Laparoscopic Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy, an Update From the International PSOGI Registry.

INTRODUCTION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are established treatments for peritoneal surface malignancies, traditionally performed via laparotomy. Recent advancements in laparoscopic approaches (L-CRS + HIPEC) have shown promising results in selected patients. METHODS: The PSOGI registry, established in November 2019, collects data from specialized centers performing L-CRS + HIPEC. Data were collected prospectively and analyzed retrospectively, excluding risk-reducing procedures without peritoneal disease. The learning curve was assessed using a 14-cases cutoff. RESULTS: Today, 323 patients have been registered, 193 were included finally. Perioperative outcomes improved after 14 cases: Length of hospital stay was 7.78 ± 3.64 days (consolidation) versus 8.8 ± 8.79 days (learning) and major morbidity was 0% (consolidation) versus 5% (learning), (p = n.s.). Estimated blood loss was lower in the consolidation phase. Oncological outcomes also improved: Recurrence rate was 8.7% (consolidation) versus 17.8% (learning). Disease-free survival 5 years, 65% (learning) versus 88% (consolidation) (p = 0.012). CONCLUSION: The L-CRS + HIPEC is a safe procedure with non-inferior oncologic outcomes which it is evaluating in an IDEAL setting by an international group. The validation of the learning curve, gives us the knowledge that a mentoring program must be setup to reduce the learning curve impact in oncologic failure.

Retrospective case-control non-inferiority analysis of ultrasound-guided erector spinae plane block in dogs undergoing mini-hemilaminectomy for intervertebral disc disease.

BACKGROUND: Veterinary medicine has seen significant advancements in locoregional anaesthesia and pain management, including the emergence of the erector spinae plane (ESP) block. However, limited clinical evidence exists on its efficacy and safety. OBJECTIVES: This study compares ultrasound-guided ESP block (ESP group) with an intraoperative intravenous ketamine infusion analgesic protocol (CRI group) in dogs undergoing thoracolumbar mini-hemilaminectomy, focusing on intraoperative opioid consumption, cardiovascular response to surgical stimulation (CR), postoperative pain scores (PS), and postoperative opioid consumption. METHODS: Retrospective, case-control, non-inferiority study conducted in a single centre. Data collected included demographics, bupivacaine dose, ESP block operator, intraoperative recorded variables (haemodynamic variables, CR, complications, rescue analgesia), pre- and postoperative analgesia, 24-hour PS and opioid administration, first food intake post-extubation and postoperative complications. Univariate and multiple regression analyses were applied. RESULTS: One-hundred dogs were included, 75 in the ESP group and 25 in the CRI group. Univariate analysis revealed no significant differences between treatment groups in terms of CR, PS, postoperative rescue analgesia, intraoperative and postoperative opioid consumption, or time to first meal intake. However, the multivariate regression analysis indicated that dogs receiving ketamine infusion had higher CR suspected to be nociception-related (p = 0.036), and higher postoperative opioid consumption (p = 0.013). CONCLUSION: Our study suggests that ultrasound-guided ESP block is as effective as intraoperative ketamine infusion providing perioperative analgesia in dogs undergoing thoracolumbar mini-hemilaminectomy for intervertebral disc disease. ESP group showed significantly lower CR suspected to be nociception-related intraoperatively and lower postoperative opioid consumption within the initial 24 hours.

Does the diversity of vegetation and diatoms correlate with soil and water factors in a tropical cloud forest's complex land use/land cover scenario?

Soil and water characteristics in micro basins with different land uses/land cover (LULC) can influence riparian vegetation diversity, stream water quality, and benthic diatom diversity. We analyzed 18 streams in the upper part of the La Antigua River basin, México, surrounded by cloud forests, livestock pastures, and coffee plantations. Concentrations of P, C, and N were elevated in the humus of forested streams compared to other land uses. In contrast, cations, ammonium, and total suspended solids (TSS) of water streams were higher in pastures and coffee plantations. These results indicate that LULC affects stream chemistry differently across land uses. Vegetation richness was highest (86-133 spp.) in forest streams and lowest in pastures (46-102), whereas pasture streams had the greatest richness of diatoms (9-24), likely due to higher light and temperatures. Some soil and water characteristics correlated with both true diversity and taxonomic diversity; soil carbon exchange capacity (CEC) correlated with vegetation diversity (r = 0.60), while water temperature correlated negatively (r = - 0.68). Diatom diversity was related to soil aluminum (r = - 0.59), magnesium (r = 0.57), water phosphorus (r = 0.88), and chlorophyll (r = 0.75). These findings suggest that land use affects riparian vegetation, while physical and chemical changes influence diatom diversity in stream water and soil. The lack of correlation between vegetation and diatom diversity indicates that one cannot predict the other. This research is an essential first step in understanding how land use changes impact vegetation and diatom diversity in mountain landscapes, providing valuable insights for environmental monitoring and conservation efforts in tropical cloud forests.

Frontoparietal network topology as a neural marker of musical perceptual abilities.

Why are some individuals more musical than others? Neither cognitive testing nor classical localizationist neuroscience alone can provide a complete answer. Here, we test how the interplay of brain network organization and cognitive function delivers graded perceptual abilities in a distinctively human capacity. We analyze multimodal magnetic resonance imaging, cognitive, and behavioral data from 200+ participants, focusing on a canonical working memory network encompassing prefrontal and posterior parietal regions. Using graph theory, we examine structural and functional frontoparietal network organization in relation to assessments of musical aptitude and experience. Results reveal a positive correlation between perceptual abilities and the integration efficiency of key frontoparietal regions. The linkage between functional networks and musical abilities is mediated by working memory processes, whereas structural networks influence these abilities through sensory integration. Our work lays the foundation for future investigations into the neurobiological roots of individual differences in musicality.

Use of Ultra-Short Echo Time MRI to Improve Temporal Bone Imaging.

OBJECTIVE: The short T2 nature of cortical bone causes it to appear similar to air on MR, forcing clinicians to rely on computed tomography imaging, with its attendant ionizing radiation exposure, to define temporal bone structures. Through the use of novel MR sequences with ultra-short echo times (UTE), short T2 structures are now able to be visualized, allowing for improved understanding of anatomical relationships. METHODS: Eight patients (50% female) undergoing MR imaging of the skull base for diagnostic purposes (62.5% for vestibular schwannoma surveillance) at a tertiary care center were enrolled to evaluate the safety and efficacy of UTE imaging. CT scans were completed in 37.5% of the patients as part of their workup and used for comparison purposes. The repetition time, short echo time, and long echo time for the UTE sequence were 11, 0.032, and 2.2 msec, respectively. RESULTS: The protocol added 6 min to the total scanning time, and all patients tolerated the sequence without issue. The ossicles, mastoid air cells, antrum, and epitympanum were able to be seen and had a high Dice similarity coefficient when compared to CT (>0.5). UTE allowed for clear delineation of all segments of the facial nerve with a signal-to-noise ratio of 35 (although the BRAVO sequences had a superior ratio of 140). Vestibular schwannomas were able to be distinguished from normal brain parenchyma. CONCLUSIONS: UTE is safe and effective for visualizing anatomic structures not normally seen on traditional MRI, potentially allowing for improved surgical planning in patients. LEVEL OF EVIDENCE: III Laryngoscope, 2024.

A novel approach to the quantitative analysis of the particulate matter in conventional cigarette smoke and heated tobacco product aerosols.

The particulate and soluble matter present in aerosols from combustible cigarettes (CCs) and Heated Tobacco Products (HTPs) was collected in liquid water. These liquids, yellowish in the experiments with cigarettes and colourless after using HTPs, were analysed by Laser Diffraction (LD) and by Transmission Electron Microscopy coupled to Energy Dispersive X-ray spectroscopy (TEM-EDX) to study the amount, size, composition, and other features of the particulate matter (PM) present in the collected aerosols. The particulate matter concentration in HTPs samples is below the limit of quantification for LD, and only samples from cigarettes show a particulate matter concentration above such limit. TEM analysis has revealed that the liquid samples (from both, cigarettes and HTPs experiments) contain particulate matter, mainly composed of carbon (C) and oxygen (O), but also of traces of inorganic elements. The TEM electron beam results in the evaporation of the particulate matter derived from HTPs, but not of that derived from cigarettes, highlighting the different nature of the particulate matter in both systems, i.e. liquid particulate matter present in the HTPs aerosols and solid particulate matter in the cigarettes smoke. A protocol for the quantitative comparison of the particulate matter present in aerosols has been applied over sixteen TEM images for each sample, confirming important differences from the point of view of the amount of particulate matter and particle size ranges. Thus, the amount of particulate matter for HTPs aerosol samples is more than one order of magnitude lower than for cigarettes smoke.

Prepartum anti-inflammatory therapies in Holstein dairy cows blocked by parity and body condition score group: Effects on metabolic stress, systemic inflammation, performance, and health.

The objective of this study was to assess the effects of prepartum administration of anti-inflammatory therapies on body condition score (BCS), ß-hydroxybutyrate (BHB) concentration, haptoglobin (HP) concentration, milk yield, milk components, rumination time, clinical health events and reproductive performance in Holstein dairy cows. At 14 d before the expected calving date, cows (PAR; n = 170) and heifers (nulliparous [NUL]; n = 63) were blocked by BCS group (optimal = 3-3.5 [OPT]; over-conditioned cows [OVERC; BCS ≥ 3.75 pts.]) and parity (NUL; PAR) and randomly allocated to one of 3 treatment groups: 1) ASA (n = 78): receive one oral administration of acetylsalicylic acid (4 boluses; 480 grain/bolus); 2) MEL (n = 76): receive one oral administration with meloxicam (1mg/kg of BW), or 3) PLC (n = 77): receive one oral treatment with gelatin capsules filled with water. Body condition score was assessed, and blood samples were collected, weekly starting one week before treatment until 3 weeks after calving. Daily milk yields and daily rumination times were collected from on-farm computer records. Dairy Herd Improvement Association (DHIA) monthly test data were collected to assess milk yield, somatic cell counts, and milk components. Furthermore, health events, culling rate, and reproductive performance data were collected from on-farm computer records. The data were analyzed using MIXED, GLIMMIX, and LIFETEST procedures of SAS as a randomized complete block design. On average, MEL-NUL cows produced 4.77 ± 0.93 kg/d and 4.81 ± 0.92 kg/d more milk from wk 6 to wk 21 of lactation compared with ASA-NUL and PLC-NUL cows, respectively. Similarly, there was a week by treatment by body condition group interaction (P = 0.01), where OVERC cows treated with MEL produced more milk from wk 10 to wk 15 of lactation compared with ASA- OVERC and PLC-OVERC cows. Parous cows treated with ASA had lower BCS compared with PAR cows treated with MEL or PLC. A lower percentage of OVERC cows treated with ASA became sick in the first 60 DIM compared with MEL- OVERC and PLC- OVERC cows (ASA = 23.88 ± 7.26%, MEL = 46.36 ± 8.57%; PLC = 46.74 ± 8.53%; P = 0.04). Parous cows treated with ASA had (P = 0.03) a higher hazard ratio to become pregnant by 300 DIM compared with PAR MEL cows. Although the study was not sized for finding treatment differences in blocking criteria groups, these results suggest that treatment with prepartum anti-inflammatory therapies may have positive effects on milk yield and postpartum health in specific groups of cows, such as NUL and OVERC cows, while it may not be recommended for other animal categories, such as parous cows and cows with optimal BCS. Larger studies are needed to strengthen the associations observed in this study.

Influence in physicochemical, nutritional, and antioxidant properties by addition Moringa oleifera leaves in Avena sativa bread.

Moringa oleifera leaves have high nutrient valor, physicochemical, and nutraceutical properties and can be used as ingredients to develop wheat-free enrich. The aim was to evaluate nutritional, chemical, and nutraceutical characterization, antioxidant capacity, along physicochemical parameters to develop four oat bread using yeast (PL), xanthan gum (PG), and 2.5% (M2) or 5.0% (M5) of moringa leaves. Morinaga leaves were a source of 23.19% protein, 12.43% ash, and 30.36% dietary fiber. The bread formulations increased the protein content by 25-50%, and decreased lipid in 52.14% compared with commercial bread. For antioxidant capacity, PLM5 had the highest with values of 11.97 mMTE/g (DPPH), 16.06 mMTE/g (ABTS), and 16.38 mMTE/g (FRAP). In the bread with MOLP were identified Epicatechin, rutin, and dihydroxybenzoic acid by HPLC. The bread with a better texture profile was PLM2. The results suggested that moringa leaves used as an oat bread ingredient can enhance the nutritional and nutraceutical content.

Targeting Unique Ligand Binding Domain Structural Features Downregulates DKK1 in Y537S ESR1 Mutant Breast Cancer Cells.

Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable. A tyrosine to serine point mutation at position 537 in the ERα ligand binding domain (LBD) is among the most common and most pathogenic alteration in this setting. It enables endocrine therapy resistance by superceding intrinsic structural-energetic gatekeepers of ER hormone-dependence, it enhances metastatic burden by enabling neomorphic ER-dependent transcriptional programs, and it resists SERM and SERD inhibiton by reducing their binding affinities and abilities to antagonize transcriptional coregulator binding. However, a subset of SERMs and SERDs can achieve efficacy by adopting poses that force the mutation to engage in a new interaction that favors the therapeutic receptor antagonist conformation. We previously described a chemically unconventional SERM, T6I-29, that demonstrates significant anti-proliferative activities in Y537S ERα breast cancer cells. Here, we use a comprehensive suite of structural-biochemical, in vitro, and in vivo approaches to better T6I-29's activities in breast cancer cells harboring Y537S ERα. RNA sequencing in cells treated with T6I-29 reveals a neomorphic downregulation of DKK1, a secreted glycoprotein known to play oncogenic roles in other cancers. Importantly, we find that DKK1 is significantly enriched in ER+ breast cancer plasma compared to healthy controls. This study shows how new SERMs and SERDs can identify new therapeutic pathways in endocrine-resistant ER+ breast cancers.

[Two new cases of X-linked intellectual developmental disorder-105 linked to a previously unreported pathogenic variant in the USP27X gene]. / Dos nuevos casos de discapacidad intelectual ligada al cromosoma X tipo 105 por variante patógena en el gen USP27X no descrita previamente.

INTRODUCTION: X-linked intellectual developmental disorder is clinically and genetically heterogeneous. The ubiquitin specific peptidase 27 X-linked gene (USP27X) has been associated with X-linked intellectual developmental disorder, and only 17 affected males have been described in the literature to date. CASE REPORT: A 6-year-old boy was assessed due to intellectual developmental disability, language delay, behavioural disorder, microcephaly and particular features. His mother had learning difficulties and a facial phenotypic overlap. A maternal uncle had an intellectual developmental disorder. Physical examination revealed an unusual phenotype (triangular facies, long palpebral fissures and eyelashes, medially eyebrow loss, prominent auricles), mild brachydactylia and hypoplasia in the distal phalanges. The clinical exome identified the probably pathogenic variant NM_001145073.3: c.692delT in the USP27X gene. The results of the family segregation analysis were positive: the mother and maternal uncle were harbourers, while healthy maternal aunt was not. CONCLUSIONS: We present two new cases of X-linked intellectual developmental disorder due to a previously unreported variant in the USP27X gene. Both patients presented neurological symptoms without any significant involvement at other levels, according to the literature. One of the cases presented microcephaly, particular features and digital anomalies, which broadens the phenotypic spectrum of this disease.

TITLE: Dos nuevos casos de discapacidad intelectual ligada al cromosoma X tipo 105 por variante patógena en el gen USP27X no descrita previamente.Introducción. La discapacidad intelectual ligada al cromosoma X es un trastorno clínica y genéticamente heterogéneo. El gen de la proteasa 27 específica de la ubiquitina ligada al cromosoma X (USP27X) se ha asociado a discapacidad intelectual ligada al cromosoma X, y en la actualidad sólo se ha descrito a 17 varones afectos en la bibliografía. Caso clínico. Niño de 6 años valorado por discapacidad intelectual, retraso del lenguaje, trastorno de la conducta, microcefalia y rasgos particulares. Madre con dificultades de aprendizaje y fenotipo facial solapante. Un tío materno con discapacidad intelectual aislada. En la exploración física destaca un fenotipo peculiar (facies triangular, fisuras palpebrales y pestañas largas, cejas menos pobladas medialmente, pabellones auriculares prominentes), leve braquidactilia e hipoplasia de falanges distales. El exoma clínico identificó la variante probablemente patógena NM_001145073.3: c.692delT en el gen USP27X. El estudio de segregación familiar fue positivo: madre y tío materno portadores, tía materna sana no portadora. Conclusiones. Describimos dos nuevos casos con discapacidad intelectual ligada al cromosoma X por variante no descrita previamente en el gen USP27X. Ambos pacientes presentan clínica neurológica sin afectación significativa a otros niveles de acuerdo con la bibliografía. Uno de los casos asocia microcefalia, rasgos particulares y anomalías digitales, lo que permite ampliar el espectro fenotípico de esta enfermedad.

Transgenerational epigenetic self-memory of Dio3 dosage is associated with Meg3 methylation and altered growth trajectories and neonatal hormones.

Intergenerational and transgenerational epigenetic effects resulting from conditions in previous generations can contribute to environmental adaptation as well as disease susceptibility. Previous studies in rodent and human models have shown that abnormal developmental exposure to thyroid hormone affects endocrine function and thyroid hormone sensitivity in later generations. Since the imprinted type 3 deiodinase gene (Dio3) regulates sensitivity to thyroid hormones, we hypothesize its epigenetic regulation is altered in descendants of thyroid hormone overexposed individuals. Using DIO3-deficient mice as a model of developmental thyrotoxicosis, we investigated Dio3 total and allelic expression and growth and endocrine phenotypes in descendants. We observed that male and female developmental overexposure to thyroid hormone altered total and allelic Dio3 expression in genetically intact descendants in a tissue-specific manner. This was associated with abnormal growth and neonatal levels of thyroid hormone and leptin. Descendant mice also exhibited molecular abnormalities in the Dlk1-Dio3 imprinted domain, including increased methylation in Meg3 and altered foetal brain expression of other genes of the Dlk1-Dio3 imprinted domain. These molecular abnormalities were also observed in the tissues and germ line of DIO3-deficient ancestors originally overexposed to thyroid hormone in utero. Our results provide a novel paradigm of epigenetic self-memory by which Dio3 gene dosage in a given individual, and its dependent developmental exposure to thyroid hormone, influences its own expression in future generations. This mechanism of epigenetic self-correction of Dio3 expression in each generation may be instrumental in descendants for their adaptive programming of developmental growth and adult endocrine function.

Assessing the impact of three biosphere reserves on the conservation of coastal ecosystems.

Biosphere Reserves (BR) manage large territories with diverse natural covers and land uses to preserve biodiversity, promote local development and preserve ecosystems. This study evaluated how their zoning (buffer and core) and policy timeframes (decree period, management plan period, and land planning period) influence four landscape management outcomes: deforestation, natural cover recovery, and anthropic and natural permanence. For three Mexican BR case studies, land use and cover transitions were calculated and compared to contrafactual sites. Observed rates of land cover change were marginal within all three BR zoning and across their policy timeframe (<0.02 % change rate), suggesting that BR effectively promote the permanence of both natural and anthropic covers. Nevertheless, the predicted probability of uncommon deforestation and recovery outcomes at local levels showed that the effect of a BR over its regulated landscape is not spatiotemporally static, contrasting the effect of individual allocation vs a group or network. Poverty, land tenure, agriculture aptitude and distance to markets adds to this dynamic and is modelled and discussed. This study shows that BR zoning schemes and its regulatory sequence influence the rates of land cover change and the predicted probability of landscape management outcomes across space and time.

Profiling and assessing the risks of image- and performance-enhancing drugs use during the COVID-19 lockdown.

Background: Image and Performance-Enhancing Drugs (IPEDs) can enhance mental and physical capabilities and impact one's overall health. Initially confined in sport environments, IPEDs use has become increasingly widespread in a high-performing society. The present study was aimed at profiling IPEDs use during the COVID-19 lockdown among an international sample of young adults. Methods: A cross-sectional observational study was carried out in eight countries (United Kingdom, Italy, Lithuania, Hungary, Portugal, Spain, Brazil, and Japan) between April and May 2020. The survey questionnaire included validated measurements such as Exercise Addiction Inventory (EAI), Appearance Anxiety Inventory (AAI), and Self-Compassion Scale (SCS) as well as questions about the type of IPEDs, purchasing methods and socio-demographic information. Results: A total of 736 IPEDs users were included in the survey. Their mean age was 33.05 years (±SD = 10.06), and 64.2% were female participants. Overall, 6.8% were found at risk of exercise addiction (EAI >24), 27.6% presented high levels of appearance anxiety, and 24.9% revealed low levels of emotional regulation's self-compassion. Most participants (55.6%) purchased IPEDs through pharmacies/specialized shops, while 41.3% purchased IPEDs on the Internet. Online IPEDs buyers were mainly men who had higher scores on the Exercise Addiction Inventory. One or more IPEDs classifiable as "potentially risky" were used by 66.3% of the sample. Users of "potentially risky IPEDs" were younger and primarily men. They showed higher scores both on the Exercise Addiction Inventory and Appearance Anxiety Inventory. Conclusion: This study profiled users of IPEDs when the most restrictive COVID-19 lockdown policies were implemented in all the participating countries. More targeted post-COVID 19 prevention strategies should be implemented according to the emerged socio-demographic and psychopathological traits and cross-cultural differences emerged. Longitudinal studies will also be needed to determine the long-term effect of the COVID-19 lockdown on IPEDs consumption.

Environmental stressor assessment of hydrocarbonoclastic bacteria biofilms from a marine oil spill.

The environmental and economic impact of an oil spill can be significant. Biotechnologies applied during a marine oil spill involve bioaugmentation with immobilised or encapsulated indigenous hydrocarbonoclastic species selected under laboratory conditions to improve degradation rates. The environmental factors that act as stressors and impact the effectiveness of hydrocarbon removal are one of the challenges associated with these applications. Understanding how native microbes react to environmental stresses is necessary for effective bioaugmentation. Herein, Micrococcus luteus and M. yunnanensis isolated from a marine oil spill mooring system showed hydrocarbonoclastic activity on Maya crude oil in a short time by means of total petroleum hydrocarbons (TPH) at 144 h: M. luteus up to 98.79 % and M. yunnanensis 97.77 % removal. The assessment of Micrococcus biofilms at different temperature (30 °C and 50 °C), pH (5, 6, 7, 8, 9), salinity (30, 50, 60, 70, 80 g/L), and crude oil concentration (1, 5, 15, 25, 35 %) showed different response to the stressors depending on the strain. According to response surface analysis, the main effect was temperature > salinity > hydrocarbon concentration. The hydrocarbonoclastic biofilm architecture was characterised using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Subtle but significant differences were observed: pili in M. luteus by SEM and the topographical differences measured by AFM Power Spectral Density (PSD) analysis, roughness was higher in M. luteus than in M. yunnanensis. In all three domains of life, the Universal Stress Protein (Usp) is crucial for stress adaptation. Herein, the uspA gene expression was analysed in Micrococcus biofilm under environmental stressors. The uspA expression increased up to 2.5-fold in M. luteus biofilms at 30 °C, and 1.3-fold at 50 °C. The highest uspA expression was recorded in M. yunnanensis biofilms at 50 °C with 2.5 and 3-fold with salinities of 50, 60, and 80 g/L at hydrocarbon concentrations of 15, 25, and 35 %. M. yunnanensis biofilms showed greater resilience than M. luteus biofilms when exposed to harsh environmental stressors. M. yunnanensis biofilms were thicker than M. luteus biofilms. Both biofilm responses to environmental stressors through uspA gene expression were consistent with the behaviours observed in the response surface analyses. The uspA gene is a suitable biomarker for assessing environmental stressors of potential microorganisms for bioremediation of marine oil spills and for biosensing the ecophysiological status of native microbiota in a marine petroleum environment.

[COPD inhaled therapy narrative review]. / Revisión narrativa de la terapia inhalatoria en la EPOC.

The basis of COPD maintenance treatment is the long-acting bronchodilators and the inhaled corticosteroids. Faced with the recent modifications in the clinical practice guidelines, we have carried out a review of studies that contrast the various therapeutic alternatives and pharmacological agents within each category, with the fundamental purpose of shedding light on which of these options prove to be more effective. Triple therapy stands out as essential in poorly controlled patients or with an eosinophilic phenotype, surpassing dual therapy. However, among the combinations of LAMA/LABA or LAMA/LABA/IC, no drug is observed to be superior in the reviewed evidence. Although triple therapies include corticosteroids, there does not appear to be a significant increase in side effects or pneumonia. Regarding monotherapy with LAMA, no significant differences are seen between the drugs, but in dual therapy with LABA/IC, the budesonide/formoterol combination seems to offer better control than fluticasone/salmeterol.

Drivers of biogenic volatile organic compound emissions in hygrophytic bryophytes.

Bryophytes can both emit and take up biogenic volatile organic compounds (BVOCs) to and from the environment. Despite the scarce study of these exchanges, BVOCs have been shown to be important for a wide range of ecological roles. Bryophytes are the most ancient clade of land plants and preserve very similar traits to those first land colonisers. Therefore, the study of these plants can help understand the early processes of BVOC emissions as an adaptation to terrestrial life. Here, we determine the emission rates of BVOCs from different bryophyte species to understand what drives such emissions. We studied 26 bryophyte species from temperate regions that can be found in mountain springs located in NE Spain. Bryophyte BVOC emission presented no significant phylogenetic signal for any of the compounds analysed. Hence, we used mixed linear models to investigate the species-specific differences and eco-physiological and environmental drivers of bryophyte BVOC emission. In general, species-specific variability was the main factor explaining bryophyte BVOC emissions; but additionally, photosynthetic rates and light intensity increased BVOC emissions. Despite emission measurements reported here were conducted at 30°, and may not directly correspond to emission rates in natural conditions, most of the screened species have never been measured before for BVOC emissions and therefore this information can help understand the drivers of the emissions of BVOCs in bryophytes.

Targeting Unique Ligand Binding Domain Structural Features Downregulates DKK1 in Y537S ESR1 Mutant Breast Cancer Cells.

Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable. A tyrosine to serine point mutation at position 537 in the ERα ligand binding domain (LBD) is among the most common and most pathogenic alteration in this setting. It enables endocrine therapy resistance by superceding intrinsic structural-energetic gatekeepers of ER hormone-dependence, it enhances metastatic burden by enabling neomorphic ER-dependent transcriptional programs, and it resists SERM and SERD inhibiton by reducing their binding affinities and abilities to antagonize transcriptional coregulator binding. However, a subset of SERMs and SERDs can achieve efficacy by adopting poses that force the mutation to engage in a new interaction that favors the therapeutic receptor antagonist conformation. We previously described a chemically unconventional SERM, T6I-29, that demonstrates significant anti-proliferative activities in Y537S ERα breast cancer cells. Here, we use a comprehensive suite of structural-biochemical, in vitro, and in vivo approaches to better T6I-29's activities in breast cancer cells harboring Y537S ERα. RNA sequencing in cells treated with T6I-29 reveals a neomorphic downregulation of DKK1, a secreted glycoprotein known to play oncogenic roles in other cancers. Importantly, we find that DKK1 is significantly enriched in ER+ breast cancer plasma compared to healthy controls. This study shows how new SERMs and SERDs can identify new therapeutic pathways in endocrine-resistant ER+ breast cancers.

Mesozooplankton assemblage in the gulf of cádiz estuaries: Taxonomic and trait-based approaches.

In this study, two different approaches based on taxonomic assemblages and on copepod functional groups were used to investigate the mesozooplankton assemblage structure and its relationship with environmental variables in the main estuaries of the Gulf of Cádiz (Guadalquivir, Guadiana and Tinto-Odiel) during the dry-warm season. In general, the mesozooplankton assemblages were dominated by copepods, especially the calanoid Acartia tonsa, which reached its highest abundance in the inner zones while the adjacent coastal zones were characterized by a mixture of copepods and cladocerans, especially Penilia avirostris. Regarding the trait-based approach, three copepod functional groups were identified, principally sorted by their feeding strategy. Group 1 (composed of omnivorous copepods displaying a mixed feeding strategy and broadcast-spawners) was found mainly in the inner areas, while Groups 2 (omnivorous cyclopoids, sac-spawners that feed via active ambush) and 3 (herbivores-omnivores employing a filter feeding strategy and mostly broadcast-spawners) were predominant in the adjacent coastal zones. The relative abundance of copepod functional groups suggested that Group 1 could be considered the most important contributor to secondary production in the estuarine systems of the Gulf of Cádiz. In relation to environmental factors, salinity was the most influential variable on mesozooplankton assemblages in both approaches. Our results suggest that the studied estuaries, although taxonomically different, have mesozooplankton assemblages that perform similar ecological functions. Both methods provide valuable and complementary information about mesozooplankton assemblage dynamics in the main estuaries of the Gulf of Cádiz.