diagnostic yield. However, time and resource constraints have limited reanalysis of genetic data in clinical laboratories setting. We developed RENEW, (REannotation of NEgative WES/WGS) an automated reannotation procedure that uses relevant new information in on-line genomic databases to enable rapid review of genomic findings. We tested RENEW in an unselected cohort of 1066 undiagnosed cases with a broad spectrum of phenotypes from the Mayo Clinic Center for Individualized Medicine using new information in ClinVar, HGMD and OMIM between the date of previous analysis/testing and April of 2022. 5741 variants prioritized by RENEW were rapidly reviewed by variant interpretation specialists. Mean analysis time was approximately 20 s per variant (32 h total time). Reviewed cases were classified as: 879 (93.0%) undiagnosed, 63 (6.6%) putatively diagnosed, and 4 (0.4%) definitively diagnosed. New strategies are needed to enable efficient review of genomic findings in unsolved cases. We report on a fast and practical approach to address this need and improve overall diagnostic success in patient testing through a recurrent reannotation process.

Suppression of host humoral immunity by Borrelia burgdorferi varies over the course of infection.

Borrelia burgdorferi, the spirochetal agent of Lyme disease, utilizes a variety of strategies to evade and suppress the host immune response, which enables it to chronically persist in the host. The resulting immune response is characterized by unusually strong IgM production and a lack of long-term protective immunity. Previous studies in mice have shown that infection with B. burgdorferi also broadly suppresses host antibody responses against unrelated antigens. Here, we show that mice infected with B. burgdorferi and concomitantly immunized with recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein had an abrogated antibody response to the immunization. To further define how long this humoral immune suppression lasts, mice were immunized at 2, 4, and 6 weeks post-infection. Suppression of host antibody production against the SARS-CoV-2 spike protein peaked at 2 weeks post-infection but continued for all timepoints measured. Antibody responses against the SARS-CoV-2 spike protein were also assessed following antibiotic treatment to determine whether this immune suppression persists or resolves following clearance of B. burgdorferi. Host antibody production against the SARS-CoV-2 spike protein returned to baseline following antibiotic treatment; however, anti-SARS-CoV-2 IgM remained high, comparable to levels found in B. burgdorferi-infected but untreated mice. Thus, our data demonstrate restored IgG responses following antibiotic treatment but persistently elevated IgM levels, indicating lingering effects of B. burgdorferi infection on the immune system following treatment.

How Do College Students Perceive Their Partner Responds to Them When They Refuse Sexual Activity?

Refusal communication is a dyadic process, with one person communicating a refusal and another person responding. To enhance our understanding of this process, we surveyed college students to assess their interpretation of their partners' responses when they declined vaginal-penile sexual activity. In an online survey, participants were prompted to describe their partners' reactions when participants refused their partner's vaginal-penile sex initiation. Through content analysis, three themes were present: (1) partner accepted the refusal, (2) partner experienced negative emotions, (3) partner ignored their refusals. Participants frequently reported their refusals were accepted. Sexual assault prevention initiatives should work to normalize refusal communication.

Our Ways, Your Ways, Both Ways - a multi-disciplinary collaboration to develop, embed and evaluate a model of social and emotional wellbeing care for Aboriginal and Torres Strait Islander young people who experience detention - Phase 1.

The National Strategic Framework for Aboriginal and Torres Strait Islander Peoples' Mental Health and Social and Emotional Wellbeing identifies building a strong Aboriginal and Torres Strait Islander led evidence-base to inform care as a key priority. Aboriginal and/or Torres Strait Islander adolescents in contact with the criminal justice system are a highly vulnerable group of Australians, with substantial unmet needs. There is limited evidence to inform culturally appropriate models of care that meet the social and emotional wellbeing needs of justice-involved Aboriginal and/or Torres Strait Islander adolescents. This project aims to develop, implement and evaluate an in-reach and community transitional model of social and emotional wellbeing care for Aboriginal and/or Torres Strait Islander adolescents (10-17 years old) who experience detention through close engagement with Aboriginal and/or Torres Strait Islander youth, Elders, researchers, practitioners and community members, and by drawing on culturally informed practice and knowledge systems. The project is based on a multi-level mixed methods design, with a strong focus on ongoing project evaluation (based on the Ngaa-bi-nya framework) and co-design. Co-design is facilitated through culturally safe and trauma informed participatory processes based on development of strong partnerships from project initiative, design, implementation and evaluation. Application of the landscape domain of the Ngaa-bi-nya framework for Aboriginal and Torres Strait Islander program evaluation will be explored in Phase one. Aboriginal and Torres Strait Islander adolescents with experience in detention will be engaged through one-on-one interviews with data collection through the Growth and Empowerment Measure (GEM) Youth (which will be adapted from the adult version and validated as part of this study), the Kessler Psychological Distress Scale (K-10), questions around alcohol and drug use, and narrative interviews exploring experience. Qualitative data will be analyzed using an inductive thematic approach, structured within the framework of the Ngaa-bi-nya landscape prompts. Quantitative data will be analyzed using descriptive statistics to provide a profile of the cohort. Findings from Phase one will be used to inform the development of a model of social and emotional wellbeing care that will be implemented and evaluated in Phase two.

A Synthetic Formula Amino Acid Diet Leads to Microbiome Dysbiosis, Reduced Colon Length, Inflammation, and Altered Locomotor Activity in C57BL/6J Mice.

The effects of synthetic, free-amino acid diets, similar to those prescribed as supplements for (phenylketonuria) PKU patients, on gut microbiota and overall health are not well understood. In the current, multidisciplinary study, we examined the effects of a synthetically-derived, low-fiber, amino acid diet on behavior, cognition, gut microbiome composition, and inflammatory markers. A cohort of 20 male C57BL/6J mice were randomly assigned to either a standard or synthetic diet (n = 10) at post-natal day 21 and maintained for 13 weeks. Sequencing of the 16S rRNA gene from fecal samples revealed decreased bacterial diversity, increased abundance of bacteria associated with disease, such as Prevotella, and a downward shift in gut microbiota associated with fermentation pathways in the synthetic diet group. Furthermore, there were decreased levels of short chain fatty acids and shortening of the colon in mice consuming the synthetic diet. Finally, we measured TNF-α, IL-6, and IL-10 in serum, the hippocampus, and colon, and found that the synthetic diet significantly increased IL-6 production in the hippocampus. These results demonstrate the importance of a multidisciplinary approach to future diet and microbiome studies, as diet not only impacts the gut microbiome composition but potentially systemic health as well.

Modular Splicing Is Linked to Evolution in the Synapse-Specificity Molecule Kirrel3.

Kirrel3 is a cell-adhesion molecule that instructs the formation of specific synapses during brain development in mouse and Kirrel3 variants may be risk factors for autism and intellectual disabilities in humans. Kirrel3 is predicted to undergo alternative splicing but brain isoforms have not been studied. Here, we present the first in-depth characterization of Kirrel3 isoform diversity in brain using targeted, long-read mRNA sequencing of mouse hippocampus. We identified 19 isoforms with predicted transmembrane and secreted forms and show that even rare isoforms generate detectable protein in the brain. We also analyzed publicly-available long-read mRNA databases from human brain tissue and found 11 Kirrel3 isoforms that, similar to mouse, encode transmembrane and secreted forms. In mice and humans, Kirrel3 diversity arises from alternative, independent use of protein-domain coding exons and alternative early translation-stop signals. Intriguingly, the alternatively spliced exons appear at branch points in the chordate phylogenetic tree, including one exon only found in humans and their closest living relatives, the great apes. Together, these results validate a simple pipeline for analyzing isoform diversity in genes with low expression and suggest that Kirrel3 function is fine-tuned by alternative splicing and may play a role in brain evolution.

Culturally Informed Australian Aboriginal and Torres Strait Islander Evaluations: A Scoping Review.

Rigorous and effective evaluations inform policy and service delivery and create evidence of program impacts and outcomes for the communities they are designed to support. Genuine engagement of communities is a key feature of effective evaluation, building trust and enhancing relevancy for communities and providing meaningful outcomes and culturally relevant findings. This applies to Indigenous peoples' leadership and perspectives when undertaking evaluations on programs that involve Indigenous communities. This systematic scoping review sought to explore the characteristics of culturally informed evaluations and the extent of their application in Australia, including the use of specific evaluation tools and types of community engagement. Academic and grey literature were searched between 2003 and 2023, with 57 studies meeting the inclusion criteria. Over time, there was an increase in the number of culturally informed evaluations undertaken, predominantly in the health and wellbeing sector. Around a quarter used a tool specifically developed for Indigenous evaluations. Half of the publications included Indigenous authorship; however, most studies lacked detail on how evaluations engaged with communities. This review highlights the need for further development of evaluation tools and standardised reporting to allow for shared learnings and improvement in culturally safe evaluation practices for Aboriginal and Torres Strait Islander communities.

Humans can detect axillary odor cues of an acute respiratory infection in others.

Background and objectives: Body odor conveys information about health status to conspecifics and influences approach-avoidance behaviors in animals. Experiments that induce sickness in otherwise healthy individuals suggest that humans too can detect sensory cues to infection in others. Here, we investigated whether individuals could detect through smell a naturally occurring acute respiratory infection in others and whether sickness severity, measured via body temperature and sickness symptoms, was associated with the accuracy of detection. Methodology: Body odor samples were collected from 20 donors, once while healthy and once while sick with an acute respiratory infection. Using a double-blind, two-alternative forced-choice method, 80 raters were instructed to identify the sick body odor from paired sick and healthy samples (i.e. 20 pairs). Results: Sickness detection was significantly above chance, although the magnitude of the effect was low (56.7%). Raters' sex and disgust sensitivity were not associated with the accuracy of sickness detection. However, we find some indication that greater change in donor body temperature, but not sickness symptoms, between sick and healthy conditions improved sickness detection accuracy. Conclusion and implications: Our findings suggest that humans can detect individuals with an acute respiratory infection through smell, albeit only slightly better than chance. Humans, similar to other animals, are likely able to use sickness odor cues to guide adaptive behaviors that decrease the risk of contagion, such as social avoidance. Further studies should determine how well humans can detect specific infections through body odor, such as Covid-19, and how multisensory cues to infection are used simultaneously.

Biological-physical interactions are fundamental to understanding and managing coastal dynamics.

There is an urgent need to address coastal dynamics as a fundamental interaction between physical and biological processes, particularly when trying to predict future biological-physical linkages under anticipated changes in environmental forcing. More integrated modelling, support for observational networks and the use of management interventions as controlled experimental exercises should now be vigorously pursued.

A test of multimodal communication in humans using 881 judgements of men and women's physical, vocal, and olfactory attractiveness.

Human mate value is assessed on numerous variables including, reproductive potential and disease resistance. Many of these variables have been correlated with judgments of physical, vocal, and odor attractiveness. While some researchers posit that attractiveness judgments made across different sensory modalities reflect the same underlying variable(s) (i.e., the information is redundant), others suggest that judgments made in different modalities reflect different variables. Previous studies of human attractiveness indicate that attractiveness judgments of others' faces, bodies, and voices are intercorrelated, which is suggested to support the redundancy hypothesis. Less is known about body odor attractiveness. Only one study has simultaneously investigated the relationships between judgments of body odor, face, and voice attractiveness finding weak positive associations, but small effect sizes. In this study, we empirically investigate the correlation between different modalities of attractiveness in men and women in the largest sample to date (N = 881 ratings). For men, we find no correlations between modalities of attractiveness. However, for women we find odor, face, and voice attractiveness are weakly correlated. Moreover, a general attractiveness factor (i.e., a common underlying variable) modestly contributed to the observed correlations between modality-specific attractiveness judgments, providing some evidence for the redundancy hypothesis.

Alcohol and other drug use before custody among Aboriginal and non-Aboriginal people in New South Wales, Australia.

OBJECTIVE: Alcohol and other drug (AoD) use is a significant factor in the poor health status of people in prison. Our aim is to explore associations of alcohol consumption with tobacco and illicit drug use among Aboriginal and non-Aboriginal people in prison to inform health services, clinical care and support. METHODS: We analysed the alcohol, tobacco and illicit drug use data of the 2015 Network Patient Health Survey of adults in custody in New South Wales (n=1,132). A comparative analysis of Aboriginal to non-Aboriginal participants including bi-variant and multivariant analysis was undertaken. RESULTS: Significantly more Aboriginal than non-Aboriginal participants reported alcohol consumption before prison that was consistent with possible dependence. More Aboriginal than non-Aboriginal participants used cannabis on a daily or almost on daily basis before prison. There was significant association between alcohol and cannabis use among Aboriginal participants. CONCLUSIONS: There are differences in Aboriginal and non-Aboriginal AoD use patterns, which should be considered when providing treatment and support programs within and post-release from prison. IMPLICATIONS FOR PUBLIC HEALTH: Specific programs are needed to assist Aboriginal people in this population who co-use alcohol and cannabis.

The Bunya Project: Protocol for a Mixed-Methods Approach to Developing a Culturally Informed Curriculum.

BACKGROUND: Indigenous peoples live across all continents, representing approximately 90 nations and cultures and 476 million people. There have long been clear statements about the rights of Indigenous peoples to self-determine services, policies, and resource allocations that affect our lives, particularly via the United Nations Declaration on the Rights of Indigenous Peoples. An area for urgent improvement is curricula that train the predominantly non-Indigenous health workforce about their responsibilities and that offer practical strategies to use when engaging with Indigenous peoples and issues. OBJECTIVE: The Bunya Project is designed to advance Indigenous community-led teaching and evaluation of the embeddedness of strategies to achieve an Indigenous Graduate Attribute in Australia. The project centers the relationships with Aboriginal community services to lead education design relating to Indigenous peoples. The project aims to articulate community recommendations for university education in allied health in the usable format of digital stories to create culturally informed andragogy, curriculum, and assessment measures for use in teaching. It also aims to understand the impact of this work on student attitudes and knowledge about Indigenous peoples' allied health needs. METHODS: Multilayered project governance was established, along with a 2-stage process using mixed methods participatory action research and critical reflection, using the reflective cycle by Gibbs. The first stage, preparing the soil, used community engagement, drew on lived experience, encouraged critical self-reflection, embodied reciprocity, and demanded working collectively. The second stage, planting the seed, requires more critical self-reflection, the development of community data through interviews and focus group discussions, the development of resources with an academic working group and community participants, the implementation of those resources with student feedback, the analysis of the feedback from students and community members, and reflection. RESULTS: The protocol for the first stage, preparing the soil, is complete. The results of the first stage are the relationships built and the trust earned and gained, and it has resulted in the development of the planting the seed protocol. As of February 2023, we have recruited 24 participants. We will analyze data shortly and expect to publish the results in 2024. CONCLUSIONS: The readiness of non-Indigenous staff to engage with Indigenous communities has not been ascertained by Universities Australia, nor can it be assured. Staff preparation and skills to support the curriculum, create a safe learning environment, and develop teaching and learning strategies to guide academics to recognize that how students learn is as important as the content students learn. This learning has broad implications and benefits for staff and students within their professional practice and for lifelong learning. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39864.

Duration of stay and rate of subsequent criminal conviction and hospitalisation for substance use among young people admitted to a short-term residential program.

INTRODUCTION: This study examined the association between program duration and rate of criminal conviction and hospitalisation for substance use up to 15 years later among young people admitted to a short-term residential program for drug and alcohol use. METHODS: Data were derived from linked administrative records of all clients referred to a modified therapeutic community for young people from January 2001 to December 2016 in New South Wales, Australia (n = 3059). Cox proportional hazards regression analyses examined the rate of conviction (separately for any offence, violent offence, non-violent offence and administrative offence) and hospitalisation for substance use, up to 15 years post-program among young people who attended treatment for 1-29 days, 30-59 days, 60-89 days and 90-120 days. RESULTS: Thirty days or more in treatment was independently associated with a lower rate of conviction for any offence and a non-violent offence, as well as hospitalisation for substance use, while 60 days or more was associated with a lower rate of conviction for a violent and administrative offence, relative to those who spent 1-29 days in the program. Additional months in the program were also associated with reduced rates of conviction and hospitalisation, although 90-120 days appeared to confer no additional benefits than 60-89 days. DISCUSSION AND CONCLUSIONS: At least 60 days may be the minimum duration needed for short-term, therapeutic community programs to reduce the risk of conviction across all crime types and hospitalisation for substance use.

Unselfish traits and social decision-making patterns characterize six populations of real-world extraordinary altruists.

Acts of extraordinary, costly altruism, in which significant risks or costs are assumed to benefit strangers, have long represented a motivational puzzle. But the features that consistently distinguish individuals who engage in such acts have not been identified. We assess six groups of real-world extraordinary altruists who had performed costly or risky and normatively rare (<0.00005% per capita) altruistic acts: heroic rescues, non-directed and directed kidney donations, liver donations, marrow or hematopoietic stem cell donations, and humanitarian aid work. Here, we show that the features that best distinguish altruists from controls are traits and decision-making patterns indicating unusually high valuation of others' outcomes: high Honesty-Humility, reduced Social Discounting, and reduced Personal Distress. Two independent samples of adults who were asked what traits would characterize altruists failed to predict this pattern. These findings suggest that theories regarding self-focused motivations for altruism (e.g., self-enhancing reciprocity, reputation enhancement) alone are insufficient explanations for acts of real-world self-sacrifice.

Altered transcriptomes, cell type proportions, and dendritic spine morphology in hippocampus of suicide deaths.

Suicide is a condition resulting from complex environmental and genetic risks that affect millions of people globally. Both structural and functional studies identified the hippocampus as one of the vulnerable brain regions contributing to suicide risk. Here, we have identified the hippocampal transcriptomes, gene ontology, cell type proportions, dendritic spine morphology, and transcriptomic signature in iPSC-derived neuronal precursor cells (NPCs) and neurons in postmortem brain tissue from suicide deaths. The hippocampal tissue transcriptomic data revealed that NPAS4 gene expression was downregulated while ALDH1A2, NAAA, and MLXIPL gene expressions were upregulated in tissue from suicide deaths. The gene ontology identified 29 significant pathways including NPAS4-associated gene ontology terms "excitatory post-synaptic potential", "regulation of postsynaptic membrane potential" and "long-term memory" indicating alteration of glutamatergic synapses in the hippocampus of suicide deaths. The cell type deconvolution identified decreased excitatory neuron proportion and an increased inhibitory neuron proportion providing evidence of excitation/inhibition imbalance in the hippocampus of suicide deaths. In addition, suicide deaths had increased dendric spine density, due to an increase of thin (relatively unstable) dendritic spines, compared to controls. The transcriptomes of iPSC-derived hippocampal-like NPCs and neurons revealed 31 and 33 differentially expressed genes in NPC and neurons, respectively, of suicide deaths. The suicide-associated differentially expressed genes in NPCs were RELN, CRH, EMX2, OXTR, PARM1 and IFITM2 which overlapped with previously published results. The previously-known suicide-associated differentially expressed genes in differentiated neurons were COL1A1, THBS1, IFITM2, AQP1, and NLRP2. Together, these findings would help better understand the hippocampal neurobiology of suicide for identifying therapeutic targets to prevent suicide.

Enhanced Adsorption of Epoxy-Functional Nanoparticles onto Stainless Steel Significantly Reduces Friction in Tribological Studies.

Epoxy-functional sterically-stabilized diblock copolymer nanoparticles (ca. 27 nm) are prepared via RAFT dispersion polymerization in mineral oil. Nanoparticle adsorption onto stainless steel is examined using a quartz crystal microbalance. Incorporating epoxy groups within the steric stabilizer chains results in a two-fold increase in the adsorbed amount, Γ, at 20 °C (7.6 mg m-2 ) compared to epoxy-core functional nanoparticles (3.7 mg m-2 ) or non-functional nanoparticles (3.8 mg m-2 ). A larger difference in Γ is observed at 40 °C; this suggests chemical adsorption of the nanoparticles rather than merely physical adsorption. A remarkable near five-fold increase in Γ is observed for ca. 50 nm epoxy-functional nanoparticles compared to non-functional nanoparticles (31.3 vs. 6.4 mg m-2 , respectively). Tribological studies confirm that chemical adsorption of the latter epoxy-functional nanoparticles leads to a significant reduction in friction between 60 °C and 120 °C.