Geographical Distribution and Trends Analysis of Osteopathic General Surgery Residents.

In recent years, the number of Doctor of Osteopathic Medicine (DO) residents entering general surgery has increased. As DOs continue to solidify their role within the surgical domain, understanding their distribution, preferences, and the dynamics of their integration into residency programs becomes crucial for general surgery applicants. Publicly available data were gathered for each DO general surgery resident from residency programs across the nation, including details such as post-graduate year, degrees held, and residency program location. A comprehensive cross-sectional analysis was conducted to determine the geographical distribution and match trends of DO residents in these residency programs. Analysis revealed a significant rise in the number of DOs entering general surgery residencies, from 153 DO trainees beginning their residency training in 2019 to 274 DO trainees beginning their residency training in 2024. This upward trend indicates a growing presence of DOs in surgical practice. Examination of the geographical locations of programs for which DO applicants have matched showed variations nationwide. This analysis allows for a deeper understanding of the evolving match trends for DOs in surgery. It highlights the importance of addressing disparities in access to surgical training opportunities for osteopathic physicians nationwide.

Clinicians' use of Health Information Exchange technologies for medication reconciliation in the U.S. Department of Veterans Affairs: a qualitative analysis.

BACKGROUND: Medication reconciliation is essential for optimizing medication use. In part to promote effective medication reconciliation, the Department of Veterans Affairs (VA) invested substantial resources in health information exchange (HIE) technologies. The objectives of this qualitative study were to characterize VA clinicians' use of HIE tools for medication reconciliation in their clinical practice and to identify facilitators and barriers. METHODS: We recruited inpatient and outpatient prescribers (physicians, nurse practitioners, physician assistants) and pharmacists at four geographically distinct VA medical centers for observations and interviews. Participants were observed as they interacted with HIE or medication reconciliation tools during routine work. Participants were interviewed about clinical decision-making pertaining to medication reconciliation and use of HIE tools, and about barriers and facilitators to use of the tools. Qualitative data were analyzed via inductive and deductive approaches using a priori codes. RESULTS: A total of 63 clinicians participated. Over half (58%) were female, and the mean duration of VA clinical experience was 7 (range 0-32) years. Underlying motivators for clinicians seeking data external to their VA medical center were having new patients, current patients receiving care from an external institution, and clinicians' concerns about possible medication discrepancies among institutions. Facilitators for using HIE software were clinicians' familiarity with the HIE software, clinicians' belief that medication information would be available within HIE, and their confidence in the ability to find HIE medication-related data of interest quickly. Six overarching barriers to HIE software use for medication coordination included visual clutter and information overload within the HIE display; challenges with HIE interface navigation; lack of integration between HIE and other electronic health record interfaces, necessitating multiple logins and application switching; concerns with the dependability of HIE medication information; unfamiliarity with HIE tools; and a lack of HIE data from non-VA facilities. CONCLUSIONS: This study is believed to be the first to qualitatively characterize clinicians' HIE use with respect to medication reconciliation. Results inform recommendations to optimize HIE use for medication management activities. We expect that healthcare organizations and software vendors will be able to apply the findings to develop more effective and usable HIE information displays.

Rapid and noninvasive estimation of human arsenic exposure based on 4-photo-set of the hand and foot photos through artificial intelligence.

Chronic exposure to arsenic is linked to the development of cancers in the skin, lungs, and bladder. Arsenic exposure manifests as variegated pigmentation and characteristic pitted keratosis on the hands and feet, which often precede the onset of internal cancers. Traditionally, human arsenic exposure is estimated through arsenic levels in biological tissues; however, these methods are invasive and time-consuming. This study aims to develop a noninvasive approach to predict arsenic exposure using artificial intelligence (AI) to analyze photographs of hands and feet. By incorporating well water consumption data and arsenic concentration levels, we developed an AI algorithm trained on 9988 hand and foot photographs from 2497 subjects. This algorithm correlates visual features of palmoplantar hyperkeratosis with arsenic exposure levels. Four pictures per patient, capturing both ventral and dorsal aspects of hands and feet, were analyzed. The AI model utilized existing arsenic exposure data, including arsenic concentration (AC) and cumulative arsenic exposure (CAE), to make binary predictions of high and low arsenic exposure. The AI model achieved an optimal area under the curve (AUC) values of 0.813 for AC and 0.779 for CAE. Recall and precision metrics were 0.729 and 0.705 for CAE, and 0.750 and 0.763 for AC, respectively. While biomarkers have traditionally been used to assess arsenic exposure, efficient noninvasive methods are lacking. To our knowledge, this is the first study to leverage deep learning for noninvasive arsenic exposure assessment. Despite challenges with binary classification due to imbalanced and sparse data, this approach demonstrates the potential for noninvasive estimation of arsenic concentration. Future studies should focus on increasing data volume and categorizing arsenic concentration statistics to enhance model accuracy. This rapid estimation method could significantly contribute to epidemiological studies and aid physicians in diagnosis.

New Processes for Ionizing Nonvolatile Compounds in Mass Spectrometry: The Road of Discovery to Current State-of-the-Art.

This Perspective covers discovery and mechanistic aspects as well as initial applications of novel ionization processes for use in mass spectrometry that guided us in a series of subsequent discoveries, instrument developments, and commercialization. Vacuum matrix-assisted ionization on an intermediate pressure matrix-assisted laser desorption/ionization source without the use of a laser, high voltages, or any other added energy was simply unbelievable, at first. Individually and as a whole, the various discoveries and inventions started to paint, inter alia, an exciting new picture and outlook in mass spectrometry from which key developments grew that were at the time unimaginable, and continue to surprise us in its simplistic preeminence. We, and others, have demonstrated exceptional analytical utility. Our current research is focused on how best to understand, improve, and use these novel ionization processes through dedicated platforms and source developments. These ionization processes convert volatile and nonvolatile compounds from solid or liquid matrixes into gas-phase ions for analysis by mass spectrometry using, e.g., mass-selected fragmentation and ion mobility spectrometry to provide accurate, and sometimes improved, mass and drift time resolution. The combination of research and discoveries demonstrated multiple advantages of the new ionization processes and established the basis of the successes that lead to the Biemann Medal and this Perspective. How the new ionization processes relate to traditional ionization is also presented, as well as how these technologies can be utilized in tandem through instrument modification and implementation to increase coverage of complex materials through complementary strengths.

Geographical Distribution of Osteopathic Neurosurgery Residents.

INTRODUCTION: The neurosurgery residency match has grown increasingly competitive, especially for osteopathic (DO) medical students, amidst the transition to a single accreditation system in 2020. This shift required former American Osteopathic Association (AOA) programs to apply for Accreditation Council for Graduate Medical Education (ACGME) accreditation, leading to a notable reduction in programs with a history of accepting DO applicants. This study aims to explore both potential geographical trends in residency match among recent DO neurosurgical residents and in the number of DO neurosurgical residents pre- and post-ACGME merger. METHODS: Neurosurgery residency programs during the 2023-2024 academic year were identified, and each program's residents, resident degrees, and resident post-graduate years were collected from residency programs' websites. Descriptive statistics were used to analyze the ratios of DO and allopathic (MD) residents, while regression analyses were used to determine the trends in DO residents between 2017 and 2024. DO residents were also collated by state to observe their geographical distribution. RESULTS: A comprehensive cross-sectional analysis of 115 neurosurgery residency programs across the United States from 2016 to 2024 reveals a significant decrease in DO residents, from 14 in 2016 to four in 2024, with an average of six DO residents per year post-merger. A geographical heatmap analysis pinpointed New Jersey, Michigan, and California as states with the highest proportions and numbers of DO neurosurgery residents. CONCLUSION: These findings show the geographical distribution of DO neurosurgery residents in the US. Recognizing and understanding these geographical trends could be essential in the strategic application planning for DO candidates and the need for residency programs to reassess selection criteria to be more inclusive of DO applicants.

Biochemical and structural insights into a 5' to 3' RNA ligase reveal a potential role in tRNA ligation.

ATP-grasp superfamily enzymes contain a hand-like ATP-binding fold and catalyze a variety of reactions using a similar catalytic mechanism. More than 30 protein families are categorized in this superfamily, and they are involved in a plethora of cellular processes and human diseases. Here, we identify C12orf29 (RLIG1) as an atypical ATP-grasp enzyme that ligates RNA. Human RLIG1 and its homologs autoadenylate on an active site Lys residue as part of a reaction intermediate that specifically ligates RNA halves containing a 5'-phosphate and a 3'-hydroxyl. RLIG1 binds tRNA in cells and can ligate tRNA within the anticodon loop in vitro. Transcriptomic analyses of Rlig1 knockout mice revealed significant alterations in global tRNA levels in the brains of female mice, but not in those of male mice. Furthermore, crystal structures of a RLIG1 homolog from Yasminevirus bound to nucleotides revealed a minimal and atypical RNA ligase fold with a conserved active site architecture that participates in catalysis. Collectively, our results identify RLIG1 as an RNA ligase and suggest its involvement in tRNA biology.

Syndrome Sinistre: Left Brachiocephalic Vein Compression and its Neurological Manifestations.

Embryologically, the left brachiocephalic vein (LBV) originates as an anastomotic channel between the right and left anterior cardinal veins. This positions the LBV between the manubrium sterni anteriorly and the innominate artery posteriorly. This pattern of adjacency of the aorta to the LBV is unique to mammals and results from a quirk of evolution. With age, the ascending aorta unfolds, elongates and dilates. Simultaneously, there is a change in the thoracic geometry that reduces the thoracic volume primarily from disc height loss and kyphosis. These transitions progressively compress the LBV. Normally, this compression is circumvented via collateral pathways and "Blood finds a way". However, traversing these circuitous pathways comes at a cost and can result in delayed transit times and venous congestion. While it is possible that compression of the LBV in the setting of adequate collateral channels may fail to provoke any pathologic sequelae, we propose a phenomenon in which such compression in the setting of inadequate collateral circulation may lead to a state of pathologic venous congestion. This anatomic anomaly and its associated clinical features, if identified, can offer a new avenue for treatment options for some of the hitherto unexplained neurologic disorders.

LightDPH: Lightweight Dual-Projection-Head Hierarchical Contrastive Learning for Skin Lesion Classification.

Effective skin cancer detection is crucial for early intervention and improved treatment outcomes. Previous studies have primarily focused on enhancing the performance of skin lesion classification models. However, there is a growing need to consider the practical requirements of real-world scenarios, such as portable applications that require lightweight models embedded in devices. Therefore, this study aims to propose a novel method that can address the major-type misclassification problem with a lightweight model. This study proposes an innovative Lightweight Dual Projection-Head Hierarchical contrastive learning (LightDPH) method. We introduce a dual projection-head mechanism to a contrastive learning framework. This mechanism is utilized to train a model with our proposed multi-level contrastive loss (MultiCon Loss), which can effectively learn hierarchical information from samples. Meanwhile, we present a distance-based weight (DBW) function to adjust losses based on hierarchical levels. This unique combination of MultiCon Loss and DBW function in LightDPH tackles the problem of major-type misclassification with lightweight models and enhances the model's sensitivity in skin lesion classification. The experimental results demonstrate that LightDPH significantly reduces the number of parameters by 52.6% and computational complexity by 29.9% in GFLOPs while maintaining high classification performance comparable to state-of-the-art methods. This study also presented a novel evaluation metric, model efficiency score (MES), to evaluate the cost-effectiveness of models with scaling and classification performance. The proposed LightDPH effectively mitigates major-type misclassification and works in a resource-efficient manner, making it highly suitable for clinical applications in resource-constrained environments. To the best of our knowledge, this is the first work that develops an effective lightweight hierarchical classification model for skin lesion detection.

Evaluating a Natural Language Processing-Driven, AI-Assisted International Classification of Diseases, 10th Revision, Clinical Modification, Coding System for Diagnosis Related Groups in a Real Hospital Environment: Algorithm Development and Validation Study.

BACKGROUND: International Classification of Diseases codes are widely used to describe diagnosis information, but manual coding relies heavily on human interpretation, which can be expensive, time consuming, and prone to errors. With the transition from the International Classification of Diseases, Ninth Revision, to the International Classification of Diseases, Tenth Revision (ICD-10), the coding process has become more complex, highlighting the need for automated approaches to enhance coding efficiency and accuracy. Inaccurate coding can result in substantial financial losses for hospitals, and a precise assessment of outcomes generated by a natural language processing (NLP)-driven autocoding system thus assumes a critical role in safeguarding the accuracy of the Taiwan diagnosis related groups (Tw-DRGs). OBJECTIVE: This study aims to evaluate the feasibility of applying an International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), autocoding system that can automatically determine diagnoses and codes based on free-text discharge summaries to facilitate the assessment of Tw-DRGs, specifically principal diagnosis and major diagnostic categories (MDCs). METHODS: By using the patient discharge summaries from Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUCHH) from April 2019 to December 2020 as a reference data set we developed artificial intelligence (AI)-assisted ICD-10-CM coding systems based on deep learning models. We constructed a web-based user interface for the AI-assisted coding system and deployed the system to the workflow of the certified coding specialists (CCSs) of KMUCHH. The data used for the assessment of Tw-DRGs were manually curated by a CCS with the principal diagnosis and MDC was determined from discharge summaries collected at KMUCHH from February 2023 to April 2023. RESULTS: Both the reference data set and real hospital data were used to assess performance in determining ICD-10-CM coding, principal diagnosis, and MDC for Tw-DRGs. Among all methods, the GPT-2 (OpenAI)-based model achieved the highest F1-score, 0.667 (F1-score 0.851 for the top 50 codes), on the KMUCHH test set and a slightly lower F1-score, 0.621, in real hospital data. Cohen κ evaluation for the agreement of MDC between the models and the CCS revealed that the overall average κ value for GPT-2 (κ=0.714) was approximately 12.2 percentage points higher than that of the hierarchy attention network (κ=0.592). GPT-2 demonstrated superior agreement with the CCS across 6 categories of MDC, with an average κ value of approximately 0.869 (SD 0.033), underscoring the effectiveness of the developed AI-assisted coding system in supporting the work of CCSs. CONCLUSIONS: An NLP-driven AI-assisted coding system can assist CCSs in ICD-10-CM coding by offering coding references via a user interface, demonstrating the potential to reduce the manual workload and expedite Tw-DRG assessment. Consistency in performance affirmed the effectiveness of the system in supporting CCSs in ICD-10-CM coding and the judgment of Tw-DRGs.

Parental Perspectives From the Survey of Sleep Quality in the PICU Validation Study on Environmental Factors Causing Sleep Disruption in Critically Ill Children.

OBJECTIVES: Sleep promotion bundles being tested in PICUs use elements adapted from adult bundles. As children may react differently than adults in ICU environments, this study investigated what parents report disrupted the sleep of their child in a PICU. DESIGN: Secondary analysis of a multicenter validation study of the Survey of Sleep quality in the PICU. SETTING: Four Northeastern U.S. PICUs, one hospital-based pediatric sleep laboratory. PATIENTS: Parents sleeping at the bedside of a child in the PICU or hospital-based sleep laboratory. INTERVENTIONS: Anonymous one-time survey eliciting parts of hospital or ICU environments that have been described as disruptive to sleep in validated adult ICU and pediatric inpatient questionnaires. MEASUREMENTS AND MAIN RESULTS: Level of sleep disruption was scored by Likert scale, with higher scores indicating more disruption. Age, demographics, baseline sleep, and PICU exposures were used to describe causes of sleep disruption in a PICU. Of 152 PICU parents, 71% of their children's sleep was disrupted significantly by at least one aspect of being in the PICU. The most prevalent were "being in pain or uncomfortable because they are sick" (38%), "not sleeping at home" (30%), "alarms on machines" (28%), and "not sleeping on their home schedule" (26%). Only 5% were disrupted by excessive nocturnal light exposure. Overall sleep disruption was not different across four PICUs or in those receiving sedation. The validation study control group, healthy children undergoing polysomnography, had less sleep disruption than those in a PICU despite sleeping in a hospital-based sleep laboratory. CONCLUSIONS: There are multiple aspects of critical care environments that affect the sleep of children, which are different from that of adults, such as disruption to home schedules. Future interventional sleep promotion bundles should include sedated children and could be applicable in multicenter settings.

Surgical Aortic Valve Replacement Using a Porcine Model: A Low-Cost Simulation for Surgical Trainees.

Simulation experiences are valuable to the training of future successful surgeons. These experiences introduce trainees to operational concepts through hands-on engagement within a low-stress environment to promote skill, information retention, and increased competency for future success in real-life scenarios. The study aimed to develop a low-cost, reproducible surgical simulation for teaching aortic valve replacement using porcine models. This study employed a single-center educational workshop design to provide trainees with a comprehensive wet laboratory experience in surgical aortic valve replacement using a porcine model. The simulation involved step-by-step procedures using porcine hearts in a wet lab environment, emphasizing specific surgical techniques such as suturing, knot tying, and valve replacement. Simulated valves were created using insulation foaming and aluminum wiring. The study was conducted at a southeastern medical school's wet lab. Thirty-eight preclinical medical students participated. The simulation was designed to provide a comprehensive overview of the steps involved in aortic valve replacement using porcine models. It emphasized the importance of teamwork, fundamental surgical skills, and effective communication within a surgical setting. The low-cost surgical simulation allowed trainees to learn technical skills that could be tailored to their proficiency level. Simulation for cardiothoracic procedures is limited by monetary spending and the availability of adequate materials to create a beneficial learning experience. This low-cost simulation allows resource-limited institutions to provide their students an additional opportunity to practice fundamental surgical principles such as suturing.

Organizational challenges for partial heart transplantation.

Partial heart transplantation (PHT) has emerged as a new treatment strategy to correct unrepairable heart valve dysfunction in pediatric patients. PHT selectively replaces the dysfunctional components of the recipient's heart and spares the native ventricles. As a result, the transplant biology of PHTs differs from heart transplants. Notably, donor hearts that are unsuitable for whole heart transplantation can be used, graft preservation can be prolonged and immunosuppression levels can be lowered. These nuances of PHT transplant biology have important implications for organizational aspects of PHT clinical application.

Partial heart transplantation (PHT) is a new way to treat children with heart defects that affect the heart valves. PHT does not replace the entire heart. Instead, PHT only replaces the part of the heart that does not function well. As a result, PHTs behave differently from heart transplants. PHT can use more donor hearts, the donor hearts can be preserved for longer, and the immune system does not need to be suppressed as much. These differences in the biology mean that the organization of PHT also differs from heart transplantation.

Characterizing Long COVID in Children and Adolescents.

Importance: Most research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment. Objective: To identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC. Design, Setting, and Participants: Multicenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: PASC and 89 prolonged symptoms across 9 symptom domains. Results: A total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents. Conclusions and Relevance: This study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.

Effects of the Amylose/Amylopectin Ratio of Starch on Borax-Crosslinked Hydrogels.

Herein, we simultaneously prepared borax-crosslinked starch-based hydrogels with enhanced mechanical properties and self-healing ability via a simple one-pot method. The focus of this work is to study the effects of the amylose/amylopectin ratio of starch on the grafting reactions and the performance of the resulting borax-crosslinked hydrogels. An increase in the amylose/ amylopectin ratio increased the gel fraction and grafting ratio but decreased the swelling ratio and pore diameter. Compared with hydrogels prepared from low-amylose starches, hydrogels prepared from high-amylose starches showed pronouncedly increased network strength, and the maximum storage modulus increased by 8.54 times because unbranched amylose offered more hydroxyl groups to form dynamic borate ester bonds with borate ions and intermolecular hydrogen bonds, leading to an enhanced crosslink density. In addition, all the hydrogels exhibited a uniformly interconnected network structure. Furthermore, owing to the dynamic borate ester bonds and hydrogen bonds, the hydrogel exhibited excellent recovery behavior under continuous step strain, and it also showed thermal responsiveness.

Mechanistic insights into a heterobifunctional degrader-induced PTPN2/N1 complex.

PTPN2 (protein tyrosine phosphatase non-receptor type 2, or TC-PTP) and PTPN1 are attractive immuno-oncology targets, with the deletion of Ptpn1 and Ptpn2 improving response to immunotherapy in disease models. Targeted protein degradation has emerged as a promising approach to drug challenging targets including phosphatases. We developed potent PTPN2/N1 dual heterobifunctional degraders (Cmpd-1 and Cmpd-2) which facilitate efficient complex assembly with E3 ubiquitin ligase CRL4CRBN, and mediate potent PTPN2/N1 degradation in cells and mice. To provide mechanistic insights into the cooperative complex formation introduced by degraders, we employed a combination of structural approaches. Our crystal structure reveals how PTPN2 is recognized by the tri-substituted thiophene moiety of the degrader. We further determined a high-resolution structure of DDB1-CRBN/Cmpd-1/PTPN2 using single-particle cryo-electron microscopy (cryo-EM). This structure reveals that the degrader induces proximity between CRBN and PTPN2, albeit the large conformational heterogeneity of this ternary complex. The molecular dynamic (MD)-simulations constructed based on the cryo-EM structure exhibited a large rigid body movement of PTPN2 and illustrated the dynamic interactions between PTPN2 and CRBN. Together, our study demonstrates the development of PTPN2/N1 heterobifunctional degraders with potential applications in cancer immunotherapy. Furthermore, the developed structural workflow could help to understand the dynamic nature of degrader-induced cooperative ternary complexes.

Polarization-sensitive optical coherence tomography and scleral collagen fiber orientation in osteogenesis imperfecta.

Osteogenesis imperfecta (OI), a rare genetic connective tissue disorder, primarily arises from pathogenic variants affecting the production or structure of collagen type I. In addition to skeletal fragility, individuals with OI may face an increased risk of developing ophthalmic diseases. This association is believed to stem from the widespread presence of collagen type I throughout various parts of the eye. However, the precise consequences of abnormal collagen type I on different ocular tissues remain unknown. Of particular significance is the sclera, where collagen type I is abundant and crucial for maintaining the structural integrity of the eye. Recent research on healthy individuals has uncovered a unique organizational pattern of collagen fibers within the sclera, characterized by fiber arrangement in both circular and radial layers around the optic nerve head. While the precise function of this organizational pattern remains unclear, it is hypothesized to play a role in providing mechanical support to the optic nerve. The objective of this study is to investigate the impact of abnormal collagen type I on the sclera by assessing the fiber organization near the optic nerve head in individuals with OI and comparing them to healthy individuals. Collagen fiber orientation of the sclera was measured using polarization-sensitive optical coherence tomography (PS-OCT), an extension of the conventional OCT that is sensitive to materials that exhibit birefringence (axial changes in light refraction). Birefringence was quantified and used as imaging contrast to extract collagen fiber orientation as well as the thickness of the radially oriented scleral layer. Three individuals with OI, exhibiting different degrees of disease severity, were assessed and analyzed, along with seventeen healthy individuals. Mean values obtained from individuals with OI were descriptively compared to those of the healthy participant group. PS-OCT revealed a similar orientation pattern of scleral collagen fibers around the optic nerve head between OI individuals and healthy individuals. However, two OI participants exhibited reduced mean birefringence of the radially oriented scleral layer compared to the healthy participant group (OI participant 1 oculus dexter et sinister (ODS): 0.34°/µm, OI participant 2: ODS 0.26°/µm, OI participant 3: OD: 0.29°/µm, OS: 0.28°/µm, healthy participants: ODS 0.38 ± 0.05°/µm). The radially oriented scleral layer was thinner in all OI participants although within ±2 standard deviations of the mean observed in healthy individuals (OI participant 1 OD: 101 µm, OS 104 µm, OI participant 2: OD 97 µm, OS 98 µm, OI participant 3: OD: 94 µm, OS 120 µm, healthy participants: OD 122.8 ± 13.6 µm, OS 120.8 ± 15.1 µm). These findings imply abnormalities in collagen organization or composition, underscoring the necessity for additional research to comprehend the ocular phenotype in OI.

High-Dimensional Single-Cell Mass Cytometry Demonstrates Differential Platelet Functional Phenotypes in Infants With Congenital Heart Disease.

BACKGROUND: Congenital heart disease (CHD) is a group of complex heart defects associated with hematologic abnormalities, including increased risk of thrombotic and bleeding events. Past studies have observed evidence of platelet hyperreactivity, while other studies showed decreased platelet activation in patients with CHD. The goal of this study was to develop a mass spectrometry approach to characterize single platelets in infants with CHD and identify potential etiology for such discrepant results. METHODS: We enrolled 19 infants with CHD along with 21 non-CHD controls at Yale New Haven Children's Heart Center. A single-cell high-dimensional mass cytometry method was developed to quantitatively interrogate platelet surface markers in whole blood. Additionally, plasma cytokine analysis was performed through a multiplexed panel of 52 vascular and inflammatory markers to assess for platelet releasates. RESULTS: We found that infants with CHD had significant differences in platelet activation and functional markers by mass cytometry compared with non-CHD controls. Based on cell surface markers, we classified the platelets into 8 subpopulations (P0 to P7). Distinct subpopulations of platelets (P1, P4, and P5) exhibiting decreased aggregatory phenotype but altered secretory phenotypes were also identified and found to be more abundant in the blood of infants with CHD. Electron microscopy identified increased proportion of hypogranular platelets in CHD. Moreover, cytokine analysis demonstrated an overall increase in plasma cytokines and biomarkers in CHD, including IL (interleukin)-6, IL-8, IL-27, RANTES, and VWF (von Willebrand factor), which are expressed in platelet granules and can be released upon activation. CONCLUSIONS: We developed a robust mass cytometry approach to identify platelet phenotypic heterogeneity. Infants with CHD had alterations in distinct subpopulations of platelets with overall reduced aggregatory phenotype and secretory dysfunction. These findings suggest that platelets in infants with CHD may be exhausted due to persistent stimulation and may explain both bleeding and thrombotic vascular complications associated with CHD.

Defining and Differentiating Congenital Vertical Talus and Congenital Oblique Talus: It's Not Primarily About the Talus.

Background: Congenital vertical talus (CVT) and congenital oblique talus (COT) are rocker-bottom foot deformities that have similar names and no objective definitions. This has led to confusion for practitioners, as well as scientific challenges for researchers. Our goal was to provide objective radiographic criteria to define and differentiate CVT and COT. Methods: We evaluated 62 pairs of maximum dorsiflexion and plantar flexion lateral radiographs of infant feet that had been clinically diagnosed with CVT. The dorsiflexion tibiotalar angle, the plantar flexion talus-first metatarsal angle, and the plantar flexion foot center of rotation of angulation (foot-CORA) were measured using transparent overlay tools. Freehand measurements were made on a subset of 10 pairs of radiographs to confirm clinical applicability. Nine contralateral pairs of radiographs of normal feet were measured for comparison. Results: Specific values for the radiographic measurements were identified that, together, reliably differentiated the shapes of rocker-bottom feet with CVT, COT, and flexible flatfoot with a short tendo-Achilles (FFF-STA), as well as the shape of the normal foot. More severe and rigid rocker-bottom foot deformities were diagnosed with CVT. Less severe and more flexible deformities were diagnosed with COT. Conclusions: CVT, COT, FFF-STA, and normal feet can be reliably differentiated using 2 angular measurements and 1 bone position measurement on dorsiflexion and plantar flexion lateral radiographs. Our data indicated that the differentiation of CVT and COT is based primarily on the rigidity of the navicular dislocation rather than the verticality of the talus. The data further supported the proposition that COT is a foot deformity along a spectrum of valgus/eversion deformities of the hindfoot that requires early treatment. Application of these diagnostic criteria should lead to clinical studies that identify a specific treatment, treatment outcome, and prognosis for each deformity. Level of Evidence: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Dynamic Ion Correlations and Ion-Pair Lifetimes in Aqueous Alkali Metal Chloride Electrolytes.

Electrolytes are central to many technological applications, as well as life itself. The behavior and properties of electrolytes are often described in terms of ion pairs, whereby ions associate as either contact ion pairs (in which ions are "touching") solvent-separated ion pairs (in which ions' solvent shells overlap) or solvent-solvent-separated ion pairs (in which ions' solvent shells are distinct). However, this paradigm is generally restricted to statistically averaged descriptions of solution structure and ignores temporal behavior. Here we elucidate the time-resolved dynamics of these ion-ion interactions in aqueous metal chloride electrolytes using the partial van Hove correlation function, based on polarizable molecular dynamics simulations. Our results show that the existence and persistence of ion pairs in aqueous metal chloride electrolytes should not be assumed a priori, but in fact are ion specific features of the solution with lifetimes on subpicosecond time scales.

A first-principles alternative to empirical solvent parameters.

The use of solvents is ubiquitous in chemistry. Empirical parameters, such as the Kamlet-Taft parameters and Gutmann donor/acceptor numbers, have long been used to predict and quantify the effects solvents have on chemical phenomena. Collectively however, such parameters are unsatisfactory, since each describes ultimately the same non-covalent solute-solvent and solute-solute interactions in completely disparate ways. Here we hypothesise that empirical solvent parameters are essentially proxy measures of the electrostatic terms that dominate solvent-solute interactions. On the basis of this hypothesis, we develop a new fundamental descriptor of these interactions, , and show that it is a self-consistent, probe-free, first principles alternative to established empirical solvent parameters.