Management of High Ankle Sprains Utilizing the Tightrope Surgical Procedure - A Novel Approach for a Rapid Return to Play.

The distal tibiofibular joint is described as a syndesmosis. The syndesmosis is important to the structural integrity of the ankle joint by maintaining the proximity of the tibia, fibula, and talus. Syndesmotic or high ankle sprains, involving the syndesmotic ligaments, pose a significant rehabilitative challenge due to their intricate anatomy, prolonged recovery periods following injury, and high susceptibility to persistent disability. Traditional management strategies have often been conservative, marked by lengthy periods of immobilization and a gradual return to activity. Severe syndesmotic injuries with diastasis have been treated surgically with screw fixation which may require a second intervention to remove the hardware and carries an inherent risk of breaking the screw during rehabilitation. Another fixation technique, the Tightrope™, has gained popularity in treating ankle syndesmosis injuries. The TightRope™ involves inserting Fiberwire® through the tibia and fibula, which allows for stabilization of the ankle mortise and normal range of motion. The accelerated rehabilitation protocol promotes early weight-bearing and has been shown to expedite the return to sport. This emerging strategy has shown promise in reducing recovery time as it is now possible to return to sport in less than 2 months after a tightrope repair and accelerated rehabilitation, compared with 3-6 months post screw fixation. This clinical commentary delves into this novel approach, highlighting the procedure, rehabilitation protocols, and the implications for physical therapy practice. Level of Evidence: V.

The Feline and the Swine: A Peculiar Case in an Allergy Clinic.

Cross-reactivity between mammalian proteins, such as that in Pork Cat Syndrome, remains a topic of great interest. This syndrome, characterized by an immunoglobulin E (IgE)-mediated response to porcine albumin triggered by sensitization through cat epithelium, has been sparsely documented. We discuss a 41-year-old female who developed a pruritic rash within 30 minutes of consuming pork. Notably, she exhibited elevated serum IgE levels with specific reactions to cat dander, dog dander, and pork. A skin prick test for pork was positive. The patient was treated conservatively with allergen avoidance, vitamin D supplementation, fexofenadine, and doxycycline for systemic reactions, and topical corticosteroids for localized skin reactions, yielding a resolution of symptoms. This case underscores the significance of recognizing rare cross-reactivities in allergy and immunology and the manifestations of Pork Cat Syndrome, necessitating a comprehensive patient history and awareness for improved diagnosis and management.

Ciguatera Toxin Syndrome from Amberjack Ingestion as a Cause of Chronic Dermatitis with Episodic Erythema.

Bioaccumulation of naturally produced ciguatoxin (CTX), such as that in ciguatera poisoning, continues to be a subject of great interest. In this condition, CTX is ingested by subtropical and tropical reef fish. Humans consume the fish species, and CTX is absorbed through the gastrointestinal tract and binds voltage-gated sodium channels on nerve terminals to cause neurological, gastrointestinal, cardiac, and rare dermatological clinical manifestations. In this present case, we discuss a 65-year-old female who presented with acute loose bowel movements and generalized pruritus of her anterior chest wall, abdomen, and bilateral upper and lower extremities 48 hours after consumption of amberjack fish. The patient was treated with intravenous corticosteroids and epinephrine and discharged with an oral corticosteroid taper. After appropriate treatment protocol, the patient continued to have pruritus with a burning sensation in her extremities with a rare skin dermatitis. Subsequent treatment included topical corticosteroids and moisturizing lotion to create a skin barrier, fexofenadine for pruritus control, and gabapentin and amitriptyline for paresthesia. This case demonstrates the need for continued research and patient education into the broad clinical manifestations that present as life-altering ciguatera poisoning.

Current and emerging therapies for Achondroplasia: The dawn of precision medicine.

Achondroplasia is a rare disease affecting bone growth and is caused by a missense mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. In the past few years, there were multiple experimental drugs entering into clinical trials for treating achondroplasia including vosoritide, the first precision medicine approved for this indication. This perspective presents the mechanism of action, benefit, and potential mechanistic limitation of the drugs currently being evaluated in clinical trials for achondroplasia. This article also discusses the potential impact of those drugs not only in increasing the growth of individuals living with achondroplasia but also in improving their quality of life.

Effects of earlens lens placement on sound field thresholds, tympanometric measurements and wideband acoustic immittance.

OBJECTIVE: The Earlens is a direct-drive hearing device consisting of a lens which physically displaces the umbo to achieve appropriate gain. The objective is to determine the clinical acceptability of clinical immittance measurements in Earlens wearers. DESIGN: Controlled before-after within-subjects repeated measures study. STUDY SAMPLE: Data is reported for measurements obtained on 15 subjects (average age of 72.2 years) with data from 30 ears. RESULTS: There was a small effect of lens placement on sound field thresholds in most subjects. The largest damping effect of 4 dB was observed at 1000 Hz. An average reduction of 0.17 mL was identified in compliance following lens placement (p < 0.05). An effect of the lens on power absorbance obtained at ambient and peak pressure was found. The lens resulted in an increase in power absorbance at low frequencies (below 500 Hz) and a decrease in the mid to high-frequency range of approximately 500-3500 Hz (p < 0.05). CONCLUSIONS: Lens wear had a small effect on audiometric thresholds and tympanometry for most patients. Clinicians who use compliance and power absorbance should take into consideration lens effects on these measurements. Additional work is required to develop clinical normative ranges of these measures for wearers of the Earlens.

Endoluminal Silicone-Covered Stenting in Children: Novel Applications and Lessons Learned.

BACKGROUND: Silicone-covered endoluminal stents have been applied to various hollow visceral disorders in adult patients with varying success. Efficacy of retrievable endoluminal stenting in children is less well-established. PURPOSE: The purpose of this study was to evaluate our experience with evolving applications of endoluminal silicone-covered stenting in children. RESEARCH DESIGN: Eight children 19 years and younger having silicone-covered stent placement for various indications at a single institution (2014-2021) were reviewed retrospectively. RESULTS: Eight patients received a total of 26 silicone-covered stents. Four stent placements (15.4%) were associated with a direct adverse event. To resolve the endoluminal disorder, four patients received multiple stents or further intervention. When evaluating novel applications, clinical benefit was noted for one patient with vaginal atresia, and another after ileal pouch anal anastomosis disruption. CONCLUSION: This experience highlights the broad and innovative applications for endoluminal silicone-covered natural orifice stenting in children. Acute processes respond well and rapidly to stenting, although chronic, established fistula may require additional manipulations or surgery.

Non-clinical Pharmacology of YTX-7739: a Clinical Stage Stearoyl-CoA Desaturase Inhibitor Being Developed for Parkinson's Disease.

Stearoyl-CoA desaturase (SCD) is a potential therapeutic target for Parkinson's and related neurodegenerative diseases. SCD inhibition ameliorates neuronal toxicity caused by aberrant α-synuclein, a lipid-binding protein implicated in Parkinson's disease. Its inhibition depletes monounsaturated fatty acids, which may modulate α-synuclein conformations and membrane interactions. Herein, we characterize the pharmacokinetic and pharmacodynamic properties of YTX-7739, a clinical-stage SCD inhibitor. Administration of YTX-7739 to rats and monkeys for 15 days caused a dose-dependent increase in YTX-7739 concentrations that were well-tolerated and associated with concentration-dependent reductions in the fatty acid desaturation index (FADI), the ratio of monounsaturated to saturated fatty acids. An approximate 50% maximal reduction in the carbon-16 desaturation index was observed in the brain, with comparable responses in the plasma and skin. A study with a diet supplemented in SCD products indicates that changes in brain C16 desaturation were due to local SCD inhibition, rather than to changes in systemic fatty acids that reach the brain. Assessment of pharmacodynamic response onset and reversibility kinetics indicated that approximately 7 days of dosing were required to achieve maximal responses, which persisted for at least 2 days after cessation of dosing. YTX-7739 thus achieved sufficient concentrations in the brain to inhibit SCD and produce pharmacodynamic responses that were well-tolerated in rats and monkeys. These results provide a framework for evaluating YTX-7739 pharmacology clinically as a disease-modifying therapy to treat synucleinopathies.

A pathogenic deletion in Forkhead Box L1 (FOXL1) identifies the first otosclerosis (OTSC) gene.

Otosclerosis is a bone disorder of the otic capsule and common form of late-onset hearing impairment. Considered a complex disease, little is known about its pathogenesis. Over the past 20 years, ten autosomal dominant loci (OTSC1-10) have been mapped but no genes identified. Herein, we map a new OTSC locus to a 9.96 Mb region within the FOX gene cluster on 16q24.1 and identify a 15 bp coding deletion in Forkhead Box L1 co-segregating with otosclerosis in a Caucasian family. Pre-operative phenotype ranges from moderate to severe hearing loss to profound sensorineural loss requiring a cochlear implant. Mutant FOXL1 is both transcribed and translated and correctly locates to the cell nucleus. However, the deletion of 5 residues in the C-terminus of mutant FOXL1 causes a complete loss of transcriptional activity due to loss of secondary (alpha helix) structure. FOXL1 (rs764026385) was identified in a second unrelated case on a shared background. We conclude that FOXL1 (rs764026385) is pathogenic and causes autosomal dominant otosclerosis and propose a key inhibitory role for wildtype Foxl1 in bone remodelling in the otic capsule. New insights into the molecular pathology of otosclerosis from this study provide molecular targets for non-invasive therapeutic interventions.

Cutaneous Secondary Syphilis Resembling Non-Melanoma Skin Cancer.

The cutaneous manifestations of secondary syphilis can vary significantly between patients, leading to a more difficult or delayed diagnosis. Here we present an instructive case of secondary syphilis in a 45-year-old, HIV-positive male patient. He presented with a solitary, crusted anterior neck nodule without concomitant systemic symptoms. Together, history and physical exam were concerning for non-melanoma skin cancer. Histopathologic evaluation of the lesion revealed an extensive infiltrate of plasma cells at the dermoepidermal junction, and immunohistochemical staining revealed numerous Treponema pallidum microorganisms. Physicians must keep syphilis in the differential diagnosis when evaluating atypical nodular lesions resembling non-melanoma skin cancer for the purpose of initiating appropriate antibiotic treatment and preventing future infectious complications.

Bone Marrow Concentrate (BMC) Therapy in Musculoskeletal Disorders: Evidence-Based Policy Position Statement of American Society of Interventional Pain Physicians (ASIPP).

BACKGROUND: The use of bone marrow concentrate (BMC) for treatment of musculoskeletal disorders has become increasingly popular over the last several years, as technology has improved along with the need for better solutions for these pathologies. The use of cellular tissue raises a number of issues regarding the US Food and Drug Administration's (FDA) regulation in classifying these treatments as a drug versus just autologous tissue transplantation. In the case of BMC in musculoskeletal and spine care, this determination will likely hinge on whether BMC is homologous to the musculoskeletal system and spine. OBJECTIVES: The aim of this review is to describe the current regulatory guidelines set in place by the FDA, specifically the terminology around "minimal manipulation" and "homologous use" within Regulation 21 CFR Part 1271, and specifically how this applies to the use of BMC in interventional musculoskeletal medicine. METHODS: The methodology utilized here is similar to the methodology utilized in preparation of multiple guidelines employing the experience of a panel of experts from various medical specialties and subspecialties from differing regions of the world. The collaborators who developed these position statements have submitted their appropriate disclosures of conflicts of interest. Trustworthy standards were employed in the creation of these position statements. The literature pertaining to BMC, its effectiveness, adverse consequences, FDA regulations, criteria for meeting the standards of minimal manipulation, and homologous use were comprehensively reviewed using a best evidence synthesis of the available and relevant literature. RESULTS/Summary of Evidence: In conjunction with evidence-based medicine principles, the following position statements were developed: Statement 1: Based on a review of the literature in discussing the preparation of BMC using accepted methodologies, there is strong evidence of minimal manipulation in its preparation, and moderate evidence for homologous utility for various musculoskeletal and spinal conditions qualifies for the same surgical exemption. Statement 2: Assessment of clinical effectiveness based on extensive literature shows emerging evidence for multiple musculoskeletal and spinal conditions. • The evidence is highest for knee osteoarthritis with level II evidence based on relevant systematic reviews, randomized controlled trials and nonrandomized studies. There is level III evidence for knee cartilage conditions. • Based on the relevant systematic reviews, randomized trials, and nonrandomized studies, the evidence for disc injections is level III. • Based on the available literature without appropriate systematic reviews or randomized controlled trials, the evidence for all other conditions is level IV or limited for BMC injections. Statement 3: Based on an extensive review of the literature, there is strong evidence for the safety of BMC when performed by trained physicians with the appropriate precautions under image guidance utilizing a sterile technique. Statement 4: Musculoskeletal disorders and spinal disorders with related disability for economic and human toll, despite advancements with a wide array of treatment modalities. Statement 5: The 21st Century Cures Act was enacted in December 2016 with provisions to accelerate the development and translation of promising new therapies into clinical evaluation and use. Statement 6: Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders and spine. With mixed results, these therapies are greatly outpacing the evidence. The reckless publicity with unsubstantiated claims of beneficial outcomes having putative potential, and has led the FDA Federal Trade Commission (FTC) to issue multiple warnings. Thus the US FDA is considering the appropriateness of using various therapies, including BMC, for homologous use. Statement 7: Since the 1980's and the description of mesenchymal stem cells by Caplan et al, (now called medicinal signaling cells), the use of BMC in musculoskeletal and spinal disorders has been increasing in the management of pain and promoting tissue healing. Statement 8: The Public Health Service Act (PHSA) of the FDA requires minimal manipulation under same surgical procedure exemption. Homologous use of BMC in musculoskeletal and spinal disorders is provided by preclinical and clinical evidence. Statement 9: If the FDA does not accept BMC as homologous, then it will require an Investigational New Drug (IND) classification with FDA (351) cellular drug approval for use. Statement 10: This literature review and these position statements establish compliance with the FDA's intent and corroborates its present description of BMC as homologous with same surgical exemption, and exempt from IND, for use of BMC for treatment of musculoskeletal tissues, such as cartilage, bones, ligaments, muscles, tendons, and spinal discs. CONCLUSIONS: Based on the review of all available and pertinent literature, multiple position statements have been developed showing that BMC in musculoskeletal disorders meets the criteria of minimal manipulation and homologous use. KEY WORDS: Cell-based therapies, bone marrow concentrate, mesenchymal stem cells, medicinal signaling cells, Food and Drug Administration, human cells, tissues, and cellular tissue-based products, Public Health Service Act (PHSA), minimal manipulation, homologous use, same surgical procedure exemption.

Inhibiting Stearoyl-CoA Desaturase Ameliorates α-Synuclein Cytotoxicity.

The lack of disease-modifying treatments for neurodegenerative disease stems in part from our rudimentary understanding of disease mechanisms and the paucity of targets for therapeutic intervention. Here we used an integrated discovery paradigm to identify a new therapeutic target for diseases caused by α-synuclein (α-syn), a small lipid-binding protein that misfolds and aggregates in Parkinson's disease and other disorders. Using unbiased phenotypic screening, we identified a series of compounds that were cytoprotective against α-syn-mediated toxicity by inhibiting the highly conserved enzyme stearoyl-CoA desaturase (SCD). Critically, reducing the levels of unsaturated membrane lipids by inhibiting SCD reduced α-syn toxicity in human induced pluripotent stem cell (iPSC) neuronal models. Taken together, these findings suggest that inhibition of fatty acid desaturation has potential as a therapeutic approach for the treatment of Parkinson's disease and other synucleinopathies.

Aqueous Assembly of Oxide and Fluoride Nanoparticles into 3D Microassemblies.

We demonstrate rapid [∼mm3/(h·L)] organic ligand-free self-assembly of three-dimensional, >50 µm single-domain microassemblies containing up to 107 individual aligned nanoparticles through a scalable aqueous process. Organization and alignment of aqueous solution-dispersed nanoparticles are induced by decreasing their pH-dependent surface charge without organic ligands, which could be temperature-sensitive or infrared light absorbing. This process is exhibited by transforming both dispersed iron oxide hydroxide nanorods and lithium yttrium fluoride nanoparticles into high packing density microassemblies. The approach is generalizable to nanomaterials with pH-dependent surface charge (e.g., oxides, fluorides, and sulfides) for applications requiring long-range alignment of nanostructures as well as high packing density.

Tattoo-induced hemangioma: An exploration of the potential for vascular proliferations following tattoo-related trauma.

With the rising popularity of tattoos, many physicians have seen complications of their application, usually transient and inflammatory in nature, although both benign and malignant neoplasms have been reported as well. We present an unusual case of a hemangioma arising after tattoo application.

Addressing Cancer Pain Inequities Through Intervention

The Power Over Pain-Coaching (POP-C) intervention was developed to improve functional status and decrease pain and pain-related distress among ambulatory African American patients with cancer. By bypassing the effects of disparities, the POP-C intervention may help to decrease suffering among African American patients with cancer pain; consequently, it contributes to improving quality of life and addressing social and other determinants of health among members of this population. 
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Structure-Property Relations in Carbon Nanotube Fibers by Downscaling Solution Processing.

At the microscopic scale, carbon nanotubes (CNTs) combine impressive tensile strength and electrical conductivity; however, their macroscopic counterparts have not met expectations. The reasons are variously attributed to inherent CNT sample properties (diameter and helicity polydispersity, high defect density, insufficient length) and manufacturing shortcomings (inadequate ordering and packing), which can lead to poor transmission of stress and current. To efficiently investigate the disparity between microscopic and macroscopic properties, a new method is introduced for processing microgram quantities of CNTs into highly oriented and well-packed fibers. CNTs are dissolved into chlorosulfonic acid and processed into aligned films; each film can be peeled and twisted into multiple discrete fibers. Fibers fabricated by this method and solution-spinning are directly compared to determine the impact of alignment, twist, packing density, and length. Surprisingly, these discrete fibers can be twice as strong as their solution-spun counterparts despite a lower degree of alignment. Strength appears to be more sensitive to internal twist and packing density, while fiber conductivity is essentially equivalent among the two sets of samples. Importantly, this rapid fiber manufacturing method uses three orders of magnitude less material than solution spinning, expanding the experimental parameter space and enabling the exploration of unique CNT sources.

Harvesting electrical energy from carbon nanotube yarn twist.

Mechanical energy harvesters are needed for diverse applications, including self-powered wireless sensors, structural and human health monitoring systems, and the extraction of energy from ocean waves. We report carbon nanotube yarn harvesters that electrochemically convert tensile or torsional mechanical energy into electrical energy without requiring an external bias voltage. Stretching coiled yarns generated 250 watts per kilogram of peak electrical power when cycled up to 30 hertz, as well as up to 41.2 joules per kilogram of electrical energy per mechanical cycle, when normalized to harvester yarn weight. These energy harvesters were used in the ocean to harvest wave energy, combined with thermally driven artificial muscles to convert temperature fluctuations to electrical energy, sewn into textiles for use as self-powered respiration sensors, and used to power a light-emitting diode and to charge a storage capacitor.

Adolescent and Young Adult Survivors of Childhood Brain Tumors: Life After Treatment in Their Own Words.

BACKGROUND: To date, there are few studies that examine the perspectives of older survivors of childhood brain tumors who are living with their families in terms of their sense of self and their role in their families. OBJECTIVE: The aim of this study was to describe how adolescent and young adult survivors of childhood brain tumors describe their health-related quality of life, that is, their physical, emotional, and social functioning. METHODS: This qualitative descriptive study included a purposive sample of 41 adolescent and young adult survivors of a childhood brain tumor who live with their families. Home interviews were conducted using a semistructured interview guide. Directed content analytic techniques were used to analyze data using health-related quality of life as a framework. RESULTS: This group of brain tumor survivors described their everyday lives in terms of their physical health, neurocognitive functioning, emotional health, social functioning, and self-care abilities. Overall, survivors struggle for normalcy in the face of changed functioning due to their cancer and the (late) effects of their treatment. CONCLUSIONS: Neurocognitive issues seemed most compelling in the narratives. The importance of families went beyond the resources, structure, and support for functioning. Their families provided the recognition that they were important beings and their existence mattered to someone. IMPLICATIONS FOR PRACTICE: The value and complexity of care coordination were highlighted by the multifaceted needs of the survivors. Advocacy for appropriate and timely educational, vocational, and social support is critical as part of comprehensive cancer survivorship care.

Elusive liver factor that causes pancreatic α cell hyperplasia: A review of literature.

Tumors and cancers of the gastrointestinal tract and pancreas are commonly derived from precursor lesions so that understanding the physiological, cellular, and molecular mechanisms underlying the pathogenesis of precursor lesions is critical for the prevention and treatment of those neoplasms. Pancreatic neuroendocrine tumors (PNETs) can also be derived from precursor lesions. Pancreatic α cell hyperplasia (ACH), a specific and overwhelming increase in the number of α cells, is a precursor lesion leading to PNET pathogenesis. One of the 3 subtypes of ACH, reactive ACH is caused by glucagon signaling disruption and invariably evolves into PNETs. In this article, the existing work on the mechanisms underlying reactive ACH pathogenesis is reviewed. It is clear that the liver secretes a humoral factor regulating α cell numbers but the identity of the liver factor remains elusive. Potential approaches to identify the liver factor are discussed.

Transitioning Adolescents and Young Adults With Sickle Cell Disease From Pediatric to Adult Health Care: Provider Perspectives.

The transition from pediatric to adult health care is often challenging for adolescents and young adults with sickle cell disease (SCD). Our study aimed to identify (1) measures of success for the transition to adult health care; and (2) barriers and facilitators to this process. We interviewed 13 SCD experts and asked them about their experiences caring for adolescents and young adults with SCD. Our interview guide was developed based on Social-Ecological Model of Adolescent and Young Adult Readiness to Transition framework, and interviews were coded using the constant comparative method. Our results showed that transition success was measured by health care utilization, quality of life, and continuation on a stable disease trajectory. We also found that barriers to transition include negative experiences in the emergency department, sociodemographic factors, and adolescent skills. Facilitators include a positive relationship with the provider, family support, and developmental maturity. Success in SCD transition is primarily determined by the patients' quality of relationships with their parents and providers and their developmental maturity and skills. Understanding these concepts will aid in the development of future evidence-based transition care models.

Assessing Suicidal Ideation and Behaviors Among Survivors of Childhood Brain Tumors and Their Mothers During Sociobehavioral Research.

PURPOSE/OBJECTIVES: To describe the development and feasibility of a protocol for nonpsychiatric subspecialty research staff members to screen research participants who endorse suicidal ideations or behaviors during data collection
. DESIGN: Descriptive protocol development.
. SETTING: The Children's Hospital of Philadelphia and the University of Pennsylvania.
. SAMPLE: 186 mother caregivers and 134 adolescent or young adult survivors of childhood brain tumors, with the protocol implemented for 5 caregivers and 11 survivors. METHODS: During telephone- and home-based interviews, the interviewer assessed the participant using the Columbia-Suicide Severity Rating Scale (C-SSRS). MAIN RESEARCH VARIABLES: Expressed suicidal ideation or behavior
. FINDINGS: Implementation of the C-SSRS by nonpsychiatric subspecialty staff members was feasible and valid. Interviewers' conclusions based on this instrument matched those of the mental health professional who followed up with participants. Process notes contained themes about the participants, including anger and sadness in survivors and the physical and emotional demands of the survivor in caregivers. Progress notes for the interviewer included a reiteration of events, whether the assessment was successful, and whether the recommendation of the interviewer was in agreement with that of the mental health professional
. CONCLUSIONS: The protocol based on the C-SSRS was useful and feasible for nonpsychiatric subspecialty staff members to use in the collection of data from survivors of childhood brain tumors and their caregivers. IMPLICATIONS FOR NURSING: Survivors of childhood brain tumors and their caregivers may experience psychosocial distress. Nurses, as research assistants or in other roles, can use tools such as the C-SSRS to assist in front-line assessments. 
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