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The complex non-centrosymmetric and chiral nature of helical structures endow materials that possess such motifs with unusual properties. However, despite their ubiquity in biological and organic systems, there is a severe lack of inorganic crystals that display helicity in extended lattices, where these unusual properties are expected to be most pronounced. Here, we report a new inorganic helical structure, gallium sulfur iodide (GaSI), within the exfoliable class of III-VI-VII (1:1:1) one-dimensional (1D) van der Waals (vdW) crystals. Through detailed structural analyses, including single-crystal X-ray diffraction, electron microscopy, and density functional theory (DFT), we elucidate the apparent noncrystallographic screw axis and the first example of an atomic scale helical structure bearing a squircular cross-section in GaSI. Crystallizing in the non-centrosymmetric P4̅ space group, we found that GaSI crystals exhibit pronounced second-harmonic generation. From diffuse reflectance spectroscopy, GaSI displays a sizeable bandgap of 3.69 eV, owing tostrong covalent interactions arising from the smaller sulfur atoms within the helix core. These results position GaSI as a promising exfoliable nonlinear optical material across a broad optical window.

Brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is increasingly used for frontline treatment of stage III/IV classical Hodgkin lymphoma (cHL). Peripheral neuropathy (PN) was the most common and treatment-limiting side effect seen in clinical trials but has not been studied in a nontrial setting, in which clinicians may have different strategies for managing it. We conducted a multisite retrospective study to characterize PN in patients who received BV + AVD for newly diagnosed cHL. One hundred fifty-three patients from 10 US institutions were eligible. Thirty-four patients (22%) had at least 1 ineligibility criteria for ECHELON-1, including stage, performance status, and comorbidities. PN was reported by 80% of patients during treatment; 39% experienced grade (G) 1, 31% G2, and 10% G3. In total, BV was modified in 44% of patients because of PN leading to BV discontinuation in 23%, dose reduction in 17%, and temporary hold in 4%. With a median follow-up of 24 months, PN resolution was documented in 36% and improvement in 33% at the last follow-up. Two-year progression-free survival (PFS) for the advanced-stage patients was 82.7% (95% confidence interval [CI], 0.76-0.90) and overall survival was 97.4% (95% CI, 0.94-1.00). Patients who discontinued BV because of PN did not have inferior PFS. In the nontrial setting, BV + AVD was associated with a high incidence of PN. In our cohort, which includes patients who would not have been eligible for the pivotal ECHELON-1 trial, BV discontinuation rates were higher than previously reported, but 2-year outcomes remain comparable.

Group B enteroviruses, including coxsackievirus B3 (CVB3), can persistently infect cardiac tissue and cause dilated cardiomyopathy. Persistence is linked to 5' terminal deletions of viral genomic RNAs that have been detected together with minor populations of full-length genomes in human infections. In this study, we explored the functions and interactions of the different viral RNA forms found in persistently infected patients and their putative role(s) in pathogenesis. Since enterovirus cardiac pathogenesis is linked to the viral proteinase 2A, we investigated the effect of different terminal genomic RNA deletions on 2A activity. We discovered that 5' terminal deletions in CVB3 genomic RNAs decreased the levels of 2A proteinase activity but could not abrogate it. Using newly generated viral reporters encoding nano-luciferase, we found that 5' terminal deletions resulted in decreased levels of viral protein and RNA synthesis in singly transfected cardiomyocyte cultures. Unexpectedly, when full-length and terminally deleted forms were cotransfected into cardiomyocytes, a cooperative interaction was observed, leading to increased viral RNA and protein production. However, when viral infections were carried out in cells harboring 5' terminally deleted CVB3 RNAs, a decrease in infectious particle production was observed. Our results provide a possible explanation for the necessity of full-length viral genomes during persistent infection, as they would stimulate efficient viral replication compared to that of the deleted genomes alone. To avoid high levels of viral particle production that would trigger cellular immune activation and host cell death, the terminally deleted RNA forms act to limit the production of viral particles, possibly as trans-dominant inhibitors. IMPORTANCE Enteroviruses like coxsackievirus B3 are able to initiate acute infections of cardiac tissue and, in some cases, to establish a long-term persistent infection that can lead to serious disease sequelae, including dilated cardiomyopathy. Previous studies have demonstrated the presence of 5' terminally deleted forms of enterovirus RNAs in heart tissues derived from patients with dilated cardiomyopathy. These deleted RNAs are found in association with very low levels of full-length enterovirus genomic RNAs, an interaction that may facilitate continued persistence while limiting virus particle production. Even in the absence of detectable infectious virus particle production, these deleted viral RNA forms express viral proteinases at levels capable of causing viral pathology. Our studies provide mechanistic insights into how full-length and deleted forms of enterovirus RNA cooperate to stimulate viral protein and RNA synthesis without stimulating infectious viral particle production. They also highlight the importance of targeting enteroviral proteinases to inhibit viral replication while at the same time limiting the long-term pathologies they trigger.

BACKGROUND: With the expanded indications for telemedicine, there is increased utility for screening methods to determine which patients are likely to progress to surgical intervention, requiring in-person visits. Patient-rated tools such as the Boston Carpal Tunnel Questionnaire (BCTQ) may be one such tool for screening patients with carpal tunnel syndrome (CTS). The aim of the study was to evaluate whether BCTQ scores were predictive of offering conservative treatment or surgical intervention for CTS. METHODS: Patients diagnosed with CTS from January 2017 to February 2020 completed BCTQ questionnaires prior to in-person office visits. Demographics, comorbidities, and highest level of intervention recommended were recorded for each patient as conservative, injection, or surgery. Pearson χ2 and independent-samples t tests were conducted to determine whether BCTQ symptom severity and functional scores were associated with intervention type. RESULTS: A total of 200 patients with CTS were included. Of these, 103 were recommended conservative or injection treatment and 97 were recommended surgery. There were no differences in comorbidities between groups, including other upper extremity pathology (P = .57), previous upper extremity surgery (P = .32), hypertension (P = .17), hypothyroidism (P = .15), rheumatoid arthritis (P = .34), and diabetes (P = .30). Between these groups, there were no differences in BCTQ symptom severity score (symptom severity scale [SSS]; P = .16) or BCTQ functional severity score (functional severity scale [FSS]; P = .96). CONCLUSIONS: There is no correlation between comorbidities and BCTQ SSS or FSS score, and offering surgery for CTS. In an era of minimizing non-essential health care visits, the BCTQ is insufficient in screening patients as potential surgical candidates.

OBJECTIVE: The purpose of this study was to compare the results of a biphasic synthetic scaffold (TruFit, Smith & Nephew) to microfracture for the treatment of knee cartilage defects and identify patient- and lesion-specific factors that influence outcomes. DESIGN: Prospectively collected data from 132 patients (mean age, 41.8 years; 69% male) with isolated chondral or osteochondral femoral defects treated with biphasic synthetic scaffolds (n = 66) or microfracture (n = 66) were reviewed. Clinical outcomes were evaluated longitudinally over 5 years with the Short Form-36 (SF-36), Activities of Daily Living of the Knee Outcome Survey (KOS-ADL), International Knee Documentation Committee (IKDC), and Marx Activity Scale. Cartilage-sensitive magnetic resonance imaging (MRI) was performed to evaluate osseous integration and cartilage fill in a subgroup of patients. Multivariate regression analysis was used to identify predictors of clinical outcomes within the scaffold group. RESULTS: Both groups demonstrated clinically significant improvements in knee clinical scores over 5 years (P < 0.01). There were no significant differences in KOS-ADL and IKDC scores between groups up to 5 years postoperatively. Marx activity level scores in the microfracture group declined over time, while significant improvements in activity level scores were observed in the scaffold group over 5 years (P < 0.01). Good-quality tissue fill and cartilage isointensity were more often observed in the scaffold group compared with the microfracture group, particularly with longer time intervals. Increasing age, high body mass index, prior microfracture, and traumatic etiology were predictors for inferior outcomes in the scaffold group. CONCLUSIONS: Activity level and MRI appearance following treatment of cartilage lesions with the biphasic synthetic scaffold were superior to microfracture over time in this nonrandomized, retrospective comparison.

ObjectiveThe purpose of this study was to compare the results of a biphasic synthetic scaffold (TruFit, Smith & Nephew) to microfracture for the treatment of knee cartilage defects and identify patient- and lesion-specific factors that influence outcomes.DesignProspectively collected data from 132 patients (mean age, 41.8 years; 69% male) with isolated chondral or osteochondral femoral defects treated with biphasic synthetic scaffolds (n = 66) or microfracture (n = 66) were reviewed. Clinical outcomes were evaluated longitudinally over 5 years with the Short Form-36 (SF-36), Activities of Daily Living of the Knee Outcome Survey (KOS-ADL), International Knee Documentation Committee (IKDC), and Marx Activity Scale. Cartilage-sensitive magnetic resonance imaging (MRI) was performed to evaluate osseous integration and cartilage fill in a subgroup of patients. Multivariate regression analysis was used to identify predictors of clinical outcomes within the scaffold group.ResultsBoth groups demonstrated clinically significant improvements in knee clinical scores over 5 years (P < 0.01). There were no significant differences in KOS-ADL and IKDC scores between groups up to 5 years postoperatively. Marx activity level scores in the microfracture group declined over time, while significant improvements in activity level scores were observed in the scaffold group over 5 years (P < 0.01). Good-quality tissue fill and cartilage isointensity were more often observed in the scaffold group compared with the microfracture group, particularly with longer time intervals. Increasing age, high body mass index, prior microfracture, and traumatic etiology were predictors for inferior outcomes in the scaffold group.ConclusionsActivity level and MRI appearance following treatment of cartilage lesions with the biphasic synthetic scaffold were superior to microfracture over time in this nonrandomized, retrospective comparison.

The poliovirus type I IRES is able to recruit ribosomal machinery only in the presence of host factor PCBP2 that binds to stem-loop IV of the IRES. When PCBP2 is cleaved in its linker region by viral proteinase 3CD, translation initiation ceases allowing the next stage of replication to commence. Here, we investigate the interaction of PCBP2 with the apical region of stem-loop IV (SLIVm) of poliovirus RNA in its full-length and truncated form. CryoEM structure reconstruction of the full-length PCBP2 in complex with SLIVm solved to 6.1 Å resolution reveals a compact globular complex of PCBP2 interacting with the cruciform RNA via KH domains and featuring a prominent GNRA tetraloop. SEC-SAXS, SHAPE and hydroxyl-radical cleavage establish that PCBP2 stabilizes the SLIVm structure, but upon cleavage in the linker domain the complex becomes more flexible and base accessible. Limited proteolysis and REMSA demonstrate the accessibility of the linker region in the PCBP2/SLIVm complex and consequent loss of affinity of PCBP2 for the SLIVm upon cleavage. Together this study sheds light on the structural features of the PCBP2/SLIV complex vital for ribosomal docking, and the way in which this key functional interaction is regulated following translation of the poliovirus genome.

Backgroundε-Aminocaproic acid (EACA) is an antifibrinolytic agent that has been shown to decrease blood loss and transfusion requirements in several populations undergoing various surgical procedures. However, the efficacy of EACA has not been assessed in pediatric patients with cerebral palsy undergoing bilateral varus rotational femoral osteotomies. The purpose of this study was to assess the efficacy of intravenous EACA in reducing calculated intraoperative blood loss and transfusions in this population.MethodsPatients aged 18 years or younger were eligible. Patients were randomized to receive EACA or placebo (saline), and randomization was stratified based on sex and whether or not additional soft tissue or osseous procedures were performed. On the basis of retrospective data, the calculated sample size was 12 patients per arm to detect a difference of 250-mL blood loss. The primary outcome was calculated intraoperative blood loss. Secondary outcomes included transfusion requirements, 24-hour drain output, length of stay, and incidence of complications.ResultsThe mean age of patients in this study was 8 years (SD: 2.4 y). There were no differences in age, sex, height, weight, type of anesthesia, operative time, and associated procedures between the EACA and placebo groups (P>0.05). Preoperative hematocrit was lower in the EACA group (37.1 vs. 40.0, P=0.04). Calculated intraoperative blood loss was 536 mL in the EACA group and 628 mL in the placebo group (P=0.45). Transfusions were required in 62% of patients in the EACA group and 67% of patients in the placebo group (P=0.68). Total 24-hour drain output was 72.5 mL in the EACA group and 103.3 mL in the placebo group (P=0.37). Length of stay was similar between both groups, and there were no drug or placebo-related complications in either group.ConclusionsThere was no difference in blood loss or transfusion requirements associated with EACA compared with placebo; however, this study is underpowered to detect smaller differences in blood loss. Additional studies with larger sample sizes are needed to confirm these findings and further elucidate the indications for antifibrinolytic agents in pediatric patients.Level of evidenceLevel I.

Backgroundε-Aminocaproic acid (EACA) is an antifibrinolytic agent that has been shown to decrease blood loss and transfusion requirements in several populations undergoing various surgical procedures. However, the efficacy of EACA has not been assessed in pediatric patients with cerebral palsy undergoing bilateral varus rotational femoral osteotomies. The purpose of this study was to assess the efficacy of intravenous EACA in reducing calculated intraoperative blood loss and transfusions in this population.MethodsPatients aged 18 years or younger were eligible. Patients were randomized to receive EACA or placebo (saline), and randomization was stratified based on sex and whether or not additional soft tissue or osseous procedures were performed. On the basis of retrospective data, the calculated sample size was 12 patients per arm to detect a difference of 250-mL blood loss. The primary outcome was calculated intraoperative blood loss. Secondary outcomes included transfusion requirements, 24-hour drain output, length of stay, and incidence of complications.ResultsThe mean age of patients in this study was 8 years (SD: 2.4 y). There were no differences in age, sex, height, weight, type of anesthesia, operative time, and associated procedures between the EACA and placebo groups (P>0.05). Preoperative hematocrit was lower in the EACA group (37.1 vs. 40.0, P=0.04). Calculated intraoperative blood loss was 536 mL in the EACA group and 628 mL in the placebo group (P=0.45). Transfusions were required in 62% of patients in the EACA group and 67% of patients in the placebo group (P=0.68). Total 24-hour drain output was 72.5 mL in the EACA group and 103.3 mL in the placebo group (P=0.37). Length of stay was similar between both groups, and there were no drug or placebo-related complications in either group.ConclusionsThere was no difference in blood loss or transfusion requirements associated with EACA compared with placebo; however, this study is underpowered to detect smaller differences in blood loss. Additional studies with larger sample sizes are needed to confirm these findings and further elucidate the indications for antifibrinolytic agents in pediatric patients.Level of evidenceLevel I.

BackgroundAn early-life anxious temperament (AT) is a risk factor for the development of anxiety, depression, and comorbid substance abuse. We validated a nonhuman primate model of early-life AT and identified the dorsal amygdala as a core component of AT's neural circuit. Here, we combine RNA sequencing, viral-vector gene manipulation, functional brain imaging, and behavioral phenotyping to uncover AT's molecular substrates.MethodsIn response to potential threat, AT and brain metabolism were assessed in 46 young rhesus monkeys. We identified AT-related transcripts using RNA-sequencing data from dorsal amygdala tissue (including central nucleus of the amygdala [Ce] and dorsal regions of the basal nucleus). Based on the results, we overexpressed the neurotrophin-3 gene, NTF3, in the dorsal amygdala using intraoperative magnetic resonance imaging-guided surgery (n = 5 per group).ResultsThis discovery-based approach identified AT-related alterations in the expression of well-established and novel genes, including an inverse association between NTRK3 expression and AT. NTRK3 is an interesting target because it is a relatively unexplored neurotrophic factor that modulates intracellular neuroplasticity pathways. Overexpression of the transcript for NTRK3's endogenous ligand, NTF3, in the dorsal amygdala resulted in reduced AT and altered function in AT's neural circuit.ConclusionsTogether, these data implicate neurotrophin-3/NTRK3 signaling in the dorsal amygdala in mediating primate anxiety. More generally, this approach provides an important step toward understanding the molecular underpinnings of early-life AT and will be useful in guiding the development of treatments to prevent the development of stress-related psychopathology.

A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The GAL4 Technique for Real-time and Clonal Expression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide.

Background: Anterior cruciate ligament (ACL) injuries are associated with a risk of post-traumatic osteoarthritis due to chondral damage. Magnetic resonance imaging (MRI) techniques provide excellent visualization and assessment of cartilage and can detect subtle and early chondral damage. This is often preceding clinical and radiographic post-traumatic osteoarthritis. Hypothesis: Morphologic and quantitative MRI techniques can assess early and progressive degenerative chondral changes after acute ACL injury. Study Design: Prospective longitudinal cohort. Level of Evidence: Level 3. Methods: Sixty-five participants with acute unilateral ACL injuries underwent bilateral knee MRI scans within 1 month of injury. Fifty-seven participants presented at 6 months, while 54 were evaluated at 12 months. MRI morphologic evaluation using a modified Noyes score assessed cartilage signal alteration, chondral damage, and subchondral bone status. Quantitative T1ρ and T2 mapping at standardized anatomic locations in both knees was assessed. Participant-reported outcomes at follow-up time points were recorded. Results: Baseline Noyes scores of MRI detectable cartilage damage were highest in the injured knee lateral tibial plateau (mean 2.5, standard error (SE) 0.20, P < 0.01), followed by lateral femoral condyle (mean 2.1, SE 0.18, P < 0.01), which progressed after 1 year. Longitudinal prolongation at 12 months in the injured knees was significant for T1ρ affecting the medial and lateral femoral condyles (P < 0.01) and trochlea (P < 0.01), whereas T2 values were prolonged for medial and lateral femoral condyles (P < 0.01) and trochlea (P < 0.01). The contralateral noninjured knees also demonstrated T1ρ and T2 prolongation in the medial and lateral compartment chondral subdivisions. Progressive chondral damage occurred despite improved patient-reported outcomes. Conclusion: After ACL injury, initial and sustained chondral damage predominantly affects the lateral tibiofemoral compartment, but longitudinal chondral degeneration also occurred in other compartments of the injured and contralateral knee. Clinical Relevance: Early identification of chondral degeneration post-ACL injury using morphological and quantitative MRI techniques could enable interventions to be implemented early to prevent or delay PTOA. [ABSTRACT FROM AUTHOR]

Background: It remains unclear which subset of patients with recurrent patellofemoral instability would benefit from a concomitant bony realignment procedure in addition to a medial patellofemoral ligament (MPFL) reconstruction. Purpose: To provide midterm results for patients who underwent an isolated MPFL reconstruction as part of an ongoing prospective trial. Study Design: Case series; Level of evidence, 4. Methods: Patients with recurrent patellar instability were prospectively enrolled in an institutional registry beginning in March 2014. Exclusion criteria included history of a previous surgery for patellar instability, an off-loadable (inferior/lateral) chondral defect, anterior knee pain ≥50% of their chief complaint, and a "jumping J" sign. All patients underwent primary, unilateral, isolated MPFL reconstruction regardless of their bony anatomic characteristics. Patient-reported outcome measures (PROMs), episodes of recurrent instability, and ability to return to sport were obtained annually. Radiographic measurements of baseline radiographs and MRI were obtained at baseline. Results: A total of 138 patients underwent isolated MPFL reconstruction between March 2014 and December 2019. The mean radiographic measurements were tibial tubercle–trochlear groove, 15.1 ± 4.9 mm; Caton-Deschamps index, 1.14 ± 0.16; patellar trochlear index, 46.9% ± 15.1%; trochlear depth index, 2.5 ± 1.2 mm; tibial tubercle to lateral trochlear ridge, −8.4 ± 5.7 mm; and patellar tendon to lateral trochlear ridge, 5.7 ± 6.2 mm. Trochlear dysplasia, defined as a trochlear depth index <3 mm, was present in 79/125 (63%) patients. A total of 50 patients reached ≥5 years, of whom 40 (80%) completed follow-up PROMs. A total of 119 patients reached ≥2 years, of whom 89 (75%) completed follow-up PROMs. Six patients (5%) reported recurrent instability with a mean time of 2.97 years after surgery. All PROMs improved over time except for the Pediatric Functional Activity Brief Scale (Pedi-FABS), which had no change. At 2 years, the mean changes from baseline for Knee injury and Osteoarthritis Outcome Score (KOOS) Quality of Life subscale (QOL), Pedi-FABS, International Knee Documentation Committee (IKDC) score, KOOS Physical Function Short Form (PS), and Kujala score were 42.1, 0.6, 35.1, –23.5, and 32.3, respectively. All changes had P values <.001 except for Pedi-FABS, which showed no change and had P >.999. At 5 years, the mean changes from baseline for KOOS-QOL, Pedi-FABS, IKDC, KOOS-PS, and Kujala score were 42.6, –2.8, 32.6, –21.5, and 31.6, respectively. All changes had P values <.001 except for Pedi-FABS, which showed no change and had P >.453. In total, 89% of patients returned to sport with a mean of 9.1 months. Conclusion: Midterm outcomes for patients who underwent isolated MPFL reconstruction were favorable and were maintained at 5 years. Outcomes for the expanded cohort of patients with a minimum 2-year follow-up support previously published results. [ABSTRACT FROM AUTHOR]

When campuses across the world needed to transition to the online format due to the COVID-19 pandemic, there were many challenges educators faced, and addressing academic integrity issues were some of the most important. Certain strategies, such as online proctoring or additional software, were not available to most institutions because the expenses and training were too much to overcome. A more pedagogical and cost-effective strategy involved modifying the assessment format in a way that minimized or discouraged cheating. This paper presents strategies that effectively minimize cheating while addressing learning outcomes.

As the need for online or virtual science courses grows, it is important to incorporate laboratory work into these courses. However, it is difficult to find cost-effective ways to integrate the laboratory work, especially as campuses across the world have had to quickly transition to the online learning environment in the midst of the COVID-19 pandemic. Thus, hands-on laboratory experiments that can be performed safely at home without the need to purchase expensive commercial laboratory kits would be valuable. This paper presents a set of laboratory exercises that are utilized in an online nonmajor science course. Student and instructor experiences are also presented.

Protein production, genomic RNA replication, and virion assembly during infection by picornaviruses like human rhinovirus and poliovirus take place in the cytoplasm of infected human cells, making them the quintessential cytoplasmic pathogens. However, a growing body of evidence suggests that picornavirus replication is promoted by a number of host proteins localized normally within the host cell nucleus. To systematically identify such nuclear proteins, we focused on those that appear to re-equilibrate from the nucleus to the cytoplasm during infection of HeLa cells with human rhinovirus via quantitative protein mass spectrometry. Our analysis revealed a highly selective re-equilibration of proteins with known mRNA splicing and transport-related functions over nuclear proteins of all other functional classes. The multifunctional splicing factor proline and glutamine rich (SFPQ) was identified as one such protein. We found that SFPQ is targeted for proteolysis within the nucleus by viral proteinase 3CD/3C, and a fragment of SFPQ was shown to migrate to the cytoplasm at mid-to-late times of infection. Cells knocked down for SFPQ expression showed significantly reduced rhinovirus titers, viral protein production, and viral RNA accumulation, consistent with SFPQ being a pro-viral factor. The SFPQ fragment that moved into the cytoplasm was able to bind rhinovirus RNA either directly or indirectly. We propose that the truncated form of SFPQ promotes viral RNA stability or replication, or virion morphogenesis. More broadly, our findings reveal dramatic changes in protein compartmentalization during human rhinovirus infection, allowing the virus to systematically hijack the functions of proteins not normally found at its cytoplasmic site of replication.

Herpes zoster (HZ) occurs at a higher age-specific rate in people living with HIV (PLWH) than in the general population. We implemented a quality improvement study to assess herpes zoster vaccine (HZV) usage among PLWH, assess HZV usage after additional reminders/prompts, and identify barriers to HZV among older PLWH. HZV rates in PLWH were determined in six institutions with varying payment structures. For the intervention, Part 1, PLWH eligible for HZV at the University of Colorado were identified, and providers were notified of patient eligibility. In Part 2, in addition to provider notification, an order for HZV was placed in the patient's chart before a clinic appointment. HZ vaccination rates ranged from 1.5% to 42.4% at six sites. Before the intervention, 21.3% of eligible University of Colorado patients had received HZV. An additional 8.3% received HZV with Part 1 and 17.8% with Part 2 interventions. At completion, a total of 53.2% of eligible patients had received HZV through routine clinical care or the interventions. Insurance coverage concern was cited as a common reason for not receiving HZV. Minor adverse reactions occurred in 26.7% patients and did not require medical care. HZV coverage was low at a majority of sites. Clinical reminders with links to vaccination orders or preplaced vaccination orders led to improved HZV coverage in our clinic, but published guidelines for use of HZV in PLWH and improvement in logistic or insurance barriers to HZV receipt are paramount to improved HZV coverage.

Background: Uncertainty continues to surround mild traumatic brain injury (mTBI) diagnosis, symptoms, prognosis, and outcome due in part to a lack of objective biomarkers of injury and recovery. As mTBI gains recognition as a serious public health epidemic, there is need to identify risk factors, diagnostic tools, and imaging biomarkers to help guide diagnosis and management. Methods: One hundred and eleven patients (15-50 years old) were enrolled acutely after mTBI and followed with up to four standardized serial assessments over 3 months. Each encounter included a clinical exam, neuropsychological assessment, and magnetic resonance imaging (MRI). Chi-square and linear mixed models were used to assess changes over time and determine potential biomarkers of mTBI severity and outcome. Results: The symptoms most frequently endorsed after mTBI were headache (91%), not feeling right (89%), fatigue (86%), and feeling slowed down (84%). Of the 104 mTBI patients with a processed MRI scan, 28 (27%) subjects had white matter changes which were deemed unrelated to age, and 26 of these findings were deemed unrelated to acute trauma. Of the neuropsychological assessments tested, 5- and 6-Digit Backward Recall, the modified Balance Error Scoring System (BESS), and Immediate 5-Word Recall significantly improved longitudinally in mTBI subjects and differentiated between mTBI subjects and controls. Female sex was found to increase symptom severity scores (SSS) at every time point. Age ≥ 25 years was correlated with increased SSS. Subjects aged ≥ 25 also did not improve longitudinally on 5-Digit Backward Recall, Immediate 5-Word Recall, or Single-Leg Stance of the BESS, whereas subjects < 25 years improved significantly. Patients who reported personal history of depression, anxiety, or other psychiatric disorder had higher SSS at each time point. Conclusions: The results of this study show that 5- and 6-Digit Backward Recall, the modified BESS, and Immediate 5-Word Recall should be considered useful in demonstrating cognitive and vestibular improvement during the mTBI recovery process. Clinicians should take female sex, older age, and history of psychiatric disorder into account when managing mTBI patients. Further study is necessary to determine the true prevalence of white matter changes in people with mTBI.