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The detection of various molecular species, including complex organic molecules relevant to biochemical and geochemical processes, in astronomical settings, such as the interstellar medium or the outer solar system, has led to the increased need for a better understanding of the chemistry occurring in these cold regions of space. In this context, the chemistry of ices prepared and processed at cryogenic temperatures has proven to be of particular interest due to the fact that many interstellar molecules are believed to originate within the icy mantles adsorbed on nano- and micro-scale dust particles. The chemistry leading to the formation of such molecules may be initiated by ionizing radiation in the form of galactic cosmic rays or stellar winds, and thus, there has been an increased interest in commissioning experimental setups capable of simulating and better characterizing this solid-phase radiation astrochemistry. In this article, we describe a new facility called AQUILA (Atomki-Queen's University Ice Laboratory for Astrochemistry), which has been purposefully designed to study the chemical evolution of ices analogous to those that may be found in the dense interstellar medium or the outer solar system as a result of their exposure to keV ion beams. The results of some ion irradiation studies of CH3OH ice at 20 K are discussed to exemplify the experimental capabilities of the AQUILA as well as to highlight its complementary nature to another laboratory astrochemistry setup at our institute.
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Primary bone tumours can pose diagnostic problems due to their overlapping radiologic and histologic features. Given the recent advancement in our understanding of the biology of bone tumours, multiple immunohistochemical and molecular markers have been devised to aid in their diagnosis. This review provides brief updates on select bone tumours, including chondrosarcomas, benign chondrogenic tumours, osteosarcomas, benign osteogenic tumours, fibroosseous lesions, vascular tumours, osteoclastic giant cell-rich or cystic tumours, chordoma, adamantinoma, small round blue cell sarcomas, and others. We discuss their salient molecular features and novel immunohistochemical correlates, along with some tips to avoid common diagnostic pitfalls.
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Neoplasias Óseas , Condrosarcoma , Osteosarcoma , Sarcoma de Células Pequeñas , Humanos , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/patología , Huesos/patología , Osteosarcoma/patología , Condrosarcoma/diagnóstico , Condrosarcoma/patologíaRESUMEN
OBJECTIVE: Liver lesion characterization is limited by the lack of an established gold standard for precise correlation of radiologic characteristics with their histologic features. The objective of this study was to demonstrate the feasibility of using an ex vivo MRI-compatible sectioning device for radiologic-pathologic co-localization of lesions in resected liver specimens. METHODS: In this prospective feasibility study, adults undergoing curative partial hepatectomy from February 2018 to January 2019 were enrolled. Gadoxetic acid was administered intraoperatively prior to hepatic vascular inflow ligation. Liver specimens were stabilized in an MRI-compatible acrylic lesion localization device (27 × 14 × 14 cm3) featuring slicing channels and a silicone gel 3D matrix. High-resolution 3D T1-weighted fast spoiled gradient echo and 3D T2-weighted fast-spin-echo images were acquired using a single channel quadrature head coil. Radiologic lesion coordinates guided pathologic sectioning. A final histopathologic diagnosis was prepared for all lesions. The proportion of successfully co-localized lesions was determined. RESULTS: A total of 57 lesions were identified radiologically and sectioned in liver specimens from 10 participants with liver metastases (n = 8), primary biliary mucinous cystic neoplasm (n = 1), and hepatic adenomatosis (n = 1). Of these, 38 lesions (67%) were < 1 cm. Overall, 52/57 (91%) of radiologically identified lesions were identified pathologically using the device. Of these, 5 lesions (10%) were not initially identified on gross examination but were confirmed histologically using MRI-guided localization. One lesion was identified grossly but not on MRI. CONCLUSIONS: We successfully demonstrated the feasibility of a clinical method for image-guided co-localization and histological characterization of liver lesions using an ex vivo MRI-compatible sectioning device. KEY POINTS: ⢠The ex vivo MRI-compatible sectioning device provides a reliable method for radiologic-pathologic correlation of small (< 1 cm) liver lesions in human liver specimens. ⢠The sectioning method can be feasibly implemented within a clinical practice setting and used in future efforts to study liver lesion characterization. ⢠Intraoperative administration of gadoxetic acid results in enhancement in ex vivo MRI images of liver specimens hours later with excellent image quality.
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Quistes , Neoplasias Hepáticas , Adulto , Humanos , Medios de Contraste/farmacología , Estudios Prospectivos , Gadolinio DTPA , Hígado/diagnóstico por imagen , Hígado/cirugía , Hígado/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Imagen por Resonancia Magnética/métodos , Quistes/patologíaRESUMEN
The glycocalyx is a cell surface sugar layer of most cell types that greatly influences the interaction of cells with their environment. Its components are glycolipids, glycoproteins, and oligosaccharides. Interestingly, cancer cells have a thicker glycocalyx layer compared to healthy cells, but to date, there has been no consensus in the literature on the exact role of cell surface polysaccharides and their derivatives in cellular adhesion and signaling. In our previous work we discovered that specific glycocalyx components of cancer cells regulate the kinetics and strength of adhesion on RGD (arginine-glycine-aspartic acid) peptide-coated surfaces [1]. Depending on the employed enzyme concentration digesting specific components both adhesion strengthening and weakening could be observed by monitoring the averaged behavior of thousands of cells. The enzyme chondroitinase ABC (ChrABC) was used to digest the chondroitin-4-sulfate, chondroitin-6-sulfate, and dermatan sulfate components in the glycocalyx of cancer cells. In the present work, a high spatial resolution label-free optical biosensor was employed to monitor the adhesivity of cancer cells both at the single-cell and population level. Population-level distributions of single-cell adhesivity were first recorded and analyzed when ChrABC was added to the adhering cells. At relatively low and high ChrABC concentrations subpopulations with remarkably large and weak adhesivity were identified. The changes in the adhesivity distribution due to the enzyme treatment were analyzed and the subpopulations most affected by the enzyme treatment were highlighted. The presented results open up new directions in glycocalyx related cell adhesion research and in the development of more meaningful targeted cancer treatments affecting adhesion.
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INTRODUCTION: Early reports have raised concerns regarding the clinical sensitivity of nasopharyngeal SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) testing for patients with COVID-19 symptoms, which has led to requests for repeat testing at our institution. However, to our knowledge, there are no reports to date of the utilization or results of repeat testing to help guide this practice. METHODS: The authors searched the institutional laboratory information system for consecutive patients who were tested for SARS-CoV-2 by RT-PCR of a nasopharyngeal specimen over a 1-month period. Characteristics and results of patients who received a single or multiple tests were documented and analyzed. RESULTS: Six thousand three (6003) tests were performed on 5757 patients; 272 (4.7%) patients were positive based on their initial test results. Two hundred thirty-six (4%) patients were tested more than once, with 226 (96%) tested twice. The largest proportion of these patients (n=160, 71%) were those who had an initial negative test followed by a repeat test for persistent symptoms. This group included all 7 patients who had discordant positive results on their second test; the result concordance rate within this group was 96%. CONCLUSION: In a population of patients with a low positive rate for SARS-CoV-2 by nasopharyngeal RT-PCR testing, repeat nasopharyngeal testing of negative patients who have persistent symptoms still yields a negative result in 96% of the cases.
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Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Betacoronavirus , COVID-19 , Prueba de COVID-19 , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Pandemias , Prevalencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2 , Sensibilidad y Especificidad , Wisconsin/epidemiologíaRESUMEN
OBJECTIVE: Kidney transplantation is generally considered to be the best treatment for end-stage renal disease. Not every patient can be operated, but many of suitable patients refuse this possibility. We aimed to explore the attitudes of patients with chronic kidney disease towards renal replacement therapies to recognize motives, thoughts, and feelings concerning accepting or refusing the treatment. We studied the attitudes towards the illness and the treatment, the appearance of depression, and the disease burden during different stages of the disease. METHODS: For this study we implemented a questionnaire that we developed (which has been described in an earlier publication of this journal) with 99 pre-dialysis patients, 99 dialysis patients, and 87 transplantation patients. We completed the attitude questionnaire designed by our team to include disease burden and depression questionnaires. RESULTS: We used discriminant analysis to describe different stages of the disease. There was a significant difference in the following factors between the three patient groups: accepting the new kidney, lack of confidence in transplantation therapy, fear of surgery, accepting self-responsibility in recovery, dependency on the transplanted kidney, confidence in recovery, subjective burden of dialysis, and denial of personal responsibility in maintaining the transplanted kidney. Significant differences were also detected in these three groups regarding the level of depression and disease burden: we measured the highest value among the dialysis patients, and the lowest value among the pre-dialysis patients. Comparing patients accepting and refusing transplantation, we found a correlation between the refusal of transplantation and the attitudes towards the illness and treatment. CONCLUSIONS: Most patients remain unmotivated to change treatment modality and refuse transplantation. Misbelief about transplantation shows a correlation with the motive of refusal. Dissemination of information may facilitate a change in the situation.
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Conocimientos, Actitudes y Práctica en Salud , Trasplante de Riñón/psicología , Insuficiencia Renal Crónica/psicología , Terapia de Reemplazo Renal/psicología , Adulto , Anciano , Depresión/psicología , Miedo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Motivación , Insuficiencia Renal Crónica/cirugía , Encuestas y CuestionariosRESUMEN
OBJECTIVE: The aim of this study was to compare an in-person, group-based behavioral weight loss intervention to technology-based interventions in adults with obesity. METHODS: Adults (N = 39; body mass index: 39.5 ± 2.8 kg m-2; age: 39.9 ± 11.5 years) participated in a 6-month program with randomization to one of three intervention groups: standard behavioral weight loss, a technology-based system combined with a monthly intervention telephone call (TECH) or an enhanced technology-based system combined with a monthly intervention telephone call (EN-TECH). All groups were prescribed an energy-restricted diet and physical activity. Assessments occurred at 0, 3 and 6 months. Separate mixed-effects models using unstructured dependence structure were fit to the outcomes. RESULTS: Weight loss (least square means ± standard error) at 6 months was -6.57 ± 1.65 kg in standard behavioral weight loss, -5.18 ± 1.72 kg in TECH and -6.25 ± 1.95 kg in EN-TECH (p-value for time effect ≤ 0.0001). A similar pattern was observed for change in body mass index, waist circumference and percent body fat. There was a decrease in total energy intake (p = 0.0005) and percent dietary fat intake (p = 0.0172), and physical activity increased (p = 0.0003). CONCLUSIONS: Findings provide initial information on the use of technology-based interventions that include wearable devices combined with brief monthly telephone calls for weight loss in adults with obesity.
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OBJECTIVE: The aim of this work was the exploration of chronic renal insufficiency patients' attitudes toward treatment, various motifs underlying their acceptance or refusal of kidney therapy, and understanding of their psychologic content. Examinations were carried out of chronic renal insufficiency patients' attitudes toward renal treatments, and a questionnaire suitable for its assessment was developed. METHODS: Suppositions of patients before and after renal transplantation were explored by means of semistructured interviews. The content-based analysis of the interview narratives revealed the system of content-categories, which we fitted with attitude questions. Transplant patients took part in the trial of the questionnaire, and the statistical analysis of their replies revealed specific variations in patients' attitudes toward transplantations. RESULTS: The results of the principal component analysis classified the replies of transplanted patients into 8 categories for interpretation: hope of recovery, effects of dialysis in deterioration of quality of life, mistrust of transplantation, refusal, anxiety in the run-up phase to transplantation, difficulty in acceptance of the disease and transplantation as a treatment, fears of living-donor transplantations, acceptance of transplantation, and curiosity about dead donors. CONCLUSIONS: Our research explored attitude variances among patients for and against transplantations. A good understanding of patients' attitudes (the exploration of valid and invalid assumptions) might exert a positive influence on patient decisions, and might improve their attitude toward their treatment and their adherence from preparation for the operation to the postoperative phase of recovery.
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Actitud Frente a la Salud , Trasplante de Riñón/psicología , Encuestas y Cuestionarios , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Componente Principal , Calidad de Vida , Diálisis Renal/psicologíaRESUMEN
The purpose of this study was to investigate the influence of exposure to ultraviolet radiation (UVB) on vitamin D status, intestinal calcium absorption and bone metabolism in growing sheep and goats. The hypothesis was that growing sheep and goats are able to synthesise vitamin D within their skin as a result of UVB exposure and that respective consequences for their vitamin D blood levels and the associated parameters can be shown. Fourteen 18-week-old lambs and goat kids were kept in an UVB-free environment and randomly assigned to two groups. One group was daily exposed to UVB (300 watt) for 12 weeks, and the other served as a control group. Except for the exposure to UVB, all animals were kept under the same conditions and fed according to their requirements. Before the start of the experiment and every second week, blood samples were taken. Also the left metatarsus of each animal was analysed by quantitative computer tomography to test for bone mineral status before the start, in week 7 and at the end of the experiment. After 12 weeks, the animals were slaughtered and samples were taken from skin, gastrointestinal tract and kidney for further analyses. In this study, exposure to UVB led to increased serum 1,25-dihydroxyvitamin D (1,25VitD) levels in goat kids, whereas in lambs, serum 25-hydroxyvitamin D (25VitD) levels were increased. In both species UVB-exposed animals showed lower 7-dehydrocholesterol (7DHC) values in skin than their respective control groups. These results indicate that growing goat kids and lambs are able to synthesise vitamin D in the skin when being exposed to UVB.
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Calcio/metabolismo , Cabras/crecimiento & desarrollo , Homeostasis/efectos de la radiación , Ovinos/crecimiento & desarrollo , Rayos Ultravioleta , Vitamina D/sangre , Animales , Desarrollo Óseo , Huesos/metabolismo , Calcio/sangre , Relación Dosis-Respuesta en la Radiación , Femenino , Cabras/sangre , Masculino , Osteocalcina/sangre , Osteocalcina/metabolismo , Ovinos/sangre , Factores de TiempoRESUMEN
Traumatic brain injury (TBI) due to explosive blast exposure is a leading combat casualty. It is also implicated as a key contributor to war related mental health diseases. A clinically important consequence of all types of TBI is a high risk for development of seizures and epilepsy. Seizures have been reported in patients who have suffered blast injuries in the Global War on Terror but the exact prevalence is unknown. The occurrence of seizures supports the contention that explosive blast leads to both cellular and structural brain pathology. Unfortunately, the exact mechanism by which explosions cause brain injury is unclear, which complicates development of meaningful therapies and mitigation strategies. To help improve understanding, detailed neuropathological analysis is needed. For this, histopathological techniques are extremely valuable and indispensable. In the following we will review the pathological results, including those from immunohistochemical and special staining approaches, from recent preclinical explosive blast studies.
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Dirofilariosis is considered to be the arthropod vector-borne disease with the fastest spread in Europe. Slovakia belongs to new endemic regions for canine and human infections. This paper reports the fourth human case, where diagnosis was confirmed using computed tomography (CT), histological and molecular examinations - for the first time in this endemic region. The epidemiological history of this case indicated the autochthonous origin, and infection manifested by intense swelling in the periocular region, where a subcutaneous nodule was localized. Microscopic analysis of cross-sections of the surgically removed nodule confirmed the presence of a single male worm of Dirofilaria repens, indicated by the external cuticular ridges, the robust muscle cells and a single male sex organ seen as one tube beside the intestine. Considering that the worm morphology was partially damaged, molecular study was performed using DNA isolated from formalin-fixed and paraffin-embedded tissue sections of the worm. In polymerase chain reactions (PCR) a set of primers specific for D. repens DNA for the CO1-encoding gene amplified the expected 246 bp product using a high concentration of DNA template. Our diagnostic approach, involving molecular techniques, showed that identification of D. repens from excised tissues is possible even when the morphology of the worm and DNA are damaged during tissue processing. It is expected that the spread of this disease will continue due to climatic changes in central Europe. This warrants higher awareness among clinicians, who will initially be approached by patients, and better co-operation with parasitologists in newly endemic countries.
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Dirofilaria repens/aislamiento & purificación , Dirofilariasis/diagnóstico , Dirofilariasis/parasitología , Enfermedades Endémicas , Animales , ADN de Helmintos/genética , ADN de Helmintos/aislamiento & purificación , Dirofilaria repens/anatomía & histología , Dirofilaria repens/clasificación , Dirofilaria repens/genética , Dirofilariasis/patología , Complejo IV de Transporte de Electrones/genética , Femenino , Histocitoquímica , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Eslovaquia/epidemiología , Tomografía Computarizada por Rayos XRESUMEN
Multiple Sclerosis (MS) is a chronic disease, but in rare fulminant cases rapid progression may lead to death shortly after diagnosis. Currently there is no diagnostic test to predict disease course. The aim of this study was to identify potential biomarkers/proteins related to rapid progression. We present the case history of a 15-year-old male MS patient. Cerebrospinal fluid (CSF) was taken at diagnosis and at the time of rapid progression leading to the patient's death. Using isobaric tag labeling and nanoflow liquid chromatography in conjunction with matrix assisted laser desorption/ionization time of flight tandem mass spectrometry we quantitatively analyzed the protein content of two CSF samples from the patient with fulminant MS as well as one relapsing-remitting (RR) MS patient and one control headache patient, whose CSF analysis was normal. Seventy-eight proteins were identified and seven proteins were found to be more abundant in both fulminant MS samples but not in the RR MS sample compared to the control. These proteins are involved in the immune response, blood coagulation, cell proliferation and cell adhesion. In conclusion, in this pilot study we were able to show differences in the CSF proteome of a rapidly progressing MS patient compared to a more typical clinical form of MS and a control subject.
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Esclerosis Múltiple/líquido cefalorraquídeo , Proteoma/metabolismo , Proteómica , Adolescente , Humanos , Masculino , Proyectos Piloto , Espectrometría de Masas en TándemRESUMEN
Numerous epidemiological studies have proposed a link between herpes simplex virus (HSV) infection and several common chronic neuropsychiatric and neurodegenerative diseases. Experimental HSV infection of mice can lead to chronic behavioral and neurological deficits and chronic pain. While neuron injury and loss are well-documented consequences of the acute phase of infection, the pathologic consequences of latent HSV infection are poorly understood. To determine whether latent HSV infection can cause neuronal injury in mice, trigeminal ganglia (TG) derived from adult BALB/c mice 1, 12 and 31 weeks after corneal HSV type 1 (HSV-1) inoculation were analyzed for evidence of productive or latent HSV-1 infection, inflammation and changes in neuron size, density and number. We found that latent HSV-1 infection between 12 and 31 weeks after corneal virus inoculation was associated with inflammation and progressive deficits in mean neuron diameter, neuronal nucleus diameter, neuron density and neuron number in the TG relative to mock-infected controls. The extent of neuronal injury during latent infection correlated with the extent of inflammation. These studies demonstrate that latent HSV infection is associated with progressive neuronal pathology and may lead to a better understanding of the role of HSV infections in chronic neurological diseases.
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Infecciones por VIH/patología , Herpesvirus Humano 1/patogenicidad , Neuronas/patología , Ganglio del Trigémino/patología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Factores de Edad , Análisis de Varianza , Animales , Recuento de Células/métodos , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Regulación Viral de la Expresión Génica , Inflamación/etiología , Inflamación/virología , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos BALB C , Neuronas/virología , Fosfoproteínas/metabolismo , Factores de Tiempo , Ganglio del Trigémino/virología , Proteínas Virales/metabolismoRESUMEN
PURPOSE: To report preliminary experiences with the treatment of aortic aneurysm sac abscesses following prior endovascular aortic aneurysm repair (EVAR) using computerized tomography (CT)-guided percutaneous drainage. CASE REPORTS: Three patients aged 73 to 78 years with aortic aneurysm sac infections following prior EVAR, 2 of which were associated with aortoduodenal fistula, underwent CT-guided percutaneous drainage and catheter placement. One patient had complete resolution of the aortic aneurysm sac abscess following percutaneous drainage; 1 patient was stabilized to eventual extraanatomic bypass, graft explantation, and fistula repair; and 1 patient was temporized to debridement and fistula repair with endograft preservation. CONCLUSION: CT-guided percutaneous drainage may be a helpful therapy in selected patients for the treatment of aortic aneurysm sac infections following EVAR.
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Absceso/cirugía , Aneurisma Infectado/cirugía , Aneurisma de la Aorta/cirugía , Implantación de Prótesis Vascular/efectos adversos , Prótesis Vascular/efectos adversos , Drenaje/métodos , Procedimientos Endovasculares/efectos adversos , Infecciones Relacionadas con Prótesis/cirugía , Absceso/diagnóstico por imagen , Absceso/microbiología , Anciano , Anciano de 80 o más Años , Aneurisma Infectado/diagnóstico por imagen , Aneurisma Infectado/microbiología , Antibacterianos/uso terapéutico , Aortografía/métodos , Implantación de Prótesis Vascular/instrumentación , Desbridamiento , Remoción de Dispositivos , Procedimientos Endovasculares/instrumentación , Humanos , Masculino , Infecciones Relacionadas con Prótesis/diagnóstico por imagen , Infecciones Relacionadas con Prótesis/microbiología , Radiografía Intervencional , Reoperación , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
To better understand melanoma resistance to herpes simplex virus type 1 (HSV-1)-mediated oncolysis, traditional two-dimensional (2D) cultures and extracellular matrix (ECM) containing three-dimensional (3D) cultures of OCM1 and C918 uveal melanoma cells were infected with an HSV-1 strain that expresses the green fluorescent protein (GFP) marker during replication. Although 2D cultures were completely destroyed within a few days of HSV-1 inoculation, viable GFP-negative tumor cells remained detectable in 3D cultures for several weeks. Tumor cells with increased resistance to HSV-1 included cells that formed vasculogenic mimicry patterns and multicellular spheroids and cells that invaded Matrigel individually. Mechanisms of tumor resistance against HSV-1 in the 3D environment included impaired virus spread in the ECM and ECM-mediated inhibition of viral replication after viral entry into tumor cells. Observations also suggested that HSV-1 established quiescent infection in some tumor cells present in multicellular spheroids and that this could revert to productive viral infection when the tumor growth pattern changed. These findings indicate that 3D tumor cell cultures can be used to identify distinct tumor cell populations with increased resistance to HSV-1 and to explore mechanisms of ECM-mediated tumor resistance to oncolytic virotherapy.
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Farmacorresistencia Viral , Herpesvirus Humano 1/patogenicidad , Melanoma/patología , Viroterapia Oncolítica , Neoplasias de la Úvea/patología , Técnicas de Cultivo de Célula , Colágeno/metabolismo , Combinación de Medicamentos , Matriz Extracelular , Humanos , Laminina/metabolismo , Melanoma/terapia , Melanoma/virología , Proteoglicanos/metabolismo , Células Tumorales Cultivadas , Neoplasias de la Úvea/terapia , Neoplasias de la Úvea/virología , Replicación ViralRESUMEN
PURPOSE: Herpes virus entry mediator (HVEM) plays a critical role in the regulation of inflammation through interaction with its natural ligands LIGHT and lymphotoxin alpha and also serves as one of the entry receptors of herpes simplex virus (HSV). The purpose of this study was to better understand the expression of HVEM in the cornea and trigeminal ganglia (TG), which are important targets of HSV infection. MATERIALS AND METHODS: Immunohistochemistry was used to define HVEM expression in the cornea and TG of normal and HSV-1 infected mice euthanized 2 to 5 days or 7 months following corneal inoculation of virus. RESULTS: We found that HVEM is widely expressed in the normal corneal epithelium and endothelium, is weakly and focally expressed in the corneal stroma, and is expressed in a portion of neurons and non-neuronal cells in the TG. Acute HSV-1 keratitis and ganglionitis were associated with increased HVEM expression in the corneal epithelium and stroma and in neurons and non-neuronal cells of TG, and many inflammatory cells in these tissues also expressed HVEM. TG derived from mice 7 months after virus inoculation demonstrated latent HSV-1 infection that was associated with increased HVEM expression in neurons and non-neuronal cells relative to uninfected control tissues. Latent TG also contained focal infiltrates of mononuclear inflammatory cells, many of which expressed HVEM. Corneas derived from latently infected mice demonstrated chronic keratitis, with no evidence of virus replication or increased HVEM expression in the corneal epithelium, and inflammatory cells present showed only weak HVEM expression. CONCLUSIONS: HVEM is expressed in the cornea and TG and therefore may serve as an HSV entry receptor in these tissues. Furthermore, these findings raise the possibility that changes in HVEM expression following ocular HSV-1 infection can modulate HSV spread and infection-induced inflammation in the cornea and TG.
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Córnea/metabolismo , Regulación de la Expresión Génica , Herpesvirus Humano 1/fisiología , Queratitis Herpética/metabolismo , Miembro 14 de Receptores del Factor de Necrosis Tumoral/biosíntesis , Ganglio del Trigémino/metabolismo , Enfermedad Aguda , Animales , Línea Celular , Córnea/patología , Córnea/virología , Cricetinae , Femenino , Humanos , Inflamación/metabolismo , Inflamación/virología , Queratitis Herpética/patología , Queratitis Herpética/virología , Ratones , Ratones Endogámicos BALB C , Miembro 14 de Receptores del Factor de Necrosis Tumoral/genética , Ganglio del Trigémino/patología , Ganglio del Trigémino/virología , Internalización del Virus , Latencia del Virus , Replicación ViralRESUMEN
The costs associated with gastrointestinal infection (GI) in the province of British Columbia, Canada, were estimated using data from a population-based survey in three health service delivery areas, namely Vancouver, East Kootenay and Northern Interior. The number of cases of disease, consequent expenditure of resources and associated economic costs were modeled as probability distributions in a stochastic model. Using 2004 prices, the estimated mean annual cost per capita of gastrointestinal infection was CAN$128.61 (207.96 euros), with a mean annual cost per case of CAN$1,342.57 (2,170.99 euros). The mean estimate of the overall economic burden to British Columbia was CAN$514.2 million (831.5 million euros) (95% CFI CAN$161.0 million to CAN$5.8 billion; 260.3 million euros to 9.38 billion euros). The major element of this cost was the loss of productivity associated with time away from paid employment by both the sick and their caregivers. Sensitivity analysis suggested that the uncertainty associated with the base model assumptions did not significantly affect the estimates. The results are comparable to those obtained in an earlier study using a similar analytical framework and data from the city of Hamilton, Ontario, Canada.
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Costo de Enfermedad , Enfermedades Gastrointestinales/economía , Enfermedades Gastrointestinales/epidemiología , Costos de la Atención en Salud , Enfermedad Aguda , Colombia Británica/epidemiología , Costos y Análisis de Costo , Estudios Transversales , Empleo/economía , Femenino , Enfermedades Gastrointestinales/complicaciones , Humanos , Masculino , Prevalencia , Estudios Retrospectivos , Vigilancia de Guardia , Ausencia por Enfermedad/economía , Procesos EstocásticosRESUMEN
PURPOSE: The human conjunctiva is a natural target for herpes simplex virus (HSV)-1 infection. The goals of this study were to investigate the cellular and molecular mechanisms of HSV-1 entry into human conjunctival epithelial (HCjE) cells. Specific features of entry studied included the method of initial viral binding to cells, pH dependency, and expression and usage of specific HSV-1 entry receptors. METHODS: To observe HSV-1 initial binding, live cell imaging was performed on HSV-1-infected HCjE cells. Reporter HSV-1 virions expressing beta-galactosidase were used to determine entry of wild-type HSV-1(KOS) and a mutant, HSV-1(KOS)Rid1, into HCjE cells. HSV-1 replication in HCjE cells was determined by plaque assays. Lysosomotropic agents were used to determine whether viral entry was pH dependent. Reverse transcription (RT)-PCR, flow cytometry, and immunohistochemistry were used to determine the expression of receptors. Receptor-specific siRNAs were used to define the role of individual entry receptors. RESULTS: HSV-1 virions attach to filopodia present on HCjE cells and use them to reach the cell body for entry. Cultured HCjE cells demonstrate susceptibility to HSV-1 entry and form plaques confirming viral replication. Blocking vesicular acidification significantly reduces entry, implicating a pH-dependent mode of entry. Multiple assays confirm the expression of entry receptors nectin-1, HVEM, and 3-O-sulfated heparan sulfate (3-OS HS) on the HCjE cell membrane. Knocking down of gD receptors by siRNAs interference implicates nectin-1 and HVEM as the major mediators of entry. CONCLUSIONS: HSV-1 entry into HCjE cells is a pH-dependent process that is aided by targeted virus travel on filopodia. HCjE cells express all three major entry receptors, with nectin-1 and HVEM playing the predominant role in mediating entry.
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Conjuntiva/virología , Células Epiteliales/virología , Herpes Simple/prevención & control , Herpesvirus Humano 1/patogenicidad , Proteínas de Filamentos Intermediarios/fisiología , Proteínas del Tejido Nervioso/fisiología , Miembro 14 de Receptores del Factor de Necrosis Tumoral/fisiología , Internalización del Virus , Animales , Células CHO , Conjuntiva/fisiología , Cricetinae , Cricetulus , Células Epiteliales/fisiología , Herpesvirus Humano 1/fisiología , Humanos , Nestina , Seudópodos/virología , Ensayo de Placa ViralRESUMEN
Herpes simplex viruses (HSV) produce age-dependent encephalitis characterized by more severe involvement of the cerebral cortex in younger hosts. To elucidate the potential role of the major neural entry receptor of HSV, nectin-1, in age-dependent susceptibility of cortical neurons to viral encephalitis, the authors examined the anatomical distribution of the receptor protein in the developing human and mouse cerebral cortex, hippocampus, and cerebellum by immunohistochemistry. Nectin-1 is expressed at high levels in guiding cells (radial glial cells and Cajal-Retzius cells) that regulate radial migration of neurons in cortical lamination, at lower levels in migrating neurons, and at variable levels in the transient ventricular and marginal zones of the cerebral cortical wall. These results may have implications regarding the selective spatiotemporal tropism of HSV to specific neuronal populations, and for the better understanding of neurodevelopmental defects caused by fetal HSV infections.
Asunto(s)
Encéfalo/citología , Moléculas de Adhesión Celular/metabolismo , Cerebelo/citología , Corteza Cerebral/citología , Neuronas/metabolismo , Animales , Movimiento Celular , Corteza Cerebral/embriología , Femenino , Ganglios/metabolismo , Humanos , Ratones , Nectinas , Neuroglía/citología , Neuroglía/metabolismo , Neuroglía/fisiología , Neuronas/fisiologíaRESUMEN
Under-reporting of infectious gastrointestinal illness (IGI) in British Columbia, Canada was calculated using simulation modelling, accounting for the uncertainty and variability of input parameters. Factors affecting under-reporting were assessed during a cross-sectional randomized telephone survey. For every case of IGI reported to the province, a mean of 347 community cases occurred (5th and 95th percentile estimates ranged from 181 to 611 community cases, respectively). Vomiting [odds ratio (OR) 2.15, 95% confidence interval (CI) 1.03-4.49] and antibiotic use in the previous 28 days (OR 3.59, 95% CI 1.17-10.97) significantly predicted health-care visits in a logistic regression model. In bivariate analyses, physicians were significantly less likely to request stool samples from patients with vomiting (RR 0.09, 95% CI 0.01-0.65) and patients of North American as opposed to non-North American cultural groups (RR 0.38, 95% CI 0.15-0.96). Physicians were more likely to request stool samples from older patients (P=0.003), patients with fewer household members (P=0.002) and those who reported anti-diarrhoeal use following illness (RR 3.33, 95% CI 1.32-8.45). People with symptoms of vomiting were under-represented in provincial communicable disease statistics. Differential degrees of under-reporting must be understood before biased surveillance data can be adjusted.