Jacobs Institute of Women's Health
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In a model of parasite-mediated exhaustion, stem-like CD8 T cells differentiate into an unconventional intermediate effector memory subset
No full textCD8 T cell exhaustion has been reported in mice susceptible to Toxoplasma gondii infection. While the differentiation of CD8 exhausted subsets has been extensively reported, most of these studies have been conducted in chronic viral and cancer models. During chronic T. gondii infection, phenotypic and transcriptomic analyses of the polyclonal antigen-specific CD8 T cell response characterize 4 populations based on KLRG1 and CD62L expression. Pop1 (KLRG1+CD62Llo) bears the attributes of a terminal effector subset, and pop2 (KLRG1-CD62Llo) is similar to effector memory CD8 T cells. Akin to chronic viral infection and cancer systems, pop3 (KLRG1-CD62Lhi) exhibits the characteristics of stem-like progenitor CD8 T cells (high Tcf7, Slamf6, and Cxcr5 expression), whereas pop4 (KLRG1+CD62Lhi) closely resembles a transitory subset (elevated Tbx21, low Tcf1, and Tox expression). During chronic viral infection, the stem-like progenitor CD8 T cells transition into a terminally differentiated exhausted subset via an intermediate population. However, in our system, pop3 (KLRG1-CD62Lhi) generates pop4 (KLRG1+CD62Lhi), which does not convert into a conventional terminally differentiated exhausted subset but instead transitions into effector pop1 (KLRG1+CD62Llo). Notably, during the chronic phase of the infection, pop1 cannot retain its functionality, irrespective of its origin, which may hamper its ability to control reactivation. Our observations emphasize that the differentiation of exhausted CD8 T cells in non-viral infections, like chronic toxoplasmosis, follows a different pattern than established models and highlights the need to develop new immune strategies better tailored for a broad range of pathogens
ILAE neuroimaging task force highlight: Tuberous sclerosis complex-related epilepsy
No full textThe ILAE Neuroimaging Task Force publishes educational case reports that highlight basic aspects of neuroimaging in epilepsy consistent with the ILAE\u27s educational mission. Tuberous sclerosis complex (TSC) is a rare, complex, and multisystem autosomal dominant genetic disorder that arises from variations in the TSC1 or TSC2 genes. While characterized by a wide range of clinical manifestations, TSC commonly presents with epilepsy, which is a clinically challenging feature of the condition. Neuroimaging plays a pivotal role in the early diagnosis, screening, and long-term monitoring of TSC patients. CT serves as the first-line imaging tool in emergency settings; yet MRI is the primary diagnostic modality for TSC. In this report, we present two patients with TSC-related epilepsy and analyze their neuroimaging findings. We also address the diagnostic and therapeutic challenges faced by TSC patients with epilepsy
Telehealth Use in Medicaid: Implications for Quality Care for Individuals With ADHD and Tourette Syndrome
No full textThe expansion of telehealth during the COVID-19 pandemic transformed behavioral health care delivery, including for individuals with attention-deficit/hyperactivity disorder (ADHD) and Tourette syndrome (TS), conditions that require ongoing treatment and monitoring. We explored the implications of telehealth on the quality of care for Medicaid beneficiaries with ADHD and TS, highlighting the benefits, challenges, and policy considerations. Telehealth has increased access to behavioral health services, including for ADHD and TS, by reducing geographic and financial barriers to care. The expanded use of telehealth has allowed patients to more easily interact with health care providers, and it particularly benefits those with limited access to specialized care. However, challenges remain, such as concerns about stimulant misuse in online ADHD treatments and the limited privacy offered in home telehealth settings. Furthermore, disparities in broadband access may exacerbate existing inequalities in care. Despite telehealth\u27s potential to increase access to specialized care, the quality of telehealth provided is not guaranteed. Current quality measures for Medicaid telehealth services, especially for ADHD and TS, are insufficient. While some Medicaid programs have integrated telehealth into quality reporting, a need exists for more tailored measures that assess the unique needs of people with ADHD and TS. We recommend the development of quality measures for ADHD and TS, performance improvement projects for these conditions, better alignment of Medicaid managed care oversight, and research into the long-term outcomes of telehealth for care of people with ADHD and TS. Such efforts would support continued Medicaid telehealth expansion while ensuring high-quality care
Paracentesis complication rates and use of ultrasound: impact of a point-of-care ultrasound training course in the veterans affairs healthcare system
No full textBACKGROUND: Point-of-care ultrasound (POCUS) training courses have been shown to increase knowledge and skills among physicians, but few studies have examined their impact on clinical outcomes. We assessed the frequency of ultrasound usage and complication rates of paracentesis after implementing a POCUS training course in the Veterans Affairs (VA) health care system. METHODS: A retrospective observational study was conducted of VA medical centers that participated in a POCUS training course ( trained facilities ) versus matched control facilities. Rates of paracentesis performed in non-radiology settings with and without ultrasound guidance and procedural complications were collected from the VA corporate data warehouse (CPT and ICD-10 procedure and diagnosis codes) and pre- and post-course surveys of course participants. A best fit linear regression line was established for quarterly rates of each group and the y-intercept and slope of each line was compared. RESULTS: Data were compared from 16 trained versus 32 matched control facilities where 10,375 and 22,103 paracenteses were performed, respectively, from October 2015 to March 2025. At baseline, ultrasound guidance was used less frequently in trained versus matched control facilities (39% vs. 78.3%, p \u3c 0.0001). However, trained facilities demonstrated a greater quarterly increase in ultrasound use (1.20% vs. -0.14% per quarter, p \u3c 0.0001). By the end of the study, trained facilities surpassed control facilities in use of ultrasound guidance (84.6% vs. 73.0%, p \u3c 0.001). The overall complication rate was low (2.4 per 1,000 procedures) and there was no significant difference in trends between trained and matched control facilities. CONCLUSIONS: Participation in a national POCUS training course was associated with increased use of ultrasound guidance for paracentesis but not with statistically significant changes in complication rates. Further study is warranted to explore effect of POCUS training on procedural outcomes of paracentesis
Quality of postnatal care for mothers and neonates in Mexico: Insights from the maternal eCohort study
No full textOBJECTIVE: The study aimed to evaluate healthcare use during the postnatal period for mothers and their babies, the content of care received, mothers\u27 perceived quality of care, and the factors influencing these perceptions. METHODS: The study analyzed data from a postnatal survey conducted within the maternal eCohort at the Mexican Institute of Social Security (IMSS). The research involved 973 women aged 18-49 who were recruited following their first antenatal care visit with a family physician at 48 family medicine clinics across eight Mexican states. We described postnatal care (PNC) use, content of care and perceived quality and used Poisson multivariable regression analysis to investigate the factors influencing women\u27s perceptions of higher quality of care during PNC. RESULTS: 29.4% of women and 12.0% of infants had no postnatal care visits within the six weeks following hospital discharge. Among women who received PNC, 72.3% accessed services exclusively through IMSS, 17.7% utilized a combination of IMSS and other providers, and 10% relied solely on private providers. Infants received 82.4% of recommended content of care, compared to 66.7% for mothers. The median perceived quality of care among women was 25 points on a scale of 8-40. Key areas for improvement include enhancing awareness of the importance of postnatal consultations among health personnel and women, reducing waiting times, and improving the content and length of consultations. Factors associated with better perceived quality included being over 35, receiving better content of care for infants, and being treated by private providers, while lower education levels, prior pregnancies, and poor health were associated with lower perceived quality. CONCLUSION: Improvements are needed to ensure all women and infants receive comprehensive postnatal care and to enhance patient-perceived quality
The common cold is associated with protection from SARS-CoV-2 Infections
No full textBACKGROUND: Adults and children often respond differently to SARS-CoV-2 infection, with adults facing a higher risk of symptomatic and severe illness. We hypothesize that children\u27s protection from symptomatic SARS-CoV-2 may be due to more frequent respiratory viral infections, which prime their airway antiviral defenses. METHODS: Using case-cohort and case-control analyses in the Human Epidemiology and Response to SARS-CoV-2 cohort, we evaluated whether infection with common respiratory viruses protects against SARS-CoV-2 infections and investigated airway molecular mechanisms by which this protection is achieved. We tested 10,493 longitudinal nasal swabs from 1,156 participants for 21 respiratory pathogens. We performed RNA-sequencing on 147 swabs (N=144 participants) collected prior SARS-CoV-2 infection and 391 swabs (N=165 participants) during and before rhinovirus infection. RESULTS: Participants with rhinovirus infection in the previous 30 days were at 48% lower risk of SARS-CoV-2 infection (aHR:0.52, p=0.034). Among participants with SARS-CoV-2 infection, recent rhinovirus infection was associated with 9.6-fold lower SARS-CoV-2 viral load (p=0.0031). Higher pre-infection expression of 57 genes was associated with lower SARS-CoV-2 viral load, including 24 antiviral defense genes; 22 of these were induced by rhinovirus infections. Relative to adults, children expressed higher levels of the antiviral gene signature (p=0.014) and were at 2.2-fold increased risk for rhinovirus infections. CONCLUSIONS: Rhinovirus infections, which trigger increased expression of antiviral airway genes, are linked to a lower risk of SARS-CoV-2 infection. Frequent rhinovirus infections may enhance this protective gene profile, partially explaining why children experience milder SARS-CoV-2 infections compared to adults. TRIAL REGISTRATION NUMBER: NCT04375761
What is the clinical evidence to support off-label rapamycin therapy in healthy adults?
No full textLow dose rapamycin therapy has been proposed as a longevity candidate in healthy aging adults. We present a review of the evidence for low dose rapamycin and rapalog therapies in healthy human adults and model the findings of one cohort study using the PhenoAge model. Despite the preclinical evidence supporting the use of sirolimus to enhance mean and maximal lifespan, the data in humans have yet to establish that rapamycin, or its analogues, is a proven seno-therapeutic that can delay aging in healthy older adults. Rapamycin and rapalogs warrant further study with larger cohorts to better establish their contribution to human aging
Improving Zero-Shot Multiclass Classification for Narrative Reports from National Violent Death Reporting System
No full textThe natural language processing pipeline powered by the BART model is a popular zero-shot text classification system. While the standard approach for using this pipeline can achieve impressive accuracies in many multiclass classification tasks, we believed that there was still room to improve and developed an improved approach for that. Both approaches were used for the classification of narrative reports, and the results showed that the improved approach could increase the accuracies significantly over the standard approach. The improved approach is made general and can be applied to other use cases as well
Treatment Guidelines and Rehabilitation in Spinal Muscular Atrophy and Duchenne\u27s Muscular Dystrophy
No full textDuchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) are childhood-onset neuromuscular disorders with substantial morbidity and significant rehabilitation needs. Recent advancements, particularly gene-based therapies, have significantly altered the disease trajectory for both conditions, necessitating updated care guidelines. This review will delve into the pathogenesis of DMD and SMA, explore the latest disease-modifying treatments available for each, and comprehensively address the multifaceted rehabilitation needs across the spectrum of disease severity. The aim is to provide a comprehensive overview of current best practices to optimize functional outcomes and quality of life for individuals with DMD and SMA
Impact of rapid antibiotic susceptibility testing for Gram-negative bacteremia varies by pathogen type and resistance: a secondary analysis of the RAPIDS GN trial
No full textIn this secondary analysis of 386 subjects with Gram-negative bacteremia enrolled in the RAPIDS GN trial, rapid antibiotic susceptibility testing had a greater benefit on the management of bacteremia caused by antibiotic-resistant compared to antibiotic-susceptible isolates, especially for Escherichia coli, Klebsiella species, and Proteus species.IMPORTANCERapid blood culture diagnostics are costly, and their use has not demonstrated clear clinical benefit for patients with Gram-negative sepsis, possibly because prior trials did not enroll sufficient numbers of patients with antibiotic-resistant infections. This analysis of patients with sepsis previously enrolled in a randomized controlled clinical trial demonstrates that rapid susceptibility testing of bacteria from blood cultures had the greatest impact for patients with antibiotic-resistant infections. Specifically, after rapid testing results were reported, patients infected with resistant bacteria received appropriate antibiotic therapy more quickly than patients with susceptible bacteria. These findings highlight the need to evaluate blood culture diagnostics in areas with high antibiotic resistance where these diagnostics are likely to have the greatest impact