Jacobs Institute of Women's Health
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Circulating proteomic profiles are associated with type 2 diabetes in Asian populations - a longitudinal study
No full textCONTEXT: Type 2 diabetes (T2D) is a major global concern, with Asia at its epicenter in recent years. Proteins, products of gene transcription, serve as dynamic biomarkers for pinpointing perturbed pathways in disease development. Previous T2D proteomic association studies primarily focused on European populations. OBJECTIVE: The aim of this study was to investigate the relationship between plasma proteins and the incidence of T2D in Asian participants. METHODS: We examined the association of 4,775 plasma proteins with incident T2D in a Singapore multi-ethnic cohort of 1,659 Asian participants (539 cases and 1,120 controls) using logistic regression. We used two-sample Mendelian randomization and colocalization analysis to evaluate the causal relationship between proteins and T2D. RESULTS: Our analysis revealed 522 proteins that were associated with incident T2D after adjusting for age, sex, and ethnicity, and 17 proteins that remained significantly associated after adjusting for other T2D risk factors such as fasting glucose, waist circumference, and triglycerides. Among the 522 proteins associated with incident T2D, the change in 205 plasma proteins, observed in parallel with the development of T2D at baseline and six-years follow-up, were further associated with incident T2D. The associated proteins showed enrichment in neuron generation, glycosaminoglycan binding, and insulin-like growth factor binding. Two-sample Mendelian randomization analysis suggested three plasma proteins, GSTA1, INHBC, and FGL1, play causal roles in the development of T2D, with colocalization evidence supporting GSTA1 and INHBC. CONCLUSIONS: Our findings reveal plasma protein profiles linked to the onset of T2D in Asian populations, offering insights into the biological mechanisms of T2D development
Caregiver food allergy self-efficacy explains the relationship between perceived food allergy severity and burden
No full textOBJECTIVE: Caregiver perceived food allergy severity is associated with food allergy burden, while caregiver food allergy self-efficacy has been linked to improved quality of life for caregivers. This study examined the mediating effect of caregiver food allergy self-efficacy on the relationship between perceived food allergy severity and caregiver food allergy burden. METHODS: Caregivers of children diagnosed with IgE-mediated food allergy were recruited from pediatric allergy clinics to complete demographic and medical questionnaires, the Food Allergy Independent Measure-Parent Form, the Food Allergy Self-Efficacy Scale for Parents, and the Food Allergy Quality of Life-Parental Burden. Hayes\u27 PROCESS was utilized to test mediation analysis. The TREND checklist is available in the Supplementary Materials section. RESULTS: Analyses consisted of 94 caregivers of children (Mage = 11.72 years, 52.7% male, 34.0% Black). Caregiver food allergy self-efficacy mediated the relationship between perceived food allergy severity and caregiver food allergy burden, B = 0.16, SE = 0.07, CI (0.04-0.33). CONCLUSIONS: Caregiver food allergy self-efficacy may play an important role in food allergy psychosocial functioning. Interventions targeting self-efficacy could reduce caregiver food allergy burden. Future research should explore additional psychosocial and medical factors to better tailor food allergy interventions to the family\u27s unique needs
Head and Neck Paraganglioma in Pacak-Zhuang Syndrome
No full textHead and neck paragangliomas (HNPGLs) are typically slow-growing, hormonally inactive tumors of parasympathetic paraganglia. Inactivation of prolyl-hydroxylase domain-containing 2 protein causing indirect gain-of-function of hypoxia-inducible factor-2α (HIF-2α), encoded by EPAS1, was recently shown to cause carotid body hyperplasia. We previously described a syndrome with multiple sympathetic paragangliomas caused by direct gain-of-function variants in EPAS1 (Pacak-Zhuang syndrome, PZS) and developed a corresponding mouse model. We evaluated a cohort of patients with PZS (n = 9) for HNPGL by positron emission tomography, magnetic resonance imaging, and computed tomography and measured carotid body size compared to literature reference values. Three patients had imaging consistent with HNPGL, one of which warranted resection and was confirmed on histology. Three additional patients had carotid body enlargement (Z-score \u3e 2.0), and three had carotid artery malformations. Using high resolution ex vivo imaging and histology, we found that nine of ten adult mutant mice had carotid body tumors and six of eight had a paraganglioma on the cranio-caval vein, the murine homologue of the superior vena cava; these were also found in four of five mutant mice at post-natal day 8. These tumors and the one resected from a patient were positive for tyrosine hydroxylase, synaptophysin, and chromogranin A. Brown fat in a resected patient tumor carried the EPAS1 pathogenic variant. These findings 1) suggest HNPGL as a feature of PZS and 2) show that these pathogenic variants are sufficient to cause the development of these tumors, which we believe represents a continuous spectrum of disease starting from hyperplasia
Charcot as a collector and critic of the arts: Relationship of the \u27founder of neurology\u27 with various aspects of art
No full textIn his teaching, Charcot often used artistic representations from previous centuries to illustrate the historical developments of various conditions, particularly hysteria, mainly with the help of his pupil Paul Richer. Charcot liked to draw portraits and sketches of colleagues during boring faculty meetings and students\u27 examinations, including caricatures of himself and others, church sculptures, landscapes, soldiers, and so on. He also used this skill in his clinical and scientific work. He drew histological or anatomic specimens, as well as patients\u27 features and demeanor. His most daring artistic experiments were drawing under the influence of hashish. Charcot\u27s tastes in art were conservative; he displayed little interest for the avant-gardes of his time, including impressionism, or for contemporary musicians, such as César Franck or Hector Berlioz. The pamphleteer Léon Daudet described Charcot\u27s home as a pseudo-gothic kitsch accumulation of heteroclite pieces of furniture and materials. However, he taught medicine not only as a science but also as an art, a style that has now been almost universally forgotten
Associations of fire smoke and other pollutants with incident rheumatoid arthritis and rheumatoid arthritis-associated interstitial lung disease
No full textOBJECTIVE: Determine whether pollutants such as fire smoke-related particulate matter smaller than 2.5 microns (PM) are associated with incident rheumatoid arthritis (RA) and RA-associated interstitial lung disease (RA-ILD). METHODS: This case-control study used Veterans Affairs data 10/1/2009-12/31/2018. We identified incident RA and RA-ILD cases using validated algorithms, matching each case to up to 10 controls on age, gender, and VA enrollment year. We obtained pollutants including fire smoke PM, carbon monoxide, nitrogen oxides (NOx), ozone overall PM PM, and sulfur dioxide (SO) at least one year before index date. We fit conditional logistic regression models to estimate adjusted odds ratios (aOR) with 95% confidence intervals (CI) for incident RA and RA-ILD, adjusted for confounders. RESULTS: We identified 9,701 incident RA cases (mean age 65, 86% male), including 531 RA-ILD cases (mean age 69, 91% male), and 68,852 matched controls. Fire smoke PM was not associated with RA (aOR 1.07, 95% CI 0.92-1.23), but was associated with RA-ILD (aOR 1.98, 95% CI 1.08-3.62, per 1 μg/m). Increased levels of NOx were associated with RA (aOR 1.16, 95% CI 1.06-1.27, highest vs. lowest quartile). The highest quartiles of ozone (aOR 1.19, 95% CI 1.06-1.34) and PM (aOR 1.25, 95% CI 1.10-1.43) were associated with seronegative RA. Carbon monoxide, overall PM, and SO were not, or negatively, associated with RA and RA-ILD. CONCLUSION: Increased fire smoke PM was associated with RA-ILD, while NOx, ozone, and PM were associated with RA risk. Thus, air pollution may increase the risk of RA and RA-ILD
Evaluating an urgent care antibiotic stewardship intervention: a multi-network collaborative effort
No full textOBJECTIVE: Urgent care centers (UCCs) have reported high rates of antibiotic prescribing for acute respiratory tract infections. Prior UCC studies have generally been limited to single networks. Broadly generalizable stewardship efforts targeting common diagnoses are needed. This study examines the effectiveness of an antibiotic stewardship intervention in reducing inappropriate prescribing for bronchitis and viral upper respiratory tract infections (URTIs) in UCCs. DESIGN: A quality improvement study comparing inappropriate antibiotic prescribing rates in UCCs after the introduction of an antibiotic stewardship intervention. SETTING: Forty-nine UCCs in 27 different networks from 18 states, including 1 telemedicine site. PARTICIPANTS: Urgent care clinicians from a national collaborative of UCCs, all members of the Urgent Care Association. METHODS: The intervention included signing a commitment statement and selecting from 5 different intervention options during 3 plan-do-study-act cycles. The primary outcome was the percentage of urgent care encounters for viral URTIs or bronchitis with inappropriate prescribing, stratified by clinician engagement and diagnosis. A 3-month baseline and 9-month intervention period were compared using a regression model using a generalized estimating equation. RESULTS: Among 15,385 encounters, the intervention was associated with decreases in inappropriate antibiotic prescribing for bronchitis (48% relative decrease, aOR = 0.52; 95% CI, 0.33-0.83) and viral URTIs (33%, aOR = 0.67; 95% CI, 0.55-0.82) among actively engaged clinicians compared to baseline. The intervention did not result in significant changes for clinicians not actively engaged. CONCLUSIONS: This intervention was associated with reductions in inappropriate prescribing among actively engaged clinicians. Implementing stewardship interventions in UCCs may reduce inappropriate antibiotic prescriptions for common diagnoses; however, active clinician engagement may be necessary
Delayed diagnosis of multiple myeloma in a young patient: a call for vigilance in diagnosis
No full textMultiple myeloma is a rare haematologic malignancy, representing about 1-2% of all cancers and 17% of haematologic malignancies in the US, predominantly affecting older adults and more common in African Americans (AAs) and men. Light-chain multiple myeloma, a subtype accounting for 15% of multiple myeloma cases, often has a more aggressive clinical course. This case report discusses a rare case of an AA female in her early 30s, diagnosed with light-chain multiple myeloma following a pathological rib fracture. Initial symptoms were atypical, and diagnosis was delayed due to her young age and lack of common multiple myeloma signs, such as anaemia and hypercalcaemia. Treatment included induction chemotherapy and autologous stem cell transplant, leading to complete remission. This case underscores the need for heightened clinical suspicion and thorough investigation in young patients presenting with unexplained bone lesions, highlighting the diverse presentations and challenges in diagnosing multiple myeloma in younger populations
Do not let perfect be the enemy of good: the current reality of Bordetella testing
No full textDiagnosis of Bordetella pertussis is made by using polymerase chain reaction (PCR) to detect insertion sequence 481 (IS481). However, IS481 is found in both B. pertussis and Bordetella holmesii. In a recent study, Cole et al. (Microbiol Spectr 12:e00783-24. https://doi.org/10.1128/spectrum.00783-24) compared the accuracy of assays performed at two different commercial laboratories that used IS481 as a molecular target against a multiplex PCR assay performed at the Centers for Disease Control and Prevention (CDC) that can differentiate the different Bordetella species. The results demonstrated that the overall agreement among the assays from the commercial laboratories and the CDC was 85%. Only a small percentage (1.4%) of specimens positive for IS481 were identified as B. holmesii. This study suggests that PCR tests using IS481 as a target provide reliable diagnosis for pertussis. However, end users should recognize the limitations of PCR testing for pertussis including the inability to differentiate and monitor transmission of non-pertussis Bordetella species
Building a growing genomic repository for maternal and fetal health through the PING Consortium
No full textBACKGROUND: Prenatally transmitted viruses can cause severe damage to the developing brain. There is unexplained variability in prenatal brain injury and postnatal neurodevelopmental outcomes, suggesting disease modifiers. Of note, prenatal Zika infection can cause a spectrum of neurodevelopmental disorders, including congenital Zika syndrome. Currently, there is no preventative treatment or cure. The Prenatal Infection and Neurodevelopmental Genetics (PING) Consortium aims to identify modulators of brain injury and adverse neurodevelopmental outcomes for Zika and other prenatal viral infections. METHODS: The Consortium pools information from eight multi-site studies conducted at 23 research centers in six countries to build a growing clinical and genomic repository, which is being mined for modifiers of virally induced brain injury. Partners include Children\u27s National Hospital (USA), Instituto Nacional de Salud (Colombia), the Natural History of Zika Virus Infection in Gestation program (Brazil), Zika Instituto Fernandes Figueira (Brazil), the Centers for Disease Control and Prevention, and the National Institutes of Health. RESULTS: We have enrolled 4102 mothers and 3877 infants with 3063 biological samples and clinical data covering over 80 phenotypic fields and 5000 variables. Thus far, we have performed whole exome sequencing on 1226 participants. CONCLUSION: Here, we present the Consortium\u27s formation and overarching study design. IMPACT: The PING Consortium brings together investigators and institutions to determine the causes of virally induced brain injury and neurological deficits. The clinical and genomic repository, with data from over 8000 patients, will serve as a foundation for a variety of basic and clinical studies
Student perceptions of U.S. based school day physical activity best practices in relation to accelerometer-based sedentary behavior and activity
No full textOBJECTIVE: To examine associations between student perceptions of school physical activity best practices and accelerometer-based physical activity during school days. METHODS: The sample was 758 students in grades 3rd-4th or 6th-7th (female-58 %; 31 % Black/African American) from 33 schools across five school districts in a Mid-Atlantic state in the U.S. Students completed the Perceptions of the Environment at School survey to assess perceived implementation of 11 school physical activity best practices and wore an Actical ankle accelerometer for 7 days between 2017 and 2019. Accelerometer cutpoints were applied for percent time in sedentary, light, and moderate-vigorous physical activity (MVPA) during school hours. Adjusted mixed effects linear regression models were used to predict percent time in each physical activity category, with separate models for elementary and middle school. RESULTS: More best practices were perceived by elementary versus middle schoolers (sum score = 3.3 versus 1.5, p \u3c .01). For every additional best practice perceived, elementary schoolers spent 0.64 % less time in sedentary behavior (B = -0.62; SE = 0.27, p = .02), equivalent to ∼12 fewer minutes/week in sedentary behaviors, and 0.58 % more time in light activity (B = 0.58; SE = 0.25, p = .02; ∼10 more minutes/week). No associations observed for middle schoolers or MVPA. CONCLUSIONS: Few best practices were perceived as being implemented in school. Elementary schoolers who perceived more best practices spent more time in light activity and less in sedentary behavior, but this relationship was not found among middle schoolers. Future research should promote implementation of school physical activity best practices and examine the linkage between implementation, student perceptions, and behavior change. Clinical Trials, NCT03432715; Registered on 02/2/2018