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SignificanceUnderstanding the impacts of urbanization and the associated urban land expansion on species is vital for informed urban planning that minimizes biodiversity loss. Predicting habitat that will be lost to urban land expansion for over 30,000 species under three different future scenarios, we find that up to 855 species are directly threatened due to unmitigated urbanization. Our projections pinpoint rapidly urbanizing regions of sub-Saharan Africa, South America, Mesoamerica, and Southeast Asia where, without careful planning, urbanization is expected to cause particularly large biodiversity loss. Our findings highlight the urgent need for an increased focus on urban land in global conservation strategies and identify high-priority areas for this engagement.
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Biodiversidade , Conservação dos Recursos Naturais , Ecossistema , Previsões , UrbanizaçãoRESUMO
To determine antimicrobial susceptibility of Neisseria gonorrhoeae, we analyzed phenotypes and genomes of 72 isolates collected in Cambodia in 2023. Of those, 9/72 (12.5%) were extensively drug resistant, a 3-fold increase from 2022. Genomic analysis confirmed expansion of newly emerging resistant clones and ongoing resistance emergence across new phylogenetic backbones.
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Antibacterianos , Gonorreia , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae , Organização Mundial da Saúde , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/genética , Camboja/epidemiologia , Humanos , Gonorreia/microbiologia , Gonorreia/epidemiologia , Gonorreia/tratamento farmacológico , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Filogenia , Masculino , Feminino , AdultoRESUMO
ABSTRACT: Congenital syphilis (CS) rates have risen in the United States since 2013. Prevention of CS requires testing and treatment of pregnant and pregnancy-capable persons at high risk for syphilis. We developed a CS Prevention Cascade to assess how effectively testing and treatment interventions reached pregnant persons with a CS outcome.
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Complicações Infecciosas na Gravidez , Sífilis Congênita , Sífilis , Gravidez , Feminino , Humanos , Estados Unidos/epidemiologia , Sífilis Congênita/epidemiologia , Sífilis Congênita/prevenção & controle , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Sífilis/diagnóstico , Sífilis/epidemiologia , Sífilis/prevenção & controleRESUMO
BACKGROUND: Prurigo nodularis (PN) is a pruritic skin disease characterized by multiple intensely itchy skin nodules in symmetrically distributed areas of the extremities. There are limited studies on the epidemiology and treatment pathways of PN, especially moderate-to-severe PN, from England. OBJECTIVES: To assess the epidemiology and treatment pathways of mild and moderate-to-severe PN in England. METHODS: This retrospective cohort study used data from the Clinical Practice Research Datalink and Hospital Episode Statistics in England. Adult patients (aged ≥ 18 years) with a PN-specific diagnosis code allocated any time between 1 April 2007 and 1 March 2019 (patient identification period) were selected. Patients were included if their first PN diagnostic code (index diagnosis date; IDD) was recorded during the identification period, with data available 6 months before and ≥ 12 months after the IDD. Patients were classified as having moderate-to-severe PN (MSPN) or mild PN (MiPN), based on the presence or absence of a prescription record, post-IDD, for either a systemic immunosuppressant or a gabapentinoid. Patients with MSPN and MiPN were matched 1 : 1 according to age, sex and IDD. Prevalence and incidence were calculated for each year from 2007 to 2019. Drugs prescribed post-IDD were analysed. RESULTS: A total of 8933 patients (MSPN, n = 2498; MiPN, n = 6435) were included in the study; 2462 patients with MiPN and 2462 with MSPN were included for the comparative analysis. The presence of atopic dermatitis, asthma and eosinophilic oesophagitis were significantly higher (all P < 0.001) in patients with MSPN compared with those with MiPN. The overall prevalence of cases of PN increased during the study period. The incidence rate also showed a similar trend. The rates of prescription of potent and super-potent topical corticosteroids (TCS), topical calcineurin inhibitors, first- and second-generation antihistamines, oral and injectable systemic corticosteroids, methotrexate, antidepressants and tacrolimus were significantly higher (all P < 0.001) in patients with MSPN compared with those with MiPN. CONCLUSIONS: The epidemiology of PN was consistent with that found in other European studies. Patients with MSPN received a significantly higher number of prescriptions for potent TCS and systemic drugs compared with patients with MiPN.
Prurigo nodularis is an itchy skin disease that can affect a person's daily life and sleep, and is often accompanied by other diseases. Skin ointments are used to treat the disease. If these are not effective, the disease is treated with oral medicine. The severity of prurigo nodularis is not well established. People with prurigo nodularis and treated with skin ointments are generally considered to have a milder form of the disease. Patients with severe disease most often require oral medicine that target the immune system. In England, there are no estimates of how often prurigo nodularis has affected the population over the last 10 years. In this study, we looked at cases of mild and moderate-to-severe prurigo nodularis in England and the treatments used by patients. We found that cases of prurigo nodularis (both mild and moderate-to-severe) increased during the study period, which was 2007 to 2019. Patients with the more severe form of the disease were more often treated with drugs that were not approved for treating it. Overall, our findings suggest that the number of patients with prurigo nodularis is increasing in England. A new and approved treatment option might be required to manage moderate-to-severe disease.
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Prurigo , Humanos , Prurigo/epidemiologia , Prurigo/tratamento farmacológico , Masculino , Feminino , Estudos Retrospectivos , Inglaterra/epidemiologia , Pessoa de Meia-Idade , Adulto , Prevalência , Incidência , Idoso , Imunossupressores/uso terapêutico , Bases de Dados Factuais , Adulto Jovem , Índice de Gravidade de Doença , Adolescente , Gabapentina/uso terapêutico , Padrões de Prática Médica/estatística & dados numéricosRESUMO
In response to an increase in HIV diagnoses among persons who inject drugs (PWID) in Kanawha County, West Virginia, West Virginia Bureau for Public Health and CDC conducted a qualitative assessment in Kanawha County to inform HIV outbreak response activities. Interviews with 26 PWID and 45 community partners were completed. Transcribed interviews were analyzed to identify barriers to accessing HIV prevention services among PWID using the risk environment framework. Participants identified numerous political, physical, social, and economic community-level barriers that influenced access to HIV prevention services among PWID. Political factors included low community support for syringe services programs (SSPs); physical factors included low SSP coverage, low coverage of HIV testing outreach events, low HIV preexposure prophylaxis availability, and homelessness; social factors included stigma and discrimination; economic factors included community beliefs that SSPs negatively affect economic investments and limited resources for HIV screening in clinical settings. Individual-level barriers included co-occurring acute medical conditions and mental illness. Community-level interventions, such as low-barrier one-stop shop models, are needed to increase access to sterile syringes through comprehensive harm reduction services.
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Usuários de Drogas , Infecções por HIV , Abuso de Substâncias por Via Intravenosa , Humanos , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , West Virginia/epidemiologia , Surtos de Doenças , Programas de Troca de AgulhasRESUMO
IV contrast media improve the diagnostic power of radiology examinations. These media include gadolinium-based contrast media and iron-oxide nanoparticles for MRI, iodinated contrast material for CT, microbubbles for ultrasound, and radiopharmaceuticals for nuclear medicine. As for all medications, contrast media carry risks, which may be heightened in the conditions of pregnancy and lactation. Radiologists must understand the potential risks from contrast media exposure to the pregnant patient, fetus, and nursing infant, as well as understand these administrations' impact on examinations' clinical utility. This article reviews the available literature on these media, along with key regulatory bodies' and professional societies' current recommendations for their use, in the settings of pregnancy and lactation. This knowledge should help radiologists make well-reasoned risk-benefit analyses regarding contrast media administration and provide informed consent discussions with pregnant and nursing patients in whom contrast media administration is being considered. This information and analysis can also assist facilities in designing policies and standard operating procedures of possible clinical benefit to the pregnant patient, fetus, or nursing infant, balancing contrast media exposure considerations versus augmented diagnostic capabilities.
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A simple and direct synthesis of 2,6-diiodophenylethanol building blocks through highly regioselective metalation (MIE)/oxirane SN2-type ring opening of 1,2,3-triiodobenzene is described. A significant impact of the nature of the R1 group on the reactivity of the reaction was discovered but not in terms of site-selectivity. The MIE quenching step is easily controlled by the use of slow-reacting electrophiles "oxiranes" providing solely the ortho-diiodinated homobenzylic alcohol derivatives (internal products) in excellent site-selectivity and with stereoretention. The reaction proceeded without any additives to activate the oxiranes and tolerated a wide range of substrates. The reaction of electron-deficient 1,2,3-triiodoarene systems and neutral oxiranes under the optimized conditions provided the highest isolated yields. The reaction is facile, scalable, efficient, general in scope, and generates handy precursors for further chemical manipulation. In silico interaction analysis revealed that compounds 7a, 7p, 7t and 7z established favourable interactions with the receptors IDO and TDO. Moreover, the molecular simulation results revealed stable dynamics, minimal internal fluctuations, tighter packing and more favourable dynamic features. Furthermore, the 7a-IDO reported a TBE of -26.22 ± 0.24 kcal mol-1, 7t-TDO reported a TBE of -46.66 ± 0.27 kcal mol-1, 7p-TDO reported a TBE of -48.02 ± 0.29 kcal mol-1 while 7z-TDO reported a TBE of -48.51 ± 0.28 kcal mol-1. This shows that these compounds potentially interact with IDO and TDO and consequently cause the inhibition of these targets. Moreover, the BFE results also revealed that this combination suggests that the gas-phase interactions between the components are favorable, but the solvation of the system is unfavorable. In the context of binding, it further means that the protein and ligand have attractive forces when in close proximity as seen in the gas phase, but when solvated, the system experiences an increase in free energy due to interactions with the solvent. This further implies that the binding might be enthalpically favorable due to favorable gas-phase interactions but entropically unfavorable due to unfavorable solvation effects. Our analysis shows that our designed compounds have unmatched pharmacological potential, far surpassing previously reported compounds. This highlights the innovative nature of these derivatives and sets a new benchmark in IDO and TDO drug discovery, indicating their significant potential as effective anticancer inhibitors.
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Antineoplásicos , Indolamina-Pirrol 2,3,-Dioxigenase , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Humanos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Estereoisomerismo , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
BACKGROUND: As the world becomes increasingly urbanised, there is recognition that public and planetary health relies upon a ubiquitous transition to sustainable cities. Disentanglement of the complex pathways of urban design, environmental exposures, and health, and the magnitude of these associations, remains a challenge. A state-of-the-art account of large-scale urban health studies is required to shape future research priorities and equity- and evidence-informed policies. OBJECTIVES: The purpose of this review was to synthesise evidence from large-scale urban studies focused on the interaction between urban form, transport, environmental exposures, and health. This review sought to determine common methodologies applied, limitations, and future opportunities for improved research practice. METHODS: Based on a literature search, 2958 articles were reviewed that covered three themes of: urban form; urban environmental health; and urban indicators. Studies were prioritised for inclusion that analysed at least 90 cities to ensure broad geographic representation and generalisability. Of the initially identified studies, following expert consultation and exclusion criteria, 66 were included. RESULTS: The complexity of the urban ecosystem on health was evidenced from the context dependent effects of urban form variables on environmental exposures and health. Compact city designs were generally advantageous for reducing harmful environmental exposure and promoting health, with some exceptions. Methodological heterogeneity was indicative of key urban research challenges; notable limitations included exposure and health data at varied spatial scales and resolutions, limited availability of local-level sociodemographic data, and the lack of consensus on robust methodologies that encompass best research practice. CONCLUSION: Future urban environmental health research for evidence-informed urban planning and policies requires a multi-faceted approach. Advances in geospatial and AI-driven techniques and urban indicators offer promising developments; however, there remains a wider call for increased data availability at local-levels, transparent and robust methodologies of large-scale urban studies, and greater exploration of urban health vulnerabilities and inequities.
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Cidades , Humanos , Exposição Ambiental , Meios de Transporte , Saúde da População Urbana , Saúde Ambiental/métodosRESUMO
BACKGROUND: Community concerns surrounding syringe waste are a common barrier to syringe services program (SSP) implementation. In Kanawha County, West Virginia, community opposition to SSPs resulted in the closure of needs-based SSPs prior to and during an HIV outbreak among persons who inject drugs (PWID). This qualitative analysis examines views of PWID and community partners on syringe waste and disposal associated with needs-based SSPs. METHODS: Qualitative interviews with 26 PWID and 45 community partners (medical and social service providers, law enforcement personnel, policymakers, and religious leaders) were conducted. Interviews were recorded, transcribed, and coded. Code summaries described participants' views on syringe waste and disposal and needs-based SSPs. RESULTS: Community partners and PWID who favored needs-based SSPs reported that needs-based SSPs had not affected or reduced syringe waste. Conversely, community partners who favored one-to-one exchange models and/or barcoded syringes described needs-based SSPs increasing syringe waste. Community partners often cited pervasive community beliefs that SSPs increased syringe waste, risk of needlesticks, drug use, and crime. Community partners were unsure how to address syringe waste concerns and emphasized that contradictory views on syringe waste posed barriers to discussing and implementing SSPs. CONCLUSIONS: Participants' views on whether syringe waste was associated with needs-based SSPs often aligned with their support or opposition for needs-based SSPs. These differing views resulted in challenges finding common ground to discuss SSP operations amid an HIV outbreak among PWID. SSPs might consider addressing syringe waste concerns by expanding syringe disposal efforts and implementing community engagement and stigma reduction activities.
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Programas de Troca de Agulhas , Abuso de Substâncias por Via Intravenosa , Humanos , Abuso de Substâncias por Via Intravenosa/psicologia , Abuso de Substâncias por Via Intravenosa/epidemiologia , Feminino , Masculino , Adulto , Seringas , Infecções por HIV/prevenção & controle , West Virginia/epidemiologia , Pessoa de Meia-Idade , Pesquisa QualitativaRESUMO
Recent advances in data science and urban environmental health research utilise large-scale databases (100s-1000s of cities) to explore the complex interplay of urban characteristics such as city form and size, climate, mobility, exposure, and environmental health impacts. Cities are still hotspots of air pollution and noise, suffer urban heat island effects and lack of green space, which leads to disease and mortality burdens preventable with better knowledge. Better understanding through harmonising and analysing data in large numbers of cities is essential to identifying the most effective means of disease prevention and understanding context dependencies important for policy.
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In a Policy Forum piece, Dr. Nicola Low and colleagues define the research agenda for Mpox virus and transmission through sexual contact.
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Mpox , Comportamento Sexual , Humanos , Mpox/transmissãoRESUMO
Introduction: Congenital syphilis cases in the United States increased 755% during 2012-2021. Syphilis during pregnancy can lead to stillbirth, miscarriage, infant death, and maternal and infant morbidity; these outcomes can be prevented through appropriate screening and treatment. Methods: A cascading framework was used to identify and classify missed opportunities to prevent congenital syphilis among cases reported to CDC in 2022 through the National Notifiable Diseases Surveillance System. Data on testing and treatment during pregnancy and clinical manifestations present in the newborn were used to identify missed opportunities to prevent congenital syphilis. Results: In 2022, a total of 3,761 cases of congenital syphilis in the United States were reported to CDC, including 231 (6%) stillbirths and 51 (1%) infant deaths. Lack of timely testing and adequate treatment during pregnancy contributed to 88% of cases of congenital syphilis. Testing and treatment gaps were present in the majority of cases across all races, ethnicities, and U.S. Census Bureau regions. Conclusions and implications for public health practice: Addressing missed opportunities for prevention, primarily timely testing and appropriate treatment of syphilis during pregnancy, is important for reversing congenital syphilis trends in the United States. Implementing tailored strategies addressing missed opportunities at the local and national levels could substantially reduce congenital syphilis.
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Complicações Infecciosas na Gravidez , Sífilis Congênita , Sífilis , Lactente , Recém-Nascido , Gravidez , Feminino , Humanos , Estados Unidos/epidemiologia , Sífilis Congênita/epidemiologia , Sífilis Congênita/prevenção & controle , Sífilis/diagnóstico , Sífilis/epidemiologia , Sífilis/prevenção & controle , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controle , Vigilância da População , Natimorto , Sinais VitaisRESUMO
Monkeypox (mpox) is a serious viral zoonosis endemic in west and central Africa. An unprecedented global outbreak was first detected in May 2022. CDC activated its emergency outbreak response on May 23, 2022, and the outbreak was declared a Public Health Emergency of International Concern on July 23, 2022, by the World Health Organization (WHO),* and a U.S. Public Health Emergency on August 4, 2022, by the U.S. Department of Health and Human Services. A U.S. government response was initiated, and CDC coordinated activities with the White House, the U.S. Department of Health and Human Services, and many other federal, state, and local partners. CDC quickly adapted surveillance systems, diagnostic tests, vaccines, therapeutics, grants, and communication systems originally developed for U.S. smallpox preparedness and other infectious diseases to fit the unique needs of the outbreak. In 1 year, more than 30,000 U.S. mpox cases were reported, more than 140,000 specimens were tested, >1.2 million doses of vaccine were administered, and more than 6,900 patients were treated with tecovirimat, an antiviral medication with activity against orthopoxviruses such as Variola virus and Monkeypox virus. Non-Hispanic Black (Black) and Hispanic or Latino (Hispanic) persons represented 33% and 31% of mpox cases, respectively; 87% of 42 fatal cases occurred in Black persons. Sexual contact among gay, bisexual, and other men who have sex with men (MSM) was rapidly identified as the primary risk for infection, resulting in profound changes in our scientific understanding of mpox clinical presentation, pathogenesis, and transmission dynamics. This report provides an overview of the first year of the response to the U.S. mpox outbreak by CDC, reviews lessons learned to improve response and future readiness, and previews continued mpox response and prevention activities as local viral transmission continues in multiple U.S. jurisdictions (Figure).
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Mpox , Minorias Sexuais e de Gênero , Masculino , Humanos , Estados Unidos/epidemiologia , Homossexualidade Masculina , Mpox/epidemiologia , Surtos de Doenças/prevenção & controle , Centers for Disease Control and Prevention, U.S.RESUMO
Iodinated contrast material (ICM) has revolutionized the field of diagnostic radiology through improvements in diagnostic performance and expansion in clinical indications for radiographic and CT examinations. Historically, nephrotoxicity was a feared complication of ICM use, thought to be associated with a significant risk of morbidity and mortality. Such fears often precluded use of ICM in imaging evaluations, commonly at the expense of diagnostic performance and timely diagnosis. Over the past 20 years, the nephrotoxic risk of ICM has become a topic of debate, as more recent evidence from higher-quality studies now suggest that many cases of what was considered contrast-induced acute kidney injury (CI-AKI) were likely cases of mistaken causal attribution; most of these cases represented either acute kidney injury (AKI) caused by any of myriad other known factors that can adversely affect renal function and were coincidentally present at the time of contrast media exposure (contrast-associated AKI (CA-AKI)) or a manifestation of the normal variation in renal function that increases with worsening renal function. This review discusses the current state of knowledge on CI-AKI and CA-AKI including the incidence, risk factors, outcomes, and prophylactic strategies in the identification and management of these clinical conditions.
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The synthesis, characterization, and solid-state structure of bulky alkoxy- and aryloxy-supported yttrium polynuclear hydrides are reported. Hydrogenolysis of the supertrityl alkoxy anchored yttrium dialkyl, Y(OTr*)(CH2SiMe3)2(THF)2 (1) (Tr* = tris(3,5-di-tert-butylphenyl)methyl), resulted in the clean conversion to the tetranuclear dihydride, [Y(OTr*)H2(THF)]4 (1a). X-ray analysis revealed a highly symmetrical structure (4Ì site symmetry) with the four Y atoms located on the corners of a compressed tetrahedron, each bonded to an OTr* and tetrahydrofuran (THF) ligand and the cluster held together by four face-capping, µ3-H, and four edge-bridging, µ2-H, hydrides. DFT calculations on the full system with and without THF, but also on model systems, clearly show that the structural preference for complex 1a is controlled by the presence and coordination of THF molecules. Contrary to the exclusive formation of the tetranuclear dihydride, hydrogenolysis of the bulky aryloxy yttrium dialkyl, Y(OAr*)(CH2SiMe3)2(THF)2 (2) (Ar* = 3,5-di-tert-butylphenyl) gave a mixture of the analogous tetranuclear 2a and trinuclear, [Y3(OAr*)4H5(THF)4], polyhydride, 2b. Similar results, i.e., a mixture of tetra-/tri-nuclear products, were obtained from hydrogenolysis of the even bulkier Y(OArAd2,Me)(CH2SiMe3)2(THF)2 compound. Experimental conditions were established to optimize the production of either the tetra- or trinuclear products. X-ray structure of 2b revealed a triangular array of three yttrium atoms with two face-capping µ3-H and three edge-bridging µ2-H hydrides, with one yttrium bonded to two aryloxy ligands while the other two have a complement of one aryloxy and two THF ligands; the solid-state structure is close to being C2 symmetric, with the C2 axis running through the unique Y and unique µ2-H hydride. As opposed to 2a, which shows distinct 1H NMR resonances for µ3/ µ2-H (δ = 5.83/6.35 ppm, respectively), no hydride signals for 2b were observed at room temperature, indicating hydride exchange on the NMR time scale. Their presence and assignment were secured at -40 °C from 1H SST (spin saturation) experiment.
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We test the hypothesis that the stability and precision of context and visual discrimination memories depend on interactions between the hippocampus (HPC) and other memory storage networks. In four experiments we tested the properties of memories acquired in the absence of the HPC. Long-Evans male rats were exclusively used in all experiments. Experiment 1 evaluated acquisition and retention of context fear memories in rats with prior partial or complete HPC damage. Confirming an earlier report (Zelikowsky et al., 2012) a very small but statistically reliable slowing in a single session of context fear conditioning was found after HPC damage. In contrast, retention of context fear memory was normal after HPC damage up to 30 d after learning. In experiment 2, we found that discrimination between a context paired with foot shocks and a different context never paired with foot shock was retained normally for 15 d. In experiment 3, we replicated the finding of intact context discrimination for at least 15 d in rats who display a significant impairment in acquisition of place learning in the Morris water task (MWT). In final experiment using an appetitive object discrimination task, we showed normal retention of the discrimination for at least 30 d after training in rats with complete HPC damage. These finding score against the idea that non HPC memory storage requires a period of interaction with HPC to establish a stable, precise memory.SIGNIFICANCE STATEMENT Contrary to expectations from systems memory consolidation, we find that in the absence of a functional hippocampus (HPC) context and visual memories are formed rapidly and exhibit normal persistence and precision. The findings suggest that the HPC is not obligatory for these features of long-term memories.
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Hipocampo/fisiologia , Aprendizagem/fisiologia , Consolidação da Memória/fisiologia , Animais , Condicionamento Clássico , Medo/fisiologia , Masculino , Ratos , Ratos Long-EvansRESUMO
In this article, members of the American College of Radiology Committee on Drugs and Contrast Media propose a new term for symptoms reported after intravascular exposure to gadolinium-based contrast agents-Symptoms Associated with Gadolinium Exposure, or SAGE. This term is advocated in lieu of other proposed nomenclature that presumes a causal relationship that has not yet been scientifically verified. The purpose of this new term, SAGE, is to assist researchers and clinical providers in describing such symptoms without prematurely causally attributing them to a disease and to standardize reporting of these symptoms to allow for coherent interpretation of related studies.
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Meios de Contraste/efeitos adversos , Hipersensibilidade a Drogas/classificação , Hipersensibilidade a Drogas/etiologia , Gadolínio/efeitos adversos , Humanos , Sociedades Médicas , Terminologia como Assunto , Estados UnidosRESUMO
Background Concerns over the neurotoxic potential of retained gadolinium in brain tissues after intravenous gadolinium-based contrast agent (GBCA) administration have led to pronounced worldwide use changes, yet the clinical sequelae of gadolinium retention remain undefined. Purpose To assess clinical and neurologic effects and potential neurotoxicity of gadolinium retention in rats after administration of various GBCAs. Materials and Methods From March 2017 through July 2018, 183 male Wistar rats received 20 intravenous injections of 2.5 mmol per kilogram of body weight (80 human equivalent doses) of various GBCAs (gadodiamide, gadobenate, gadopentetate, gadoxetate, gadobutrol, gadoterate, and gadoteridol) or saline over 4 weeks. Rats were evaluated 6 and 34 weeks after injection with five behavioral tests, and inductively coupled plasma mass spectrometry, transmission electron microscopy, and histopathology were performed on urine, serum, cerebrospinal fluid (CSF), basal ganglia, dentate nucleus, and kidney samples. Dunnett post hoc test and Wilcoxon rank sum test were used to compare differences between treatment groups. Results No evidence of differences in any behavioral test was observed between GBCA-exposed rats and control animals at either 6 or 34 weeks (P = .08 to P = .99). Gadolinium concentrations in both neuroanatomic locations were higher in linear GBCA-exposed rats than macrocyclic GBCA-exposed rats at 6 and 34 weeks (P < .001). Gadolinium clearance over time varied among GBCAs, with gadobutrol having the largest clearance (median: 62% for basal ganglia, 70% for dentate) and gadodiamide having no substantial clearance. At 34 weeks, gadolinium was largely cleared from the CSF and serum of gadodiamide-, gadobenate-, gadoterate-, and gadobutrol-exposed rats, especially for the macrocyclic agents (range: 70%-98% removal for CSF, 34%-94% removal for serum), and was nearly completely removed from urine (range: 96%-99% removal). Transmission electron microscopy was used to detect gadolinium foci in linear GBCA-exposed brain tissue, but no histopathologic differences were observed for any GBCA. Conclusion In this rat model, no clinical evidence of neurotoxicity was observed after exposure to linear and macrocyclic gadolinium-based contrast agents at supradiagnostic doses. © RSNA, 2022 Online supplemental material is available for this article.
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Encéfalo/efeitos dos fármacos , Meios de Contraste/administração & dosagem , Gadolínio/administração & dosagem , Administração Intravenosa , Animais , Encéfalo/metabolismo , Meios de Contraste/metabolismo , Gadolínio/metabolismo , Masculino , Modelos Animais , Ratos , Ratos WistarRESUMO
BACKGROUND: Syphilis can cause neurologic, ocular, or otic manifestations, possibly resulting in permanent disability or death. In 2018, the Centers for Disease Control and Prevention began collecting syphilis clinical manifestation data via the National Notifiable Diseases Surveillance System. We present the first reported US syphilis neurologic, ocular, and otic manifestation prevalence estimates. METHODS: We reviewed 2019 National Notifiable Diseases Surveillance System data to identify jurisdictions reporting 70% or greater of syphilis cases 15 years or older with clinical manifestation data (considered "complete reporting"). Among these jurisdictions, we determined reported neurologic, ocular, and otic manifestation prevalence, stratified by demographic, behavioral, and clinical characteristics. RESULTS: Among 41,187 syphilis cases in 16 jurisdictions with complete reporting, clinical manifestations were infrequently reported overall: neurologic (n = 445, 1.1%), ocular (n = 461, 1.1%), otic (n = 166, 0.4%), any (n = 807, 2.0%). Reported clinical manifestation prevalence was highest among cases 65 years or older (neurologic, 5.1%; ocular, 3.5%; otic, 1.2%) and those reporting injection drug use (neurologic: 2.8%; ocular: 3.4%; otic: 1.6%). Although reported neurologic and ocular manifestation prevalence was slightly higher among human immunodeficiency virus (HIV)-infected versus HIV-negative persons, approximately 40% of cases with manifestations were HIV-negative. Reported otic manifestation prevalence was similar regardless of HIV status. When stratifying by HIV status and syphilis stage, reported prevalence was highest among HIV-infected persons with unknown duration/late syphilis (neurologic, 3.0%; ocular, 2.3%; otic, 0.7%). CONCLUSIONS: Reported neurologic, ocular, and otic manifestation prevalence was low among syphilis cases, but these data are likely an underestimate given potential underreporting. Reported clinical manifestation frequency, including among HIV-negative persons, emphasizes the importance of evaluating all syphilis cases for signs/symptoms of neurosyphilis, ocular syphilis, and otosyphilis.
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Infecções Oculares Bacterianas , Infecções por HIV , Neurossífilis , Sífilis , Infecções Oculares Bacterianas/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Neurossífilis/diagnóstico , Neurossífilis/epidemiologia , Prevalência , Sífilis/diagnóstico , Sífilis/epidemiologiaRESUMO
Since May 2022, 27,558 monkeypox cases have been identified in the United States (1). Gay, bisexual, and other men who have sex with men (MSM) represent the most affected demographic group in the current multinational outbreak (2). As of October 18, 2022, Louisiana had reported 273 monkeypox cases with 187 (68.5%) among residents of the Louisiana Department of Health (LDH) Southeast Region, which includes the city of New Orleans (3).