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Background: The transgender patient seeking transition from male to female suffers a significant stigma from the prominent male thyroid cartilage. Natal men and women may seek elective reduction of the “Adam's apple” as well. There are various techniques for performing chondrolaryngoplasty, but these techniques and their associated outcomes are poorly described in the literature. Methods: A literature review was performed for articles related to esthetic chondrolaryngoplasty. Data related to outcomes and complications were extracted. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The authors also present the case of a transgender 58 year-old male-to-female patient who underwent chondrolaryngoplasty. Results: Four case series, including 69 patients who had esthetic chondrolaryngoplasty, were identified that met inclusion criteria. Qualitative assessment of patient satisfaction was reported in two studies (n = 62), with a 98.4% satisfaction rate. The most common complications were odynophagia in 20.3% of patients, hoarseness in 36.2% of patients, and laryngospasm in 1.4% of patients. Of patients that had postoperative hoarseness, 96% had resolution within 20 days. In our patient's case, chondrolaryngoplasty was performed with a tracheal shave in combination with high-speed burring for fine contouring. The patient experienced hoarseness for 1 week postoperatively that self-resolved. Conclusion: Overall, chondrolaryngoplasty for reduction of the thyroid cartilage appears to be a safe and effective procedure. The complications that occurred in identified case series were mild and self-limiting. Although serious complications are certainly possible, we were not able to identify their occurrence in the literature. Recent modifications in chondrolaryngoplasty involve protecting the anterior commissure tendon to prevent iatrogenic voice modification. Keywords: Chondrolaryngoplasty, Facial feminization, Male-to-female, Tracheal shave, Transgender

High levels of lipoprotein(a) [Lp(a)] are causal for atherosclerotic cardiovascular disease (ASCVD). Lp(a) is the most prevalent inherited dyslipidemia and strongest genetic ASCVD risk factor. This risk persists in the presence of at target, guideline-recommended, LDL-C levels and adherence to lifestyle modifications. Epidemiological and genetic evidence supporting its causal role in ASCVD and calcific aortic stenosis continues to accumulate, although various facets regarding Lp(a) biology (genetics, pathophysiology, and expression across race/ethnic groups) are not yet fully understood. The evolving nature of clinical guidelines and consensus statements recommending universal measurements of Lp(a) and the scientific data supporting its role in multiple disease states reinforce the clinical merit to start population screening for Lp(a) now. There is a current gap in the implementation of recommendations for primary and secondary cardiovascular disease (CVD) prevention in those with high Lp(a), in part due to a lack of protocols for management strategies. Importantly, targeted apolipoprotein(a) [apo(a)]-lowering therapies that reduce Lp(a) levels in patients with high Lp(a) are in phase 3 clinical development. This review focuses on the identification and clinical management of patients with high Lp(a). Specifically, we highlight the clinical value of measuring Lp(a) and its use in determining Lp(a)-associated CVD risk by providing actionable guidance, based on scientific knowledge, that can be utilized now to mitigate risk caused by high Lp(a).

Background:. Chest masculinization surgery is increasing in prevalence. However, the ideal location of the nipple-areolar complex (NAC) is unknown. Our purpose was to determine the most aesthetically favorable male NAC position for use in chest masculinization through crowdsourcing. Methods:. Using Adobe Photoshop CC 2017, 8 locations for the NAC were created based on previous literature descriptions. Amazon Mechanical Turk was utilized as a crowdsourcing interface—respondents were asked to rank the top 3 most favorable and least favorable images. Analysis of variance with subsequent Tukey HSD was used for a statistical comparison of favorability scores for different NAC localizations. Values were considered significant with P < 0.05. Results:. Eight hundred nineteen respondents participated in the survey. NAC positions of Images C (mean score = 1.9222) and A (mean score = 1.7365) received higher favorability scores than those of Images D, E, F, G, and H (all P < 0.05). There were no significant differences between Images C and A (C versus A: P = 0.6412). NAC localizations from Images G (mean score = −2.0353) and H (mean score = −1.6908) received lower favorability scores than Images A, B, C, D, E, and F (all P < 0.05). There were no significant differences between Images G and H (P = 0.2279). Conclusions:. Most respondents preferred Images C and A, and few favored Images G and H, suggesting that lateral NAC placement is favored over more medial localizations. Additionally, both Images C and A utilize relatively inferior NAC placements. Therefore, we recommend a location inferior and lateral to the NAC. Ultimately, NAC localization during chest masculinization will be the result of shared decision-making between the patient and the surgeon to fulfill each patient’s aesthetic goals.

Oligodendrocyte precursor cells (OPCs) have long been regarded as progenitors of oligodendrocytes, yet recent advances have illuminated their multifaceted nature including their emerging immune functions. This review seeks to shed light on the immune functions exhibited by OPCs, spanning from phagocytosis to immune modulation and direct engagement with immune cells across various pathological scenarios. Comprehensive understanding of the immune functions of OPCs alongside their other roles will pave the way for targeted therapies in neurological disorders.

Introduction Traumatic rib fractures present a considerable risk to patient well-being, contributing to morbidity and mortality in trauma patients. To address the risks associated with rib fractures, evidence-based interventions have been implemented, including effective pain management, pulmonary hygiene, and early walking. Vancouver General Hospital, a level 1 trauma center in British Columbia, Canada, developed a comprehensive multidisciplinary chest trauma clinical practice guideline (CTCPG) to optimize the management of patients with rib fractures. This prospective cohort study aimed to assess the impact of the CTCPG on pain management interventions and patient outcomes.Methods The study involved patients admitted between January 1, 2021 and December 31, 2021 (post-CTCPG cohort) and a historical control group admitted between November 1, 2018 and December 31, 2019 (pre-CTCPG cohort). Patient data were collected from patient charts and the British Columbia Trauma Registry, including demographics, injury characteristics, pain management interventions, and relevant outcomes.Results Implementation of the CTCPG resulted in an increased use of multimodal pain therapy (99.4% vs 96.1%; p=0.03) and a significant reduction in the incidence of delirium in the post-CTCPG cohort (OR 0.43, 95% CI 0.21 to 0.80, p=0.0099). There were no significant differences in hospital length of stay, ICU (intensive care unit) days, non-invasive positive pressure ventilation requirement, ventilator days, pneumonia incidence, or mortality between the two cohorts.Discussion Adoption of a CTCPG improved chest trauma management by enhancing pain management and reducing the incidence of delirium. Further research, including multicenter studies, is warranted to validate these findings and explore additional potential benefits of the CTCPG in the management of chest trauma patients.Level of evidence IIb.

High levels of lipoprotein(a) [Lp(a)] are causal for atherosclerotic cardiovascular disease (ASCVD). Lp(a) is the most prevalent inherited dyslipidemia and strongest genetic ASCVD risk factor. This risk persists in the presence of at target, guideline-recommended, LDL-C levels and adherence to lifestyle modifications. Epidemiological and genetic evidence supporting its causal role in ASCVD and calcific aortic stenosis continues to accumulate, although various facets regarding Lp(a) biology (genetics, pathophysiology, and expression across race/ethnic groups) are not yet fully understood. The evolving nature of clinical guidelines and consensus statements recommending universal measurements of Lp(a) and the scientific data supporting its role in multiple disease states reinforce the clinical merit to start population screening for Lp(a) now. There is a current gap in the implementation of recommendations for primary and secondary cardiovascular disease (CVD) prevention in those with high Lp(a), in part due to a lack of protocols for management strategies. Importantly, targeted apolipoprotein(a) [apo(a)]-lowering therapies that reduce Lp(a) levels in patients with high Lp(a) are in phase 3 clinical development. This review focuses on the identification and clinical management of patients with high Lp(a). Specifically, we highlight the clinical value of measuring Lp(a) and its use in determining Lp(a)-associated CVD risk by providing actionable guidance, based on scientific knowledge, that can be utilized now to mitigate risk caused by high Lp(a).

Today, there exists a large number of different embedded hardware platforms for accelerating the inference of Deep Neural Networks (DNNs). To enable rapid application development, a number of prediction frameworks have been proposed to estimate the DNN inference latency on a wide range of hardware platforms. This work presents a novel smart padding benchmarking method, which allows the profiling of hardware platforms without requiring detailed per-layer reports. To mitigate the measurement inaccuracies inherent in the black-box approach, a confidence framework comprising three metrics has been developed. These metrics not only enhance the interpretation of prediction results but also significantly contribute to the refinement of the estimation framework itself, as they facilitate to improve the coverage of the training dataset for relevant layers and detect weaknesses in the training dataset. Empirical results demonstrate the method’s robustness, with average prediction errors minimized to below 10% for smart padding benchmarking-based ANNETTE predictions for the Jetson Xavier, NXP i.MX93, and NXP i.MX8M+.

ObjectiveTo identify, quantify and compare clinical and concurrent imaging findings of occipital hypoplasia (OH), syringomyelia (SM) and atlanto-occipital overlapping (AO) in dogs with or without brachycephaly.MethodsA focused systematic search for literature was performed in the Web of Science™, PubMed and Google Scholar databases. Both authors screened and classified the identified articles using EndNote and appraised the articles using the Critical Appraisal Skills Program checklists. The main clinical and concurrent imaging features were extracted and evaluated for coexistence of OH, SM, AO, and other imaging findings.ResultsThirty-one articles were included in this minireview. For articles focusing on descriptions of OH, SM and AO, 249 dogs had at least one of these conditions, and 3 of these 249 dogs (1%) had coexistence of all three conditions. For articles focusing on descriptions of the dogs, OH, SM, and AO were identified in 552/19/11/11, 574/2/0/6, and 100/0/0/0 small brachycephalic, small non-brachycephalic, large brachycephalic, and large non-brachycephalic breeds, respectively. For all small brachycephalic dogs, the percentages of affected animals were 40% for OH (p = 0.01), 42% for SM (p

NSG (NOD/Scid IL2Rγnull) mice reconstituted with PBMCs donated by patients with ulcerative colitis or Crohn’s disease highly reflect the respective pathological phenotype. To determine whether these findings could be applicable to atopic dermatitis (AD) and psoriasis vulgaris (PV), PBMCs isolated from patients with AD and PV were first subjected to immunological profiling. Subsequently, NSG mice were reconstituted with these PBMCs. Hierarchical clustering and network analysis revealed a distinct profile of patients with AD and PV with activated CD4+ T cells (CD69, CD25) occupying a central position in the AD network and CD4+ CD134+ cells acting as the main hub in the PV network. After dermal application of DMSO, both NSG mice reconstituted with PBMCs from donors with AD (ie, NSG-AD mice) and NSG mice reconstituted with PBMCs from donors with PV (ie, NSG-PV mice) exhibited increased clinical, skin, and histological scores. Immunohistochemical analysis, frequencies of splenic human leukocytes, and cytokine expression levels indicated that CD4+ CD69+ cells, M1 and TSLP receptor–expressing monocytes, switched B cells, and monocyte chemoattractant protein 3 were the driving factors of inflammation in NSG-AD mice. In contrast, inflammation in NSG-PV mice was characterized by an increase in fibroblasts in the epidermis, frequencies of CD1a-expressing monocytes, and IL-17 levels. Therefore, the pathological phenotypes of NSG-AD mice and NSG-PV mice differ and partially reflect the respective human diseases.

Abstract Background Dilated cardiomyopathy (DCM) is a life-threatening heart disease and a common cause of heart failure due to systolic dysfunction and subsequent left or biventricular dilatation. A significant number of cases have a genetic etiology; however, as a complex disease, the exact genetic risk factors are largely unknown, and many patients remain without a molecular diagnosis. Methods We performed GWAS followed by whole-genome, transcriptome, and immunohistochemical analyses in a spontaneously occurring canine model of DCM. Canine gene discovery was followed up in three human DCM cohorts. Results Our results revealed two independent additive loci associated with the typical DCM phenotype comprising left ventricular systolic dysfunction and dilatation. We highlight two novel candidate genes, RNF207 and PRKAA2, known for their involvement in cardiac action potentials, energy homeostasis, and morphology. We further illustrate the distinct genetic etiologies underlying the typical DCM phenotype and ventricular premature contractions. Finally, we followed up on the canine discoveries in human DCM patients and discovered candidate variants in our two novel genes. Conclusions Collectively, our study yields insight into the molecular pathophysiology of DCM and provides a large animal model for preclinical studies.

In the past, feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) was considered fatal. Today, highly efficient drugs, such as GS-441524, can lead to complete remission. The currently recommended treatment duration in the veterinary literature is 84 days. This prospective randomized controlled treatment study aimed to evaluate whether a shorter treatment duration of 42 days with oral GS-441524 obtained from a licensed pharmacy is equally effective compared to the 84-day regimen. Forty cats with FIP with effusion were prospectively included and randomized to receive 15 mg/kg of GS-441524 orally every 24h (q24h), for either 42 or 84 days. Cats were followed for 168 days after treatment initiation. With the exception of two cats that died during the treatment, 38 cats (19 in short, 19 in long treatment group) recovered with rapid improvement of clinical and laboratory parameters as well as a remarkable reduction in viral loads in blood and effusion. Orally administered GS-441524 given as a short treatment was highly effective in curing FIP without causing serious adverse effects. All cats that completed the short treatment course successfully were still in complete remission on day 168. Therefore, a shorter treatment duration of 42 days GS-441524 15 mg/kg can be considered equally effective.

Abstract Argumentation is crucial to fostering scientific reasoning and problem-solving in science education. However, researchers and teachers still report problems facilitating argumentation in the classroom. This may be influenced by the design of the corresponding professional development programs (PDPs) and the focus of the underlying research. To describe the state of the research regarding science teacher PDPs on facilitating argumentation, we systematically reviewed publications from the last 20 years in terms of their design, with selected low- and high-inference characteristics, for example, in terms of the addressed professional competence and the argumentation framework. The results illustrate a broad spectrum of teacher PDPs on argumentation in terms of formal-structural aspects (e.g., sample size) and interests (e.g., methodology). We found, for example, that pre-service teachers’ argumentation PDPs are less frequent than in-service teachers’ argumentation PDPs and that research rarely focuses on situation-specific competencies, such as professional vision or decision-making. Additionally, we report challenges in analyzing the argumentation framework and discuss possible reasons for this. We critically evaluate these and other findings, point to fruitful directions for further research and reviews, and inform practitioners of professional development of argumentation.

Objective: G-protein-coupled receptor (GPCR) kinases (GRKs) abrogate GPCR signaling by promoting receptor desensitization and internalization. Accumulating evidence suggests that GRK2 represents an important regulator of GPCR-mediated effects on systemic glucose metabolism, obesity, and insulin resistance. Despite the key role of the liver in maintaining euglycemia, the potential metabolic relevance of hepatic GRK2 has yet to be examined. Thus, the goal of this study was to explore the potential role of hepatic GRK2 in maintaining glucose homeostasis and other key metabolic functions. Methods: To address this question, we generated mice that showed a ∼90% reduction in GRK2 protein expression selectively in hepatocytes (Hep-GRK2-KO mice) and subjected these mice, together with their control littermates, to systematic metabolic phenotyping studies. Results: We found that Hep-GRK2-KO mice maintained on regular chow did not differ significantly from their control littermates in glycemia, glucose tolerance, insulin sensitivity, in vivo gluconeogenesis, and glucagon-induced hyperglycemia. We obtained similar findings when we analyzed Hep-GRK2-KO mice and control littermates consuming an obesogenic high-fat diet. Likewise, plasma levels of insulin, glucagon, free fatty acids, and ketone bodies remained unaffected by the lack of hepatocyte GRK2. The same was true when we examined the expression levels of key genes regulating hepatic glucose and fatty acid metabolism. Conclusion: In summary, our data suggest that hepatocyte GRK2 is dispensable for systemic glucose homeostasis and other key metabolic functions in both lean and obese mice. This finding suggests that drug development efforts aimed at inhibiting GRK2 to improve impaired glucose homeostasis and insulin sensitivity need to focus on other metabolically important tissues.

The article deals with the pedagogical content knowledge of mathematical modelling as part of the professional competence of pre-service teachers. With the help of a test developed for this purpose from a conceptual model, we examine whether this pedagogical content knowledge can be promoted in its different facets--especially knowledge about modelling tasks and about interventions--by suitable university seminars. For this purpose, the test was administered to three groups in a seminar for the teaching of mathematical modelling: (1) to those respondents who created their own modelling tasks for use with students; (2) to those trained to intervene in mathematical modelling processes; and (3) participating students who are not required to address mathematical modelling. The findings of the study--based on variance analysis--indicate that certain facets (knowledge of modelling tasks, modelling processes, and interventions) have increased significantly in both experimental groups but to varying degrees. By contrast, pre-service teachers in the control group demonstrated no significant change to their level of pedagogical content knowledge.

Therapeutic Area: ASCVD/CVD Risk Reduction Background: Elevated lipoprotein(a) [Lp(a)] is the most common inherited dyslipidemia leading to an increased risk of atherosclerotic cardiovascular disease (ASCVD). Several cohort studies have reported elevated Lp(a) prevalence in the general population; however, there is a paucity of data in those with established ASCVD. This sub-analysis of the Lp(a)HERITAGE study (NCT03887520) assessed Lp(a) levels in United States (US) participants with ASCVD, stratified by race, ethnicity, and sex. Methods: This cross-sectional study assessed the prevalence of elevated Lp(a) in adult participants (18–80 years of age) with a history of myocardial infarction or ischemic stroke ≥3 months to ≤10 years prior to enrollment (April 2019–July 2021) or symptomatic peripheral artery disease, across 192 US sites. Lp(a) and low-density lipid-cholesterol (LDL-C) levels were obtained using US central laboratory or historical data. Results: In total, 8,295 US participants were enrolled. The sub-analysis included 7,679 participants with Lp(a) measured in nmol/L, of which 66.4% were male, 80.5% were White, 16.9% were Black, and 8.0% had Hispanic ethnicity. Compared with the overall population, median Lp(a) was >2.5-fold higher in Black participants (132.0 vs 52.1 nmol/L) and was 21.8% lower in Hispanic participants (40.7 vs 52.1 nmol/L); in females, median Lp(a) levels were >1.5-fold higher than in male participants (69.4 vs 45.6 nmol/L) (Table). Overall, 33.3% of participants had Lp(a) ≥125 nmol/L. Prevalence of Lp(a) ≥125 nmol/L was highest among Black participants (52.0%) and lowest among Hispanic participants (25.6%); a greater proportion of females had Lp(a) ≥125 nmol/L compared with males (38.9% vs 30.4%) (Table). Conclusions: In the Lp(a)HERITAGE study, 33.3% of US participants with established ASCVD had Lp(a) levels ≥125 nmol/L. Compared with the overall population, the proportion of patients with Lp(a) ≥125 nmol/L was higher in Black (52.0%) and female (38.9%) participants and was lower in Hispanic participants (25.6%). These findings support more aggressive Lp(a) screening strategies among patients with established ASCVD, particularly female or Black patients. Furthermore, elevated Lp(a) levels can be used to inform the intensification of lifestyle and other risk factor management in clinical practice and may have implications for potential future therapies targeting Lp(a).