Obtention and Characterization of Microcrystalline Cellulose from Industrial Melon Residues Following a Biorefinery Approach.

Residual melon by-products were explored for the first time as a bioresource of microcrystalline cellulose (MCC) obtention. Two alkaline extraction methods were employed, the traditional (4.5% NaOH, 2 h, 80 °C) and a thermo-alkaline in the autoclave (2% NaOH, 1 h, 100 °C), obtaining a yield of MCC ranging from 4.76 to 9.15% and 2.32 to 3.29%, respectively. The final MCCs were characterized for their chemical groups by Fourier-transform infrared spectroscopy (FTIR), crystallinity with X-ray diffraction, and morphology analyzed by scanning electron microscope (SEM). FTIR spectra showed that the traditional protocol allows for a more effective hemicellulose and lignin removal from the melon residues than the thermo-alkaline process. The degree of crystallinity of MCC ranged from 51.51 to 61.94% and 54.80 to 55.07% for the thermo-alkaline and traditional processes, respectively. The peaks detected in X-ray diffraction patterns indicated the presence of Type I cellulose. SEM analysis revealed microcrystals with rough surfaces and great porosity, which could remark their high-water absorption capacity and drug-carrier capacities. Thus, these findings could respond to the need to valorize industrial melon by-products as raw materials for MCC obtention with potential applications as biodegradable materials.

Elevating Skincare Science: Grape Seed Extract Encapsulation for Dermatological Care.

The skin is the largest organ in the human body and serves multiple functions such as barrier protection and thermoregulation. The maintenance of its integrity and healthy structure is of paramount importance. Accordingly, technological advances in cosmetic sciences have been directed towards optimizing these factors. Plant-derived ingredients have been explored for their bioactivity profiles and sustainable sources. Grape by-products contain a group of bioactive molecules that display important biological activities. Nonetheless, many of these molecules (e.g., phenolic compounds) are unstable and susceptible to degradation. So, their encapsulation using nano/microsystems (i.e., microdispersions) has been explored as a promising solution. In this work, two grape seed extracts were obtained, one from a single grape variety (GSE-Ov) and another from a mix of five grape varieties (GSE-Sv). These extracts were analysed for their antioxidant and antimicrobial activities, as well as their chemical composition and molecular structure. The extract that showed the most promising properties was GSE-Ov with a DPPH IC50 of 0.079 mg mL-1. This extract was encapsulated in soy lecithin microdispersions coated with pectin, with an encapsulation efficiency of 88.8%. They showed an in vitro release of polyphenols of 59.4% during 24 h. The particles displayed a zeta potential of -20.3 mV and an average diameter of 13.6 µm. Microdispersions proved to be safe under 5 and 2.5 mg mL-1 in HaCaT and HDF cell models, respectively. Additionally, they demonstrated anti-inflammatory activity against IL-1α when tested at 2 mg mL-1. This work enabled the valorisation of a by-product from the wine industry by using natural extracts in skincare products.

JUN Regulation of Injury-Induced Enhancers in Schwann Cells.

Schwann cells play a critical role after peripheral nerve injury by clearing myelin debris, forming axon-guiding bands of Büngner, and remyelinating regenerating axons. Schwann cells undergo epigenomic remodeling to differentiate into a repair state that expresses unique genes, some of which are not expressed at other stages of Schwann cell development. We previously identified a set of enhancers that are activated in Schwann cells after nerve injury, and we determined whether these enhancers are preprogrammed into the Schwann cell epigenome as poised enhancers before injury. Poised enhancers share many attributes of active enhancers, such as open chromatin, but are marked by repressive histone H3 lysine 27 (H3K27) trimethylation rather than H3K27 acetylation. We find that most injury-induced enhancers are not marked as poised enhancers before injury indicating that injury-induced enhancers are not preprogrammed in the Schwann cell epigenome. Injury-induced enhancers are enriched with AP-1 binding motifs, and the c-JUN subunit of AP-1 had been shown to be critical to drive the transcriptional response of Schwann cells after injury. Using in vivo chromatin immunoprecipitation sequencing analysis in rat, we find that c-JUN binds to a subset of injury-induced enhancers. To test the role of specific injury-induced enhancers, we focused on c-JUN-binding enhancers upstream of the Sonic hedgehog (Shh) gene, which is only upregulated in repair Schwann cells compared with other stages of Schwann cell development. We used targeted deletions in male/female mice to show that the enhancers are required for robust induction of the Shh gene after injury.SIGNIFICANCE STATEMENT The proregenerative actions of Schwann cells after nerve injury depends on profound reprogramming of the epigenome. The repair state is directed by injury-induced transcription factors, like JUN, which is uniquely required after nerve injury. In this study, we test whether the injury program is preprogrammed into the epigenome as poised enhancers and define which enhancers bind JUN. Finally, we test the roles of these enhancers by performing clustered regularly interspaced short palindromic repeat (CRISPR)-mediated deletion of JUN-bound injury enhancers in the Sonic hedgehog gene. Although many long-range enhancers drive expression of Sonic hedgehog at different developmental stages of specific tissues, these studies identify an entirely new set of enhancers that are required for Sonic hedgehog induction in Schwann cells after injury.

A trial-based cost-effectiveness analysis of antibiotic prescription strategies for non-complicated respiratory tract infections in children.

BACKGROUND: Antibiotic prescription for respiratory tract infections (RTIs) in children attending primary care centres is almost double that predicted according to bacterial prevalence. Delayed antibiotic prescription (DAP) is designed to deploy a more rational use of antibiotics. While studies have evaluated DAP efficacy and safety for children with RTIs, little research has been conducted on the economic implications. METHODS: Our trial compared cost-effectiveness for DAP, immediate antibiotic prescription (IAP), and no antibiotic prescription (NAP) for children aged 2-14 years with acute uncomplicated RTIs attended to in 39 primary care centres in Spain. The main outcome was the incremental cost-effectiveness ratio (ICER), measured in euros per gained quality-adjusted life days (QALDs). Net monetary benefit (NMB) was also calculated as a tool for decision making. The analysis was performed from a societal perspective for a time horizon of 30 days, and included healthcare direct costs, non-healthcare direct and indirect costs, and the antimicrobial resistance (AMR) cost. RESULTS: DAP was the most cost-effective strategy, even when the cost of AMR was included. QALD values for the three strategies were very similar. IAP compared to DAP was more costly (109.68 vs 100.90 euros) and similarly effective (27.88 vs 27.94 QALDs). DAP compared to NAP was more costly (100.90 vs 97.48 euros) and more effective (27.94 vs. 27.82 QALDs). The ICER for DAP compared to NAP was 28.84 euros per QALD. The deterministic sensitivity analysis indicated that non-healthcare indirect costs had the greatest impact on the ICER. The cost-effectiveness acceptability curve showed that DAP was the preferred option in approximately 81.75% of Monte Carlo iterations, assuming a willingness-to-pay value of 82.2 euros per gained QALD. CONCLUSIONS: When clinicians are in doubt about whether an antibiotic is needed for children with RTIs attending PC centres, those treated with the DAP strategy will have slightly better efficiency outcomes than those treated with IAP because its costs are lower than those of IAP. DAP is also the most cost-effective strategy over a time horizon of 30 days if AMR is considered, despite higher short-term costs than NAP. However, if in the long term the costs of AMR are larger than estimated, NAP could also be an alternative strategy. TRIAL REGISTRATION: This trial has been registered at www. CLINICALTRIALS: gov (identifier NCT01800747; Date: 28/02/2013 (retrospectively registered).

Spent Yeast Waste Streams as a Sustainable Source of Bioactive Peptides for Skin Applications.

Spent yeast waste streams are a byproduct obtained from fermentation process and have been shown to be a rich secondary source of bioactive compounds such as phenolic compounds and peptides. The latter are of particular interest for skin care and cosmetics as they have been shown to be safe and hypoallergenic while simultaneously being able to exert various effects upon the epidermis modulating immune response and targeting skin metabolites, such as collagen production. As the potential of spent yeast's peptides has been mainly explored for food-related applications, this work sought to understand if peptide fractions previously extracted from fermentation engineered spent yeast (Saccharomyces cerevisiae) waste streams possess biological potential for skin-related applications. To that end, cytotoxic effects on HaCat and HDFa cells and whether they were capable of exerting a positive effect upon the production of skin metabolites relevant for skin health, such as collagen, hyaluronic acid, fibronectin and elastin, were evaluated. The results showed that the peptide fractions assayed were not cytotoxic up to the highest concentration tested (500 µg/mL) for both cell lines tested. Furthermore, all peptide fractions showed a capacity to modulate the various target metabolites production with an overall positive effect being observed for the four fractions over the six selected targets (pro-collagen IαI, hyaluronic acid, fibronectin, cytokeratin-14, elastin, and aquaporin-9). Concerning the evaluated fractions, the overall best performance (Gpep > 1 kDa) was of an average promotion of 41.25% over the six metabolites and two cell lines assessed at a concentration of 100 µg/mL. These results showed that the peptide fractions assayed in this work have potential for future applications in skin-related products at relatively low concentrations, thus providing an alternative solution for one of the fermentation industry's waste streams and creating a novel and highly valuable bioactive ingredient with encompassing activity to be applied in future skin care formulations.

Acute and 24 h effect of kinesio taping on lower back muscle soreness during continued practice of cross-country skiing among collegiate students. A double-blind, randomized, placebo-controlled trial.

To examine the effects of kinesio taping on lower back muscle soreness immediately after its application and after 24 h during a cross-country skiing camp in collegiate students. The present study followed a double-blind, randomized, placebo-controlled trial design. Out of the 60 participants in a winter skiing camp, 54 volunteered to participate in the study (aged 21.3 years old, 20 females and 34 males). After 3 days of practical cross-country ski lessons (4 h per day), volunteers were, balanced by sex, randomly divided into three groups. One group had kinesio taping applied on the lower back, another had placebo tape applied and the third group nothing. The two-way ANOVA with the Bonferroni adjustment showed that the lower back muscle soreness levels in the kinesio taping group decreased statistically significantly from baseline to after 24 h of the kinesio taping application (p= 0.020). Kinesio taping reduced low back muscle soreness 24 h after its application produce by several days of cross-country skiing in physically active collegiate students. Kinesio taping method may be beneficial in reducing post-exercise delayed onset muscle soreness in healthy sport collegiate students.

Overlapping neuropathological findings in an asymptomatic SPAST gene mutation carrier.

Hereditary spastic paraparesis (HSP) caused by mutations in the SPAST (SPG4) gene are autosomal-dominant inherited disorders characterized by weakness of lower extremities, spasticity and hyperreflexia. Some cases with cognitive decline have been repored. Herein we present an asymptomatic carrier of a SPAST gene mutation who developed an adult-onset cognitive decline, compatible with Alzheimer's disease with co-pathologies such as argyrophylic grain disease and cerebrovascular pathology. No pathological changes described in HSP patients were present in this case.

Design of whey protein nanostructures for incorporation and release of nutraceutical compounds in food.

Whey proteins are widely used as nutritional and functional ingredients in formulated foods because they are relatively inexpensive, generally recognized as safe (GRAS) ingredient, and possess important biological, physical, and chemical functionalities. Denaturation and aggregation behavior of these proteins is of particular relevance toward manufacture of novel nanostructures with a number of potential uses. When these processes are properly engineered and controlled, whey proteins may be formed into nanohydrogels, nanofibrils, or nanotubes and be used as carrier of bioactive compounds. This review intends to discuss the latest understandings of nanoscale phenomena of whey protein denaturation and aggregation that may contribute for the design of protein nanostructures. Whey protein aggregation and gelation pathways under different processing and environmental conditions such as microwave heating, high voltage, and moderate electrical fields, high pressure, temperature, pH, and ionic strength were critically assessed. Moreover, several potential applications of nanohydrogels, nanofibrils, and nanotubes for controlled release of nutraceutical compounds (e.g. probiotics, vitamins, antioxidants, and peptides) were also included. Controlling the size of protein networks at nanoscale through application of different processing and environmental conditions can open perspectives for development of nanostructures with new or improved functionalities for incorporation and release of nutraceuticals in food matrices.

ß-Lactoglobulin microparticles obtained by high intensity ultrasound as a potential delivery system for bioactive peptide concentrate.

This work attempted to assess the effect of high intensity ultrasound (HIUS) upon development of bio-based delivery systems, from ß-lactoglobulin (ß-Lg) gelled microparticles, for encapsulation of a bioactive peptide concentrate (PepC). Solutions of 150 g L-1 of commercial ß-Lg and 30 g L-1 PepC, at various pH values (3.0, 4.0 and 5.5), were accordingly subjected to gelation for 30 min using a dry bath kept at 80 °C. The gelled systems were then exposed to HIUS at 0-4 °C, and the effect of processing time (2.5-20.0 min) was ascertained. Laser light scattering and confocal microscopy were used to characterize the particle size distribution, prior to and immediately after HIUS treatment. Gels obtained at pH 5.5 and 4.0 were harder than those obtained at pH 3.0. Ultrasound treatment of gels produced an important reduction in particle mean diameter as sonication time elapsed. Confocal microscopy indicated that application of HIUS led to almost round and monodispersed particles, at both pH 5.5 and 4.0. The peptide encapsulation efficiency was assessed by chromatography and accompanied by assay for bioactivity, after precipitation of the encapsulated material and analysis of the soluble peptides therein.

An upstream regulator of the 26S proteasome modulates organ size in Arabidopsis thaliana.

In both animal and plant kingdoms, body size is a fundamental but still poorly understood attribute of biological systems. Here we report that the Arabidopsis NAC transcription factor 'Regulator of Proteasomal Gene Expression' (RPX) controls leaf size by positively modulating proteasome activity. We further show that the cis-element recognized by RPX is evolutionarily conserved between higher plant species. Upon over-expression of RPX, plants exhibit reduced growth, which may be reversed by a low concentration of the pharmacological proteasome inhibitor MG132. These data suggest that the rate of protein turnover during growth is a critical parameter for determining final organ size.

Straightforward selection of broadly neutralizing single-domain antibodies targeting the conserved CD4 and coreceptor binding sites of HIV-1 gp120.

Few broadly neutralizing antibodies targeting determinants of the HIV-1 surface envelope glycoprotein (gp120) involved in sequential binding to host CD4 and chemokine receptors have been characterized. While these epitopes show low diversity among various isolates, HIV-1 employs many strategies to evade humoral immune response toward these sensitive sites, including a carbohydrate shield, low accessibility to these buried cavities, and conformational masking. Using trimeric gp140, free or bound to a CD4 mimic, as immunogens in llamas, we selected a panel of broadly neutralizing single-domain antibodies (sdAbs) that bind to either the CD4 or the coreceptor binding site (CD4BS and CoRBS, respectively). When analyzed as monomers or as homo- or heteromultimers, the best sdAb candidates could not only neutralize viruses carrying subtype B envelopes, corresponding to the Env molecule used for immunization and selection, but were also efficient in neutralizing a broad panel of envelopes from subtypes A, C, G, CRF01_AE, and CRF02_AG, including tier 3 viruses. Interestingly, sdAb multimers exhibited a broader neutralizing activity spectrum than the parental sdAb monomers. The extreme stability and high recombinant production yield combined with their broad neutralization capacity make these sdAbs new potential microbicide candidates for HIV-1 transmission prevention.

MiniCD4 microbicide prevents HIV infection of human mucosal explants and vaginal transmission of SHIV(162P3) in cynomolgus macaques.

In complement to an effective vaccine, development of potent anti-HIV microbicides remains an important priority. We have previously shown that the miniCD4 M48U1, a functional mimetic of sCD4 presented on a 27 amino-acid stable scaffold, inhibits a broad range of HIV-1 isolates at sub-nanomolar concentrations in cellular models. Here, we report that M48U1 inhibits efficiently HIV-1(Ba-L) in human mucosal explants of cervical and colorectal tissues. In vivo efficacy of M48U1 was evaluated in nonhuman primate (NHP) model of mucosal challenge with SHIV(162P3) after assessing pharmacokinetics and pharmacodynamics of a miniCD4 gel formulation in sexually matured female cynomolgus macaques. Among 12 females, half were treated with hydroxyethylcellulose-based gel (control), the other half received the same gel containing 3 mg/g of M48U1, one hour before vaginal route challenge with 10 AID(50) of SHIV(162P3). All control animals were infected with a peak plasma viral load of 10(5)-10(6) viral RNA (vRNA) copies per mL. In animals treated with miniCD4, 5 out of 6 were fully protected from acquisition of infection, as assessed by qRT-PCR for vRNA detection in plasma, qPCR for viral DNA detection in PBMC and lymph node cells. The only infected animal in this group had a delayed peak of viremia of one week. These results demonstrate that M48U1 miniCD4 acts in vivo as a potent entry inhibitor, which may be considered in microbicide developments.

Relative displacement method for track-structure interaction.

The track-structure interaction effects are usually analysed with conventional FEM programs, where it is difficult to implement the complex track-structure connection behaviour, which is nonlinear, elastic-plastic and depends on the vertical load. The authors developed an alternative analysis method, which they call the relative displacement method. It is based on the calculation of deformation states in single DOF element models that satisfy the boundary conditions. For its solution, an iterative optimisation algorithm is used. This method can be implemented in any programming language or analysis software. A comparison with ABAQUS calculations shows a very good result correlation and compliance with the standard's specifications.

Linguistic Disparities in Diabetes Care Quality in California Community Health Centers Before and During the COVID-19 Pandemic.

BACKGROUND: Disparities in diabetes care quality may have increased for patients with limited English language proficiency (LEP) compared to non-LEP patients during the COVID-19 pandemic. Changes in diabetes care quality for adult LEP and non-LEP patients of community health centers (CHCs) were examined from 2019 to 2020. METHODS: Adults with Type 2 diabetes (n = 15 965) of 88 CHC sites in California and with 1+ visit/year in 2019 and 2020 from OCHIN electronic health record data were included. Multivariable regression models estimated the association of LEP status and changes in diabetes care quality from 2019 to 2020, controlling for patient sociodemographic and clinical characteristics. Interaction terms (LEP × 2020) were used to estimate differential over time changes in (1) blood pressure screening, (2) blood pressure control (<140/90 mm Hg), and (3) hemoglobin A1c control (HbA1c <8%) for LEP versus non-LEP patients. RESULTS: LEP and non-LEP patients with diabetes had comparable blood pressure screening and control in 2019 and in 2020. LEP patients were less likely than non-LEP patients to have their HbA1c under control in 2019 (OR = 0.85, 95% CI = 0.77, 0.96, P = .006) and 2020 (OR = 0.83, 95% CI = 0.75, 0.92, P = .001). There were no differential changes in HbA1c control over time for LEP and non-LEP patients. DISCUSSION: Although LEP patients were less likely than non-LEP patients to have their HbA1c under control, CHCs maintained quality of care equally for LEP and non-LEP patients with diabetes during the early pandemic period.

Insights into PCSK9-LDLR Regulation and Trafficking via the Differential Functions of MHC-I Proteins HFE and HLA-C.

PCSK9 is implicated in familial hypercholesterolemia via targeting the cell surface PCSK9-LDLR complex toward lysosomal degradation. The M2 repeat in the PCSK9's C-terminal domain is essential for its extracellular function, potentially through its interaction with an unidentified "protein X". The M2 repeat was recently shown to bind an R-x-E motif in MHC-class-I proteins (implicated in the immune system), like HLA-C, and causing their lysosomal degradation. These findings suggested a new role of PCSK9 in the immune system and that HLA-like proteins could be "protein X" candidates. However, the participation of each member of the MHC-I protein family in this process and their regulation of PCSK9's function have yet to be determined. Herein, we compared the implication of MHC-I-like proteins such as HFE (involved in iron homeostasis) and HLA-C on the extracellular function of PCSK9. Our data revealed that the M2 domain regulates the intracellular sorting of the PCSK9-LDLR complex to lysosomes, and that HFE is a new target of PCSK9 that inhibits its activity on the LDLR, whereas HLA-C enhances its function. This work suggests the potential modulation of PCSK9's functions through interactions of HFE and HLA-C.

Ultrasound-assisted extraction of bioactive compounds from goji berries: Optimization, bioactivity, and intestinal permeability assessment.

Lycium barbarum L. berries have a remarkable chemical composition and extensive biological activities, being a valuable component of health and nutraceutical practices. Nevertheless, a deep insight on the intestinal permeation of the pro-healthy bioactive compounds is urgently needed to predict the real effects on human body. This study attempted, for the first time, to optimize the Ultrasound-Assisted Extraction (UAE) of goji berries using a Response Surface Methodology approach and establish the intestinal permeation of the principal pro-healthy compounds. The optimal extraction conditions were a solid:liquid ratio of 8.75 % for 56.21 min, using an intensity of 59.05 W/m2. The optimal extract displayed a remarkable antioxidant capacity, with LC/DAD-ESI-MS analysis unveiled a diverse phytochemical profile, encompassing different compounds (e.g. glu-lycibarbarspermidine F, 2-glu-kukoamine, rutin, 3,5-dicaffeoylquinic acid). The intestinal co-culture model demonstrated that glu-lycibarbarspermidine F (isomer 2) (73.70 %), 3,5-dicaffeoylquinic acid (52.66 %), and isorhamnetin-3-O-rutinoside (49.31 %) traversed the intestinal cell layer, exerting beneficial health-promoting effects.

Circular economyeast: Saccharomyces cerevisiae as a sustainable source of glucans and its safety for skincare application.

Glucans, a polysaccharide naturally present in the yeast cell wall that can be obtained from side streams generated during the fermentation process, have gained increasing attention for their potential as a skin ingredient. Therefore, this study focused on the extraction method to isolate and purify water-insoluble glucans from two different Saccharomyces cerevisiae strains: an engineered strain obtained from spent yeast in an industrial fermentation process and a wild strain produced through lab-scale fermentation. Two water-insoluble extracts with a high glucose content (> 90 %) were achieved and further subjected to a chemical modification using carboxymethylation to improve their water solubility. All the glucans' extracts, water-insoluble and carboxymethylated, were structurally and chemically characterized, showing almost no differences between both yeast-type strains. To ensure their safety for skin application, a broad safety assessment was undertaken, and no cytotoxic effect, immunomodulatory capacity (IL-6 and IL-8 regulation), genotoxicity, skin sensitization, and impact on the skin microbiota were observed. These findings highlight the potential of glucans derived from spent yeast as a sustainable and safe ingredient for cosmetic and skincare formulations, contributing to the sustainability and circular economy.

High throughput screening identifies disulfide isomerase DsbC as a very efficient partner for recombinant expression of small disulfide-rich proteins in E. coli.

BACKGROUND: Disulfide-rich proteins or DRPs are versatile bioactive compounds that encompass a wide variety of pharmacological, therapeutic, and/or biotechnological applications. Still, the production of DRPs in sufficient quantities is a major bottleneck for their complete structural or functional characterization. Recombinant expression of such small proteins containing multiple disulfide bonds in the bacteria E. coli is considered difficult and general methods and protocols, particularly on a high throughput scale, are limited. RESULTS: Here we report a high throughput screening approach that allowed the systematic investigation of the solubilizing and folding influence of twelve cytoplasmic partners on 28 DRPs in the strains BL21 (DE3) pLysS, Origami B (DE3) pLysS and SHuffle® T7 Express lysY (1008 conditions). The screening identified the conditions leading to the successful soluble expression of the 28 DRPs selected for the study. Amongst 336 conditions tested per bacterial strain, soluble expression was detected in 196 conditions using the strain BL21 (DE3) pLysS, whereas only 44 and 50 conditions for soluble expression were identified for the strains Origami B (DE3) pLysS and SHuffle® T7 Express lysY respectively. To assess the redox states of the DRPs, the solubility screen was coupled with mass spectrometry (MS) to determine the exact masses of the produced DRPs or fusion proteins. To validate the results obtained at analytical scale, several examples of proteins expressed and purified to a larger scale are presented along with their MS and functional characterization. CONCLUSIONS: Our results show that the production of soluble and functional DRPs with cytoplasmic partners is possible in E. coli. In spite of its reducing cytoplasm, BL21 (DE3) pLysS is more efficient than the Origami B (DE3) pLysS and SHuffle® T7 Express lysY trxB(-)/gor(-) strains for the production of DRPs in fusion with solubilizing partners. However, our data suggest that oxidation of the proteins occurs ex vivo. Our protocols allow the production of a large diversity of DRPs using DsbC as a fusion partner, leading to pure active DRPs at milligram scale in many cases. These results open up new possibilities for the study and development of DRPs with therapeutic or biotechnological interest whose production was previously a limitation.

Modeling of the hypothalamic-pituitary-adrenal axis-mediated interaction between the serotonin regulation pathway and the stress response using a Boolean approximation: a novel study of depression.

Major depressive disorder (MDD) is a multifactorial disorder known to be influenced by both genetic and environmental factors. MDD presents a heritability of 37%, and a genetic contribution has also been observed in studies of family members of individuals with MDD that imply that the probability of suffering the disorder is approximately three times higher if a first-degree family member is affected. Childhood maltreatment and stressful life events (SLEs) have been established as critical environmental factors that profoundly influence the onset of MDD. The serotonin pathway has been a strong candidate for genetic studies, but it only explains a small proportion of the heritability of the disorder, which implies the involvement of other pathways. The serotonin (5-HT) pathway interacts with the stress response pathway in a manner mediated by the hypothalamic-pituitary-adrenal (HPA) axis. To analyze the interaction between the pathways, we propose the use of a synchronous Boolean network (SBN) approximation. The principal aim of this work was to model the interaction between these pathways, taking into consideration the presence of selective serotonin reuptake inhibitors (SSRIs), in order to observe how the pathways interact and to examine if the system is stable. Additionally, we wanted to study which genes or metabolites have the greatest impact on model stability when knocked out in silico. We observed that the biological model generated predicts steady states (attractors) for each of the different runs performed, thereby proving that the system is stable. These attractors changed in shape, especially when anti-depressive drugs were also included in the simulation. This work also predicted that the genes with the greatest impact on model stability were those involved in the neurotrophin pathway, such as CREB, BDNF (which has been associated with major depressive disorder in a variety of studies) and TRkB, followed by genes and metabolites related to 5-HT synthesis.

[Protection against ionizing radiation by leaded glass googles during interventional cardiology]. / ¿Es suficiente la protección otorgada por gafas plomadas en cardiología intervencionista?

BACKGROUND: It is not known whether leaded glass goggles with 0.25 mm Pb equivalency, used in interventional cardiology procedures, attenuate radiation below the levels established by the latest recommendation of the International Commission on Radiological Protection (ICRP). AIM: To assess if the degree of attenuation of the secondary ionizing radiation achieved by the use of 0.25 mm Pb leaded glass goggles, in occupationally exposed workers in interventional cardiology procedures, meets the latest ICRP recommendations. MATERIAL AND METHODS: A prospective investigation was carried out to compare the eye exposure to secondary ionizing radiation received by occupationally exposed personnel in a 9 months period. A set of two thermo luminescent dosimeters was arranged in the front and back of leaded glass goggles in a cohort of seven members of an interventional cardiology service, exposed to 1057 consecutive procedures. RESULTS: The monthly dose equivalent measurement performed in front of the goggles ranged between 1.1 and 6.5 mSv, for paramedics and interventional cardiologists. The radiation measured in the back of the glass varied between 0.66 and 2.75 mSv, respectively. The degree of attenuation of the dose at eye level ranged from 40% to 57.7%, respectively. The projected annual exposure would reach 33 mSv for the interventional cardiologist. CONCLUSIONS: With a similar load of work and wearing 0.25 mm Pb equivalent glass goggles, interventional cardiologists will exceed the crystalline equivalent dose limit recommended by the ICRP (20 mSv/year averaged over the past 5 years).