A phase I dose escalation and expansion trial of the next-generation oral SERD camizestrant in women with ER-positive, HER2-negative advanced breast cancer: SERENA-1 monotherapy results.

BACKGROUND: SERENA-1 (NCT03616587) is a phase I, multi-part, open-label study of camizestrant in pre- and post-menopausal women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Parts A and B aim to determine the safety and tolerability of camizestrant monotherapy and define doses for clinical evaluation. PATIENTS AND METHODS: Women aged ≥18 years with metastatic or recurrent ER+, HER2- breast cancer, refractory (or intolerant) to therapy, were assigned 25 mg up to 450 mg once daily (QD; escalation) or 75, 150, or 300 mg QD (expansion). Safety and tolerability, antitumor efficacy, pharmacokinetics, and impact on mutations in the estrogen receptor gene (ESR1m) circulating tumor (ct)DNA levels were assessed. RESULTS: By 9 March 2021, 108 patients received camizestrant monotherapy at 25-450 mg doses. Of these, 93 (86.1%) experienced treatment-related adverse events (TRAEs), 82.4% of which were grade 1 or 2. The most common TRAEs were visual effects (56%), (sinus) bradycardia (44%), fatigue (26%), and nausea (15%). There were no TRAEs grade 3 or higher, or treatment-related serious adverse events at doses ≤150 mg. Median tmax was achieved ∼2-4 h post-dose at all doses investigated, with an estimated half-life of 20-23 h. Efficacy was observed at all doses investigated, including in patients with prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and/or fulvestrant treatment, with and without baseline ESR1 mutations, and with visceral disease, including liver metastases. CONCLUSIONS: Camizestrant is a next-generation oral selective ER antagonist and degrader (SERD) and pure ER antagonist with a tolerable safety profile. The pharmacokinetics profile supports once-daily dosing, with evidence of pharmacodynamic and clinical efficacy in heavily pre-treated patients, regardless of ESR1m. This study established 75-, 150-, and 300-mg QD doses for phase II testing (SERENA-2, NCT04214288 and SERENA-3, NCT04588298).

RITS: a toolbox for assessing complex interventions via interrupted time series models.

BACKGROUND: Various interacting and interdependent components comprise complex interventions. These components create difficulty in assessing the true impact of interventions designed to improve patient-centered outcomes. Interrupted time series (ITS) designs borrow from case-crossover designs and serve as quasi-experimental methodology able to retrospectively assess the impact of an intervention while accounting for temporal correlation. While ITS designs are aptly situated for studying the impacts of large-scale public health policies, existing ITS software implement rigid ITS methodology that often assume the pre- and post-intervention phases are fully differentiated (by a known change-point or set of time points) and do not allow for changes in both the mean functions and correlation structure. RESULTS: This article describes the Robust Interrupted Time Series (RITS) toolbox, a stand-alone user-friendly application researchers can use to implement flexible ITS models that estimate the lagged effect of an intervention on an outcome, level and trend changes, and post-intervention changes in the correlation structure, for single and multiple ITS. The RITS toolbox incorporates a formal test for the existence of a change in the outcome and estimates a change-point over a set of possible change-points defined by the researcher. In settings with multiple ITS, RITS provides a global over-all units change-point and allows for unit-specific changes in the mean functions and correlation structures. CONCLUSIONS: The RITS toolbox is the first piece of software that allows researchers to use flexible ITS models that test for the existence of a change-point, estimate the change-point (if estimation is desired), and allow for changes in both the mean functions and correlation structures at the change point. RITS does not require any knowledge of a statistical (or otherwise) programming language, is freely available to the community, and may be downloaded and used on a local machine to ensure data protection.

Immediate and 24-h post-marathon cardiac troponin T is associated with relative exercise intensity.

PURPOSE: We aimed at exploring whether cardiopulmonary fitness, echocardiographic measures and relative exercise intensity were associated with high-sensitivity cardiac troponin T (hs-TNT) rise and normalization following a marathon. METHODS: Nighty-eight participants (83 men, 15 women; 38.72 ± 3.63 years) were subjected to echocardiographic assessment and a cardiopulmonary exercise test (CPET) before the race. hs-TNT was measured before, immediately after and at 24, 48, 96, 144 and 192 h post-race. Speed and mean heart rate (HR) during the race were relativized to CPET values: peak speed (%VVMAX), peak HR (HR%MAX), speed and HR at the second ventilatory threshold (HR%VT2 and %VVT2). RESULTS: Hs-TNT increased from pre- to post-race (5.74 ± 5.29 vs. 50.4 ± 57.04 ng/L; p < 0.001), seeing values above the Upper Reference Limit (URL) in 95% of the participants. At 24 h post-race, 39% of the runners still exceeded the URL (High hs-TNT group). hs-TNT rise was correlated with marathon speed %VVT2 (r = 0.22; p = 0.042), mean HR%VT2 (r = 0.30; p = 0.007), and mean HR%MAX (r = 0.32; p = 0.004). Moreover, the High hs-TNT group performed the marathon at a higher Speed %VVT2 (88.21 ± 6.53 vs. 83.49 ± 6.54%; p = 0.002) and Speed %VVMAX (72 ± 4.25 vs. 69.40 ± 5.53%; p = 0.009). hs-TNT showed no significant associations with cardiopulmonary fitness and echocardiographic measures, except for a slight correlation with left ventricular end systolic diameter (r = 0.26; p = 0.018). CONCLUSION: Post-race hs-TNT was above the URL in barely all runners. Magnitude of hs-TNT rise was correlated with exercise mean HR; whereas, its normalization kept relationship with marathon relative speed.

Differences between migrants and Spanish-born population through the HIV care cascade, Catalonia: an analysis using multiple data sources.

Migrants are considered a key group at risk for HIV infection. This study describes differences between migrants and the Spanish-born population as they progress through the HIV care cascade in Catalonia, Spain. This study found that among people reached by prevention activities, migrants had a higher number of barriers to access HIV testing services than Spanish-born people, driven primarily by shared risk factors. Between 2001 and 2013, 9829 new HIV diagnoses were reported in Catalonia, the proportion of migrants increasing from 24% in 2001 to 41% in 2013. Compared with Spanish-born people, migrants had a higher proportion of women at diagnosis (24·6% vs. 16·7%), and were younger (median age of 33 vs. 37). The most frequent at-risk population was MSM (men who have sex with men) in both migrants and Spanish-born people, (40% and 43%, respectively), although there were significant differences by region of origin. People from sub-Saharan Africa had the highest proportion of late diagnosis (63·7%). Compared with the Spanish-born population, migrants on follow-up had a lower proportion of people on antiretroviral therapy (ART) (93·7% vs. 90·8%, P < 0·001) and with viral suppression (87·2% vs. 82·9%, P < 0·001). Migrants have higher number of barriers to access HIV testing services, lower retention rates and proportions on ART as compared with Spanish-born people, these differences not being uniform between migrants from different regions.

ARFI elastography: changes after direct-acting antiviral treatment in transplanted livers with relapse of hepatitis C virus infection. / Elastografía tipo ARFI: modificación tras tratamiento antiviral en el trasplante hepático con recidiva por VHC.

OBJECTIVE: To evaluate the changes in the values obtained in acoustic radiation force impulse (ARFI) elastography of the liver after antiviral treatment in patients with liver transplants and hepatitis C virus (HVC) infection recurring after transplantation. MATERIAL AND METHODS: We studied 15 patients infected with HVC who had received liver transplants where an HVC infection recurring in the graft within one year after the transplant was treated with direct-acting antivirals. All patients underwent ultrasonography including Doppler and ARFI elastography in the three months before starting treatment with direct-acting antivirals (baseline study) and again in the three months after finishing the treatment. In the same week when the elastography study was done, liver function tests were done and the viral load (HCV RNA) was determined in peripheral blood with the polymerase chain reaction method. We used the Wilcoxon test for paired samples to compare the changes in the shear wave velocities before and after treatment. RESULTS: All patients achieved a virologic response that was sustained at 3 months after the end of treatment. On elastography, median shear wave velocities decreased after treatment (1.97m/s before treatment vs. 1.58m/s after treatment; p=0.001). CONCLUSION: The shear wave velocity decreased significantly after antiviral treatment in patients who had relapsed HVC infection after liver transplantation.

A methyl transferase links the circadian clock to the regulation of alternative splicing.

Circadian rhythms allow organisms to time biological processes to the most appropriate phases of the day-night cycle. Post-transcriptional regulation is emerging as an important component of circadian networks, but the molecular mechanisms linking the circadian clock to the control of RNA processing are largely unknown. Here we show that PROTEIN ARGININE METHYL TRANSFERASE 5 (PRMT5), which transfers methyl groups to arginine residues present in histones and Sm spliceosomal proteins, links the circadian clock to the control of alternative splicing in plants. Mutations in PRMT5 impair several circadian rhythms in Arabidopsis thaliana and this phenotype is caused, at least in part, by a strong alteration in alternative splicing of the core-clock gene PSEUDO RESPONSE REGULATOR 9 (PRR9). Furthermore, genome-wide studies show that PRMT5 contributes to the regulation of many pre-messenger-RNA splicing events, probably by modulating 5'-splice-site recognition. PRMT5 expression shows daily and circadian oscillations, and this contributes to the mediation of the circadian regulation of expression and alternative splicing of a subset of genes. Circadian rhythms in locomotor activity are also disrupted in dart5-1, a mutant affected in the Drosophila melanogaster PRMT5 homologue, and this is associated with alterations in splicing of the core-clock gene period and several clock-associated genes. Our results demonstrate a key role for PRMT5 in the regulation of alternative splicing and indicate that the interplay between the circadian clock and the regulation of alternative splicing by PRMT5 constitutes a common mechanism that helps organisms to synchronize physiological processes with daily changes in environmental conditions.

Possible land management uses of common cypress to reduce wildfire initiation risk: a laboratory study.

Accurate determination of flammability is required in order to improve knowledge about vegetation fire risk. Study of the flammability of different plant species is essential for the Mediterranean area, where most ecosystems are adapted to natural fire but vulnerable to recurrent human-induced fires, which are the main cause of forest degradation. However, the methods used to evaluate vegetation flammability have not yet been standardized. Cupressus sempervirens is a native or naturalized forest tree species in the Mediterranean area that is able to tolerate prolonged drought and high temperatures. The aim of this study was to characterize the flammability of C. sempervirens var. horizontalis at particle level by using different bench-scale calorimetry techniques (mass loss calorimeter, epiradiator and oxygen bomb) to determine the main flammability descriptors (ignitability, sustainability, combustibility and consumability) in live crown and litter samples. Our findings indicate that this variety of cypress is relatively resistant to ignition because of the high ash content, the high critical heat flux, the high time to ignition displayed by both crown and litter samples and the ability of the leaves to maintain a high water content during the summer. We also discuss the possibility of exploiting some morphological, functional and ecological traits of the species to construct a barrier system (with selected varieties of cypress) as a promising complementary land management tool to reduce the fire spread and intensity in a Mediterranean context.

Electrode Surface Area Impacts Measurement of High Frequency Oscillations in Human Intracranial EEG.

OBJECTIVE: High-frequency oscillations (HFOs) are a promising prognostic biomarker of surgical outcome in patients with epilepsy. Their rates of occurrence and morphology have been studied extensively using recordings from electrodes of various geometries. While electrode size is a potential confounding factor in HFO studies, it has largely been disregarded due to a lack of consistent evidence. Therefore, we designed an experiment to directly test the impact of electrode size on HFO measurement. METHODS: We first simulated HFO measurement using a lumped model of the electrode-tissue interaction. Then eight human subjects were each implanted with a high-density 8x8 grid of subdural electrodes. After implantation, the electrode sizes were altered using a technique recently developed by our group, enabling intracranial EEG recordings for three different electrode surface areas from a static brain location. HFOs were automatically detected in the data and their characteristics were calculated. RESULTS: The human subject measurements were consistent with the model. Specifically, HFO rate measured per area of tissue decreased significantly as electrode surface area increased. The smallest electrodes recorded more fast ripples than ripples. Amplitude of detected HFOs also decreased as electrode surface area increased, while duration and peak frequency were unaffected. CONCLUSION: These results suggest that HFO rates measured using electrodes of different surface areas cannot be compared directly. SIGNIFICANCE: This has significant implications for HFOs as a tool for surgical planning, particularly for individual patients implanted with electrodes of multiple sizes and comparisons of HFO rate made across patients and studies.

Longitudinal Study after Sputnik V Vaccination Shows Durable SARS-CoV-2 Neutralizing Antibodies and Reduced Viral Variant Escape to Neutralization over Time.

Recent studies have shown a temporal increase in the neutralizing antibody potency and breadth to SARS-CoV-2 variants in coronavirus disease 2019 (COVID-19) convalescent individuals. Here, we examined longitudinal antibody responses and viral neutralizing capacity to the B.1 lineage virus (Wuhan related), to variants of concern (VOC; Alpha, Beta, Gamma, and Delta), and to a local variant of interest (VOI; Lambda) in volunteers receiving the Sputnik V vaccine in Argentina. Longitudinal serum samples (N = 536) collected from 118 volunteers obtained between January and October 2021 were used. The analysis indicates that while anti-spike IgG levels significantly wane over time, the neutralizing capacity for the Wuhan-related lineages of SARS-CoV-2 and VOC is maintained within 6 months of vaccination. In addition, an improved antibody cross-neutralizing ability for circulating variants of concern (Beta and Gamma) was observed over time postvaccination. The viral variants that displayed higher escape to neutralizing antibodies with respect to the original virus (Beta and Gamma variants) were the ones showing the largest increase in susceptibility to neutralization over time after vaccination. Our observations indicate that serum neutralizing antibodies are maintained for at least 6 months and show a reduction of VOC escape to neutralizing antibodies over time after vaccination. IMPORTANCE Vaccines have been produced in record time for SARS-CoV-2, offering the possibility of halting the global pandemic. However, inequalities in vaccine accessibility in different regions of the world create a need to increase international cooperation. Sputnik V is a recombinant adenovirus-based vaccine that has been widely used in Argentina and other developing countries, but limited information is available about its elicited immune responses. Here, we examined longitudinal antibody levels and viral neutralizing capacity elicited by Sputnik V vaccination. Using a cohort of 118 volunteers, we found that while anti-spike antibodies wane over time, the neutralizing capacity to viral variants of concern and local variants of interest is maintained within 4 months of vaccination. In addition, we observed an increased cross-neutralization activity over time for the Beta and Gamma variants. This study provides valuable information about the immune response generated by a vaccine platform used in many parts of the world.

The week after running a marathon: Effects of running vs elliptical training vs resting on neuromuscular performance and muscle damage recovery.

Our aim was to compare the effects of two exercise modalities vs resting on the time course of neuromuscular performance and muscle damage recovery during the week after running a marathon. Sixty-four finishers from a road marathon completed the study (54 men and 10 women; 39 ± 4 years; 3 h 35 min ± 21 min). The day before the race, within 15 min after finishing the marathon and at 24, 48, 96, 144 and 192 h postrace, lactate dehydrogenase and creatine kinase were analysed. Participants also performed a squat jump (SJ) test before and after the marathon and at 48, 96 and 144 h postrace. On their arrival to the finish line, participants were randomized into one of the three intervention groups: running (RUN), elliptical training (ELIP) and resting recovery (REST). RUN and ELIP groups exercised continuously for 40 min at a moderate intensity (95-105% of the HR corresponding to the first ventilatory threshold) at 48, 96 and 144 h after the marathon. Neither 'Intervention' factor nor 'Intervention x Time' interaction effects were revealed for muscle damage blood markers (p > 0.05). On the other hand, RUN group evidenced an enhancement in SJ performance 96 h post-marathon as compared with REST group (108.29 ± 10.64 vs 100.58 ± 9.16%, p = 0.020, d = 0.80). Consequently, return to running at 48 h post-marathon does not seem to have a negative impact on muscle damage recovery up to eight days post-race and it could be recommended in order to speed up neuromuscular recovery.

Do cone age and heating mode determine the opening of serotinous cones during wildfires? A new bench scale approach applied to Pinus halepensis Mill.

Serotiny is a well-known fire adaptive trait in some species, as the Mediterranean conifer Pinus halepensis. However, information about cone opening mechanisms during wildfires and consequences on post fire dispersal is scarce. In addition, standardized methods allowing a realistic simulation of heating modes at bench-scale are not available. In this study, we address for the first time the interacting effects of radiation, convection and direct flame on the opening and seed release of serotinous cones, following a novel repeatable methodology. Using a Mass Loss Calorimeter (MLC) device and a wide range of heat exposures (between 5 and 75 kW m-2) with or without ignition, we intended to simulate realistic cone heating during surface and crown fires in laboratory conditions. Additionally, we included the effect of contrasting serotinous cone ages interacting with heating mode and considering the random individual variation. The proposed methodology has shown a high potential to simulate the complex process of crown fires in relation to cone opening under controlled conditions, detecting a threshold of heat exposure (25-30 kW m-2) for cone opening. We confirmed that heating mode had a highly significant effect in cone opening, interacting with cone age, while cone age effect on its own was marginal. Particularly, ignition significantly increased the efficacy of cone opening and seed release. Moreover, young and old cones behave differently in seed release, both in surface and crown fire simulations. Implementing and adjusting this methodology in other species will allow more realistic and reliable quantitative comparisons than previously attained.

Sputnik V vaccine elicits seroconversion and neutralizing capacity to SARS-CoV-2 after a single dose.

Massive vaccination offers great promise for halting the global COVID-19 pandemic. However, the limited supply and uneven vaccine distribution create an urgent need to optimize vaccination strategies. We evaluate SARS-CoV-2-specific antibody responses after Sputnik V vaccination of healthcare workers in Argentina, measuring IgG anti-spike titers and neutralizing capacity after one and two doses in a cohort of naive or previously infected volunteers. By 21 days after receiving the first dose of the vaccine, 94% of naive participants develop spike-specific IgG antibodies. A single Sputnik V dose elicits higher antibody levels and virus-neutralizing capacity in previously infected individuals than in naive ones receiving the full two-dose schedule. The high seroconversion rate after a single dose in naive participants suggests a benefit of delaying administration of the second dose to increase the number of people vaccinated. The data presented provide information for guiding public health decisions in light of the current global health emergency.

It's a matter of time: the role of transcriptional regulation in the circadian clock-pathogen crosstalk in plants.

Most living organisms possess an internal timekeeping mechanism known as the circadian clock, which enhances fitness by synchronizing the internal timing of biological processes with diurnal and seasonal environmental changes. In plants, the pace of these biological rhythms relies on oscillations in the expression level of hundreds of genes tightly controlled by a group of core clock regulators and co-regulators that engage in transcriptional and translational feedback loops. In the last decade, the role of several core clock genes in the control of defense responses has been addressed, and a growing amount of evidence demonstrates that circadian regulation is relevant for plant immunity. A reciprocal connection between these pathways was also established following the observation that in Arabidopsis thaliana, as well as in crop species like tomato, plant-pathogen interactions trigger a reconfiguration of the circadian transcriptional network. In this review, we summarize the current knowledge regarding the interaction between the circadian clock and biotic stress responses at the transcriptional level, and discuss the relevance of this crosstalk in the plant-pathogen evolutionary arms race. A better understanding of these processes could aid in the development of genetic tools that improve traditional breeding practices, enhancing tolerance to plant diseases that threaten crop yield and food security all around the world.

Assessing the age- and gender-dependence of the severity and case fatality rates of COVID-19 disease in Spain.

Background: The assessment of the severity and case fatality rates of coronavirus disease 2019 (COVID-19) and the determinants of its variation is essential for planning health resources and responding to the pandemic. The interpretation of case fatality rates (CFRs) remains a challenge due to different biases associated with surveillance and reporting. For example, rates may be affected by preferential ascertainment of severe cases and time delay from disease onset to death. Using data from Spain, we demonstrate how some of these biases may be corrected when estimating severity and case fatality rates by age group and gender, and identify issues that may affect the correct interpretation of the results. Methods: Crude CFRs are estimated by dividing the total number of deaths by the total number of confirmed cases. CFRs adjusted for preferential ascertainment of severe cases are obtained by assuming a uniform attack rate in all population groups, and using demography-adjusted under-ascertainment rates. CFRs adjusted for the delay between disease onset and death are estimated by using as denominator the number of cases that could have a clinical outcome by the time rates are calculated. A sensitivity analysis is carried out to compare CFRs obtained using different levels of ascertainment and different distributions for the time from disease onset to death. Results: COVID-19 outcomes are highly influenced by age and gender. Different assumptions yield different CFR values but in all scenarios CFRs are higher in old ages and males. Conclusions: The procedures used to obtain the CFR estimates require strong assumptions and although the interpretation of their magnitude should be treated with caution, the differences observed by age and gender are fundamental underpinnings to inform decision-making.

Inference on Long-Range Temporal Correlations in Human EEG Data.

Detrended Fluctuation Analysis (DFA) is a statistical estimation algorithm used to assess long-range temporal dependence in neural time series. The algorithm produces a single number, the DFA exponent, that reflects the strength of long-range temporal correlations in the data. No methods have been developed to generate confidence intervals for the DFA exponent for a single time series segment. Thus, we present a statistical measure of uncertainty for the DFA exponent in electroencephalographic (EEG) data via application of a moving-block bootstrap (MBB). We tested the effect of three data characteristics on the DFA exponent: (1) time series length, (2) the presence of artifacts, and (3) the presence of discontinuities. We found that signal lengths of ∼5 minutes produced stable measurements of the DFA exponent and that the presence of artifacts positively biased DFA exponent distributions. In comparison, the impact of discontinuities was small, even those associated with artifact removal. We show that it is possible to combine a moving block bootstrap with DFA to obtain an accurate estimate of the DFA exponent as well as its associated confidence intervals in both simulated data and human EEG data. We applied the proposed method to human EEG data to (1) calculate a time-varying estimate of long-range temporal dependence during a sleep-wake cycle of a healthy infant and (2) compare pre- and post-treatment EEG data within individual subjects with pediatric epilepsy. Our proposed method enables dynamic tracking of the DFA exponent across the entire recording period and permits within-subject comparisons, expanding the utility of the DFA algorithm by providing a measure of certainty and formal tests of statistical significance for the estimation of long-range temporal dependence in neural data.

Bacterial Infection Disrupts Clock Gene Expression to Attenuate Immune Responses.

The circadian clock modulates immune responses in plants and animals; however, it is unclear how host-pathogen interactions affect the clock. Here we analyzed clock function in Arabidopsis thaliana mutants with defective immune responses and found that enhanced disease susceptibility 4 (eds4) displays alterations in several circadian rhythms. Mapping by sequencing revealed that EDS4 encodes the ortholog of NUCLEOPORIN 205, a core component of the inner ring of the nuclear pore complex (NPC). Consistent with the idea that the NPC specifically modulates clock function, we found a strong enrichment in core clock genes, as well as an increased nuclear to total mRNA accumulation, among genes that were differentially expressed in eds4 mutants. Interestingly, infection with Pseudomonas syringae in wild-type (WT) plants downregulated the expression of several morning core clock genes as early as 1 h post-infection, including all members of the NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED (LNK) gene family, and this effect was attenuated in eds4. Furthermore, lnk mutants were more susceptible than the WT to P. syringae infection. These results indicate that bacterial infection, acting in part through the NPC, alters core clock gene expression and/or mRNA accumulation in a way that favors bacterial growth and disease susceptibility.

[Persistent pulmonary hypertension of the newborn following ingestion of nonsteroidal anti-inflammatory drugs during pregnancy]. / Hipertensión pulmonar neonatal grave tras ingestión de antiinflamatorios no esteroideos durante el embarazo.

Nonsteroidal anti-inflammatory drugs induce the inhibition of prostaglandin synthesis, which can cause constriction of the fetal ductus arteriosus in the pregnancy. We report two cases of antenatal closure of ductus arteriosus with severe pulmonary hypertension following maternal ingestion of nonsteroidal anti-inflammatory drugs (niflumic acid and acetylsalicylic acid) in the last days before delivery. To our knowledge, this is only the second case in literature describing antenatal closure of ductus arteriosus after the administration of niflúmic acid. Prescription of nonsteroidal anti-inflammatory drugs must be avoided during pregnancy. Fetal echocardiography must be monitored in those women treated with nonsteroidal anti-inflammatory drugs.

Short-term effects of prescribed burning on litterfall biomass in mixed stands of Pinus nigra and Pinus pinaster and pure stands of Pinus nigra in the Cuenca Mountains (Central-Eastern Spain).

Fire severity, defined as the magnitude of fire effects in an ecosystem, is a key factor to consider in planning management strategies for protecting forests against fire. Although prescribed burning has been used as a fuel reduction tool in forest ecosystems, it is quite limited in the Mediterranean region. Furthermore, little is known about how tree crowns are affected by prescribed underburning aimed at reducing fire severity in conifer stands. As part of an ongoing study to assess the effects of prescribed burning on the tree canopy, litterfall is currently being monitored in a network of experimental plots located in mixed (Pinus nigra and Pinus pinaster) and pure (P. nigra) conifer stands in the Cuenca Mountains (Castilla La Mancha, Spain). A total of 12 study plots (30m×30m) were established in a completely randomized experimental design to determine the effect of burning, with 2 treatments: no burning (control) and burning (i.e. with three replicate plots for each treatment and site). Burning was conducted in May 2016. In each plot, 8 litterfall collectors were installed at regular intervals, according to international protocols (ICP Forests), and all biomass falling into the collectors is being monitored monthly. The specific objective of this study is to assess how prescribed burning affects the rate of generation of foliar and non-foliar litterfall biomass due to the fire. In addition, the Leaf Area Index was estimated before burning and one year later to verify possible changes in the structure of the stands. This information could be used to help minimize the negative impacts of prescribed underburning on litterfall. To our knowledge, this study represents the first attempt to evaluate the effect of prescribed burning on litterfall biomass in Europe.

Tumor glómico del septum nasal / Glomic tumor of the nasal septum

Presentamos el caso clínico de una mujer de 58 años que consulta por episodios de epis-taxis autolimitadas por fosa nasal derecha asociados a hipersensibilidad al manipular dicha fosa nasal. A la exploración se evidenció en el septum nasal una lesión mucosa nodular, de consistencia dura y aspecto violáceo. Se llevó a cabo exéresis de la misma por vía endonasal, con resultado histopatológico de tumor glómico (TG) del septum nasal. El TG es una neoplasia benigna perivascular, derivada de las células musculares lisas presentes en el cuerpo glómico; estructura con función termorreguladora, formada por un shunt entre arteriolas y vénulas, sin presencia de red capilar. Los cuerpos glómicos están presentes, mayoritariamente, en extremidades (lecho ungueal). Los tumores glómicos son, verdaderamente, excepcionales en el área ORL, existiendo sólo una treintena de casos publicados hasta la fecha a nivel nasosinusal. La mayoría de casos se presentan entre la 5ᵃ y 6ᵃ década de la vida y más, frecuentemente, en mujeres. Plantea diagnóstico diferencial, fundamentalmente, con dos entidades: el paraganglioma (con el que no debe ser confundido desde el punto de vista terminológico ni histológico), y con el tumor fibroso solitario (antiguo hemangiopericitoma). El comportamiento es benigno y el tratamiento es la cirugía

We present the clinical case of a 58-year-old woman who consulted for episodes of self-limited epistaxis in the right nostril associated with hypersensitivity to manipulation of this nostril. Examination revealed a nodular mucosal lesion in the nasal septum, with a hard consistency and purplish appearance. The lesion was excised endonasally, with histopatho-logical result of a glomus tumor (GT) of the nasal septum. The GT is a benign perivascular neoplasm, derived from smooth muscle cells present in the glomus body; structure with thermoregulatory function, formed by a shunt between arterioles and venules, without the presence of capillary network. Glomus bodies are mostly present in the extremities (nail bed). Glomus tumors are truly exceptional in the ENT area, with only about thirty cases published to date at the nasosinusal level. Most cases occur between the 5th and 6th decade of life and more frequently in women. It raises differential diagnosis fundamentally with two entities: paraganglioma (with which it should not be confused from the terminological or histological point of view) and with solitary fibrous tumor (former hemangiopericytoma). The behavior is benign and the treatment is surgery.

Transcriptional and post-transcriptional control of the plant circadian gene regulatory network.

The circadian clock drives rhythms in multiple physiological processes allowing plants to anticipate and adjust to periodic changes in environmental conditions. These physiological rhythms are associated with robust oscillations in the expression of thousands of genes linked to the control of photosynthesis, cell elongation, biotic and abiotic stress responses, developmental processes such as flowering, and the clock itself. Given its pervasive effects on plant physiology, it is not surprising that circadian clock genes have played an important role in the domestication of crop plants and in the improvement of crop productivity. Therefore, identifying the principles governing the dynamics of the circadian gene regulatory network in plants could strongly contribute to further speed up crop improvement. Here we provide an historical as well as a current description of our knowledge of the molecular mechanisms underlying circadian rhythms in plants. This work focuses on the transcriptional and post-transcriptional regulatory layers that control the very core of the circadian clock, and some of its complex interactions with signaling pathways that help synchronize plant growth and development to daily and seasonal changes in the environment. This article is part of a Special Issue entitled: Plant Gene Regulatory Mechanisms and Networks, edited by Dr. Erich Grotewold and Dr. Nathan Springer.