Right-side diverticulitis.

Colonic diverticula develop at specific weak spots, where the vasa recta enter the colonic circular smooth muscle layer.1 They are usually seen in the left colon. Their most common complication is diverticulitis, with mild cases resolving even without antibiotic therapy.2 Right-side diverticulitis develops in only 1.5% of cases, primarily on the anterior aspect of the cecum, proximal to the ileocecal valve (80%).4 Given its low incidence, location, and the fact that it involves younger patients, a differential diagnosis is needed to rule out abdominal inflammatory conditions such as appendicitis or ileitis, as well as gynecological disorders. Diverticulitis is diagnosed using imaging modalities. Computed tomography (CT) is the modality of choice,5 and confirmation is required after clinical remission, primarily using colonoscopy. We studied a series of 3 cases of patients initially diagnosed with acute, uncomplicated right-side diverticulitis who were admitted to the Gastroenterology Department, Hospital de León, from January to December 2023. Our goal was to confirm a presumptive diagnosis of right-side diverticulitis using delayed endoscopy or barium enema to ascertain the presence of right-side diverticulosis and rule out other conditions manifesting with abdominal pain in the right iliac fossa. Cases 1 and 3 were admitted with an accurate diagnosis of right-side diverticulitis. Case 1 was confirmed by ambulatory colonoscopy, and case 3 was confirmed by barium enema because of a history of previous colonoscopy without findings. All three patients required surgical assessment to rule out appendicular involvement. The imaging technique of choice was CT, using the WSES scale for severity grading. Case 2 was diagnosed with right-side diverticulitis by means of ultrasonography, and its origin was later confirmed to be in the sigmoid colon. The remaining clinical, laboratory, and diagnostic characteristics are listed in Table 1.

mRNA Display Identifies Potent, Paralog-Selective Peptidic Ligands for ARID1B.

The ARID1A and ARID1B subunits are mutually exclusive components of the BAF variant of SWI/SNF chromatin remodeling complexes. Loss of function mutations in ARID1A are frequently observed in various cancers, resulting in a dependency on the paralog ARID1B for cancer cell proliferation. However, ARID1B has never been targeted directly, and the high degree of sequence similarity to ARID1A poses a challenge for the development of selective binders. In this study, we used mRNA display to identify peptidic ligands that bind with nanomolar affinities to ARID1B and showed high selectivity over ARID1A. Using orthogonal biochemical, biophysical, and chemical biology tools, we demonstrate that the peptides engage two different binding pockets, one of which directly involves an ARID1B-exclusive cysteine that could allow covalent targeting by small molecules. Our findings impart the first evidence of the ligandability of ARID1B, provide valuable tools for drug discovery, and suggest opportunities for the development of selective molecules to exploit the synthetic lethal relationship between ARID1A and ARID1B in cancer.

Dryland microbiomes reveal community adaptations to desertification and climate change.

Drylands account for 45% of the Earth's land area, supporting ~40% of the global population. These regions support some of the most extreme environments on Earth, characterized by extreme temperatures, low and variable rainfall, and low soil fertility. In these biomes, microorganisms provide vital ecosystem services and have evolved distinctive adaptation strategies to endure and flourish in the extreme. However, dryland microbiomes and the ecosystem services they provide are under threat due to intensifying desertification and climate change. In this review, we provide a synthesis of our current understanding of microbial life in drylands, emphasizing the remarkable diversity and adaptations of these communities. We then discuss anthropogenic threats, including the influence of climate change on dryland microbiomes and outline current knowledge gaps. Finally, we propose research priorities to address those gaps and safeguard the sustainability of these fragile biomes.

Discovery of Ligands for TRIM58, a Novel Tissue-Selective E3 Ligase.

Redirecting E3 ligases to neo-substrates, leading to their proteasomal disassembly, known as targeted protein degradation (TPD), has emerged as a promising alternative to traditional, occupancy-driven pharmacology. Although the field has expanded tremendously over the past years, the choice of E3 ligases remains limited, with an almost exclusive focus on CRBN and VHL. Here, we report the discovery of novel ligands to the PRY-SPRY domain of TRIM58, a RING ligase that is specifically expressed in erythroid precursor cells. A DSF screen, followed by validation using additional biophysical methods, led to the identification of TRIM58 ligand TRIM-473. A basic SAR around the chemotype was established by utilizing a competitive binding assay employing a short FP peptide probe derived from an endogenous TRIM58 substrate. The X-ray co-crystal structure of TRIM58 in complex with TRIM-473 gave insights into the binding mode and potential exit vectors for bifunctional degrader design.

Developing a mobile health app for chronic illness management: Insights from focus groups.

Background: Mobile applications have the potential to assist patients and caregivers in managing chronic diseases, but current offerings are typically limited to a single disease or only focused on patients. A multifaceted app could expand the user base and provide more comprehensive support for patients who usually suffer from diverse chronic conditions at the same time and their caregivers. Objectives: This study aimed to design, develop, and evaluate a mobile application that could aid chronic patients and their caregivers in managing the range of chronic conditions. Methods: Focus group meetings were conducted with patients and caregivers to identify their needs, which were translated into app functionalities. The final version of the app was evaluated through a survey and analysis of the most used features. Results: Five focus group (FG) meetings were held, involving 39 patients and 22 caregivers. The app included medication aids, self-monitoring aids, activation reminders, messages for caregiver shifts, remote monitoring, medicine management, and informative videos. Testing by 65 patients revealed that medication reminders (96.8% positive responses), medicine information (96.8%), messages for caregiver shifts (90.3%), and ease of use (80.6%) were the most valued aspects. The most frequently used feature was the health data record check. Conclusions: A multifaceted mobile application can address the needs of a variety of chronic patients and their caregivers, while still being easy to use. The app's most used functionalities were aligned with the needs expressed in the FG, which reflects the success of this study and suggests that future research could benefit from incorporating similar user-centered design methodologies.

Active cancer as the main predictor of mortality for COVID-19 in oncology patients in a specialized center.

Introduction: The role of the type, stage and status of cancer in the outcome of COVID-19 remains unclear. Moreover, the characteristic pathological changes of severe COVID-19 reveled by laboratory and radiological findings are similar to those due to the development of cancer itself and antineoplastic therapies. Objective: To identify potential predictors of mortality of COVID-19 in cancer patients. Materials and methods: A retrospective and cross-sectional study was carried out in patients with clinical suspicion of COVID-19 who were confirmed for COVID-19 diagnosis by RT-PCR testing at the National Institute of Neoplastic Diseases between April and December 2020. Demographic, clinical, laboratory and radiological data were analyzed. Statistical analyses included area under the curve and univariate and multivariate logistic regression analyses. Results: A total of 226 patients had clinical suspicion of COVID-19, the diagnosis was confirmed in 177 (78.3%), and 70/177 (39.5%) died. Age, active cancer, leukocyte count ≥12.8 × 109/L, urea ≥7.4 mmol/L, ferritin ≥1,640, lactate ≥2.0 mmol/L, and lung involvement ≥35% were found to be independent predictors of COVID-19 mortality. Conclusion: Active cancer represents the main prognosis factor of death, while the role of cancer stage and type is unclear. Chest CT is a useful tool in the prognosis of death from COVID-19 in cancer patients. It is a challenge to establish the prognostic utility of laboratory markers as their altered values it could have either oncological or pandemic origins.

Prevalence of Antimicrobial Resistance in Gram-Negative Bacteria Bloodstream Infections in Peru and Associated Outcomes: VIRAPERU Study.

Surveillance of antimicrobial resistance among gram-negative bacteria (GNB) is of critical importance, but data for Peru are not available. To fill this gap, a non-interventional hospital-based surveillance study was conducted in 15 hospitals across Peru from July 2017 to October 2019. Consecutive unique blood culture isolates of key GNB (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter spp.) recovered from hospitalized patients were collected for centralized antimicrobial susceptibility testing, along with linked epidemiological and clinical data. A total of 449 isolates were included in the analysis. Resistance to third-generation cephalosporins (3GCs) was present in 266 (59.2%) GNB isolates. Among E. coli (n = 199), 68.3% showed 3GC resistance (i.e., above the median ratio for low- and middle-income countries in 2020 for this sustainable development goal indicator). Carbapenem resistance was present in 74 (16.5%) GNB isolates, with wide variation among species (0% in E. coli, 11.0% in K. pneumoniae, 37.0% in P. aeruginosa, and 60.8% in Acinetobacter spp. isolates). Co-resistance to carbapenems and colistin was found in seven (1.6%) GNB isolates. Empiric treatment covered the causative GNB in 63.3% of 215 cases. The in-hospital case fatality ratio was 33.3% (92/276). Pseudomonas aeruginosa species and carbapenem resistance were associated with higher risk of in-hospital death. In conclusion, an important proportion of bloodstream infections in Peru are caused by highly resistant GNB and are associated with high in-hospital mortality.

Coping Strategies Used by Health Care Workers in Ecuador During the COVID-19 Pandemic: Observational Study to Enhance Resilience and Develop Training Tools.

BACKGROUND: The COVID-19 pandemic has generated immense health care pressure, forcing critical decisions to be made in a socially alarmed environment. Adverse conditions have led to acute stress reactions, affective pathologies, and psychosomatic reactions among health personnel, which have been exacerbated by the successive waves of the pandemic. The recovery of the entire health system and its professionals has been hindered, making it essential to increase their resilience. OBJECTIVE: This study aimed to achieve 2 primary objectives. First, it sought to identify coping strategies, both individual and organizational, used by health care workers in Ecuador to navigate the acute stress during the early waves of the pandemic. Second, it aimed to develop training materials to enhance team leaders' capabilities in effectively managing high-stress situations. METHODS: The study used qualitative research techniques to collect information on institutional and personal coping strategies, as well as consensus-building techniques to develop a multimedia psychological tool that reinforces the resilience of professionals and teams in facing future crises. RESULTS: The findings from the actions taken by health care workers in Ecuador were categorized into 4 types of coping strategies based on Lazarus' theories on coping strategies. As a result of this study, a new audiovisual tool was created, comprising a series of podcasts, designed to disseminate these strategies globally within the Spanish-speaking world. The tool features testimonials from health care professionals in Ecuador, narrating their experiences under the pressures of providing care during the pandemic, with a particular emphasis on the coping strategies used. CONCLUSIONS: Ensuring the preparedness of health professionals for potential future outbreaks is imperative to maintain quality and patient safety. Interventions such as this one offer valuable insights and generate new tools for health professionals, serving as a case study approach to train leaders and improve the resilience capacity and skills of their teams.

Defect-Engineering by Solvent Mediated Mild Oxidation as a Tool to Induce Exchange Bias in Metal Doped Ferrites.

The crystal site occupancy of different divalent ions and the induction of lattice defects represent an additional tool for modifying the intrinsic magnetic properties of spinel ferrites nanoparticles. Here, the relevance of the lattice defects is demonstrated in the appearance of exchange-bias and in the improvement of the magnetic properties of doped ferrites of 20 nm, obtained from the mild oxidation of core@shell (wüstite@ferrite) nanoparticles. Three types of nanoparticles (Fe0.95 O@Fe3 O4 , Co0.3 Fe0.7 O@Co0.8 Fe2.2 O4 and Ni0.17 Co0.21 Fe0.62 O@Ni0.4 Co0.3 Fe2.3 O4 ) are oxidized. As a result, the core@shell morphology is removed and transformed in a spinel-like nanoparticle, through a topotactic transformation. This study shows that most of the induced defects in these nanoparticles and their magnetic properties are driven by the inability of the Co(II) ions at the octahedral sites to migrate to tetrahedral sites, at the chosen mild oxidation temperature. In addition, the appearance of crystal defects and antiphase boundaries improves the magnetic properties of the starting compounds and leads to the appearance of exchange bias at room temperature. These results highlight the validity of the proposed method to impose novel magnetic characteristics in the technologically relevant class of nanomaterials such as spinel ferrites, expanding their potential exploitation in several application fields.

Remanence Increase in SrFe12O19/Fe Exchange-Decoupled Hard-Soft Composite Magnets Owing to Dipolar Interactions.

In the search for improved permanent magnets, fueled by the geostrategic and environmental issues associated with rare-earth-based magnets, magnetically hard (high anisotropy)-soft (high magnetization) composite magnets hold promise as alternative magnets that could replace modern permanent magnets, such as rare-earth-based and ceramic magnets, in certain applications. However, so far, the magnetic properties reported for hard-soft composites have been underwhelming. Here, an attempt to further understand the correlation between magnetic and microstructural properties in strontium ferrite-based composites, hard SrFe12O19 (SFO) ceramics with different contents of Fe particles as soft phase, both in powder and in dense injection molded magnets, is presented. In addition, the influence of soft phase particle dimension, in the nano- and micron-sized regimes, on these properties is studied. While Fe and SFO are not exchange-coupled in our magnets, a remanence that is higher than expected is measured. In fact, in composite injection molded anisotropic (magnetically oriented) magnets, remanence is improved by 2.4% with respect to a pure ferrite identical magnet. The analysis of the experimental results in combination with micromagnetic simulations allows us to establish that the type of interaction between hard and soft phases is of a dipolar nature, and is responsible for the alignment of a fraction of the soft spins with the magnetization of the hard. The mechanism unraveled in this work has implications for the development of novel hard-soft permanent magnets.

Discovery of New Binders for DCAF1, an Emerging Ligase Target in the Targeted Protein Degradation Field.

In this study, we describe the rapid identification of potent binders for the WD40 repeat domain (WDR) of DCAF1. This was achieved by two rounds of iterative focused screening of a small set of compounds selected on the basis of internal WDR domain knowledge followed by hit expansion. Subsequent structure-based design led to nanomolar potency binders with a clear exit vector enabling DCAF1-based bifunctional degrader exploration.

Epidemiological study on gender bias and low-value practices in primary care: a study protocol.

INTRODUCTION: Evidence shows that gender has a substantial impact on health behaviours, access to and use of health systems and health system responses. This study aims to assess gender bias in patients subjected to low-value practices in the primary care setting and to develop recommendations for reducing adverse events that women experience for this reason. METHODS AND ANALYSIS: A Delphi study will be performed to reach a consensus on the 'Do Not Do' recommendations with a possible gender bias. A retrospective cohort study in a random selection of medical records will then be carried out to identify the frequency of adverse events that occur when the selected 'Do Not Do' recommendations are ignored. Qualitative research techniques (consensus conference and nominal group) will be carried out to develop recommendations to address any gender bias detected, considering barriers and facilitators in clinical practice. ETHICS AND DISSEMINATION: The study was approved by the ethics committee of San Juan de Alicante Hospital (San Juan de Alicante, Spain) Reference N. 21/061. We will disseminate the research findings via peer-reviewed articles, presentations at national and international scientific forums and webinars. TRIAL REGISTRATION NUMBER: The study was registered at ClinicalTrials.gov (NCT05233852) on 10 February 2022.

Patient Engagement Using Telemedicine in Primary Care during COVID-19 Pandemic: A Trial Study.

The correct treatment of most non-transmissible diseases requires, in addition to adequate medication, adherence to physical activity and diet guidelines, as well as health data monitoring and patient motivation. The restrictions caused by the COVID-19 pandemic made telemedicine tools and mobile apps the best choice for monitoring patient compliance. The objective of this study was to analyze the benefits of an m-Health solution designed specifically for chronic patients during the COVID-19 pandemic. A pragmatic clinical trial with pre-post measurements of a single group was carried out with 70 patients (aged 40+) with one or more chronic conditions. Patients were provided with an ad hoc mobile app and health data measuring devices according to their diseases. The health status of the patients was monitored remotely by health professionals who could also modify the patient's objectives according to their evolution. The results obtained show an average fulfillment of objectives of 77%. Higher fulfillment values: medication adherence (98%) and oxygen saturation (82%); lower fulfillment values: weight (48%), glucose (57%), and distance walked (57%). Globally, the ad hoc app was rated 8.72 points out of 10 (standard deviation 1.10). Concerning the pre-post analysis, there were significant improvements vs. prior apps used by the participants in the following items: improved physical activation and better control of blood pressure, diet, weight, glucose, and oxygen saturation. In conclusion, the telemedicine tool developed was useful in increasing patient engagement and adherence to treatment.

Iron acquisition and mineral transformation by cyanobacteria living in extreme environments.

Iron is an essential micronutrient for most living organisms, including cyanobacteria. These microorganisms have been found in Earth's driest polar and non-polar deserts, including the Atacama Desert, Chile. Iron-containing minerals were identified in colonized rock substrates from the Atacama Desert, however, the interactions between microorganisms and iron minerals remain unclear. In the current study, we determined that colonized gypsum rocks collected from the Atacama Desert contained both magnetite and hematite phases. A cyanobacteria isolate was cultured on substrates consisting of gypsum with embedded magnetite nanoparticles. Transmission electron microscopy imaging revealed a significant reduction in the size of magnetite nanoparticles due to their dissolution, which occurred around the microbial biofilms. Concurrently, hematite was detected, likely from the oxidation of the magnetite nanoparticles. Higher cell counts and production of siderophores were observed in cultures with magnetite nanoparticles suggesting that cyanobacteria were actively acquiring iron from the magnetite nanoparticles. Magnetite dissolution and iron acquisition by the cyanobacteria was further confirmed using large bulk magnetite crystals, uncovering a survival strategy of cyanobacteria in these extreme environments.

Adaptations of endolithic communities to abrupt environmental changes in a hyper-arid desert.

The adaptation mechanisms of microbial communities to natural perturbations remain unexplored, particularly in extreme environments. The extremophilic communities of halite (NaCl) nodules from the hyper-arid core of the Atacama Desert are self-sustained and represent a unique opportunity to study functional adaptations and community dynamics with changing environmental conditions. We transplanted halite nodules to different sites in the desert and investigated how their taxonomic, cellular, and biochemical changes correlated with water availability, using environmental data modeling and metagenomic analyses. Salt-in strategists, mainly represented by haloarchaea, significantly increased in relative abundance at sites characterized by extreme dryness, multiple wet/dry cycles, and colder conditions. The functional analysis of metagenome-assembled genomes (MAGs) revealed site-specific enrichments in archaeal MAGs encoding for the uptake of various compatible solutes and for glycerol utilization. These findings suggest that opportunistic salt-in strategists took over the halite communities at the driest sites. They most likely benefited from compounds newly released in the environment by the death of microorganisms least adapted to the new conditions. The observed changes were consistent with the need to maximize cellular bioenergetics when confronted with lower water availability and higher salinity, providing valuable information on microbial community adaptations and resilience to climate change.

Hardening of Cobalt Ferrite Nanoparticles by Local Crystal Strain Release: Implications for Rare Earth Free Magnets.

In this work, we demonstrate that the reduction of the local internal stress by a low-temperature solvent-mediated thermal treatment is an effective post-treatment tool for magnetic hardening of chemically synthesized nanoparticles. As a case study, we used nonstoichiometric cobalt ferrite particles of an average size of 32(8) nm synthesized by thermal decomposition, which were further subjected to solvent-mediated annealing at variable temperatures between 150 and 320 °C in an inert atmosphere. The postsynthesis treatment produces a 50% increase of the coercive field, without affecting neither the remanence ratio nor the spontaneous magnetization. As a consequence, the energy product and the magnetic energy storage capability, key features for applications as permanent magnets and magnetic hyperthermia, can be increased by ca. 70%. A deep structural, morphological, chemical, and magnetic characterization reveals that the mechanism governing the coercive field improvement is the reduction of the concomitant internal stresses induced by the low-temperature annealing postsynthesis treatment. Furthermore, we show that the medium where the mild annealing process occurs is essential to control the final properties of the nanoparticles because the classical annealing procedure (T > 350 °C) performed on a dried powder does not allow the release of the lattice stress, leading to the reduction of the initial coercive field. The strategy here proposed, therefore, constitutes a method to improve the magnetic properties of nanoparticles, which can be particularly appealing for those materials, as is the case of cobalt ferrite, currently investigated as building blocks for the development of rare-earth free permanent magnets.

RecMin Variograms: Visualisation and Three-Dimensional Calculation of Variograms in Block Modelling Applications in Geology and Mining.

Variogram calculation is a fundamental tool for studying ore grade data in mineral deposits. It allows the discovery of hidden structures within the data and preferential directions of mineralization where the geological continuity is longer. The variogram allows us to classify samples and to define both the search radii for interpolation and the use of kriging as an interpolation and resource classification method. It is not difficult to use it in one dimension; complexity increases in two dimensions as the necessity to search for possible grade anisotropies in all directions arises. Three-dimensionally it is even more difficult to try to define the parameters of lag, bandwidth, and tolerances that define the data of the variogram calculation algorithm. There are rules of thumb to help in the development, but a trial-and-error approach is used in order to find enough sample pairs to allow the generation of variograms truly representative of the data. In this paper, two strategies are shown to help in variogram construction, the use of variogram maps and the graphical representation of the pair search areas (cones or pencils). The freeware tool RecMin Variograms has been developed and is freely available for download at its website; it is easy to learn and use. R code based on RGeostats libraries is used to check the operation and results of RecMin Variograms. Applying geostatistics to mineral deposits is essential to know the areas with the highest grades, thus allowing exact planning of future mining exploitation and minimizing mine footprint and environmental impact.

Extension of Non-invasive Ventilation Capabilities of MASI for the Care of Patients Affected by COVID-19.

The MASI mechanical ventilator was developed in a state of emergency to meet the demand for ventilators caused by COVID-19. Although it has obtained positive results in its use with patients in intensive care units, not having an optimal quality non-invasive ventilation (NIV) modality prevents it from being used in the early treatment of patients, which has been shown to prevent admission to the ICU and reduce mortality. Therefore, the following study focuses on evaluating MASI's ability to provide NIV using different accessories in order to compare their performance and determine which one would work best with MASI, and under which conditions. To do this, the high-flow nasal cannula, facial mask, and ventilation helmet accessories were tested under different pressure parameter settings. The data was collected using a gas flow analyzer. After that, a statistical analysis of the results was carried out, which showed that the face mask is the best accessory to use for NIV with MASI, and that it performs with optimal accuracy and precision when the peak inspiratory pressure is set at a value lower than 25 cmH20. Clinical Relevance- This study presents an optimization of the non-invasive ventilation (NIV) modality of the MASI me-chanical ventilator by evaluating its performance with different accessories.

The First Class of Small Molecules Potently Disrupting the YAP-TEAD Interaction by Direct Competition.

Inhibition of the YAP-TEAD protein-protein interaction is an attractive therapeutic concept under intense investigation with the objective to treat cancers associated with a dysregulation of the Hippo pathway. However, owing to the very extended surface of interaction of the two proteins, the identification of small drug-like molecules able to efficiently prevent YAP from binding to TEAD by direct competition has been elusive so far. We disclose here the discovery of the first class of small molecules potently inhibiting the YAP-TEAD interaction by binding at one of the main interaction sites of YAP at the surface of TEAD. These inhibitors, providing a path forward to pharmacological intervention in the Hippo pathway, evolved from a weakly active virtual screening hit advanced to high potency by structure-based design.

Adaptation of Cyanobacteria to the Endolithic Light Spectrum in Hyper-Arid Deserts.

In hyper-arid deserts, endolithic microbial communities survive in the pore spaces and cracks of rocks, an environment that enhances water retention and filters UV radiation. The rock colonization zone is enriched in far-red light (FRL) and depleted in visible light. This poses a challenge to cyanobacteria, which are the primary producers of endolithic communities. Many species of cyanobacteria are capable of Far-Red-Light Photoacclimation (FaRLiP), a process in which FRL induces the synthesis of specialized chlorophylls and remodeling of the photosynthetic apparatus, providing the ability to grow in FRL. While FaRLiP has been reported in cyanobacteria from various low-light environments, our understanding of light adaptations for endolithic cyanobacteria remains limited. Here, we demonstrated that endolithic Chroococcidiopsis isolates from deserts around the world synthesize chlorophyll f, an FRL-specialized chlorophyll when FRL is the sole light source. The metagenome-assembled genomes of these isolates encoded chlorophyll f synthase and all the genes required to implement the FaRLiP response. We also present evidence of FRL-induced changes to the major light-harvesting complexes of a Chroococcidiopsis isolate. These findings indicate that endolithic cyanobacteria from hyper-arid deserts use FRL photoacclimation as an adaptation to the unique light transmission spectrum of their rocky habitat.