Scalable live-attenuated SARS-CoV-2 vaccine candidate demonstrates preclinical safety and efficacy.

Successfully combating the COVID-19 pandemic depends on mass vaccination with suitable vaccines to achieve herd immunity. Here, we describe COVI-VAC, the only live attenuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine currently in clinical development. COVI-VAC was developed by recoding a segment of the viral spike protein with synonymous suboptimal codon pairs (codon-pair deoptimization), thereby introducing 283 silent (point) mutations. In addition, the furin cleavage site within the spike protein was deleted from the viral genome for added safety of the vaccine strain. Except for the furin cleavage site deletion, the COVI-VAC and parental SARS-CoV-2 amino acid sequences are identical, ensuring that all viral proteins can engage with the host immune system of vaccine recipients. COVI-VAC was temperature sensitive in vitro yet grew robustly (>107 plaque forming units/mL) at the permissive temperature. Tissue viral loads were consistently lower, lung pathology milder, and weight loss reduced in Syrian golden hamsters (Mesocricetus auratus) vaccinated intranasally with COVI-VAC compared to those inoculated with wild-type (WT) virus. COVI-VAC inoculation generated spike IgG antibody levels and plaque reduction neutralization titers similar to those in hamsters inoculated with WT virus. Upon challenge with WT virus, COVI-VAC vaccination reduced lung challenge viral titers, resulted in undetectable virus in the brain, and protected hamsters from almost all SARS-CoV-2-associated weight loss. Highly attenuated COVI-VAC is protective at a single intranasal dose in a relevant in vivo model. This, coupled with its large-scale manufacturing potential, supports its potential use in mass vaccination programs.

Protein Adsorption on Mixed Self-Assembled Monolayers: Influence of Chain Length and Terminal Group.

Mixed self-assembled monolayers (SAMs) are often used as highly tunable substrates for biomedical and biosensing applications. It is well documented, however, that mixed SAMs can be highly disordered at the molecular level and do not pack as closely or homogeneously as single-component SAMs, particularly when the chain lengths and head groups of the SAM thiol components are significantly different. In this study, we explore the impact of SAM structure and mixing ratio (-OH and -CH3 termini) on the weak physisorption behavior of bovine serum albumin (BSA), which adsorbs more readily to hydrophobic, methyl-terminated SAMs. Our results suggest that once the mixture includes 50% or more of the methyl terminus, the mixing ratio alone is a relatively good predictor of adsorption, regardless of the relative chain lengths of the thiols used in the mixture. This trend persists at any mixing ratio for SAMs where methyl- and hydroxyl-terminated groups are the same length or where the hydroxyl-terminated thiol is longer. The only variance observed is at low mixing ratios (<50% methyl-terminated) for a mixed SAM where the methyl-terminated component has a longer chain length. Relative protein adsorption increases on these mixtures, perhaps due to the disordered exposure of the excess alkane backbone. Taken together, however, we do not find significant evidence that varying chain lengths for mixed SAMs prepared on polycrystalline substrates and analyzed in air have an outsized influence on nanoscopic adsorption behavior, despite molecular-level disorder in the SAM itself.

Induction of programmed cell death in Trypanosoma cruzi by Lippia alba essential oils and their major and synergistic terpenes (citral, limonene and caryophyllene oxide).

BACKGROUND: Chagas Disease caused by Trypanosoma cruzi infection, is one of the most important neglected tropical diseases (NTD), without an effective therapy for the successful parasite eradication or for the blocking of the disease's progression, in its advanced stages. Due to their low toxicity, wide pharmacologic spectrum, and potential synergies, medicinal plants as Lippia alba, offer a promising reserve of bioactive molecules. The principal goal of this work is to characterize the inhibitory properties and cellular effects of the Citral and Carvone L. alba chemotype essential oils (EOs) and their main bioactive terpenes (and the synergies among them) on T. cruzi forms. METHODS: Twelve L. alba EOs, produced under diverse environmental conditions, were extracted by microwave assisted hydrodistillation, and chemically characterized using gas chromatography coupled mass spectrometry. Trypanocidal activity and cytotoxicity were determined for each oil, and their major compounds, on epimastigotes (Epi), trypomastigotes (Tryp), amastigotes (Amas), and Vero cells. Pharmacologic interactions were defined by a matrix of combinations among the most trypanocidal terpenes (limonene, carvone; citral and caryophyllene oxide). The treated cell phenotype was assessed by fluorescent and optic microscopy, flow cytometry, and DNA electrophoresis assays. RESULTS: The L. alba EOs displayed significant differences in their chemical composition and trypanocidal performance (p = 0.0001). Citral chemotype oils were more trypanocidal than Carvone EOs, with Inhibitory Concentration 50 (IC50) of 14 ± 1.5 µg/mL, 22 ± 1.4 µg/mL and 74 ± 4.4 µg/mL, on Epi, Tryp and Amas, respectively. Limonene exhibited synergistic interaction with citral, caryophyllene oxide and Benznidazole (decreasing by 17 times its IC50) and was the most effective and selective treatment. The cellular analysis suggested that these oils or their bioactive terpenes (citral, caryophyllene oxide and limonene) could be inducing T. cruzi cell death by an apoptotic-like mechanism. CONCLUSIONS: EOs extracted from L. alba Citral chemotype demonstrated significant trypanocidal activity on the three forms of T. cruzi studied, and their composition and trypanocidal performance were influenced by production parameters. Citral, caryophyllene oxide, and limonene showed a possible induction of an apoptotic-like phenotype. The best selective anti-T. cruzi activity was achieved by limonene, the effects of which were also synergic with citral, caryophyllene oxide and benznidazole.

Dopamine-dependent long-term depression at subthalamo-nigral synapses is lost in experimental parkinsonism.

Impairments of synaptic plasticity are a hallmark of several neurological disorders, including Parkinson's disease (PD) which results from the progressive loss of dopaminergic neurons of the substantia nigra pars compacta leading to abnormal activity within the basal ganglia (BG) network and pathological motor symptoms. Indeed, disrupted plasticity at corticostriatal glutamatergic synapses, the gateway of the BG, is correlated to the onset of PD-related movement disorders and thus has been proposed to be a key neural substrate regulating information flow and motor function in BG circuits. However, a critical question is whether similar plasticity impairments could occur at other glutamatergic connections within the BG that would also affect the inhibitory influence of the network on the motor thalamus. Here, we show that long-term plasticity at subthalamo-nigral glutamatergic synapses (STN-SNr) sculpting the activity patterns of nigral neurons, the main output of the network, is also affected in experimental parkinsonism. Using whole-cell patch-clamp in acute rat brain slices, we describe a molecular pathway supporting an activity-dependent long-term depression of STN-SNr synapses through an NMDAR-and D1/5 dopamine receptor-mediated endocytosis of synaptic AMPA glutamate receptors. We also show that this plastic property is lost in an experimental rat model of PD but can be restored through the recruitment of dopamine D1/5 receptors. Altogether, our findings suggest that pathological impairments of subthalamo-nigral plasticity may enhance BG outputs and thereby contribute to PD-related motor dysfunctions.

Microencapsulation of Theobroma cacao L polyphenols: A high-value approach with in vitro anti-Trypanosoma cruzi, immunomodulatory and antioxidant activities.

Chagas disease (CHD) is the highest economic burden parasitosis worldwide and the most important cardiac infection, without therapeutic alternatives to halt or reverse its progression. In CHD-experimental models, antioxidant and anti-inflammatory compounds have demonstrated therapeutic potential in cardiac dysfunction. Theobroma cacao polyphenols are potent natural antioxidants with cardioprotective and anti-inflammatory action, which are susceptible to degradation, requiring technological approaches to guarantee their protection, stability, and controlled release. Here, 21 cocoa polyphenol-rich microencapsulates were produced by spray-drying and freeze-drying techniques using two wall materials (maltodextrin and gum arabic). Chemical (total and individual phenolic content and antioxidant activity), structural (morphology), and biological parameters (cytotoxicity, trypanocidal, antioxidant, and immunomodulatory activities) were assessed to determine the most efficient microencapsulation conditions on Trypanosoma cruzi-infected myocardioblast and macrophage cells. Significant antiproliferative properties against infected cells (superior to benznidazole) were found in two microencapsulates which also exhibited cardioprotective properties against oxidative stress, inflammation, and cell death.

Clinical predictors for mechanical ventilation assistance in Guillain-Barré syndrome.

Background: Guillain-Barré syndrome (GBS) frequently leads to respiratory failure and autonomic dysfunction, resulting in approximately one-third of patients requiring mechanical ventilation. Objective: This study aimed to identify clinical predictors for mechanical ventilation in patients with GBS. Methods: This research was conducted from 2010 to 2021 using registries from a tertiary hospital in an upper middle-income Latin American country. Participants were categorized into two groups based on their ventilation status. Demographic data were collected, and independent predictors of the need for mechanical ventilation were determined through multivariate logistic regression analysis. Results: Dysautonomic events occurred in 36% of the patients, with 17% requiring mechanical ventilation; the average duration of intubation was 1.16 ± 3.18 days. The multivariate analysis indicated that bulbar dysfunction significantly increased the likelihood of requiring mechanical ventilation by 19-fold (OR 18.67, 95% CI 5.85-59.42), followed by ophthalmoplegia, which increased the likelihood by sixfold (OR 5.68, 95% CI 1.28-25.19). Conclusion: Bulbar dysfunction, dysautonomia, and lower Medical Research Council (MRC) scores were significant predictors of the need for mechanical ventilation in hospitalized GBS patients. These findings support the need for close monitoring and early admission to the intensive care unit (ICU) admission for at-risk patients.

Citral-rich fractions of Lippia alba essential oils as immunoresponsive and anti-Candida albicans additives for collagen membranes in guided bone regeneration.

PURPOSE: The aim of this study was to optimize the immunoresponsive and anti-Candida albicans (C. albicans) properties of guided bone regeneration-resorbable membranes (collagen) using additives based on synergistic mixtures of chlorhexidine with terpene-enriched fractions from Lippia alba essential oils (EO). METHODS: The anti-C. albicans activity of the fractions (individually or combined with chlorhexidine) was evaluated using planktonic and sessile cultures. J774A.1 murine macrophage cells were used to determine the cytotoxicity and immunoresponsive effects of the therapies. RESULTS: The anti-planktonic and anti-sessile performance of chlorhexidine on C. albicans was improved 2- to 4-fold by supplementation with citral-rich fractions. On macrophages, this fraction also exhibited a potentially cytoprotective action against the toxic effects of chlorhexidine, minimizing damage to the cell membrane, mitochondrial membrane potential, and nuclear integrity. Macrophages growing on collagen-membrane fragments and stimulated with the citral fraction (alone or with chlorhexidine) showed a significant increase in releasing the osteogenic cytokine TNF-α and enhancing the IL-4. CONCLUSION: This combined therapy appears as a promising platform for the development of a prophylactic or therapeutic biocidal solution that can optimize the pharmacological characteristics of chlorhexidine (epithelium tolerance and anti-C. albicans consolidation on surfaces), as well as potentiating the immunoresponsive properties of collagen membranes.

Lippia origanoides Essential Oil or Thymol in Combination with Fluconazole Produces Damage to Cells and Reverses the Azole-Resistant Phenotype of a Candida tropicalis Strain.

Candida tropicalis is one of the most pathogenic species within the genus. Increased antifungal resistance has been reported, which is in part due to the organism's ability to form biofilms. In natural products derived from plants, such as essential oils (EOs) or their major components, there is significant potential to develop new antifungals or to both enhance the efficacy and reduce the toxicity of conventional antifungals. This study aimed to evaluate the effect of combining an EO of Lippia origanoides or thymol with fluconazole on an azole-resistant C. tropicalis strain. Synergism was observed in the combination of fluconazole with the EO and with thymol, and minimal inhibitory concentrations for fluconazole decreased at least 32-fold. As a consequence of the synergistic interactions, mitochondrial membrane potential was reduced, and mitochondrial superoxide production increased. Alteration in nuclear morphology, cell surface, and ultrastructure was also observed. In conclusion, the synergistic interaction between L. origanoides EO or thymol with fluconazole reverted the azole-resistant C. tropicalis phenotype. These findings suggest that L. origanoides EO or thymol alone, or in combination with fluconazole, have the potential for development as antifungal therapies for this yeast, including resistant strains.

Cognitive and executive functions in ADHD.

INTRODUCTION: Some studies have reported that attention-deficit/hyperactivity disorder (ADHD) children show alterations in different cognitive functions. Recently, a deficiency in the executive functions (EF) is proposed as the cause underlying all of these symptoms. However discrepancies exist about these findings. OBJECTIVE: Assessment of cognitive and executive functions of subjects with both ADHD hyperactive-impulsive type and combined type, in order to reveal their neuropsychological characteristics and analyze if those functions are related to hyperactive-impulsive behavior. METHOD: Neuropsychological Battery, Stroop test, Wisconsin Card Sorting test and London Tower test were applied to 51 children between 7 and 12 years old (25 controls and 26 ADHD). RESULTS: ADHD children showed worst performance in sustained attention, rapid serial naming of figures and colors, comprehension of written instructions, word dictation, number comparison, arithmetical problems, visual working memory, long term memory and the scores of WCST. Variables related to hyperactivity-impulsivity were: errors and decreased velocity in rapid serial naming of colors and figures, comprehension of written instructions, arithmetical problems and the scores of total errors, perseverating errors and perseverating responses of WCST. CONCLUSION: ADHD children show a great variety of cognitive deficiencies and had deficit only in some domains of executive functions. These deficiencies could explain to some extent the hyperactive and impulsive behavior.

Characterization of Three Variants of SARS-CoV-2 In Vivo Shows Host-Dependent Pathogenicity in Hamsters, While Not in K18-hACE2 Mice.

Animal models are used in preclinical trials to test vaccines, antivirals, monoclonal antibodies, and immunomodulatory drug therapies against SARS-CoV-2. However, these drugs often do not produce equivalent results in human clinical trials. Here, we show how different animal models infected with some of the most clinically relevant SARS-CoV-2 variants, WA1/2020, B.1.617.2/Delta, B.1.1.529/Omicron, and BA5.2/Omicron, have independent outcomes. We show that in K18-hACE2 mice, B.1.617.2 is more pathogenic, followed by WA1, while B.1.1.529 showed an absence of clinical signs. Only B.1.1.529 was able to infect C57BL/6J mice, which lack the human ACE2 receptor. B.1.1.529-infected C57BL/6J mice had different T cell profiles compared to infected K18-hACE2 mice, while viral shedding profiles and viral titers in lungs were similar between the K18-hACE2 and the C57BL/6J mice. These data suggest B.1.1.529 virus adaptation to a new host and shows that asymptomatic carriers can accumulate and shed virus. Next, we show how B.1.617.2, WA1 and BA5.2/Omicron have similar viral replication kinetics, pathogenicity, and viral shedding profiles in hamsters, demonstrating that the increased pathogenicity of B.1.617.2 observed in mice is host-dependent. Overall, these findings suggest that small animal models are useful to parallel human clinical data, but the experimental design places an important role in interpreting the data. Importance: There is a need to investigate SARS-CoV-2 variant phenotypes in different animal models due to the lack of reproducible outcomes when translating experiments to the human population. Our findings highlight the correlation of clinically relevant SARS-CoV-2 variants in animal models with human infections. Experimental design and understanding of correct animal models are essential to interpreting data to develop antivirals, vaccines, and other therapeutic compounds against COVID-19.

Responses of resources and consumers to experimental flow pulses in a temporary Mediterranean stream.

Determining the resistance and resilience of resources and benthic invertebrates connected to instream refuges and species re-colonization in post-flood periods may help to elucidate mechanisms behind community recovery. This experiment simulated flow pulses in a small temporary stream in an extremely wet year, using upstream control and downstream flooded reaches at three sites in order to assess community resistance and resilience (benthos and drift), and analyse resources (periphyton and benthic organic matter) and invertebrates at pre- and post-flood time periods. The hyporheos was sampled in order to explore species exchanges with benthos. Fewer resources and benthic invertebrates at the beginning of the experiment were found than in previous studies when base flow conditions prevailed. Resource stocks and benthic invertebrates showed high resistance to the flow pulse. Interestingly, there was low resilience of benthic organic matter to natural seasonal flooding. Chlorophyll a did not recover after experimental floods; instead, it was reduced after floods, despite the more benign flow conditions and non-limiting irradiance levels, pointing to top-down control by consumers. Additionally, the experimental flood significantly disturbed only the invertebrate composition in the groundwater-fed stream, which was inhabited by the fewest adapted-to-flood-disturbances macroinvertebrates. Despite the low resilience observed, richness and densities of benthos increased during the study, evidencing progressive colonization. Around 50-60% of macroinvertebrates were present in both benthos and hyporheos. Richness increased after flooding, suggesting that the hyporheic zone could be the main source of colonizers. Three species traits characterized the hyporheos: small size, cocoons and feeders of microorganisms within the fine sediment matrix. The main results indicate that longer-than-normal flood periods in early spring may constrain invertebrate succession before the next summer drought in temporary streams. This study underscores the importance of hyporheic fauna as a significance source of colonizers, highlighting the importance of connectivity to the groundwater.

Immunomodulatory, trypanocide, and antioxidant properties of essential oil fractions of Lippia alba (Verbenaceae).

BACKGROUND: Parasite persistence, exacerbated and sustained immune response, and continuous oxidative stress have been described to contribute to the development of the cardiac manifestations in Chronic Chagas Disease. Nevertheless, there are no efficient therapies to resolve the Trypanosoma cruzi infection and prevent the disease progression. Interestingly, trypanocide, antioxidant, and immunodulatory properties have been reported separately for some major terpenes, as citral (neral plus geranial), limonene, and caryophyllene oxide, presents in essential oils (EO) extracted from two chemotypes (Citral and Carvone) of Lippia alba. The aim of this study was to obtain L. alba essential oil fractions enriched with the aforementioned bioactive terpenes and to evaluate the impact of these therapies on trypanocide, oxidative stress, mitochondrial bioenergetics, genotoxicity, and inflammatory markers on T. cruzi-infected macrophages. METHODS: T. cruzi-infected J774A.1 macrophage were treated with limonene-enriched (ACT1) and citral/caryophyllene oxide-enriched (ACT2) essential oils fractions derived from Carvone and Citral-L. alba chemotypes, respectively. RESULTS: ACT1 (IC50 = 45 ± 1.7 µg/mL) and ACT2 (IC50 = 80 ± 1.9 µg/mL) exhibit similar trypanocidal effects to Benznidazole (BZN) (IC50 = 48 ± 2.5 µg/mL), against amastigotes. Synergistic antiparasitic activity was observed when ACT1 was combined with BZN (∑FIC = 0.52 ± 0.13 µg/mL) or ACT2 (∑FIC = 0.46 ± 1.7 µg/mL). ACT1 also decreased the oxidative stress, mitochondrial metabolism, and genotoxicity of the therapies. The ACT1 + ACT2 and ACT1 + BZN experimental treatments reduced the pro-inflammatory cytokines (IFN-γ, IL-2, and TNF-α) and increased the anti-inflammatory cytokines (IL-4 and IL-10). CONCLUSION: Due to its highly trypanocidal and immunomodulatory properties, ACT1 (whether alone or in combination with BZN or ACT2) represents a promising L. alba essential oil fraction for further studies in drug development towards the Chagas disease control.

Effect of Distracting Background Speech in an Auditory Brain-Computer Interface.

Studies so far have analyzed the effect of distractor stimuli in different types of brain-computer interface (BCI). However, the effect of a background speech has not been studied using an auditory event-related potential (ERP-BCI), a convenient option when the visual path cannot be adopted by users. Thus, the aim of the present work is to examine the impact of a background speech on selection performance and user workload in auditory BCI systems. Eleven participants tested three conditions: (i) auditory BCI control condition, (ii) auditory BCI with a background speech to ignore (non-attentional condition), and (iii) auditory BCI while the user has to pay attention to the background speech (attentional condition). The results demonstrated that, despite no significant differences in performance, shared attention to auditory BCI and background speech required a higher cognitive workload. In addition, the P300 target stimuli in the non-attentional condition were significantly higher than those in the attentional condition for several channels. The non-attentional condition was the only condition that showed significant differences in the amplitude of the P300 between target and non-target stimuli. The present study indicates that background speech, especially when it is attended to, is an important interference that should be avoided while using an auditory BCI.

Knowledge, Attitude, and Practice (KAP) Survey toward Skin Cancer among Ecuadorian Population.

BACKGROUND: Skin cancer is one of the most common cancers, and melanoma is a highly preventable cancer. In Ecuador, few studies have evaluated the awareness levels of the population about the disease. For this reason, the objective of this study was to measure the level of knowledge, attitudes, and practices regarding skin cancer and its determining factors. METHODS: A cross-sectional analysis using an online self-assessment questionnaire containing 40 questions was delivered. A total of 537 participants were included in this study. Knowledge, attitude, and practice scores were assigned to each participant based on the number of correct or appropriate responses. Logistic regression analysis was used to calculate crude and adjusted odds ratios. RESULTS: In total, 75% of participants referenced knowledge of the harmful effects related to noncontrolled solar exposure. Concerning sunscreen, 76.7% knew the reason for using it. The female group was 1.68 times more likely to get a higher score than the male group, and the groups between 61-70 and 71-80 years were 0.30 and 0.17 times less likely to get a higher score compared with the less than 20-years-old group, respectively. CONCLUSIONS: The findings of this study indicate the requirement to increase the population's knowledge about skin cancer and possible protection measures. For this reason, the prevention and health promotion programs at a national level from primary healthcare centers are recommended. Due to the limitation of the representativeness of the sample, the use of more studies among Ecuadorian residents of the low socioeconomic level and replication in different provinces of Ecuador is justified.

Marine litter arrived: Distribution and potential sources on an unpopulated atoll in the Seaflower Biosphere Reserve, Caribbean Sea.

The Albuquerque atoll was studied as a representative natural laboratory to explore the role of sea-based sources of marine litter. This work aimed to identify the small-scale spatial distribution of marine litter (i.e., plastic, glass, paper, and others) as well as to explore the connectivity among the atoll habitats (sand beach, water surface, and reef) to give insights of potential sources of marine litter (>5 cm), mainly plastics. Marine litter was dominated by plastic items, as expected, with an average value of 0.5 items/m2. Large microplastics (1-5 mm) were also sampled on beaches with an average value of 90 particles/m2. In the atoll inner lagoon, marine litter was also composed by plastic, mainly fragments (average 0.059 items/m3). The predominance of plastic fragments on both the sea surface and beaches of the atoll makes inferences on sources limited. However, o fishing activities and sea-based sources might be relevant since local sources are very limited.

Performance Analysis With Different Types of Visual Stimuli in a BCI-Based Speller Under an RSVP Paradigm.

Brain-Computer Interface (BCI) systems enable an alternative communication channel for severely-motor disabled patients to interact with their environment using no muscular movements. In recent years, the importance of research into non-gaze dependent brain-computer interface paradigms has been increasing, in contrast to the most frequently studied BCI-based speller paradigm (i.e., row-column presentation, RCP). Several visual modifications that have already been validated under the RCP paradigm for communication purposes have not been validated under the most extended non-gaze dependent rapid serial visual presentation (RSVP) paradigm. Thus, in the present study, three different sets of stimuli were assessed under RSVP, with the following communication features: white letters (WL), famous faces (FF), neutral pictures (NP). Eleven healthy subjects participated in this experiment, in which the subjects had to go through a calibration phase, an online phase and, finally, a subjective questionnaire completion phase. The results showed that the FF and NP stimuli promoted better performance in the calibration and online phases, being slightly better in the FF paradigm. Regarding the subjective questionnaires, again both FF and NP were preferred by the participants in contrast to the WL stimuli, but this time the NP stimuli scored slightly higher. These findings suggest that the use of FF and NP for RSVP-based spellers could be beneficial to increase information transfer rate in comparison to the most frequently used letter-based stimuli and could represent a promising communication system for individuals with altered ocular-motor function.

5'UTR methylation in different genes from workers exposed to volatile organic compounds: A new insight for considering an epigenetic mark as a functional correlate.

Gene-specific methylation has been related with transcriptional/translational consequences in different cells; also, this epigenetic modification is affected by environmental exposures. In previous studies, CYP2E1 activity in toluene-exposed workers was decreased compared to controls, however, CYP2E1 promoter methylation levels did not show significant differences. Here, we compared gene-specific methylation levels at the 5'UTR region, in a subset of workers whom already participated in two former studies, compared to controls. METHODS: DNA was obtained from whole blood in five different groups: occupationally exposed to a mixture of volatile organic compounds (VOC): high levels (n = 19); low levels (n = 19) and very low levels (n = 17), toluene-exposed workers (n = 19) and control group (n = 19). We performed PCR-pyrosequencing at the 5'UTR region from four genes: CYP2E1, IL-6, SOD1 and TNF-α. RESULTS: In participants exposed to high levels of a VOC mixture, we found significant differences: lower methylation levels for IL-6, and higher methylation levels for TNF-α compared to controls. In toluene-exposed workers, we found significant, lower methylation levels for CYP2E1 compared to controls. CONCLUSION: Lower methylation levels at the 5'UTR region from CYP2E1 in toluene exposed-workers, suggests that this epigenetic modification could represent a functional correlate regarding enzymatic activity, as a response to toluene biotransformation.

Possible role of n-hexane as an endocrine disruptor in occupationally exposed women at reproductive age.

Human exposure to n-hexane has been associated with subfertility and, experimentally, with a decrease in follicular development. In order to assess occupational exposure to n-hexane on ovarian function and gonadotropic hormones, we studied Mexican women labouring in a leather shoe factory (n = 34). Individual environmental levels for seven solvents, n-hexane included, were measured; also, urinary 2,5-hexanedione (2,5-HD) was determined. For ovarian function and hormonal status, FSH, LH, oestradiol and anti-Müllerian hormone (AMH) levels were determined. We performed all determinations also in a reference group, administrative workers with no exposure to solvents (n = 32). Results: N-hexane and urinary 2,5-HD levels were higher in exposed group (p < 0.001). More cases of oligomenorrhea as well as longer time for getting pregnant were observed in exposed women compared with controls; a positive association was found between menstrual cycle length and "time for getting pregnant" (p = 0.010); significant associations between FSH serum levels and 2,5-HD urinary levels (post-shift sample) were observed in non-smokers participants presenting oligomenorrhea from exposed group. Also, we found a trend for lower oestradiol levels in exposed participants with current smoking habit (p = 0.059). Conclusions: 2,5-HD urinary levels are associated with decreased gonadotropins levels; hence, n-hexane should be considered an endocrine disruptor in reproductive-age women.

Nutritional assessment of female patients newly diagnosed with breast cancer in a northern region of Spain.

INTRODUCTION: Background: evidence from research suggests that the development of cancer disease is associated with environmental factors. There are few studies evaluating nutritional status in women suffering from cancer in Spain. Objectives: this study aimed to assess the nutritional status in breast cancer female patients at diagnosis in a northern region of Spain (Asturias), where breast cancer rates are particularly high when compared to the rest of Spain. Material and methods: a cross-sectional study was conducted in a sample of 76 newly diagnosed female cancer patients. Lifestyle factors, anthropometry, biochemical, and dietary intake data were collected immediately after diagnosis and prior to the initiation of the prescribed treatment. Results: a high percentage of these women diagnosed with cancer were sedentary (59.2%). Their average body mass index (BMI) was 27.3 ± 5.5 kg/m2. They also showed a high percentage of body fat, 38.3%, as well as a large waist circumference of 92.2 cm. Patients reported a low intake of fruits, vegetables, legumes, and nuts, and a high intake of red meat, meat products, and sweet foodstuffs as compared to the Spanish dietary guidelines (p < 0.01). Conclusion: the results showed a low intake of folate, calcium, and vitamin D, which is particularly relevant in women. In conclusion, these breast cancer patients showed overweight and high sedentarism levels, and reported unbalanced dietary patterns at the time of diagnosis.

INTRODUCCIÓN: Introducción: la evidencia actual indica que el desarrollo de algunos tipos de cáncer está asociado a factores ambientales. Pocos estudios realizados en España han evaluado el estado nutricional de las mujeres con cáncer. Objetivos: el objetivo de este estudio ha sido evaluar el estado nutricional de las mujeres en el momento de ser diagnosticadas de cáncer de mama (CM) en una región del norte de España (Asturias), donde las cifras de cáncer de mama son particularmente elevadas en comparación con el resto de España. Material y Métodos: se realizó un estudio transversal con una muestra de 76 mujeres recién diagnosticadas de cáncer de mama. Se recopilaron datos sobre su estilo de vida, antropometría, ingesta, bioquímica y dieta de forma inmediata tras el diagnóstico y antes del inicio del tratamiento. Resultados: un alto porcentaje de estas mujeres diagnosticadas de cáncer eran sedentarias (59,2%). El valor medio de su índice de masa corporal (IMC) era de 27,3 ± 5,5 kg/m2. Asimismo, estas pacientes mostraron un alto porcentaje de grasa corporal, del 38,3%, y un elevado perímetro de la cintura, de 92,2 cm. La dieta de todas las pacientes incluía una escasa ingesta de frutas, verduras, legumbres y frutos secos, y en cambio una ingesta elevada de carnes rojas y procesadas y alimentos dulces, en comparación con las recomendaciones dietéticas españolas (p < 0,01). Conclusión: los resultados mostraron unas escasas ingestas de folato, calcio y vitamina D, particularmente preocupantes en las mujeres. En conclusión, la mayoría de las voluntarias con CM presentaban sobrepeso, altos niveles de sedentarismo y un patrón de dieta no equilibrada en el momento del diagnóstico.

Protein Expression Analysis in Uterine Cervical Cancer for Potential Targets in Treatment.

Specific markers in lesions of the human uterine cervix cancer (UCC) are still needed for prognostic, diagnostic and/or therapeutic purposes. In this study we evaluated key molecules at protein level between normal epithelium, cervical intraepithelial neoplasia (CIN1-3) and invasive cancer of a group of molecules previously reported at mRNA level. For that purpose, human formalin-fixed paraffin embedded tissue microarrays (TMAs) were constructed containing 205 Mexican tissue core specimens. Immunohistochemistry and quantitative analysis of histological staining was performed against twenty-two distinct proteins for each core and the processing platform ImageJ. In the progression of the disease we found key statistical differences for the proteins SEL1, Notch3 and SOCS3. High expressions of SEL1L, Notch3 and SOCS3 have potential value to increase the prognostic of UCC in combination with markers such as p16INK4a. This study identified key drivers in cervical carcinogenesis that should be evaluated for the development of UCC therapies.