Cost-effectiveness analysis of mosunetuzumab for treatment of relapsed or refractory follicular lymphoma after two or more lines of systemic therapy in the United States.

AIMS: Mosunetuzumab has received accelerated approval by the US Food and Drug Administration for adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy. We evaluated the cost-effectiveness of mosunetuzumab for the treatment of R/R FL from a US private payer perspective. MATERIALS AND METHODS: A partitioned survival model simulated lifetime costs and outcomes of mosunetuzumab against seven comparators: axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), tazemetostat (taz, EZH2 wild-type only), rituximab plus lenalidomide (R-Len) or bendamustine (R-Benda), obinutuzumab plus bendamustine (O-Benda), and a retrospective real-world cohort (RW) based on current patterns of care derived from US electronic health records (Flatiron Health). Efficacy data for mosunetuzumab were from the pivotal Phase II GO29781 trial (NCT02500407). Relative treatment efficacy was estimated from indirect treatment comparisons (ITCs). Costs included were related to treatment, adverse events, routine care, and terminal care. Except for drug costs (March 2023), all costs were inflated to 2022 US dollars. Costs and quality-adjusted life-years (QALYs) were used to calculate incremental cost-effectiveness ratios (ICERs). Net monetary benefit (NMB) was calculated using a willingness-to-pay (WTP) threshold of $150,000/QALY. RESULTS: Mosunetuzumab dominated taz, tisa-cel, and axi-cel with greater QALYs and lower costs. Mosunetuzumab was projected to be cost-effective against R-Benda, O-Benda, and RW with ICERs of $78,607, $42,731, and $21,434, respectively. Mosunetuzumab incurred lower costs but lower QALYs vs. R-Len. NMBs showed that mosunetuzumab was cost-effective against comparators except R-Len. LIMITATIONS: Without head-to-head comparative data, the model had to rely on ITCs, some of which were affected by residual bias. Model inputs were obtained from multiple sources. Extensive sensitivity analyses assessed the importance of these uncertainties. CONCLUSION: Mosunetuzumab is estimated to be cost-effective compared with approved regimens except R-Len for the treatment of adults with R/R FL.

Association between bacterial community and cadmium distribution across Colombian cacao crops.

Assessing the bacterial community composition across cacao crops is important to understand its potential role as a modulator of cadmium (Cd) translocation to plant tissues under field conditions; Cd mobility between soil and plants is a complex and multifactorial problem that cannot be captured only by experimentation. Although microbes have been shown to metabolize and drive the speciation of Cd under controlled conditions, regardless of the link between soil bacterial community (SBC) dynamics and Cd mobilization in the rhizosphere, only a few studies have addressed the relationship between soil bacterial community composition (SBCC) and Cd content in cacao seeds (Cdseed). Therefore, this study aimed to explore the association between SBCC and different factors influencing the distribution of Cd across cacao crop systems. This study comprised 225 samples collected across five farms, where we used an amplicon sequencing approach to characterize the bacterial community composition. The soil Cd concentration alone (Cdsoil) was a poor predictor of Cdseed. Still, we found that this relationship was more apparent when the variation within farms was controlled, suggesting a role of heterogeneity within farms in modulating Cd translocation and, thus, seed Cd content. Our results provide evidence of the link between soil bacterial communities and the distribution of Cd across Colombian cacao crops, and highlight the importance of incorporating fine-spatial-scale studies to advance the understanding of factors driving Cd uptake and accumulation in cacao plants. IMPORTANCE: Cadmium (Cd) content in cacao crops is an issue that generates interest due to the commercialization of chocolate for human consumption. Several studies provided evidence about the non-biological factors involved in its translocation into the cacao plant. However, factors related to this process, including soil bacterial community composition (SBCC), still need to be addressed. It is well known that soil microbiome could impact compounds' chemical transformation, including Cd, on the field. Here, we found the first evidence of the link between soil bacterial community composition and Cd concentration in cacao soils and seeds. It highlights the importance of including the variation of bacterial communities to assess the factors driving the Cd translocation into cacao seeds. Moreover, the results highlight the relevance of the spatial heterogeneity within and across cacao farms, influencing the variability of Cd concentrations.

Parkinsonism-hyperpyrexia, a rare consequence of deep brain stimulator malfunction in advanced Parkinson's disease.

Parkinsonism-hyperpyrexia syndrome (PHS) is a rare neurological emergency that shares clinical features with neuroleptic malignant syndrome. It is usually due to sudden deprivation of dopaminergic treatment, although there are cases related to failure of the deep brain stimulation system.

Unveiling the crystal and magnetic texture of iron oxide nanoflowers.

Iron oxide nanoflowers (IONF) are densely packed multi-core aggregates known for their high saturation magnetization and initial susceptibility, as well as low remanence and coercive field. This study reports on how the local magnetic texture originating at the crystalline correlations among the cores determines the special magnetic properties of individual IONF over a wide size range from 40 to 400 nm. Regardless of this significant size variation in the aggregates, all samples exhibit a consistent crystalline correlation that extends well beyond the IONF cores. Furthermore, a nearly zero remnant magnetization, together with the presence of a persistently blocked state, and almost temperature-independent field-cooled magnetization, support the existence of a 3D magnetic texture throughout the IONF. This is confirmed by magnetic transmission X-ray microscopy images of tens of individual IONF, showing, in all cases, a nearly demagnetized state caused by the vorticity of the magnetic texture. Micromagnetic simulations agree well with these experimental findings, showing that the interplay between the inter-core direct exchange coupling and the demagnetizing field is responsible for the highly vortex-like spin configuration that stabilizes at low magnetic fields and appears to have partial topological protection. Overall, this comprehensive study provides valuable insights into the impact of crystalline texture on the magnetic properties of IONF over a wide size range, offering a deeper understanding of their potential applications in fields such as biomedicine and water remediation.

Atezolizumab in Combination with Bevacizumab for the Management of Patients with Hepatocellular Carcinoma in the First-Line Setting: Systematic Literature Review and Meta-Analysis.

Background: In 2020, atezolizumab-bevacizumab became the new standard of care (SOC) for first-line unresectable hepatocellular carcinoma (HCC) patients, following a decade where sorafenib was the preferred first-line treatment. In the last few years, a number of novel systemic treatments with non-inferiority and superiority to sorafenib have been approved as first-line treatments. Objectives: The objective of this systematic literature review (SLR) and network meta-analysis (NMA) was to compare randomised controlled trial evidence for atezolizumab-bevacizumab with globally relevant pharmacological comparators for first-line treatment of patients with unresectable HCC. Methods: Randomised controlled trials investigating first-line treatment of HCC in adults with no prior systemic treatment were eligible for inclusion into the SLR and were retrieved from Embase, MEDLINE, and Evidence-Based Medicine (EBM) Reviews. Interventions of interest for the NMA included atezolizumab-bevacizumab, sorafenib, lenvatinib, durvalumab (including in combination with tremelimumab), cabozantinib (including in combination with atezolizumab), camrelizumab (including in combination with rivoceranib), pembrolizumab (including in combination with lenvatinib), and tislelizumab. Random effects NMA was conducted for survival endpoints within a Bayesian framework with an informative prior distribution for between-study heterogeneity. The hazard ratios for relative treatment effect were estimated with 95% credible intervals (CrIs). Results: The SLR identified 49 studies, of which eight formed a connected evidence network permitting the indirect treatment comparison of atezolizumab-bevacizumab with comparators of interest. The indirect comparisons suggested an improved overall survival (OS) with atezolizumab-bevacizumab versus most comparators. All indirect treatment comparison results for atezolizumab-bevacizumab included the null value within the 95% CrI (n = 1) for OS and progression-free survival (PFS). Conclusions: The results of the NMA indicate atezolizumab-bevacizumab is associated with superior or comparable OS and PFS together with a manageable safety profile compared with globally relevant comparators in the unresected HCC indication. The findings support that atezolizumab-bevacizumab remains SOC for the management of first-line unresectable HCC patients.

Multiple Real-World Data Sources in a Bayesian Framework to Inform Long-Term Survival Estimates of Mosunetuzumab in Patients with Follicular Lymphoma.

INTRODUCTION: Patients with follicular lymphoma (FL) receiving third-line or later (3L +) therapy have long survival, which can make estimating long-term overall survival (OS) from trial data challenging. The objective of this study was to estimate long-term OS for mosunetuzumab from the GO29781 trial (NCT02500407) using multiple real-world databases (RWDs) in a Bayesian framework. METHODS: Seven RWD sources for patients with FL receiving 3L + therapy and the expansion cohort in the GO29781 trial for mosunetuzumab were used. Hazard trends from the RWD sources were analyzed, and disease-wide pointwise OS and its corresponding uncertainty were estimated using Bayesian random-effects meta-analysis from the RWD sources. Pointwise OS obtained was used as an informative prior in Bayesian survival extrapolations to data from patients receiving mosunetuzumab. Results after adjusting for background mortality were compared to equivalent frequentist extrapolations using trial data only. RESULTS: Hazard patterns from RWD sources supported a constant or linearly decreasing hazard. Mean pointwise OS for patients with FL receiving 3L + therapy was estimated at 0.52 (95% credible interval, 0.29-0.85) at 8 years. Bayesian extrapolations for mosunetuzumab produced median survival estimates of 11.6 (6.7-20.7) years to 17.0 (6.4-22.7) years depending on the distribution used, reducing uncertainty by 20% to 46% relative to the frequentist estimation. CONCLUSION: Multiple RWD sources can be synthesized to augment the credibility of data with short follow-up, long patient survival, and few events to effectively estimate long-term survival and reduce estimated uncertainty. This method can be applied to other indications with similar characteristics. CLINICAL TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: NCT02500407, July 16, 2015.

Arrhythmic Effects Evaluated on Caenorhabditis elegans: The Case of Polypyrrole Nanoparticles.

Experimental studies and clinical trials of nanoparticles for treating diseases are increasing continuously. However, the reach to the market does not correlate with these efforts due to the enormous cost, several years of development, and off-target effects like cardiotoxicity. Multicellular organisms such as the Caenorhabditis elegans (C. elegans) can bridge the gap between in vitro and vertebrate testing as they can provide extensive information on systemic toxicity and specific harmful effects through facile experimentation following 3R EU directives on animal use. Since the nematodes' pharynx shares similarities with the human heart, we assessed the general and pharyngeal effects of drugs and polypyrrole nanoparticles (Ppy NPs) using C. elegans. The evaluation of FDA-approved drugs, such as Propranolol and Racepinephrine reproduced the arrhythmic behavior reported in humans and supported the use of this small animal model. Consequently, Ppy NPs were evaluated due to their research interest in cardiac arrhythmia treatments. The NPs' biocompatibility was confirmed by assessing survival, growth and development, reproduction, and transgenerational toxicity in C. elegans. Interestingly, the NPs increased the pharyngeal pumping rate of C. elegans in two slow-pumping mutant strains, JD21 and DA464. Moreover, the NPs increased the pumping rate over time, which sustained up to a day post-excretion. By measuring pharyngeal calcium levels, we found that the impact of Ppy NPs on the pumping rate could be mediated through calcium signaling. Thus, evaluating arrhythmic effects in C. elegans offers a simple system to test drugs and nanoparticles, as elucidated through Ppy NPs.

SARS-CoV-2-Mediated Lung Edema and Replication Are Diminished by Cystic Fibrosis Transmembrane Conductance Regulator Modulators.

Coronaviruses (CoVs) of genera α, ß, γ, and δ encode proteins that have a PDZ-binding motif (PBM) consisting of the last four residues of the envelope (E) protein (PBM core). PBMs may bind over 400 cellular proteins containing PDZ domains (an acronym formed by the combination of the first letter of the names of the three first proteins where this domain was identified), making them relevant for the control of cell function. Three highly pathogenic human CoVs have been identified to date: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. The PBMs of the three CoVs were virulence factors. SARS-CoV mutants in which the E protein PBM core was replaced by the E protein PBM core from virulent or attenuated CoVs were constructed. These mutants showed a gradient of virulence, depending on whether the alternative PBM core introduced was derived from a virulent or an attenuated CoV. Gene expression patterns in the lungs of mice infected with SARS-CoVs encoding each of the different PBMs were analyzed by RNA sequencing of infected lung tissues. E protein PBM of SARS-CoV and SARS-CoV-2 dysregulated gene expression related to ion transport and cell homeostasis. Decreased expression of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA, essential for alveolar edema resolution, was shown. Reduced CFTR mRNA levels were associated with edema accumulation in the alveoli of mice infected with SARS-CoV and SARS-CoV-2. Compounds that increased CFTR expression and activity, significantly reduced SARS-CoV-2 growth in cultured cells and protected against mouse infection, suggesting that E protein virulence is mediated by a decreased CFTR expression. IMPORTANCE Three highly pathogenic human CoVs have been identified: SARS-CoV, MERS-CoV, and SARS-CoV-2. The E protein PBMs of these three CoVs were virulence factors. Gene expression patterns associated with the different PBM motifs in the lungs of infected mice were analyzed by deep sequencing. E protein PBM motif of SARS-CoV and SARS-CoV-2 dysregulated the expression of genes related to ion transport and cell homeostasis. A decrease in the mRNA expression of the cystic fibrosis transmembrane conductance regulator (CFTR), which is essential for edema resolution, was observed. The reduction of CFTR mRNA levels was associated with edema accumulation in the lungs of mice infected with SARS-CoV-2. Compounds that increased the expression and activity of CFTR drastically reduced the production of SARS-CoV-2 and protected against its infection in a mice model. These results allowed the identification of cellular targets for the selection of antivirals.

Efectividad de la vacuna para SARS-CoV-2 sobre hospitalizaciones por COVID-19 durante la cuarta ola epidémica en Querétaro, México Vacunación y hospitalización en COVID-19

Objetivo: Evaluar el efecto protector de la vacuna para SARS-CoV-2 para hospitalizaciones por COVID-19 durante la cuarta ola epidémica en Querétaro, México. Métodos: Diseño de cohorte retrospectiva en pacientes con COVID-19 durante la cuarta ola (19 de diciembre de 2021 al 9 de enero de 2022). Grupos expuestos, antecedente de vacuna anti COVID-19 (vacuna de adenovirus modificado genéticamente y vacuna de ácido ribonucleico mensajero), grupo no expuesto, no vacuna. El diagnóstico de COVID-19 se realizó con la prueba antigénica rápida en exudado orofaringeo, prueba practicada entre el primero y quinto día del inicio de sintomatología. Se incluyeron todos los pacientes que acudieron al servicio de salud por sintomatología, con prueba positiva y dos dosis de la vacuna. El análisis estadístico incluyó chi cuadrada, riesgo relativo e intervalo de confianza para riesgo relativo. Resultados: Se estudiaron 52 pacientes con vacuna de adenovirus modificado genéticamente, 119 con vacuna de ácido ribonucleico mensajero y 336 pacientes no vacunados. En pacientes no vacunados la incidencia de hospitalización fue 62,2%, en pacientes con vacuna adenovirus modificado genéticamente la hospitalización fue 23,1% (p<0.001), riesgo relativo de 0,37 (IC 95%; 0,22-0,61); y en pacientes con vacuna de ácido ribonucleico mensajero la incidencia de hospitalización fue 1,7% (p<0.001), riesgo relativo de 0,03 (IC 95%; 0,006-0,10). Conclusiones: La vacuna anti COVID-19 en el ámbito poblacional es efectiva para evitar hospitalización en pacientes que presentan cuadro agudo de COVID-19 en la cuarta ola.

Objective: To assess the protective effect of the vaccine against SARS-CoV-2 upon hospitalizations due to COVID-19 during the fourth epidemic wave in Queretaro, Mexico. Methods: This investigation was designed as a retrospective cohort study in patients with COVID-19 during the fourth wave of the epidemic (December 19th, 2021, to January 9th, 2022). The exposed group consisted in those subjects who had received a vaccine against COVID-19 (genetically modified adenovirus vaccine and messenger ribonucleic acid vaccine); and the non-exposed group consisted in those people who were not vaccinated. Diagnosis of COVID-19 was made with a rapid antigenic test in oropharyngeal exudate, and the test was performed between the first and fifth day after the onset of symptoms. All patients who came to healthcare facilities because of symptoms, with a positive test and having received two doses of the vaccine. Statistical analysis included chi-square, relative risk, and confidence intervals (CI) for the relative risk. Results: Fifty-two patients who received a genetically modified vaccine, 119 who received a messenger ribonucleic acid vaccine, and 336 non vaccinated subjects were included in the study. The frequency of hospitalization was 62,2% in non-vaccinated persons, this rate was 23,1% (p<0.001), and relative risk was 0,37 (95% CI; 0,22-0,61) in those who received a genetically modified adenovirus vaccine, and it was 1.7% (p<0.001), and relative risk was 0,03 (95% CI; 0,006-0,10) in those who received the messenger ribonucleic acid vaccine. Conclusions: From a population point of view, the vaccine against COVID-19 was effective for preventing hospitalization in patients with acute COVID-19 disease during the fourth epidemic wave.

Budget impact analysis of bevacizumab biosimilars for cancer treatment in adult patients in Spain.

OBJECTIVE: To assess the economic impact of introducing biosimilars of bevacizumab for the management of cancer patients receiving systemic bevacizumab in the National Health System (SNHS) of Spain. METHODS: A 3-year budget impact analysis model was adapted to estimate the cost of introducing biosimilars of bevacizumab in the SNHS for the adult population who were candidates to receive treatment with bevacizumab. Values for the estimation of the population were obtained from the literature and were validated by an expert panel. In this analysis only pharmaceutical costs (€, year 2021) obtained from official databases were considered. A sensitivity analysis was performed to examine the robustness of the model. RESULTS: The introduction of bevacizumab biosimilars would generate an annual cost saving of €11 558 268 (-5.1%) for the first year with a penetration share of biosimilars from 30.0%, €29 126 373 (-8.5%) for the second year with a share of 50.0% and €52 361 778 (-13.6%) for the third year with a share of 80.0%. The total pharmaceutical costs of the scenario without biosimilars are €227 033 352 for the first year, €342 663 209 for the second year and €385 013 076 for the third year. In contrast, the pharmaceutical costs of the scenario with bevacizumab biosimilars are €215 475 084, €313 536 836 and €332 651 297 for years 1, 2 and 3, respectively. CONCLUSIONS: The introduction of biosimilars in the Spanish Health System would generate saving costs in the pharmacological budget to boost biological drugs from the first year.

[How to assess health outcomes in chronic non-cancer pain? Qualitative research]. / ¿Cómo evaluar los resultados en salud en el dolor crónico no oncológico? Investigación cualitativa.

INTRODUCTION AND OBJECTIVES: There is a lack of indicators that evaluate the health results of the non-cancer chronic pain (NCCP). The objective of this study was to agree on how to evaluate health outcomes in NCCP in Spain, as well as to propose lines of action to have an optimal evaluation framework not only for patients, but for healthcare professionals and managers as well. MATERIAL AND METHODS: This was a qualitative research study through directed group interviews which followed a script based on structured questions using the PICO methodology. RESULTS: More than the intensity of pain, the main points to be measured are pain-free time, improved rest/sleep, improved mood, recovery of daily activities and adherence to treatment, in addition to -in the scope of management- resource consumption. The therapeutic objective must be defined individually, based on the adjustment of expectations between the healthcare professional and the patients, taking into account their preferences and involving them in the therapeutic process. Patients and caregivers must be informed and trained with special emphasis on the psycho-emotional sphere of pain. CONCLUSIONS: It is necessary to evaluate the health outcomes in NCCP in Spain. Lines of action are proposed that might provide an adequate assessment framework for the patient, the healthcare professionals and the health managers.

Cambios en la estructura y función cardiaca evaluados por ecocardiografía en pacientes con preeclampsia / Changes in cardiac structure and function assessed by echocardiography in patients with preeclampsia

Resumen OBJETIVO: Analizar los cambios en la estructura y función cardiaca valorados por ecocardiografía en pacientes con preeclampsia. MATERIALES Y MÉTODOS: Estudio observacional, analítico, prospectivo y longitudinal efectuado en pacientes con preeclampsia atendidas en el Hospital de Especialidades 2 Lic. Luis Donaldo Colosio Murrieta, Instituto Mexicano del Seguro Social, Ciudad Obregón, Sonora, entre los meses de septiembre a diciembre del 2021. Las participantes se seleccionaron de manera no probabilística por serie consecutiva de casos. Con la finalidad de describir los cambios se practicaron ecocardiogramas en el puerperio inmediato, al mes y tres meses después. Para evaluar las diferencias se aplicaron estadística descriptiva y análisis inferencial, χ2 de Pearson, y t de Student. Se consideró significativo un valor de p < 0.05. RESULTADOS: Se estudiaron 43 pacientes con embarazos complicados por la preeclampsia. Todas tuvieron diagnóstico de preeclampsia con datos de severidad. La mediana de semanas de gestación al diagnóstico fue de 36 (RIQ 6) y a las 37 (RIQ 5). En 17 pacientes se catalogó preeclampsia de inicio temprano. La tensión arterial sistólica y diastólica fue de 160 (RIQ 10) y 102 mmHg (RIQ 15), respectivamente. Solo 9 pacientes recibieron tratamiento antihipertensivo durante el embarazo. CONCLUSIÓN: Hubo cambios en la estructura y función cardiaca valorada en el electrocardiograma durante el puerperio caracterizados por una disminución de la deformación miocárdica longitudinal global, aumento del volumen telediastólico del ventrículo izquierdo y volumen telesistólico del ventrículo izquierdo indexado y alteración de la geometría ventricular. Esas alteraciones persistieron en el seguimiento un mes posterior al parto y revirtieron a los tres meses posparto.

Abstract OBJECTIVE: To analyze the changes in cardiac structure and function assessed by echocardiography in patients with pre-eclampsia. MATERIALS AND METHODS: Observational, analytical, prospective and longitudinal study carried out in patients with pre-eclampsia attending the Hospital de Especialidades 2 Lic. Luis Donaldo Colosio Murrieta, Instituto Mexicano del Seguro Social, Ciudad Obregón, Sonora, between September and December 2021. Participants were selected non-probabilistically through consecutive case series. To describe the changes, echocardiograms were performed in the immediate postpartum period, one month and three months later. Descriptive statistics and inferential analysis, Pearson's χ2 and t Student were used to assess differences. A value of p < 0.05 was considered significant. RESULTS: Forty-three patients with pregnancies complicated by pre-eclampsia were studied. All had a diagnosis of pre-eclampsia with severity data. The median gestational age at diagnosis was 36 (RIQ 6) and 37 (RIQ 5) weeks. Early onset pre-eclampsia was classified in 17 patients. Systolic and diastolic blood pressure were 160 (RIQ 10) and 102 mmHg (RIQ 15), respectively. Only 9 patients received antihypertensive treatment during pregnancy. CONCLUSION: There were changes in cardiac structure and function assessed by electrocardiogram during the puerperium, characterized by decreased global longitudinal myocardial deformation, increased left ventricular end-diastolic volume and indexed left ventricular end-systolic volume, and altered ventricular geometry. These changes persisted at follow-up one month postpartum and reversed at three months postpartum.

Talaromyces santanderensis: A New Cadmium-Tolerant Fungus from Cacao Soils in Colombia.

Inorganic pollutants in Colombian cocoa (Theobroma cacao L.) agrosystems cause problems in the production, quality, and exportation of this raw material worldwide. There has been an increased interest in bioprospecting studies of different fungal species focused on the biosorption of heavy metals. Furthermore, fungi constitute a valuable, profitable, ecological, and efficient natural soil resource that could be considered in the integrated management of cadmium mitigation. This study reports a new species of Talaromyces isolated from a cocoa soil sample collected in San Vicente de Chucurí, Colombia. T. santanderensis is featured by Lemon Yellow (R. Pl. IV) mycelium on CYA, mono-to-biverticillade conidiophores, and acerose phialides. T. santanderensis is distinguished from related species by its growth rate on CYAS and powdery textures on MEA, YES and OA, high acid production on CREA and smaller conidia. It is differentiated from T. lentulus by its growth rate on CYA medium at 37 °C without exudate production, its cream (R. PI. XVI) margin on MEA, and dense sporulation on YES and CYA. Phylogenetic analysis was performed using a polyphasic approach, including different phylogenetic analyses of combined and individual ITS, CaM, BenA, and RPB2 gene sequences that indicate that it is new to science and is named Talaromyces santanderensis sp. nov. This new species belongs to the Talaromyces section and is closely related to T. lentulus, T. soli, T. tumuli, and T. pratensis (inside the T. pinophilus species complex) in the inferred phylogeny. Mycelia growth of the fungal strains was subjected to a range of 0-400 mg/kg Cd and incorporated into malt extract agar (MEA) in triplicates. Fungal radial growth was recorded every three days over a 13-day incubation period and In vitro cadmium tolerance tests showed a high tolerance index (0.81) when the mycelium was exposed to 300 mg/kg of Cd. Results suggest that T. santanderensis showed tolerance to Cd concentrations that exceed the permissible limits for contaminated soils, and it is promising for its use in bioremediation strategies to eliminate Cd from highly contaminated agricultural soils.

Effects of Ultraviolet Radiation on Sediment Burial Parameters and Photo-Oxidative Response of the Intertidal Anemone Anthopleura hermaphroditica.

Anthopleura hermaphroditica is an intertidal anemone that lives semi-buried in soft sediments of estuaries and releases its brooded embryos directly to the benthos, being exposed to potentially detrimental ultraviolet radiation (UVR) levels. In this study, we investigated how experimental radiation (PAR: photosynthetically active radiation; UVA: ultraviolet A radiation; and UVB: ultraviolet B radiation) influences burrowing (time, depth and speed) in adults and juveniles when they were exposed to PAR (P, 400-700 nm), PAR + UVA (PA, 315-700 nm) and PAR + UVA + UVB (PAB, 280-700 nm) experimental treatments. The role of sediment as a physical shield was also assessed by exposing anemones to these radiation treatments with and without sediment, after which lipid peroxidation, protein carbonyls and total antioxidant capacity were quantified. Our results indicate that PAB can induce a faster burial response compared to those anemones exposed only to P. PAB increased oxidative damage, especially in juveniles where oxidative damage levels were several times higher than in adults. Sediment offers protection to adults against P, PA and PAB, as significant differences in their total antioxidant capacity were observed compared to those anemones without sediment. Conversely, the presence or absence of sediment did not influence total antioxidant capacity in juveniles, which may reflect that those anemones have sufficient antioxidant defenses to minimize photooxidative damage due to their reduced tolerance to experimental radiation. Burrowing behavior is a key survival skill for juveniles after they have been released after brooding.

Phytochemical Characterization of a Tree Tomato (Solanum betaceum Cav.) Breeding Population Grown in the Inter-Andean Valley of Ecuador.

Tree tomato (Solanum betaceum Cav.) is an Andean fruit crop that is grown in Ecuador. It is an exceptional source of minerals and vitamins, thus has nutraceutical properties. The objective of this research was to carry out a phytochemical characterization of a breeding population composed of 90 segregants. Pulp (including mesocarp, mucilage, seeds and placenta) was ground and sieved in order to obtain the liquid pulp to be lyophilized for the chemical analyzes. Antioxidants compounds were determined by spectrophotometry and vitamin C by reflectometry. Data were analyzed by principal components, grouping, and variance analyses; in addition, Z Score estimation was carried out to select elite individuals. There was a broad variability in the data obtained for the breeding population, polyphenol content varied from 5.11 to 16.59 mg GAE g-1, flavonoids from 1.24 to 6.70 mg cat g-1, carotenoids from 50.39 to 460.72 µg ß-carotene g-1, anthocyanins from 1.06 to 240.49 mg cy-3-glu 100 g-1, antioxidant capacity from 49.51 to 312.30 µm Trolox g-1, and vitamin C from 78.29 to 420.16 mg 100 g-1. It can be concluded that tree tomato is a good source of beneficial biocompounds and has a high antioxidant capacity.

Enfermedades crónicas degenerativas como factor de riesgo de letalidad por COVID-19 en México / Chronic degenerative conditions as risk factors for lethal COVID-19 / Doenças crônicas degenerativas como fator de risco para letalidade por COVID-19

RESUMEN Objetivo. Determinar el riesgo de letalidad de las enfermedades crónicas degenerativas en pacientes con COVID-19. Métodos. Se realizo un estudio de cohorte, en expedientes clínicos electrónicos de pacientes con RT-PCR positiva para COVID-19 en atención ambulatoria o intrahospitalaria en una Institución de Seguridad Social de marzo 2020 a marzo 2021. Se integraron 2 grupos de estudio, el grupo expuesto se dividió en cuatro subgrupos, cada uno con diagnóstico único y exclusivo de una patología crónica (diabetes, hipertensión, obesidad o enfermedad renal crónica); el grupo no expuesto lo integraron expedientes de pacientes sin comorbilidades. Se revisaron 1 114 expedientes en total utilizando técnica muestral aleatoria simple, una vez obtenido el tamaño mínimo de muestra se calculó el riesgo relativo para cada enfermedad crónica, se realizaron combinaciones de 2, 3 y 4, con cada uno de ellos se realizó el análisis. Resultados. En ausencia de enfermedad crónica degenerativa la prevalencia de letalidad en COVID-19 es 3,8%; en presencia de diabetes mellitus tipo 2 la letalidad es 15,8; en hipertensión arterial de 15,6%; y en obesidad 15,0%. Cuando se combinan diabetes e hipertensión la letalidad es 54,1%; en diabetes y obesidad 36,8%; y en obesidad e hipertensión 28,1%. Conclusiones. En pacientes con COVID-19 el riesgo relativo para letalidad de letalidad en diabetes es 4,17; en hipertensión 4,13; y en obesidad 3,96. Cuando se combinan dos enfermedades crónicas el riesgo relativo se duplica o triplica, para diabetes e hipertensión el riesgo relativo para letalidad es 14,2; para diabetes y obesidad 9,73; y para obesidad e hipertensión 7,43. Es verdad que las enfermedades crónicas no se presentan solas, generalmente se encuentra asociadas, y desde esa perspectiva los riesgos relativos para letalidad ofrecidos en este artículo adquieren relevancia.

ABSTRACT Objective. To determine the relative risk of a lethal outcome associated with chronic degenerative conditions in patients with COVID-19. Methods. A cohort study was conducted using electronic medical records belonging to patients who tested positive for COVID-19 on RT-PCR while receiving care as outpatients or inpatients in a social security system facility between March 2020 and March 2021. Two study groups were formed. The exposed group was divided into four subgroups, each of which was diagnosed with one and only one chronic condition (diabetes, hypertension, obesity, or chronic kidney disease); the unexposed group was obtained from the medical records of patients without comorbidities. A total of 1 114 medical records were examined using simple random sampling. Once the minimum sample size was reached, the relative risk was calculated for each chronic condition. Combinations of two, three, and four conditions were created, and each of them was included in the analysis. Results. In the absence of a chronic degenerative condition, the prevalence of a lethal outcome from COVID-19 is 3.8%; in the presence of type 2 diabetes mellitus, 15.8%; in the presence of arterial hypertension, 15.6%; and in the presence of obesity, 15.0%. For diabetes and hypertension combined, the prevalence of a lethal outcome is 54.1%; for diabetes and obesity combined, 36.8%, and for obesity and hypertension combined, 28.1%. Conclusion. In patients with COVID-19, the relative risk of a lethal outcome is 4.17 for those with diabetes, 4.13 for those with hypertension, and 3.96 for those with obesity. For two chronic conditions combined, the relative risk doubles or triples. The relative risk of a lethal outcome is 14.27 for diabetes plus hypertension; 9.73 for diabetes plus obesity, and 7.43 for obesity plus hypertension. Chronic conditions do not present alone; they generally occur together, hence the significance of the relative risks for lethal outcomes presented in this paper.

RESUMO Objetivo. Determinar o risco de letalidade conferido por doenças crônicas degenerativas em pacientes com COVID-19. Métodos. Foi realizado um estudo de coorte em prontuários eletrônicos de pacientes com RT-PCR positivo para COVID-19 em atendimento ambulatorial ou hospitalar em uma instituição de previdência social, no período de março de 2020 a março de 2021. Foram constituídos dois grupos de estudo. O grupo exposto foi dividido em quatro subgrupos, cada um com diagnóstico único e exclusivo de uma doença crônica (diabetes, hipertensão, obesidade ou doença renal crônica). O grupo não exposto foi constituído por prontuários de pacientes sem comorbidades. Foram revisados 1.114 prontuários no total, utilizando técnica de amostragem aleatória simples. Uma vez obtido o tamanho mínimo da amostra, foi calculado o risco relativo para cada doença crônica. Foram realizadas combinações de 2, 3 e 4, tendo sido feita a análise com cada uma delas. Resultados. Na ausência de doença crônica degenerativa, a prevalência de letalidade na COVID-19 é de 3,8%; na presença de diabetes mellitus tipo 2, a letalidade é de 15,8%; na presença de hipertensão arterial, 15,6%; e na presença de obesidade, 15%. Quando tanto diabetes como hipertensão estão presentes, a letalidade é de 54,1%; com diabetes e obesidade, 36,8%; e obesidade com hipertensão, 28,1%. Conclusões. Em pacientes com COVID-19, o risco relativo de letalidade é de 4,17 naqueles com diabetes; 4,13 naqueles com hipertensão; e 3,96 naqueles com obesidade. Quando duas doenças crônicas são combinadas, o risco relativo dobra ou triplica. Para diabetes e hipertensão, o risco relativo de letalidade é 14,27; para diabetes e obesidade, 9,73; e para obesidade e hipertensão, 7,43. As doenças crônicas não ocorrem sozinhas (geralmente estão associadas), e nessa perspectiva os riscos relativos de letalidade apresentados neste artigo tornam-se relevantes.

Safety and diagnostic performance of parathyroid hormone assay in fine-needle aspirate in suspicious parathyroid adenomas.

OBJECTIVE: To evaluate the safety and diagnostic performance of parathyroid hormone assay in fine-needle aspirate (PTH-FNA) in patients with primary hyperparathyroidism and suspicious parathyroid adenomas. METHODOLOGY: A retrospective observational study was performed in 47 patients (57.7 ±â€¯11.2 years of average age, 74% women) attending an endocrinology clinic for primary hyperparathyroidism (average calcemia: 11.6 ±â€¯1.6 mg/dl and PTH: 276 ±â€¯477 pg/mL) in which PTH-FNA was made. Sensibility, specificity, positive predictive value and negative predictive value were calculated in all surgical patients. RESULTS: Forty-seven lesions were punctured (mean adenoma maximum diameter: 1.8 ±â€¯2.6 cm): negative image in the sestamibi scan (26 patients); the discordance between ultrasonography and the sestamibi scan (6 patients); possible intrathyroidal adenomas (4 patients); a positive sestamibi scan in 2 or more localizations (4 patients); ectopic adenoma (3 patients); persistent primary hyperparathyroidism (2 patients) and atypical adenomas (2 patients). Mean PTH-FNA was 2853 ±â€¯3957 pg/mL and 68% were considered positive (PTH-FNA ≥ 100 pg/mL). No complications were detected during or after the puncture. Thirty-seven patients were operated on, 95% were cured and no parathyromatosis cases were detected. PTH-FNA ≥ 100 pg/mL as a diagnostic test had a sensitivity of 93.7%, a specificity of 100%, a positive predictive value of 100% and an negative predictive value of 71.4%. CONCLUSION: PTH-FNA is an easy and safe diagnostic test and has a high sensitivity and specificity for differentiating between parathyroid adenomas and other cervical masses in patients with primary hyperparathyroidism.

Repression of the Hox gene abd-A by ELAV-mediated Transcriptional Interference.

Intergenic transcription is a common feature of eukaryotic genomes and performs important and diverse cellular functions. Here, we investigate the iab-8 ncRNA from the Drosophila Bithorax Complex and show that this RNA is able to repress the transcription of genes located at its 3' end by a sequence-independent, transcriptional interference mechanism. Although this RNA is expressed in the early epidermis and CNS, we find that its repressive activity is limited to the CNS, where, in wild-type embryos, it acts on the Hox gene, abd-A, located immediately downstream of it. The CNS specificity is achieved through a 3' extension of the transcript, mediated by the neuronal-specific, RNA-binding protein, ELAV. Loss of ELAV activity eliminates the 3' extension and results in the ectopic activation of abd-A. Thus, a tissue-specific change in the length of a ncRNA is used to generate a precise pattern of gene expression in a higher eukaryote.