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Antihyperthermic treatment decreases perihematomal hypodensity
Get PDFOBJECTIVE: To investigate the effect on perihematomal hypodensity and outcome of a decrease in body temperature in the first 24 hours in patients with intracerebral hemorrhage (ICH). METHODS: In this retrospective study on a prospectively registered database, among the 1,100 patients, 795 met all the inclusion criteria. Temperature variations in the first 24 hours and perihematomal hypodensity (PHHD) were recorded. Patients >/=37.5 degrees C were treated with antihyperthermic drugs for at least 48 hours. The main objective was to determine the association among temperature variation, PHHD, and outcome at 3 months. RESULTS: The decrease in temperature in the first 24 hours increased the possibility of good outcome 11-fold. Temperature decrease, lower PHHD volume, and a good outcome were observed in 31.8% of the patients who received antihyperthermic treatment. CONCLUSION: The administration of early antihyperthermic treatment in patients with spontaneous ICH with a basal axillary temperature >/=37.5 degrees C resulted in good outcome in a third of the treated patients
Psychophysical Olfactory Tests and Detection of COVID-19 in Patients With Sudden Onset Olfactory Dysfunction: A Prospective Study
Get PDFOBJECTIVE: To investigate the coronavirus disease 2019 (COVID-19) status of patients with initial sudden olfactory anosmia (ISOA) through nasopharyngeal swabs for reverse transcription-polymerase chain reaction (RT-PCR) analysis and to explore their olfactory dysfunctions with psychophysical olfactory evaluation. METHODS: A total of 78 ISOA patients were recruited from April 6, 2020, to April 10, 2020, through a public call of University of Mons (Mons, Belgium). Patients benefited from nasopharyngeal swabs and fulfilled the patient-reported outcome questionnaire. Among them, 46 patients performed psychophysical olfactory evaluation using olfactory identification testing. Based on the duration of the ISOA, 2 groups of patients were compared: patients with olfactory dysfunction duration 12 days (group 2). RESULTS: In group 1, 42 patients (87.5%) had a positive viral load determined by RT-PCR and 6 patients (12.5%) were negative. In group 2, 7 patients (23%) had a positive viral load and 23 patients (77%) were negative. The psychophysical olfactory evaluation reported that anosmia and hyposmia occurred in 24 (52%) and 11 (24%) patients, respectively. Eleven patients were normosmic. The viral load was significantly higher in patients of group 1 compared with those of group 2. CONCLUSIONS: Coronavirus disease 2019 was detected in a high proportion of ISOA patients, especially over the first 12 days of olfactory dysfunction. Anosmia is an important symptom to consider in the detection of COVID-19 infection
Training intensity and improvements in exercise capacity in elderly patients undergoing European cardiac rehabilitation - the EU-CaRE multicenter cohort study
Get PDFOBJECTIVES: Guidelines for exercise intensity prescription in Cardiac Rehabilitation (CR) are inconsistent and have recently been discussed controversially. We aimed (1) to compare training intensities between European CR centres and (2) to assess associations between training intensity and improvement in peak oxygen consumption ([Formula: see text]O2) in elderly CR patients. METHODS: Peak [Formula: see text]O2, heart rate and work rate (WR) at the first and second ventilatory thresholds were measured at start of CR. Training heart rate was measured during three sessions spread over the CR. Multivariate models were used to compare training characteristics between centres and to assess the effect of training intensity on change in peak [Formula: see text]O2. RESULTS: Training intensity was measured in 1011 out of 1633 EU-CaRE patients in 7 of 8 centers and the first and secondary ventilatory threshold were identified in 1166 and 817 patients, respectively. The first and second ventilatory threshold were found at 44% (SD 16%) and 78% (SD 9%) of peak WR and 78% (SD 9%) and 89% (SD 5%) of peak heart rate, respectively. Training intensity and session duration varied significantly between centres but change in peak [Formula: see text]O2 over CR did not. Training above the first individual threshold (beta 0.62, 95% confidence interval [0.25-1.02]) and increase in training volume per hour (beta 0.06, 95%CI [0.01-0.12]) were associated with a higher change in peak [Formula: see text]O2. CONCLUSION: While training intensity and volume varied greatly amongst current European CR programs, changes in peak [Formula: see text]O2 were similar and the effect of training characteristics on these changes were small
GFRα 1-2-3-4 co-receptors for RET Are co-expressed in Pituitary Stem Cells but Individually Retained in Some Adenopituitary Cells
Get PDFThe RET tyrosine kinase receptor is expressed by the endocrine somatotroph cells of the pituitary where it has important functions regulating survival/apoptosis. However, RET is also expressed by the GPS pituitary stem cells localized in a niche between the adenopituitary and the intermediate lobe. To bind any of its four ligands, RET needs one of four co-receptors called GFRalpha1-4. It has been previously shown that GFRalpha1 is expressed by somatotroph cells and acromegaly tumors. GFRalpha2 was shown to be expressed by pituitary stem cells. GFRalpha4 was proposed as not expressed in the pituitary. Here we study the RNA and protein expression of the four GFRalpha co-receptors for RET in rat and human pituitary. The four co-receptors were abundantly expressed at the RNA level both in rat and human pituitary, although GFRalpha4 was the less abundant. Multiple immunofluorescence for each co-receptor and beta-catenin, a marker of stem cell niche was performed. The four GFRalpha co-receptors were co-expressed by the GPS cells at the niche colocalizing with beta-catenin. Isolated individual scattered cells positive for one or other receptor could be found through the adenopituitary with low beta-catenin expression. Some of them co-express GFRalpha1 and PIT1. Immunohistochemistry in normal human pituitary confirmed the data. Our data suggest that the redundancy of GFRalpha co-expression is a self-supportive mechanism which ensures niche maintenance and proper differentiation
Carbohydrates, Starch, Total Sugar, Fiber Intakes and Food Sources in Spanish Children Aged One to <10 Years-Results from the EsNuPI Study
No full textDiet quality is a modifiable factor that may contribute to the onset of diet-related chronic diseases. Currently, in Spain there are no studies that examine the intakes and sources for total carbohydrates, starch, total sugar, and fiber by both children consuming all kind of milks and children regularly consuming adapted milk formulas. Our goal was to evaluate the contribution of different food groups to total carbohydrates, starch, total sugar, and fiber consumption within the EsNuPI study participants by assessing their usual intakes by applying two 24 h dietary recalls that were completed by 1448 children (1 to <10 years) divided into two cohorts: one Spanish Reference Cohort (SRS) of the general population (n = 707) and another cohort which included children consuming adapted milks including follow-on milk, toddler's or growing up milk, fortified and enriched milks, here called Adapted Milk Consumers Cohort" (AMS) (n = 741). Estimation of the usual intake showed that nutrient intake increased with age for all nutrients except for fiber. The percentage of children by age and gender who met the reference intake (RI) range for total carbohydrates, was in all groups more than 50% of individuals, except for girls aged 6 to <10 years from the reference cohort in which only 46.9% complied the RI. Median fiber intake, both in the SRS and the AMS, was well below the adequate intake (AI) for children between 3 and 10 years. Main total carbohydrates sources were cereals, followed by milk and dairy products, fruits, bakery and pastry, vegetables and sugars and sweets. The highest contributors to starch intakes were cereals, bakery and pastry, vegetables, and fruits. Major sources of total sugar intakes were milk and dairy products, fruits, bakery and pastry, sugars and sweets, vegetables, and cereals. Nonetheless, milk and dairy products, and fruits, mainly provided lactose and fructose, respectively, which are not considered free sugars. Higher contribution to fiber intakes was provided by fruits, cereals, vegetables and bakery and pastry. There were no significant differences in relation with the total sugar intake according to the body mass index (BMI) between SRS and AMS. The present study suggests a high proportion of children had total carbohydrates intakes in line with recommendations by public health authorities, but still a significant number presented insufficient total carbohydrate and fiber intakes, while total sugar consumption was high, with no major differences between SRS and AMS cohorts
Detection and dynamics of circulating tumor cells in patients with high-risk prostate cancer treated with radiotherapy and hormones: a prospective phase II study
Get PDFBACKGROUND: Circulating tumor cells (CTCs) are an established prognostic marker in castration-resistant prostate cancer but have received little attention in localized high-risk disease. We studied the detection rate of CTCs in patients with high-risk prostate cancer before and after androgen deprivation therapy and radiotherapy to assess its value as a prognostic and monitoring marker. PATIENTS AND METHODS: We performed a prospective analysis of CTCs in the peripheral blood of 65 treatment-naive patients with high-risk prostate cancer. EpCAM-positive CTCs were enumerated using the CELLSEARCH system at 4 timepoints. A cut off of 0 vs >/= 1 CTC/7.5 ml blood was defined as a threshold for negative versus positive CTCs status. RESULTS: CTCs were detected in 5/65 patients (7.5%) at diagnosis, 8/62 (12.9%) following neoadjuvant androgen deprivation and 11/59 (18.6%) at the end of radiotherapy, with a median CTC count/7.5 ml of 1 (range, 1-136). Only 1 patient presented a positive CTC result 9 months after radiotherapy. Positive CTC status (at any timepoint) was not significantly associated with any clinical or pathologic factors. However, when we analyzed variations in CTC patterns following treatment, we observed a significant association between conversion of CTCs and stages T3 (P = 0.044) and N1 (P = 0.002). Detection of CTCs was not significantly associated with overall survival (P > 0.40). CONCLUSIONS: Our study showed a low detection rate for CTCs in patients with locally advanced high-risk prostate cancer. The finding of a de novo positive CTC count after androgen deprivation therapy is probably due to a passive mechanism associated with the destruction of the tumor. Further studies with larger samples and based on more accurate detection of CTCs are needed to determine the potential prognostic and therapeutic value of this approach in non-metastatic prostate cancer. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01800058
Biological Activities of Cyclic and Acyclic B-Type Laxaphycins in SH-SY5Y Human Neuroblastoma Cells
Get PDFLaxaphycins are a family of non-ribosomal lipopeptides that have been isolated from several cyanobacteria. Some of these compounds have presented cytotoxic activities, but their mechanism of action is poorly understood. In this work, the already described laxaphycins B and B3, and acyclolaxaphycins B and B3 were isolated from the marine cyanobacteria Anabaena torulosa. Moreover, two new acyclic compounds, [des-(Ala(4)-Hle(5))] acyclolaxaphycins B and B3, were purified from the herviborous gastropod Stylocheilus striatus, with this being the first description of biotransformed laxaphycins. The structure of these new compounds was elucidated, together with the absolute configuration of acyclolaxaphycins B and B3. The bioactivities of the six peptides were determined in SH-SY5Y human neuroblastoma cells. Laxaphycins B and B3 were cytotoxic (IC50: 1.8 and 0.8 microM, respectively) through the induction of apoptosis. In comparison, acyclic laxaphycins did not show cytotoxicity but affected mitochondrial functioning, so their effect on autophagy-related protein expression was analyzed, finding that acyclic peptides affected this process by increasing AMPK phosphorylation and inhibiting mTOR. This work confirms the pro-apoptotic properties of cyclic laxaphycins B and is the first report indicating the effects on autophagy of their acyclic analogs. Moreover, gastropod-derived compounds presented ring opening and amino-acids deletion, a biotransformation that had not been previously described
Impact of Tumor LINE-1 Methylation Level and Neoadjuvant Treatment and Its Association with Colorectal Cancer Survival
Get PDFRecent studies suggest that long-interspersed nucleotide element-1 (LINE-1) hypomethylation is commonly found in colorectal cancer (CRC), and is associated with worse prognosis. However, the utility of LINE-1 methylation on the prognosis of CRC is still controversial, and may be due to the fact that some clinical and pathological features may affect LINE-1 methylation. Thus, the aim of this study was to assess the prognostic value of tumor LINE-1 methylation in CRC, through their association with the CRC clinical and pathological characteristics. Survival of sixty-seven CRC patients was evaluated according to the median of tumor LINE-1 methylation, as well as pathological and oncological variables. We also studied the association between LINE-1 methylation and pathological features, and finally, we assessed the overall and disease-free survival of LINE1 methylation, stratified by neoadjuvant treatment and further checked by multivariate Cox regression to assess the statistical interactions. LINE-1 was hypomethylated in the CRC tumor with respect to the tumor adjacent-free area (p < 0.05), without association with any other clinical and oncological features, nor with overall and disease-free survival rates for CRC. Relevantly, in neoadjuvant treatment, LINE-1 methylation was associated with survival rates. Thus, disease-free and overall survival rates of treated CRC patients were worse in the hypomethylated LINE-1 tumors than those with normal LINE-1 methylation (p = 0.004 and 0.0049, respectively). Indeed, LINE-1 was hypermethylated more in the treated patients than in the non-treated patients (p < 0.05). The present study showed that tumor LINE-1 hypomethylation was associated with worse survival rates in only treated patients. Our data suggest an interactive effect of neoadjuvant treatment and tumor LINE-1 methylation, which could be a specific-tissue biomarker to predict survival of the treated patients, and help to personalize treatment in CRC
Genomic Profiling of Uterine Aspirates and cfDNA as an Integrative Liquid Biopsy Strategy in Endometrial Cancer
No full textThe incidence and mortality of endometrial cancer (EC) have risen in recent years, hence more precise management is needed. Therefore, we combined different types of liquid biopsies to better characterize the genetic landscape of EC in a non-invasive and dynamic manner. Uterine aspirates (UAs) from 60 patients with EC were obtained during surgery and analyzed by next-generation sequencing (NGS). Blood samples, collected at surgery, were used for cell-free DNA (cfDNA) and circulating tumor cell (CTC) analyses. Finally, personalized therapies were tested in patient-derived xenografts (PDXs) generated from the UAs. NGS analyses revealed the presence of genetic alterations in 93% of the tumors. Circulating tumor DNA (ctDNA) was present in 41.2% of cases, mainly in patients with high-risk tumors, thus indicating a clear association with a more aggressive disease. Accordingly, the results obtained during the post-surgery follow-up indicated the presence of ctDNA in three patients with progressive disease. Moreover, 38.9% of patients were positive for CTCs at surgery. Finally, the efficacy of targeted therapies based on the UA-specific mutational landscape was demonstrated in PDX models. Our study indicates the potential clinical applicability of a personalized strategy based on a combination of different liquid biopsies to characterize and monitor tumor evolution, and to identify targeted therapies
Sequential Colocalization of ERa, PR, and AR Hormone Receptors Using Confocal Microscopy Enables New Insights into Normal Breast and Prostate Tissue and Cancers
Get PDFMultiplex immunohistochemistry (mIHC) use markers staining different cell populations applying widefield optical microscopy. Resolution is low not resolving subcellular co-localization. We sought to colocalize markers at subcellular level with antibodies validated for clinical diagnosis, including the single secondary antibody (combination of anti-rabbit/mouse-antibodies) used for diagnostic IHC with any primary antibody, and confocal microscopy. We explore colocalization in the nucleus (ColNu) of nuclear hormone receptors (ERa, PR, and AR) along with the baseline marker p63 in paired samples of breast and prostate tissues. We established ColNu mIHCF as a reliable technique easily implemented in a hospital setting. In ERa+ breast cancer, we identified different colocalization patterns (nuclear or cytoplasmatic) with PR and AR on the luminal epithelium. A triple-negative breast-cancer case expressed membrane-only ERa. A PR-only case was double positive PR/p63. In normal prostate, we identified an ERa+/p63+/AR-negative distinct population. All prostate cancer cases characteristically expressed ERa on the apical membrane of the AR+ epithelium. We confirmed this using ERa IHC and needle-core biopsies. ColNu mIHCF is feasible and already revealed a new marker for prostate cancer and identified sub-patterns in breast cancer. It could be useful for pathology as well as for functional studies in normal prostate and breast tissues