Expression of CD28, FAS, PD1, and CTLA4 molecules in the blood of women with triple-negative breast cancer.

BACKGROUND: Locally advanced triple-negative breast cancer (TNBC) represents a public health problem in Brazil. Its standard treatment consists of neoadjuvant chemotherapy (NAC). METHODS: This was a longitudinal study with follow-up performed between the years 2015 and 2017. Thirty women with locally advanced TNBC submitted to NAC, and 30 healthy were included. Peripheral blood samples were collected before NAC (Pre-NAC) and after NAC (Post-NAC). RESULTS: Patients with TNBC had elevated levels of CD28+ T, FAS+ T, CTLA4+ T, PD1+ T, CD28+CD4+ T, PD1+CD4+ T and CD8+ T and PD1+ CD8+ T cells compared to controls (p < 0.05). Patients with pathological complete response (pCR) had low FAS+ T cells, FAS+CD4+ T cells, and PD1+CD8+ T cells compared to the non-pCR (p < 0.05). Significant differences were observed in the levels of CD28+ T cells, FAS+ T and PD1+ T, CD4+ T, CD28+CD4+ T, FAS+CD4+ T, PD1+CD4+ T, CD8+ T, and PD1+CD8+ T cells between Pre-NAC and Post-NAC groups (p < 0.05). CONCLUSION: Alterations in the circulating FAS+CD4+ T and PD1+CD8+ T cell levels Pre-NAC are associated with pCR, suggesting potential predictive biomarkers of NAC response in TNBC. The largest changes in the cellular immune response profile Post-NAC showed that chemotherapy treatment can modulate the immune response and that it is associated with prognosis in TNBC.

Cognitive reserve moderates the relationship between childhood maltreatment, objective and subjective cognition, and psychosocial functioning in individuals with first-episode psychosis.

OBJECTIVE: This study aimed to assess the relationship between childhood maltreatment (CM), objective and subjective cognition, and psychosocial functioning in adults with first-episode psychosis (FEP) by examining the moderating role of cognitive reserve (CR). A secondary objective was to explore whether unique CM subtypes (physical and/or emotional abuse, sexual abuse, physical and/or emotional neglect) were driving this relationship. METHOD: Sixty-six individuals with FEP (Mage = 27.3, SD = 7.2 years, 47% male) completed a comprehensive neuropsychological test battery, the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA), the Functioning Assessment Short Test (FAST), the Childhood Trauma Questionnaire (CTQ), and the Cognitive Reserve Assessment Scale in Health (CRASH). Linear regression analyses were conducted to evaluate the interaction effect of CR between CM and cognitive and psychosocial variables, controlling for age, sex, and social desirability (CTQ-denial-minimization). RESULTS: In adults with FEP overall CM interacted with CR to predict COBRA-subjective cognitive complaints, but not neurocognitive or psychosocial functioning. Sexual abuse and physical neglect interacted with CR to predict verbal memory. Most of the CM subtypes interacted with CR to predict FAST-leisure time, whereas only emotional neglect interacted with CR to predict FAST-interpersonal relationships. Overall, greater CR was related to better functioning. CONCLUSIONS: The current results indicate that associations between specific CM subtypes, subjective and objective cognition, and psychosocial domains are moderated through CR with greater functioning. Early interventions focused on CR seeking to improve cognitive and psychosocial outcomes, with emphasis on improving subjective cognitive functions would be beneficial for individuals with FEP and CM. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Intercomparison exercises as a tool for improving the quality of radiochemical measurements in drinking waters - Radon-222 determinations.

The results of a European intercomparison on 222Rn in water were analyzed to evaluate the performances of standard and non-standard methods. Then, results obtained with a specific LSC method (ISO 13164-4) based on two-phase liquid scintillation counting which has been employed by a considerable number of participants were examined in detail. This ISO LSC method was proved to be accurate, reliable and its reproducibility has been also sufficient. The intercomparison could be used as a collaborative study and the analysis of its results allowed to estimate the method reproducibility.

Core-binding factor leukemia hijacks the T-cell-prone PU.1 antisense promoter.

The blood system serves as a key model for cell differentiation and cancer. It is orchestrated by precise spatiotemporal expression of crucial transcription factors. One of the key master regulators in the hematopoietic systems is PU.1. Reduced levels of PU.1 are characteristic for human acute myeloid leukemia (AML) and are known to induce AML in mouse models. Here, we show that transcriptional downregulation of PU.1 is an active process involving an alternative promoter in intron 3 that is induced by RUNX transcription factors driving noncoding antisense transcription. Core-binding factor (CBF) fusions RUNX1-ETO and CBFß-MYH11 in t(8;21) and inv(16) AML, respectively, activate the PU.1 antisense promoter that results in a shift from sense toward antisense transcription and myeloid differentiation blockade. In patients with CBF-AML, we found that an elevated antisense/sense transcript and promoter accessibility ratio represents a hallmark compared with normal karyotype AML or healthy CD34+ cells. Competitive interaction of an enhancer with the proximal or the antisense promoter forms a binary on/off switch for either myeloid or T-cell development. Leukemic CBF fusions thus use a physiological mechanism used by T cells to decrease sense transcription. Our study is the first example of a sense/antisense promoter competition as a crucial functional switch for gene expression perturbation by oncogenes. Hence, this disease mechanism reveals a previously unknown Achilles heel for future precise therapeutic targeting of oncogene-induced chromatin remodeling.

Synergy in the heart: RV systolic function plays a key role in optimizing LV performance during exercise.

The right ventricle (RV) is often overlooked in the evaluation of cardiac performance and treatment of left ventricular (LV) heart diseases. However, recent evidence suggests the RV may play an important role in maintaining systemic cardiac function and delivering stroke volume (SV). We used exercise cardiac magnetic resonance and biomechanical modeling to investigate the role of the RV in LV stroke volume regulation. We studied SV augmentation during exercise by pharmacologically inducing negative chronotropy (sHRi) in healthy volunteers and investigating training-induced SV augmentation in endurance athletes. SV augmentation during exercise after sHRi is achieved differently in the two ventricles. In the RV, the larger SV is driven by increasing contraction down to lower end-systolic volume (ESV; P < 0.001). In the LV, SV augmentation is achieved through an increase in end-diastolic volume (EDV; P < 0.001), avoiding contraction to a lower ESV. The same mechanism underlies the enhanced SV response observed in athletes. Changes in atrial area during SV augmentation suggest that the improved LV EDV response is sustained by the larger RV contractions. Using our biomechanical model, we explain this behavior by showing that the RV systolic function-driven regulation of LV SV optimizes the energetic cost of LV contraction and leads to minimization of the total costs of biventricular contraction. In conclusion, this work provides mechanistic understanding of the pivotal role of the RV in optimizing LV SV during exercise. It demonstrates why optimizing RV function needs to become a key part of therapeutic strategies in patients and training for athletes.NEW & NOTEWORTHY The right ventricle appears to have an important impact on maintaining systemic cardiac function and delivering stroke volume. However, its exact role in supporting left ventricular function has so far been unclear. This study demonstrates a new mechanism of ventricular interaction that provides mechanistic understanding of the key importance of the right ventricle in driving cardiac performance.

Potential Source Apportionment and Meteorological Conditions Involved in Airborne 131I Detections in January/February 2017 in Europe.

Traces of particulate radioactive iodine (131I) were detected in the European atmosphere in January/February 2017. Concentrations of this nuclear fission product were very low, ranging 0.1 to 10 µBq m-3 except at one location in western Russia where they reached up to several mBq m-3. Detections have been reported continuously over an 8-week period by about 30 monitoring stations. We examine possible emission source apportionments and rank them considering their expected contribution in terms of orders of magnitude from typical routine releases: radiopharmaceutical production units > sewage sludge incinerators > nuclear power plants > spontaneous fission of uranium in soil. Inverse modeling simulations indicate that the widespread detections of 131I resulted from the combination of multiple source releases. Among them, those from radiopharmaceutical production units remain the most likely. One of them is located in Western Russia and its estimated source term complies with authorized limits. Other existing sources related to 131I use (medical purposes or sewage sludge incineration) can explain detections on a rather local scale. As an enhancing factor, the prevailing wintertime meteorological situations marked by strong temperature inversions led to poor dispersion conditions that resulted in higher concentrations exceeding usual detection limits in use within the informal Ring of Five (Ro5) monitoring network.

INTERNATIONAL STANDARDS ON FOOD AND ENVIRONMENTAL RADIOACTIVITY MEASUREMENT FOR RADIOLOGICAL PROTECTION: STATUS AND PERSPECTIVES.

Radiological protection is a matter of concern for members of the public and thus national authorities are more likely to trust the quality of radioactivity data provided by accredited laboratories using common standards. Normative approach based on international standards aims to ensure the accuracy or validity of the test result through calibrations and measurements traceable to the International System of Units. This approach guarantees that radioactivity test results on the same types of samples are comparable over time and space as well as between different testing laboratories. Today, testing laboratories involved in radioactivity measurement have a set of more than 150 international standards to help them perform their work. Most of them are published by the International Standardization Organization (ISO) and the International Electrotechnical Commission (IEC). This paper reviews the most essential ISO standards that give guidance to testing laboratories at different stages from sampling planning to the transmission of the test report to their customers, summarizes recent activities and achievements and present the perspectives on new standards under development by the ISO Working Groups dealing with radioactivity measurement in connection with radiological protection.

A systematic review of image segmentation methodology, used in the additive manufacture of patient-specific 3D printed models of the cardiovascular system.

BACKGROUND: Shortcomings in existing methods of image segmentation preclude the widespread adoption of patient-specific 3D printing as a routine decision-making tool in the care of those with congenital heart disease. We sought to determine the range of cardiovascular segmentation methods and how long each of these methods takes. METHODS: A systematic review of literature was undertaken. Medical imaging modality, segmentation methods, segmentation time, segmentation descriptive quality (SDQ) and segmentation software were recorded. RESULTS: Totally 136 studies met the inclusion criteria (1 clinical trial; 80 journal articles; 55 conference, technical and case reports). The most frequently used image segmentation methods were brightness thresholding, region growing and manual editing, as supported by the most popular piece of proprietary software: Mimics (Materialise NV, Leuven, Belgium, 1992-2015). The use of bespoke software developed by individual authors was not uncommon. SDQ indicated that reporting of image segmentation methods was generally poor with only one in three accounts providing sufficient detail for their procedure to be reproduced. CONCLUSIONS AND IMPLICATION OF KEY FINDINGS: Predominantly anecdotal and case reporting precluded rigorous assessment of risk of bias and strength of evidence. This review finds a reliance on manual and semi-automated segmentation methods which demand a high level of expertise and a significant time commitment on the part of the operator. In light of the findings, we have made recommendations regarding reporting of 3D printing studies. We anticipate that these findings will encourage the development of advanced image segmentation methods.

Validation of a method for measuring (226)Ra in drinking waters by LSC.

A simple method for measuring (226)Ra in drinking waters has been validated and validation parameters are provided. It is based on the measurement by LSC of (222)Rn, at equilibrium with (226)Ra, which is absorbed into a water immiscible scintillation cocktail (Ultima Gold F) inside the counting vial. The validated application field ranges between the detection limit (2·10(-3) Bq/kg) to 150 Bq/kg. The method has proven to be reliable, effective and suitable for wide-range measuring campaigns. A summary of results obtained in recent years is also given.

Estonian waterworks treatment plants: clearance of residues, discharge of effluents and efficiency of removal of radium from drinking water.

Considerable levels of radium were detected in a certain fraction of the Estonian drinking water supply network. Some of these waterworks have treatment systems for the removal of (mainly) iron and manganese from drinking water. Three of these waterworks and another one equipped with a radium removal pilot plant were examined, and a specific study was conducted in order to assess the environmental compatibility of effluents and residues produced in the plants. (226)Ra and (228)Ra activity concentrations were analysed in both liquid (backwash water) and solid (sand filter and sediment) materials to evaluate their compliance, from the radiological point of view, with current Estonian legislation and international technical documents that propose reference levels for radium in effluents and residues. Also with regard to water treatment by-products, a preliminary analysis was done of possible consequences of the transposition of the European Basic Safety Standards Draft into Estonian law. Radium removal efficiency was also tested in the same plants. Iron and manganese treatment plants turned out to be scarcely effective, whilst the radium mitigation pilot plant showed a promising performance.

ISO standards on test methods for water radioactivity monitoring.

Water is vital to humans and each of us needs at least 1.5L of safe water a day to drink. Beginning as long ago as 1958 the World Health Organization (WHO) has published guidelines to help ensure water is safe to drink. Focused from the start on monitoring radionuclides in water, and continually cooperating with WHO, the International Standardization Organization (ISO) has been publishing standards on radioactivity test methods since 1978. As reliable, comparable and 'fit for purpose' results are an essential requirement for any public health decision based on radioactivity measurements, international standards of tested and validated radionuclide test methods are an important tool for production of such measurements. This paper presents the ISO standards already published that could be used as normative references by testing laboratories in charge of radioactivity monitoring of drinking water as well as those currently under drafting and the prospect of standardized fast test methods in response to a nuclear accident.

[Incidence of Modic degenerative changes in patients with chronic lumbar pain at Monterrey Regional ISSSTE Hospital]. / Incidencia de cambios degenerativos tipo Modic en pacientes con dolor lumbar crónico en el Hospital Regional ISSSTE Monterrey.

BACKGROUND: Several papers have studied the degenerative changes of endplates, but there are no publications referring to the Mexican population. OBJECTIVE: The purpose of the study is to report the incidence of Modic degenerative changes in the patients seen at the Spine Service, Monterrey Regional ISSSTE Hospital. Specific objectives are: to describe the type of Modic change and the most frequent location, to describe the degeneration patterns and to report the incidence of the various diagnoses made during 2009. METHODS: Incidence study using the MRI records at the Radiology Department, Monterrey Regional ISSSTE Hospital, interpreted blindly and independently by two observers. RESULTS: A total of 240 lumbar spine MRIs were reviewed, for a total of 1,200 intervertebral spaces. They were divided by age groups. Group I included 16 patients, Group II 32, Group III 80, and Group IV 112. No patients in Group I had Modic changes. Four patients (12.5%) in Group II had type II Modic changes with < 25% of endplate involvement. Eight patients in Group III had Modic changes with > 25% involvement of L4-L5 (10%); 32% of Group IV patients had changes, with L5-S1 as the most affected level. Most Modic changes (85%) were located in L4-L5 and L5-S1, with the latter as the most frequently affected level. Type I represented 5%, Type II 30%, and Type III 65%. The percentage of patients with Modic changes increased with age, which confirms that degenerative changes are age related. Morphologic disc changes are expressed as the percentage of affected patients in each group. Besides the severity of degeneration, the number of affected levels also increases with age. Thirty percent of patients ages 30-39 years have one or two degenerated levels, while 50% of those over age 50 have 3 or more degenerated levels. The most frequently degenerated level was L5-S1, followed by L4-L5 and L3-L4. The most frequent degeneration pattern was lower segment degeneration (L4-L5, L5-S1). A small proportion of patients over age 50 (4%) did not have disc degeneration, suggesting that age is not the only factor that determines their occurrence. CONCLUSIONS: The prevalence of Modic changes was 22% (52 patients). Eight patients had Type II Modic changes at two levels. The most affected levels were L4-L5 and L5-S1, in 85% of cases. Patients over 50 years of age were the most affected age group; frequency increased with age. The most frequent disc degeneration pattern was degeneration of the lower lumbar levels. Risk factors need to be further studied and the correlation with the degree of pain needs to be determined to obtain more information.

Viral agents causing lower respiratory tract infections in hospitalized children: evaluation of the Speed-Oligo® RSV assay for the detection of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is the viral agent which is more frequently involved in lower respiratory tract infections (LRTIs) in infants under 1 year of age in developed countries. A new oligochromatographic assay, Speed-Oligo® RSV, was designed and optimized for the specific detection and identification of RSV subtypes A and B. The test was evaluated in 289 clinical samples from 169 hospitalized children using an immunochromatography (IC) test, virus isolation by culture, and an in-house real-time polymerase chain reaction (RT-PCR). Other viruses causing LRTIs were investigated by cell culture or PCR-based tests. Sixty-two patients were infected by RSV (36.7%). In addition, adenovirus, influenza B, parainfluenza 2, and human metapneumovirus were detected in rates ranging from 5 to 8%. A proportion of 10.1% of the patients had mixed infections. The sensitivity, specificity, and positive and negative predictive values were, respectively, 94.9, 99.4, 98.9, and 97.4% for Speed-Oligo® RSV, 92.9, 96.3, 92.9, and 96.3% for RT-PCR/RSV, and 58.4, 98.1, 93.3, and 82.6% for IC. Our rates of viral detection and co-infection were similar to those of previously reported series. Finally, we find that Speed-Oligo® RSV is a rapid and easy-to-perform technique for the detection of RSV and the identification of subtypes A and B.

International standardisation work on the measurement of radon in air and water.

Radon is considered to be the main source of human exposure to natural radiation. As stated by the World Health Organization, the exposure due to the inhalation of indoor radon is much greater than the one via the ingestion of water as radon degasses from water during handling. In response to these concerns about the universal presence of radon, environmental assessment studies are regularly commissioned to assess the radon exposure of public and workers. The credibility of such studies relies on the quality and reliability of radon analysis as well as on the sample representativeness of the radiological situation. The standard-setting approach, based on consensus, seemed to lend itself to a settlement of technical aspects of potential comparison. At present, two Working Groups of the International Standardization Organization are focussing on drafting standards on radon and its decay products measurement in air and water. These standards, which aim for a set of rigorous metrology practices, will be useful for persons in charge of the initial characterisation of a site with respect to natural radioactivity as well as to those performing the routine surveillance of specific sites.

Red wine prevents the postprandial increase in plasma cholesterol oxidation products: a pilot study.

Moderate wine consumption has been shown to lower cardiovascular risk. One of the mechanisms could involve the control of postprandial hyperlipaemia, a well-defined risk factor for atherosclerosis, reasonably by reducing the absorption of lipid oxidised species from the meal. The objective of the present study was to investigate whether wine consumption with the meal is able to reduce the postprandial increase in plasma lipid hydroperoxides and cholesterol oxidation products, in human subjects. In two different study sessions, twelve healthy volunteers consumed the same test meal rich in oxidised and oxidisable lipids (a double cheeseburger), with 300 ml of water (control) or with 300 ml of red wine (wine). The postprandial plasma concentration of cholesterol oxidation products was measured by GC-MS. The control meal induced a significant increase in the plasma concentration of lipid hydroperoxides and of two cholesterol oxidation products, 7-ß-hydroxycholesterol and 7-ketocholesterol. The postprandial increase in lipid hydroperoxides and cholesterol oxidation products was fully prevented by wine when consumed with the meal. In conclusion, the present study provides evidence that consumption of wine with the meal could prevent the postprandial increase in plasma cholesterol oxidation products.

Radium isotopes in Estonian groundwater: measurements, analytical correlations, population dose and a proposal for a monitoring strategy.

In some areas of Estonia, groundwater contains a significant number of natural radionuclides, especially radium isotopes, which may cause radiation protection concern depending on the geological structure of the aquifer. Indeed, the parametric value of 0.1 mSv y⁻¹ for the total indicative dose established by European Directive 98/83/EC, adopted as a limit value in Estonian national legislation, is often exceeded. A Twinning Project between Estonia and Italy was carried out within the framework of the Estonian Transition Facility Programme, sponsored by the European Union. Its aims were to assess the radiological situation of Estonian groundwater and related health consequences. The first step was a study of Estonian aqueducts and the population served by them, and a thorough analysis of the radiological database for drinking water, from which the relevant effective doses for the population were obtained. Particular attention was devoted to doses to children and infants. Correlations between the chemical parameters were investigated, in order to suggest the best possible analytical approach. Lastly, a monitoring strategy, i.e. sampling points and sampling frequencies, was proposed.

Enhancement of anxiety, facilitation of avoidance behavior, and occurrence of adult-onset obesity in mice lacking mitochondrial cyclophilin D.

In this report, we have assessed the behavioral responses of mice missing the Ppif gene (CyPD-KO), encoding mitochondrial cyclophilin D (CyPD). Mitochondrial CyPD is a key modulator of the mitochondrial permeability transition which is involved in the regulation of calcium- and oxidative damage-induced cell death. Behavioral screening of CyPD-KO mice (ranging between 4 and 15 months of age) was accomplished using a battery of behavioral paradigms which included testing of motor functions, exploratory activity, and anxiety/emotionality, as well as learning and memory skills. We found that, compared with wild-type mice, CyPD-KO mice were (i) more anxious and less explorative in open field and elevated plus maze and (ii) performed better in learning and memory of avoidance tasks, such as active and passive avoidance. However, the absence of CyPD did not alter the nociceptive threshold for thermal stimuli. Finally, deletion of CyPD caused also an abnormal accumulation of white adipose tissue resulting in adult-onset obesity, which was not dependent on increased food and/or water intake. Taken together, our results suggest a new fundamental role of mitochondrial CyPD in basal brain functions and body weight homeostasis.

Melatonin increases following convulsive seizures may be related to its anticonvulsant properties at physiological concentrations.

Melatonin ( N-acetyl-5-methoxytryptamine, aMT) is an indoleamine produced by several organs and tissues including the pineal gland. Melatonin (aMT) modulates the activity of the brain, mainly acting on both GABA and glutamate receptors. Previous studies have shown the participation of melatonin in the control of convulsive crises, suggesting that aMT concentration increases during seizures, and that patients with seizures of diverse origins show an alteration of the aMT rhythm. However, what is not known is the duration of the aMT response to seizures, and whether aMT changes during seizures could be a marker of the disease. For this reason, the serum levels of aMT in 54 children with a convulsive crisis, febrile and epileptic, were analyzed during the crisis, as well as at 1 h and 24 hours after the seizure. The results show that aMT significantly increases during the seizure (Day group, 75.64+/-45.91 and Night group, 90.69+/-51.85 pg/mL), with normal values being recovered 1 h later (Day group, 26.33+/-10.15 and Night group, 27.78+/-7.82 pg/mL) and maintained for up to 24 hours, when the circadian variation of aMT returns to the normal acrophase. Due to the interindividual variation of aMT levels among healthy people, a single determination of the indoleamine concentration is not a suitable marker of the existence of a convulsive crisis unless the circadian profile of aMT secretion in the patient is known. The results obtained also support the view that the stimulation of aMT production by the convulsive crisis may participate in the response of the organism against the seizures.