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The Plasmodium falciparum chloroquine resistance transporter (PfCRT) is a key contributor to multidrug resistance and is also essential for the survival of the malaria parasite, yet its natural function remains unresolved. We identify host-derived peptides of 4-11 residues, varying in both charge and composition, as the substrates of PfCRT in vitro and in situ, and show that PfCRT does not mediate the non-specific transport of other metabolites and/or ions. We find that drug-resistance-conferring mutations reduce both the peptide transport capacity and substrate range of PfCRT, explaining the impaired fitness of drug-resistant parasites. Our results indicate that PfCRT transports peptides from the lumen of the parasite’s digestive vacuole to the cytosol, thereby providing a source of amino acids for parasite metabolism and preventing osmotic stress of this organelle. The resolution of PfCRT’s native substrates will aid the development of drugs that target PfCRT and/or restore the efficacy of existing antimalarials. Plasmodium falciparum chloroquine resistance transporter (PfCRT) mediates multidrug resistance, but its natural function remains unclear. Here, Shafik et al. show that PfCRT transports host-derived peptides of 4-11 residues but not other ions or metabolites, and that drug-resistance-conferring PfCRT mutants have reduced peptide transport.

Current diagnosis of chronic hypersensitivity pneumonitis (cHP) involves considering a combination of clinical, radiological, and pathological information in multidisciplinary team discussions. However, this approach is highly variable with poor agreement between centers. We aimed to identify diagnostic criteria for cHP that reach consensus among international experts. A 3-round modified Delphi survey was conducted between April and August 2017. Forty-five experts in interstitial lung disease from 14 countries participated in the online survey. Diagnostic items included in round 1 were generated using expert interviews and literature review. During rounds 1 and 2, experts rated the importance of each diagnostic item on a 5-point Likert scale. The a priori threshold of consensus was ≥ 75% of experts rating a diagnostic item as very important or important. In the third round, experts graded the items that met consensus as important and provided their level of diagnostic confidence for a series of clinical scenarios. Consensus was achieved on 18 of the 40 diagnostic items. Among these, experts gave the highest level of importance to the identification of a causative antigen, time relation between exposure and disease, mosaic attenuation on chest imaging, and poorly formed non-necrotizing granulomas on pathology. In clinical scenarios, the diagnostic confidence of experts in cHP was heightened by the presence of these diagnostic items. This consensus-based approach for the diagnosis of cHP represents a first step towards the development of international guidelines for the diagnosis of cHP.

This research explored the origins of risk-taking in art, focusing on three significant artists from the canon: Richard Diebenkorn, Jasper Johns, and Egon Schiele. It examined what distinguished these artists from the conventional methods of their time and how that earned them a seat in art history. Further, artistic periods were analyzed to determine whether the cultural climate and historical context or the trailblazer’s personality played a more significant role in shaping the artistic movement. The study focused on the artistic movements of: Cubism, De Stijl, and Abstract Expressionism (Color Field).The study posits that a combination of the zeitgeist, individual uniqueness, and narcissistic tendencies may have contributed to significant shifts in art history. To support this analysis, personal accounts from friends and loved ones of the artists were reviewed to identify narcissistic behaviors based on criteria from the Diagnostic and Statistical Manual of Mental Disorders. Importantly, the study did not seek to diagnose the artists but aimed to understand the origins of creative risk-taking and provide insights for contemporary artists.The studio component of the research involved experimental processes designed to replicate and document the experience of risk-taking. By blending artistic methods and mediums never before combined, this exploration sought to better understand the motivations and sensations associated with the risk-taking behaviors taken by trailblazers from the canon.

Purpose: To examine optimal threshold score on the General Risk Assessment for Pediatric Inpatient Falls (GRAF-PIF) scale for nurse assessment of fall risk on child and adolescent inpatient psychiatry units. Method: A retrospective observational study on two child and adolescent inpatient psychiatry units in a large health system was conducted from July 1, 2019, to August 31, 2023. We calculated falls per 1,000 patient days and examined different GRAF-PIF cut-offs for changes in positive predictive value (PPV), sensitivity, and specificity. Results: Fall rate was 1.10 per 1,000 patient days. The literature-recommended threshold of 2 yielded a sensitivity, specificity, and PPV of 87.5%, 60.3%, and 0.23%, respectively. The highest PPV (8.7%) occurred with a score of 4 but sensitivity was 46.9%. Conclusion: The optimum GRAF-PIF threshold considerably overestimated fall risk in this population, limiting clinical utility for nurses. Future research is needed to explore more accurate ways to assess fall risk for children and adolescents on inpatient psychiatry units.

BackgroundUltrasound-guided percutaneous needle tenotomy (USPNT) has been proposed as an alternative treatment to surgical intervention for lateral epicondylitis (LE). The Tenex system (Tenex Health Inc., Lake Forest, CA, USA) for USPNT is an ultrasonic device involving a needle which oscillates at high frequency to debride and aspirate diseased tendon under ultrasound image guidance. This investigation evaluates the efficacy of USPNT using the Tenex system for LE refractory to conservative management. We also seek to evaluate patient-specific factors which may correlate with treatment response.Materials and methodsPRTEE (Patient-Rated Tennis Elbow Evaluation) and DASH (Disabilities of the Arm, Shoulder, and Hand) questionnaires were completed before performing the Tenex USPNT for all consecutive patients over a course of 38 months (Feb 2015–Mar 2018). Patients were contacted for follow-up evaluations. Paired t test was used to evaluate significant changes in treatment response (p < 0.05). The univariate Tobit regression model was applied followed by multivariate Tobit model with forward selection algorithm. All models were adjusted by preoperative score and follow-up duration.ResultsA total of 37 patients (average age 51± 9 years, M/F:15/22) with refractory LE were included (mean follow-up, 531 days; range, 65–1148 days). Tenex USPNT significantly improved PRTEE and DASH scores (p < 0.001). In some patients, this decrease persisted for up to 3 years after intervention. A significant association between treatment response and post-procedure physical therapy (PT) was present. Post-procedure PT contributes to 60, 68, 59, and 50% of reduction in PRTEE pain, function, total scores, and DASH score, respectively (p < 0.001). No tendon ruptures, post-procedural infections, or other complications were noted.ConclusionUSPNT with Tenex significantly improves symptoms and function in individuals with LE even with long-term follow-up for 3 years. Post-procedure PT is associated with improved treatment response and should be considered after USPNT.

To examine optimal threshold score on the General Risk Assessment for Pediatric Inpatient Falls (GRAF-PIF) scale for nurse assessment of fall risk on child and adolescent inpatient psychiatry units. A retrospective observational study on two child and adolescent inpatient psychiatry units in a large health system was conducted from July 1, 2019, to August 31, 2023. We calculated falls per 1,000 patient days and examined different GRAF-PIF cut-offs for changes in positive predictive value (PPV), sensitivity, and specificity. Fall rate was 1.10 per 1,000 patient days. The literature-recommended threshold of 2 yielded a sensitivity, specificity, and PPV of 87.5%, 60.3%, and 0.23%, respectively. The highest PPV (8.7%) occurred with a score of 4 but sensitivity was 46.9%. The optimum GRAF-PIF threshold considerably overestimated fall risk in this population, limiting clinical utility for nurses. Future research is needed to explore more accurate ways to assess fall risk for children and adolescents on inpatient psychiatry units.

To examine optimal threshold score on the General Risk Assessment for Pediatric Inpatient Falls (GRAF-PIF) scale for nurse assessment of fall risk on child and adolescent inpatient psychiatry units. A retrospective observational study on two child and adolescent inpatient psychiatry units in a large health system was conducted from July 1, 2019, to August 31, 2023. We calculated falls per 1,000 patient days and examined different GRAF-PIF cut-offs for changes in positive predictive value (PPV), sensitivity, and specificity. Fall rate was 1.10 per 1,000 patient days. The literature-recommended threshold of 2 yielded a sensitivity, specificity, and PPV of 87.5%, 60.3%, and 0.23%, respectively. The highest PPV (8.7%) occurred with a score of 4 but sensitivity was 46.9%. The optimum GRAF-PIF threshold considerably overestimated fall risk in this population, limiting clinical utility for nurses. Future research is needed to explore more accurate ways to assess fall risk for children and adolescents on inpatient psychiatry units.

It remains unclear why female general surgery residents perform fewer cases than male peers. This exploratory study investigated possible contributors to gender-based disparities and solutions for improving equity in operative experience. Surveys, including Likert scale and free-text questions, were distributed to 21 accredited general surgery residency programs. There were 96 respondents, of whom 69% were female. 22% of females personally experienced barriers to operative experience versus 13% of males (p ​= ​0.41), while 52% of female residents believed operative training was affected by gender (p ​= ​0.004). Inductive analysis revealed the most common barrier to operating room participation was floor work/clinical tasks. The most common barrier for female residents was perceived sexism/gender bias, with subthemes of “misidentification,” “feeling unwelcome,” and “poor trust/autonomy.” To improve parity, residents proposed structured program-level review, feedback, and transparent expectations about case assignments. Female general surgery residents believe gender bias impacts training. Further mixed-methods research is crucial to determine the cause of gender-based disparities in operative experience. [Display omitted] •Prior studies reveal gender and sex-based differences in general surgery case logs and operative experience.•In this multicenter study, 53% of female general surgery residents felt that gender influences training quality.•Sexism and gender bias were the predominant perceived barriers to operating room participation for female residents.

Clinical determination of bone fracture healing remains qualitative, typically determined through the combination of plain film radiographs, clinical assessment, and patient-reported pain. Importantly, standard radiographs can only detect bone formation in the fracture site after sufficient tissue mineralization has occurred, restricting utility to the later stages of bone repair. A more rigorous method for determining fracture healing progression could significantly improve patient care. Quantitative biomarkers have gained diagnostic value in many clinical indications. Multiple bone turnover biomarkers have been successfully utilized for diagnosis and clinical management of osteoporosis. However, there remains limited evidence for the correlation and diagnostic efficacy of these biomarkers when applied to fracture repair. Here we present data from a large cohort of participants without (n = 111) or with (n = 153) fracture with the primary outcome of interest our blood-based biomarker which detects the degradation product of the trimeric collagen X protein (CXM). Collagen X is a transient extracellular matrix protein synthesized by hypertrophic chondrocytes during the soft callus phase of endochondral fracture repair. Our data show that healthy patients with an age range of 21-85 years without fracture (enrolled 2018-2020) have low circulating levels of CXM (median = 563.4 pg/mL; interquartile range (IQR) [483.2, 771.1]) that do not vary independently with age (r = 0.04, p = 0.26) or sex (p = 0.42). Fracture data includes patients with an acute closed or low grade open (Gustilo type I or II) tibial or femoral shaft fracture from a secondary analysis of the VitaShock study (NCT02786498, n = 102: enrolled through the University of Maryland 2016-2019), complemented by a new prospectively enrolled observational study that recruited from the Oregon Health & Science University level 1 academic trauma center (n = 51: enrolled 2019-2023) that were followed until the patient was deemed clinically healed or until they failed to return for follow-up. We show that in serum CXM positively correlates to the bone biomarkers N-terminal propeptide of type I procollagen (P1NP, r = 0.50, p < 0.0001), C-terminal telopeptide of type I collagen (CTX, r = 0.40, p < 0.0001), and osteocalcin (r = 0.26, p = 0.0411); with a negative correlation to the obesity biomarker leptin (r = -0.31, p = 0.0138). Further, patients with early healing exhibited a peak in CXM at 6 weeks of 1,092 pg/mL (95% confidence interval (CI) [804.8, 1,379]), which was significantly higher than patients with normal healing of 630.8 pg/mL (95% CI [399.9, 861.8]; p = 0.016). We then show that we can reliably transfer this assay from serum collection through venipuncture to a dried blood spot (DBS) collected by finger prick (r = 0.75, Serum = 0.4217*DBS + 181.9, p < 0.0001). Using DBS, the prospective clinical observational study finally suggests that median time-to-peak CXM is at 25.5 days following the elimination of outliers (n = 6) using Robust Regression and Outlier Removal (ROUT, Q = 1%). This study did not find significant differences in CXM expression according to age, sex, or bone that are likely due to the main limitation of an observational study. This rigorous data set supports the future prospective use of the CXM biomarker collected by finger prick in interventional fracture studies and/or in observational studies requiring quantitative assessments of long-bone healing.

Introduction Adolescent and youth‐friendly health services (AYFHS) have been promoted as a best practice for adolescents and young people living with HIV (AYLH). However, thorough descriptions of AYFHS for AYLH remain scarce. We sought to characterize adolescent‐friendly HIV services in a global paediatric research consortium. Methods Cross‐sectional data were collected from 16 global sites in the Adolescent and Young Adult Network of IeDEA (AYANI) of the International epidemiology Databases to Evaluate AIDS consortium between August 2020 and October 2022 using a standardized site assessment tool that collected data on clinic, patient and provider characteristics, differentiated care, and transition to adult services processes. Descriptive analyses characterized the health services available across the participating sites, using frequencies and proportions for categorical variables and medians and interquartile range for continuous variables. Data were analysed using RStudio. Results Overall, 13 of 16 sites (81%) reported having dedicated adolescent services, which most often consisted of dedicated clinic days (62%, n = 8/13), primarily offered on weekdays. Across all sites, nurses and counsellors delivered services to adolescents. Over half of all clinics (69%, n = 11/16) reported offering health education to adolescents to facilitate adolescent health literacy. Peer educators and navigators were involved in delivering services at 62% of sites, primarily in those with dedicated adolescent services (69%, n = 9/13). There was limited integration of sexual and reproductive health services into HIV clinics for adolescents. With 63% of clinics conducting pregnancy screening, 50% providing family planning methods and 38% providing cervical cancer screening. Under half of all HIV clinics screened for physical abuse or violence (44%, n = 7/16) and sexual abuse or rape (38%, n = 6/16). A low proportion of clinics screened for risk factors related to young key populations, including drug use (56%, n = 9/16), homelessness (38%, n = 6/16) young men having sex with men (31%, n = 5/16) and transactional sex (31%, n = 5/16). Mental health screening for concerns was variable. Conclusions Findings suggest gaps in AYFHS for AYLH across the HIV clinics included in this analysis. There is a vital need to design health services for AYLH that are accessible, equitable, and effective and meet the global standards for delivering high‐quality healthcare to adolescents.