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.

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.

"It's about Rights": The Bunya Project's Indigenous Australian Voices on Health Care Curricula and Practice.

Indigenous community-controlled health care organizations provide timely, sustained, and culturally safe care. However, their expertise is often excluded from health professional education. This limits the transfer of knowledges and protocols to future practitioners-those positioned to shape health care systems and practices that could achieve the health rights of Indigenous people and reduce health and social inequities. In Australia, despite national government commitments to transforming curricula, services, and systems related to Indigenous health, health care training organizations such as universities generally have low numbers of Indigenous staff and few strategies to engage Indigenous experts. The authors of this paper are part of the Bunya Project, an Indigenous-led participatory action research effort designed to support non-Indigenous university staff and curriculum development through partnerships with Indigenous community-controlled organizations. We conducted 24 interviews with Indigenous individuals to ascertain recommendations for health care curricula. Three themes emerged: (1) role-modeling and leadership of Indigenous-controlled health organizations; (2) specific learnings for health professionals; and (3) achieving human rights in practice. Interviews also highlighted the need for health professionals' extension beyond clinical caregiving, and staff and students' development of knowledge, skills, and actions regarding client self-determination in order to promote clients' rights across all aspects of their health care. Critical self-reflection by health professionals is a foundational individual-level skill necessary for cultural safety.

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.

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.

Inhibitory neurons marked by a connectivity molecule regulate memory precision.

The CA3 region is central to hippocampal function during learning and memory and has a unique connectivity. CA3 pyramidal neurons are the targets of huge, excitatory mossy fiber synapses from DG axons and have a high degree of excitatory recurrent connectivity. Thus, inhibition likely plays an outsized importance in constraining excitation and shaping CA3 ensembles during learning and memory. Here, we investigate the function of a never-before studied set of dendrite-targeting, GABAergic neurons defined by expression of the synaptic adhesion molecule, Kirrel3. We discovered that activating Kirrel3-expressing GABAergic neurons specifically impairs memory discrimination and inhibits CA3 pyramidal neurons in novel contexts. Kirrel3 is required for DG-to-GABA synapse formation and variants in Kirrel3 are strong risk factors for neurodevelopmental disorders. Thus, our work suggests that Kirrel3-GABA neurons are a critical source of feed-forward inhibition from DG to CA3 during the encoding and retrieval of contextual memories, a function which may be specifically disrupted in some brain disorders.

Navicular bone fracture and severe deep digital flexor tendinopathy after palmar digital neurectomy in two horses.

Background: Navicular syndrome is a common cause of forelimb lameness in horses. Beyond changes to the navicular bone itself, horses with a clinical diagnosis of navicular syndrome often have pathology associated with other components of the navicular apparatus, including the navicular bursa, deep digital flexor (DDF) tendon, collateral sesamoidean ligaments, and impar ligament. Palmar digital neurectomy (PDN) is often used as a salvage procedure for horses diagnosed with navicular syndrome that become unresponsive to medical management. There are many potential complications associated with PDN, some of which are debilitating. Case Description: This report describes two cases of navicular bone fracture with severe DDF tendinopathy and distal interphalangeal joint subluxation/hyperextension that occurred 12 and 19 weeks after bilateral forelimb PDN. Conclusion: These two cases highlight the importance of proper patient selection before PDN due to the high incidence of undiagnosed soft tissue pathology in conjunction with radiographic evidence of navicular syndrome. Advanced imaging of the digit is recommended to identify and characterize any soft tissue pathology associated with the navicular apparatus before pursuing PDN to avoid disease progression and catastrophic injury.