Whole person care: Outcomes from a 5-year care model integrating primary care into a behavioral health clinic.

Introduction: Integrated mental and physical health care has the potential to improve health outcomes. A behavioral health organization established a reverse integration program site using a co-located model to provide primary care services to patients receiving behavioral health services. We ask whether this model of co-located care was effective in improving a range of physical health outcomes for clients.

Functional Deimmunization of Botulinum Neurotoxin Protease Domain via Computationally Driven Library Design and Ultrahigh-Throughput Screening.

Botulinum neurotoxin serotype A (BoNT/A) is a widely used cosmetic agent that also has diverse therapeutic applications; however, adverse antidrug immune responses and associated loss of efficacy have been reported in clinical uses. Here, we describe computational design and ultrahigh-throughput screening of a massive BoNT/A light-chain (BoNT/A-LC) library optimized for reduced T cell epitope content and thereby dampened immunogenicity. We developed a functional assay based on bacterial co-expression of BoNT/A-LC library members with a Förster resonance energy transfer (FRET) sensor for BoNT/A-LC enzymatic activity, and we employed high-speed fluorescence-activated cell sorting (FACS) to identify numerous computationally designed variants having wild-type-like enzyme kinetics.

UPRLIMET: UPstream Regional LiDAR Model for Extent of Trout in stream networks.

Predicting the edges of species distributions is fundamental for species conservation, ecosystem services, and management decisions. In North America, the location of the upstream limit of fish in forested streams receives special attention, because fish-bearing portions of streams have more protections during forest management activities than fishless portions. We present a novel model development and evaluation framework, wherein we compare 26 models to predict upper distribution limits of trout in streams.

Effect of zinc source (zinc sulfate or zinc hydroxychloride) on relative abundance of fecal spp. in lactating dairy cows.

Previous research revealed a potential effect of dietary trace mineral source on both ruminal and fecal microbiota. However, the effect of Zn source, specifically, has not previously been considered. Based on reported postruminal solubility, we hypothesized that Zn hydroxychloride would decrease spp.

Membrane-Tethered Mucin 1 Is Stimulated by Interferon and Virus Infection in Multiple Cell Types and Inhibits Influenza A Virus Infection in Human Airway Epithelium.

Influenza A virus (IAV) causes significant morbidity and mortality in the human population. Tethered mucin 1 (MUC1) is highly expressed in airway epithelium, the primary site of IAV replication, and also by other cell types that influence IAV infection, including macrophages. MUC1 has the potential to influence infection dynamics through physical interactions and/or signaling activity, yet MUC1 modulation and its impact during viral pathogenesis remain unclear.

Chikungunya Virus Vaccine Candidate Incorporating Synergistic Mutations Is Attenuated and Protects Against Virulent Virus Challenge.

Background: Chikungunya virus (CHIKV) is an arbovirus that periodically emerges to cause large epidemics of arthritic disease. Although the robust immunity elicited by live-attenuated virus (LAV) vaccine candidates makes them attractive, CHIKV vaccine development has been hampered by a high threshold for acceptable adverse events.

Methods: We evaluated the vaccine potential of a recently described LAV, skeletal muscle-restricted virus (SKE), that exhibits diminished replication in skeletal muscle due to insertion of target sequences for skeletal muscle-specific miR-206.

A SARS-CoV-2 Neutralization Assay Using Single Molecule Arrays.

Coronavirus disease 2019 (COVID-19) manifests with high clinical variability and warrants sensitive and specific assays to analyze immune responses in infected and vaccinated individuals. Using Single Molecule Arrays (Simoa), we developed an assay to assess antibody neutralization with high sensitivity and multiplexing capabilities based on antibody-mediated blockage of the ACE2-spike interaction. The assay does not require live viruses or cells and can be performed in a biosafety level 2 laboratory within two hours.

Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier.

BACKGROUNDWeeks after SARS-CoV-2 infection or exposure, some children develop a severe, life-threatening illness called multisystem inflammatory syndrome in children (MIS-C). Gastrointestinal (GI) symptoms are common in patients with MIS-C, and a severe hyperinflammatory response ensues with potential for cardiac complications. The cause of MIS-C has not been identified to date.

Building blocks and blueprints for bacterial autolysins.

Bacteria utilize a wide variety of endogenous cell wall hydrolases, or autolysins, to remodel their cell walls during processes including cell division, biofilm formation, and programmed death. We here systematically investigate the composition of these enzymes in order to gain insights into their associated biological processes, potential ways to disrupt them via chemotherapeutics, and strategies by which they might be leveraged as recombinant antibacterial biotherapies. To do so, we developed LEDGOs (lytic enzyme domains grouped by organism), a pipeline to create and analyze databases of autolytic enzyme sequences, constituent domain annotations, and architectural patterns of multi-domain enzymes that integrate peptidoglycan binding and degrading functions.

"I just need to be with my family": resettlement experiences of asylum seeker and refugee survivors of torture.

A global migration of individuals fleeing persecution, violence and armed conflict reached almost 60 million world-wide in 2015. This world-wide crisis of displacement reflects people seeking safety across borders and oceans; dangerous journeys that compound the trauma endured by these women, men and children. Refugees/asylum seekers face barriers upon entry to the U.

Bioinformatics-driven discovery of novel Clostridioides difficile lysins and experimental comparison with highly active benchmarks.

Clostridioides difficile is the single most deadly bacterial pathogen in the United States, and its global prevalence and outsized health impacts underscore the need for more effective therapeutic options. Towards this goal, a novel group of modified peptidoglycan hydrolases with significant in vitro bactericidal activity have emerged as potential candidates for treating C. difficile infections (CDI).

Uniting Public Health and Primary Care for Healthy Communities in the COVID-19 Era and Beyond.

The Coronavirus disease 2019 (COVID-19) pandemic has laid bare the dis-integrated health care system in the United States. Decades of inattention and dwindling support for public health, coupled with declining access to primary care medical services have left many vulnerable communities without adequate COVID-19 response and recovery capacity. "Health is a Community Affair" is a 1966 effort to build and deploy local communities of solution that align public health, primary care, and community organizations to identify health care problem sheds, and activate local asset sheds.

Mental Health and Illness.

Circumstances forcing individuals and families to flee set the stage for disruptions in mental health and forge resilience. Individual characteristics and conditions premigration, perimigration, and postmigration influence health, mental health, care-seeking behavior, and stages of well-being and successful resettlement. Primary care providers have strategies to promote mental well-being, including focusing on resilience and social determinants of health.

Nonclassical antagonism between human lysozyme and AMPs against Pseudomonas aeruginosa.

Combinations of human lysozyme (hLYS) and antimicrobial peptides (AMPs) are known to exhibit either additive or synergistic activity, and as a result, they have therapeutic potential for persistent and antibiotic-resistant infections. We examined hLYS activity against Pseudomonas aeruginosa when combined with six different AMPs. In contrast to prior reports, we discovered that some therapeutically relevant AMPs manifest striking antagonistic interactions with hLYS across particular concentration ranges.

Electrostatic-Mediated Affinity Tuning of Lysostaphin Accelerates Bacterial Lysis Kinetics and Enhances Efficacy.

Drug-resistant bacterial pathogens are a serious threat to global health, and antibacterial lysins are at the forefront of innovative treatments for these life-threatening infections. While lysins' general mechanism of action is well understood, the design principles that might enable engineering of performance-enhanced variants are still being formulated. Here, we report a detailed analysis of molecular determinants underlying the efficacy of lysostaphin, a canonical anti-MRSA (methicillin-resistant ) lysin.

Deimmunized Lysostaphin Synergizes with Small-Molecule Chemotherapies and Resensitizes Methicillin-Resistant to β-Lactam Antibiotics.

There is an urgent need for novel agents to treat drug-resistant bacterial infections, such as multidrug-resistant (MRSA). Desirable properties for new antibiotics include high potency, narrow species selectivity, low propensity to elicit new resistance phenotypes, and synergy with standard-of-care (SOC) chemotherapies. Here, we describe analysis of the antibacterial potential exhibited by F12, an innovative anti-MRSA lysin that has been genetically engineered to evade detrimental antidrug immune responses in human patients.

Barriers to the use of trained interpreters in consultations with refugees in four resettlement countries: a qualitative analysis using normalisation process theory.

Background: Increasing numbers of primary care practitioners in refugee resettlement countries are providing care to refugees. Access to trained interpreters is a priority for these practitioners, but there are many barriers to the implementation of interpreted consultations in routine care. There is a lack of international, theoretically informed research.

Photon-directed multiplexed enzymatic DNA synthesis for molecular digital data storage.

New storage technologies are needed to keep up with the global demands of data generation. DNA is an ideal storage medium due to its stability, information density and ease-of-readout with advanced sequencing techniques. However, progress in writing DNA is stifled by the continued reliance on chemical synthesis methods.

Chikungunya Virus Strains from Each Genetic Clade Bind Sulfated Glycosaminoglycans as Attachment Factors.

Chikungunya virus (CHIKV) is an arthritogenic alphavirus that causes debilitating musculoskeletal disease. CHIKV displays broad cell, tissue, and species tropism, which may correlate with the attachment factors and entry receptors used by the virus. Cell surface glycosaminoglycans (GAGs) have been identified as CHIKV attachment factors.

Globally deimmunized lysostaphin evades human immune surveillance and enables highly efficacious repeat dosing.

There is a critical need for novel therapies to treat methicillin-resistant (MRSA) and other drug-resistant pathogens, and lysins are among the vanguard of innovative antibiotics under development. Unfortunately, lysins' own microbial origins can elicit detrimental antidrug antibodies (ADAs) that undermine efficacy and threaten patient safety. To create an enhanced anti-MRSA lysin, a novel variant of lysostaphin was engineered by T cell epitope deletion.