Uveodermatologic syndrome presenting with concurrent aseptic meningoencephalitis in a dog.

Canine uveodermatologic syndrome (UDS) resembles human Vogt-Koyanagi-Harada syndrome but typically lacks associated neurological signs. We report a 3-year-old Australian shepherd dog diagnosed with UDS following bilateral enucleation and histopathology. Twelve days postoperatively, neurological symptoms developed, including head tilt, circling, and deafness.

Adjuvant-dependent impacts on vaccine-induced humoral responses and protection in preclinical models of nasal and genital colonization by pathogenic Neisseria.

Neisseria gonorrhoeae, which causes the sexually transmitted infection gonorrhea and Neisseria meningitidis, a leading cause of bacterial meningitis and septicemia, are closely related human-restricted pathogens that inhabit distinct primary mucosal niches. While successful vaccines against invasive meningococcal disease have been available for decades, the rapid rise in antibiotic resistance has led to an urgent need to develop an effective gonococcal vaccine. Several surface antigens are shared among these two pathogens, making cross-species protection an exciting prospect.

Rational selection of TbpB variants yields a bivalent vaccine with broad coverage against Neisseria gonorrhoeae.

Neisseria gonorrhoeae is an on-going public health problem due in part to the lack of success with efforts to develop an efficacious vaccine to prevent this sexually transmitted infection. The gonococcal transferrin binding protein B (TbpB) is an attractive candidate vaccine antigen. However, it exhibits high levels of antigenic variability, posing a significant obstacle in evoking a broadly protective immune response.

LDB1 establishes multi-enhancer networks to regulate gene expression.

How specific enhancer-promoter pairing is established remains mostly unclear. Besides the CTCF/cohesin machinery, few nuclear factors have been studied for a direct role in physically connecting regulatory elements. Using a murine erythroid cell model, we show via acute degradation experiments that LDB1 directly and broadly promotes connectivity among regulatory elements.

Validation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [C]UCB-J PET.

Simplified methods of acquisition and quantification would facilitate the use of synaptic density imaging in multicenter and longitudinal studies of Alzheimer disease (AD). We validated a simplified tissue-to-reference ratio method using SUV ratios (SUVRs) for estimating synaptic density with [C]UCB-J PET. Participants included 31 older adults with AD and 16 with normal cognition.

Rational selection of TbpB variants elucidates a bivalent vaccine formulation with broad spectrum coverage against .

is the causative agent of gonorrhea, an on-going public health problem due in part to the lack of success with efforts to develop an efficacious vaccine to prevent this sexually transmitted infection. An attractive candidate vaccine antigen because of its essential function and surface exposure, the gonococcal transferrin binding protein B (TbpB) exhibits high levels of antigenic variability which poses a significant obstacle in evoking a broadly protective vaccine composition. Here, we utilize phylogenetic information to rationally select TbpB variants for inclusion into a potential gonococcal vaccine and identify two TbpB variants that when formulated together elicit a highly cross-reactive antibody response in both rabbits and mice against a diverse panel of TbpB variants and clinically relevant gonococcal strains.

LDB1 establishes multi-enhancer networks to regulate gene expression.

How specific enhancer-promoter pairing is established is still mostly unclear. Besides the CTCF/cohesin machinery, only a few nuclear factors have been studied for a direct role in physically connecting regulatory elements. Here, we show via acute degradation experiments that LDB1 directly and broadly promotes enhancer-promoter loops.

YY1-controlled regulatory connectivity and transcription are influenced by the cell cycle.

Few transcription factors have been examined for their direct roles in physically connecting enhancers and promoters. Here acute degradation of Yin Yang 1 (YY1) in erythroid cells revealed its requirement for the maintenance of numerous enhancer-promoter loops, but not compartments or domains. Despite its reported ability to interact with cohesin, the formation of YY1-dependent enhancer-promoter loops does not involve stalling of cohesin-mediated loop extrusion.

Assessing the association between antibody status and symptoms of long COVID: A multisite study.

The association between SARS-CoV-2 humoral immunity and post-acute sequelae of COVID-19 (long COVID) remains uncertain. The objective of this population-based cohort study was to assess the association between SARS-CoV-2 seropositivity and symptoms consistent with long COVID. English and Spanish-speaking members ≥ 18 years old with SARS-CoV-2 serologic testing conducted prior to August 2021 were recruited from Kaiser Permanente Southern California and Kaiser Permanente Colorado.

Genome folding principles uncovered in condensin-depleted mitotic chromosomes.

During mitosis, condensin activity is thought to interfere with interphase chromatin structures. To investigate genome folding principles in the absence of chromatin loop extrusion, we codepleted condensin I and condensin II, which triggered mitotic chromosome compartmentalization in ways similar to that in interphase. However, two distinct euchromatic compartments, indistinguishable in interphase, emerged upon condensin loss with different interaction preferences and dependencies on H3K27ac.

Prophylactic Biosynthetic Retrorectus Mesh Placement During Stoma Reversal Reduces the Rate of Stoma Site Incisional Hernia.

Introduction: Stoma site incisional hernias (SSIHs) are associated with substantial long-term morbidity, and the rate can be as high as 30% to 40%. Recent efforts using prophylactic mesh reinforcement (PMR) to reduce the development of hernias have shown encouraging outcomes. The objective of this study was to assess the use of prophylactic biosynthetic mesh at the time of stoma reversal on the overall SSIH rate.

Longitudinal Analysis of Mpox Virus DNA Detectability From Multiple Specimen Types During Acute Illness: A Cohort Study.

Background: Longitudinal data on the detectability of monkeypox virus (MPXV) genetic material in different specimen types are scarce.

Methods: We describe MPXV-specific polymerase chain reaction (PCR) results from adults with confirmed mpox infection from Toronto, Canada, including a cohort undergoing weekly collection of specimens from multiple anatomic sites until 1 week after skin lesions had fully healed. We quantified the time from symptom onset to resolution of detectable viral DNA (computed tomography [Ct] ≥ 35) by modeling exponential decay in Ct value as a function of illness day for each site, censoring at the time of tecovirimat initiation.

Genome folding principles revealed in condensin-depleted mitotic chromosomes.

During mitosis, condensin activity interferes with interphase chromatin structures. Here, we generated condensin-free mitotic chromosomes to investigate genome folding principles. Co-depletion of condensin I and II, but neither alone, triggered mitotic chromosome compartmentalization in ways that differ from interphase.

A multi-specific, multi-affinity antibody platform neutralizes sarbecoviruses and confers protection against SARS-CoV-2 in vivo.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has been responsible for a global pandemic. Monoclonal antibodies (mAbs) have been used as antiviral therapeutics; however, these therapeutics have been limited in efficacy by viral sequence variability in emerging variants of concern (VOCs) and in deployment by the need for high doses. In this study, we leveraged the multi-specific, multi-affinity antibody (Multabody, MB) platform, derived from the human apoferritin protomer, to enable the multimerization of antibody fragments.

Adopting high reliability organization principles to lead a large scale clinical transformation.

Building high reliable healthcare systems to reduce avoidable patient harm is a global priority. However, there is variability in the application and understanding of the previously identified High Reliability Organization (HRO) principles to make improvements. We describe specific organizational activities exemplifying the five HRO principles during the planning and go-live periods of the new Electronic Health Record (EHR) system at a multi-site academic health sciences centre in Ontario, Canada.

Robotic Versus Laparoscopic Surgery for Rectal Cancer: A Comprehensive Review of Oncological Outcomes.

The treatment of rectal cancer is complex and involves specialized multidisciplinary care, although the tenet is still rooted in a high-quality total mesorectal excision. The robotic platform is one of many tools in the arsenal to assist dissection in the low pelvis. This article is a comprehensive review of the oncological outcome comparing robotic vs laparoscopic rectal cancer resection, with a particular focus on total mesorectal excision.

Profiling mentally ill offenders in Hong Kong: A 10-year retrospective review study.

Introduction: This study aimed to analyze the estimated prevalence of mental disorders among offenders and compare the estimated crime rate between mentally ill patients and the total population in Hong Kong.

Methods: Service data of offenders referred to psychiatrists at the Siu Lam Psychiatric Centre from January 2011 to December 2020 were analyzed. Demographic data of gender, age on admission, educational level, principal psychiatric diagnosis, index offense, and assessment outcome were collected.

CTCF and transcription influence chromatin structure re-configuration after mitosis.

During mitosis, transcription is globally attenuated and chromatin architecture is dramatically reconfigured. We exploited the M- to G1-phase progression to interrogate the contributions of the architectural factor CTCF and the process of transcription to genome re-sculpting in newborn nuclei. Depletion of CTCF during the M- to G1-phase transition alters short-range compartmentalization after mitosis.

Wide-Range Motion Recognition Through Insole Sensor Using Multi-Walled Carbon Nanotubes and Polydimethylsiloxane Composites.

High linearity/sensitivity and a wide dynamic sensing range are the most desirable features for pressure sensors to accurately detect and respond to external pressure stimuli. Even though a number of recent studies have demonstrated a low-cost pressure sensing device for a smart insole system by using scalable and deformable conductive materials, they still lack stretchability and desirable properties such as high sensitivity, hysteresis, linearity, and fast response time to obtain accurate and reliable data. To resolve this issue, a flexible and stretchable piezoresistive pressure sensor with high linear response over a wide pressure range is developed and integrated in a wearable insole system.

Engineering three-dimensional genome folding.

Animal genomes are partitioned and folded at various scales that contribute distinctly to nuclear processes. While structural features have been disrupted either globally or at select loci in loss-of-function studies, gain-of-function studies that probe the role of genome architecture have lagged behind. Here we examine recent advances in experimentally creating chromatin loops, contact domains, boundaries and compartments.

Cognitive insight is correlated with cognitive impairments and contributes to medication adherence in schizophrenia patients.

Objective: Cognitive insight refers to the ability to distance oneself from and evaluate one's own beliefs and interpretations. Little is known about whether cognitive insight could influence medication adherence in schizophrenia patients. This study examined the role of cognitive insight in medication adherence and how it would interact with neuropsychological functions.

LEFTY1 Is a Dual-SMAD Inhibitor that Promotes Mammary Progenitor Growth and Tumorigenesis.

SMAD pathways govern epithelial proliferation, and transforming growth factor β (TGF-β and BMP signaling through SMAD members has distinct effects on mammary development and homeostasis. Here, we show that LEFTY1, a secreted inhibitor of NODAL/SMAD2 signaling, is produced by mammary progenitor cells and, concomitantly, suppresses SMAD2 and SMAD5 signaling to promote long-term proliferation of normal and malignant mammary epithelial cells. In contrast, BMP7, a NODAL antagonist with context-dependent functions, is produced by basal cells and restrains progenitor cell proliferation.