المؤلفون: La Charite, Jaime, Tucker, Elizabeth W, Rosenberg, Julia, Young, Janine, Gupta, Nikita, Hoops, Katherine

المصدر: Laws. 12(1)

مصطلحات موضوعية: Clinical Research, Pediatric Research Initiative, Pediatric, Good Health and Well Being, child health, health disparities, immigration, children of immigrant families, detention, Criminology, Law

الوصف: Little is known of pediatric clinicians’ experiences with and approaches to taking care of immigrant children who have been in US custody. The objectives of this article are to (1) recognize the challenges facing pediatric clinicians in caring for immigrant children previously in custody, and (2) propose ways that healthcare and legal professionals can collaborate to optimize the wellbeing of formerly detained immigrant children. We identify themes by assessing answers to multiple choice and short responses from a national survey. These findings can help to identify current issues faced by both detained immigrant children and pediatric clinicians, and suggest approaches to addressing these issues.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7dr697zcTest

المؤلفون: Tucker, Elizabeth W., Ruiz-Bedoya, Camilo A., Mota, Filipa, Erice, Clara, Kim, John, de Jesus, Patricia, Jahdav, Ravindra, Bahr, Melissa, Flavahan, Kelly, Chen, Xueyi, Peloquin, Charles A., Freundlich, Joel S., Jain, Sanjay K.

المساهمون: National Institutes of Health

المصدر: International Journal of Antimicrobial Agents ; volume 63, issue 1, page 107048 ; ISSN 0924-8579

مصطلحات موضوعية: Pharmacology (medical), Infectious Diseases, Microbiology (medical), General Medicine

الإتاحة: https://doi.org/10.1016/j.ijantimicag.2023.107048Test
https://api.elsevier.com/content/article/PII:S0924857923003370?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0924857923003370?httpAccept=text/plainTest

المؤلفون: Ordonez, Alvaro A, Parker, Matthew FL, Miller, Robert J, Plyku, Donika, Ruiz-Bedoya, Camilo A, Tucker, Elizabeth W, Luu, Justin M, Dikeman, Dustin A, Lesniak, Wojciech G, Holt, Daniel P, Dannals, Robert F, Miller, Lloyd S, Rowe, Steven P, Wilson, David M, Jain, Sanjay K

المصدر: JCI Insight. 7(1)

مصطلحات موضوعية: Clinical Research, Infectious Diseases, Emerging Infectious Diseases, Antimicrobial Resistance, Biomedical Imaging, Bioengineering, Aetiology, 2.2 Factors relating to the physical environment, Infection, 4-Aminobenzoic Acid, Adult, Animals, Carbon Radioisotopes, Contrast Media, Female, Humans, Male, Methicillin-Resistant Staphylococcus aureus, Positron-Emission Tomography, Rabbits, Rats, Staphylococcal Infections, Tissue Distribution, Young Adult, Bacterial infections, Diagnostic imaging, Infectious disease

الوصف: Tools for noninvasive detection of bacterial pathogens are needed but are not currently available for clinical use. We have previously shown that para-aminobenzoic acid (PABA) rapidly accumulates in a wide range of pathogenic bacteria, motivating the development of related PET radiotracers. In this study, 11C-PABA PET imaging was used to accurately detect and monitor infections due to pyogenic bacteria in multiple clinically relevant animal models. 11C-PABA PET imaging selectively detected infections in muscle, intervertebral discs, and methicillin-resistant Staphylococcus aureus-infected orthopedic implants. In what we believe to be first-in-human studies in healthy participants, 11C-PABA was safe, well-tolerated, and had a favorable biodistribution, with low background activity in the lungs, muscles, and brain. 11C-PABA has the potential for clinical translation to detect and localize a broad range of bacteria.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1qg1f3v1Test

المؤلفون: Ordonez, Alvaro A, Tucker, Elizabeth W, Anderson, Carolyn J, Carter, Claire L, Ganatra, Shashank, Kaushal, Deepak, Kramnik, Igor, Lin, Philana L, Madigan, Cressida A, Mendez, Susana, Rao, Jianghong, Savic, Rada M, Tobin, David M, Walzl, Gerhard, Wilkinson, Robert J, Lacourciere, Karen A, Via, Laura E, Jain, Sanjay K

المصدر: The Journal of clinical investigation. 131(5)

مصطلحات موضوعية: Animals, Humans, Mycobacterium tuberculosis, Tuberculosis, Molecular Imaging, Biomarkers, Rare Diseases, Biodefense, Vaccine Related, Lung, Prevention, Orphan Drug, Emerging Infectious Diseases, Infectious Diseases, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, Infection, Immunology, Medical and Health Sciences

الوصف: Nearly 140 years after Robert Koch discovered Mycobacterium tuberculosis, tuberculosis (TB) remains a global threat and a deadly human pathogen. M. tuberculosis is notable for complex host-pathogen interactions that lead to poorly understood disease states ranging from latent infection to active disease. Additionally, multiple pathologies with a distinct local milieu (bacterial burden, antibiotic exposure, and host response) can coexist simultaneously within the same subject and change independently over time. Current tools cannot optimally measure these distinct pathologies or the spatiotemporal changes. Next-generation molecular imaging affords unparalleled opportunities to visualize infection by providing holistic, 3D spatial characterization and noninvasive, temporal monitoring within the same subject. This rapidly evolving technology could powerfully augment TB research by advancing fundamental knowledge and accelerating the development of novel diagnostics, biomarkers, and therapeutics.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/18g313x4Test

المؤلفون: Donovan, Joseph, Cresswell, Fiona V, Thuong, Nguyen Thuy Thuong, Boulware, David R, Thwaites, Guy E, Bahr, Nathan C, Aarnoutse, Rob E, Anderson, Suzanne TB, Bang, Nguyen D, Boyles, Tom, te Brake, Lindsey HM, Chandra, Satish, Chow, Felicia C, van Crevel, Reinout, Davis, Angharad G, Dian, Sofiati, Dooley, Kelly E, Figaji, Anthony, Ganiem, A Rizal, Garg, Ravindra Kumar, Gibb, Diana M, Hamers, Raph L, Hiep, Nguyen TT, Imran, Darma, Imron, Akhmad, Jain, Sanjay K, Jain, Sunil K, Kalita, Jayantee, Kumar, Rashmi, Kumar, Vinod, van Laarhoven, Arjan, Lai, Rachel P-J, Manesh, Abi, Marais, Suzaan, Mave, Vidya, Meintjes, Graeme, Meya, David B, Misra, Usha K, Modi, Manish, Ordonez, Alvaro A, Phu, Nguyen H, Pradhan, Sunil, Prasad, Kameshwar, Proust, Alize M, Ramakrishnan, Lalita, Rohlwink, Ursula, Ruslami, Rovina, Schoeman, Johannes F, Seddon, James A, Sharma, Kusum, Siddiqi, Omar, Solomons, Regan S, Thuong, Nguyen TT, van Toorn, Ronald, Tucker, Elizabeth W, Wasserman, Sean A, Wilkinson, Robert J

المصدر: Clinical Infectious Diseases. 71(8)

مصطلحات موضوعية: Rare Diseases, Tuberculosis, Infectious Diseases, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Good Health and Well Being, Diagnostic Tests, Routine, Humans, Molecular Diagnostic Techniques, Mycobacterium tuberculosis, Sensitivity and Specificity, Tuberculosis, Meningeal, Tuberculous Meningitis International Research Consortium, Ultra, Xpert, cerebrospinal fluid, diagnosis, tuberculous meningitis, Biological Sciences, Medical and Health Sciences, Microbiology

الوصف: The delayed diagnosis of tuberculous meningitis (TBM) leads to poor outcomes, yet the current diagnostic methods for identifying Mycobacterium tuberculosis in cerebrospinal fluid (CSF) are inadequate. The first comparative study of the new GeneXpert MTB/RIF Ultra (Xpert Ultra) for TBM diagnosis suggested increased sensitivity of Xpert Ultra. Two subsequent studies have shown Xpert Ultra has improved sensitivity, but has insufficient negative predictive value to exclude TBM. Collecting and processing large volumes of CSF for mycobacterial testing are important for optimal diagnostic test performance. But clinical, radiological, and laboratory parameters remain essential for TBM diagnosis and empiric therapy is often needed. We therefore caution against the use of Xpert Ultra as a single diagnostic test for TBM; it cannot be used to "rule out" TBM.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7f99n0w0Test

المؤلفون: Davis, Angharad G, Nightingale, Sam, Springer, Priscilla E, Solomons, Regan, Arenivas, Ana, Wilkinson, Robert J, Anderson, Suzanne T, Chow, Felicia C, Aarnoutse, Rob E, Anderson, Suzanne TB, Bahr, Nathan C, Bang, Nguyen D, Boulware, David R, Boyles, Tom, Brake, Lindsey HM te, Chandra, Satish, Cresswell, Fiona V, van Crevel, Reinout, Dian, Sofiati, Donovan, Joseph, Dooley, Kelly E, Figaji, Anthony, Ganiem, A Rizal, Garg, Ravindra Kumar, Gibb, Diana M, Hamers, Raph L, Hiep, Nguyen TT, Imran, Darma, Imron, Akhmad, Jain, Sanjay K, Jain, Sunil K, Jeejeebhoy, Byramee, Kalita, Jayantee, Kumar, Rashmi, Kumar, Vinod, van Laarhoven, Arjan, Lai, Rachel P-J, Manesh, Abi, Marais, Suzaan, Mave, Vidya, Meintjes, Graeme, Meya, David B, Misra, Usha K, Modi, Manish, Ordonez, Alvaro A, Phu, Nguyen H, Pradhan, Sunil, Prasad, Kameshwar, Proust, Alize M, Ramakrishnan, Lalita, Rohlwink, Ursula, Ruslami, Rovina, Schoeman, Johannes F, Seddon, James A, Sharma, Kusum, Siddiqi, Omar, Solomons, Regan S, Thuong, Nguyen TT, Thwaites, Guy E, van Toorn, Ronald, Tucker, Elizabeth W, Wasserman, Sean A

مصطلحات موضوعية: Biomedical and Clinical Sciences, Health Sciences, Neurosciences, Brain Disorders, Behavioral and Social Science, Mental health, Good Health and Well Being, Tuberculous Meningitis International Research Consortium, Functional, Neurobehavioural, Neurocognitive, Neurodevelopmental, Psychiatric, Tuberculous Meningitis, Biomedical and clinical sciences, Health sciences

الوصف: In those who survive tuberculous meningitis (TBM), the long-term outcome is uncertain; individuals may suffer neurocognitive, functional and psychiatric impairment, which may significantly affect their ability to lead their lives as they did prior to their diagnosis of TBM. In children who survive, severe illness has occurred at a crucial timepoint in their development, which can lead to behavioural and cognitive delay. The extent and nature of this impairment is poorly understood, particularly in adults. This is in part due to a lack of observational studies in this area but also inconsistent inclusion of outcome measures which can quantify these deficits in clinical studies. This leads to a paucity of appropriate rehabilitative therapies available for these individuals and their caregivers, as well as burden at a socioeconomic level. In this review, we discuss what is known about neurocognitive impairment in TBM, draw on lessons learnt from other neurological infections and discuss currently available and emerging tools to evaluate function and cognition and their value in TBM. We make recommendations on which measures should be used at what timepoints to assess for impairment, with a view to optimising and standardising assessment of neurocognitive and functional impairment in TBM research.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9kc307xdTest

المؤلفون: Imran, Darma, Hill, Philip C, McKnight, Jacob, van Crevel, Reinout, Aarnoutse, Rob E, Anderson, Suzanne TB, Bahr, Nathan C, Bang, Nguyen D, Boulware, David R, Boyles, Tom, Brake, Lindsey HM te, Chandra, Satish, Chow, Felicia C, Cresswell, Fiona V, Davis, Angharad G, Dian, Sofiati, Donovan, Joseph, Dooley, Kelly E, Figaji, Anthony, Ganiem, A Rizal, Garg, Ravindra Kumar, Gibb, Diana M, Hamers, Raph L, Hiep, Nguyen TT, Imron, Akhmad, Jain, Sanjay K, Jain, Sunil K, Jeejeebhoy, Byramee, Kalita, Jayantee, Kumar, Rashmi, Kumar, Vinod, van Laarhoven, Arjan, Lai, Rachel P-J, Manesh, Abi, Marais, Suzaan, Mave, Vidya, Meintjes, Graeme, Meya, David B, Misra, Usha K, Modi, Manish, Ordonez, Alvaro A, Phu, Nguyen H, Pradhan, Sunil, Prasad, Kameshwar, Proust, Alize M, Ramakrishnan, Lalita, Rohlwink, Ursula, Ruslami, Rovina, Schoeman, Johannes F, Seddon, James A, Sharma, Kusum, Siddiqi, Omar, Solomons, Regan S, Thuong, Nguyen TT, Thwaites, Guy E, van Toorn, Ronald, Tucker, Elizabeth W, Wasserman, Sean A, Wilkinson, Robert J

مصطلحات موضوعية: Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Infectious Diseases, Health Services, Tuberculosis, HIV/AIDS, Clinical Research, Rare Diseases, 8.1 Organisation and delivery of services, Health and social care services research, Infection, Good Health and Well Being, Tuberculous Meningitis International Research Consortium, cascade of care, health systems, meningitis, patient pathway analysis, tuberculosis, Biomedical and clinical sciences, Health sciences

الوصف: Meningitis is a relatively rare form of tuberculosis, but it carries a high mortality rate, reaching 50% in some settings, with higher rates among patients with HIV co-infection and those with drug-resistant disease. Most studies of tuberculosis meningitis (TBM) tend to focus on better diagnosis, drug treatment and supportive care for patients in hospital. However, there is significant variability in mortality between settings, which may be due to specific variation in the availability and quality of health care services, both prior to, during, and after hospitalization. Such variations have not been studied thoroughly, and we therefore present a theoretical framework that may help to identify where efforts should be focused in providing optimal services for TBM patients. As a first step, we propose an adjusted cascade of care for TBM and patient pathway studies that might help identify factors that account for losses and delays across the cascade. Many of the possible gaps in the TBM cascade are related to health systems factors; we have selected nine domains and provide relevant examples of systems factors for TBM for each of these domains that could be the basis for a health needs assessment to address such gaps. Finally, we suggest some immediate action that could be taken to help make improvements in services. Our theoretical framework will hopefully lead to more health system research and improved care for patients suffering from this most dangerous form of tuberculosis.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/39k9983fTest

المؤلفون: Travassos, Mark A., Rohlwink, Ursula K., Tucker, Elizabeth W.

المصدر: Frontiers in Neurology ; volume 14 ; ISSN 1664-2295

مصطلحات موضوعية: Neurology (clinical), Neurology

الإتاحة: https://doi.org/10.3389/fneur.2023.1198518Test

المؤلفون: Mota, Filipa, Ruiz-Bedoya, Camilo A., Tucker, Elizabeth W., Holt, Daniel P., De Jesus, Patricia, Lodge, Martin A., Erice, Clara, Chen, Xueyi, Bahr, Melissa, Flavahan, Kelly, Kim, John, Brosnan, Mary Katherine, Ordonez, Alvaro A., Peloquin, Charles A., Dannals, Robert F., Jain, Sanjay K.

المساهمون: U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases, U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute

المصدر: Nature Communications ; volume 13, issue 1 ; ISSN 2041-1723

مصطلحات موضوعية: General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary

الوصف: Pretomanid is a nitroimidazole antimicrobial active against drug-resistant Mycobacterium tuberculosis and approved in combination with bedaquiline and linezolid (BPaL) to treat multidrug-resistant (MDR) pulmonary tuberculosis (TB). However, the penetration of these antibiotics into the central nervous system (CNS), and the efficacy of the BPaL regimen for TB meningitis, are not well established. Importantly, there is a lack of efficacious treatments for TB meningitis due to MDR strains, resulting in high mortality. We have developed new methods to synthesize 18 F-pretomanid (chemically identical to the antibiotic) and performed cross-species positron emission tomography (PET) imaging to noninvasively measure pretomanid concentration-time profiles. Dynamic PET in mouse and rabbit models of TB meningitis demonstrates excellent CNS penetration of pretomanid but cerebrospinal fluid (CSF) levels does not correlate with those in the brain parenchyma. The bactericidal activity of the BPaL regimen in the mouse model of TB meningitis is substantially inferior to the standard TB regimen, likely due to restricted penetration of bedaquiline and linezolid into the brain parenchyma. Finally, first-in-human dynamic 18 F-pretomanid PET in six healthy volunteers demonstrates excellent CNS penetration of pretomanid, with significantly higher levels in the brain parenchyma than in CSF. These data have important implications for developing new antibiotic treatments for TB meningitis.

الإتاحة: https://doi.org/10.1038/s41467-022-35730-3Test
https://www.nature.com/articles/s41467-022-35730-3.pdfTest
https://www.nature.com/articles/s41467-022-35730-3Test

المؤلفون: Singh, Gabriela, Tucker, Elizabeth W., Rohlwink, Ursula K.

المصدر: Frontiers in Neurology ; volume 12 ; ISSN 1664-2295

مصطلحات موضوعية: Neurology (clinical), Neurology

الوصف: Central nervous system (CNS) infections remain a major burden of pediatric disease associated with significant long-term morbidity due to injury to the developing brain. Children are susceptible to various etiologies of CNS infection partly because of vulnerabilities in their peripheral immune system. Young children are known to have reduced numbers and functionality of innate and adaptive immune cells, poorer production of immune mediators, impaired responses to inflammatory stimuli and depressed antibody activity in comparison to adults. This has implications not only for their response to pathogen invasion, but also for the development of appropriate vaccines and vaccination strategies. Further, pediatric immune characteristics evolve across the span of childhood into adolescence as their broader physiological and hormonal landscape develop. In addition to intrinsic vulnerabilities, children are subject to external factors that impact their susceptibility to infections, including maternal immunity and exposure, and nutrition. In this review we summarize the current evidence for immune characteristics across childhood that render children at risk for CNS infection and introduce the link with the CNS through the modulatory role that the brain has on the immune response. This manuscript lays the foundation from which we explore the specifics of infection and inflammation within the CNS and the consequences to the maturing brain in part two of this review series.

الإتاحة: https://doi.org/10.3389/fneur.2021.805643Test