Skin in the game: a review of single-cell and spatial transcriptomics in dermatological research.

Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) are two emerging research technologies that uniquely characterize gene expression microenvironments on a cellular or subcellular level. The skin, a clinically accessible tissue composed of diverse, essential cell populations, serves as an ideal target for these high-resolution investigative approaches. Using these tools, researchers are assembling a compendium of data and discoveries in healthy skin as well as a range of dermatologic pathophysiologies, including atopic dermatitis, psoriasis, and cutaneous malignancies. The ongoing advancement of single-cell approaches, coupled with anticipated decreases in cost with increased adoption, will reshape dermatologic research, profoundly influencing disease characterization, prognosis, and ultimately clinical practice.

Benefit-risk assessment for the Novavax COVID-19 vaccine (NVX-CoV2373).

A benefit-risk assessment of NVX-CoV2373, a vaccine to prevent COVID-19, was conducted to determine if the benefits of vaccination outweigh the risks of myocarditis/pericarditis. This analysis used data on myocarditis/pericarditis cases observed in the NVX-CoV2373 clinical studies, real-world data of mRNA COVID vaccine effectiveness against predominant SARS-CoV-2 strains in early 2023, and recent COVID-19 burden of disease data from the United States. The benefits of NVX-CoV2373 vaccination were estimated as the number of COVID-19 cases, hospitalizations, and deaths prevented. The risks of myocarditis/pericarditis cases and related hospitalizations and deaths occurring within 7 days of vaccination were also estimated. In our analysis, vaccination with NVX-CoV2373, per 100,000 vaccinated, resulted in an estimated 1805 COVID-19 cases prevented compared with an estimated 5.3 excess myocarditis/pericarditis cases. The number of COVID-19 hospitalizations and deaths prevented were also greater than vaccine-associated myocarditis/pericarditis hospitalizations and deaths. Our analysis indicates a positive benefit-risk balance for NVX-CoV2373.

Optic atrophy 1 mediates muscle differentiation by promoting a metabolic switch via the supercomplex assembly factor SCAF1.

Myogenic differentiation is integral for the regeneration of skeletal muscle following tissue damage. Though high-energy post-mitotic muscle relies predominantly on mitochondrial respiration, the importance of mitochondrial remodeling in enabling muscle differentiation and the players involved are not fully known. Here we show that the mitochondrial fusion protein OPA1 is essential for muscle differentiation. Our study demonstrates that OPA1 loss or inhibition, through genetic and pharmacological means, abolishes in vivo muscle regeneration and in vitro myotube formation. We show that both the inhibition and genetic deletion of OPA1 prevent the early onset metabolic switch required to drive myoblast differentiation. In addition, we observe an OPA1-dependent upregulation of the supercomplex assembly factor, SCAF1, at the onset of differentiation. Importantly, preventing the upregulation of SCAF1, through OPA1 loss or siRNA-mediated SCAF1 knockdown, impairs metabolic reprogramming and muscle differentiation. These findings reveal the integral role of OPA1 and mitochondrial reprogramming at the onset of myogenic differentiation.

The Brighton collaboration standardized module for vaccine benefit-risk assessment.

Vaccine Benefit-Risk (B-R) assessment consists of evaluating the benefits and risks of a vaccine and making a judgment whether the expected key benefits outweigh the potential key risks associated with its expected use. B-R supports regulatory and public health decision-making throughout the vaccine's lifecycle. In August 2021, the Brighton Collaboration's Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Benefit-Risk Assessment Module working group was established to develop a standard module to support the planning, conduct and evaluation of structured B-R assessments for vaccines from different platforms, based on data from clinical trials, post-marketing studies and real-world evidence. It enables sharing of relevant information via value trees, effects tables and graphical depictions of B-R trade-offs. It is intended to support vaccine developers, funders, regulators and policy makers in high-, middle- or low-income countries to help inform decision-making and facilitate transparent communication concerning development, licensure, deployment and other lifecycle decisions.

Evaluating mitochondrial length, volume, and cristae ultrastructure in rare mouse adult stem cell populations.

Since changes in mitochondrial morphology regulate key functions of stem cells, it is important to assess their structure under physiological and pathophysiological conditions. Here, we present techniques optimized in rare adult muscle stem cells (MuSCs). For evaluating mitochondrial length and volume within a compact cytoplasmic area in MuSCs on intact myofibers, we describe steps for mitochondrial staining, imaging, and quantification. For evaluating mitochondrial ultrastructure in small cell numbers, we describe steps for agarose embedding and quantification by TEM. For complete details on generation and use of this protocol, please refer to Baker et al. (2022).1.

Implementation of a Standardized Premedication Bundle to Improve Procedure Success for Nonemergent Neonatal Intubations.

The American Academy of Pediatrics recommends premedication for all nonemergent neonatal intubations, yet there remains significant variation in this practice nationally. We aimed to standardize our unit's premedication practices for improved intubation success and reduced adverse events. Methods: The study workgroup developed educational material and protocol content. Process measures included premedication use, education, and audit form completion. Primary (success on first intubation attempt and adverse event rates) and secondary (trainee success) study outcomes are displayed using statistical process control charts and pre-post cohort comparisons. Results: Forty-seven percent (97/206) of nurses completed educational intervention before protocol release, with an additional 20% (42/206) following a staff reminder. Two hundred sixteen (216) patients were intubated per protocol with 81% (174/216) audit completion. Compared with baseline (n = 158), intubation attempts decreased from 2 (IQR, 1-2) to 1 (IQR, 1-2) (P = 0.03), and success on the first attempt increased from 40% (63/158) to 57% (124/216) (P < 0.01), with a notable improvement in trainee success from less than 1% (1/40) to 43% (31/72) (P < 0.01). The rate of severe and rare adverse events remained stable; however, there was a rise in nonsevere events from 30% (48/158) to 45% (98/216). The tachycardia rate increased with atropine use. There was no change in chest wall rigidity, number of infants unable to extubate following surfactant, or decompensation awaiting medications. Conclusions: Standardizing procedural care delivery reduced intubation attempts and increased the attempt success rate. However, this was accompanied by an increase in the rate of nonsevere adverse events.

On diabetic foot ulcer knowledge gaps, innovation, evaluation, prediction markers, and clinical needs.

Diabetic foot ulcers (DFUs) remain a very prevalent and challenging complication of diabetes worldwide due to high morbidity, high risks of lower extremity amputation and associated mortality. Despite major advances in diabetes treatment in general, there is a paucity of FDA approved technologies and therapies to promote successful healing. Furthermore, accurate biomarkers to identify patients at risk of non-healing and monitor response-to-therapy are significantly lacking. To date, research has been slowed by a lack of coordinated efforts among basic scientists and clinical researchers and confounded by non-standardized heterogenous collection of biospecimen and patient associated data. Novel technologies, especially those in the single and 'multiomics' arena, are being used to advance the study of diabetic foot ulcers but require pragmatic study design to ensure broad adoption following validation. These high throughput analyses offer promise to investigate potential biomarkers across wound trajectories and may support information on wound healing and pathophysiology not previously well understood. Additionally, these biomarkers may be used at the point-of-care. In combination with national scalable research efforts, which seek to address the limitations and better inform clinical practice, coordinated and integrative insights may lead to improved limb salvage rates.

Thromboembolism after treatment with 4-factor prothrombin complex concentrate or plasma for warfarin-related bleeding.

Limited data exist in large, representative populations about whether the risk of thromboembolic events varies after receiving four-factor human prothrombin complex concentrate (4F-PCC) versus treatment with human plasma for urgent reversal of oral vitamin K antagonist therapy. We conducted a multicenter observational study to compare the 45-day risk of thromboembolic events in adults with warfarin-associated major bleeding after treatment with 4F-PCC (Kcentra®) or plasma. Hospitalized patients in two large integrated healthcare delivery systems who received 4F-PCC or plasma for reversal of warfarin due to major bleeding from January 1, 2008 to March 31, 2020 were identified and were matched 1:1 on potential confounders and a high-dimensional propensity score. Arterial and venous thromboembolic events were identified up to 45 days after receiving 4F-PCC or plasma from electronic health records and adjudicated by physician review. Among 1119 patients receiving 4F-PCC and a matched historical cohort of 1119 patients receiving plasma without a recent history of thromboembolism, mean (SD) age was 76.7 (10.5) years, 45.6% were women, and 9.4% Black, 14.6% Asian/Pacific Islander, and 15.7% Hispanic. The 45-day risk of thromboembolic events was 3.4% in those receiving 4F-PCC and 4.1% in those receiving plasma (P = 0.26; adjusted hazard ratio 0.76; 95% confidence interval 0.49-1.16). The adjusted risk of all-cause death at 45 days post-treatment was lower in those receiving 4F-PCC compared with plasma. Among a large, ethnically diverse cohort of adults treated for reversal of warfarin-associated bleeding, receipt of 4F-PCC was not associated with an excess risk of thromboembolic events at 45 days compared with plasma therapy.

The mitochondrial protein OPA1 regulates the quiescent state of adult muscle stem cells.

Quiescence regulation is essential for adult stem cell maintenance and sustained regeneration. Our studies uncovered that physiological changes in mitochondrial shape regulate the quiescent state of adult muscle stem cells (MuSCs). We show that MuSC mitochondria rapidly fragment upon an activation stimulus, via systemic HGF/mTOR, to drive the exit from deep quiescence. Deletion of the mitochondrial fusion protein OPA1 and mitochondrial fragmentation transitions MuSCs into G-alert quiescence, causing premature activation and depletion upon a stimulus. OPA1 loss activates a glutathione (GSH)-redox signaling pathway promoting cell-cycle progression, myogenic gene expression, and commitment. MuSCs with chronic OPA1 loss, leading to mitochondrial dysfunction, continue to reside in G-alert but acquire severe cell-cycle defects. Additionally, we provide evidence that OPA1 decline and impaired mitochondrial dynamics contribute to age-related MuSC dysfunction. These findings reveal a fundamental role for OPA1 and mitochondrial dynamics in establishing the quiescent state and activation potential of adult stem cells.

Results of the 2019 Survey of Engineered Nanomaterial Occupational Health and Safety Practices.

In collaboration with RTI International, the U.S. National Institute for Occupational Safety and Health (NIOSH) administered a survey to North American companies working with nanomaterials to assess health and safety practices. The results would contribute to understanding the impact of the efforts made by the NIOSH Nanotechnology Research Center (NTRC) in communicating occupational health and safety (OHS) considerations for workers when handling these materials. The survey, developed by RAND Corporation, was conducted online from September 2019-December 2019. Forty-five companies or organizations in the U.S. and Canada that fabricate, manufacture, handle, dispose, or otherwise use nanomaterials completed the survey. The survey was designed to answer research questions regarding the nanomaterials in use, which resources the companies have consulted for OHS guidance, and the overall OHS culture at the companies. Other questions specifically addressed whether the companies interacted with NIOSH or NIOSH resources to inform OHS policies and practices. Among participating companies, 57.8% had a maximum of 50 employees. Gold nanoparticles and polymers were most common (n = 20; 45.5% each), followed by graphene (36.4%), carbon nanotubes and nanofibers (34.1%), and zinc oxide nanoparticles (31.8%). Environmental monitoring was performed by 31.8% of the companies. While 88.9% of the companies had laminar flow cabinets, only 67.5% required it to be used with ENMs. Information and training programs were indicated by 90% of the sample, and only 29.6% performed specific health surveillance for ENM workers. Personal protective equipment primarily included gloves (100%) and eye/face protection (97.7%). More than a third (37.8%) of the respondents reported using at least one NIOSH resource to acquire information about safe handling of ENMs. The small number of companies that responded to and completed the survey is a considerable limitation to this study. However, the survey data are valuable for gauging the reach and influence of the NIOSH NTRC on nano OHS and for informing future outreach, particularly to small businesses.

Psychiatric Consequences of Skin Conditions: Multiple Case Study Analysis with Literature Review.

This review of current literature demonstrates the psychological implications of skin conditions. Skin conditions of varying severity can impact the quality of patients' lives and have psychiatric consequences. This impact provides a need for healthcare providers to consider the psychological implications of one's skin conditions and their effect on quality of life. The psychological challenges that arise from varying skin conditions show the potential need for both dermatological and psychiatric interventions. The following literature review details the psychiatric consequences of skin conditions under various conditions. It first looks at literature highlighting the psychiatric consequences experienced through various age ranges, from adults to adolescents and children. The paper then explores multiple skin conditions and their psychological effect before highlighting some of the interactions that stress has on the skin that could further exacerbate one's condition. Finally, it examines how patients characterize their experience with their skin condition and goes into some clinical case studies of patients with psychological implications as a result of their skin disorder. The paper also highlights the magnitude of dermatologic patients experiencing psychological conditions in conjunction with their skin conditions.

Evaluation of enhanced darkfield microscopy and hyperspectral imaging for rapid screening of TiO2 and SiO2 nanoscale particles captured on filter media.

Here we report on initial efforts to evaluate enhanced darkfield microscopy (EDFM) and light scattering Vis-NIR hyperspectral imaging (HSI) as a rapid screening tool for the offline analysis of mixed cellulose ester (MCE) filter media used to collect airborne nanoparticulate from work environments. For this study, the materials of interest were nanoscale titanium dioxide (TiO2 ) and silicon dioxide (SiO2 ; silica), chosen for their frequent use in consumer products. TiO2 and SiO2 nanoscale particles (NPs) were collected on MCE filter media and were imaged and analyzed via EDFM-HSI. When visualized by EDFM, TiO2 and SiO2 NPs were readily apparent as bright spherical structures against a dark background. Moreover, TiO2 and SiO2 NPs were identified in hyperspectral images. EDFM-HSI images and data were compared to scanning transmission electron microscopy (STEM), a NIST-traceable technique for particle size analysis, and the current gold standard for offline analysis of filter media. As expected, STEM provided more accurate sizing and morphology data when compared to EDFM-HSI, but is not ideal for rapid screening of the presence of NPs of interest since it is a costly, low-throughput technique. In this study, we demonstrate the utility of EDFM-HSI in rapidly visualizing and identifying TiO2 and SiO2 NPs on MCE filters. This screening method may prove useful in expediting time-to-knowledge compared to electron microscopy. Future work will expand this evaluation to other industrially relevant NPs, other filter media types, and real-world filter samples from occupational exposure assessments.

Evaluation of classification methods for identifying multiwalled carbon nanotubes collected on mixed cellulose ester filter media.

Enhanced darkfield microscopy (EDFM) and hyperspectral imaging (HSI) are being evaluated as a potential rapid screening modality to reduce the time-to-knowledge for direct visualisation and analysis of filter media used to sample nanoparticulate from work environments, as compared to the current analytical gold standard of transmission electron microscopy (TEM). Here, we compare accuracy, specificity, and sensitivity of several hyperspectral classification models and data preprocessing techniques to determine how to most effectively identify multiwalled carbon nanotubes (MWCNTs) in hyperspectral images. Several classification schemes were identified that are capable of classifying pixels as MWCNT(+) or MWCNT(-) in hyperspectral images with specificity and sensitivity over 99% on the test dataset. Functional principal component analysis (FPCA) was identified as an appropriate data preprocessing technique, testing optimally when coupled with a quadratic discriminant analysis (QDA) model with forward stepwise variable selection and with a support vector machines (SVM) model. The success of these methods suggests that EDFM-HSI may be reliably employed to assess filter media exposed to MWCNTs. Future work will evaluate the ability of EDFM-HSI to quantify MWCNTs collected on filter media using this classification algorithm framework using the best-performing model identified here - quadratic discriminant analysis with forward stepwise selection on functional principal component data - on an expanded sample set.

Exposures during wet production and use processes of nanomaterials: a summary of 11 worksite evaluations.

From 2011-2015, the National Institute for Occupational Safety and Health Nanotechnology Field Studies Team conducted 11 evaluations at worksites that either produced engineered nanomaterials (ENMs) via a wet process or used ENMs in a wetted, suspended, or slurry form. Wet handling or processing of ENMs reduces potential exposure compared to dry handling or processing; however, air sampling data indicated exposures may still occur. Information was gathered about each company, production processes, ENMs of interest, and control measures. Exposure assessments included air sampling using filter media, surface wipe sampling, and real-time particle counting by direct-reading instruments. Electron microscopy analysis of air filters confirmed the presence of ENMs of interest (10 of 11 sites). When a method was available, chemical analysis of filters was also used to detect the presence of ENMs (nine of 11 sites). Wipe samples were collected at four of the 11 sites, and, in each case, confirmed the presence of ENMs on surfaces. Direct-reading data showed potential nanomaterial emissions (nine of 11 sites). Engineering controls included fume hoods, cleanrooms, and enclosed processes. Personal protective equipment was required during all 11 evaluations. Recommendations to address potential exposures were provided to each company following the hierarchy of controls.

Atypical KRASG12R Mutant Is Impaired in PI3K Signaling and Macropinocytosis in Pancreatic Cancer.

Allele-specific signaling by different KRAS alleles remains poorly understood. The KRAS G12R mutation displays uneven prevalence among cancers that harbor the highest occurrence of KRAS mutations: It is rare (∼1%) in lung and colorectal cancers, yet relatively common (∼20%) in pancreatic ductal adenocarcinoma (PDAC), suggesting context-specific properties. We evaluated whether KRASG12R is functionally distinct from the more common KRASG12D- or KRASG12V-mutant proteins (KRASG12D/V). We found that KRASG12D/V but not KRASG12R drives macropinocytosis and that MYC is essential for macropinocytosis in KRASG12D/V- but not KRASG12R-mutant PDAC. Surprisingly, we found that KRASG12R is defective for interaction with a key effector, p110α PI3K (PI3Kα), due to structural perturbations in switch II. Instead, upregulated KRAS-independent PI3Kγ activity was able to support macropinocytosis in KRASG12R-mutant PDAC. Finally, we determined that KRASG12R-mutant PDAC displayed a distinct drug sensitivity profile compared with KRASG12D-mutant PDAC but is still responsive to the combined inhibition of ERK and autophagy. SIGNIFICANCE: We determined that KRASG12R is impaired in activating a key effector, p110α PI3K. As such, KRASG12R is impaired in driving macropinocytosis. However, overexpression of PI3Kγ in PDAC compensates for this deficiency, providing one basis for the prevalence of this otherwise rare KRAS mutant in pancreatic cancer but not other cancers.See related commentary by Falcomatà et al., p. 23.This article is highlighted in the In This Issue feature, p. 1.

Comparative risk of malignancies and infections in patients with rheumatoid arthritis initiating abatacept versus other biologics: a multi-database real-world study.

BACKGROUND: Patients with rheumatoid arthritis (RA) are at an increased risk of developing certain cancers and infections compared with the general population. Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are effective treatment options for RA, but limited evidence is available on the comparative risks among b/tsDMARDs. We assessed the risk of malignancies and infections in patients with RA who initiated abatacept versus other b/tsDMARDs in a real-world setting. METHODS: This retrospective, observational study used administrative data from three large US healthcare databases (MarketScan, PharMetrics, and Optum) to identify patients treated with abatacept or other b/tsDMARDs. In both groups, age-stratified incidence rates (IRs) with 95% confidence intervals (CIs) were calculated for total malignancy and hospitalized infections; propensity score matching and Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% CIs for total malignancy, lung cancer, lymphoma, breast cancer, non-melanoma skin cancer (NMSC), hospitalized infections, opportunistic infections, and tuberculosis (TB), both within individual databases and in meta-analyses across the three databases. RESULTS: A rounded total of 19.2, 13.6, and 4.2 thousand patients initiating abatacept and 55.3, 40.8, and 13.8 thousand initiating other b/tsDMARDs were identified in the MarketScan, PharMetrics, and Optum databases, respectively. The IRs for total malignancy and hospitalized infections were similar between the two groups in each age stratum. In meta-analyses, total malignancy risk (HR [95% CI] 1.09 [1.02-1.16]) of abatacept versus other b/tsDMARDs was slightly but statistically significantly increased; small, but not statistically significant, increases were seen for lung cancer (1.10 [0.62-1.96]), lymphoma (1.27 [0.94-1.72]), breast cancer (1.15 [0.92-1.45]), and NMSC (1.10 [0.93-1.30]). No significant increase in hospitalized infections (0.96 [0.84-1.09]) or opportunistic infections (1.06 [0.96-1.17]) was seen. For TB, low event counts precluded meta-analysis. CONCLUSIONS: In this real-world multi-database study, the risks for specific cancers and infections did not differ significantly between patients in the abatacept and other b/tsDMARDs groups. The slight increase in total malignancy risk associated with abatacept needs further investigation. These results are consistent with the established safety profile of abatacept.

Linking mitochondrial dynamics, cristae remodeling and supercomplex formation: How mitochondrial structure can regulate bioenergetics.

The dynamic and fluid nature of mitochondria allows for modifications in mitochondrial shape, connectivity and cristae architecture. The precise balance of mitochondrial dynamics is among the most critical features in the control of mitochondrial function. In the past few years, mitochondrial shape has emerged as a key regulatory factor in the determination of the bioenergetic capacity of cells. This is mostly due to the recent discoveries linking changes in cristae organization with supercomplex assembly of the electron transport chain (ETC), also defined as the formation of respirosomes. Here we will review the most current advances demonstrating the impact of mitochondrial dynamics and cristae shape on oxidative metabolism, respiratory efficiency, and redox state. Furthermore, we will discuss the implications of mitochondrial dynamics and supercomplex assembly under physiological and pathological conditions.

A Qualitative Study Exploring Female College Students' Instagram Use and Body Image.

Research demonstrates that mainstream media negatively impacts women's body image; less is known about social media, specifically Instagram. The purpose of the study was to explore how female college students use Instagram, and if using Instagram impacts body image. Since little is known, a descriptive qualitative approach was used. Six face-to-face focus groups with a total of 27 participants, aged 18-22 years, were conducted. The data were analyzed using a thematic analysis. Three themes related to Instagram use emerged: effortful posting, promotion of self, and seeking engagement. Participants put substantial effort into what they were posting, were careful to select the best images of themselves, and placed a lot of importance on receiving likes and comments. Three themes surfaced pertaining to body image: responding to beauty ideals, comparing self with others, and display of self. Participants recognized and strove to adhere to a variety of beauty standards; some discussed experiencing appearance dissatisfaction when trying to measure up to these ideals. Moreover, participants frequently compared their looks or the number of likes/comments with others. Additionally, when posting photos of self, participants took an audience perspective, expressing concern with how others perceived their appearance.

Sample preparation method for visualization of nanoparticulate captured on mixed cellulose ester filter media by enhanced darkfield microscopy and hyperspectral imaging.

A significant hurdle in conducting effective health and safety hazard analysis and risk assessment for the nanotechnology workforce is the lack of a rapid method for the direct visualization and analysis of filter media used to sample nanomaterials from work environments that represent potential worker exposure. Current best-known methods include transmission electron microscopy (TEM) coupled with energy dispersive x-ray spectroscopy (EDS) for elemental identification. TEM-EDS is considerably time-, cost-, and resource-intensive, which may prevent timely health and safety recommendations and corrective actions. A rapid screening method is currently being explored using enhanced darkfield microscopy with hyperspectral imaging (EDFM-HSI). For this approach to be effective, rapid, and easy, sample preparation that is amenable to the analytical technique is needed. Here, we compare the sample preparation steps for mixed cellulose ester (MCE) filter media specified in NIOSH Method 7400-Asbestos and Other Fibers by Phase Contrast Microscopy (PCM)-against a new method, which involves saturation of the filter media with acetone. NIOSH Method 7400 was chosen as a starting point since it is an established technique for preparing transparent MCE filters for optical microscopy. Limitations in this method led to the development and comparison of a new method. The new method was faster, easier, and rendered filters more transparent, resulting in improved visualization and analysis of nanomaterials via EDFM-HSI. This new method is suitable for a rapid screening protocol due to its speed, ease of use, and the improvement in image acquisition and analysis.

The female athlete triad: special considerations for adolescent female athletes.

The number of adolescent girls participating in sports has dramatically increased throughout the last few decades. In the early 1990's, an association between amenorrhea, osteoporosis, and disordered eating was recognized and eventually labeled the 'Female Athlete Triad'. In 1997, the Task Force on Women's Issues of American College of Sports Medicine (ACSM) published a position statement on this triad of conditions that were becoming increasingly more prevalent amongst female athletes. Initially, the 'Female Athlete Triad' was characterized by disordered eating, amenorrhea, and osteoporosis. However, as the number of adolescent female athletes has continued to grow, there has been further research and investigation into this field and the triad has evolved in definition. It is essential for all health care practitioners and other professionals who care for adolescent athletes to be attentive to the clinical signs, detection, evaluation, and management of the female athlete triad, as the sequelae can have a significant impact on the health and well-being of a young person both in the short and long-term.