Developing Workforce Skills and Capacity in Telehealth: What LEND Trainees Need to Know.

INTRODUCTION: The COVID-19 pandemic significantly impacted the way health-related services are delivered, rapidly shifting from in-person to telehealth visits. To ensure that future healthcare providers are fully prepared to deliver services to families of youth with neurodevelopmental disabilities (NDD), understanding telehealth's advantages and barriers is vital. To this end, data were gathered to inform the development of a nationally available telehealth curriculum aimed at training future healthcare professionals from the Leadership Education in Neurodevelopmental Disabilities (LEND) network. METHODS: Surveys were sent out nationally to current LEND trainees, practicing healthcare professionals, and family members of youth with NDD in November of 2020. Multiple choice and free response questions were completed and analyzed. A total of N = 208 surveys were completed (88 LEND trainees, 94 practicing professionals, 23 family members). RESULTS: Most survey respondents reported having positive experiences with telehealth. LEND trainees and current healthcare professionals cited increased access to care and engagement as the top benefit of telehealth. Most family members reported using telehealth services (78%) and felt it was superior to in-person visits in terms of location of visit, scheduling, and meeting transportation needs. Trainees and professionals agreed the top barriers to telehealth for families were lack of broadband access and complexity of implementation and use. LEND trainees agreed telehealth basics should be included in LEND curriculum. DISCUSSION: Trainees, professionals, and family members all agreed that knowing the basics of telehealth is essential for effective telehealth service delivery. Emerging healthcare professionals need to understand how those they will be serving engage with technology, their levels of experience in this area, and effective strategies for engaging children and youth with NDD through telehealth. This will bridge the engagement gap many families of children with disabilities face when not meeting in person. Findings from this study contributed to the design of learning materials that currently support LEND trainees across the country in developing these skills.

Correlating structure and photophysical properties in thiazolo[5,4-d]thiazole crystal derivatives for use in solid-state photonic and fluorescence-based optical devices.

There is a growing demand for new fluorescent small molecule dyes for solid state applications in the photonics and optoelectronics industry. Thiazolo[5,4-d]thiazole (TTz) is an organic heterocycle moiety which has previously shown remarkable properties as a conjugated polymer and in solution-based studies. For TTz-based small molecules to be incorporated in solid-state fluorescence-based optical devices, a thorough elucidation of their structure-photophysical properties needs to be established. Herein, we have studied four TTz-based materials functionalized with alkyl appendages of varying carbon chain lengths. We report the single crystal structures of the TTz derivatives, three of which were previously unknown. The packing modes of the crystals reveal that molecular arrangements are largely governed by a chorus of synergistic intermolecular non-covalent interactions. Three crystals packed in herringbone mode and one crystal packed in slipped stacks proving that alkyl appendages modulate structural organization in TTz-based materials. Steady state and time-resolved photophysical properties of these crystals were studied via diffuse-reflectance, micro-Raman, and photoluminescence spectroscopy. The crystals fluoresce from orange-red to blue spanning through the whole gamut of the visible spectrum. We have established that photophysical properties are a function of crystal packing in symmetrically substituted TTz-based materials. This correlation was then utilized to fabricate crystalline blends. We demonstrate, for the first time, that symmetrically substituted donor-acceptor-donor TTz-based materials can be used for phosphor-converted color-tuning and white-light emission. Given the cost effectiveness, ease of synthesis and now a structure-photophysics correlation, we present a compelling case for the adoption of TTz-based materials in solid-state photonic and fluorescence-based optical devices.

Microscopy Visualization of Carrier Transport in CdSeTe/CdTe Solar Cells.

Solar cells are essentially minority carrier devices, and it is therefore of central importance to understand the pertinent carrier transport processes. Here, we advanced a transport imaging technique to directly visualize the charge motion and collection in the direction of relevant carrier transport and to understand the cell operation and degradation in state-of-the-art cadmium telluride solar cells. We revealed complex carrier transport profiles in the inhomogeneous polycrystalline thin-film solar cell, with the influence of electric junction, interface, recombination, and material composition. The pristine cell showed a unique dual peak in the carrier transport light intensity decay profile, and the dual peak feature disappeared on a degraded cell after light and heat stressing in the lab. The experiments, together with device modeling, suggested that selenium diffusion plays an important role in carrier transport. The work opens a new forum by which to understand the carrier transport and bridge the gap between atomic/nanometer-scale chemical/structural and submicrometer optoelectronic knowledge.

Altered Immunoglobulin Repertoire and Decreased IgA Somatic Hypermutation in the Gut during Chronic HIV-1 Infection.

Humoral immune perturbations contribute to pathogenic outcomes in persons with HIV-1 infection (PWH). Gut barrier dysfunction in PWH is associated with microbial translocation and alterations in microbial communities (dysbiosis), and IgA, the most abundant immunoglobulin (Ig) isotype in the gut, is involved in gut homeostasis by interacting with the microbiome. We determined the impact of HIV-1 infection on the antibody repertoire in the gastrointestinal tract by comparing Ig gene utilization and somatic hypermutation (SHM) in colon biopsies from PWH (n = 19) versus age and sex-matched controls (n = 13). We correlated these Ig parameters with clinical, immunological, microbiome and virological data. Gene signatures of enhanced B cell activation were accompanied by skewed frequencies of multiple Ig Variable genes in PWH. PWH showed decreased frequencies of SHM in IgA and possibly IgG, with a substantial loss of highly mutated IgA sequences. The decline in IgA SHM in PWH correlated with gut CD4+ T cell loss and inversely correlated with mucosal inflammation and microbial translocation. Diminished gut IgA SHM in PWH was driven by transversion mutations at A or T deoxynucleotides, suggesting a defect not at the AID/APOBEC3 deamination step but at later stages of IgA SHM. These results expand our understanding of humoral immune perturbations in PWH that could have important implications in understanding mucosal immune defects in individuals with chronic HIV-1 infection. IMPORTANCE The gut is a major site of early HIV-1 replication and pathogenesis. Extensive CD4+ T cell depletion in this compartment results in a compromised epithelial barrier that facilitates the translocation of microbes into the underlying lamina propria and systemic circulation, resulting in chronic immune activation. To date, the consequences of microbial translocation on the mucosal humoral immune response (or vice versa) remains poorly integrated into the panoply of mucosal immune defects in PWH. We utilized next-generation sequencing approaches to profile the Ab repertoire and ascertain frequencies of somatic hypermutation in colon biopsies from antiretroviral therapy-naive PWH versus controls. Our findings identify perturbations in the Ab repertoire of PWH that could contribute to development or maintenance of dysbiosis. Moreover, IgA mutations significantly decreased in PWH and this was associated with adverse clinical outcomes. These data may provide insight into the mechanisms underlying impaired Ab-dependent gut homeostasis during chronic HIV-1 infection.

Imaging findings and interventional management of deep venous thrombosis.

Deep venous thrombosis (DVT) is a subtype of venous thromboembolism. Lower extremity DVT affects about 1-2% of hospitalized patients. If not managed properly, these thrombi can embolize, causing further complications. Thrombosis risk factors include vascular endothelial injury, venous stasis, and hypercoagulability states. This triad is also known as Virchow's triad. Although clinical features of lower extremity DVT are nonspecific and many patients are asymptomatic, physicians should maintain a high index of suspicion in patients presenting with leg swelling, pain, warmth, and erythema. Several diagnostic approaches for suspected first DVT have been proposed, and management depends on multiple factors such as location, duration of symptoms, cause of the thrombosis, and recurrence rate.

SAMHD1 Promotes the Antiretroviral Adaptive Immune Response in Mice Exposed to Lipopolysaccharide.

SAMHD1 is a potent HIV-1 restriction factor that blocks reverse transcription in monocytes, dendritic cells and resting CD4+ T cells by decreasing intracellular dNTP pools. However, SAMHD1 may diminish innate immune sensing and Ag presentation, resulting in a weaker adaptive immune response. To date, the role of SAMHD1 on antiretroviral immunity remains unclear, as mouse SAMHD1 had no impact on murine retrovirus replication in prior in vivo studies. Here, we show that SAMHD1 significantly inhibits acute Friend retrovirus infection in mice. Pretreatment with LPS, a significant driver of inflammation during HIV-1 infection, further unmasked a role for SAMHD1 in influencing immune responses. LPS treatment in vivo doubled the intracellular dNTP levels in immune compartments of SAMHD1 knockout but not wild-type mice. SAMHD1 knockout mice exhibited higher plasma infectious viremia and proviral DNA loads than wild-type mice at 7 d postinfection (dpi), and proviral loads inversely correlated with a stronger CD8+ T cell response. SAMHD1 deficiency was also associated with weaker NK, CD4+ T and CD8+ T cell responses by 14 dpi and weaker neutralizing Ab responses by 28 dpi. Intriguingly, SAMHD1 influenced these cell-mediated immune (14 dpi) and neutralizing Ab (28 dpi) responses in male but not female mice. Our findings formally demonstrate SAMHD1 as an antiretroviral factor in vivo that could promote adaptive immune responses in a sex-dependent manner. The requirement for LPS to unravel the SAMHD1 immunological phenotype suggests that comorbidities associated with a "leaky" gut barrier may influence the antiviral function of SAMHD1 in vivo.

Toward Complete, Candid, and Unbiased International Consensus Statements on Concussion in Sport.

Five international consensus statements on concussion in sports have been published. This commentary argues that there is a strong need for a new approach to them that foregrounds public health expertise and patient-centered guidance. Doing so will help players, parents and practitioners keep perspective about these potentially life-altering injuries especially when they recur.

Balloons up: shorter time to angioembolization is associated with reduced mortality in patients with shock and complex pelvic fractures (original study).

BACKGROUND: Angioembolization has been the gold standard for management of pelvic arterial bleeding, but applicability has been limited by delays in access at many trauma centers. We hypothesized that a quality improvement program to reduce time to start of angiography would be associated with lower in-hospital mortality in patients with pelvic fractures and shock. METHODS: Retrospective study of adults with a pelvic fracture and vital signs consistent with shock admitted to a level I trauma center after the initiation of a quality improvement project to reduce the time to angioembolization (2012 to 2016). Time from admission to procedure start for hemorrhage control was examined based on destination and time of day. In-hospital mortality was the primary outcome and was compared with US benchmarks in the literature. RESULTS: The study group included 424 patients with a mean Injury Severity Score of 41±14. Of these, 212 (50%) responded to resuscitation and were admitted to the intensive care unit; 143 (34%) patients went directly to interventional radiology (IR) with a median time to start of angiography of 86 minutes (IQR 66 to 116); and 69 (16%) patients went directly to the OR with a median time to start of operation of 52 minutes (IQR 37 to 73). There were no significant differences in time to procedures based on time of day or transfer status. In-hospital mortality for patients in shock on admission was 15%. DISCUSSION: Patients with pelvic fracture and hemorrhagic shock, with a median time to angioembolization of <90 min, had a lower in-hospital mortality compared with published US benchmarks. These times were achieved by protocolization of pelvic fracture management that includes expeditious mobilization of the IR team, bypassing the CT scanner, and institutional quality metrics for compliance. STUDY TYPE: Case series. LEVEL OF EVIDENCE: IV.

Fluoroscopically-guided interventions with radiation doses exceeding 5000 mGy reference point air kerma: a dosimetric analysis of 89,549 interventional radiology, neurointerventional radiology, vascular surgery, and neurosurgery encounters.

PURPOSE: To quantify and categorize fluoroscopically-guided procedures with radiation doses exceeding 5000 mGy reference point air kerma (Ka,r). Ka,r > 5000 mGy has been defined as a "significant radiation dose" by the Society of Interventional Radiology. Identification and analysis of interventions with high radiation doses has the potential to reduce radiation-induced injuries. MATERIALS AND METHODS: Radiation dose data from a dose monitoring system for 19 interventional suites and 89,549 consecutive patient encounters from January 1, 2013 to August 1, 2019 at a single academic institution were reviewed. All patient encounters with Ka,r > 5000 mGy were included. All other encounters were excluded (n = 89,289). Patient demographics, medical specialty, intervention type, fluoroscopy time (minutes), dose area product (mGy·cm2), and Ka,r (mGy) were evaluated. RESULTS: There were 260 (0.3%) fluoroscopically-guided procedures with Ka,r > 5000 mGy. Of the 260 procedures which exceeded 5000 mGy, neurosurgery performed 81 (30.5%) procedures, followed by interventional radiology (n = 75; 28.2%), neurointerventional radiology (n = 55; 20.7%), and vascular surgery (n = 49; 18.4%). The procedures associated with the highest Ka,r were venous stent reconstruction performed by interventional radiology, arteriovenous malformation embolization performed by neurointerventional radiology, spinal hardware fixation by neurosurgery, and arterial interventions performed by vascular surgery. Neurointerventional radiology had the highest mean Ka,r (7,799 mGy), followed by neurosurgery (7452 mGy), vascular surgery (6849 mGy), and interventional radiology (6109 mGy). The mean Ka,r for interventional radiology performed procedures exceeding 5000 mGy was significantly lower than that for neurointerventional radiology, neurosurgery, and vascular surgery. CONCLUSIONS: Fluoroscopically-guided procedures with radiation dose exceeding 5000 mGy reference point air kerma are uncommon. The results of this study demonstrate that a large proportion of cases exceeding 5000 mGy were performed by non-radiologists, who likely do not receive the same training in radiation physics, radiation biology, and dose reduction techniques as radiologists.

Percutaneous Extra-Anatomic Double-Barrel Bypass for Salvage of Hemodialysis Access and Treatment of Venous Occlusive Disease.

A woman with an upper extremity brachioaxillary arteriovenous dialysis graft presented with a 9-month history of profound ipsilateral arm swelling and numbness secondary to chronic axillosubclavian vein occlusion. Previous endovascular and open venous recanalization attempts were unsuccessful. A totally percutaneous extra-anatomic venous bi-bypass was created to salvage the dialysis access circuit and reconstruct the deep venous system. Using overlapping Viabahn stent-grafts, two parallel bypasses were created from the arteriovenous graft and brachial vein, respectively, to the brachiocephalic vein. The hemodialysis graft regained function. Upper extremity symptoms resolved within 48 h. This is the first reported percutaneous double-barrel technique of extra-anatomic venous bypass creation for simultaneous management of a failed dialysis access and chronic venous occlusive disease.

A Comparison of Buprenorphine, Sustained release Buprenorphine, and High concentration Buprenorphine in Male New Zealand White Rabbits.

Pain management in rabbits can be difficult because they are adept at hiding pain and can be stressed by handling and restraint for injection. The use of opioid analgesics with prolonged durations of activity could alleviate pain, but associated adverse effects including gastrointestinal ileus, inappetence, and tissue reactions have been reported. In this study, we compared gross tissue reactions at the site of injection, food consumption, and fecal production after single injections of buprenorphine HCl (Bup; n = 7), sustained-release buprenorphine (BupSR; n = 8), and high-concentration buprenorphine (BupHC; n = 7) during the first 3 d after minor survival surgery. We also measured plasma concentrations of the parent drug, buprenorphine, and 3 metabolites (buprenorphine-3-glucuronide (B3G), norbuprenorphine-3ß-glucuronide (N3G), and norbuprenorphine (NB)). Plasma levels of buprenorphine remained above the theoretical minimal analgesic concentration for 4 h for Bup and 42 h for BupHC. For BupSR, plasma levels of buprenorphine remained above the theoretical minimal analgesic concentration for approximately 77 h, starting 15 h after administration. For all 3 formulations, N3G was the most prominent metabolite in the blood. No injection site reactions were visible grossly in any rabbit. Relative to baseline measures and compared with controls (n = 8), food consumption was suppressed on days 1 through 3 in rabbits that received BupSR and on days 2 through 3 in those given BupHC. Feces production on day 3 was reduced to a greater extent in BupSR rabbits than control animals. Two rabbits in the BupHC group exhibited neurologic signs after drug administration. These adverse effects should be considered when choosing a long-lasting buprenorphine formulation to manage pain in rabbits.

Percutaneous Extra-Anatomic Lymphovenous Bypass Creation: Toward Treatment of Central Conducting Lymphatic Obstructions.

INTRODUCTION: Protein-losing enteropathy manifests as a loss of serum proteins through the gastrointestinal tract, resulting in hypoproteinemia, extravascular fluid retention, and edema. Management consists of nutritional maintenance in conjunction with interventions targeted at treating the underlying etiology. MATERIALS AND METHODS: This report describes a patient with protein-losing enteropathy from a central conducting lymphatic obstruction who was treated with percutaneous extra-anatomic lymphovenous bypass creation. RESULTS: A modified gun-sight technique was used to create a lymphovenous bypass between an occluded terminal thoracic duct and the left internal jugular vein. CONCLUSION: A percutaneous technique to reconstruct the terminal thoracic duct via lymphovenous bypass creation was feasible.

Eructation Treated with Single-Session CBT: A Case Illustration.

Chronic gastrointestinal disorders are disruptive to patients physically and psychologically, and benefit from multidisciplinary care, including targeted psychological interventions. This case study details a case of a 42-year-old Caucasian female with idiopathic eructation, who was identified as having psychological contributors to her 3-year history of GI symptoms. Following extensive medical testing, she was diagnosed with excessive, likely supragastric belching and referred for psychological care. She noted initial reticence to psychological approaches but was offered psychoeducation and CBT interventions targeting eructation disorder and anxiety. Although the patient paused treatment after only a single session of psychological contact (including assessment and brief intervention), her GI symptoms effectively resolved with application of anxiolytic breathing, psychoeducation, and other cognitive behavioral techniques, suggesting rapid efficacy of CBT interventions, when diligently applied.

Survival of aging CD264+ and CD264- populations of human bone marrow mesenchymal stem cells is independent of colony-forming efficiency.

In vivo mesenchymal stem cell (MSC) survival is relevant to therapeutic applications requiring engraftment and potentially to nonengraftment applications as well. MSCs are a mixture of progenitors at different stages of cellular aging, but the contribution of this heterogeneity to the survival of MSC implants is unknown. Here, we employ a biomarker of cellular aging, the decoy TRAIL receptor CD264, to compare the survival kinetics of two cell populations in human bone marrow MSC (hBM-MSC) cultures. Sorted CD264+ hBM-MSCs from two age-matched donors have elevated ß-galactosidase activity, decreased differentiation potential and form in vitro colonies inefficiently relative to CD264- hBM-MSCs. Counterintuitive to their aging phenotype, CD264+ hBM-MSCs exhibited comparable survival to matched CD264- hBM-MSCs from the same culture during in vitro colony formation and in vivo when implanted ectopically in immunodeficient NIH III mice. In vitro and in vivo survival of these two cell populations were independent of colony-forming efficiency. These findings have ramifications for the preparation of hBM-MSC therapies given the prevalence of aging CD264+ cells in hBM-MSC cultures and the popularity of colony-forming efficiency as a quality control metric in preclinical and clinical studies with MSCs.

Ethical considerations for HIV cure-related research at the end of life.

BACKGROUND: The U.S. National Institute of Allergies and Infectious Diseases (NIAID) and the National Institute of Mental Health (NIMH) have a new research priority: inclusion of terminally ill persons living with HIV (PLWHIV) in HIV cure-related research. For example, the Last Gift is a clinical research study at the University of California San Diego (UCSD) for PLWHIV who have a terminal illness, with a prognosis of less than 6 months. DISCUSSION: As end-of-life (EOL) HIV cure research is relatively new, the scientific community has a timely opportunity to examine the related ethical challenges. Following an extensive review of the EOL and HIV cure research ethics literature, combined with deliberation from various stakeholders (biomedical researchers, PLWHIV, bioethicists, and socio-behavioral scientists) and our experience with the Last Gift study to date, we outline considerations to ensure that such research with terminally ill PLWHIV remains ethical, focusing on five topics: 1) protecting autonomy through informed consent, 2) avoiding exploitation and fostering altruism, 3) maintaining a favorable benefits/risks balance, 4) safeguarding against vulnerability through patient-participant centeredness, and 5) ensuring the acceptance of next-of-kin/loved ones and community stakeholders. CONCLUSION: EOL HIV cure-related research can be performed ethically and effectively by anticipating key issues that may arise. While not unique to the fields of EOL or HIV cure-related research, the considerations highlighted can help us support a new research approach. We must honor the lives of PLWHIV whose involvement in research can provide the knowledge needed to achieve the dream of making HIV infection curable.

Mass Shootings, Mental Illness, and Gun Control.

In the wake of the Stoneman Douglas School shooting, Republican and Democratic leaders-like the American electorate they represent-remain sharply divided in their responses to gun violence. They are united in their condemnation of these mass shootings, but they disagree about whether stricter or looser gun control laws are the answer. Those on the right side of the political aisle suggest that the issue is one of mental illness rather than gun control. Conversely, those who are more liberal or progressive in their political learnings are quick to condemn attempts to reframe the issue of mass shootings as a mental health problem. Both sides are wrong. Mass shootings are indeed partially a mental health problem, albeit one poorly addressed by our current laws and policies. But the solution to mass shootings also needs to consider strategies that may reduce gun violence in general.