RESUMEN
BACKGROUND AND OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is known for its unfavorable prognosis. Gaining insights into the molecular mechanisms that contribute to its progression is crucial for developing effective therapies. In this study, our objective was to investigate the molecular pathways associated with short-term survival in patients with PDAC. METHODS: Immune profiles were analyzed from both long-term survivors (n = 10) and short-term survivors (n = 10) after surgical resection. Pathway scores were calculated to compare the two groups. RESULTS: The "Adhesion" pathway emerged as the most significant pathway, exhibiting a notably higher score in the samples of short-term survivors (P < 0.009). Within this pathway, significant findings were observed in genes related to integrins and CEACAM. CONCLUSION: The role of integrins in the tumor microenvironment of pancreatic cancer is of utmost importance, as they are found to be overexpressed in short-term survivors. These findings provide valuable insights into the underlying biology of PDAC and have potential implications for the development of therapeutic strategies.
Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/patología , Pronóstico , Transducción de Señal , Integrinas , Microambiente TumoralRESUMEN
BACKGROUND: Defining the tumor immune microenvironment (TIME) of patients using transcriptome analysis is gaining more popularity. Here, we examined and discussed the pros and cons of using RNA sequencing for fresh frozen samples and targeted gene expression immune profiles (NanoString) for formalin-fixed, paraffin-embedded (FFPE) samples to characterize the TIME of ependymoma samples. RESULTS: Our results showed a stable expression of the 40 housekeeping genes throughout all samples. The Pearson correlation of the endogenous genes was high. To define the TIME, we first checked the expression of the PTPRC gene, known as CD45, and found it was above the detection limit in all samples by both techniques. T cells were identified consistently using the two types of data. In addition, both techniques showed that the immune landscape was heterogeneous in the 6 ependymoma samples used for this study. CONCLUSIONS: The low-abundant genes were detected in higher quantities using the NanoString technique, even when FFPE samples were used. RNA sequencing is better suited for biomarker discovery, fusion gene detection, and getting a broader overview of the TIME. The technique that was used to measure the samples had a considerable effect on the type of immune cells that were identified. The limited number of tumor-infiltrating immune cells compared to the high density of tumor cells in ependymoma can limit the sensitivity of RNA expression techniques regarding the identification of the infiltrating immune cells.
Asunto(s)
Ependimoma , Transcriptoma , Humanos , Fijación del Tejido/métodos , Formaldehído , Perfilación de la Expresión Génica/métodos , Ependimoma/genética , Análisis de Secuencia de ARN/métodos , Adhesión en Parafina , Microambiente Tumoral/genéticaRESUMEN
Pregnancy is one of the risk factors for biliary sludge (BS) formation. In this cross-sectional study, a total of 959 pregnant women were included. Serum aspartate aminotransferase, alanine aminotransferase, sodium, potassium, triglycerides, cholesterol levels and the presence of ketones in urine were determined. The presence of BS was investigated using maternal abdominal ultrasound. The incidence of BS in pregnancies complicated by hyperemesis gravidarum (HG) was 14%. The degree of ketonuria and low birth weight were statistically higher in pregnancies with maternal BS than women without sludge. Total weight gain during pregnancies with BS was statistically lower than controls. The incidence of BS in pregnancies with HG does not appear to increase due to HG-related complications, such as dehydration, starvation and weight loss. However, the severity of HG may be worse when HG is associated with sludge.Impact StatementWhat is already known on this subject? The incidence of biliary sludge (BS) in pregnant women ranges between 10.9% and 36%. Some clinical conditions, such as pregnancy, prolonged fasting, total parenteral nutrition, rapid weight loss and ceftriaxone treatment can play a role in the formation of gallbladder sludge.What do the results of this study add? This is the first study to investigate the incidence of BS in hyperemesis gravidarum (HG) pregnancies. Results show that HG may transiently be associated with BS. HG is more likely to cause a transient increase in new sludge formation. The symptoms and complications related to HG may be more severe when HG is associated with BS.What are the implications of these findings for clinical practice and/or further research? Our study showed that BS can be found in HG patients, and HG can be a predisposing factor for new sludge formation, although this association is generally driven by advanced maternal age and increased baseline serum lipid and alanine aminotransferase levels. BS may also be independently associated with an increased risk of subsequent preterm delivery in women with HG.
Asunto(s)
Hiperemesis Gravídica , Alanina Transaminasa , Aspartato Aminotransferasas , Bilis , Ceftriaxona , Colesterol , Estudios Transversales , Femenino , Humanos , Incidencia , Recién Nacido , Cetonas , Lípidos , Potasio , Embarazo , Primer Trimestre del Embarazo , Aguas del Alcantarillado , Sodio , Triglicéridos , Pérdida de PesoRESUMEN
It can be misleading to think that the new severe acute respiratory syndrome coronavirus (SARS-CoV2) which has a very strong mutation and adaptation capabilities, uses only the angiotensin-converting enzyme II (ACE2) pathway to reach target cells. Despite all the precautions taken, the pandemic attack continues and the rapid increase in the number of deaths suggest that this virus has entered the cell through different pathways and caused damage through different mechanisms. The main reason why the ACE2 pathway comes to the fore in all scientific studies is that this receptor is located at the entry point of basic mechanisms that provide alveolo-capillary homeostasis. SARS-CoV-2 has to use nuclear factor-κB (NF-kB), caveloae, clathrin, lipoxin, serine protease and proteasome pathways in addition to ACE2 to enter the target cell and initiate damage. For this reason, while new drug development studies are continuing, in order to be beneficial to patients in their acute period, it is imperative that we are able to come up with drugs that activate or inhibit these pathways and are currently in clinical use. It is also critical that we adopt these new pathways to the treatment of pregnant women affected by SARS-CoV-2, based on the scientific data we use to treat the general population.
Asunto(s)
Betacoronavirus/metabolismo , Caveolina 1/metabolismo , Infecciones por Coronavirus/metabolismo , Lipoxinas/metabolismo , FN-kappa B/metabolismo , Neumonía Viral/metabolismo , Complicaciones Infecciosas del Embarazo/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Enzima Convertidora de Angiotensina 2 , Anticolesterolemiantes/uso terapéutico , Sitios de Unión , COVID-19 , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Descubrimiento de Drogas/métodos , Reposicionamiento de Medicamentos/métodos , Femenino , Humanos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , FN-kappa B/antagonistas & inhibidores , Uso Fuera de lo Indicado , Pandemias , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/transmisión , Neumonía Viral/virología , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Inhibidores de Proteasoma/uso terapéutico , SARS-CoV-2 , Serina Endopeptidasas/metabolismo , Inhibidores de Serina Proteinasa/uso terapéutico , Internalización del VirusRESUMEN
BACKGROUND: Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus of the genus Nairovirus family Bunyaviridae, which are enveloped viruses containing tripartite, negative polarity, single-stranded RNA. CCHF is characterized by high case mortality, occurring in Asia, Africa, the Middle East and Europe. Currently, there are no specific treatments or licensed vaccines available for CCHFV. Recently, two research groups have found adult mice with defective interferon responses allowed to lethal CCHFV infection. These mouse models could provide invaluable information for further studies. Efforts to develop a vaccine against CCHFV are being made. To determine the efficacy of vaccine candidates it is important to conduct serological studies that can accurately measure levels of protective antibodies. In the present study, a pseudo-plaque reduction neutralization test (PPRNT) based on enzyme-catalyzed color development of infected cells probed with anti-CCHFV antibodies was used to measure neutralization antibody of CCHFV. METHODS: Sixty-nine human serum samples (20 acute and 49 convalescent) were tested. The presence of CCHFV antibodies was determined and confirmed by a commercial ELISA kit. CCHFV RNA was determined by RT-PCR. All the samples were analyzed by PPRNT and fluorescent focus reduction neutralization test (FFRNT) to measure of CCHFV-neutralizing antibodies. RESULTS: Pseudo-plaque reduction neutralization test showed a high sensitivity (98%), specificity (100%) and agreement (96,6%) in qualitative comparison with those of the FFRNT. There was a high correlation between the titers obtained in PPRNT and FFRNT (R2 = 0.92). The inter- and intra-assay variation of PPRNT revealed good reproducibility and positive cut-off of PPRNT was defined as 1:4 by the geometric mean titers for the individual samples distributed. CONCLUSION: The pseudo-plaque reduction neutralization test described in this study is a fast, reproducible and sensitive method for the measurement of CCHF neutralizing antibodies. This novel assay could serve as useful tools for CCHF research in epidemiology, vaccine development and other studies of immunity. It also provides an alternative to PRNT when viruses with no or poor CPE in cell culture.
Asunto(s)
Anticuerpos Neutralizantes/sangre , Virus de la Fiebre Hemorrágica de Crimea-Congo/inmunología , Fiebre Hemorrágica de Crimea/inmunología , Pruebas de Neutralización/métodos , Ensayo de Placa Viral/métodos , Animales , Chlorocebus aethiops , Ensayo de Inmunoadsorción Enzimática , Virus de la Fiebre Hemorrágica de Crimea-Congo/genética , Fiebre Hemorrágica de Crimea/virología , Humanos , ARN Viral/genética , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Células VeroRESUMEN
INTRODUCTION: Since lung adenocarcinoma (LUAD) biopsies are usually small, it is questionable if their prognostic and predictive information is comparable to what is offered by large resection specimens. This study compares LUAD biopsies and resection specimens for their ability to provide prognostic and predictive parameters. METHODS: We selected 187 biopsy specimens with stage I and II LUAD. In 123 cases, subsequent resection specimens were also available. All specimens were evaluated for growth pattern, nuclear grade, fibrosis, inflammation, and genomic alterations. Findings were compared using non-parametric testing for categorical variables. Model performance was assessed using the area under the curve for both biopsies and resection specimens, and overall (OS) and disease-free survival (DFS) was calculated. RESULTS: The overall growth pattern concordance between biopsies and resections was 73.9%. The dominant growth pattern correlated with OS and DFS in resected adenocarcinomas and for high-grade growth pattern in biopsies. Multivariate analysis of biopsy specimens revealed that T2-tumors, N1-status, KRAS mutations and a lack of other driver mutations were associated with poorer survival. Model performance using clinical, histological and genetic data from biopsy specimens for predicting OS and DSF demonstrated an AUC of 0.72 and 0.69, respectively. CONCLUSIONS: Our data demonstrated the prognostic relevance of a high-grade growth pattern in biopsy specimens of LUAD. Combining clinical, histological and genetic information in one model demonstrated a suboptimal performance for DFS prediction and good performance for OS prediction. However, for daily practice, more robust (bio)markers are required to predict prognosis and stratify patients for therapy and follow-up.
Asunto(s)
Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Adenocarcinoma/genética , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/cirugía , Biopsia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , PronósticoRESUMEN
BACKGROUND: Homeobox genes A10 (HOXA10) and A11 (HOXA11), members of the abdominal B gene family, are responsible for embryonic survival and implantation. This study was planned to investigate whether endometrial injury alters the expression of both transcripts in women with implantation failure. METHODS: A total of 54 women with implantation failure were divided into two equal groups as experimental (scratching) and sham (no scratching). Participants in the scratching group were exposed to endometrial injury in the mid-luteal phase, and those in the sham group were exposed to endometrial flushing. The scratching group, but not the sham group, underwent prior endometrial sampling. A second endometrial sampling was performed on the scratching group in the mid-luteal phase of the following cycle. The mRNA and protein levels of the HOXA10 and 11 transcripts were determined in endometrial samples collected before and after injury/flushing. Participants in each group underwent IVF/ET in the cycle after the second endometrial sampling. RESULTS: Endometrial injury caused a 60.1-fold (p < 0.01) increase in HOXA10 mRNA and a 9.0-fold increase in HOXA11 mRNA (p < 0.02). Injury resulted in a significant increase in both HOXA10 (p < 0.001) and HOXA11 protein expression (p < 0.003). There was no significant change in HOXA10 and 11 mRNA expressions after flushing. Clinical pregnancy, live birth, and miscarriage rates of the both groups were similar. CONCLUSIONS: Endometrial injury increases homeobox transcript expression at both mRNA and protein levels.
Asunto(s)
Implantación del Embrión , Infertilidad Femenina , Femenino , Humanos , Embarazo , Implantación del Embrión/genética , Endometrio/metabolismo , Infertilidad Femenina/genética , Nacimiento Vivo , Factores de Transcripción/metabolismoRESUMEN
Background: Indonesia's national Tuberculosis (TB) strategy is public-private mix (PPM). The PPM aims to treat patients who have lost sight during TB treatment as these patients are TB carriers and at risk of transmitting TB. The purpose of this study was to identify predictive factors for loss to follow-up (LFTU) among TB patients receiving treatment when the PPM was at place in Indonesia. Methods: The design of this study was a retrospective cohort study. The data used in this study was sourced from the Tuberculosis Information System (SITB) of Semarang which was recorded routinely during 2020-2021. Univariate analysis, crosstabulation, and logistic regression were performed on 3434 TB patients meeting the minimum variables. Results: The participation of health facilities in reporting TB during the PPM era in Semarang reached 97.6% consisting of 37 primary healthcare center (100%), 8 public hospitals (100%), 19 private hospitals (90.5%), and a community-based pulmonary health center (100%). The regression analysis reveal that the predictive factors of LTFU-TB during the PPM are the year of diagnosis (AOR=1.541; p-value=<0.001; 95% CI=1.228-1.934), referral status (AOR=1.562, p-value=0.007; 95% CI=1.130-2160), healthcare and social security insurance ownership (AOR=1.638; p-value=<0.001; 95% CI=1.263-2.124), drugs source (AOR=4.667; p-value=0.035; 95% CI=1.117-19.489). Conclusions: The PPM strategy in dealing with LTFU patients should focus on TB patients without Healthcare and Social Security Insurance and who receive TB treatment rather than program drugs.
Asunto(s)
Perdida de Seguimiento , Tuberculosis , Humanos , Estudios Retrospectivos , Indonesia , Tuberculosis/tratamiento farmacológico , Tuberculosis/diagnóstico , Atención a la SaludRESUMEN
BACKGROUND: To investigate the effect of three different surface treatments on the microhardness and colour change of artificial enamel lesions. MATERIALS AND METHODS: One hundred bovine teeth were randomly assigned into four groups. Artificial enamel lesions were created using demineralizing solution for all groups except the sound enamel group. Different surface treatments were then performed G1: resin-infiltrant; G2: Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP); G3: artificial saliva; G4: Sound Enamel. Each group was subdivided into three subgroups, where each subgroup was subjected to a different testing method. Subgroup 1: surface microhardness; subgroup 2: cross-sectional microhardness; subgroup 3: colour measurement. Statistical analysis was performed by ANOVA, followed by Tukey's post hoc test. RESULTS: Sound enamel group recorded the highest surface and cross-sectional microhardness results. No significant difference was found between the resin-infiltrant group and CPP-ACP regarding surface and cross-sectional microhardness at different lesion depths. Resin-infiltrant group showed the least colour change (∆E) results compared to the other groups. CONCLUSION: Resin-infiltrant can effectively enhance surface microhardness and enamel resistance to demineralization, additionally, reduces the staining susceptibility of white spot lesions (WSLs) after treatment. CPP-ACP application for 4 weeks seems to improve surface microhardness; however, has a limited effect in resisting staining of WSLs after treatment. © 2022 Australian Dental Association.
Asunto(s)
Caseínas , Fosfopéptidos , Animales , Bovinos , Caseínas/farmacología , Color , Esmalte Dental , Fosfopéptidos/farmacología , Saliva Artificial/farmacologíaRESUMEN
Despite the importance of layered double hydroxides (LDHs) in catalysis, medicine and water treatment, the crystallisation process of these materials is seldom investigated. In this study, in situ characterisation techniques granted unprecedented experimental access to the formation dynamics of carbonate-intercalated Mg2+/Al3+ LDHs as model system when applying the most relevant co-precipitation approaches by exploring the effects of temperature and concentration of reactants. For this purpose, a combinatorial multi-modal characterisation approach was applied involving in situ measurements of pH, ion conductivity and light scattering, as well as synchrotron-based in situ X-ray diffraction (XRD). Shortly after beginning the addition of basic solutions (i.e., sodium carbonate and sodium hydroxide) to the solutions of magnesium nitrate hexahydrate and aluminium nitrate nonahydrate, a stable pH was reached due to the uptake of hydroxyl ions for nuclei formation. Shortly after, crystal growth phase was detected by an increase in the light scattering signal and confirmed via in situ XRD. Increasing the concentration of reactants accelerated the onset of crystal growth by 70% without significantly changing the crystallite size. On the other hand, increasing the temperature up to 65 °C showed a smaller influence on the reaction kinetics but resulted in a two-fold increase in crystallite size. Adding the solution of metal precursors to the basic solution, saturation was rapidly reached, without an induction period, favouring the formation of very small crystallites of approximately 10 nm.
RESUMEN
Objective: Since the benefits of Nano-material usage have been well documented in orthopedic surgery, this study was conducted to explore the effect of polyvinyl alcohol/nano-hydroxyapatite/polyamide 66 (PVA/n-HA/P66) on repairing of traumatic cartilage defects in rabbit knee joint. Methods: New Zealand white rabbits were used to make a rabbit knee traumatic cartilage defect animal model. All rabbits were randomly located in three groups. Group-A (PVA/n-HA+PA66 implanted in cartilage defects); Group-B (HA nanospheres implanted in cartilage defects)/Gelatin sponge composite scaffold); Group-C (only cartilage defect without implant). The repairment of articular cartilage defects and the general observation were studied by using pathological staining and gene expression of collagen using RT-PCR after 12 weeks. Results: After 12 weeks, we observed a small amount of fibrous tissue growth in group C without soft cell filling. The repaired tissue in group B was stained with immunohistochemical and toluidine blue staining for collagen and type II collagen is positive, but chondrocyte structure is more visible. The relative mRNA expression of type II collagen was higher in group B in comparison to other groups. The results of the Wakitani score were 5.50±2.59 for group A, 8.83±2.79 for group B, 11.50±1.05 for group C. Results showed no significant difference between group B and C; however, significant differences were found in the scoring results between groups A and B, and between-group A and C. Conclusion: This study showed the high effectiveness of PVA/n-HA+PA66 in the treatment of cartilage defects through increasing the expression of type II collagen.
Asunto(s)
Cartílago Articular , Animales , Cartílago Articular/patología , Cartílago Articular/cirugía , Colágeno/farmacología , Colágeno Tipo II/genética , Colágeno Tipo II/farmacología , Modelos Teóricos , Conejos , RegeneraciónRESUMEN
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is notorious for its poor prognosis even after curative resection. Responses to immunotherapy are rare and related to inadequate T-cell priming. We previously demonstrated the potency of allogeneic lysate-dendritic cell (DC) vaccination in a preclinical model. Here we translate this concept to patients. METHODS: In this phase I study, patients with resected PDAC were included when they demonstrated no radiologic signs of recurrence after standard-of-care treatment. Allogeneic tumour lysate-loaded autologous monocyte-derived DCs were injected at weeks 0, 2, 4 and at months 3 and 6. Objectives are feasibility, safety and immunogenicity of allogeneic tumour-DCs. The presence of tumour antigens shared between the vaccine and patient tumours was investigated. Immunological analyses were performed on peripheral blood, skin and tumour. RESULTS: Ten patients were included. DC production and administration were successful. All patients experienced a grade 1 injection-site and infusion-related reaction. Two patients experienced a grade 2 fever and 1 patient experienced a grade 3 dyspnoea. No vaccine-related serious adverse events were observed. Shared tumour antigens were found between the vaccine and patient tumours. All evaluated patients displayed a vaccine-induced response indicated by increased frequencies of Ki67+ and activated PD-1+ circulating T-cells. In addition, treatment-induced T-cell reactivity to autologous tumour of study patients was detected. Seven out of ten patients have not experienced disease recurrence or progression at a median follow-up of 25 months (15-32 months). CONCLUSION: Allogeneic tumour lysate-DC treatment is feasible, safe and induces immune reactivity to PDAC expressed antigens.
Asunto(s)
Vacunas contra el Cáncer , Trasplante de Células Madre Hematopoyéticas , Neoplasias Pancreáticas , Antígenos de Neoplasias , Vacunas contra el Cáncer/efectos adversos , Células Dendríticas , Humanos , Inmunoterapia/efectos adversos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Linfocitos T , Neoplasias PancreáticasRESUMEN
Takayasu's arteritis is a rare form of aortic vasculitis, typically described in young Asian females. In this article, we report a unique presentation of type V Takayasu's arteritis in a Hispanic male. To the best of our knowledge, this is the first case of Takayasu's arteritis presenting with the triad of angina, amaurosis fugax, and subclavian steal syndrome. On diagnostic imaging, he was found to have left subclavian and axillary artery stenosis requiring balloon angioplasty. The patient responded to the combination of medical and surgical treatment with full recovery.
Asunto(s)
Amaurosis Fugax/etiología , Angina de Pecho/etiología , Síndrome del Robo de la Subclavia/etiología , Arteritis de Takayasu/diagnóstico , Vértigo/etiología , Corticoesteroides/uso terapéutico , Adulto , Amaurosis Fugax/terapia , Angina de Pecho/terapia , Angioplastia de Balón , Aortografía , Humanos , Angiografía por Resonancia Magnética , Masculino , Inhibidores de Agregación Plaquetaria/uso terapéutico , Síndrome del Robo de la Subclavia/terapia , Arteritis de Takayasu/complicaciones , Arteritis de Takayasu/terapia , Resultado del Tratamiento , Vértigo/terapiaRESUMEN
BACKGROUND: To assess pointwise corneal elevation changes after forced eyelid closure test (FECT) in the eyes of healthy subjects and in eyes with keratoconus. METHODS: Twenty-nine subjects with keratoconus and 31 healthy volunteers were evaluated. Patients with keratoconus who had corneal hydrops, apical scarring, corneal thickness ≤ 400 µm, ocular surface disease, contact lens wear on the examination day and a history of corneal cross-linking were excluded. Exclusion criteria for healthy participants were spherical error > +3.00 D and < -3.00 D, corneal astigmatism > 1.50 D, corneal curvature > 47 D, ocular allergy, clinical findings and family history of keratoconus. Pentacam was performed before and after 20 seconds of FECT and raw data were extracted from the built-in software. Pointwise anterior and posterior elevation changes in the central 8 mm cornea were assessed using paired samples t-test and heat maps were constructed to reflect mean changes and statistically significant data points. Statistical significance was assumed at p < 0.01. RESULTS: Age and gender were similar between healthy subjects (24.5 ± 1.6 years, 46.4 per cent female) and subjects with keratoconus (28.6 ± 9.2 years, 46.4 per cent female, p = 0.19, 0.61, respectively). Healthy eyes displayed posterior depression clustering in the inferotemporal and inferonasal areas (mean change: -4.5 ± 7.8 µm and -5.2 ± 9.8 µm, respectively, all p < 0.01). In contrast, keratoconus eyes exhibited a wider area of posterior elevation clustering in the inferior cornea (mean change: 8.1 ± 14.5 µm, all p < 0.01) with a small extension in the inferotemporal cornea (mean change: 12.1 ± 22.3 µm, all p < 0.01). CONCLUSION: FECT elicits corneal elevation changes mainly in the inferior cornea with the change being more pronounced and wider in eyes with keratoconus.
Asunto(s)
Topografía de la Córnea , Párpados/fisiopatología , Queratocono/fisiopatología , Adulto , Femenino , Voluntarios Sanos , Humanos , MasculinoRESUMEN
The human complement system is represents the main effector arm of innate immunity and its ambivalent function in cancer has been subject of ongoing dispute. Glioma stem-like cells (GSC) residing in specific niches within glioblastomas (GBM) are capable of self-renewal and tumor proliferation. Recent data are indicative of the influence of the complement system on the maintenance of these cells. It appears that the role of the complement system in glial tumorigenesis, particularly its influence on GSC niches and GSC maintenance, is significant and warrants further exploration for therapeutic interventions.
Asunto(s)
Neoplasias Encefálicas/metabolismo , Proteínas del Sistema Complemento/metabolismo , Glioblastoma/metabolismo , Células Madre Neoplásicas/metabolismo , Neoplasias Encefálicas/patología , Glioblastoma/patología , HumanosRESUMEN
Glioblastomas (glioblastoma multiforme, GBM) are most malignant brain tumors characterized by profound vascularization. The activation of macrophages strongly contributes to tumor angiogenesis during GBM development. Previously, we showed that extracellular adenosine deaminase protein Cat Eye Syndrome Critical Region Protein 1 (CECR1) is highly expressed by M2-like macrophages in GBM where it defines macrophage M2 polarization and contributes to tumor expansion. In this study, the effect of CECR1 in macrophages on tumor angiogenesis was investigated. Immunohistochemical evaluation of GBM tissue samples showed that the expression of CECR1 correlates with microvascular density in the tumors, confirming data from the TCGA set. In a three-dimensional co-culture system consisting of human pericytes, human umbilical vein endothelial cells and THP1-derived macrophages, CECR1 knockdown by siRNA and CECR1 stimulation of macrophages inhibited and promoted new vessel formation, respectively. Loss and gain of function studies demonstrated that PDGFB mRNA and protein levels in macrophages are modulated by CECR1. The proangiogenic properties of CECR1 in macrophages were partially mediated via paracrine activation of pericytes by PDGFB-PDGFRß signaling. CECR1-PDGFB-PDGFRß cross-activation between macrophages and pericytes promoted pericyte migration, shown by transwell migration assay, and enhanced expression and deposition of periostin, a matrix component with proangiogenic properties. CECR1 function in (M2-like) macrophages mediates cross talk between macrophages and pericytes in GBM via paracrine PDGFB-PDGFRß signaling, promoting pericyte recruitment and migration, and tumor angiogenesis. Therefore, CECR1 offers a new portent target for anti-angiogenic therapy in GBM via immune modulation.
Asunto(s)
Adenosina Desaminasa/metabolismo , Neoplasias Encefálicas/irrigación sanguínea , Comunicación Celular/fisiología , Glioblastoma/irrigación sanguínea , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Adenosina Desaminasa/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Línea Celular , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , TransfecciónRESUMEN
BACKGROUND: Allergic rhinitis (AR) is a disease that reduces athletic performance. Environmental allergen exposure is higher in outdoor sports (such as orienteering) than indoor sports. The main purpose of this study was to investigate the AR frequency in orienteers comparing with indoor athletes. METHODS: Sixty adolescent athletes (33 orienteers, 27 basketball players) enrolled this prospective study. AR diagnosis was made by both history (ISAAC questionnaire) and physical examination. Nasal endoscopy was performed to observe objective findings (concha hypertrophy, mucosal paleness, serosity, septum deviation, adenoid hypertrophy). Epidermal prick test, pulmonary function test, total IgE and serum eosinophil levels were also assessed. RESULTS: AR was diagnosed in 21 (35%) athletes. 14 (42.4%) were orienteers and 7 (25.9%) were basketball players (P=0.144). Endoscopic findings and skin test positivity were also seen at higher percentages in orienteers with no significance. Training age (sport duration), total IgE levels and skin test positivity were significantly higher in rhinitic orieenters than non-rhinitic orieenters (P=0.046, P=0.0001, and P=0.004, respectively). CONCLUSIONS: Although adolescent orieenters had some higher allergic parameters than indoor athletes, they were not found more susceptible to AR. It seems that the frequency of AR increases with longer training age in orieentering sport. This study is the first report about AR in adolescent orienteers. Future researchs should more focus on comparing allergic conditions between outdoor and indoor sports.
Asunto(s)
Atletas , Rinitis Alérgica/epidemiología , Deportes , Adolescente , Atletas/estadística & datos numéricos , Rendimiento Atlético/fisiología , Baloncesto , Niño , Femenino , Humanos , Incidencia , Masculino , Orientación Espacial/fisiología , Estudios Prospectivos , Factores de Riesgo , Pruebas Cutáneas/estadística & datos numéricosRESUMEN
PURPOSE: To perform a quadrantwise comparison of the minimum distance between the posterior iris and the anterior lens in eyes with pseudoexfoliation syndrome (PXS) and age-matched controls. PATIENTS AND METHODS: This study was designed as a prospective cross-sectional study. The study population consisted of 60 patients with PXS and 50 age-matched controls. Anterior segment Scheimpflug images of segments 90 to 270, 135 to 315, 180 to 360, and 225 to 45 degrees were exported as high-quality JPEG images (1920 pixels wide, 1048 pixels high; each pixel having a physical dimension of 8.064×8.064 µm) for further evaluation. The images were analyzed by Image J software. Minimum lens-iris distance (MLID) of the superior, inferior, nasal, and temporal quadrants were analyzed and compared between the groups. Anterior chamber depth, anterior chamber angle, pupillary diameter, average of K1 and K2 (Km), and cataract grading system by Scheimpflug imaging [Oculus Pentacam Nucleus Grading System (PNS)] were also assessed. RESULTS: The MLIDs of all quadrants in eyes with PXS were shorter than controls and these differences were statistically significant (P<0.05). The shortest distance was recorded in the inferior quadrant followed by the superior, temporal, and nasal quadrants in both groups. Pupillary diameter was the only variable found to be correlated with mean global MLID at a statistically significant level (r=-0.465, P<0.001; adjusted for age, sex, anterior chamber angle, anterior chamber depth, PNS, and Km). CONCLUSION: Eyes with PXS manifested with shorter mean MLID than controls.
Asunto(s)
Síndrome de Exfoliación/patología , Glaucoma de Ángulo Abierto/patología , Iris/patología , Cristalino/patología , Anciano , Anciano de 80 o más Años , Estudios Transversales , Técnicas de Diagnóstico Oftalmológico/instrumentación , Femenino , Humanos , Presión Intraocular , Masculino , Persona de Mediana Edad , Fotograbar/instrumentación , Estudios ProspectivosRESUMEN
Burn injuries are a leading cause of morbidity and mortality, with 195,000 deaths annually. This study was conducted to identify the demographics of burn victims and the effect of different variables on the outcome of their injuries. 4016 patients admitted to the Burns Centre, Civil Hospital Karachi from January 2006 to December 2011 were retrospectively analyzed. Demographics, burn injury details and their outcome were recorded in a pre-designed questionnaire. Injuries were categorized as: fire, chemical, scald or electrical. To estimate total body surface area (TBSA) burned in adults, the rule of nines was used. For children and infants, the Lund-Browder chart was employed. SPSS v16.0 software was used for analysis. Frequencies and percentages of all variables, and the measure of central tendencies and dispersion for continuous variables were calculated. Cross tabs were used to assess mortality. Mean age was 28.13 years. More than half of the cases (n=2337, 58.2%) were aged between 16-30 years. Labourers, housewives and students were the most commonly affected groups. Burn injuries by flame/fire and electricity were most common. Most cases were accidental, followed by suicide attempts and homicides. Mean percentage of TBSA affected was 35.49%. Mean duration of hospital stay was 16.45 days. 50.6% of the expired cases were females. The mean age of expired patients was 30.07 while for patients who survived it was 27.01 years. The outcome of burn injuries is related to various demographic factors. Female gender, increasing age, burn injuries following suicide attempts and greater surface area involvement predict poor outcome.
Les brûlures sont l'une des principales causes de morbidité et de mortalité avec 195.000 morts annuellement. Cette étude a été entreprise pour identifier les facteurs démographiques des patients brûlés et les différentes variables sur les résultats thérapeutiques. 4016 patients ont été admis au Centre des Brûlés de l'Hôpital Civil de Karachi de janvier 2006 à décembre 2011 et leurs dossiers furent analysés rétrospectivement. Les facteurs démographiques, les détails de la brûlure et les résultats furent enregistrés sur un questionnaire; la cause étiologie de la brûlures était précisée: feu, chimique, ébouillantement, électrique. Pour évaluer la surface brûlée corporelle (TBSA), c'est la règle des 9 qui était utilisée chez les adultes, et la règle de Lund et Browder chez les enfants. SPSS v16.0 fut utilisée pour l'analyse. La fréquence et les pourcentages de tous les facteurs et la mesure des constantes et leur variation étaient calculées. Cross tabs furent utilisées pour évaluer la mortalité. La moyenne d'âge était de 28 ans; plus de la moitié des cas (n=2337, 58.2 %) étaient âgés de 16 à 30 ans. Ouvriers, femmes au foyer, et étudiants constituaient le groupe le plus important. Les brûlures par flamme et électriques étaient les plus fréquentes. La plupart des cas était de cause accidentelle, suivi par les tentatives de suicide, et les homicides. Le pourcentage moyen (TBSA) était de 35.49%. La moyenne du temps d'hospitalisation était de 16,45 jours. 50.6% des cas mortels étaient des femmes. L'âge moyen des patients décédés était de 30.07, alors que celle des survivants était de 27.01 années. Le résultat du traitement des brûlures dépend des divers facteurs démographiques. Le sexe féminin, le grand âge, les brûlures lors de tentatives de suicide, et les brûlures de grande surface sont de mauvais pronostic.
RESUMEN
One hundred and sixty patients with louse-borne relapsing fever were treated with a combination therapy of procaine penicillin and tetracycline. Fortified procaine penicillin B.P. was given as 400,000 units in the first day. This was followed the next day by 2 g tetracycline orally in divided doses for seven days. A mild rise in temperature was observed in 22 (13-7%) patients within four hours of administering penicillin. Rigors and hypotension occurred in one patient. Relapse occurred in two patients, of whom one had concomitant typhoid and one visceral leishmaniasis. The combined therapy has been found to be effective and safe. It lacks the disadvantages of penicillin (relapses) and tetracycline (severe reaction), when each drug is used alone.