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INTRODUCTION: Anatomic total shoulder arthroplasty (TSA) is a common surgical intervention for various shoulder pathologies, predominantly glenohumeral osteoarthritis. While generally considered safe and effective, complications remain a challenge. Short stem implants, aim to preserve bone stock and reduce complications. However, concerns about a specific short stem implant (Univers Apex; Arthrex, Naples, FL, USA) have surfaced due to high reported rates relatively early aseptic loosening. METHODS: This retrospective study analyzed 116 consecutive TSA patients with Univers Apex implants from 2004 to 2022. 15 revision cases were assessed for radiographic loosening, and explanted implants were examined for damage using a 0-3 scale. Histopathological analysis evaluated cellular responses to wear debris. RESULTS: Of the patients, 13% (15/116) required revision at 23.2 months on average. A distinct radiographic loosening pattern was identified, with humeral component subsidence and thinning of the proximal humeral cortex. Histopathology revealed a robust inflammatory response to wear debris, with a potential association between macrophage infiltration, hinge damage, and polyethylene wear. CONCLUSION: This study reveals a notable rate of early aseptic humeral loosening with the Univers Apex short stem implant, emphasizing concerns raised in previous reports and providing a potential explanation for the high rate of early failure. Surgeons should exercise caution and closely monitor patients with this implant design.
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Introduction: Patient encounters perceived to be challenging are common and contribute to both suboptimal patient health outcomes and provider burnout. A trauma-informed care (TIC) approach to these encounters is critical, as many of the characteristics associated with challenging patient encounters can be linked to a history of trauma exposure. Methods: Our team created and delivered a 1-hour synchronous virtual session intended to bolster provider knowledge of TIC principles and their application to challenging adolescent encounters. Participants were all faculty and staff engaged in pediatric primary care at an urban academic center, including physicians, nurse practitioners, psychologists, and social workers. The content was rooted in adult learning principles and included didactic components anchored to case-based learning with facilitated group discussions and opportunities for reflection. We used paired pre- and postsession self-assessments of provider knowledge, confidence, and practice related to TIC using Likert-scale and free-text questions. Descriptive statistics and a paired t test were used to determine the impact of the session on these metrics. Results: In 24 paired surveys, there were statistically significant increases (p ≤ .001) in participant perceived knowledge, confidence, and practice, with 100% of participants having a statistically significant improvement in one or more of these domains. There were also strongly positive Likert-scale and free-text responses regarding content relevance and delivery. Discussion: We demonstrate that a brief session can create improvement in pediatric providers' perceived knowledge about the application of TIC principles to challenging adolescent encounters as well as confidence in their ability to put these into practice.
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Pediatras , Humanos , Adolescente , Encuestas y Cuestionarios , Pediatras/psicología , Desarrollo de Personal/métodos , Femenino , Masculino , Pediatría/métodos , Heridas y Lesiones/terapiaRESUMEN
BACKGROUND AND OBJECTIVES: To understand the challenges and facilitators of a successful academic neurology research career broadly and to identify gender-based disparities specifically. METHODS: In 2019, participants self-identifying as researchers, preregistered for the American Academy of Neurology (AAN) Annual Meeting, ≥7 years out of residency, and authors of ≥1 AAN meeting abstract submission (2006-2009) were selected to participate in the qualitative study (purposeful sampling strategy). To increase diversity, 15 participants were invited by members involved in the AAN until interviews were complete. The AAN at the time of the study asked gender using sex-based terms. Participants were asked predetermined and open-ended questions. Themes were generated using a flexible coding methodology. RESULTS: Sixty neurologists (31 women, 29 men) participated in the focus groups and individual interviews. Six predetermined domains relevant to a successful neurology research career were explored: success definitions, facilitators, barriers, biases and harassment, mitigation strategies, and participant recommendations. Gender-based differences were noted during discussions focused on barriers and biases and harassment. Lack of women mentors, under-representation of women in senior faculty positions, and competing responsibilities when children are young were identified as barriers to women's success. Participants acknowledged that known gender disparities in compensation, academic promotion, and publications disproportionately affect women. Women shared more experiences of bias and harassment. Some men felt that gender-based biases were minimal to nonexistent. Participants shared their recommendations on ways to mitigate gender disparities and pursue a neurology research career. Leadership involvement locally and nationally in advocating and implementing change outside academic institutions was also mentioned as being valuable. DISCUSSION: Our findings may not be generalizable to academic neurologists outside the United States. Women academic neurology researchers experienced disparities across several domains affecting success: lower compensation, fewer women mentors, bias, and harassment. Women are less likely to be promoted, have less research success, and job satisfaction. Shared experiences of bias and harassment among women neurology researchers indicate continuing opportunity for education among departments and colleagues for preventive measures. These qualitative results indicate gender disparities among US-based neurology researchers and highlight the importance of the continued need to work toward equality and equity in disparate gender-related issues in the careers of neurology researchers.
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Neurología , Investigación Cualitativa , Sexismo , Humanos , Femenino , Masculino , Adulto , Médicos Mujeres , Mentores , Neurólogos , Persona de Mediana Edad , Docentes MédicosRESUMEN
Background: There is evidence for a significant excess of kinetic upper limb tremor in non-FXTAS female FMR1 premutation carriers. The present study explores the possibility that this tremor is associated with various other features reminiscent of those occurring in syndromic FXTAS. Sample/methods: This study analyzed the data from an Australian cohort of 48 asymptomatic premutation women. We utilized spiral drawings from CRST, representing action tremor; the CRST total tremor; and ICARS- kinetic tremors/cerebellar ataxia scales. Cognitive tests (involving executive functioning) included SDMT, TMT, two subtests of the WAIS-III: MR and Similarities. Spearman Rank correlations assessed the relationships between the above measures, and the Chi-square tested hypothesis about the association between the white matter hyperintensities (wmhs) in the splenium of corpus callosum assessed from MR images and spiral drawings scores. Results: The spiral drawing scores were significantly correlated with all three non-verbal cognitive test scores, and with the CRST scores; the latter correlated with all four cognitive test measures. Similarities (verbal) scores correlated with CRST, ICARS, and with the remaining cognitive scores. Ordered spiral scores' categories were significantly associated with the degree of splenium involvement. Conclusion: This study showed that, in non-FXTAS premutation female carriers, sub-symptomatic forms of kinetic tremor were associated with a broader motor, and cognitive (especially executive) dysfunction.
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Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/etnología , Población Negra , Masculino , FemeninoRESUMEN
The use of highly crosslinked ultra-high molecular weight polyethylene (XLPE) has significantly reduced the volumetric wear of acetabular liners, thereby reducing the incidence of osteolysis. However, contemporary components tend to generate smaller wear particles, which can no longer be identified using conventional histology. This technical limitation can result in imprecise diagnosis. Here, we report on two uncemented total hip arthroplasty cases (~7 years in situ) revised for periprosthetic fracture of the femur and femoral loosening, respectively. Both liners exhibited prominent wear. The retrieved pseudocapsular tissue exhibited a strong macrophage infiltration without microscopically identifiable polyethylene particles. Yet, using Fourier-transform infrared micro-spectroscopic imaging (FTIR-I), we demonstrated the prominent intracellular accumulation of polyethylene debris in both cases. This study shows that particle induced osteolysis can still occur with XLPE liners, even under 10 years in situ. Furthermore, we demonstrate the difficulty of determining the presence of polyethylene debris within periprosthetic tissue. Considering the potentially increased bioactivity of finer particles from XLPE compared to conventional liners, an accurate detection method is required, and new histopathological hallmarks of particle induced osteolysis are needed. FTIR-I is a great tool to that end and can help the accurate determination of foreign body tissue responses.
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Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Falla de Prótesis , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Prótesis de Cadera/efectos adversos , Femenino , Polietilenos/química , Osteólisis/etiología , Osteólisis/patología , Osteólisis/diagnóstico , Anciano , Masculino , Reoperación , Polietileno/química , Polietileno/efectos adversos , Persona de Mediana EdadRESUMEN
BACKGROUND: Despite the high frequency of tinnitus and its impact on wellbeing, little is known about its economic burden and no data to our knowledge are available on out-of-pocket (OOP) expenses. METHODS: In 2022 a survey was conducted on OOP costs of tinnitus. We enrolled 679 participants with slight, moderate and severe tinnitus in Italy, United Kingdom, Netherlands, Germany and Spain. We estimated annual OOP expenses for tinnitus-related healthcare visits, treatments, medications and alternative medicine practices. Prevalence of tinnitus in the general population, obtained from a representative survey we conducted in Europe in 2017-2018, was used to generalise costs for people with any tinnitus at the national level. RESULTS: OOP expenses were 368 (95% confidence intervals (CI), 78-690), 728 (95% CI, 316-1,288), and 1,492 (95% CI, 760-2,688) for slight, moderate, and severe tinnitus, respectively, with annual expenditure of 565 for people with any tinnitus: 209 for healthcare visits, 93 for treatments, 16 for drugs, 64 for hearing supporting systems and 183 for acupuncture, homeopathy and osteopathy. Individuals with slight, moderate, and severe tinnitus expressed a willingness to invest 1.6, 4.3, and 7.0 times their monthly income, respectively, to achieve complete relief from tinnitus. CONCLUSIONS: This study offers for the first time insights into the OOP expenses incurred by individuals with tinnitus. OOP expenses exhibited substantial variations based on severity status, accounting for more than 17 thousand million in the countries considered. In terms of financial burden, these findings align tinnitus to the recognised leading disabilities, including back pain and migraine.
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BACKGROUND: Modular dual mobility (DM) bearings have a junction between a cobalt chrome alloy (CoCrMo) liner and titanium shell, and the risk of tribocorrosion at this interface remains a concern. The purpose of this study was to determine whether liner malseating and liner designs are associated with taper tribocorrosion. METHODS: We evaluated 28 retrieved modular DM implants with a mean in situ duration of 14.6 months (range, 1 to 83). There were 2 manufacturers included (12 and 16 liners, respectively). Liners were considered malseated if a distinct divergence between the liner and shell was present on postoperative radiographs. Tribocorrosion was analyzed qualitatively with the modified Goldberg Score and quantitatively with an optical coordinate-measuring machine. An acetabular shell per manufacturer was sectioned for metallographic analysis. RESULTS: There were 6 implants (22%) that had severe grade 4 corrosion, 6 (22%) had moderate grade 3, 11 (41%) had mild grade 2, and 5 (18.5%) had grade 1 or no visible corrosion. The average volumetric material loss at the taper was 0.086 ± 0.19 mm3. There were 7 liners (25%) that had radiographic evidence of malseating, and all were of a single design (P = .01). The 2 liner designs were fundamentally different from one another with respect to the cobalt chrome alloy type, taper surface finish, and shape deviations. Malseating was an independent risk factor for increased volumetric material loss (P = .017). CONCLUSIONS: DM tribocorrosion with quantifiable material loss occurred more commonly in malseated liners. Specific design characteristics may make liners more prone to malseating, and the interplay between seating mechanics, liner characteristics, and patient factors likely contributes to the shell/liner tribocorrosion environment. LEVEL OF EVIDENCE: Level III.
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Artroplastia de Reemplazo de Cadera , Aleaciones de Cromo , Prótesis de Cadera , Diseño de Prótesis , Falla de Prótesis , Humanos , Corrosión , Artroplastia de Reemplazo de Cadera/instrumentación , Anciano , Persona de Mediana Edad , Femenino , Masculino , Anciano de 80 o más Años , Titanio , Adulto , Estudios RetrospectivosRESUMEN
FXTAS is a neurodegenerative disorder occurring in some Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene premutation carriers (PMCs) and is characterized by cerebellar ataxia, tremor, and cognitive deficits that negatively impact balance and gait and increase fall risk. Dual-tasking (DT) cognitive-motor paradigms and challenging balance conditions may have the capacity to reveal markers of FXTAS onset. Our objectives were to determine the impact of dual-tasking and sensory and stance manipulation on balance in FXTAS and potentially detect subtle postural sway deficits in FMR1 PMCs who are asymptomatic for signs of FXTAS on clinical exam. Participants with FXTAS, PMCs without FXTAS, and controls underwent balance testing using an inertial sensor system. Stance, vision, surface stability, and cognitive demand were manipulated in 30 s trials. FXTAS participants had significantly greater total sway area, jerk, and RMS sway than controls under almost all balance conditions but were most impaired in those requiring vestibular control. PMCs without FXTAS had significantly greater RMS sway compared with controls in the feet apart, firm, single task conditions both with eyes open and closed (EC) and the feet together, firm, EC, DT condition. Postural sway deficits in the RMS postural sway variability domain in asymptomatic PMCs might represent prodromal signs of FXTAS. This information may be useful in providing sensitive biomarkers of FXTAS onset and as quantitative balance measures in future interventional trials and longitudinal natural history studies.
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Ataxia , Síndrome del Cromosoma X Frágil , Equilibrio Postural , Temblor , Humanos , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/fisiopatología , Temblor/genética , Temblor/fisiopatología , Equilibrio Postural/fisiología , Masculino , Persona de Mediana Edad , Femenino , Ataxia/genética , Ataxia/fisiopatología , Anciano , Biomarcadores , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/metabolismo , Adulto , Síntomas ProdrómicosRESUMEN
OBJECTIVE: Mutations in the glucocerebrosidase (GBA1) gene and subthalamic nucleus deep brain stimulation (STN-DBS) are independently associated with cognitive dysfunction in persons with Parkinson's disease (PwP). We hypothesized that PwP with both GBA1 mutations and STN-DBS are at greater risk of cognitive dysfunction than PwP with only GBA1 mutations or STN-DBS, or neither. In this study, we determined the pattern of cognitive dysfunction in PwP based on GBA1 mutation status and STN-DBS treatment. METHODS: PwP who are GBA1 mutation carriers with or without DBS (GBA1+DBS+, GBA1+DBS-), and noncarriers with or without DBS (GBA1-DBS+, GBA1-DBS-) were included. Using the NIH Toolbox, cross-sectional differences in response inhibition, processing speed, and episodic memory were compared using analysis of variance with adjustment for relevant covariates. RESULTS: Data were available for 9 GBA1+DBS+, 14 GBA1+DBS-, 17 GBA1-DBS+, and 26 GBA1-DBS- PwP. In this cross-sectional study, after adjusting for covariates, we found that performance on the Flanker test (measure of response inhibition) was lower in GBA1+DBS+ PwP compared with GBA1-DBS+ PwP (P = 0.030). INTERPRETATION: PwP who carry GBA1 mutations and have STN-DBS have greater impaired response inhibition compared with PwP with STN-DBS but without GBA1 mutations. Longitudinal data, including preoperative scores, are required to definitively determine whether GBA1 mutation carriers respond differently to STN-DBS, particularly in the domain of response inhibition.
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Estimulación Encefálica Profunda , Enfermedad de Parkinson , Núcleo Subtalámico , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/terapia , Estudios Transversales , Glucosilceramidasa/genéticaRESUMEN
Cyberbullying has become a prominent risk for youth and an increasing concern for parents. To help parents reduce their child's cyberbullying risk, anti-bullying apps (ABAs)-mobile applications for identifying and preventing instances of cyberbullying-have been developed in recent years. Given that ABAs are an emerging technology, limited research has been conducted to understand the factors predicting parents' intentions to use them. Drawing on three interdisciplinary theoretical frameworks, a sample of parents in the U.S. recruited through Amazon Mechanical Turk completed an online survey to assess parents' knowledge of, attitudes about, and intentions to use ABAs. Participants also rated the importance of a range of ABA functions and provided information about their child's social media use and bullying history. A series of path analyses revealed that the importance parents placed on an app's ability to provide information about their child's cyberbullying risk predicted more positive attitudes toward ABAs and greater perceived usefulness of them. Stronger intentions to use ABAs were predicted by greater cyberbullying concern, greater importance of social recommendations, greater perceived usefulness, more positive attitudes toward the apps, and lower ratings of the importance of ease of use. These findings shed light on the factors predicting parents' intentions to use ABAs and the app features they view as most important. Crucial directions for future research and implications for anti-bullying efforts are discussed.
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The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5' untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death. Clinically, premutation carriers may exhibit a wide range of symptoms and phenotypes. Any of the problems associated with the premutation can appropriately be called FXPAC. Fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND) can fall under FXPAC. Understanding the molecular and clinical aspects of the premutation of the FMR1 gene is crucial for the accurate diagnosis, genetic counseling, and appropriate management of affected individuals and families. This paper summarizes all the known problems associated with the premutation and documents the presentations and discussions that occurred at the International Premutation Conference, which took place in New Zealand in 2023.
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Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Síndrome del Cromosoma X Frágil , Humanos , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/metabolismo , Mutación/genética , ARN Mensajero/metabolismo , Expansión de Repetición de Trinucleótido/genética , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/terapiaRESUMEN
BACKGROUND: An understanding of the genetic mechanisms underlying diseases in ancestrally diverse populations is an important step towards development of targeted treatments. Research in African and African admixed populations can enable mapping of complex traits, because of their genetic diversity, extensive population substructure, and distinct linkage disequilibrium patterns. We aimed to do a comprehensive genome-wide assessment in African and African admixed individuals to better understand the genetic architecture of Parkinson's disease in these underserved populations. METHODS: We performed a genome-wide association study (GWAS) in people of African and African admixed ancestry with and without Parkinson's disease. Individuals were included from several cohorts that were available as a part of the Global Parkinson's Genetics Program, the International Parkinson's Disease Genomics Consortium Africa, and 23andMe. A diagnosis of Parkinson's disease was confirmed clinically by a movement disorder specialist for every individual in each cohort, except for 23andMe, in which it was self-reported based on clinical diagnosis. We characterised ancestry-specific risk, differential haplotype structure and admixture, coding and structural genetic variation, and enzymatic activity. FINDINGS: We included 197â918 individuals (1488 cases and 196â430 controls) in our genome-wide analysis. We identified a novel common risk factor for Parkinson's disease (overall meta-analysis odds ratio for risk of Parkinson's disease 1·58 [95% CI 1·37-1·80], p=2·397â×â10-14) and age at onset at the GBA1 locus, rs3115534-G (age at onset ß=-2·00 [SE=0·57], p=0·0005, for African ancestry; and ß=-4·15 [0·58], p=0·015, for African admixed ancestry), which was rare in non-African or non-African admixed populations. Downstream short-read and long-read whole-genome sequencing analyses did not reveal any coding or structural variant underlying the GWAS signal. The identified signal seems to be associated with decreased glucocerebrosidase activity. INTERPRETATION: Our study identified a novel genetic risk factor in GBA1 in people of African ancestry, which has not been seen in European populations, and it could be a major mechanistic basis of Parkinson's disease in African populations. This population-specific variant exerts substantial risk on Parkinson's disease as compared with common variation identified through GWAS and it was found to be present in 39% of the cases assessed in this study. This finding highlights the importance of understanding ancestry-specific genetic risk in complex diseases, a particularly crucial point as the Parkinson's disease field moves towards targeted treatments in clinical trials. The distinctive genetics of African populations highlights the need for equitable inclusion of ancestrally diverse groups in future trials, which will be a valuable step towards gaining insights into novel genetic determinants underlying the causes of Parkinson's disease. This finding opens new avenues towards RNA-based and other therapeutic strategies aimed at reducing lifetime risk of Parkinson's disease. FUNDING: The Global Parkinson's Genetics Program, which is funded by the Aligning Science Across Parkinson's initiative, and The Michael J Fox Foundation for Parkinson's Research.
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Pueblo Africano , Enfermedad de Parkinson , Humanos , Población Negra/genética , Sitios Genéticos , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Desequilibrio de Ligamiento , Enfermedad de Parkinson/etnología , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple/genética , Pueblo Africano/genéticaRESUMEN
Background: Understanding the genetic mechanisms underlying diseases in ancestrally diverse populations is a critical step towards the realization of the global application of precision medicine. The African and African admixed populations enable mapping of complex traits given their greater levels of genetic diversity, extensive population substructure, and distinct linkage disequilibrium patterns. Methods: Here we perform a comprehensive genome-wide assessment of Parkinson's disease (PD) in 197,918 individuals (1,488 cases; 196,430 controls) of African and African admixed ancestry, characterizing population-specific risk, differential haplotype structure and admixture, coding and structural genetic variation and polygenic risk profiling. Findings: We identified a novel common risk factor for PD and age at onset at the GBA1 locus (risk, rs3115534-G; OR=1.58, 95% CI = 1.37 - 1.80, P=2.397E-14; age at onset, BETA =-2.004, SE =0.57, P = 0.0005), that was found to be rare in non-African/African admixed populations. Downstream short- and long-read whole genome sequencing analyses did not reveal any coding or structural variant underlying the GWAS signal. However, we identified that this signal mediates PD risk via expression quantitative trait locus (eQTL) mechanisms. While previously identified GBA1 associated disease risk variants are coding mutations, here we suggest a novel functional mechanism consistent with a trend in decreasing glucocerebrosidase activity levels. Given the high population frequency of the underlying signal and the phenotypic characteristics of the homozygous carriers, we hypothesize that this variant may not cause Gaucher disease. Additionally, the prevalence of Gaucher's disease in Africa is low. Interpretation: The present study identifies a novel African-ancestry genetic risk factor in GBA1 as a major mechanistic basis of PD in the African and African admixed populations. This striking result contrasts to previous work in Northern European populations, both in terms of mechanism and attributable risk. This finding highlights the importance of understanding population-specific genetic risk in complex diseases, a particularly crucial point as the field moves toward precision medicine in PD clinical trials and while recognizing the need for equitable inclusion of ancestrally diverse groups in such trials. Given the distinctive genetics of these underrepresented populations, their inclusion represents a valuable step towards insights into novel genetic determinants underlying PD etiology. This opens new avenues towards RNA-based and other therapeutic strategies aimed at reducing lifetime risk. Evidence Before this Study: Our current understanding of Parkinson's disease (PD) is disproportionately based on studying populations of European ancestry, leading to a significant gap in our knowledge about the genetics, clinical characteristics, and pathophysiology in underrepresented populations. This is particularly notable in individuals of African and African admixed ancestries. Over the last two decades, we have witnessed a revolution in the research area of complex genetic diseases. In the PD field, large-scale genome-wide association studies in the European, Asian, and Latin American populations have identified multiple risk loci associated with disease. These include 78 loci and 90 independent signals associated with PD risk in the European population, nine replicated loci and two novel population-specific signals in the Asian population, and a total of 11 novel loci recently nominated through multi-ancestry GWAS efforts.Nevertheless, the African and African admixed populations remain completely unexplored in the context of PD genetics. Added Value of this Study: To address the lack of diversity in our research field, this study aimed to conduct the first genome-wide assessment of PD genetics in the African and African admixed populations. Here, we identified a genetic risk factor linked to PD etiology, dissected African-specific differences in risk and age at onset, characterized known genetic risk factors, and highlighted the utility of the African and African admixed risk haplotype substructure for future fine-mapping efforts. We identified a novel disease mechanism via expression changes consistent with decreased GBA1 activity levels. Future large scale single cell expression studies should investigate the neuronal populations in which expression differences are most prominent. This novel mechanism may hold promise for future efficient RNA-based therapeutic strategies such as antisense oligonucleotides or short interfering RNAs aimed at preventing and decreasing disease risk. We envisage that these data generated under the umbrella of the Global Parkinson's Genetics Program (GP2) will shed light on the molecular mechanisms involved in the disease process and might pave the way for future clinical trials and therapeutic interventions. This work represents a valuable resource in an underserved population, supporting pioneering research within GP2 and beyond. Deciphering causal and genetic risk factors in all these ancestries will help determine whether interventions, potential targets for disease modifying treatment, and prevention strategies that are being studied in the European populations are relevant to the African and African admixed populations. Implications of all the Available Evidence: We nominate a novel signal impacting GBA1 as the major genetic risk factor for PD in the African and African admixed populations. The present study could inform future GBA1 clinical trials, improving patient stratification. In this regard, genetic testing can help to design trials likely to provide meaningful and actionable answers. It is our hope that these findings may ultimately have clinical utility for this underrepresented population.
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Recent studies have documented increases in anti-Asian hate throughout the COVID-19 pandemic. Yet relatively little is known about how anti-Asian content on social media, as well as positive messages to combat the hate, have varied over time. In this study, we investigated temporal changes in the frequency of anti-Asian and counter-hate messages on Twitter during the first 16 months of the COVID-19 pandemic. Using the Twitter Data Collection Application Programming Interface, we queried all tweets from January 30, 2020 to April 30, 2021 that contained specific anti-Asian (e.g., #chinavirus, #kungflu) and counter-hate (e.g., #hateisavirus) keywords. From this initial data set, we extracted a random subset of 1,000 Twitter users who had used one or more anti-Asian or counter-hate keywords. For each of these users, we calculated the total number of anti-Asian and counter-hate keywords posted each month. Latent growth curve analysis revealed that the frequency of anti-Asian keywords fluctuated over time in a curvilinear pattern, increasing steadily in the early months and then decreasing in the later months of our data collection. In contrast, the frequency of counter-hate keywords remained low for several months and then increased in a linear manner. Significant between-user variability in both anti-Asian and counter-hate content was observed, highlighting individual differences in the generation of hate and counter-hate messages within our sample. Together, these findings begin to shed light on longitudinal patterns of hate and counter-hate on social media during the COVID-19 pandemic.
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COVID-19 , Medios de Comunicación Sociales , Humanos , Odio , Pandemias , Recolección de DatosRESUMEN
Background: The Lane plate was one of the first widely used bone plates, utilized in the first decades of the twentieth century. Here we present the results of a retrieval analysis on a Lane plate, and a review of the history of these plates. Our patient underwent plating of her femur with a Lane plate in 1938. She developed a sciatic nerve palsy, managed surgically later that year by Dr. Arthur Steindler at the University of Iowa. Her femur healed, her nerve recovered, and she did well until 2020, at age 94, when she presented to the University of Iowa with a draining sinus that appeared to communicate with the plate. She underwent irrigation and debridement with hardware removal. The plate was sectioned, and its composition and structure characterized. Methods: We retrieved hard copies of the patient's archived medical records from 1938, which document in detail the treatments performed by Dr. Steindler. The plate was analyzed using scanning electron microscopy (SEM) to characterize the surface of the plate. A cross section was taken from the plate, and the composition of the alloy was determined using energy dispersive x-ray spectroscopy (EDS). A review of the literature surrounding early plating techniques was conducted. Results: Our patient recovered from her surgery and soon returned to her baseline state of health. Intraoperative cultures grew C. acnes. Analysis of the surface of the plate demonstrated significant corrosion, and the crystal structure seen on SEM suggested a strong alloy that is prone to corrosion. Analysis of the cross section with EDS demonstrated an alloy containing 94.9% iron, 1.7% aluminum, 1.2% chromium, and 1.1% manganese. Conclusion: The Lane plate was introduced around 1907 by Sir William Arbuthnot Lane, a British surgeon, and was one of the first widely used devices for the plating of fractures. Given that this patient was likely one of the last to be treated with a Lane plate, this may be the final opportunity for such a retrieval analysis. Level of Evidence: IV.