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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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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 , Gonorrea , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae , Organización Mundial de la Salud , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/genética , Cambodia/epidemiología , Humanos , Gonorrea/microbiología , Gonorrea/epidemiología , Gonorrea/tratamiento farmacológico , Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Filogenia , Masculino , Femenino , AdultoRESUMEN
BACKGROUND: Prurigo nodularis (PN) is a pruritic skin disease characterised by multiple, intensely itchy skin nodules in symmetrically distributed areas of the extremities. There are very limited studies on the epidemiology and treatment pathways for 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 (CPRD) and Hospital Episode Statistics (HES) in England. Adult patients (≥18 years) with a PN specific diagnosis code 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 pre- and ≥12 months post-IDD. Patients were classified into 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 for age, gender and IDD. Prevalence and incidence were calculated for each year from 2007 to 2019. Drugs prescribed post IDD were analysed. RESULTS: A total of 8,933 patients (MSPN: 2,498 patients; MiPN: 6,539 patients) were included for the study; 2,462 patients each with MiPN and MSPN were included for the comparative analysis. Atopic dermatitis, asthma and eosinophilic oesophagitis were significantly higher (all p<0.001) in patients with MSPN (vs MiPN). The prevalence of overall PN cases 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 corticosteroid, methotrexate, antidepressants and tacrolimus were significantly higher (all p <0.001) in patients with MSPN (vs MiPN). CONCLUSIONS: The epidemiology of PN was consistent with other European studies. Patients with MSPN received a significantly higher number of prescriptions for potent TCS and systemic drugs, as compared with milder patients.
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An oxygen sensor-mounted fine-needle biopsy tool was used for in vivo measurement of oxygen levels in tumor xenografts. The system provides a means of measuring the oxygen content in harvested tumor tissue from specific locations. Oxygen in human tumor xenografts in a murine model was observed for over 1 min. Tissues were mapped in relation to oxygen tension (pO2) readings and sampled for conventional cytological examination. Careful modeling of the pO2 readings over 60 seconds yielded a diffusion coefficient for oxygen at the sensor tip, providing additional diagnostic information about the tissue before sampling. Oxygen level measurement may provide a useful adjunct to the use of biomarkers in tumor diagnosis.
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Purpose: Prurigo nodularis (PN) is a skin disease characterized by intensely itchy skin nodules and is associated with a significant healthcare resource utilization (HCRU). This study aimed to estimate the HCRU of patients in England with PN overall and moderate-to-severe PN (MSPN) in particular.Methods: This retrospective cohort study used data from the Clinical Practice Research Datalink and Hospital Episode Statistics in England. Patients with Mild PN (MiPN) were matched to patients with MSPN by age and gender for the primary analysis. Patients were enrolled in the study between 1st April 2007 and 1st March 2019. All-cause HCRU was calculated, including primary and secondary care contacts and costs (cost-year 2022).Results: Of 23,522 identified patients, 8,933 met the inclusion criteria, with a primary matched cohort of 2,479 PN patients. During follow up, the matched cohort's primary care visits were 21.27 per patient year (PPY) for MSPN group and 11.35 PPY for MiPN group. Any outpatient visits were 10.72 PPY and 4.87 PPY in MSPN and MiPN groups, respectively. Outpatient dermatology visits were 1.96 PPY and 1.14 PPY in MSPN and MiPN groups, respectively.Conclusion: PN, especially MSPN, has a high HCRU burden in England, highlighting the need for new and improved disease management treatments.
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Bases de Datos Factuales , Prurigo , Humanos , Femenino , Masculino , Prurigo/economía , Prurigo/terapia , Inglaterra , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Anciano , Índice de Severidad de la Enfermedad , Adulto Joven , Costo de Enfermedad , Costos de la Atención en Salud/estadística & datos numéricos , Adolescente , Aceptación de la Atención de Salud/estadística & datos numéricosRESUMEN
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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Ciudades , Humanos , Exposición a Riesgos Ambientales , Transportes , Salud Urbana , Salud Ambiental/métodosRESUMEN
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 Intercambio de Agujas , Abuso de Sustancias por Vía Intravenosa , Humanos , Abuso de Sustancias por Vía Intravenosa/psicología , Abuso de Sustancias por Vía Intravenosa/epidemiología , Femenino , Masculino , Adulto , Jeringas , Infecciones por VIH/prevención & control , West Virginia/epidemiología , Persona de Mediana Edad , Investigación CualitativaRESUMEN
Harvesting energy from the human body is an area of growing interest. While several techniques have been explored, the focus in the field is converging on using Glucose Fuel Cells (GFCs) that use glucose oxidation reactions at an anode and oxygen reduction reactions (ORRs) at a cathode to create a voltage gradient that can be stored as power. To facilitate these reactions, catalysts are immobilized at an anode and cathode that result in electrochemistry that typically produces two electrons, a water molecule, and gluconic acid. There are two competing classes of these catalysts: enzymes, which use organic proteins, and abiotic options, which use reactive metals. Enzymatic catalysts show better specificity towards glucose, whereas abiotic options show superior operational stability. The most advanced enzymatic test showed a maximum power density of 119 µW/cm2 and an efficiency loss of 4% over 15 hours of operation. The best abiotic experiment resulted in 43 µW/cm2 and exhibited no signs of performance loss after 140 hours. Given the range of existing implantable devices' power budget from 10µW to 100mW and expected operational duration of 10 years or more, GFCs hold promise, but considerable advances need to be made to translate this technology to practical applications.
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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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Consumidores de Drogas , Infecciones por VIH , Abuso de Sustancias por Vía Intravenosa , Humanos , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/epidemiología , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , West Virginia/epidemiología , Brotes de Enfermedades , Programas de Intercambio de AgujasRESUMEN
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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Complicaciones Infecciosas del Embarazo , Sífilis Congénita , Sífilis , Embarazo , Femenino , Humanos , Estados Unidos/epidemiología , Sífilis Congénita/epidemiología , Sífilis Congénita/prevención & control , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/prevención & control , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Sífilis/diagnóstico , Sífilis/epidemiología , Sífilis/prevención & controlRESUMEN
Trichorhinophalangeal syndrome type 1 (TRPS1) has been reported to be a sensitive and specific immunohistochemical (IHC) marker for breast carcinomas, especially when determining primary site of origin. However, there is limited data on TRPS1 expression in prostate and bladder cancers. A two-phase study was performed with 1) an exploratory cohort analyzing TRPS1 gene alterations in prostate, bladder, and breast carcinoma and TPRS1 mRNA expression data in prostate and bladder carcinoma; and 2) TRPS1 and GATA3 IHC in a confirmatory cohort in prostate, bladder, and breast carcinoma samples. Gene alterations were identified in a subset of breast, bladder, and prostate carcinomas and mRNA was consistently detected. In the IHC cohort, 183/210 (87.1 %) of breast, 22/69 (31.9 %) of prostate, and 20/73 (27.4 %) of urothelial carcinomas showed staining with TRPS1. Intermediate to high expression of TRPS1 was observed in 173/210 (82.8 %) of breast, 17/69 (24.6 %) of prostate, and 15/73 (20.5 %) of urothelial carcinomas. Furthermore, in prostate cancer, 26.9 % of pelvic lymph node metastases and 50 % in sites of distant metastases showed expression. Increased TRPS1 mRNA expression (p = 0.032) and IHC expression (p = 0.040) correlated with worse overall survival in bladder cancer. By comparison, GATA3 IHC stained 136/210 (64.8 %) of breast, 0/69 (0 %) of prostate, and 63/73 (93 %) of bladder carcinomas. Intermediate to high expression of GATA3 was seen in 131/210 (62.4 %) of breast and 63/73 (93 %) of bladder carcinomas. This study shows there is significant staining of TRPS1 in bladder and prostate cancers. As a result, comprehensive studies are needed to establish the true specificity of TRPS1 IHC stain across various tumor types before its widespread clinical adoption.
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Adenocarcinoma , Neoplasias de la Mama , Carcinoma de Células Transicionales , Neoplasias de la Próstata , Neoplasias de la Vejiga Urinaria , Masculino , Humanos , Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/patología , Vejiga Urinaria/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Próstata/patología , Neoplasias de la Mama/patología , Adenocarcinoma/patología , ARN Mensajero , Músculos/metabolismo , Músculos/patología , Factor de Transcripción GATA3/metabolismo , Proteínas Represoras/genéticaRESUMEN
OBJECTIVE: To assess the effects of patient variables, examination variables, and seasonality on allergic-like and physiologic reactions to iodinated contrast material (ICM). PATIENTS AND METHODS: All ICM-enhanced computed tomography (CT) examinations performed from June 1, 2009, to May 9, 2017, at our institution were included. Reactions were identified and categorized as allergic-like or physiologic and mild, moderate, or severe. The effect of patient and examination variables on reactions was evaluated by logistic regression models. RESULTS: A total of 359,977 CT examinations performed on 176,886 unique patients were included. A total of 1150 allergic-like reactions (0.32%; 19 severe [0.005%]) and 679 physiologic reactions (0.19%; 3 severe [0.0008%]) occurred. On multivariable analysis, iopromide had higher rates of reactions compared with iohexol (allergic-like reactions: odds ratio [OR], 3.07 [95% CI, 2.37 to 3.98], P<.0001; physiologic reactions: OR, 2.60 [1.92 to 3.52], P<.0001). Non-White patients had higher rates of reactions compared with White patients (allergic-like reactions: OR, 1.77 [1.36-2.30], P<.0001; physiologic reactions: OR, 1.76 [1.27-2.42], P=.0006). Patient age, sex, prior ICM reaction, ICM dose, CT location, and CT type were also significantly associated with reactions. No significant seasonality trend was observed (P=.07 and .80). CONCLUSION: Non-White patients and patients administered iopromide had higher rates of acute reactions compared with White patients and patients administered iohexol. Younger patients (<50 years vs 51 to 60 years), female sex, history of ICM allergy or other allergies, ICM dose, and contrast-enhanced CT location and type also correlated with higher acute reaction rates.
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Medios de Contraste , Hipersensibilidad a las Drogas , Humanos , Femenino , Medios de Contraste/efectos adversos , Yohexol/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/epidemiología , Hipersensibilidad a las Drogas/etiologíaRESUMEN
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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Complicaciones Infecciosas del Embarazo , Sífilis Congénita , Sífilis , Lactante , Recién Nacido , Embarazo , Femenino , Humanos , Estados Unidos/epidemiología , Sífilis Congénita/epidemiología , Sífilis Congénita/prevención & control , Sífilis/diagnóstico , Sífilis/epidemiología , Sífilis/prevención & control , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/prevención & control , Vigilancia de la Población , Mortinato , Signos VitalesRESUMEN
Education, occupation, and an active lifestyle, comprising enhanced social, physical, and mental components are associated with improved cognitive functions in aged people and may delay the progression of various neurodegenerative diseases including Alzheimer's disease. To investigate this protective effect, 3-month-old APPNL-G-F/NL-G-F mice were exposed to repeated single- or multi-domain cognitive training. Cognitive training was given at the age of 3, 6, & 9 months. Single-domain cognitive training was limited to a spatial navigation task. Multi-domain cognitive training consisted of a spatial navigation task, object recognition, and fear conditioning. At the age of 12 months, behavioral tests were completed for all groups. Then, mice were sacrificed, and their brains were assessed for pathology. APPNL-G-F/NL-G-F mice given multi-domain cognitive training compared to APPNL-G-F/NL-G-F control group showed an improvement in cognitive functions, reductions in amyloid load and microgliosis, and a preservation of cholinergic function. Additionally, multi-domain cognitive training improved anxiety in APPNL-G-F/NL-G-F mice as evidenced by measuring thigmotaxis behavior in the Morris water maze. There were mild reductions in microgliosis in the brain of APPNL-G-F/NL-G-F mice with single-domain cognitive training. These findings provide causal evidence for the potential of certain forms of cognitive training to mitigate the cognitive deficits in Alzheimer disease.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Ratones , Animales , Anciano , Lactante , Enfermedad de Alzheimer/prevención & control , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides , Precursor de Proteína beta-Amiloide , Entrenamiento Cognitivo , Ratones Transgénicos , Disfunción Cognitiva/etiología , Disfunción Cognitiva/prevención & control , Ansiedad/etiología , Ansiedad/prevención & control , Proteínas AmiloidogénicasRESUMEN
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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The amygdala has been implicated in a variety of functions linked to emotions. One popular view is that the amygdala modulates consolidation in other brain systems thought to be mainly involved in learning and memory processes. This series of experiments represents a further exploration into the role of the amygdala in memory modulation and consolidation. One interesting line of research has shown that drugs of abuse, like amphetamine, produce dendritic changes in select brain regions and these changes are thought to be equivalent to a usurping of normal plasticity processes. We were interested in the possibility that this modulation of plasticity processes would be dependent on interactions with the amygdala. According to the modulation view of amygdala function, amphetamine would activate modulation mechanisms in the amygdala that would alter plasticity processes in other brain regions. If the amygdala was rendered dysfunctional, these effects should not occur. Accordingly, this series of experiments evaluated the effects of extensive neurotoxic amygdala damage on amphetamine-induced dendritic changes in the nucleus accumbens and prefrontal cortex. The results showed that rats with large lesions of the amygdala showed the normal pattern of dendritic changes in these brain regions. This pattern of results suggests that the action of not all memory modulators, activated during emotional events, require the amygdala to impact memory.
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OBJECTIVE: CD47 is an antiphagocytic molecule that plays a critical role in immune surveillance. A variety of malignancies have been shown to evade the immune system by increasing the expression of CD47 on the cell surface. As a result, anti-CD47 therapy is under clinical investigation for a subset of these tumors. Interestingly, CD47 overexpression is associated with negative clinical outcomes in lung and gastric cancers; however, the expression and functional significance of CD47 in bladder cancer is not fully understood. MATERIALS AND METHODS: We retrospectively studied patients with muscle invasion bladder cancer (MIBC) who underwent a transurethral resection of bladder tumor (TURBT) and subsequently underwent radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC). CD47 expression was examined by IHC in both TURBT and matched RC specimens. The difference in CD47 expression levels between TURBT and RC was also compared. The association of CD47 levels (TURBT) with clinicopathological parameters and survival outcomes was evaluated by Pearson's chi-squared tests and the Kaplan-Meier method, respectively. RESULTS: A total of 87 MIBC patients were included. The median age was 66 (39-84) years. Most patients were Caucasian (95%), male (79%), and aged >60 (63%) and most often (75%) underwent NAC prior to RC. Of those who received NAC, 35.6% were responders and 64.4% were non-responders. The final reported stages as per AJCC for all patients were as follows: stage 0 (32%), stage 1 (1%), stage 2 (20%), stage 3 (43%), and stage 4a (5%). A total of 60% of patients were alive; of those, 30% had disease recurrence and 40% died from bladder cancer at a median follow-up of 3.1 (0.2-14.2) years. CD47 levels were detectable in 38 (44%) TURBT samples. There was no association between CD47 levels and clinicopathological parameters such as age, gender, race, NAC, final stage, disease recurrence, and overall survival (OS). Patients aged >60 (p = 0.006), non-responders (p = 0.002), and at stage ≥ 3 (p < 0.001) were associated with worse OS by a univariate analysis and stage ≥ 3 remained significant even after a multivariate analysis. In patients managed with NAC, there were decreased CD47 levels in RC specimens compared to the TURBT specimens, but this did not reach statistical significance. CONCLUSION: CD47 expression was not a predictive nor prognostic marker for MIBC patients. However, expression of CD47 was detected in nearly half of MIBCs, and future studies are needed to explore the potential role of anti-CD47 therapy in these patients. Furthermore, there was a slight positive trend in decreased CD47 levels (from TURBT to RC) in patients receiving NAC. As a result, more research is needed to understand how NAC may modify immune surveillance mechanisms in MIBC.
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Matrix assisted laser desorption/ionization imaging has greatly improved our understanding of spatial biology, however a robust bioinformatic pipeline for data analysis is lacking. Here, we demonstrate the application of high-dimensionality reduction/spatial clustering and histopathological annotation of matrix assisted laser desorption/ionization imaging datasets to assess tissue metabolic heterogeneity in human lung diseases. Using metabolic features identified from this pipeline, we hypothesize that metabolic channeling between glycogen and N-linked glycans is a critical metabolic process favoring pulmonary fibrosis progression. To test our hypothesis, we induced pulmonary fibrosis in two different mouse models with lysosomal glycogen utilization deficiency. Both mouse models displayed blunted N-linked glycan levels and nearly 90% reduction in endpoint fibrosis when compared to WT animals. Collectively, we provide conclusive evidence that lysosomal utilization of glycogen is required for pulmonary fibrosis progression. In summary, our study provides a roadmap to leverage spatial metabolomics to understand foundational biology in pulmonary diseases.
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Fibrosis Pulmonar , Ratones , Animales , Humanos , Glucógeno , Metabolómica/métodos , Polisacáridos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodosRESUMEN
Prenatal experiences can influence offspring physiology and behaviour through the lifespan. Various forms of prenatal stress impair adult learning and memory function and can lead to increased occurrence of anxiety and depression. Clinical work suggests that prenatal stress and maternal depression lead to similar outcomes in children and adolescents, however the long-term effects of maternal depression are less established, particularly in well controlled animal models. Social isolation is common in depressed individuals and during the recent COVID-19 pandemic. Accordingly, for this study we were interested in the effects of maternal stress induced via social isolation on adult offspring cognitive functions including spatial, stimulus-response, and emotional learning and memory that are mediated by different networks centered on the hippocampus, dorsal striatum, and amygdala, respectively. Tasks included a discriminative contextual fear conditioning task and cue-place water task. Pregnant dams in the social isolation group were single housed prior to and throughout gestation. Once offspring reached adulthood the male offspring were trained on a contextual fear conditioning task in which rats were trained to associate one of two contexts with an aversive stimulus and the opposing context remained neutral. Afterwards a cue-place water task was performed during which they were required to navigate to both a visible and invisible platform. Fear conditioning results revealed that the adult offspring of socially isolated mothers, but not controls, were impaired in associating a specific context with a fear-inducing stimulus as assessed by conditioned freezing and avoidance. Results from the water task indicate that adult offspring of mothers that were socially isolated showed place learning deficits but not stimulus-response habit learning on the same task. These cognitive impairments, in the offspring of socially isolated dams, occurred in the absence of maternal elevated stress hormone levels, anxiety, or altered mothering. Some evidence suggested that maternal blood-glucose levels were altered particularly during gestation. Our results provide further support for the idea that learning and memory networks, centered on the amygdala and hippocampus are particularly susceptible to the negative impacts of maternal social isolation and these effects can occur without elevated glucocorticoid levels associated with other forms of prenatal stress.