Obstetric risk profiles and causes of death: Estimating their association with cesarean sections among maternal deaths in Mexico.

BACKGROUND: Maternal mortality is a critical indicator of healthcare quality, and in Mexico, this has become increasingly concerning due to the stagnation in its decline, alongside a concurrent increase in cesarean section (C-section) rates. This study characterizes maternal deaths in Mexico, focusing on estimating the association between obstetric risk profiles, cause of death, and mode of delivery. METHODS: Utilizing a retrospective observational design, 4,561 maternal deaths in Mexico from 2010-2014 were analyzed. Data were sourced from the Deliberate Search and Reclassification of Maternal Deaths database, alongside other national databases. An algorithm was developed to extract the Robson Ten Group Classification System from clinical summaries text, facilitating a nuanced analysis of C-section rates. Information on the reasons for the performance of a C-section was also obtained. Logistic regression and multinomial logistic regression models were used to estimate the relation between obstetric risk factors, mode of delivery and causes of maternal death, adjusting for covariates. RESULTS: Among maternal deaths in Mexico from 2010-2014, 47.1% underwent a C-section, with a significant history of previous C-sections observed in 31.4% of these cases, compared to 17.4% for vaginal deliveries (p<0.001). Early prenatal care in the first trimester was more common in C-section cases (46.8%) than in vaginal deliveries (38.3%, p<0.001). A stark contrast was noted in the place of death, with 82.4% of post-C-section deaths occurring in public institutions versus 69.1% following vaginal births. According to Robson's classification, the highest C-section rates were in Group 4 (67.2%, p<0.001) and Group 8 (66.9%, p<0.001). Logistic regression analysis revealed no significant difference in the odds of receiving a C-section in private versus other settings after adjusting for Robson criteria (OR: 1.21; 95% CI: 0.92, 1.60). A prior C-section significantly increased the likelihood of another (OR: 2.38; CI 95%: 2.01, 2.81). The analysis also indicated C-sections were significantly tied to deaths from hypertensive disorders (RRR = 1.25, 95% CI [1.12, 1.40]). In terms of indications, 6.3% of C-sections were performed under inadequate indications, while the indication was not identifiable in 33.1% of all C-sections. CONCLUSIONS: This study highlights a significant overuse of C-sections among maternal deaths in Mexico (2010-2014), revealed through the Robson classification and ana analysis of the reported indications for the procedure. It underscores the need for revising clinical decision-making to promote evidence-based guidelines and favor vaginal deliveries when possible. High C-section rates, especially noted disparities between private and public sectors, suggest economic and non-clinical factors may be at play. The importance of accurate data systems and further research with control groups to understand C-section practices' impact on maternal health is emphasized.

Expression of Mitochondrial Long Non-Coding RNAs, MDL1 and MDL1AS, Are Good Prognostic and/or Diagnostic Biomarkers for Several Cancers, Including Colorectal Cancer.

Non-coding RNAs provide new opportunities to identify biomarkers that properly classify cancer patients. Here, we study the biomarker status of the mitochondrial long non-coding RNAs, MDL1 and MDL1AS. Expression of these genes was studied in public transcriptomic databases. In addition, a cohort of 69 locally advanced rectal cancer (LARC) patients with a follow-up of more than 5 years was used to determine the prognostic value of these markers. Furthermore, cell lines of colorectal (HCT116) and breast (MDA-MB-231) carcinoma were employed to study the effects of downregulating MDL1AS in vitro. Expression of MDL1AS (but not MDL1) was significantly different in tumor cells than in the surrounding tissue in a tumor-type-specific context. Both MDL1 and MDL1AS were accurate biomarkers for the 5-year survival of LARC patients (p = 0.040 and p = 0.007, respectively) with promising areas under the curve in the ROC analyses (0.820 and 0.930, respectively). MDL1AS downregulation reduced mitochondrial respiration in both cell lines. Furthermore, this downregulation produced a decrease in growth and migration on colorectal cells, but the reverse effects on breast cancer cells. In summary, MDL1 and MDL1AS can be used as reliable prognostic biomarkers of LARC, and MDL1AS expression provides relevant information on the diagnosis of different cancers.

Structure-Guided Approach for the Development of MUC1-Glycopeptide-Based Cancer Vaccines with Predictable Responses.

Mucin-1 (MUC1) glycopeptides are exceptional candidates for potential cancer vaccines. However, their autoantigenic nature often results in a weak immune response. To overcome this drawback, we carefully engineered synthetic antigens with precise chemical modifications. To be effective and stimulate an anti-MUC1 response, artificial antigens must mimic the conformational dynamics of natural antigens in solution and have an equivalent or higher binding affinity to anti-MUC1 antibodies than their natural counterparts. As a proof of concept, we have developed a glycopeptide that contains noncanonical amino acid (2S,3R)-3-hydroxynorvaline. The unnatural antigen fulfills these two properties and effectively mimics the threonine-derived antigen. On the one hand, conformational analysis in water shows that this surrogate explores a landscape similar to that of the natural variant. On the other hand, the presence of an additional methylene group in the side chain of this analog compared to the threonine residue enhances a CH/π interaction in the antigen/antibody complex. Despite an enthalpy-entropy balance, this synthetic glycopeptide has a binding affinity slightly higher than that of its natural counterpart. When conjugated with gold nanoparticles, the vaccine candidate stimulates the formation of specific anti-MUC1 IgG antibodies in mice and shows efficacy comparable to that of the natural derivative. The antibodies also exhibit cross-reactivity to selectively target, for example, human breast cancer cells. This investigation relied on numerous analytical (e.g., NMR spectroscopy and X-ray crystallography) and biophysical techniques and molecular dynamics simulations to characterize the antigen-antibody interactions. This workflow streamlines the synthetic process, saves time, and reduces the need for extensive, animal-intensive immunization procedures. These advances underscore the promise of structure-based rational design in the advance of cancer vaccine development.

The Arousal-Related "Central Thalamus" Stimulation Site Simultaneously Innervates Multiple High-Level Frontal and Parietal Areas.

In human and nonhuman primates, deep brain stimulation applied at or near the internal medullary lamina of the thalamus [a region referred to as "central thalamus," (CT)], but not at nearby thalamic sites, elicits major changes in the level of consciousness, even in some minimally conscious brain-damaged patients. The mechanisms behind these effects remain mysterious, as the connections of CT had not been specifically mapped in primates. In marmoset monkeys (Callithrix jacchus) of both sexes, we labeled the axons originating from each of the various CT neuronal populations and analyzed their arborization patterns in the cerebral cortex and striatum. We report that, together, these CT populations innervate an array of high-level frontal, posterior parietal, and cingulate cortical areas. Some populations simultaneously target the frontal, parietal, and cingulate cortices, while others predominantly target the dorsal striatum. Our data indicate that CT stimulation can simultaneously engage a heterogeneous set of projection systems that, together, target the key nodes of the attention, executive control, and working-memory networks of the brain. Increased functional connectivity in these networks has been previously described as a signature of consciousness.SIGNIFICANCE STATEMENT In human and nonhuman primates, deep brain stimulation at a specific site near the internal medullary lamina of the thalamus ["central thalamus," (CT)] had been shown to restore arousal and awareness in anesthetized animals, as well as in some brain-damaged patients. The mechanisms behind these effects remain mysterious, as CT connections remain poorly defined in primates. In marmoset monkeys, we mapped with sensitive axon-labeling methods the pathways originated from CT. Our data indicate that stimulation applied in CT can simultaneously engage a heterogeneous set of projection systems that, together, target several key nodes of the attention, executive control, and working-memory networks of the brain. Increased functional connectivity in these networks has been previously described as a signature of consciousness.

Evaluating the Effectiveness of Return-to-Work Interventions for Individuals with Work-Related Mental Health Conditions: A Systematic Review and Meta-Analysis.

The workplace is a vital setting to support positive mental health. Mental health conditions in the workforce contribute to decreased work engagement and participation. There is existing literature on return-to-work (RTW) interventions for individuals with work-related mental health conditions, however, there lacks consensus on their effectiveness. Therefore, the primary aim of this systematic review was to synthesize the literature and evaluate the effectiveness of return-to-work interventions on return-to-work rates, quality of life, and psychological wellbeing for individuals with work-related mental health conditions. Selected articles were organized and identified using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and the Population/Intervention/Comparison/Outcome (PICO) framework. Quality assessment of the included studies was completed using the Critical Appraisal Skills Programme randomized controlled trials checklist and the Joanna Briggs Institute quasi-experimental studies checklist. A random effects meta-analysis model was performed using DerSimonian-Laird weighting to calculate standard mean difference and risk ratios to assess the impact of RTW interventions on return-to-work rates, absenteeism, stress symptoms, depression symptoms, and quality of life. A total of 28 out of 26,153 articles met the inclusion criteria. Diagnoses for participants in the studies ranged from work-related stress to work-related PTSD following exposure to a psychologically traumatizing event in the workplace. No significant differences were found for the meta-analyses examining return-to-work rates, absenteeism, depression, stress, and quality of life. The most effective interventions were found to be a multi-domain intervention (67% of participants RTW full time) and a health-focused intervention (85% RTW rate). Future research may consider establishing effective interventions to develop programs or policies supporting the RTW of employees and promote mental well-being among employees experiencing work-related mental health conditions.

Terapia fotodinámica antimicrobiana sobre Candida albicans en superficies acrílicas de prótesis dentales. Estudio in vitro / Antimicrobial photodynamic therapy on Candida albicans on acrylic surfaces of dental prostheses. In vitro study

Frecuentemente, se hayan especies del género Candida en la microbiota oral de los humanos. Objetivo: comparar la efectividad antimicrobiana de la terapia fotodinámica sobre las cepas de Candida albicans en superficies acrílicas para prótesis dentales, empleando láser con 660nm de longitud de onda y azul de metileno como agente fotosensibilizador, con respecto a otros métodos terapéuticos. Metodología: estudio in vitro, empleando 60 discos de acrílico de termocurado sumergidos en una suspensión de C. albicans, generando una simulación de biofilm sobre la superficie de una prótesis dental. Luego se conformaron cinco grupos al azar de 12 unidades a los que se aplicó diferentes procedimientos terapéuticos: G1 (suero fisiológico), G2 (clorhexidi-na al 0,12%), G3 (nistatina en solución tópica en 0,001ml/ul), G4 (azul de metileno al 0,005% + láser diodo con λ=660nm, 100mW, 32J/cm2) y G5 (azul de metileno 0,01% + láser diodo con λ=660nm, 100mW, 321J/cm2). Resultados: Se observó una diferencia estadísticamente significativa al comparar los grupos G4 y G5 con respecto a los G1 y G3 (p<0,05). Conclusión: la eficacia en la reducción del número de UFC viables de C. albicans resultó superior en los grupos donde se empleó radiación láser con una longitud de onda de 660nm con diferentes concentraciones de azul de metileno. El uso de nistatina y de suero fisiológico tuvieron los menores valores de eficacia.

Species of the genus Candida are frequently found in the oral microbiota of humans. Objective: to compare the antimicrobial effectiveness of photodynamic therapy on Candida albicansstrains on acrylic surfaces for dental prostheses by using a 660nm wavelength laser and methyle-ne blue as a photosensitizing agent, with respect to other therapeutic methods. Methodology: in vitro study, using 60 thermosetting acrylic discs immersed in a suspension of C. albicans, gene-rating a biofilm simulation on the surface of a dental prosthesis. After that, five random groups of 12 units were formed to apply them different therapeutic procedures: G1 (saline solution), G2 (chlorhexidine 0.12%), G3 (nystatin in topical solution at 0.001ml/ul), G4 (0.005% methylene blue + diode laser with λ=660nm, 100mW, 32J/cm2) and G5 (0.01% methylene blue + diode laser with λ=660nm, 100mW, 321J/cm2). Results: a statistically significant difference was observed when comparing groups G4 and G5 with respect to G1 and G3 (p<0.05). Conclusion: the efficacy in reducing the number of viable C. albicans CFU was higher in the groups where laser radiation with a wavelength of 660nm was used with different concentrations of methylene blue. The use of nystatin and physiological saline had the lowest efficacy values

Not so rigid capsids based on cyclodextrin complexes: Keys to design.

HYPOTHESIS: Membranes based on cyclodextrin complexes can be used as functional nanocarrier envelopers by chemical modifications of the cyclodextrin hydroxyl groups or by encapsulating different ligands in their cavities. EXPERIMENTS: Molecular dynamics simulations of monolayers and bilayers based on supramolecular complexes consisting of two α or ß-cyclodextrin and one sodium dodecylsulfate or dodecane at 283 K and at 298 K were performed. FINDINGS: It is shown that the structure and main interactions stabilizing the membranes, as well as their permeability to water and ions can be tuned by changing the cyclodextrin, the ligand, the number of layers or/and the temperature. These results provide new evidences about both their dynamic nature and the interactions responsible for the stabilization of the membranes and will facilitate the design of new functional capsides and applications based on cyclodextrin complexes.

Miositis por Bartonella henselae: caso clínico en una adolescente / Bartonella henselae myositis: case report in an adolescent

La miositis de origen vírico o bacteriano es frecuente en la edad pediátrica. Causa dolor muscular y debilidad, con fiebre y malestar general. Una causa es la infección por Bartonella henselae, bacteria implicada en la enfermedad por arañazo de gato que, a veces, causa afectación multisistémica. Se presenta el caso de una adolescente que acudió al servicio de urgencias por mialgia intensa, malestar, adelgazamiento y esplenomegalia. En el labortorio se observaron parámetros inflamatorios elevados. Refería contacto con un gato. Entre los estudios realizados, la resonancia magnética (RM) de miembros inferiores mostró una imagen compatible con miositis inflamatoria bilateral. En la RM abdominal, se observaron tres lesiones esplénicas no detectadas previamente y el fondo de ojo mostraba una lesión compatible con oclusión arterial retiniana o vasculitis. Se indicó tratamiento antibiótico por vía intravenosa durante 21 días con cefotaxima y cloxacilina, tras los cuales desaparecieron los signos y síntomas, aunque los reactantes inflamatorios persistieron elevados. Con base en el cuadro clínico (miositis + coriorretinitis + absceso esplénico) se pensó en una posible infección por B. henselae y se inició tratamiento oral con azitromicina y rifampicina durante 14 días. Luego del tratamiento, los valores de laboratorio fueron normales, así como la RM de control, y se constató una IgG positiva para la bacteria

Infectious myositis, whether viral or bacterial, is frequent in pediatric age. It causes muscle pain and weakness, associated with fever and general malaise. One cause is Bartonella henselae, responsible for cat scratch disease, which sometimes causes systemic symptoms. We report the case of an adolescent who came to the emergency room with intense myalgia, malaise, weight loss and splenomegaly. Blood tests showed high inflammatory markers. She had been in touch with a cat. Studies were carried out including: lower limbs MRI suggestive of bilateral inflammatory myositis, abdominal MRI with three previously undetected splenic lesions and dilated fundus examination that showed possible retinal arterial occlusion or vasculitis. After 21 days of intravenous antibiotic therapy (cefotaxime + cloxaciline), she became asymptomatic, but inflammatory markers remained high. Suspecting Bartonella henselaeinfection (myositis + chorioretinitis + splenic abscess), oral azithromycin and rifampicin were prescribed for 14 days. Blood tests and control MRI became normal, and IgG was positive.

Molecular Dynamics Simulations of Transmembrane Cyclic Peptide Nanotubes Using Classical Force Fields, Hydrogen Mass Repartitioning, and Hydrogen Isotope Exchange Methods: A Critical Comparison.

Self-assembled cyclic peptide nanotubes with alternating D- and L-amino acid residues in the sequence of each subunit have attracted a great deal of attention due to their potential for new nanotechnology and biomedical applications, mainly in the field of antimicrobial peptides. Molecular dynamics simulations can be used to characterize these systems with atomic resolution at different time scales, providing information that is difficult to obtain via wet lab experiments. However, the performance of classical force fields typically employed in the simulation of biomolecules has not yet been extensively tested with this kind of highly constrained peptide. Four different classical force fields (AMBER, CHARMM, OPLS, and GROMOS), using a nanotube formed by eight D,L-α-cyclic peptides inserted into a lipid bilayer as a model system, were employed here to fill this gap. Significant differences in the pseudo-cylindrical cavities formed by the nanotubes were observed, the most important being the diameter of the nanopores, the number and location of confined water molecules, and the density distribution of the solvent molecules. Furthermore, several modifications were performed on GROMOS54a7, aiming to explore acceleration strategies of the MD simulations. The hydrogen mass repartitioning (HMR) and hydrogen isotope exchange (HIE) methods were tested to slow down the fastest degrees of freedom. These approaches allowed a significant increase in the time step employed in the equation of the motion integration algorithm, from 2 fs up to 5-7 fs, with no serious changes in the structural and dynamical properties of the nanopores. Subtle differences with respect to the simulations with the unmodified force fields were observed in the concerted movements of the cyclic peptides, as well as in the lifetime of several H-bonds. All together, these results are expected to contribute to better understanding of the behavior of self-assembled cyclic peptide nanotubes, as well as to support the methods tested to speed up general MD simulations; additionally, they do provide a number of quantitative descriptors that are expected to be used as a reference to design new experiments intended to validate and complement computational studies of antimicrobial cyclic peptides.

[Bartonella henselae myositis: case report in an adolescent]. / Miositis por Bartonella henselae: caso clínico en una adolescente.

Infectious myositis, whether viral or bacterial, is frequent in pediatric age. It causes muscle pain and weakness, associated with fever and general malaise. One cause is Bartonella henselae, responsible for cat scratch disease, which sometimes causes systemic symptoms. We report the case of an adolescent who came to the emergency room with intense myalgia, malaise, weight loss and splenomegaly. Blood tests showed high inflammatory markers. She had been in touch with a cat. Studies were carried out including: lower limbs MRI suggestive of bilateral inflammatory myositis, abdominal MRI with three previously undetected splenic lesions and dilated fundus examination that showed possible retinal arterial occlusion or vasculitis. After 21 days of intravenous antibiotic therapy (cefotaxime + cloxaciline), she became asymptomatic, but inflammatory markers remained high. Suspecting Bartonella henselae infection (myositis + chorioretinitis + splenic abscess), oral azithromycin and rifampicin were prescribed for 14 days. Blood tests and control MRI became normal, and IgG was positive.

La miositis de origen vírico o bacteriano es frecuente en la edad pediátrica. Causa dolor muscular y debilidad, con fiebre y malestar general. Una causa es la infección por Bartonella henselae, bacteria implicada en la enfermedad por arañazo de gato que, a veces, causa afectación multisistémica. Se presenta el caso de una adolescente que acudió al servicio de urgencias por mialgia intensa, malestar, adelgazamiento y esplenomegalia. En el labortorio se observaron parámetros inflamatorios elevados. Refería contacto con un gato. Entre los estudios realizados, la resonancia magnética (RM) de miembros inferiores mostró una imagen compatible con miositis inflamatoria bilateral. En la RM abdominal, se observaron tres lesiones esplénicas no detectadas previamente y el fondo de ojo mostraba una lesión compatible con oclusión arterial retiniana o vasculitis. Se indicó tratamiento antibiótico por vía intravenosa durante 21 días con cefotaxima y cloxacilina, tras los cuales desaparecieron los signos y síntomas, aunque los reactantes inflamatorios persistieron elevados. Con base en el cuadro clínico (miositis + coriorretinitis + absceso esplénico) se pensó en una posible infección por B. henselae y se inició tratamiento oral con azitromicina y rifampicina durante 14 días. Luego del tratamiento, los valores de laboratorio fueron normales, así como la RM de control, y se constató una IgG positiva para la bacteria.

Single Mutation on Trastuzumab Modulates the Stability of Antibody-Drug Conjugates Built Using Acetal-Based Linkers and Thiol-Maleimide Chemistry.

Antibody-drug conjugates (ADCs) are a class of targeted therapeutics used to selectively kill cancer cells. It is important that they remain intact in the bloodstream and release their payload in the target cancer cell for maximum efficacy and minimum toxicity. The development of effective ADCs requires the study of factors that can alter the stability of these therapeutics at the atomic level. Here, we present a general strategy that combines synthesis, bioconjugation, linker technology, site-directed mutagenesis, and modeling to investigate the influence of the site and microenvironment of the trastuzumab antibody on the stability of the conjugation and linkers. Trastuzumab is widely used to produce targeted ADCs because it can target with high specificity a receptor that is overexpressed in certain breast cancer cells (HER2). We show that the chemical environment of the conjugation site of trastuzumab plays a key role in the stability of linkers featuring acid-sensitive groups such as acetals. More specifically, Lys-207, located near the reactive Cys-205 of a thiomab variant of the antibody, may act as an acid catalyst and promote the hydrolysis of acetals. Mutation of Lys-207 into an alanine or using a longer linker that separates this residue from the acetal group stabilizes the conjugates. Analogously, Lys-207 promotes the beneficial hydrolysis of the succinimide ring when maleimide reagents are used for conjugation, thus stabilizing the subsequent ADCs by impairing the undesired retro-Michael reactions. This work provides new insights for the design of novel ADCs with improved stability properties.

[Hospital care of patients with chronic pathology]. / Atención hospitalaria de pacientes con patología crónica.

Advances in medical care have increased the survival of children with complex chronic pathology (CCP). OBJECTIVE: to analyze the epidemiological and clinical characteristics of a cohort of children with CCP. PATIENTS AND METHOD: retrospective descriptive study performed in a tertiary hospital bet ween June 2017 and June 2020, which included patients with CCP criteria. Epidemiological, clinical, admissions, and services involved data were collected and analyzed. Statistical analysis was perfor med using SPSS v22.0 software. RESULTS: 323 patients (mean age 7 years) were included. 93.1% had a multisystem disease, with neurological (87.3%) and gastrointestinal (34.1%) as the most frequent chronic conditions. 39.9% were technology dependent. The main diagnoses were Infantile Cerebral Palsy (23.5%) and Epileptic Encephalopathy (13.9%). Each patient was in follow-up by 5 specialists on average. Of the patients, 85.1% were admitted at some time, with a total of 739 admissions. The mean length of stay was 8.7 days. Technology-dependent patients accounted for 54.7% of hospi talizations. The reasons for admission were acute illness (64.3%), surgery (20.3%), and diagnostic procedure (15%). ICU was required in 23.1%. 62 admissions were partially carried out by the Home Hospitalization Unit. CONCLUSIONS: Children with CCP require an increased number of admissions and multiple specialists. The implementation of specialized referral units may be useful to improve their care.

Unsupervised bubble calorimetry analysis: Surface tension from isothermal titration calorimetry.

HYPOTHESIS: The injection of air into the sample cell of an isothermal titration calorimeter containing a liquid provides a rich-in-information signal, with a periodic contribution arising from the creation, growing and release of bubbles. The identification and analysis of such contributions allow the accurate determination of the surface tension of the target liquid. EXPERIMENTS: Air is introduced at a constant rate into the sample cell of the calorimeter containing either a pure liquid or a solution. The resulting calorimetric signal is analyzed by a new algorithm, which is implemented into a computational code. FINDINGS: The thermal power generated by our experiments is often noisy, thus hiding the periodic signal arising from the bubbles' formation and release. The new algorithm was tested with a range of different types of calorimetric raw data, some of them apparently being just noise. In all cases, the contribution of the bubbles to the signal was isolated and the corresponding period was successfully determined in an automated way. It is also shown that two reference measurements suffice to calibrate the instrument at a given temperature, regardless the injection rate, allowing the direct determination of surface tension values for the liquid contained in the sample cell.

Differential Entropy: An Appropriate Analysis to Interpret the Shape Complexity of Self-Similar Organic Islands.

Differential entropy, along with fractal dimension, is herein employed to describe and interpret the shape complexity of self-similar organic islands. The islands are imaged with in situ Atomic Force Microscopy, following, step-by-step, the evolution of their shape while deposition proceeds. The fractal dimension shows a linear correlation with the film thickness, whereas the differential entropy presents an exponential plateau. Plotting differential entropy versus fractal dimension, a linear correlation can be found. This analysis enables one to discern the 6T growth on different surfaces, i.e., native SiOx or 6T layer, and suggests a more comprehensive interpretation of the shape evolution. Changes in fractal dimension reflect rougher variations of the island contour, whereas changes in differential entropy correlates with finer contour details. The computation of differential entropy therefore helps to obtain more physical information on the island shape dependence on the substrate, beyond the standard description obtained with the fractal dimension.

Bioorthogonal Self-Immolative Linker Based on Grob Fragmentation.

A self-immolative bioorthogonal conditionally cleavable linker based on Grob fragmentation is described. It is derived from 1,3-aminocyclohexanols and allows the release of sulfonate-containing compounds in aqueous media. Modulation of the amine pKa promotes fragmentation even at slightly acidic pH, a common feature of several tumor environments. The Grob fragmentation can also occur under physiological conditions in living cells, highlighting the potential bioorthogonal applicability of this reaction.

Simple ApproximaTion for Aggregation Number Determination by Isothermal Titration Calorimetry: STAND-ITC.

A new proposal to obtain aggregation numbers from isothermal titration calorimetry dilution experiments is described and tested using dodecyl trimethyl ammonium bromide, dodecyl methylimidazolium chloride, dodecyl methylimidazolium sulfonate, and didecyl methylimidazolium chloride aqueous solutions at different temperatures. The results were compared to those obtained from fluorescence measurements and also with data from the literature. In addition to the aggregation number, the molar free energy to transfer a solute molecule from the aggregate to the bulk solution, the enthalpy corresponding to the formation of the self-assembled suprastructures, the molar heat corresponding to the dilution of monomers and aggregates, and an offset parameter to account for unpredictable external contributions are simultaneously obtained using the same method. The new equations are compared to those obtained from previous proposals, and they are also analyzed in detail to assess the impact of each fitting parameter in the profile of the calorimetric isotherm. This new approach has been implemented in a computational code that automatically determines the fitting parameters as well as the corresponding statistical uncertainties for the large variety of calorimetric profiles that have been tested. Given the high sensitivity of the dilution experiments to the aggregation number for relatively small assemblies, our approach is proposed also to quantify the oligomerization state of biomolecules such as proteins and peptides.

Even Lower Latency in IIoT: Evaluation of QUIC in Industrial IoT Scenarios.

In this paper we analyze the performance of QUIC as a transport alternative for Internet of Things (IoT) services based on the Message Queuing Telemetry Protocol (MQTT). QUIC is a novel protocol promoted by Google, and was originally conceived to tackle the limitations of the traditional Transmission Control Protocol (TCP), specifically aiming at the reduction of the latency caused by connection establishment. QUIC use in IoT environments is not widespread, and it is therefore interesting to characterize its performance when in over such scenarios. We used an emulation-based platform, where we integrated QUIC and MQTT (using GO-based implementations) and compared their combined performance with the that exhibited by the traditional TCP/TLS approach. We used Linux containers as end devices, and the ns-3 simulator to emulate different network technologies, such as WiFi, cellular, and satellite, and varying conditions. The results evince that QUIC is indeed an appropriate protocol to guarantee robust, secure, and low latency communications over IoT scenarios.

Transmembrane Self-Assembled Cyclic Peptide Nanotubes Based on α-Residues and Cyclic δ-Amino Acids: A Computational Study.

Self-assembling cyclic peptide nanotubes have been shown to function as synthetic, integral transmembrane channels. The combination of natural and nonnatural aminoacids in the sequence of cyclic peptides enables the control not only of their outer surface but also of the inner cavity behavior and properties, affecting, for instance, their permeability to different molecules including water and ions. Here, a thorough computational study on a new class of self-assembling peptide motifs, in which δ-aminocycloalkanecarboxylic acids are alternated with natural α-amino acids, is presented. The presence of synthetic δ-residues creates hydrophobic regions in these α,δ-SCPNs, which makes them especially attractive for their potential implementation in the design of new drug or diagnostic agent carrier systems. Using molecular dynamics simulations, the behavior of water molecules, different ions (Li+, Na+, K+, Cs+, and Ca2+), and their correspondent counter Cl- anions is extensively investigated in the nanoconfined environment. The structure and dynamics are mutually combined in a diving immersion inside these transmembrane channels to discover a fascinating submarine nanoworld where star-shaped water channels guide the passage of cations and anions therethrough.

Fluid interface calorimetry.

HYPOTHESIS: Amphiphilic molecules spontaneously adsorb to fluid polar-nonpolar interfaces. The timescale of such adsorption depends on the molecular size and structure of the solute. This process should be accompanied by a power heat exchange that could be detected by commercial isothermal calorimeters. EXPERIMENTS: Air is injected in the bulk of different aqueous solutions contained in the sample cell of an isothermal titration calorimeter. The formation of the resulting bubbles leads to a liquid/air interface to which the solute molecules spontaneously adsorb. Continuous injection experiments to produce multiple bubbles as well as experiments with static bubbles stand from the capillary tip, aiming to observe slow adsorption processes, were performed. FINDINGS: The power associated with the formation, growth and release of air bubbles in different liquids was measured. Different independent contributions that can be associated to the pressure change in the gas phase, the evaporation-condensation of the solvent, the increase of interfacial area, the change in the heat capacity of the sample cell content, and the release of the bubble were observed. The periodic pattern produced by the continuous injection of air at a constant rate is used to determine the surface tension of different liquids, including solutions of different molecules and (bio)macromolecules.

Experimental rewilding may restore abandoned wood-pastures if policy allows.

Large herbivores play key roles in terrestrial ecosystems. Continuous defaunation processes have produced cascade effects on plant community composition, vegetation structure, and even climate. Wood-pastures were created by traditional management practices that have maintained open structures and biodiversity for millennia. In Europe, despite the broad recognition of their biological importance, such landscapes are declining due to land-use changes. This calls for finding urgent solutions for wood-pasture conservation. To test whether introducing an ecological replacement of an extinct wild horse could have positive effects on wood-pasture restoration, we designed a 3-year rewilding experiment. Horses created a more open wood-pasture structure by browsing on seedlings and saplings, affected tree composition via selective browsing and controlled the colonization of woody vegetation in grassland-dominated areas. Thus, rewilding could be a potential avenue for wood-pasture restoration and biodiversity conservation. However, such benefits may not materialize without a necessary paradigm and political shift.