Determination of the Terbium-152 half-life from mass-separated samples from CERN-ISOLDE and assessment of the radionuclide purity.

Terbium-152 is one of four terbium radioisotopes that together form a potential theranostic toolbox for the personalised treatment of tumours. As 152 Tb decay by positron emission it can be utilised for diagnostics by positron emission tomography. For use in radiopharmaceuticals and for activity measurements by an activity calibrator a high radionuclide purity of the material and an accurate and precise knowledge of the half-life is required. Mass-separation and radiochemical purification provide a production route of high purity 152Tb. In the current work, two mass-separated samples from the CERN-ISOLDE facility have been assayed at the National Physical Laboratory to investigate the radionuclide purity. These samples have been used to perform four measurements of the half-life by three independent techniques: high-purity germanium gamma-ray spectrometry, ionisation chamber measurements and liquid scintillation counting. From the four measurement campaigns a half-life of 17.8784(95) h has been determined. The reported half-life shows a significant difference to the currently evaluated half-life (ζ-score = 3.77), with a relative difference of 2.2 % and an order of magnitude improvement in the precision. This work also shows that under controlled conditions the combination of mass-separation and radiochemical separation can provide high-purity 152Tb.

Acute phase characteristics and long-term complications of pulmonary embolism in COVID-19 compared to non-COVID-19 cohort: a large single-centre study.

BACKGROUND: To compare the severity of pulmonary embolism (PE) and the long-term complications between patients with and without COVID-19, and to investigate whether the tools for risk stratification of death are valid in this population. METHODS: We retrospectively included hospitalized patients with PE from 1 January 2016 to 31 December 2022. Comparisons for acute episode characteristics, risk stratification of the PE, outcomes, and long-term complications were made between COVID and non-COVID patients. RESULTS: We analyzed 116 (27.5%) COVID patients and 305 (72.4%) non-COVID patients. In patients with COVID-19, the traditional risk factors for PE were absent, and the incidence of deep vein thrombosis was lower. COVID patients showed significantly higher lymphocyte count, lactate dehydrogenase, lactic acid, and D-dimer levels. COVID patients had PE of smaller size (12.3% vs. 25.5% main pulmonary artery, 29.8% vs. 37.1% lobar, 44.7% vs. 29.5% segmental and 13.2% vs. 7.9% subsegmental, respectively; p < 0.001), less right ventricular dysfunction (7.7% vs. 17.7%; p = 0.007) and higher sPESI score (1.66 vs. 1.11; p < 0.001). The need for mechanical ventilation was significantly higher in COVID patients (8.6% vs. 1.3%; p < 0.001); However, the in-hospital death was less (5.2% vs. 10.8%; p = 0.074). The incidence of long-term complications was lower in COVID cohort (p < 0.001). PE severity assessed by high sPESI and intermediate and high-risk categories were independently associated with in-hospital mortality in COVID patients. CONCLUSION: The risk of in-hospital mortality and the incidence of long-term complications were lower in COVID-19. The usual tools for risk stratification of PE are valid in COVID patients.

Morphometric variants of the paranasal sinuses in a Mexican population: expected changes according to age and gender.

BACKGROUND: There are developmental variations in the paranasal sinuses. Our objective was to determine their dimensions and volume stratified by age and sex and define the expected growth pattern. MATERIALS AND METHODS: A retrospective, observational study was performed including computed tomography (CT) of patients between 1 and 20 years of age. The volumes of the frontal, sphenoid, and maxillary sinuses were obtained. RESULTS: A total of 210 CT were included with a mean age of 10 ± 6.1 years, 106 (50.5%) were female. Groups were categorised in ranges of 5 years. Spearman correlation coefficients between the right and left sides were 0.843, 0.711, 0.916 for the frontal, sphenoid and maxillary sinuses. Post-hoc for the categorical age groups demonstrated statistically significant differences with values of p < 0.01, except between age groups 11-15 against ≥ 16 years of age (p = 0.8). Gender-related differences were evident with a higher air volume in girls in the 5-10-year-old group, while boys predominated in the rest of the groups. CONCLUSIONS: Computed tomography is ideal for pre-surgical sinus assessment. The maximum volume of paranasal sinuses is reached at the age of 15. There is a clear volumetric difference between age and gender groups. There is a direct relationship between a volume and its contralateral counterpart.

Effect of obesity on fragility fractures, BMD and vitamin D levels in postmenopausal women. Influence of type 2 diabetes mellitus.

AIMS: To see the effects of obesity on risk fracture, bone density (BMD), and vitamin D levels in a group of postmenopausal women, and consider how comorbid type 2 diabetes mellitus (T2DM) modifies them. METHODS: 679 postmenopausal women were grouped into obese and non-obese. Obese women were grouped into those with T2DM and those without. 25(OH)-vitamin D, PTH and BMD were measured, and prevalent fragility fractures were gathered. RESULTS: Obese women had higher prevalence of T2DM, than non-obese women. Levels of 25(OH)-vitamin D were lower and those of PTH higher in obese women, BMD values were higher in obese women. Diabetic-obese women had a higher prevalence of non-vertebral fractures than non-diabetic-obese. Multivariate logistic regression model showed association of fragility fractures with age, total hip BMD, BMI and T2DM. Obese women have higher BMD and lower 25(OH)-vitamin D values (and higher PTH) than non-obese, without diabetes. CONCLUSIONS: T2DM confers an increased risk of non-vertebral fractures in postmenopausal obese women.

Transcriptional activity and splicing factors are preserved during physiological apoptosis.

Apoptosis is the best-known programmed cell death that maintains tissue homeostasis in eukaryotic cells. The morphological characteristics include nuclear and cytoplasmic contraction and cytoplasmic blebbing, its biochemical hallmarks include caspase protease activity and DNA fragmentation. In rat ovaries, cell death is a normal process that occurs throughout the organism's life. Granulosa cells, the more abundant cell type forming the ovarian follicles, are eliminated via different routes of cell death. Most granulosa cells are eliminated through apoptotic cell death. In this work, we analyzed the behavior of nuclear components throughout the apoptotic process and determined how they are regionalized and conserved during follicular atresia in rat ovaries. Apoptosis was detected based on caspase-3 activity and DNA fragmentation using the TUNEL technique. We identified the transcription markers H3ac and RNA Pol II, and splicing factor SC35 by immunodetection. The nucleolar components were analyzed via light microscopy and transmission electron microscopy through immunodetection of the proteins nucleolin and nucleophosmin-1. The nuclear ultrastructure was analyzed using standard contrast and preferential ribonucleoprotein contrast. Our results demonstrate that during the progression of apoptosis, chromatin is remodeled to constitute apoptotic bodies; transcription and spliceosome elements are reorganized along with the nucleolar components. Additionally, the splicing and transcription factors are segregated into specific territories inside the apoptotic bodies, suggesting that transcriptional elements are reorganized during the apoptotic process. Our results indicate that apoptotic bodies not only are compacted, and chromatin degraded but all the nuclear components are progressively reorganized during cell elimination; moreover, the transcriptional components are preserved.

Histological reinterpretation of paraphysis cerebri in Ambystoma mexicanum.

Intraventricular and extraventricular choroid plexuses are neuroepithelial folds which arise from the roof of the diencephalon. We describe the circumventricular structure of the diencephalon roof (paraphysis cerebri) during the various development stages of Ambystoma mexicanum. The parasagittal sections of the larvae epithalamus exhibit the presence, in addition to the epiphysis, of two dorsal primordia in nearby areas, which appear to be extraventricular saccular evaginations of different origin that give rise to two structures we define as the anterior extraventricular choroid plexus (AEP) and posterior extraventricular choroid plexus (PEP). During larvae development, the primordia arise perpendicular to each other, grow and show luminal folds and invaginations. Later, the two extraventricular evaginations, which are separate units, become interrelated. As the PEP grows, it covers the AEP dorsally, but it is difficult to define the borders of these organs. AEP is formed by alveolar-acinar epithelial aggregates with evidence of secretion-like content. PEP structure is like a choroid plexus, but its position is extraventricular and dorsal to the AEP. The PEP is always between the AEP and the meninges and can be small or large in size. This means that in A. mexicanum, the paraphysis cerebri is made up of two adjacent organs, which arise almost simultaneously from two different primordia (the AEP and the PEP) and as the posterior one grows, it overlaps the anterior one and masks itself. In conclusion, we suggest that AEP and PEP are homologous to paraphysis cerebri and the dorsal sac, respectively.

Analysis of patient outcomes after urological surgery during the second and third waves of SARS-CoV-2 pandemic in a high incidence area.

OBJECTIVE: To analyze surgical safety through postoperative COVID-19 incidence and mortality at the urology department of a tertiary hospital located in Madrid (Spain). METHODS: Observational, prospective study including all patients undergoing urological surgery from 1st March 2020 to 28th February 2021. According to the hospital organization and local epidemiological situation we delimitate three epidemic waves. A set of screening and protective measures was applied from 4th May onwards. Demographic, baseline, surgical and perioperative variables, as well as postoperative outcomes, were collected. Telephone follow-up was performed at least 3 weeks after hospital discharge. RESULTS: 940 urological surgeries were performed, 12 of them had to be rescheduled due to active or recent SARS-CoV-2 infection identified by the screening protocol. Thirty-one patients developed COVID-19 (3.3% incidence) and 7 died (22.6% mortality). The average time to onset of symptoms was 62.6 days after discharge, being 25 cases attributable to community transmission. The remaining 6 cases, due to in-hospital transmission, had worse outcomes. Five of them were identified during the first wave, especially when no preoperative PCR was obtained. In contrast, during the second and third waves, fewer and milder cases were diagnosed, with just 1 in-hospital transmission among 857 urological patients. CONCLUSIONS: After implementing complete protective measures, postoperative in-hospital COVID-19 cases almost disappeared, even during the second and third waves. Most of the cases were due to community transmission and thus driven by the general epidemiological situation. While hospitals follow recommendations to avoid COVID-19 infection, urological surgery remains safe and can be maintained.

Determination of the 161Tb half-life.

There is significant interest in the use of terbium radioisotopes for applications in cancer therapy and diagnosis. Of these, 161Tb, as a medium energy beta-emitter, is being investigated as a potential alternative to 177Lu. The relatively high proportion of conversion electron and Auger electron emissions per decay make 161Tb an attractive targeted therapeutic. As a product of nuclear fission, 161Tb is also of importance to nuclear forensics. The standard uncertainty of the current evaluated half-life of 6.89(2) d contributes significantly to the standard uncertainty of any decay corrected activity determination made. Furthermore, the accuracy of this evaluated half-life has been called into question by measurements reported in 2020 at the Institute of Radiation Physics (IRA), Switzerland, who reported a half-life of 6.953(2) d. In the current work, the half-life of the 161Tb ground state decay has been measured at three independent laboratories located in the United Kingdom and the United States of America for a total of six determinations using three independent measurement techniques; gamma-ray spectrometry, ionisation chamber measurement and liquid scintillation counting. The half-life determined for 161Tb of 6.9637(29) d confirms the observed 1% relative increase observed by IRA, though the reported half-lives in this work and at IRA are significantly different (ζ-score = 3.1).

Saccharification of water hyacinth biomass by a combination of steam explosion with enzymatic technologies for bioethanol production.

In the present work, bioethanol was produced by sugar fermentation obtained from water hyacinth using a novelty hybrid method composed of steam explosion and enzymatic hydrolysis, using hydrolytic enzymes produced by solid-state fermentation and water hyacinth as substrate. The highest activity, 42 U for xylanase and 2 U for cellulase per gram of dry matter, respectively, was obtained. Steam explosion pretreatment was performed at 190 â„ƒ for 1, 5, and 10 min, using water hyacinth sampled from the Maria Lizamba Lagoon, the Arroyo Hondo and the Amapa River. The highest amounts of reducing sugars of water hyacinth were obtained form the samples from the lagoon (5.4 g/50 g of dry matter) after 10 min of treatment. Steamed biomass was hydrolysed using the enzymes obtained by solid-state fermentation, obtained reducing sugars (maximum 15.5 g/L); the efficiency of enzymatic hydrolysis was 0.51 g of reducing sugars per gram of water hyacinth. Finally, reducing sugars were fermented using Saccharomyces cerevisiae for conversion to ethanol, with the highest ethanol concentration (7.13 g/L) and an ethanol yield of 0.23 g/g of dry matter.

[Thoracic insufficiency syndrome]. / Síndrome de insuficiencia torácica.

The compendium of disorders that affect the normal growth or function of the thorax will cause Thoracic Insufficiency Syndrome (TIS). TIS is defined as the inability of the chest to sustain normal breathing and/or lung growth. The etiology of the syndrome may be secondary to spinal deformities, global deformities of the chest, neuromuscular dysfunction or the combination of any these. Its manifestation is based on a history that highlights respiratory symptoms, a physical examination that demonstrates chest deformity, abnormal radiographic findings and/or computed tomography of the chest, accompanied by alterations in lung function or other studies of respiratory function. This syndrome must be treated with haste since it progressively worsens with the aggravation of the underlying condition(s) which is unfavorable to the irreversible physiological changes of the lung that occur during development, and are directly related to the respiratory insufficiencies. The vertical expandable prosthetic titanium rib (VEPTR) was developed as a treatment procedure that aims to restore the volume and function of the thorax with the purpose of enabling thoracic growth during the development of the child or adolescent. The treatment targets the components of the rib cage as a unit, in order to prevent or treat respiratory insufficiencies. Its indications include children with early development scoliosis who are prone to develop SIT. The proposed procedure entails a high incidence of complications and conflicting results that limit its efficacy as a treatment, which is why it is a subject of great controversy in the medical literature.

Los procesos que afecten el crecimiento normal o la función del tórax causarán el síndrome de insuficiencia torácica (SIT). Éste se define como la incapacidad del tórax de sostener una respiración normal y/o crecimiento pulmonar. La etiología del síndrome puede ser secundaria a deformidades de la columna, deformidades globales del tórax, disfunción neuromuscular o la combinación de éstas. Su manifestación se basa en un historial que resalta síntomas respiratorios, un examen físico que demuestra deformidad del tórax, hallazgos anormales radiográficos y/o tomografía computarizada del pecho, acompañados de alteración en la función pulmonar o de otros estudios de la función respiratoria. Este síndrome debe ser tratado con premura debido a que progresivamente empeora con el agravamiento de la condición subyacente, lo que resulta irreversiblemente desfavorable en los cambios fisiológicos del pulmón y se relaciona con insuficiencia respiratoria durante el desarrollo. El tratamiento expansor de costilla conocido en inglés como vertical expandable prosthetic titanium rib (VEPTR) propone restaurar el volumen y la función torácica con el propósito de permitir el crecimiento del tórax a través del desarrollo del paciente. El tratamiento se dirige a los componentes de la caja torácica como una unidad, con el fin de prevenir o tratar la insuficiencia respiratoria. Sus indicaciones incluyen niños con escoliosis de desarrollo temprano que sean propensos a desarrollar el SIT. El procedimiento propuesto conlleva una alta incidencia de complicaciones y resultados conflictivos que limitan su eficacia como tratamiento, por lo que es un tema de gran controversia en la literatura médica.

[Effectiveness of the use of standing devices in the prevention of hip dislocation in children and adolescents with spastic cerebral palsy, GMFCS III, IV and V. A systematic review]. / Efectividad del uso de bipedestadores en la prevención de la luxación de cadera en niños y adolescentes con parálisis cerebral espástica, GMFCS III, IV y V. Revisión sistemática.

The standing devices are used as a preventive therapy for hip dislocation in patients with cerebral palsy. This review seeks to assess the effectiveness of standing devices in the prevention of hip dislocation of patients under 18 years old with a diagnosis of spastic cerebral palsy, GMFCS III-V. A systematic search was conducted in 10 biomedical databases, selecting randomized, quasi-experimental clinical trials and cohort studies. The use of standing devices with physical therapy, orthosis and/or soft tissue surgeries was compared. The percentage of migration of the femoral head was considered as the main result. The risk of bias was assessed using the Rob 2.0 and Robins I guidelines. As a result of the analysis of 6 primary studies, it is obtained that the use of standing devices maintained the percentage of migration of the femoral head within normal limits (MP:13-23%, p<.01), increased vertebral trabecular volumetric bone mineral density (8.16mg/cm3, p=.01), bone mineral content (p=.010) and hamstring muscle length (phase B1 p<.01 and B2 p=.03). However, the risk of bias in these studies was categorized as of some concern to moderate. In conclusion, it is stated that there is limited evidence of the effectiveness of the use of standing devices in the prevention of hip dislocation in the study population, due to the methodological heterogeneity and risk of bias of the included studies. A greater number of studies with a high level of evidence are required in order to generate a recommendation for its use. Registration in PROSPERO: CRD42018087641.

Gene expression changes by high-polyphenols cocoa powder intake: a randomized crossover clinical study.

PURPOSE: To assess the effect of the intake of a single dose of high-polyphenols cocoa on gene expression in peripheral mononuclear cells (PBMCs), and analyze conjugated (-)-epicatechin metabolites in plasma, which may be related with an antioxidant response in healthy human. METHODS: A randomized, controlled, double-blind, cross-over, clinical trial in healthy young adults who consumed a single dose of high-polyphenols cocoa powder and maltodextrins as control, with a one-week washout period. Analysis of circulating metabolites, plasma antioxidant capacity and gene expression changes in PBMCs were performed under fasting conditions and 2-h after treatment using microarray in a subsample. Pathway analysis was conducted using Ingenuity Pathway Analysis (IPA). RESULTS: Twenty healthy participants (9 F) were included in the study. A significant increase in circulating (-)-epicatechin metabolites was found after cocoa intake in all participants without related changes in antioxidant capacity of plasma. The metabolites profile slightly varied across subjects. Treatments triggered different transcriptional changes in PBMC. A group of 98 genes showed changes in expression after cocoa treatment, while only 18 were modified by control. Differentially expressed genes included inflammatory cytokines and other molecules involved in redox balance. Gene and network analysis after cocoa intake converged in functions annotated as decreased production of reactive oxygen species (p = 9.58E-04), decreased leukocyte activation (p = 4E-03) and calcium mobilization (p = 2.51E-05). CONCLUSIONS: No association was found between conjugated metabolites in plasma and antioxidant capacity. Changes in PBMCs gene expression suggest anti-inflammatory effects.

Effect of stirring on growth and cellulolytic enzymes production by Trichoderma harzianum in a novel bench-scale solid-state fermentation bioreactor.

A novel bench-scale stirred bioreactor for solid-state fermentation was used to determine the effect of the stirring rate on growth and enzymes production by Trichoderma harzianum PBLA. Lab-scale static tubular bioreactors were first used to assess the effect of bioreactor diameter on heat accumulation, growth, and production of cellulases and xylanases. The increased diameters (1.8-4.2 cm) led to increases in temperature up to 36 °C (at a rate of 1.08 °C/cm), which negatively affected the growth and enzyme production. Afterward, in the bench-scale bioreactor operated at rates up to 3.0 rpm, maximum xylanases production (107 ±â€¯0.3 U/g dm) was attained at rates of 0.5 and 1.0 rpm, reaching a maximum of 34 ±â€¯0.3 °C. Cellulases production was reduced (up to 79%) due to stirring. Therefore, the production of xylanases by T. harzianum can be performed in this cross-flow stirred SSF bioreactor at rates up to 1.0 rpm, avoiding heat accumulation and damage on metabolic activity.

[Past and present of monitoring the functional immune response developed against Epstein-Barr and Adenovirus in hematopoietic stem cell transplantation]. / Pasado y presente de la monitorización de la respuesta funcional inmunológica desarrollada frente a Epstein-Barr y Adenovirus en el trasplante de progenitores hematopoyéticos.

Epstein-Barr (EBV) and Adenovirus (AdV) viral infections represent a significant cause of morbi-mortality in allogeneic hematopoietic stem cell transplantation recipients due to the use of immunomyelosuppressive treatments and the prolonged period of immunodeficiency that they generate. To date, the post-transplant protective role of EBV and AdV specific CD8+ T lymphocytes (CTLs) has been demonstrated. However, other factors are increasingly important in regulating the reconstitution and activity of CTLs specific to these viruses such as different cell subpopulations (CD4 + T lymphocytes, regulatory T lymphocytes, dendritic cells, Natural Killer cells, etc.), molecular mechanisms of immunoregulation and the drugs administered to the patient as prophylaxis for a possible graft-versus-host disease. The aim of this review is to analyze the importance of monitoring the functional EBV and AdV-specific cellular response in the management of post-transplant recipients.

Acquisition, remission, and persistence of eczema, asthma, and rhinitis in children.

BACKGROUND: Allergic sensitization is associated with eczema, asthma, and rhinitis. However, it is unknown whether and how allergic sensitization is associated over time with acquisition, remission, and persistence of these diseases and their comorbidity. OBJECTIVE: To gain a better understanding of factors including allergic sensitization transitions that influence the temporal pattern of asthma, eczema, and rhinitis and their comorbidity during childhood. METHODS: In the Isle of Wight birth cohort, information on allergic sensitization to common allergens was collected at ages 4, 10, and 18 years along with asthma, rhinitis, and eczema status determined by clinical diagnosis. Logistic regressions were used to estimate subsequent and concurrent odds ratios of diseases transition with allergic sensitization transition status as the main independent variable. Two transition periods were considered, 4 to 10 years of age and 10 to 18 years of age. RESULTS: The odds of new diagnosis of allergic disease (no-yes) was increased among subjects with acquired or persistent allergic sensitization to common allergens compared to subjects with no sensitization (acquisition of sensitization odds ratio [OR]=3.22, P < .0001; persistence of sensitization, OR=6.33, P < .0001). The odds of remission of allergic diseases (yes-no) was lower among subjects with acquired or sustained allergic sensitization (acquisition, OR=0.18, P = .0001; persistence, OR=0.085, P < .0001), compared to subjects not sensitized. Subjects with acquired or persistent allergic sensitization were also had higher odds for persistence of disease (yes-yes) than subjects not sensitized (acquisition, OR=5.49, P = .0001; persistence, OR=11.79, P < .0001). CONCLUSION: Transition of allergic sensitizations to common allergens is a prognostic factor for subsequent or concurrent transition of eczema, asthma, and rhinitis. Prevention or reduction in allergic sensitization has a potential to lead to remission of these conditions.

Comparison of conventional cytomorphology, flow cytometry immunophenotyping, and automated cell counting of CSF for detection of CNS involvement in acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVE: Cytospin conventional cytomorphology (CCC) is the standard method for detecting lymphoblasts in cerebrospinal fluid (CSF) of patients with acute lymphoblastic leukemia (ALL) and for guiding treatment decisions. We evaluated flow cytometry immunophenotyping (FCI) performance for improving detection of central nervous system (CNS) involvement in ALL. METHODS: This prospective study included analysis of consecutive CSF samples of patients of all ages with ALL at 3 clinical stages: new diagnosis, relapse suspicion, and after relapse treatment. Manual, cytospin, automated, and FCI methods were compared and their performance statistically assessed. Using FCI as the reference method, optimal CSF cutoff cell count that better correlated with presence of lymphoblasts was established by receiver operating characteristic (ROC) curve analysis. RESULTS: Seventy-seven CSF samples were investigated, 35 (45.4%) from newly diagnosed cases, 30 (39%) suspicion of relapse, and 12 (15.6%) after treatment for relapse. Median manual WBC count in patients with CNS involvement detected by FCI was 3.75 cells/µL (0.0-1280), and this was also the count that best correlated with CNS infiltration (sensitivity, 50.0%; specificity, 82.2%). Compared with FCI, CCC sensitivity and specificity were 28.6% and 100%. Automated CSF WBC count in patients with CNS involvement detected by FCI was 5 (0.0-1578). For automated count, optimal WBC cutoff was 4.5 cells/µL (sensitivity, 62.5%; specificity, 70.5%). CONCLUSION: Flow cytometry immunophenotyping complements conventional cytospin analysis for detection of lymphoblasts in the CSF of ALL patients at any clinical stage.