Epithelial-specific ERBB3 deletion results in a genetic background-dependent increase in intestinal and colon polyps that is mediated by EGFR.

ERBB3 has gained attention as a potential therapeutic target to treat colorectal and other types of cancers. To confirm a previous study showing intestinal polyps are dependent upon ERBB3, we generated an intestinal epithelia-specific ERBB3 deletion in C57BL/6-ApcMin/+ mice. Contrary to the previous report showing a significant reduction in intestinal polyps with ablation of ERBB3 on a B6;129 mixed genetic background, we observed a significant increase in polyp number with ablation of ERBB3 on C57BL/6J compared to control littermates. We confirmed the genetic background dependency of ERBB3 by also analyzing polyp development on B6129 hybrid and B6;129 advanced intercross mixed genetic backgrounds, which showed that ERBB3 deficiency only reduced polyp number on the mixed background as previously reported. Increased polyp number with ablation of ERBB3 was also observed in C57BL/6J mice treated with azoxymethane showing the effect is model independent. Polyps forming in absence of ERBB3 were generally smaller than those forming in control mice, albeit the effect was greatest in genetic backgrounds with reduced polyp numbers. The mechanism for differential polyp number in the absence of ERBB3 was through altered proliferation. Backgrounds with increased polyp number with loss of ERBB3 showed an increase in cell proliferation even in non-tumor epithelia, while backgrounds showing reduced polyp number with loss of ERBB3 showed reduced cellular proliferation. Increase polyp number caused by loss of ERBB3 was mediated by increased epidermal growth factor receptor (EGFR) expression, which was confirmed by deletion of Egfr. Taken together, this study raises substantial implications on the use of ERBB3 inhibitors against colorectal cancer. The prediction is that some patients may have increased progression with ERBB3 inhibitor therapy, which is consistent with observations reported for ERBB3 inhibitor clinical trials.

Extracellular Vesicles from Immune Cells: A Biomedical Perspective.

Research on the role of extracellular vesicles (sEV) in physiology has demonstrated their undoubted importance in processes such as the transportation of molecules with significance for cell metabolism, cell communication, and the regulation of mechanisms such as cell differentiation, inflammation, and immunity. Although the role of EVs in the immune response is actively investigated, there is little literature revising, in a comprehensive manner, the role of small EVs produced by immune cells. Here, we present a review of studies reporting the release of sEV by different types of leukocytes and the implications of such observations on cellular homeostasis. We also discuss the function of immune cell-derived sEV and their relationship with pathological states, highlighting their potential application in the biomedical field.

Analysis of drug of abuse compounds using passive sampling and ultrahigh-liquid chromatography coupled to mass spectrometry.

The present study proposes the monitoring of compounds of drugs of abuse through the use of passive samplers in water systems. Initially, four positive ion compounds of interest were determined according to national surveys, and then composite sampling and passive sampling were implemented using continuous-flow passive samplers containing two types of sorbents, the Empore disk and Gerstel Twister. Two study sites were established at the beginning and at the end of the middle Bogotá River basin. After 4 days, the sorbents were removed so that they could be desorbed and analyzed using UHPLC-MS in the laboratory. For the composite samples, the results were below the first calibration curve point (FCCP) of the chromatographic method, and for passive sampling, peaks of benzoylecgonine (BE) (21427.3 pg mL-1), methamphetamine (MET) (67101.5 pg mL-1), MDMA (ecstasy) (225844.8 pg mL-1) and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) (15908.4 pg mL-1) were found. Therefore, passive sampling could be suggested as an alternative to composite sampling for the monitoring of compounds.

A micro-CT analysis of radicular dentine thickness in mandibular first premolars presenting C-shaped root canals: Identification of potential danger zones.

AIM: To describe the radicular dentine thickness in mandibular first premolars presenting C-shaped root canals, to identify the canal walls with less thickness as potential danger zones. In addition, to describe the internal and external anatomical characteristics of these teeth and associate them with the dentine thickness. METHODOLOGY: A total of 70 mandibular first premolars presenting C-shaped root canals were examined. Their internal morphology was analysed using Vertucci's and Fan's criteria, and their external morphology was analysed using the ASUDAS score. Besides, the dentine thickness around the root canals was two/three-dimensionally determined at five root planes and quantified in the distal and the mesial aspects. RESULTS: According to Fan's, ASUDAS, and Vertucci's classifications, the most common canal configurations were category C3, grade 3, and type V, respectively. In Vertucci's type III anatomy, the mesial root wall of the lingual canal showed significantly less dentine thickness than the distal wall in the middle plane (p = .031). Similarly, in Vertucci's type V anatomy, significantly less dentine thickness was observed in the mesial root wall of the buccal and lingual canals in the middle plane (p < .001) and the buccal canal in the middle-apical plane (p = .014) than the distal root wall of these canals. In teeth with ASUDAS grade 3 and 4 scores, significantly less dentine thickness was observed in the mesial in comparison with the distal root wall of these canals. These differences were demonstrated in the middle and middle-apical planes (p < .001) of grade 3 teeth and the middle-apical plane (p < .001) of grade 4 teeth. In these root planes, the Ver1-AS3 and VerV-AS3 combinations presented a 4-times greater risk of presenting walls with a critical dentine thickness of 0.6 mm (odds ratio [OR] = 4, p = .025) than the combinations Ver1-AS2, VerV-AS2, VerV-AS4, and VerIII-AS3. CONCLUSIONS: The root canal system configuration of mandibular first premolars with C-shaped canals showed a wide range of anatomical variations. The lowest dentine thickness was located in the mesial wall of the canals in the middle and apical root thirds of Vertucci's type III and V anatomies and in teeth with deep radicular grooves scored as ASUDAS grades 3 and 4. In the middle and middle-apical planes, the presence of the combinations Ver1-AS3 and VerV-AS3 showed a high risk of presenting a critical dentine thickness of 0.6 mm. Therefore, these root canal walls with less dentine thickness represent potential instrumentation danger zones in mandibular first premolars with C-shaped canals.

Occurrence of leaf rust disease in Oxalis triangularis caused by Puccinia oxalidis in Valdivia, Chile.

False shamrock (Oxalis triangularis), native to South America, is an ornamental and popular plant bulb, commercialized for their attractive shape and color (purple triangular leaves) (Taha et al., 2013). In Chile, a rust was detected in O. triangularis plants growing from April to June in several gardens (n=10) in the city of Valdivia, estimating a disease incidence between 80 and 100%. The symptoms appeared as diffuse chlorotic spots from the upperside of leaves, where infected tissues eventually become completely necrotic, and yellow rust pustules were observed on the underside of leaves. Severe symptoms on infected leaves were consistently observed, showing necrosis on entire leaves. Symptomatic plants (n=50) were collected, and three representative isolates from different localities (OX1, OX2, and OX3) were used for morphological and genetic identification. Uredinia (n=20) were hypophyllous, erumpent, yellow, and irregularly distributed, with sizes from 340 to 850 µm in diameter. Urediniospores (n=150) were yellow, subglobose to globose, equinulate, with measures of 14.2 - 17.7 x 14.7 - 17.2 µm. Teliospores were absent. Based on morphological characters, this rust was identified as a Puccinia sp. These morphological characteristics coincided with those indicated by Safránková (2014), Abbasi et al. (2018), and Khouader et al. (2018). To classify this rust genetically, sequences analyses were performed using the ITS region of the rDNA (ITS4/ITS5) (White et al., 1990). The DNA was extracted using a commercial kit. The results indicated 99% similarity with two reference sequences of P. oxalidis (MH325473 and MH325474) available at GenBank (NCBI http://www.ncbi.nlm.nih.gov/BLAST/). The sequences obtained were deposited in GenBank (ON259085 to ON259087). Based on the maximum parsimony phylogenetic tree, the sequences of Chilean isolates were clustered with those of P. oxalidis references. Pathogenicity tests were conducted using three isolates (OX1 to OX3). Surface disinfection of leaves of O. triangularis (n=36 plants), were performed by spraying 1% NaOCl solution for 1 min. Subsequently, 2 mL of urediniospores suspensions of each isolate (OX1 to OX3) at a concentration of 106 urediniospores/mL, were sprayed with an atomizer on the underside of the leaves of all plants. Urediniospores were obtained following the methodology proposed by Ferrada et al. (2020). Control leaves were disinfested and inoculated with sterile distilled water. Plants of O. triangularis of 90-day-old were incubated in a humid chamber (24°C, 80% HR), with a photoperiod of 12 light /12 dark. At 11 days post-inoculation, all leaves inoculated developed chlorosis spots and pulverulent pustules (averaged 10.9 to 25.4 pustules per leaf), and then at 26 days post-inoculation, affected leaves showed necrotic tissues. The identity of these isolates was confirmed morphologically. The symptoms in the control leaves were negative. To our knowledge, this is the first report of multiple occurrences of the leaf rust disease on gardens of false shamrock caused by P. oxalidis in Valdivia, south of Chile. Previously, P. oxalidis has been reported to cause leaf rust disease in O. triangularis in the Czech Republic (Safránková, 2014) and O. debilis in Korea (Lee et al., 2018). The leaf rust disease could represent a threat to the ornamental gardens of O. triangularis in Valdivia. Currently, epidemiological studies of leaf rust disease are necessary to develop management strategies in gardens of O. triangularis.

Senescent CD4+CD28- T Lymphocytes as a Potential Driver of Th17/Treg Imbalance and Alveolar Bone Resorption during Periodontitis.

Senescent cells express a senescence-associated secretory phenotype (SASP) with a pro-inflammatory bias, which contributes to the chronicity of inflammation. During chronic inflammatory diseases, infiltrating CD4+ T lymphocytes can undergo cellular senescence and arrest the surface expression of CD28, have a response biased towards T-helper type-17 (Th17) of immunity, and show a remarkable ability to induce osteoclastogenesis. As a cellular counterpart, T regulatory lymphocytes (Tregs) can also undergo cellular senescence, and CD28- Tregs are able to express an SASP secretome, thus severely altering their immunosuppressive capacities. During periodontitis, the persistent microbial challenge and chronic inflammation favor the induction of cellular senescence. Therefore, senescence of Th17 and Treg lymphocytes could contribute to Th17/Treg imbalance and favor the tooth-supporting alveolar bone loss characteristic of the disease. In the present review, we describe the concept of cellular senescence; particularly, the one produced during chronic inflammation and persistent microbial antigen challenge. In addition, we detail the different markers used to identify senescent cells, proposing those specific to senescent T lymphocytes that can be used for periodontal research purposes. Finally, we discuss the existing literature that allows us to suggest the potential pathogenic role of senescent CD4+CD28- T lymphocytes in periodontitis.

Short run "rebound effect" of COVID on the transport carbon footprint.

The COVID-19 pandemic completely transformed the mobility of cities. The restrictions on movement led to "empty cities" throughout the world, with some environmental effects in terms of clean air and the reduction of CO2 emissions. This research considers how COVID-19 mobility restrictions have affected the carbon footprint of four medium-sized Chilean cities (Coronel, Temuco, Valdivia, and Osorno) that have environmental problems and are highly dependent on motorized systems. The study uses data from 2400 household surveys at three distinct times: pre-pandemic - T0 (winter 2019), the time of implementation of restrictive mobility policies to contain the pandemic - T1 (winter 2020), and six months later when those restrictions were gradually lifted - T2 (summer 2021). The analysis suggests that CO2 emissions actually went up, declining in the winter 2020, but then increasing with the greater use of cars in the summer 2021 due to the temporary effects of commuting to work, ultimately reaching levels higher than the pre-pandemic values, known as the "rebound effect."

Genetic differences in ethanol consumption: effects on iron, copper, and zinc regulation in mouse hippocampus.

One common characteristic of neurodegenerative diseases is dysregulation of iron, usually with observed increases in its concentration in various regions. Heavy alcohol consumption is believed to contribute to such iron dysregulation in the brain with accompanying dementia. To examine this effect and related genetic-based individual differences in an animal model, we subjected female mice from 12 BXD recombinant inbred strains to 16 weeks of alcohol consumption using the drinking in the dark (DID) method. Daily consumption was recorded and at the end of 16 weeks hippocampus tissues harvested. Concentrations of iron, copper and zinc were measured using X-ray fluorescence technology. The results showed that, DID increased iron overall across all strains, ranging from 3 to 68%. Copper and Zinc both decreased, ranging from 0.4-42 and 5-35% respectively. Analysis of variance revealed significant strain by treatment interactions for all three metals. Additionally, in the DID group, we observed strain differences in reduction of hippocampus mass. These findings are particularly interesting to us because high alcohol consumption in humans has been associated with neurodegeneration and dementia related to disruption of iron regulation. The findings of alcohol consumption associated decreases in copper and zinc are novel. The role of copper regulation and neurological function related to alcohol consumption is as yet largely unexplored. The role of zinc is better known as a neuromodulator in the hippocampus and appears to be protective against neurological damage. It would seem then, that the alcohol-related decrease in zinc in the hippocampus would be of concern and warrants further study.

Natural Killer T (NKT) Cells and Periodontitis: Potential Regulatory Role of NKT10 Cells.

Natural killer T (NKT) cells constitute a unique subset of T lymphocytes characterized by specifically interacting with antigenic glycolipids conjugated to the CD1d receptor on antigen-presenting cells. Functionally, NKT cells are capable of performing either effector or suppressor immune responses, depending on their production of proinflammatory or anti-inflammatory cytokines, respectively. Effector NKT cells are subdivided into three subsets, termed NKT1, NKT2, and NKT17, based on the cytokines they produce and their similarity to the cytokine profile produced by Th1, Th2, and Th17 lymphocytes, respectively. Recently, a new subgroup of NKT cells termed NKT10 has been described, which cooperates and interacts with other immune cells to promote immunoregulatory responses. Although the tissue-specific functions of NKT cells have not been fully elucidated, their activity has been associated with the pathogenesis of different inflammatory diseases with immunopathogenic similarities to periodontitis, including osteolytic pathologies such as rheumatoid arthritis and osteoporosis. In the present review, we revise and discuss the pathogenic characteristics of NKT cells in these diseases and their role in the pathogenesis of periodontitis; particularly, we analyze the potential regulatory role of the IL-10-producing NKT10 cells.

Interleukin-35 inhibits alveolar bone resorption by modulating the Th17/Treg imbalance during periodontitis.

AIM: T lymphocytes play a central role during the pathogenesis of periodontitis, and the imbalance between the pathogenic T-helper type 17 (Th17) and protective T-regulatory (Treg) lymphocytes determines the tooth-supporting alveolar bone resorption. Interleukin (IL)-35 is a novel anti-inflammatory cytokine with therapeutic properties in diseases whose pathogenesis is associated with the Th17/Treg imbalance; however, its role during periodontitis has not been established yet. This study aimed to elucidate whether IL-35 inhibits the alveolar bone resorption during periodontitis by modulating the Th17/Treg imbalance. MATERIALS AND METHODS: Mice with ligature-induced periodontitis were treated with locally or systemically administrated IL-35. As controls, periodontitis-affected mice without IL-35 treatment and non-ligated mice were used. Alveolar bone resorption was measured by micro-computed tomography and scanning electron microscopy. The Th17/Treg pattern of the immune response was analysed by qPCR, ELISA, and flow cytometry. RESULTS: IL-35 inhibited alveolar bone resorption in periodontitis mice. Besides, IL-35 induced less detection of Th17 lymphocytes and production of Th17-related cytokines, together with higher detection of Treg lymphocytes and production of Treg-related cytokines in periodontitis-affected tissues. CONCLUSION: IL-35 is beneficial in the regulation of periodontitis; particularly, IL-35 inhibited alveolar bone resorption and this inhibition was closely associated with modulation of the periodontal Th17/Treg imbalance.

Inhibitory effect of serotype a of Aggregatibacter actinomycetemcomitans on the increased destructive potential of serotype b.

OBJECTIVE: The serotype b of Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) induces higher cytokine production in dendritic cells (DCs) compared with the other serotypes. However, this increased immunostimulatory potential was modified when DCs were co-infected with the other A. actinomycetemcomitans serotypes. This study aimed to analyze whether the production of interferon gamma (IFN-γ), C-reactive protein (CRP), matrix metalloproteinase (MMP)-2, and MMP-9, as well as the activity of osteoclasts, also varies when DCs are co-infected with the A. actinomycetemcomitans serotypes. MATERIALS AND METHODS: Human DCs were stimulated with the A. actinomycetemcomitans serotypes using the following stimulatory conditions: serotype a/b/c/a+b/a+c/b+c/a+b+c. The IFN-γ, CRP, and MMP-2 levels were quantified by ELISA. The active form of MMP-9 was quantified using fluorescent functional assays. The MMP-2 gelatinolytic activity was identified by zymogram. The osteoclast activity was determined by quantifying the TRAP expression and resorption-pit formation using cytochemistry and osteoassays. RESULTS: Higher levels of IFN-γ, CRP, MMP-2, MMP-9, and osteoclast activity were detected when DCs were stimulated with the serotype b of A. actinomycetemcomitans compared with the others. This increased immunostimulatory potential attributed to serotype b diminished when DCs were co-infected with the serotype a. CONCLUSIONS: This study provides new insights into the virulence of A. actinomycetemcomitans and reveals important differences in the immunostimulatory and pro-destructive potential among its serotypes.

Diverse tumour susceptibility in Collaborative Cross mice: identification of a new mouse model for human gastric tumourigenesis.

OBJECTIVE: The Collaborative Cross (CC) is a mouse population model with diverse and reproducible genetic backgrounds used to identify novel disease models and genes that contribute to human disease. Since spontaneous tumour susceptibility in CC mice remains unexplored, we assessed tumour incidence and spectrum. DESIGN: We monitored 293 mice from 18 CC strains for tumour development. Genetic association analysis and RNA sequencing were used to identify susceptibility loci and candidate genes. We analysed genomes of patients with gastric cancer to evaluate the relevance of genes identified in the CC mouse model and measured the expression levels of ISG15 by immunohistochemical staining using a gastric adenocarcinoma tissue microarray. Association of gene expression with overall survival (OS) was assessed by Kaplan-Meier analysis. RESULTS: CC mice displayed a wide range in the incidence and types of spontaneous tumours. More than 40% of CC036 mice developed gastric tumours within 1 year. Genetic association analysis identified Nfκb1 as a candidate susceptibility gene, while RNA sequencing analysis of non-tumour gastric tissues from CC036 mice showed significantly higher expression of inflammatory response genes. In human gastric cancers, the majority of human orthologues of the 166 mouse genes were preferentially altered by amplification or deletion and were significantly associated with OS. Higher expression of the CC036 inflammatory response gene signature is associated with poor OS. Finally, ISG15 protein is elevated in gastric adenocarcinomas and correlated with shortened patient OS. CONCLUSIONS: CC strains exhibit tremendous variation in tumour susceptibility, and we present CC036 as a spontaneous laboratory mouse model for studying human gastric tumourigenesis.

IL-22-expressing CD4+ AhR+ T lymphocytes are associated with RANKL-mediated alveolar bone resorption during experimental periodontitis.

BACKGROUND AND OBJECTIVE: Over the past few years, the importance of interleukin-22 (IL-22) and T-helper (Th)22 lymphocytes in the pathogenesis of periodontitis has become apparent; however, there are still aspects that are not addressed yet. Cells expressing IL-22 and aryl hydrocarbon receptor (AhR), transcription factor master switch gene implicated in the differentiation and function of Th22 lymphocytes, have been detected in periodontal tissues of periodontitis-affected patients. In addition, IL-22 has been associated with osteoclast differentiation and their bone resorptive activity in vitro. However, the destructive potential of IL-22-expressing AhR+ Th22 lymphocytes over periodontal tissues during periodontitis has not been demonstrated in vivo yet. Therefore, this study aimed to analyze whether IL-22-expressing CD4+ AhR+ T lymphocytes detected in periodontal lesions are associated with alveolar bone resorption during experimental periodontitis. MATERIAL AND METHODS: Using a murine model of periodontitis, the expression levels of IL-22 and AhR, as well as the Th1-, Th2-, Th17- and T regulatory-associated cytokines, were analyzed in periodontal lesions using qPCR. The detection of CD4+ IL-22+ AhR+ T lymphocytes was analyzed in periodontal lesions and cervical lymph nodes that drain these periodontal lesions using flow cytometry. In addition, the expression of the osteoclastogenic mediator called receptor activator of nuclear factor-κB ligand (RANKL) was analyzed by qPCR, western blot, and immunohistochemistry. Finally, alveolar bone resorption was analyzed using micro-computed tomography and scanning electron microscopy, and the bone resorption levels were correlated with IL-22 and RANKL expression. RESULTS: Higher levels of IL-22, AhR, and RANKL, as well as IL-1ß, IL-6, IL-12, IL-17, IL-23, and TNF-α, were expressed in periodontal lesions of infected mice compared with periodontal tissues of sham-infected and non-infected controls. Similarly, high RANKL immunoreaction was observed in periodontal tissues of infected mice; however, few or absent RANKL immunoreaction was observed in controls. This association between RANKL and periodontal infection was ratified by western blot. Furthermore, a higher detection of CD4+ IL-22+ AhR+ T lymphocytes was found in periodontal lesions and cervical lymph nodes that drain these periodontal lesions in infected mice compared with non-infected controls. Finally, the increased IL-22 and RANKL expression showed positive correlation between them and with the augmented alveolar bone resorption observed in experimental periodontal lesions. CONCLUSION: This study demonstrates the increase of IL-22-expressing CD4+ AhR+ T lymphocytes in periodontitis-affected tissues and shows a positive correlation between IL-22, RANKL expression, and alveolar bone resorption.

Normality Ranges of Menstrual Fluid Volume During Reproductive Life Using Direct Quantification of Menses with Vaginal Cups.

OBJECTIVE: To determine the normal limits of menstrual fluid volume during reproductive life, quantified by direct measurement. METHODS: This was an observational, prospective clinical trial of healthy women aged 20-49 years old, with normal menstrual periods, recruited in a Natural Family Planning Unit. Women collected their menstrual fluid for at least 3 menstrual periods using a vaginal cup. Menstrual volume and different covariables were evaluated using a multilevel mixed-effects linear regression. RESULTS: Ninety-six cycles from 28 patients between 24 and 49 years old were analyzed. The average menstrual volume was 86.7 mL with a range from 15 to 271 mL. The 50th percentile of all samples was 81 mL and the 95th percentile was 162 mL. For multiparous patients the 50th percentile was 93 mL and the 95th was 169 mL. Menstrual fluid volume was higher in multigravida (99.1 mL) than in nulliparous women (45.9 Ml; p < 0.02). No statistically significant associations were identified between different variables and menstrual volume. CONCLUSION: A menstrual volume over 169 mL should be considered abnormal on multiparous patients. Age was not associated with changes on menstrual fluid volume.

Regulatory T Lymphocytes in Periodontitis: A Translational View.

Periodontitis is a chronic immuno-inflammatory disease in which the disruption of the balance between host and microbiota interactions is key to the onset and progression of the disease. The immune homeostasis associated with periodontal health requires a regulated immuno-inflammatory response, during which the presence of regulatory T cells (Tregs) is essential to ensure a controlled response that minimizes collateral tissue damage. Since Tregs modulate both innate and adaptive immunity, pathological conditions that may resolve by the acquisition of immuno-tolerance, such as periodontitis, may benefit by the use of Treg immunotherapy. In recent years, many strategies have been proposed to take advantage of the immuno-suppressive capabilities of Tregs as immunotherapy, including the ex vivo and in vivo manipulation of the Treg compartment. Ongoing research in both basic and translational studies let us gain a better understanding of the diversity of Treg subsets, their phenotypic plasticity, and suppressive functions, which can be used as a substrate for new immunotherapies. Certainly, as our knowledge of Treg biology increases, we will be capable to develop new therapies designed to enhance the stability and function of Tregs during periodontitis.

A 30-month worksite-based lifestyle program to promote cardiovascular health in middle-aged bank employees: Design of the TANSNIP-PESA randomized controlled trial.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide. With atherosclerosis as the underlying cause for many CVD events, prevention or reduction of subclinical atherosclerotic plaque burden (SAPB) through a healthier lifestyle may have substantial public health benefits. OBJECTIVE: The objective was to describe the protocol of a randomized controlled trial investigating the effectiveness of a 30-month worksite-based lifestyle program aimed to promote cardiovascular health in participants having a high or a low degree of SAPB compared with standard care. METHODS: We will conduct a randomized controlled trial including middle-aged bank employees from the Progression of Early Subclinical Atherosclerosis cohort, stratified by SAPB (high SAPB n=260, low SAPB n=590). Within each stratum, participants will be randomized 1:1 to receive a lifestyle program or standard care. The program consists of 3 elements: (a) 12 personalized lifestyle counseling sessions using Motivational Interviewing over a 30-month period, (b) a wrist-worn physical activity tracker, and (c) a sit-stand workstation. Primary outcome measure is a composite score of blood pressure, physical activity, sedentary time, body weight, diet, and smoking (ie, adapted Fuster-BEWAT score) measured at baseline and at 1-, 2-, and 3-year follow-up. CONCLUSIONS: The study will provide insights into the effectiveness of a 30-month worksite-based lifestyle program to promote cardiovascular health compared with standard care in participants with a high or low degree of SAPB.

Neonatal exposure to monosodium glutamate induces morphological alterations in suprachiasmatic nucleus of adult rat.

Neonatal exposure to monosodium glutamate (MSG) induces circadian disorders in several physiological and behavioural processes regulated by the suprachiasmatic nucleus (SCN). The objective of this study was to evaluate the effects of neonatal exposure to MSG on locomotor activity, and on morphology, cellular density and expression of proteins, as evaluated by optical density (OD), of vasopressin (VP)-, vasoactive intestinal polypeptide (VIP)- and glial fibrillary acidic protein (GFAP)-immunoreactive cells in the SCN. Male Wistar rats were used: the MSG group was subcutaneously treated from 3 to 10 days of age with 3.5 mg/g/day. Locomotor activity was evaluated at 90 days of age using 'open-field' test, and the brains were processed for immunohistochemical studies. MSG exposure induced a significant decrease in locomotor activity. VP- and VIP-immunoreactive neuronal densities showed a significant decrease, while the somatic OD showed an increase. Major axes and somatic area were significantly increased in VIP neurons. The cellular and optical densities of GFAP-immunoreactive sections of SCN were significantly increased. These results demonstrated that newborn exposure to MSG induced morphological alterations in SCN cells, an alteration that could be the basis for behavioural disorders observed in the animals.

Increased nuclear ß-catenin expression in oral potentially malignant lesions: A marker of epithelial dysplasia.

BACKGROUND: Deregulation of ß-catenin is associated with malignant transformation; however, its relationship with potentially malignant and malignant oral processes is not fully understood. The aim of this study was to determine and compare the nuclear ß-catenin expression in oral dysplasia and oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: Cross sectional study. Immunodetection of ß-catenin was performed on 72 samples, with the following distribution: 21 mild dysplasia, 12 moderate dysplasia, severe dysplasia 3, 36 OSCC including 19 well differentiated, 15 moderately differentiated and 2 poorly differentiated. Through microscopic observation the number of positive cells per 1000 epithelial cells was counted. For the statistical analysis, the Kruskal Wallis test was used. RESULTS: Nuclear expression of ß-catenin was observed in all samples with severe and moderate dysplasia, with a median of 267.5, in comparison to mild dysplasia whose median was 103.75. Only 10 samples (27.7%) with OSCC showed nuclear expression, with statistically significant differences between groups (p < 0.05). CONCLUSIONS: Our results are consistent with most of the reports which show increased presence of ß-catenin in severe and moderate dysplasia compared to mild dysplasia; however the expression of nuclear ß-catenin decreased after starting the invasive neoplastic process. This suggests a role for this protein in the progression of dysplasia and early malignant transformation to OSCC. Immunodetection of ß-catenin could be a possible immune marker in the detection of oral dysplasia.

A temporal analysis of the consequences of the drought regime on the water footprint of agriculture in the Guadalupe Valley, Mexico.

Changes in water availability have a substantial impact on the sustainability and maintenance of agriculture, with water footprint (WF) being a robust methodology to assess these transformations. The Guadalupe Valley is one of the places with the highest agricultural production in Mexico. Despite its semi-arid climatic conditions, it provides high-quality crops that are well-positioned in the world. The historical trend of rainfall and temperatures between 1987 and 2017 was analyzed to identify climatic patterns in the territory. Through the calculations of the water footprint of Grapevine and Olive crops, the sensitivity of the crops to recurrent water deficit and their adaptation in their yields to drought episodes was identified. The reduction in precipitation and occurrence of extreme temperatures have contributed significantly towards augmenting crop evapotranspiration and, consequently, intensifying crop irrigation demands. As a result, there has been an apparent increase in the consumption of WFagricultural since 2007. Thus, the period of highest WFagricultural consumption was 2014 (Extremely dry), as opposed to 2011 (Very wet). In particular, the lowest WFgreen consumptions were observed in extremely dry years, that is, > 20% of the WFagricultural intensifying drought events. Therefore, these periods were compensated with higher uses of WFblue and WFgray, which are inversely correlated with precipitation, where vine crops consume 73% more WFagricultural compared to olive plantations, showing greater interannual variability. These results contribute to analyzing the temporal evolution of water consumption for agriculture, providing a basis for rational water use strategies.

Chronic Undernutrition in Ovine Twin Pregnancies Abolishes Differences in Birth Weight Due to Sex: An Evaluation of the Role of Nutritional and Antioxidant Supplementation.

In twin pregnancies of discordant sex, the male fetus grows larger than the female co-twin. Our study aimed to determine the effect of the sex of co-twins on lambs' birth weight in ovine pregnancies developed under natural undernourishment. Additionally, we investigated whether the nutritional and/or antioxidant supplementation provided to ewes during pregnancy could modulate the potential effects associated with the sex of co-twins. Ninety-six birth records of twin pregnancies of sheep grazing the natural Patagonian prairies were analyzed. The animals were divided into four groups: control (no supplementation), N (concentrate supplementation, 100% NRC), A (antioxidant supplementation), and NA (concentrate + antioxidant supplementation). Supplementation occurred from day 35 of gestation onwards until lambing. There were no differences in female or male birth weight in the control undernourished group. However, in group N, females or males with sex-discordant co-twins had a higher birth weight than did those with co-twins of the same sex. Group A males with female co-twins had a higher birth weight compared to males whose co-twins were also males. In NA lambs, males had a higher birth weight compared to females, regardless of their co-twin's sex. Therefore, chronic undernutrition abolished the differences in birth weight due to fetal sex. Restoring maternal nutrition or antioxidant supplementation tends to normalize birth weight and restore the differences between females and males. This effect is enhanced with the combined supplementation of concentrated food and antioxidants.