Now showing items 1-20 of 6237

    • Whole genome sequence analysis of Salmonella Typhi provides evidence of phylogenetic linkage between cases of typhoid fever in Santiago, Chile in the 1980s and 2010-2016.

      Maes, Mailis; Sikorski, Michael J; Carey, Megan E; Higginson, Ellen E; Dyson, Zoe A; Fernandez, Alda; Araya, Pamela; Tennant, Sharon M; Baker, Stephen; Lagos, Rosanna; et al. (Public Library of Science, 2022-06-29)
      Typhoid fever epidemiology was investigated rigorously in Santiago, Chile during the 1980s, when Salmonella enterica serovar Typhi (S. Typhi) caused seasonal, hyperendemic disease. Targeted interventions reduced the annual typhoid incidence rates from 128-220 cases/105 population occurring between 1977-1984 to <8 cases/105 from 1992 onwards. As such, Santiago represents a contemporary example of the epidemiologic transition of an industrialized city from amplified hyperendemic typhoid fever to a period when typhoid is no longer endemic. We used whole genome sequencing (WGS) and phylogenetic analysis to compare the genotypes of S. Typhi cultured from acute cases of typhoid fever occurring in Santiago during the hyperendemic period of the 1980s (n = 74) versus the nonendemic 2010s (n = 80) when typhoid fever was rare. The genotype distribution between "historical" (1980s) isolates and "modern" (2011-2016) isolates was similar, with genotypes 3.5 and 2 comprising the majority of isolations, and 73/80 (91.3%) of modern isolates matching a genotype detected in the 1980s. Additionally, phylogenomically 'ancient' genotypes 1.1 and 1.2.1, uncommon in the global collections, were also detected in both eras, with a notable rise amongst the modern isolates. Thus, genotypes of S. Typhi causing acute illness in the modern nonendemic era match the genotypes circulating during the hyperendemic 1980s. The persistence of historical genotypes may be explained by chronic typhoid carriers originally infected during or before the 1980s.
    • Vaccines, Antibodies and Donors: Varying Attitudes and Policies Surrounding COVID-19 and Heart Transplantation.

      Defilippis, Ersilia M; Allen, Larry A; Bhatt, Ankeet S; Joseph, Susan; Kittleson, Michelle; Vardeny, Orly; Drazner, Mark H; Lala, Anuradha (Elsevier, 2022-06-16)
      Introduction: There are varied opinions in the United States regarding many aspects of care related to COVID-19. The purpose of this study was to examine the opinions of health care personnel and the policies of heart transplant centers concerning practices for the prevention and treatment of COVID-19 in donors and recipients of heart transplants. Methods: Two anonymous, electronic web-based surveys were developed: 1 was administered to health care personnel through a mailing list maintained by the Heart Failure Society of America (HFSA); another was administered to U.S. medical adult and pediatric heart transplant (HT) program directors. Individual and group e-mails were sent with an embedded link to the respective surveys in February 2022. Results: A total of 176 individuals (8.6%) responded to the survey administered through the HFSA. Of medical directors of transplant programs, 78 (54% response rate) completed a separate survey on their centers' policies. Although 95% (n = 167) of individuals indicated vaccination against COVID-19 should be required prior to HT, only 67% (n = 52) of centers mandated that practice. Similarly, 61% of individuals thought vaccination should be required prior to HT for caregivers, but only 13% of transplant centers mandated caregiver vaccination. Of the centers, 63% reported considering donors despite histories of recent COVID-19 infection (within 3 months), and 47% considered donors with current positive polymerase chain reaction tests. Regarding post-transplant care, only 22% of programs routinely measured antibodies to COVID-19, and 71% used tixagevimab/cilgavimab (Evusheld) for pre-exposure prophylaxis. Conclusions: There were significant differences between individual preferences and centers' practices with respect to COVID-19 management of candidates for and recipients of HT. Additionally, there was wide variation in policies among centers, reflecting the need for further study to inform consistent guidance and recommendations across centers to optimize equitable care for this high-risk patient population.
    • Nociceptive signaling through transient receptor potential vanilloid 1 is regulated by Cyclin Dependent Kinase 5-mediated phosphorylation of T407 in vivo.

      Cho, Andrew; Hall, Bradford E; Limaye, Advait S; Wang, Sheng; Chung, Man-Kyo; Kulkarni, Ashok B (SAGE Publications Inc., 2022-04)
      Cyclin dependent kinase 5 (Cdk5) is a key neuronal kinase whose activity can modulate thermo-, mechano-, and chemo-nociception. Cdk5 can modulate nociceptor firing by phosphorylating pain transducing ion channels like the transient receptor potential vanilloid 1 (TRPV1), a thermoreceptor that is activated by noxious heat, acidity, and capsaicin. TRPV1 is phosphorylated by Cdk5 at threonine-407 (T407), which then inhibits Ca2+ dependent desensitization. To explore the in vivo implications of Cdk5-mediated TRPV1 phosphorylation on pain perception, we engineered a phospho-null mouse where we replaced T407 with alanine (T407A). The T407A point mutation did not affect the expression of TRPV1 in nociceptors of the dorsal root ganglia and trigeminal ganglia (TG). However, behavioral tests showed that the TRPV1T407A knock-in mice have reduced aversion to oral capsaicin along with a trend towards decreased facial displays of pain after a subcutaneous injection of capsaicin into the vibrissal pad. In addition, the TRPV1T407A mice display basal thermal hypoalgesia with increased paw withdrawal latency while tested on a hot plate. These results indicate that phosphorylation of TRPV1 by Cdk5 can have important consequences on pain perception, as loss of the Cdk5 phosphorylation site reduced capsaicin- and heat-evoked pain behaviors in mice.
    • Refractory Splenic Marginal Zone Lymphoma Responsive to Combination Venetoclax and Bortezomib (Velcade) (V) Therapy.

      Roche, Kyle C; DeRosa, Peter A; Liu, Min-Ling; Nava, Victor E; Aggarwal, Anita (MDPI AG, 2022-06-06)
      Standard treatment regimens for the management of patients with refractory splenic marginal zone lymphoma (SMZL) are currently unavailable. Here, we report a case of SMZL, which, after failing multiple therapeutics, demonstrated an impressive clinical response to combined Venetoclax and Velcade (V2), a treatment combination currently being investigated in the setting of refractory multiple myeloma. We also report a unique histopathology and mutational profile that may have important implications for the characterization and prognosis of SMZL.
    • Genome Sequencing in the Parkinson Disease Clinic.

      Hill, Emily J; Robak, Laurie A; Al-Ouran, Rami; Deger, Jennifer; Fong, Jamie C; Vandeventer, Paul Jerrod; Schulman, Emily; Rao, Sindhu; Saade, Hiba; Savitt, Joseph M; et al. (Wolters Kluwer Health, 2022-06-09)
      In 203 subjects with PD (age = 63 years, 67% male), genome sequencing was performed and filtered using a custom panel, including 49 genes associated with PD, parkinsonism, or related disorders, as well as a 90-variant PD genetic risk score. Based on the results, 231 patients (age = 67 years, 63% male) were surveyed on interest in genetic testing and responses to vignettes covering (1) familial risk of PD (LRRK2); (2) risk of PD dementia (GBA); (3) PD genetic risk score; and (4) secondary, medically actionable variants (BRCA1).
    • Tuberculosis the great masquerader.

      Wang, Elizabeth Wenqian; Okwesili, Christine N; Doub, James B (Elsevier, 2022-06-18)
      With increased use of disease-modifying antirheumatic drugs, screening for latent tuberculosis infection is more important than ever. However, even with appropriate screening, reactivation of tuberculosis can occur in patients who have had significant epidemiological exposures. Herein, we present a case of a seventy-four-year-old woman with severe rheumatoid arthritis on long-term disease-modifying antirheumatic drugs who developed cryptic miliary tuberculosis. Histopathological findings from an abdominal lymph node biopsy showed caseating granulomas which were initially attributed to her rheumatoid arthritis given screening tests and sputum acid-fast cultures were negative for tuberculosis. It was not until tuberculosis spondylitis developed that the diagnosis was finally elucidated. This case highlights the need for clinicians to be vigilant about discussing historical epidemiological exposures to tuberculosis instead of relying solely on screening testing.
    • Xenotransplantation: A New Era.

      Carrier, Amber N; Verma, Anjali; Mohiuddin, Muhammad; Pascual, Manuel; Muller, Yannick D; Longchamp, Alban; Bhati, Chandra; Buhler, Leo H; Maluf, Daniel G; Meier, Raphael P H (Frontiers Media S.A., 2022-06-09)
      Organ allotransplantation has now reached an impassable ceiling inherent to the limited supply of human donor organs. In the United States, there are currently over 100,000 individuals on the national transplant waiting list awaiting a kidney, heart, and/or liver transplant. This is in contrast with only a fraction of them receiving a living or deceased donor allograft. Given the morbidity, mortality, costs, or absence of supportive treatments, xenotransplant has the potential to address the critical shortage in organ grafts. Last decade research efforts focused on creation of donor organs from pigs with various genes edited out using CRISPR technologies and utilizing non-human primates for trial. Three groups in the United States have recently moved forward with trials in human subjects and obtained initial successful results with pig-to-human heart and kidney xenotransplantation. This review serves as a brief discussion of the recent progress in xenotransplantation research, particularly as it concerns utilization of porcine heart, renal, and liver xenografts in clinical practice.
    • Editorial: Real-World Evidence of Pediatric Exposure to Psychopharmacologic Medications.

      Zito, Julie M; dosReis, Susan; Carleton, Bruce (Frontiers Media S.A., 2022-06-10)
    • Acute Inpatient Rehabilitation Improves Function Independent of Comorbidities in Medically Complex Patients.

      Zhang, Shangming; Lin, Dan; Wright, Megan E; Swallow, Nicole (Elsevier, 2022-01-12)
      Objectives: (1) To evaluate the benefits of acute inpatient rehabilitation for a medically complex patient population and (2) to assess the effect of comorbid conditions on rehabilitation outcomes. Design: Retrospective cohort study. Setting: Freestanding inpatient rehabilitation facility. Participants: A total of 270 medically complex adult patients including those with cardiac, pulmonary, and orthopedic conditions, with mean age of 73.6 years; 52.6% were female and 47.4% were male (N=270). Interventions: Not applicable. Main outcome measures: Functional Independence Measure (FIM) gain, FIM efficiency, rehabilitation length of stay (RLOS), home discharge rate, and readmission to acute care (RTAC). Results: Among 270 medically complex patients, mean total FIM gain, mean RLOS, and mean FIM efficiency with SD were 26.0±13.6 points, 12.6±5.9 days, and 2.3±1.6, respectively. A total of 71.9% of patients were discharged to home, 12.2% for RTAC, and 15.9% to a skilled nursing facility (SNF). Hypertension (HTN) was the only comorbidity significantly associated with FIM gain (53.7% [total FIM gain ≥27] vs 67.2% [total FIM gain <27]; P=.024) and FIM efficiency (53.3% [FIM efficiency ≥2.12] vs 67.4% [FIM efficiency <2.12]; P=.025), independent of age, body mass index, sex, race, ethnicity, insurance type, and Charlson Comorbidity Index. The 5 most common reasons for RTAC were cardiac, pulmonary, acute blood loss anemia, infection, and neurologic conditions. Conclusions: Among 270 medically complex patients, 71.9% were discharged to home, 15.9% to an SNF, and 12.2% for RTAC with a mean RLOS 12.6 days, mean total FIM gain of 26 points, and mean FIM efficiency of 2.3, which were all better than those of all admissions at our facility in 2018. Furthermore, RLOS, total FIM gain and FIM efficiency in this study were all better than their corresponding eRehabData weighted national benchmarks (RLOS, 15.82 days; FIM gain, 25.57; FIM efficiency, 2.13) for a total of 202,520 discharges in 2018. These findings support acute inpatient rehabilitation for this patient population. With the exception of HTN, no medical comorbidities or demographic variables were associated with rehabilitation outcomes.
    • Antimicrobial susceptibility and genomic profiling of from bloodstream infections at a tertiary referral hospital in Lusaka, Zambia, 2018-2019.

      Yamba, Kaunda; Kapesa, Christine; Mpabalwani, Evans; Hachaambwa, Lottie; Smith, Anthony Marius; Young, Andrea Liezl; Gally, David; Mainda, Geoffrey; Mukuma, Mercy; Samutela, Mulemba Tillika; et al. (Elsevier, 2022-04-25)
      Objectives: This study investigated antimicrobial susceptibility and genomic profiling of S. enterica isolated from bloodstream infections at a tertiary referral hospital in Lusaka, Zambia, 2018-2019. Method: This was a prospective hospital-based study involving routine blood culture samples submitted to the microbiology laboratory at the University Teaching Hospital. Identification of S. enterica and determination of antimicrobial susceptibility profiles was achieved through conventional and automated methods. Whole-genome sequencing (WGS) was conducted, and the sequence data outputs were processed for species identification, serotype determination, multilocus sequence typing (MLST) profile determination, identification of antimicrobial resistance determinants, and phylogeny. Results: Seventy-six Salmonella enterica were isolated and 64 isolates underwent WGS. Salmonella Typhi (72%) was the most prevalent serotype. Notable was the occurrence of invasive non-typhoidal Salmonella Typhimurium ST313 (3%), resistance to cephalosporins (4%) and ciprofloxacin (5%), multidrug resistance (46%), and reduced susceptibility to ciprofloxacin (30%) and imipenem (3%). Phylogenetic cluster analysis showed multiple Salmonella serovars with a wide range of genetic diversity. Conclusion: The genetic diversity of Salmonella Typhi, high prevalence of multidrug resistance, and the emergence of ciprofloxacin and cephalosporin resistance warrants improved hygiene and water and sanitation provision, continued surveillance to apprise antibiograms and inform policy, and the introduction of the typhoid conjugate vaccine.
    • Medication for opioid use disorder at hospital discharge is not associated with intravenous antibiotic completion in post-acute care facilities.

      Traver, Edward C; Ching, Patrick R; Narayanan, Shivakumar (SAGE Publications Inc., 2022-06-21)
      A total of 161 patient encounters were included; the mean age was 43.4 years and 56% of patients were male. In 48% of the encounters, the patient was homeless and in 68% they recently injected drugs. The most common infectious syndrome was osteoarticular (44.1%). Medication for opioid use disorder was prescribed at discharge in 103 of 161 encounters and was newly started in 27 encounters. Similar rates of outpatient parenteral antimicrobial therapy completion were found in those who received (65/103) and did not receive (33/58) medication for opioid use disorder at discharge (odds ratio: 1.29; 95% confidence interval: 0.68-2.54; p = 0.44).
    • A Direct Comparison of Physical Versus Dihydrocapsaicin-Induced Hypothermia in a Rat Model of Traumatic Spinal Cord Injury.

      Sarkar, Amrita; Kim, Kevin T; Tsymbalyuk, Orest; Keledjian, Kaspar; Wilhelmy, Bradley E; Sherani, Nageen A; Jia, Xiaofeng; Gerzanich, Volodymyr; Simard, J Marc (Mary Ann Liebert Inc., 2021-10-07)
      Spinal cord injury (SCI) is a devastating neurological condition with no effective treatment. Hypothermia induced by physical means (cold fluid) is established as an effective therapy in animal models of SCI, but its clinical translation to humans is hampered by several constraints. Hypothermia induced pharmacologically may be noninferior or superior to physically induced hypothermia for rapid, convenient systemic temperature reduction, but it has not been investigated previously in animal models of SCI. We used a rat model of SCI to compare outcomes in three groups: (1) normothermic controls; (2) hypothermia induced by conventional physical means; (3) hypothermia induced by intravenous (IV) dihydrocapsaicin (DHC). Male rats underwent unilateral lower cervical SCI and were treated after a 4-hour delay with physical cooling or IV DHC (∼0.60 mg/kg total) cooling (both 33.0 ± 1.0°C) lasting 4 hours; controls were kept normothermic. Telemetry was used to monitor temperature and heart rate during and after treatments. In two separate experiments, one ending at 48 hours, the other at 6 weeks, "blinded" investigators evaluated rats in the three groups for neurological function followed by histopathological evaluation of spinal cord tissues. DHC reliably induced systemic cooling to 32-33°C. At both the time points examined, the two modes of hypothermia yielded similar improvements in neurological function and lesion size compared with normothermic controls. Our results indicate that DHC-induced hypothermia may be comparable with physical hypothermia in efficacy, but more clinically feasible to administer than physical hypothermia.
    • Bearing Witness.

      Mulasi, Ila (Wolters Kluwer Health, 2022-05-19)
    • Polyamine Depletion Strategies in Cancer: Remodeling the Tumor Immune Microenvironment to Enhance Anti-Tumor Responses.

      Chin, Alexander; Bieberich, Charles J; Stewart, Tracy Murray; Casero, Robert A (MDPI AG, 2022-06-10)
      Polyamine biosynthesis is frequently dysregulated in cancers, and enhanced flux increases intracellular polyamines necessary for promoting cell growth, proliferation, and function. Polyamine depletion strategies demonstrate efficacy in reducing tumor growth and increasing survival in animal models of cancer; however, mechanistically, the cell-intrinsic and cell-extrinsic alterations within the tumor microenvironment underlying positive treatment outcomes are not well understood. Recently, investigators have demonstrated that co-targeting polyamine biosynthesis and transport alters the immune landscape. Although the polyamine synthesis-targeting drug 2-difluoromethylornithine (DFMO) is well tolerated in humans and is FDA-approved for African trypanosomiasis, its clinical benefit in treating established cancers has not yet been fully realized; however, combination therapies targeting compensatory mechanisms have shown tolerability and efficacy in animal models and are currently being tested in clinical trials. As demonstrated in pre-clinical models, polyamine blocking therapy (PBT) reduces immunosuppression in the tumor microenvironment and enhances the therapeutic efficacy of immune checkpoint blockade (ICB). Thus, DFMO may sensitize tumors to other therapeutics, including immunotherapies and chemotherapies.
    • Outcomes of Endovascular Repair of Aortic Aneurysms with the GORE® Thoracic Branch Endoprosthesis for Left Subclavian Artery Preservation.

      Dake, Michael D; Brinkman, William T; Han, Sukgu M; Matsumura, Jon S; Sweet, Matthew P; Patel, Himanshu J; Taylor, Bradley S; Oderich, Gustavo S (Elsevier, 2022-06-13)
      Objective or background: Thoracic endovascular aortic repair has emerged as the dominant paradigm for treatment of patients with descending thoracic aortic aneurysms. For aneurysms involving the aortic arch in the region of the left subclavian artery (LSA), branch vessel preservation to maintain blood flow to the LSA is recommended. Branched aortic endografts are an alternative to surgical revascularization of the LSA. Methods: Across 34 investigative sites, 84 patients with Zone 2 aneurysm were enrolled in a nonrandomized, prospective study of a single branched aortic endograft. The thoracic branch endoprosthesis device allows for graft placement proximal to the LSA and incorporates a single side branch for left subclavian perfusion. Results: Over half of the patients were male (63%). Their average age was 70 (±11) years. The aneurysm morphology was fusiform in 43 and saccular in 41 patients. The mean aneurysm diameter at screening was 56.2 mm. The mean follow up was 30 months (range 2.6 to 50.7 months). Reported here are the patient outcomes at 1 and 12 months. Pre-defined technical success with implantation of the device in landing Zone 2 was achieved in 92% (n=77) of patients. There were no cases of aortic rupture, lesion-related mortality, or new onset renal failure. There was no peri-operative (30-day) mortality. A single case each of permanent paraplegia and paraparesis occurred. Three patients experienced a procedure-related stroke. Through 12 months, four patients died; none of the deaths were adjudicated as related to the device or procedure. One aortic reintervention was required. A single case of aortic enlargement (core laboratory) was reported at 6 months. Type 1 (n=3) and III (n=5) endoleaks occurred in 9.8% of patients of which one (Type III) required reintervention. Conclusions: Results from this device study in patients with Zone 2 aneurysm demonstrate that early safety and efficacy outcomes are maintained up to 12 months after the endovascular procedure with low mortality and reintervention rates and an acceptable frequency of procedural complications, including neurologic complications.
    • Stroke recovery phenotyping through network trajectory approaches and graph neural networks.

      Krishnagopal, Sanjukta; Lohse, Keith; Braun, Robynne (Springer Nature, 2022-06-19)
      Stroke is a leading cause of neurological injury characterized by impairments in multiple neurological domains including cognition, language, sensory and motor functions. Clinical recovery in these domains is tracked using a wide range of measures that may be continuous, ordinal, interval or categorical in nature, which can present challenges for multivariate regression approaches. This has hindered stroke researchers' ability to achieve an integrated picture of the complex time-evolving interactions among symptoms. Here, we use tools from network science and machine learning that are particularly well-suited to extracting underlying patterns in such data, and may assist in prediction of recovery patterns. To demonstrate the utility of this approach, we analyzed data from the NINDS tPA trial using the Trajectory Profile Clustering (TPC) method to identify distinct stroke recovery patterns for 11 different neurological domains at 5 discrete time points. Our analysis identified 3 distinct stroke trajectory profiles that align with clinically relevant stroke syndromes, characterized both by distinct clusters of symptoms, as well as differing degrees of symptom severity. We then validated our approach using graph neural networks to determine how well our model performed predictively for stratifying patients into these trajectory profiles at early vs. later time points post-stroke. We demonstrate that trajectory profile clustering is an effective method for identifying clinically relevant recovery subtypes in multidimensional longitudinal datasets, and for early prediction of symptom progression subtypes in individual patients. This paper is the first work introducing network trajectory approaches for stroke recovery phenotyping, and is aimed at enhancing the translation of such novel computational approaches for practical clinical application.
    • Glucose dysregulation and subclinical cardiac dysfunction in older adults: The Cardiovascular Health Study.

      Garg, Parveen K; Biggs, Mary L; Kizer, Jorge R; Shah, Sanjiv J; Psaty, Bruce; Carnethon, Mercedes; Gottdiener, John S; Siscovick, David; Mukamal, Kenneth J (Springer Nature, 2022-06-20)
      Objective: We evaluated whether measures of glucose dysregulation are associated with subclinical cardiac dysfunction, as assessed by speckle-tracking echocardiography, in an older population. Methods: Participants were men and women in the Cardiovascular Health Study, age 65+ years and without coronary heart disease, atrial fibrillation, or heart failure at baseline. We evaluated fasting insulin resistance (IR) with the homeostatic model of insulin resistance (HOMA-IR) and estimated the Matsuda insulin sensitivity index (ISI) and insulin secretion with an oral glucose tolerance test. Systolic and diastolic cardiac mechanics were measured with speckle-tracking analysis of echocardiograms. Multi-variable adjusted linear regression models were used to investigate associations of insulin measures and cardiac mechanics. Results: Mean age for the 2433 included participants was 72.0 years, 33.6% were male, and 3.7% were black. After adjustment for age, sex, race, site, speckle-tracking analyst, echo image and quality score, higher HOMA-IR, lower Matsuda ISI, and higher insulin secretion were each associated with worse left ventricular (LV) longitudinal strain and LV early diastolic strain rate (p-value < 0.005); however, associations were significantly attenuated after adjustment for waist circumference, with the exception of Matsuda ISI and LV longitudinal strain (increase in strain per standard deviation increment in Matsuda ISI = 0.18; 95% confidence interval = 0.03-0.33). Conclusion: In this cross-sectional study of older adults, associations of glucose dysregulation with subclinical cardiac dysfunction were largely attenuated after adjusting for central adiposity.
    • Implementation strategies to promote measurement-based care in schools: evidence from mental health experts across the USA.

      Connors, Elizabeth H; Lyon, Aaron R; Garcia, Kaylyn; Sichel, Corianna E; Hoover, Sharon; Weist, Mark D; Tebes, Jacob K (Springer Nature, 2022-06-21)
      Background: Despite an established taxonomy of implementation strategies, minimal guidance exists for how to select and tailor strategies to specific practices and contexts. We employed a replicable method to obtain stakeholder perceptions of the most feasible and important implementation strategies to increase mental health providers' use of measurement-based care (MBC) in schools. MBC is the routine use of patient-reported progress measures throughout treatment to inform patient-centered, data-driven treatment adjustments. Methods: A national sample of 52 school mental health providers and researchers completed two rounds of modified Delphi surveys to rate the relevance, importance, and feasibility of 33 implementation strategies identified for school settings. Strategies were reduced and definitions refined using a multimethod approach. Final importance and feasibility ratings were plotted on "go-zone" graphs and compared across providers and researchers to identify top-rated strategies. Results: The initial 33 strategies were rated as "relevant" or "relevant with changes" to MBC in schools. Importance and feasibility ratings were high overall for both survey rounds; on a scale of 1 to 5, importance ratings (3.61-4.48) were higher than feasibility ratings (2.55-4.06) on average. Survey 1 responses resulted in a reduced, refined set of 21 strategies, and six were rated most important and feasible on Survey 2: (1) assess for readiness and identify barriers and facilitators; (2) identify and prepare champions; (3) develop a usable implementation plan; (4) offer a provider-informed menu of free, brief measures; (5) develop and provide access to training materials; and (6) make implementation easier by removing burdensome documentation tasks. Provider and researcher ratings were not significantly different, with a few exceptions: providers reported higher feasibility and importance of removing burdensome paperwork than researchers, providers reported higher feasibility of train-the trainer approaches than researchers, and researchers reported higher importance of monitoring fidelity than providers. Conclusions: The education sector is the most common setting for child and adolescent mental health service delivery in the USA. Effective MBC implementation in schools has the potential to elevate the quality of care received by many children, adolescents, and their families. This empirically derived, targeted list of six implementation strategies offers potential efficiencies for future testing of MBC implementation in schools.
    • Arrhythmia Monitoring and Outcomes in Patients With Cardiac Sarcoidosis: Insights From the Cardiac Sarcoidosis Consortium.

      Bressi, Edoardo; Crawford, Thomas C; Bogun, Frank M; Gu, Xiaokui; Ellenbogen, Kenneth A; Chicos, Alexandra B; Roukoz, Henri; Zimetbaum, Peter J; Kalbfleisch, Steven J; Murgatroyd, Francis D; et al. (American Heart Association, 2022-06-22)
    • Exploration of the Nurse Shark (Ginglymostoma cirratum) Plasma Immunoproteome Using High-Resolution LC-MS/MS.

      Bakke, Fiona K; Gundappa, Manu Kumar; Matz, Hanover; Stead, David A; Macqueen, Daniel J; Dooley, Helen (Frontiers Media S.A., 2022-06-06)
      Many animals of scientific importance lack species-specific reagents (e.g., monoclonal antibodies) for in-depth studies of immune proteins. Mass spectrometry (MS)-based proteomics has emerged as a useful method for monitoring changes in protein abundance and modifications in non-model species. It can be used to quantify hundreds of candidate immune molecules simultaneously without the generation of new reagents. Here, we used MS-based proteomics to identify and quantify candidate immune proteins in the plasma of the nurse shark (Ginglymostoma cirratum), a cartilaginous fish and representative of the most basal extant vertebrate lineage with an immunoglobulin-based immune system. Mass spectrometry-based LC-MS/MS was performed on the blood plasma of nurse sharks immunized with human serum albumin (n=4) or sham immunized (n=1), and sampled at days 0 (baseline control), 1, 2, 3, 5, 7, 14, 21, 28, 25, 42 and 49. An antigen-specific antibody response was experimentally confirmed post-immunization. To provide a high-quality reference to identify proteins, we assembled and annotated a multi-tissue de novo transcriptome integrating long- and short-read sequence data. This comprised 62,682 contigs containing open reading frames (ORFs) with a length >80 amino acids. Using this transcriptome, we reliably identified 626 plasma proteins which were broadly categorized into coagulation, immune, and metabolic functional groups. To assess the feasibility of performing LC-MS/MS proteomics in nurse shark in the absence of species-specific protein annotations, we compared the results to an alternative strategy, mapping peptides to proteins predicted in the genome assembly of a related species, the whale shark (Rhincodon typus). This approach reliably identified 297 proteins, indicating that useful data on the plasma proteome may be obtained in many instances despite the absence of a species-specific reference protein database. Among the plasma proteins defined against the nurse shark transcriptome, fifteen showed consistent changes in abundance across the immunized shark individuals, indicating a role in the immune response. These included alpha-2-macroglobulin (A2M) and a novel protein yet to be characterized in diverse vertebrate lineages. Overall, this study enhances genetic and protein-level resources for nurse shark research and vastly improves our understanding of the elasmobranch plasma proteome, including its remodelling following immune stimulation.