Continuation of Gender-Affirming Hormone Therapy in Transgender and Gender-Diverse Individuals: A Systematic Review.

OBJECTIVE: Gender-affirming hormone therapy (GAHT) is often used by transgender and gender-diverse individuals to align their physical appearance with their gender identity. Discontinuation rates and factors leading to discontinuation of GAHT are not fully understood. We aimed to assess the continuation and discontinuation rates of GAHT and the factors leading to discontinuation of GAHT in a systematic review of the literature. METHODS: We searched PubMed from 2009 until April 01, 2024, for all published studies that described initiation, discontinuation, and reasons for discontinuation of GAHT. Studies were screened by 2 authors independently. We included 6 studies that met the inclusion and exclusion criteria published between 2021 and 2024. RESULTS: Five studies reported GAHT discontinuation rates under 10%, whereas 1 study reported a discontinuation/lost to follow-up rate of 30.8%. Only 1 study was prospective, whereas all other studies were retrospective. Reasons for discontinuation of GAHT were described in only 2 studies. One study reported GAHT discontinuation primarily from external factors, whereas the other study suggested that GAHT discontinuation occurred due to change in gender identity. CONCLUSION: Current data on discontinuation of GAHT show that the rates of GAHT discontinuation appear to be low and the reasons include both external pressures and internal change of gender identity. A better understanding of the internal and external pressures that impact the decision to continue GAHT is needed in future studies.

Overcoming strong retention barriers of A- and V-series nerve agents on silica sorbents.

The present study explores the potential of silica solid phase extraction for gas chromatography mass spectrometric analyses of A- and V-series nerve agents. Owing to the presence of basic amidine and amine moieties, these analyte undergo strong ionic interactions with inherently acidic silica surfaces, producing poor recoveries. Subtle optimizations in the elution composition empowered the analytes to overcome the retention barriers from sorbent surfaces. Acetone containing 10 % (v/v) NH4OH effectively minimized strong analyte-sorbent interactions allowing good to excellent recoveries. Recoveries for A-series agents ranged from 88 to 96 %. VX, which is reported to be poorly recoverable from such sorbent matrices offered best data so far, reaching up to 74 % under optimized conditions. The method detection limits for the selected analytes in mass spectrometric analysis ranged from 47 to 171 ng/ml. Strong affinities of analytes towards silica sorbent were further exploited to expand the scope of analysis and establish the method's efficacy for a wide range of organic matrices. The applicability of the method to the real world applications was also validated in blind spiking exercises in diverse organic liquid samples received in 48th, 50th and 52nd proficiency tests conducted by the Organization for the Prohibition of Chemical Weapons (OPCW).

A randomized phase 1 study of safety, tolerability, and pharmacokinetics of MK-1088, a novel dual adenosine receptor antagonist, in healthy adult participants.

This phase 1 first-in-human study evaluated the safety, tolerability, and pharmacokinetics of MK-1088, a novel, small-molecule dual inhibitor of adenosine A2A and A2B receptors. Healthy adult participants were enrolled in two panels (n = 8 each) and randomly assigned to receive MK-1088 (n = 6) or placebo (n = 2) orally in each of five treatment periods. Participants in panel A received single ascending doses of MK-1088 at 1, 10, 50, and 150 mg or placebo in a fasted or fed (50 mg only) state. Participants in panel B received MK-1088 at 3, 25, 100, and 224 mg or placebo in a fasted state. Primary objectives were to evaluate safety, tolerability, and plasma pharmacokinetics following a single dose of MK-1088. The secondary objective was to evaluate the effects of a high-fat meal on pharmacokinetics. All participants (n = 16) completed the study (median age: 33 years [range: 20-43]; all were male). Treatment-related adverse events (AEs) occurred in 1 of 6 (17%), 4 of 6 (67%), 4 of 6 (67%), and 2 of 6 (33%) participants after receiving MK-1088 at 3, 25, 100, and 224 mg, respectively. No serious AEs or deaths due to any cause occurred. MK-1088 was rapidly absorbed after a single dose; half-life was ~ 11 h in the 100-224 mg dose range. The target concentration at 12 h (> 0.3 µM) was exceeded at the 50-mg dose level. MK-1088 plasma pharmacokinetics increased dose proportionately. A high-fat meal did not significantly affect pharmacokinetics at the 50-mg dose. MK-1088 was well tolerated and demonstrated dose-proportional pharmacokinetic properties that were not affected by a high-fat meal.

Chemical Derivatization Leads to the Discovery Of Novel Analogs of Azotochelin, a Natural Siderophore, as Promising Anticancer Agents.

Siderophores are structurally unique medicinal natural products and exhibit considerable therapeutic potential. Herein, we report the design and synthesis of azotochelin, a natural siderophore, and an extensive library of azotochelin analogs and their anticancer properties. We modified the carboxylic acid and the aromatic ring of azotochelin using various chemical motifs. We evaluated the cytotoxicity of the compounds against six different cancer cell lines (KB-3-1, SNB-19, MCF-7, K-562, SW-620, and NCI-H460) and a non-cancerous cell line (HEK-293). Among the twenty compounds tested, the IC50 values of nine compounds (14, 32, 35-40, and 54) were between 0.7 and 2.0 µM against a lung cancer cell line (NCI-H460). Moreover, several compounds showed good cytotoxicity profile (IC50 <10 µM) against the tested cancer cell lines. The flow cytometry analysis showed that compounds 36 and 38 induced apoptosis in NCI-H460 in a dose-dependent manner. The cell cycle analysis indicated that compounds 36 and 38 significantly arrested the cell cycle at the S phase to block cancer cell proliferation in the NCI-H460 cell line. The study has produced various novel azotochelin analogs that are potentially effective anticancer agents and lead compounds for further synthetic and medicinal chemistry exploration.

Double trouble - dual outflow tract obstruction in congenital heart disease: a case report.

BACKGROUND: Double chambered right ventricle is a rare congenital heart disease that is characterised by the presence of an anomalous muscle bundle that divides the right ventricle into a low pressure superior (distal) chamber and a high pressure inferior (proximal) chamber. It is found in association with a ventricular septal defect in 90% cases with other associations being tetralogy of Fallot, transposition of great vessels, atrial septal defect and Ebstein's anomaly. On the other hand, subaortic membrane is a form of discrete subaortic stenosis that is characterised by a membranous diaphragm in the subvalvular location of the left ventricular outflow tract. Both of these entities are responsible for causing subvalvular outflow tract obstruction. The occurrence of double chambered right ventricle in association with subaortic membrane is an extremely rare entity with only a few case reports available in the literature. CASE REPORT: A 13-year-old male child with history of chest pain and palpitations presented to the outpatient department of a tertiary care center. Transthoracic echocardiography revealed a subaortic membrane producing a pressure gradient across the left ventricular outflow tract with dilatation of the right atrium and right ventricle which could not be fully evaluated on echocardiography. Cardiac computed tomography was then performed which additionally revealed an anomalous muscle bundle coursing across the right ventricle from the septum to the subinfundibular region creating a double chambered right ventricle. The patient was then taken up for reconstruction of right ventricular outflow tract and resection of subaortic membrane. CONCLUSION: Right and left outflow tract obstructions are rare congenital lesions which when seen in combination, become even more infrequent. Echocardiography is a robust tool that detects turbulent flow to identify such lesions. However, poor acoustic window may sometimes result in missing these lesions and computed tomography in such situations can play an important role in detection as well as complete preoperative imaging evaluation.

Neglected Superior Dislocation of the Shoulder Joint: A Case Report.

The anterior subtype of shoulder dislocations constitutes the vast majority that either reduces instantly or is reduced at the point of care with no serious complexities. The posterior ones are infrequent and inferior and superior dislocations are even more rare. Rupture of the deltoid is considered to be linked with superior dislocation; regardless, very few articles are available pertaining to the mechanism of onset and the management of a superior shoulder dislocation. In the line of traumatic shoulder dislocations, we present a one-year-old neglected case of a 23-year-old male who sustained an open injury over the right outstretched upper arm, abducted at an angle of approximately 45° due to a fall from a height of approximately 18 feet. This unique report outlines the various surgical modalities available, given the patient's late presentation due to neglect.

Gas chromatography tandem mass spectrometric analysis of alkylphosphonofluoridic acids as verification targets of nerve agents.

Alkylphosphonofluoridic Acids (APFA) are the major thermal degradation products of G- and A-series nerve agents and thus play a vital role in the verification analysis of Chemical Weapons Convention. Present study focuses on the development of sample clean-up, derivatization procedures and gas chromatography tandem mass spectrometric analysis of APFA in aqueous samples. APFA were found to be much more delicate than the corresponding alkylphosphonic acids and thus required subtle optimizations. Retention of analytes on silica and polymer-based anion exchangers followed by elution under alkaline conditions yielded best recoveries. Elution under acidic conditions led to partial or complete degradation of the analytes to alkylphosphonic acids. Silylation reactions, particularly with MTBSTFA were found the best in terms of chromatographic responses and resolution of the derivative peaks. Methylations with diazomethane, which requires acidic reaction media, failed to produce desired yields of the derivatives. Under optimized conditions, the analytes produced the recoveries ranging from 76.9 to 94.5% with RSD ≤9.2%. The best LOD's in the tandem mass spectrometric analysis ranged from 13 to 56 ng/ml. The applicability of the method was tested by spiking the analytes in the retained aqueous samples received for the 52nd proficiency test conducted by the Organization for the Prohibition of Chemical Weapons (OPCW).

Understanding Collective Intelligence: Investigating the Role of Collective Memory, Attention, and Reasoning Processes.

As society has come to rely on groups and technology to address many of its most challenging problems, there is a growing need to understand how technology-enabled, distributed, and dynamic collectives can be designed to solve a wide range of problems over time in the face of complex and changing environmental conditions-an ability we define as "collective intelligence." We describe recent research on the Transaction Systems Model of Collective Intelligence (TSM-CI) that integrates literature from diverse areas of psychology to conceptualize the underpinnings of collective intelligence. The TSM-CI articulates the development and mutual adaptation of transactive memory, transactive attention, and transactive reasoning systems that together support the emergence and maintenance of collective intelligence. We also review related research on computational indicators of transactive-system functioning based on collaborative process behaviors that enable agent-based teammates to diagnose and potentially intervene to address developing issues. We conclude by discussing future directions in developing the TSM-CI to support research on developing collective human-machine intelligence and to identify ways to design technology to enhance it.

Malunion of a Clavicle Fracture in a Young Adult: A Case Report and Surgical Intervention.

This case study examines the medical complexity of managing a neglected clavicle in a young patient, resulting in a complicated interstitial non-union. Despite initial therapeutic efforts, the fracture was not treated, resulting in significant pain as well as functional and aesthetic disabilities. This case outlines accurate clinical presentation and diagnostic methods. In addition, malunion clavicle fractures require multifaceted therapeutic approaches including surgical interventions, rehabilitation programs, and psychological support. Through comprehensive research and long-term follow-up, this report reveals the complexity of traumatic fractures, highlighting the importance of early recognition and intervention. To address the issue effectively, it is essential to follow a multidisciplinary approach that includes physical assessment, pharmacotherapy, and physiotherapy. This case report aims to highlight the critical role of comprehensive individual care in improving the patient's condition and emphasizes the importance of vigilant healthcare practices.

Lacertus Fibrosus Syndrome: A Case Report.

Lacertus fibrosus syndrome is described as compression of the median nerve, which takes place beneath a layer of ligamentous tissue (lacertus fibrosus, also known as bicipital aponeurosis) slightly beyond the elbow joint. Both sexes can develop lacertus fibrosus syndrome, most often after the age of 35. The possible risk factors are repetition of movements, overwork, and manual work while the forearm is pronated. Lacertus fibrosus syndrome presents a distinct diagnostic challenge because it is a somewhat unknown and non-documented disease. Its symptoms are often mistaken for those of carpal tunnel syndrome, which complicates the differential diagnosis and management of the patient. All patients who report tingling, numbness, loss of strength, muscle loss, manual endurance, or dexterity should be investigated and tested for both carpal tunnel syndrome and lacertus syndrome. Here, a case of a 43-year-old woman is discussed, who presented with chief complaints of pain and tingling sensation in the left upper limb, which was associated with loss of thumb pinch grip. The pain was aggravated with elbow extension and relieved with rest. The patient underwent left elbow median nerve decompression and was discharged in steady condition. This case report highlights the accurate clinical presentation and surgical intervention for the syndrome, for which the outcome turned out to be satisfying.

Ipsilateral Intertrochanteric Fracture with Posterior Dislocation of Hip.

Introduction: High-energy trauma has increased the incidence of traumatic hip dislocation and dislocation is often associated with fractures. However, a hip fracture-dislocation extending to the ipsilateral femoral trochanter is exceedingly rare and only a few cases have been described. We report a case of irreducible posterior dislocation of the hip with ipsilateral intertrochanteric fracture managed by open reduction and osteosynthesis. Case Report: A 50-year-old male presented with a history of fall from an electricity pole with pain in the left hip and an inability to bear weight on his left lower limb. Radiographs confirmed the presence of posterior dislocation of the left hip with comminuted intertrochanteric fracture on the same side. Conclusion: Posterior dislocation of the hip with same side inter trochanteric fracture is a rare traumatic entity, with only few case being reported. Literature does not provide any classification for such rare traumatic fracture dislocation. Management of such fracture requires early diagnosis and intervention which can result in good prognosis.

Giant Cell Tumor: A Case Series of Seven Patients with GCT at Atypical Sites.

Introduction: Giant cell tumor (GCT) represents 5% of all primary bone tumors and 20% of biopsy analyzed benign tumors. More than half of these lesions occur in the 3rd and 4th decades of life. There is no absolute treatment method selection. Techniques ranging from intralesional curettage to wide resection can be used. Goal is to eradicate the tumor, preserve limb function, and prevent local recurrence and distant metastasis. Case Report: We are presenting seven cases of GCT at five different and rare sites involving tibia, calcaneum, metatarsal, proximal humerus, and clavicle with tumor being limited to bone in all seven cases not involving the soft tissue. There were three male patients and four female patients. Six patients underwent intralesional curettage using high-speed burr and curette, along with adjuvant irrigation with hydrogen peroxide and normal saline followed by polymethyl methacrylate reconstruction. One patient with GCT clavicle underwent wide resection. Results: In all seven cases, we were able to able to remove the tumor completely. Six patients had a gradual and complete recovery with return to near normal activity within 6 month-1 year after surgery. One patient with proximal humerus GCT had a recurrence which got resolved with injection denosumab. All patients have been followed up for a minimum duration of 2 years. Conclusion: Intervention in the early stages can avoid radical procedures such as wide local excision or amputation. We recommend aggressive surgical approach with close follow-up to detect recurrence if any, at an early stage.

Atypical Cervical Potts Spine with Multiple Level Epidural Collection: A Case Series of Three Patients.

Introduction: Cervical Pott's constitutes about 10% of all Pott's spine cases. In tuberculous spondylitis, initially there occurs destruction of vertebral bodies and further progression may result in adjacent abscesses, leading to cord compression. Objective is to excise the diseased focus and to provide spinal stability. Case Report: We are presenting 3 rare cases of cervical Pott's spine with epidural collection at multiple levels in the cervical region without significant vertebral body destruction that were followed up for a period of 1 year postoperatively. Patients underwent single-level corpectomy and decompression from anterior aspect. In all three cases, we were able to decompress the cord and remove all the collections and also achieved spinal stabilization. Patients had a gradual and complete recovery of motor power within 6 months to 1 year after surgery. Conclusion: Technique used allows accurate visual assessment of the extent of the disease and allows complete decompression of the cord at multiple levels in cervical spine without causing much instability.

Unique Procedure to Remove Pedicle Screw without Compatible Instrumentation: Case Report and Review of Literature.

Introduction: As the number of patients undergoing spine fixation has increased, the requirement for revision surgery has also increased. Difficulty faced while doing revision surgery is mostly in removing polyaxial pedicle screws, especially if we do not have the desired instrumentation. Case Report: A 55-year-old patient previously operated for D12 fracture presented to us with implant failure due to backing out of pedicle screws. Compatible instrumentation to remove the implant was not available as even the cap screw could not be removed due to screwdriver mismatch. Hence, we had to design our own method to address the problem which we did successfully. At present, the patient is on our regular follow-up, is pain free, is able to walk without support, and has not reported any new complaints. Conclusion: Method used in our case simplifies and accelerates the screw removal process and provides guidance to any surgeon who faces a similar problem.

Dermatologic care of patients with differences of sex development.

Background: Differences of sex development (DSD or disorders of sex development) are uncommon congenital conditions, characterized by atypical development of chromosomal, gonadal, or anatomic sex. Objective: Dermatologic care is an important component of the multidisciplinary care needed for individuals with DSD. This article discusses the most common primary dermatologic manifestations of DSD in addition to the cutaneous manifestations of hormonal and surgical therapies in individuals with DSD. Data sources: Published articles including case series and case reports on PubMed. Study selections: Selection was conducted by examining existing literature with a team of multidisciplinary specialists. Methods: Narrative review. Limitations: This article was not conducted as a systematic review. Results: In Klinefelter syndrome, refractory leg ulcers and incontinentia pigmenti have been described. Turner syndrome is associated with lymphatic malformations, halo nevi, dermatitis, and psoriasis. Virilization can be seen in some forms of congenital adrenal hyperplasia, where acne and hirsutism are common. Conclusion: Dermatologists should consider teratogenic risk for treatments of skin conditions in DSD depending on pregnancy potential. Testosterone replacement, commonly used for Klinefelter syndrome, androgen insensitivity syndrome, 5-alpha reductase deficiency, gonadal dysgenesis, or ovotesticular DSD, may cause acne.

Common Peroneal Nerve Splitting in Proximal Fibular Osteochondroma: A Rare Presentation.

Introduction: Osteochondroma is the most common benign tumor of bone. Tumors are metaphyseal in origin and commonly involve distal femur, proximal tibia, and proximal fibula in the lower extremity. Osteochondroma located at proximal fibula can change the normal path of nerves and it may lead to the compression of vessels or peroneal nerve, leading to paralysis. Case Report: We are reporting a case of an 18-year-old female with proximal fibular osteochondroma causing splitting of common peroneal nerve without any neuropathy. Conclusion: We strive to make the surgeons aware that, when removing osteochondroma located at proximal fibula, care should be taken to identify the entire nerve at the site of lesion before the removal as a procedure done in a hurry in such a case can cause irreversible damage to the patient.

Exploring the Impact of Legislation Aiming to Ban Gender-Affirming Care on Pediatric Endocrine Providers: A Mixed-Methods Analysis.

Context: Access to gender-affirming medical care is associated with better mental health outcomes in transgender and gender diverse youth. In 2021 and 2022, legislation aiming to ban gender-affirming medical care for youth was proposed in 24 states. Objective: This study aimed to (1) assess the impact of this legislation on pediatric providers based on legislative status of their state of practice and (2) identify the themes of concerns reported by them. Methods: A mixed-methods study was conducted via an anonymous survey distributed to pediatric endocrinology providers. Survey responses were stratified based on US state of practice, with attention to whether legislation aiming to ban gender-affirming care had been considered. Data were analyzed both quantitatively and qualitatively. Results: Of 223 respondents, 125 (56.0%) were currently providing gender-affirming medical care. A total of 103 (45.7%) respondents practiced in a state where legislation aiming to ban gender-affirming care had been proposed and/or passed between January 2021 to June 2022. Practicing in legislation-affected states was associated with negative experiences for providers including (1) institutional pressure that would limit the ability to provide care, (2) threats to personal safety, (3) concerns about legal action being taken against them, (4) concerns about their career, and (5) institutional concerns about engagement with media. Major qualitative themes emerging for providers in legislation-affected states included safety concerns and the impact of laws on medical practice. Conclusion: This study suggests that legislation aiming to ban health care for transgender youth may decrease access to qualified providers in affected states.

Fostering Collective Intelligence in Human-AI Collaboration: Laying the Groundwork for COHUMAIN.

Artificial Intelligence (AI) powered machines are increasingly mediating our work and many of our managerial, economic, and cultural interactions. While technology enhances individual capability in many ways, how do we know that the sociotechnical system as a whole, consisting of a complex web of hundreds of human-machine interactions, is exhibiting collective intelligence? Research on human-machine interactions has been conducted within different disciplinary silos, resulting in social science models that underestimate technology and vice versa. Bringing together these different perspectives and methods at this juncture is critical. To truly advance our understanding of this important and quickly evolving area, we need vehicles to help research connect across disciplinary boundaries. This paper advocates for establishing an interdisciplinary research domain-Collective Human-Machine Intelligence (COHUMAIN). It outlines a research agenda for a holistic approach to designing and developing the dynamics of sociotechnical systems. In illustrating the kind of approach, we envision in this domain, we describe recent work on a sociocognitive architecture, the transactive systems model of collective intelligence, that articulates the critical processes underlying the emergence and maintenance of collective intelligence and extend it to human-AI systems. We connect this with synergistic work on a compatible cognitive architecture, instance-based learning theory and apply it to the design of AI agents that collaborate with humans. We present this work as a call to researchers working on related questions to not only engage with our proposal but also develop their own sociocognitive architectures and unlock the real potential of human-machine intelligence.

Adherence to Gender Affirming Hormone Therapy in Transgender Adolescents and Adults: A Retrospective Cohort Study.

CONTEXT: Transgender and gender diverse (TGD) individuals often seek gender-affirming hormone therapy (GAHT). While receipt of GAHT has been associated with improved well-being, the risk of GAHT discontinuation and its reasons are not well known. OBJECTIVE: There were two main objectives: (1) To investigate the proportion of TGD individuals who discontinue therapy after an average of 4 years (maximum 19 years) since GAHT initiation; and (2) to explore reasons for GAHT discontinuation. This was a retrospective cohort study at academic centers providing care to TGD adolescents and adults. TGD individuals prescribed estradiol or testosterone between January 1, 2000, and January 1, 2019, were included. GAHT continuation was ascertained using a 2-phase process. In phase 1, Kaplan-Meier survival analyses were used to examine likelihood of GAHT discontinuation and compare discontinuation rates by age and sex assigned at birth. In phase 2, reasons for stopping GAHT were investigated by reviewing records and by contacting study participants who discontinued therapy. The main outcome measures were incidence and determinants of GAHT discontinuation. RESULTS: Among 385 eligible participants, 231 (60%) were assigned male at birth and 154 (40%) were assigned female at birth. Less than one-third of participants (n = 121) initiated GAHT prior to their 18th birthday, constituting the pediatric cohort (mean age 15 years), and the remaining 264 were included in the adult cohort (mean age 32 years). In phase 1, 6 participants (1.6%) discontinued GAHT during follow-up, and of those only 2 discontinued GAHT permanently (phase 2). CONCLUSION: GAHT discontinuation is uncommon when therapy follows Endocrine Society guidelines. Future research should include prospective studies with long-term follow-up of individuals receiving GAHT.