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.

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.

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.

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.

Coexpression of NOS2 and COX2 accelerates tumor growth and reduces survival in estrogen receptor-negative breast cancer.

Proinflammatory signaling pathways are commonly up-regulated in breast cancer. In estrogen receptor-negative (ER-) and triple-negative breast cancer (TNBC), nitric oxide synthase-2 (NOS2) and cyclooxygenase-2 (COX2) have been described as independent predictors of disease outcome. We further explore these findings by investigating the impact of their coexpression on breast cancer survival. Elevated coexpression of NOS2/COX2 proteins is a strong predictor of poor survival among ER- patients (hazard ratio: 21). Furthermore, we found that the key products of NOS2 and COX2, NO and prostaglandin E2 (PGE2), respectively, promote feed-forward NOS2/COX2 crosstalk in both MDA-MB-468 (basal-like) and MDA-MB-231 (mesenchymal-like) TNBC cell lines in which NO induced COX2 and PGE2 induced NOS2 proteins. COX2 induction by NO involved TRAF2 activation that occurred in a TNFα-dependent manner in MDA-MB-468 cells. In contrast, NO-mediated TRAF2 activation in the more aggressive MDA-MB-231 cells was TNFα independent but involved the endoplasmic reticulum stress response. Inhibition of NOS2 and COX2 using amino-guanidine and aspirin/indomethacin yielded an additive reduction in the growth of MDA-MB-231 tumor xenografts. These findings support a role of NOS2/COX2 crosstalk during disease progression of aggressive cancer phenotypes and offer insight into therapeutic applications for better survival of patients with ER- and TNBC disease.

AFFINImeter: A software to analyze molecular recognition processes from experimental data.

The comprehension of molecular recognition phenomena demands the understanding of the energetic and kinetic processes involved. General equations valid for the thermodynamic analysis of any observable that is assessed as a function of the concentration of the involved compounds are described, together with their implementation in the AFFINImeter software. Here, a maximum of three different molecular species that can interact with each other to form an enormous variety of supramolecular complexes are considered. The corrections currently employed to take into account the effects of dilution, volume displacement, concentration errors and those due to external factors, especially in the case of ITC measurements, are included. The methods used to fit the model parameters to the experimental data, and to generate the uncertainties are described in detail. A simulation tool and the so called kinITC analysis to get kinetic information from calorimetric experiments are also presented. An example of how to take advantage of the AFFINImeter software for the global multi-temperature analysis of a system exhibiting cooperative 1:2 interactions is presented and the results are compared with data previously published. Some useful recommendations for the analysis of experiments aimed at studying molecular interactions are provided.

On the Combination of Multi-Cloud and Network Coding for Cost-Efficient Storage in Industrial Applications.

The adoption of both Cyber⁻Physical Systems (CPSs) and the Internet-of-Things (IoT) has enabled the evolution towards the so-called Industry 4.0. These technologies, together with cloud computing and artificial intelligence, foster new business opportunities. Besides, several industrial applications need immediate decision making and fog computing is emerging as a promising solution to address such requirement. In order to achieve a cost-efficient system, we propose taking advantage from spot instances, a new service offered by cloud providers, which provide resources at lower prices. The main downside of these instances is that they do not ensure service continuity and they might suffer from interruptions. An architecture that combines fog and multi-cloud deployments along with Network Coding (NC) techniques, guarantees the needed fault-tolerance for the cloud environment, and also reduces the required amount of redundant data to provide reliable services. In this paper we analyze how NC can actually help to reduce the storage cost and improve the resource efficiency for industrial applications, based on a multi-cloud infrastructure. The cost analysis has been carried out using both real AWS EC2 spot instance prices and, to complement them, prices obtained from a model based on a finite Markov chain, derived from real measurements. We have analyzed the overall system cost, depending on different parameters, showing that configurations that seek to minimize the storage yield a higher cost reduction, due to the strong impact of storage cost.

Error Resilient Coding Techniques for Video Delivery over Vehicular Networks.

Nowadays, more and more vehicles are equipped with communication capabilities, not only providing connectivity with onboard devices, but also with off-board communication infrastructures. From road safety (i.e., multimedia e-call) to infotainment (i.e., video on demand services), there are a lot of applications and services that may be deployed in vehicular networks, where video streaming is the key factor. As it is well known, these networks suffer from high interference levels and low available network resources, and it is a great challenge to deploy video delivery applications which provide good quality video services. We focus our work on supplying error resilience capabilities to video streams in order to fight against the high packet loss rates found in vehicular networks. So, we propose the combination of source coding and channel coding techniques. The former ones are applied in the video encoding process by means of intra-refresh coding modes and tile-based frame partitioning techniques. The latter one is based on the use of forward error correction mechanisms in order to recover as many lost packets as possible. We have carried out an extensive evaluation process to measure the error resilience capabilities of both approaches in both (a) a simple packet error probabilistic model, and (b) a realistic vehicular network simulation framework. Results show that forward error correction mechanisms are mandatory to guarantee video delivery with an acceptable quality level , and we highly recommend the use of the proposed mechanisms to increase even more the final video quality.

Effects of Estrogen and Phytoestrogen Treatment on an In Vitro Model of Recurrent Stroke on HT22 Neuronal Cell Line.

An increase of stroke incidence occurs in women with the decline of estrogen levels following menopause. This ischemic damage may recur, especially soon after the first insult has occurred. We evaluated the effects of estrogen and phytoestrogen treatment on an in vitro recurrent stroke model using the HT22 neuronal cell line. HT22 cells were treated with 17ß-estradiol or genistein 1 h after the beginning of the first of two oxygen and glucose deprivation/reoxygenation (OGD/R) cycles. During the second OGD, there was a deterioration of some components of the electron transport chain, such as cytochrome c oxidase subunit 1 with a subsequent increase of reactive oxygen species (ROS) production. Accordingly, there was also an increase of apoptotic phenomena demonstrated by poly(ADP-ribose) polymerase 1 cleavage, Caspase-3 activity, and Annexin V levels. The recurrent ischemic injury also raised the hypoxia-inducible factor 1α and glucose transporter 1 levels, as well as the ratio between the lipidated and cytosolic forms of microtubule-associated protein 1A/1B-light chain 3 (LC3-II/LC3-I). We found a positive effect of estradiol and genistein treatment by partially preserving the impaired cell viability after the recurrent ischemic injury; however, this positive effect does not seem to be mediated neither by blocking apoptosis processes nor by decreasing ROS production. This work contribute to the better understanding of the molecular mechanisms triggered by recurrent ischemic damage in neuronal cells and, therefore, could help with the development of an effective treatment to minimize the consequences of this pathology.

STAND: Surface Tension for Aggregation Number Determination.

Taking advantage of the extremely high dependence of surface tension on the concentration of amphiphilic molecules in aqueous solution, a new model based on the double equilibrium between free and aggregated molecules in the liquid phase and between free molecules in the liquid phase and those adsorbed at the air/liquid interface is presented and validated using literature data and fluorescence measurements. A key point of the model is the use of both the Langmuir isotherm and the Gibbs adsorption equation in terms of free molecules instead of the nominal concentration of the solute. The application of the model should be limited to non ionic compounds since it does not consider the presence of counterions. It requires several coupled nonlinear fittings for which we developed a software that is publicly available in our server as a web application. Using this tool, it is straightforward to get the average aggregation number of an amphiphile, the micellization free energy, the adsorption constant, the maximum surface excess (and so the minimum area per molecule), the distribution of solute in the liquid phase between free and aggregate species, and the surface coverage in only a couple of seconds, just by uploading a text file with surface tension vs concentration data and the corresponding uncertainties.

Loss of GLUT4 induces metabolic reprogramming and impairs viability of breast cancer cells.

Metabolic reprogramming strategies focus on the normalization of metabolism of cancer cells and constitute promising targets for cancer treatment. Here, we demonstrate that the glucose transporter 4 (GLUT4) has a prominent role in basal glucose uptake in MCF7 and MDA-MB-231 breast cancer cells. We show that shRNA-mediated down-regulation of GLUT4 diminishes glucose uptake and induces metabolic reprogramming by reallocating metabolic flux to oxidative phosphorylation. This reallocation is reflected on an increased activity of the mitochondrial oxidation of pyruvate and lower lactate release. Altogether, GLUT4 inhibition compromises cell proliferation and critically affects cell viability under hypoxic conditions, providing proof-of-principle for the feasibility of using pharmacological approaches to inhibit GLUT4 in order to induce metabolic reprogramming in vivo in breast cancer models.

[Return to work enablers for workers with work-related mental illness]. / Facilitadores del reintegro laboral en trabajadores con patología mental de origen laboral: una revisión sistemática.

BACKGROUND: There is growing interest in the treatment and return-to-work of workers with labor related mental illnesses. AIM: To perform a systematic review of practices and interventions that improve return to work. MATERIAL AND METHODS: Systematic literature review. Thirty articles were selected for in- depth analysis. RESULTS: Self efficacy perception, work motivation, a lower age and a better socioeconomic status were identified as worker-related return to work facilitators. Among work environment facilitators, good communication practices, supervisor support, a good assessment and modification of work load, adjustment of expectations, a good relationship between employers and employees and positive work experiences were identified. Treatment may improve return to work using a multidisciplinary approach, reducing stress and identifying psychosocial determinants of mental problems rather than symptoms and providing a timely health care. CONCLUSIONS: Return to work of workers with labor related mental illnesses requires a constant sharing of information between health care workers, employers and employees to identify common therapeutic objectives.

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.

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.

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.

Solving problems in social-ecological systems: definition, practice and barriers of transdisciplinary research.

Translating policies about sustainable development as a social process and sustainability outcomes into the real world of social-ecological systems involves several challenges. Hence, research policies advocate improved innovative problem-solving capacity. One approach is transdisciplinary research that integrates research disciplines, as well as researchers and practitioners. Drawing upon 14 experiences of problem-solving, we used group modeling to map perceived barriers and bridges for researchers' and practitioners' joint knowledge production and learning towards transdisciplinary research. The analysis indicated that the transdisciplinary research process is influenced by (1) the amount of traditional disciplinary formal and informal control, (2) adaptation of project applications to fill the transdisciplinary research agenda, (3) stakeholder participation, and (4) functional team building/development based on self-reflection and experienced leadership. Focusing on implementation of green infrastructure policy as a common denominator for the delivery of ecosystem services and human well-being, we discuss how to diagnose social-ecological systems, and use knowledge production and collaborative learning as treatments.

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.

Unveiling the diversity of thalamocortical neuron subtypes.

Our current understanding of thalamocortical (TC) circuits is largely based on studies investigating so-called 'specific' thalamic nuclei, which receive and transmit sensory-triggered input to specific cortical target areas. TC neurons in these nuclei have a striking point-to-point topography and a stereotyped laminar pattern of termination in the cortex, which has made them ideal models to study the organization, plasticity, and development of TC circuits. However, despite their experimental importance, neurons within these nuclei only represent a fraction of all thalamic neurons and do not reflect the diversity of the TC neuron population. Here we review the distinct subtypes of projection neurons that populate the thalamus, both within and across anatomically-defined nuclei, with regard to differences in their morphology, input/output connectivity and target specificity, as well as more recent findings on their neuron type-specific gene expression and development. We argue that a detailed understanding of the biology of TC neurons is critical to understand the role of the thalamus in normal and pathological perception, voluntary movement, cognition and attention.

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.