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1.
Proc Natl Acad Sci U S A ; 121(5): e2315667121, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38252829

RESUMEN

Water striders are abundant in areas with high humidity and rainfall. Raindrops can weigh more than 40 times the adult water strider and some pelagic species spend their entire lives at sea, never contacting ground. Until now, researchers have not systematically investigated the survival of water striders when impacted by raindrops. In this experimental study, we use high-speed videography to film drop impacts on water striders. Drops force the insects subsurface upon direct contact. As the ensuing crater rebounds upward, the water strider is propelled airborne by a Worthington jet, herein called the first jet. We show the water strider's locomotive responses, low density, resistance to wetting when briefly submerged, and ability to regain a super-surface rest state, rendering it impervious to the initial impact. When pulled subsurface during a second crater formation caused by the collapsing first jet, water striders face the possibility of ejection above the surface or submersion below the surface, a fate determined by their position in the second crater. We identify a critical crater collapse acceleration threshold ∼ 5.7 gravities for the collapsing second crater which determines the ejection and submersion of passive water striders. Entrapment by submersion makes the water strider poised to penetrate the air-water interface from below, which appears impossible without the aid of a plastron and proper locomotive techniques. Our study is likely the first to consider second crater dynamics and our results translate to the submersion dynamics of other passively floating particles such as millimetric microplastics atop the world's oceans.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38969073

RESUMEN

BACKGROUND AND AIMS: Vibration-controlled transient elastography (VCTE) is used in clinical practice to risk-stratify liver transplant (LT) recipients; however, there are currently little data demonstrating the relationship between VCTE and clinical outcomes. METHODS: A total of 362 adult LT recipients with successful VCTE examination between 2015 and 2022 were included. Presence of advanced fibrosis was defined as liver stiffness measurement (LSM) ≥10.5 kPa and hepatic steatosis as controlled attenuation parameter (CAP) ≥270 dB/m. The outcomes of interest included all-cause mortality, myocardial infarction (MI), and graft cirrhosis using cumulative incidence analysis that accounted for the competing risks of these outcomes. RESULTS: The LSM was elevated in 64 (18%) and CAP in 163 (45%) LT recipients. The baseline LSM values were similar in patients with elevated vs normal CAP values. After a median follow-up of 65 (interquartile range, 20-140) months from LT to baseline VCTE, 66 (18%) patients died, 12 (3%) developed graft cirrhosis, and 18 (5%) experienced an MI. Baseline high LSM was independently associated with all-cause mortality (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.11-3.50; P = .02) and new onset cirrhosis (HR, 6.74; 95% CI, 2.08-21.79; P < .01). A higher CAP value was significantly and independently associated with increased risk of experiencing a MI over study follow-up (HR, 4.14; 95% CI, 1.29-13.27; P = .017). CONCLUSIONS: The VCTE-based parameters are associated with clinical outcomes and offer the potential to be incorporated into clinical risk-stratification strategies to improve outcomes among LT recipients.

3.
Liver Transpl ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38775570

RESUMEN

BACKGROUND AIMS: The Sustained Alcohol use post-Liver Transplant (SALT) and the High-Risk Alcohol Relapse (HRAR) scores were developed to predict return to alcohol use after liver transplant (LT) for alcohol associated liver disease (ALD). METHODS: A retrospective analysis of deceased donor LT 10/2018 to 4/2022 was performed. All patients (pts) underwent careful pre-LT psychosocial evaluation. Data on alcohol use, substance abuse, prior rehabilitation, and legal issues were collected. Post-LT, all were encouraged to participate in rehabilitation programs and underwent interval phosphatidylethanol (PeTH) testing. Pts with ALD were stratified by < or > 6 month sobriety prior to listing. Those with <6 month were further stratified as acute alcoholic hepatitis (AH) by NIAAA criteria and non-AH. The primary outcome was utility of the SALT (<5 vs. ≥5) and HRAR (<3 vs. ≥3) scores to predict return to alcohol use (+PeTH) within 1 year after LT. RESULTS: Of the 365 LT, 86 had > 6 month sobriety and 85 had <6 month sobriety; 41 with AH and 44 non-AH. In those with AH, the mean time of abstinence to LT was 58 days, and 71% failed prior rehabilitation. Following LT, return to drinking was similar in the AH (24%) compared to <6M non-AH (15%) and >6M ALD (22%). Only 4% had returned to heavy drinking. The accuracy of both the SALT and HRAR scores to predict return to alcohol was low (accuracy 61-63%) with poor sensitivity (46% and 37%), specificity (67-68%), positive predictive value (22-26%) with moderate negative predictive value (NPV) (81-83%), respectively with higher NPVs (95%) in predicting return to heavy drinking. CONCLUSIONS: Both SALT and HRAR scores had good NPV in identifying patients at low risk for recidivism.

4.
Dig Dis Sci ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38987444

RESUMEN

BACKGROUND AND AIMS: Impact of type 2 diabetes mellitus (T2DM) in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT) remains poorly defined. The objective of the present study is to evaluate the relationship between T2DM and clinical outcomes among patients with LT waitlist registrants. We hypothesize that the presence of T2DM will be associated with worse clinical outcomes. METHODS: 593 patients adult (age 18 years or older) who were registered for LT between 1/2010 and 1/2017 were included in this retrospective analysis. The impact of T2DM on liver-associated clinical events (LACE), survival, hospitalizations, need for renal replacement therapy, and likelihood of receiving LT were evaluated over a 12-month period. LACE was defined as variceal hemorrhage, hepatic encephalopathy, and ascites. Kaplan-Meier and Cox regression analysis were used to determine the association between T2DM and clinical outcomes. RESULTS: The baseline prevalence of T2DM was 32% (n = 191) and patients with T2DM were more likely to have esophageal varices (61% vs. 47%, p = 0.002) and history of variceal hemorrhage (23% vs. 16%, p = 0.03). The presence of T2DM was associated with increased risk of incident ascites (HR 1.91, 95% CI 1.11, 3.28, p = 0.019). Patients with T2DM were more likely to require hospitalizations (56% vs. 49%, p = 0.06), hospitalized with portal hypertension-related complications (22% vs. 14%; p = 0.026), and require renal replacement therapy during their hospitalization. Patients with T2DM were less likely to receive a LT (37% vs. 45%; p = 0.03). Regarding MELD labs, patients with T2DM had significantly lower bilirubin at each follow-up; however, no differences in INR and creatinine were noted. CONCLUSION: Patients with T2DM are at increased risk of clinical outcomes. This risk is not captured in MELD score, which may potentially negatively affect their likelihood of receiving LT.

5.
Dig Dis Sci ; 69(5): 1844-1851, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38499735

RESUMEN

INTRODUCTION: Vibration-controlled transient elastography (VCTE) based liver stiffness measurement (LSM) is an excellent 'rule-out' test for advanced hepatic fibrosis in liver transplant (LT) recipients, however, its ability to 'rule-in' the disease is suboptimal. The study aimed to improve diagnostic performance of LSM in LT recipients. METHODS: Adult LT recipients with a liver biopsy and VCTE were included (N = 150). Sequential covering analysis was performed to create rules to identify patients at low or high risk for advanced fibrosis (stage 3-4). RESULTS: Advanced hepatic fibrosis was excluded in patients with either LSM < 7.45 kPa (n = 72) or 7.45 ≤ LSM < 12.1 kPa and time from LT < 5.6 years (n = 25). Conversely, likelihood of advanced fibrosis was 95% if patients had LSM > 14.1 and controlled attenuation parameter > 279 dB/m (n = 21). Thus, 118 (79%) were correctly identified and 32 (21%) would have required a biopsy to establish the diagnosis. Compared to previously established LSM based cutoff values of 10.5 kPa (Youden index) and 13.3 kPa (maximized specificity), the false positive rates of sequential covering analysis was 1% compared to 16.5% with LSM ≥ 10.5 kPa and 8.3% with LSM ≥ 13.3 kPa. The true positive rates were comparable at 87% for sequential covering analysis, 93% for LSM ≥ 10.5 kPa and 83% for LSM ≥ 13.3 kPa. CONCLUSION: The proposed clinical sequential covering analysis allows for better risk stratification when evaluating for advanced fibrosis in LT recipients compared to LSM alone. Additional efforts are necessary to further reduce the number of patients with indeterminate results in whom a liver biopsy may be required.


Asunto(s)
Algoritmos , Diagnóstico por Imagen de Elasticidad , Cirrosis Hepática , Trasplante de Hígado , Vibración , Humanos , Diagnóstico por Imagen de Elasticidad/métodos , Trasplante de Hígado/efectos adversos , Persona de Mediana Edad , Femenino , Masculino , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Adulto , Biopsia , Anciano , Hígado/patología , Hígado/diagnóstico por imagen , Estudios Retrospectivos
6.
Eur J Orthop Surg Traumatol ; 34(3): 1253-1258, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38085371

RESUMEN

This review presents the principal features of paediatric femoral shaft fractures including the contemporary management strategies and relevant supporting evidence. The article is an overview of information relevant to clinical practice, in addition to preparation for the FRCS (Orth) examination.


Asunto(s)
Fracturas del Fémur , Humanos , Niño , Fracturas del Fémur/diagnóstico , Fracturas del Fémur/cirugía , Estudios Retrospectivos
7.
Prostate ; 82 Suppl 1: S3-S12, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35657157

RESUMEN

BACKGROUND: An important fraction (>/~10%) of men with high-risk, localized prostate cancer and metastatic prostate cancer carry germline (heritable) pathogenic and likely pathogenic variants (also known as mutations) in DNA repair genes. These can represent known or suspected autosomal dominant cancer predisposition syndromes. Growing evidence suggests that pathogenic variants in key genes involved in homologous recombination and mismatch DNA repair are important in prostate cancer initiation and/or the development of metastases. AIMS: Here we provide a comprehensive review regarding individual genes and available literature regarding risks for developing prostate cancer, and discuss current national guidelines for germline genetic testing in the prostate cancer population and treatment implications. RESULTS: The association with prostate cancer risk and treatment implications is best understood for those with germline mutations of BRCA2, with emerging data supporting associations with ATM, CHEK2, BRCA1, HOXB13, MSH2, MSH6, PALB2, TP53 and NBN. Treatment implications in the metastatic castration resistant prostate cancer setting include rucaparib and olaparib, and pembrolizumab with potential clinical trial opportunities in earlier disease settings. DISCUSSION: The data summarized in this review has led to the expansion of national guidelines for germline genetic testing in prostate cancer. We review these guidelines, and discuss the importance of cascade genetic testing of relatives, diverse populations with attention to inclusion, as well as prostate cancer screening updates and clinical trial opportunities for men who carry genetic risk factors for prostate cancer.


Asunto(s)
Neoplasias de la Próstata , Detección Precoz del Cáncer , Predisposición Genética a la Enfermedad , Células Germinativas/patología , Mutación de Línea Germinal , Humanos , Masculino , Antígeno Prostático Específico/genética , Neoplasias de la Próstata/patología
8.
J Korean Med Sci ; 37(6): e44, 2022 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-35166080

RESUMEN

BACKGROUND: With greater use of social media platforms for promotions of research articles, retracted articles tend to receive approximately the same attention. We systematically analyzed retracted articles from retractionwatch.com to look at the Altmetric Attention Scores (AAS) garnered over a period of time in order to highlight the role of social media and other platforms in advertising retracted articles and its effect on the spread of misinformation. METHODS: Retractionwatch.com was searched for coronavirus disease 2019 related retracted papers on November 6th, 2021. Articles were excluded based on lack of digital object identifier (DOI), if they were preprint articles, absent AAS, and incomplete AAS of pre retraction, post retraction, or both scores. RESULTS: A total of 196 articles were found on the Retraction Watch website of which 189 were retracted papers and 7 were expression of concern (EOC). We then identified 175 articles after excluding those that did not have a DOI and 30 preprint articles were also excluded giving 145 articles. Further exclusion of articles with absent AAS and incomplete AAS resulted in a total of 22 articles. CONCLUSION: Retracted articles receive significant online attention. Twitter and Mendeley were the most popular medium for publicizing retracted articles, therefore more focus should be given by journals and their Twitter accounts to discredit all their retracted articles. Preprints should be reconsidered as a whole by journals due to the huge risk they carry in disseminating false information.


Asunto(s)
Bibliometría , COVID-19 , Retractación de Publicación como Asunto , SARS-CoV-2 , Humanos , Difusión de la Información , Medios de Comunicación Sociales
9.
Int J Health Plann Manage ; 37(3): 1199-1204, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34939218

RESUMEN

The COVID-19 pandemic is having an unprecedented and consequential impact on global economies, businesses, and workforces. Foreign nationals account for the majority of the population in the Middle East. Throughout this article, the authors address the negative ramifications the COVID-19 pandemic has had on the migrant workforce in the Middle East. This pandemic has intensified various socio-economic and public health crises such as unemployment, income cuts, depletion of savings, repatriation difficulties, inadequate living conditions, and associated burden on healthcare facilities by the COVID-19 infection.


Asunto(s)
COVID-19 , Migrantes , Humanos , Medio Oriente/epidemiología , Pandemias , SARS-CoV-2
10.
Int J Health Plann Manage ; 37(1): 547-552, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34462959

RESUMEN

With the overwhelming COVID-19 pandemic in Africa, many other severe epidemics have been given low priority, such as viral hepatitis. Patient mortality due to viral hepatitis has raised concern to COVID-19 patients due to compromise with undiagnosed hepatitis in Africa. The pandemic has worsened the control of the viral hepatitis epidemic as healthcare control facilities have moved their focus towards curbing COVID-19 infections. However, different challenges have arisen to viral hepatitis patients because of low health attention that declines the progress of already diagnosed hepatitis patients. Follow-up plans, routine testing and treatment plans for viral hepatitis are no longer as strict with the human resources transferred towards combating the pandemic. Thus, a global effort is required to abide by renewed recommendations to eradicate viral hepatitis in Africa that also fit the current picture of the COVID-19 pandemic. The article discusses the current challenges viral hepatitis patients faced during the COVID-19 pandemic and important recommendations that can see through these challenges in Africa.


Asunto(s)
COVID-19 , Hepatitis Viral Humana , África/epidemiología , Hepatitis Viral Humana/epidemiología , Hepatitis Viral Humana/prevención & control , Humanos , Pandemias/prevención & control , SARS-CoV-2
11.
Rheumatol Int ; 41(10): 1773-1783, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34357454

RESUMEN

This study aimed at understanding the perception and perspectives of rheumatology trainees about specialist training in India. Rheumatology trainees (Doctorate of Medicine, Diplomate of National Board) in Indian universities (2010 onwards) were contacted to complete a validated e-survey consisting of 41 questions to evaluate the current rheumatology training in India. Of 53 respondents (M:F 3.4:1, mean age 37 years ± 12.7), 81.1% trained at government hospitals, and 15.1% trained at private hospitals. During training period, 37.5% respondents were exposed to 6-7 h of didactics/week. They treated nearly 175 patients (175 ± 35.4) per week and reported a reasonable level of independence in management of patients with common rheumatic diseases (RDs) during their training (7.5 ± 0.7 SD). However, nearly one-third of the trainees were not exposed to basic immunology and laboratory techniques. Similarly, placement in the radiology department was not a part of the curriculum for nearly half of the trainees, 80% were not confident to manage paediatric RDs and soft tissue rheumatism. Almost 60% did not feel comfortable in addressing ancillary care including patient counselling as they had not received formal training. Among the participants, 59% were not satisfied by the current system of assessment, 86.8% suggested for multiple time point-based assessment systems and 45.3% preferred objective and subjective assessment in final examinations. Rheumatology training in India offers notable exposure to patients and independence in managing cases. However, there is an unmet need for improvement in training in the field of laboratory, radiology and ancillary care, and to overhaul assessment system by including objective evaluation.


Asunto(s)
Curriculum , Reumatología/educación , Adulto , Estudios Transversales , Femenino , Humanos , India , Masculino , Encuestas y Cuestionarios
12.
Eur J Orthop Surg Traumatol ; 31(1): 105-109, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32715327

RESUMEN

INTRODUCTION: The novel coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organisation on 11 March 2020. The aim of this study is to assess the impact of COVID-19 on orthopaedic practice and training in the UK. METHODS: Surgeons throughout UK hospitals were asked to complete an electronic survey relating to orthopaedic practice and training in their hospital. The nationwide survey was conducted during the first peak of COVID-19 cases in the UK between 20 March 2020 and 20 April 2020. RESULTS: All 202 UK participants reported disruption to their daily practice. 91% reported all elective operating had been cancelled and trauma continued as normal in only 24% of cases. 70% reported disruption to trauma operating. Elective clinic capacity significantly reduced with no elective clinics running as normal. 55% reported their elective clinics completely cancelled, whilst 38% reported elective clinics running at a reduced capacity, with non-urgent appointments postponed. Only 9% of fracture clinics ran as normal, and 69% had a reduced service. 67% reported teaching and study leave cancelled. Significantly, 69% of participants felt the pandemic would result in a delay to completion of registrar training programmes. CONCLUSION: This is the first nationwide survey assessing the impact of the coronavirus disease 2019 on UK orthopaedic practice and training, during the peak of the pandemic. It highlights the scale of the challenge ahead for the specialty, including during the recovery phase and post-recovery phase of the pandemic.


Asunto(s)
COVID-19/epidemiología , Procedimientos Ortopédicos/estadística & datos numéricos , Ortopedia/educación , Pandemias , Instituciones de Atención Ambulatoria/estadística & datos numéricos , Procedimientos Quirúrgicos Electivos/estadística & datos numéricos , Humanos , Encuestas y Cuestionarios , Reino Unido/epidemiología
13.
Eur J Orthop Surg Traumatol ; 31(5): 893-900, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33786664

RESUMEN

INTRODUCTION: Premature physeal arrest (PPA) of the distal radius is considered a rare complication of physeal wrist fractures. Standardised guidelines for duration of follow up do not exist. The aim of this review is to recognise the risk factors of PPA and guide follow up protocols. The secondary aim is to understand the typical presenting symptoms of PPA. METHOD: A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, MEDLINE, EMBASE, the Cochrane Library, and grey literature were searched from inception to October 2020. Studies included were: (i) original articles, (ii) distal radius physeal injuries, (iii) with at least a partial study population that developed PPA. RESULTS: Thirteen studies were included with 616 physeal injuries. There were 114 PPAs reported with a mean age at time of injury of 10.6 years (1-16). The rate of PPA with radiological follow up was 7-23%. Intraarticular fractures and repeated manipulations increased the rate of PPA. K-wire fixation, open reduction and malunion did not. The most common presenting symptom of PPA was: pain (70%), deformity (55%), restricted range of movement (40%), reduced grip strength (40%) and snapping or clicking (30%). All patients with radial shortening of 10 mm or more were symptomatic. CONCLUSION: There were no risk factors that reliably predicted all PPA. The majority of patients who develop PPA will remain asymptomatic until significant shortening or deformity have occurred. We recommend a minimum of 18 months radiological follow up for every distal radius physeal injury.


Asunto(s)
Huesos del Carpo , Fracturas del Radio , Humanos , Radio (Anatomía) , Fracturas del Radio/diagnóstico por imagen , Factores de Riesgo , Articulación de la Muñeca
14.
Am J Otolaryngol ; 40(1): 78-82, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30472122

RESUMEN

PURPOSE: To evaluate radiographic findings in US Navy recruits found to have asymmetric sensorineural hearing loss (ASNHL) during routine medical screening. MATERIALS AND METHODS: Retrospective analysis of US Navy recruits receiving screening audiometry and medical suitability evaluation from January 2011 to October 2016. Single-institution, institutional review board-approved study of US Navy recruits screened for hearing loss over a six-year period. All recruits with ASNHL were evaluated by an otolaryngologist and received diagnostic radiographic evaluation. Audiometric and imaging results were retrospectively reviewed for this population and compared to common screening criteria. RESULTS: ASNHL was identified in 674 of 228,504 total recruits screened. This population was 91% male and between 17 and 29 years old (mean age 21.1). Six-hundred fifty-three (97%) met criteria for further ASNHL evaluation. Subjective hearing loss was reported in only 6% of patients. Six-hundred sixty-one (99%) received magnetic resonance imaging of the internal auditory canals. Intracranial pathology was identified in 43 (6.3%) patients and 2 (0.3%) had a causative intracranial lesion corresponding to ASNHL. No patients were found to have a vestibular schwannoma. CONCLUSIONS: In a population of healthy young adults with audiometric proven ASNHL, 0.3% had radiographic proven intracranial pathology explaining the hearing loss. Intracranial masses may be less likely to cause ASNHL in this population; further research is needed to determine appropriate MRI screening methods for young adults with ASNHL.


Asunto(s)
Pérdida Auditiva Sensorineural/diagnóstico por imagen , Pérdida Auditiva Sensorineural/etiología , Personal Militar , Adolescente , Adulto , Audiometría , Femenino , Pérdida Auditiva Sensorineural/epidemiología , Humanos , Imagen por Resonancia Magnética , Masculino , Prevalencia , Estudios Retrospectivos , Estados Unidos , Adulto Joven
17.
Mol Phylogenet Evol ; 81: 49-60, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25245952

RESUMEN

BACKGROUND: Understanding the genetic mechanisms underlying the organismal complexity and origin of novelties during vertebrate history is one of the central goals of evolutionary biology. Ohno (1970) was the first to postulate that whole genome duplications (WGD) have played a vital role in the evolution of new gene functions: permitting an increase in morphological, physiological and anatomical complexity during early vertebrate history. RESULTS: Here, we analyze the evolutionary history of human FGFR-bearing paralogon (human autosome 4/5/8/10) by the phylogenetic analysis of multigene families with triplicate and quadruplicate distribution on these chromosomes. Our results categorized the histories of 21 families into discrete co-duplicated groups. Genes of a particular co-duplicated group exhibit identical evolutionary history and have duplicated in concert with each other, whereas genes belonging to different groups have dissimilar histories and have not duplicated concurrently. CONCLUSION: Taken together with our previously published data, we submit that there is sufficient empirical evidence to disprove the 1R/2R hypothesis and to support the general prediction that vertebrate genome evolved by relatively small-scale, regional duplication events that spread across the history of life.


Asunto(s)
Evolución Molecular , Duplicación de Gen , Familia de Multigenes , Filogenia , Animales , Evolución Biológica , Cromosomas , Cromosomas Humanos Par 10 , Cromosomas Humanos Par 4 , Cromosomas Humanos Par 5 , Cromosomas Humanos Par 8 , Genoma Humano , Humanos , Análisis de Secuencia de ADN
18.
Mol Neurobiol ; 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38485841

RESUMEN

In recent years, there has been a surge in interest in investigating the mechanisms underlying memory consolidation. However, our understanding of the behavioural tagging (BT) model and its establishment in diverse brain regions remains limited. This study elucidates the contributions of the anterior cingulate cortex (ACC) and hippocampus in the formation of long-term memory (LTM) employing behaviour tagging as a model for studying the underlying mechanism of LTM formation in rats. Existing knowledge highlights a protein synthesis-dependent phase as imperative for LTM. Brain-derived neurotrophic factor (BDNF) stands as a pivotal plasticity-related protein (PRP) in mediating molecular alterations crucial for long-term synaptic plasticity and memory consolidation. Our study offers evidence suggesting that tropomyosin receptor kinase B (TrkB), the receptor of BDNF, may act as a combined "behavioural tag/PRP". Interfering with the expression of these molecules resulted in impaired LTM after 24 h. Furthermore, augmenting BDNF expression led to an elevation in Arc protein levels in both the ACC and hippocampus regions. Introducing novelty around weak inhibitory avoidance (IA) training resulted in heightened step-down latencies and expression of these molecules, respectively. We also demonstrate that the increase in Arc expression relies on BDNF synthesis, which is vital for the memory consolidation process. Additionally, inhibiting BDNF using an anti-BDNF function-blocking antibody impacted Arc expression in both the ACC and hippocampus regions, disrupting the transformations from labile to robust memory. These findings mark the initial identification of a "behavioural tag/PRP" combination and underscore the involvement of the TrkB-BDNF-Arc cascade in the behavioural tagging model of learning and memory.

19.
J Leukoc Biol ; 116(1): 132-145, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38416405

RESUMEN

Lymph node stromal cells (LNSCs) are an often overlooked component of the immune system but play a crucial role in maintaining tissue homeostasis and orchestrating immune responses. Our understanding of the functions these cells serve in the context of bacterial infections remains limited. We previously showed that Listeria monocytogenes, a facultative intracellular foodborne bacterial pathogen, must replicate within an as-yet-unidentified cell type in the mesenteric lymph node (MLN) to spread systemically. Here, we show that L. monocytogenes could invade, escape from the vacuole, replicate exponentially, and induce a type I interferon response in the cytosol of 2 LNSC populations infected in vitro, fibroblastic reticular cells (FRCs) and blood endothelial cells (BECs). Infected FRCs and BECs also produced a significant chemokine and proinflammatory cytokine response after in vitro infection. Flow cytometric analysis confirmed that GFP+  L. monocytogenes were associated with a small percentage of MLN stromal cells in vivo following foodborne infection of mice. Using fluorescent microscopy, we showed that these cell-associated bacteria were intracellular L. monocytogenes and that the number of infected FRCs and BECs changed over the course of a 3-day infection in mice. Ex vivo culturing of these infected LNSC populations revealed viable, replicating bacteria that grew on agar plates. These results highlight the unexplored potential of FRCs and BECs to serve as suitable growth niches for L. monocytogenes during foodborne infection and to contribute to the proinflammatory environment within the MLN that promotes clearance of listeriosis.


Asunto(s)
Listeria monocytogenes , Listeriosis , Ganglios Linfáticos , Células del Estroma , Animales , Listeriosis/inmunología , Listeriosis/microbiología , Listeriosis/patología , Ganglios Linfáticos/microbiología , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Células del Estroma/microbiología , Células del Estroma/metabolismo , Ratones , Ratones Endogámicos C57BL , Citocinas/metabolismo , Células Endoteliales/microbiología , Células Endoteliales/metabolismo , Susceptibilidad a Enfermedades , Femenino
20.
J Clin Oncol ; 41(16): 3051-3058, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37071839

RESUMEN

Patients with cancer face an array of financial consequences as a result of their diagnosis and treatment, collectively referred to as financial toxicity (FT). In the past 10 years, the body of literature on this subject has grown tremendously, with a recent focus on interventions and mitigation strategies. In this review, we will briefly summarize the FT literature, focusing on the contributing factors and downstream consequences on patient outcomes. In addition, we will put FT into context with our emerging understanding of the role of social determinants of health and provide a framework for understanding FT across the cancer care continuum. We will then discuss the role of the oncology community in addressing FT and outline potential strategies that oncologists and health systems can implement to reduce this undue burden on patients with cancer and their families.


Asunto(s)
Neoplasias , Oncólogos , Humanos , Costo de Enfermedad , Estrés Financiero , Neoplasias/tratamiento farmacológico , Oncología Médica
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