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Sepiapterin as a treatment for people living with phenylketonuria: a plain language summary of the APHENITY trial
Full text linkWhat is this summary about?: This plain language summary is based on an article about the APHENITY trial that was published in The Lancet journal in October 2024. The APHENITY trial was a phase 3 clinical trial to find out whether sepiapterin helped people living with phenylketonuria (PKU) and to learn more about its safety. PKU is a rare, genetic condition that causes high levels of phenylalanine (Phe) to build up in the body. High levels of Phe in the body can cause symptoms such as seizures, rashes, and problems with movement, and can also affect brain development, thinking skills, and behaviour. These symptoms can have an impact on people's health-related quality of life.
What happened in the aphenity trial?: Previous studies have shown that sepiapterin is able to decrease Phe levels in the blood. In the APHENITY trial, the researchers wanted to learn more about the efficacy and safety of sepiapterin in a large group of people living with PKU over the course of 8 weeks of treatment. The researchers wanted to: Assess the efficacy of sepiapterin by seeing whether sepiapterin decreased Phe levels in the blood compared with a placebo Assess the safety of sepiapterin by seeing how many health complaints the participants who took sepiapterin had compared with those who took the placebo The APHENITY trial was carried out in two parts: During Part 1, the participants took sepiapterin for 2 weeks to find out if it decreased their Phe levels During Part 2, the participants who benefitted from sepiapterin during Part 1 were randomly assigned to either continue taking sepiapterin or start taking a placebo for a further 6 weeks.
What were the results?: During Part 1, the researchers found that 114 out of 156 participants benefitted from sepiapterin. This was 73% or about 7 in 10 participants. During Part 2, the researchers found that the participants who took sepiapterin had reduced blood Phe levels compared with those who took the placebo. The researchers also found that compared with those who took the placebo, more of the participants who took sepiapterin reduced their blood Phe levels to within the ranges recommended by treatment guidelines. For both parts of the trial, the participants did not have any serious health complaints. So, the researchers concluded that no safety concerns were seen with sepiapterin in this trial.
What do the results of the trial mean?: These results showed that sepiapterin helped to reduce blood Phe levels in the participants, and there were no unexpected safety concerns in people living with PKU
Understanding Alternate Work Schedules and Their Potential to Improve Work-Life Well-Being for Veterans Affairs Nurses
No full textBackground: The employee experience of clinical personnel, especially nurses, is increasingly vital for health care organizations and is now part of health care's quintuple aim, which includes improving patient experience, population health, cost, and health equity. Nurse burnout and turnover intentions have heightened since the COVID-19 pandemic, with high workload and inadequate staffing as key organizational drivers. Flexible work schedules, such as 72/80 (where one works three 12-h shifts per week but receives the pay equivalent of 80 h), have been a longstanding countermeasure, but postpandemic data on their impact are limited.
Objective: This national evaluation investigates the impact of the 72/80 work schedule on Veterans Health Administration (VHA) nurses. We hypothesized that nurses on a 72/80 schedule experience less burnout, higher job satisfaction, greater work engagement, and lower turnover intentions.
Design: We conducted a web-based survey including self-reported 72/80 work status and employee experience measures, alongside existing administrative data on employee outcomes. We analyzed the data using Mann-Whitney U tests, mixed effects, and linear regression models.
Sample: Eight thousand five hundred forty-five VHA nurses from 170 Veterans Affairs Medical Centers nationwide working in 24/7 bedded units completed the survey.
Results: The 72/80 schedule was significantly associated with lower emotional exhaustion and depersonalization, and greater personal accomplishment. In addition, 72/80 status correlated with higher workplace engagement, job satisfaction, organizational satisfaction, and lower turnover intention.
Conclusions: The 72/80 work schedule shows significant potential as a transformative workforce strategy, providing substantial benefits in recruitment, retention, and employee satisfaction
Reproducibility and Diagnostic Utility of a Simplified Oil Red O Test in Infant Bronchoalveolar Lavage Samples
No full textIntroduction: Aspiration in infants is a diagnostic challenge. The lipid-laden macrophage index (LLMI) developed in 1987 has been used as a supportive test; however, numerous recent studies have questioned its value and reproducibility. We evaluated a simplified LLMI in bronchoalveolar lavage (BAL) specimens from a pediatric cohort to assess its diagnostic utility.
Methods: BALs from infants were prospectively collected over a 6-month period for Oil Red O (ORO) staining to evaluate aspiration. BALs from adults with non-aspiration pathologies were simultaneously collected for comparison. Clinical and demographic data were gathered to assess the diagnostic accuracy of the test. Only samples containing ≥ 100 evaluable macrophages and free of obscuring blood or inflammation were included. Positive staining was assessed at low magnification (10×), with only clearly positive cells (Colombo-Hallberg scores 3 and 4) considered. A dichotomous threshold of < 50% or ≥ 50% positive macrophages was established through multidisciplinary consensus. To ensure consistency, a training session was conducted for the entire cytopathology division on the newly developed interpretation criteria.
Results: 88/134 (66%) pediatric BAL samples with suspected aspiration and 63/75 (84%) adult samples with various non-aspiration pathologies were adequate for analysis. Aspiration status in children was determined using multidisciplinary aerodigestive group evaluation (MAGE) and videofluoroscopic swallow study (VFSS). Test performance was assessed at various cutoffs. In the pediatric cohort (mean age 16.5 months, 58% male), aspiration was diagnosed in 47% by MAGE. Strong associations were seen with atopia/asthma (83%), functional dysphagia (64%), and congenital/developmental disorders (43%). A significant difference in ≥ 50% lipid-laden macrophage involvement was observed between pediatric (12%) and adult (51%) samples (p < 0.00001). Using MAGE and VFSS as gold standards, the test showed poor discriminatory power for detecting aspiration in infants (AUC 0.506-0.587). A 10% cutoff yielded the best performance (AUC 0.587, sensitivity 27%, specificity 93%), while a 50% cutoff offered practical advantages in workflow and reproducibility.
Conclusions: The modified LLMI demonstrates limited diagnostic value for aspiration in infants. While a 10% cutoff offers slightly improved performance, the test may be phased out in favor of more reliable diagnostic methods
Practice Patterns Vary Among Orthopedic, Plastic, and General Surgeons Resecting Soft Tissue Tumors of the Extremities and Pelvis
Full text linkBackground: Resection of extremity soft tissue tumors is common and frequently performed by orthopedic, plastic, and general surgeons. It is unknown if tumor location, Preoperative workup, and Postoperative care varies by specialty, which is the aim of this study.
Methods: A retrospective review was performed of 4,223 soft tissue tumors resected from the extremities and pelvis within a large single-state health system between 2009 and 2019. A more detailed cross-sectional review was performed on 450 tumors resected in 2016. Demographic and tumor characteristics, surgeon specialty (orthopedic, plastic, general), Preoperative workup (imaging, biopsy), and Postoperative management were collected and analyzed.
Results: General surgeons were more likely to resect tumors superficial to fascia (82.1%), compared to plastic and orthopedic surgeons (53.7% and 27.9%). Orthopedic surgeons were more likely to resect malignant tumors (28.2%) than plastic and general surgeons (14.0% and 4.5%). 16.3% of tumors resected by general surgeons had either Preoperative MRI or tissue diagnosis, compared to 42.6% for plastic surgeons and 90.5% for orthopedic surgeons (p < 0.001). Of the tumors resected by general surgeons without Preoperative MRI or tissue diagnosis, 2.6% were malignant. Finally, Postoperative documentation of neurovascular status, range of motion, and referral to physical therapy were more likely performed by orthopedic surgeons (all p < 0.001).
Conclusion: Practice patterns vary significantly among orthopedic, plastic, and general surgeons treating soft tissue tumors of the extremities and pelvis. These findings highlight the need for multidisciplinary engagement and standardization of treatment algorithms and training practices across the various surgical specialties
Current landscape and clinical progress of targeted alpha radioimmunotherapy
No full textTheranostics is an interesting area of cancer research that describes the use of radiotracers to first diagnose and then treat
cancer. By coupling a radioisotope to an agent that selectively targets malignant cells, one can distribute focused radiation to disease
sites. There are a variety of different radiopharmaceutical vectors that have been utilized in this way, such as peptides, small molecules
and antibodies. Because antibodies bind to highly specific antigens, radioimmunotherapy (RIT) offers a promising route to precisely
targeted treatments with reduced systemic toxicity compared to conventional radiotherapy. Beta (β)-emitting isotopes (e.g., 131I, 90Y)
have been more commonly coupled in RIT, but the use of alpha (α)-emitters (e.g., 225Ac, 212Pb), for RIT (α-RIT) has rising popularity due to
their shorter tissue range and higher linear energy transfer. These characteristics decrease off-target effects in neighboring tissues and
increase tumor cell destruction, respectively. However, there are several challenges to RIT. The production of daughter isotopes from α
decay makes dosimetric assessments difficult and could potentially cause off target toxicities. Additionally, whole antibodies tend to ac-
cumulate in liver tissue and have long biological clearance times, which may cause excess radiation to the blood, marrow and liver. Yet,
there are a variety of α-RIT agents currently in development to treat prostate cancer, hematologic malignancies, and other solid tumors.
Many agents show promise, like 227Th-epratuzumab, a CD22-targeting antibody used in the treatment of relapsed or refractory acute
myeloid leukemia (R/R AML). While notoriously deadly and difficult to treat, the disease control rate in patients with R/R AML taking 227Th-
epratuzumab was 38%. Like many α-RIT therapies, follow-up studies are needed to continue to improve efficacy. Strategies to widen the
therapeutic indices of these agents have been investigated such as pretargeting, use of antibody fragments, chelator optimization and
combination therapies. This review describes the current landscape and clinical progress of targeted α radioimmunotherapy.Indiana Clinical and Translational Sciences Institute, UL1TR002529 from the National Institutes of Healt
MicroRNA profiling of testicular Leydig cell tumors identifies a microRNA signature associated with malignancy and miR-196b-5p as a potentially useful biomarker
No full textApproximately 10% of testicular Leydig cell tumors (LCTs) are clinically malignant and unresponsive to systemic treatment. Predicting their clinical behavior can be problematic because there are no biomarkers that can consistently discriminate between benign and malignant LCTs. We assessed microRNA expression profiles of LCTs to identify differentially expressed microRNAs that could potentially distinguish benign from malignant neoplasms. The study consisted of two phases. In the first (discovery) phase, we interrogated 768 microRNAs in a series of 11 LCTs (six malignant and five benign) using Taqman Low-Density Array (TLDA) microRNA profiling. In the second phase, we validated the top differentially expressed microRNA targets with real-time quantitative PCR on a series of 35 LCTs (17 malignant and 18 benign), assessing their clinical performance for distinguishing malignant from benign LCTs. Target biologic pathways were analyzed using the miRTargetLink 2.0 tool. A total of 50 microRNAs were differentially regulated in malignant LCTs (27 upregulated, 23 downregulated). The top six microRNA candidates (top three upregulated and top three downregulated) were validated, showing good performance for discriminating between malignant and benign LCTs, with an area under the curve (AUC) ranging between 0.69 and 0.87. MiR-196b-5p showed the best performance, with sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of 82%, 83%, 83%, 82%, and 83%, respectively. A panel (i.e. combined) analysis reached 100% sensitivity and 83% specificity. Pathway analysis revealed significant overlap in the biological process targeted by the upregulated microRNAs in malignant LCTs, including proliferation, development, metabolism, hormone synthesis, and cell death. Our results support the idea that malignant LCTs are associated with a distinct microRNA signature. MiR-196b-5p was identified as a potentially useful biomarker to distinguish benign from malignant tumors. The shared downstream targets of the top upregulated microRNAs suggest that dysregulation of cell proliferation and apoptosis underlie aggressive biologic behavior in LCTs and may offer opportunities for targeted therapies
A Systematic Review of Secondary Traumatic Stress in School Personnel: A Synthesis of Quantitative Findings
No full textBackground: Secondary traumatic stress (STS) in school personnel is under-researched, with limited data on its frequency and susceptibility. This systematic review examines the extent of STS and the factors contributing to it among school personnel, defined as individuals employed or contracted by US school systems.
Methods: The review includes only studies that utilized the Professional Quality of Life Scale (ProQOL) and/or the STS Scale (STSS). A comprehensive search identified 18 peer-reviewed publications (2012-2021).
Findings: Thirteen authors used the ProQOL, while six used the STSS, with half of the latter reporting moderate or higher STS levels. Studies using ProQOL scoring methods found average STS levels. Limitations include a lack of sample diversity, as most participants were white (32.4%-97.2%), female (70.9%-93.2%), and teachers (12/18 studies). Many variables had inconsistent findings across studies. Other variables such as leadership practices and school safety showed significant associations with STS.
Implications: These data can be used to better understand factors associated with STS and to inform the development of effective preventative and reactive strategies to reduce the impact of STS on school personnel.
Conclusion: Continued research needs to occur assessing STS in school personnel to better inform best practices for prevention and reactive strategies
Understanding Actin Dynamics and Its Regulatory Mechanisms in Developing Stereocilia
No full textIUIStereocilia, the actin-based protrusions of auditory hair cells, are essential for converting mechanical stimuli into electrical signals. Their formation and maintenance require tightly regulated actin dynamics, including elongation and widening through filamentous actin (F-actin) incorporation. Here, we show that newly expressed actin first incorporates at stereocilia tips and then extends along the shaft to promote widening, with additional filaments assembling at the periphery of a stable actin core. Notably, we detected signals of both barbed and pointed ends present at stereocilia tips, revealing a previously unrecognized population of short actin filaments that contribute to stereocilia growth. Overexpression of actin further enriched short filaments along the shaft, linking their abundance to widening. Short filament levels correlated with the presence of the unconventional myosins MYO3A/B and MYO15A at stereocilia tips, implicating these motors in generating or stabilizing filaments required for elongation and widening. Focusing on class III myosins, we demonstrate that MYO3A is the predominant paralog in cochlear inner hair cells, indispensable for determining bundle dimensions and preventing overgrowth. Although MYO3B accumulates at tips in the absence of MYO3A, it provides only partial compensation, failing to maintain short filament populations or transport cargo such as ESPN-L1 to stereocilia tips. Strikingly, simultaneous deletion of MYO3A and ESPN1 eliminated MYO3B from stereocilia tips and sharply reduced tip width, suggesting that MYO3 complexes regulate actin incorporation specifically at the upper shaft. Moreover, kinase-deficient MYO3 mutants produced excessively long stereocilia and disrupted the distribution of MYO7A and EPS8L2, uncovering an unexpected role for the kinase domain in controlling tip-localized actin dynamics. Together, these findings establish a mechanism by which stereocilia widen and uncover MYO3A as a central regulator of tip widening in cochlear hair cells, providing mechanistic insights into how its dysfunction leads to DFNB30-associated hearing loss
A randomized, double blind, placebo-controlled pilot study to assess the efficacy of erenumab in individuals with temporomandibular disorder
Full text linkBackground: Erenumab has proven efficacious in treating migraine headache. Temporomandibular disorder (TMD) is a painful disorder which has high co-occurrence rates with migraine. We hypothesized that erenumab-aooe may also be beneficial in reducing pain in TMD-related myalgia.
Methods: This phase II randomized placebo-controlled clinical trial evaluated the safety and efficacy of the off-label use of erenumab in reducing TMD-related pain. The TMD diagnosis was established using the Diagnostic Criteria for Temporomandibular Disorders. The primary outcome was pain interference as assessed by the 0-to-10-point Brief Pain Inventory (BPI). Secondary outcomes were depression, anxiety and somatic symptoms; jaw function; and percent of days taking pain medication. Subjects were randomized at baseline to receive either erenumab 140 mg or placebo administered subcutaneously every 4 weeks for a total of five treatments. Outcome assessments were conducted at baseline, 4, 8, 12, 16, 20 and 24 weeks.
Results: Thirty subjects were enrolled with 15 randomized to each treatment group. Baseline pain was mild (BPI interference of 2.19; BPI severity of 2.95). There were no significant treatment effects at any time points with the between-group BPI interference at 24 weeks being -0.19 (95% confidence interval -1.94 to 1.56; p = 0.82). The outcomes were similar between erenumab and placebo for all outcomes except the Patient Health Questionnaire 4-item scale (PHQ-4) which showed that depression/anxiety symptoms were modestly worse (p = 0.03) in the erenumab group. Five participants withdrew during the trial (4 in erenumab arm, 1 in placebo arm).
Conclusions: Erenumab was not efficacious in reducing TMD myalgic pain in this phase II trial of 30 subjects with relatively mild pain
State of Indiana's Health Workforce 2025 Report
Full text linkThis report, prepared by the Indiana Professional Licensing Agency in collaboration with the Bowen Center for Health Workforce Research and Policy, provides an overview of Indiana’s health workforce as of 2025. It compiles licensure data and supplemental information collected during the 2023–2024 biennial license renewal process, as mandated by IC 25-1-2-10