Título del artículo:

Pancoast tumor in a patient with shoulder pain

We present the case of a patient with long-term right hemithorax pain managed as rotator cuff syndrome who underwent a chest X-ray with a report of an ill-defined image in the right upper hemithorax and later a chest CT scan with a mass of neoplastic appearance described in the right upper lobe that was later confirmed as malignant with histological diagnosis.

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Atencion Primaria Practica

Título del artículo:

Purple urine bag syndrome

The case of a patient with urinary urinary incontinence due to hemiplegia who comes to the consultation for fever and general malaise is presented, it is striking that he brings a collection bag of purple coloration, urinary tract infection is identified and with antibiotic management resolves purple coloration of the bag, a semiological finding is described by a chemical reaction that involves urine, plastic and certain enzymes of some bacteria that produce sulfatases and phosphatases.

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Atencion Primaria Practica

Título del artículo:

Advancing the global public health agenda for NAFLD: a consensus statement

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics — from epidemiology, awareness, care and treatment to public health policies and leadership — that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD.

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Nature Reviews Gastroenterology and Hepatology

Título del artículo:

Arbuscular mycorrhizal fungal association boosted the arsenic resistance in crops with special responsiveness to rice plant

Arsenic (As) is a potentially toxic metalloid classified as a group 1 carcinogen, released in the soil environment because of natural as well as different anthropogenic activities. The presence of excess As content in soil and irrigation water enhances the As accumulation in rice grains. Millions of people who consume these contaminated grains are exposed to severe health issues. Increased arsenic uptake causes oxidative stress in plants, which combats by inducing the expression of several genes and signaling the biosynthesis of various antioxidants and phytochelatins. As toxicity reduces crop productivity, so it\'s critical to improve plant growth in As-contaminated environments while minimizing metal translocation to grains. Arbuscular mycorrhiza fungi (AMF) is considered a sustainable way to tolerate As toxicity. Organic pollutants metabolism by AMF, degradation of these soil contaminants by AMF exudation enzymes, and elimination of the pollutants by plant uptake and accumulation are the principal mechanisms of AMF mediated bioremediation. However, plant responses are established to vary with the host plant and the species of AMF. In our review, we showed that understanding the community composition, diversity, and gene regulation of AMF in the rice ecosystem played a critical role in maximizing As uptake and their potential in sustainable rice and other crops production. It has been reviewed that AMF has the potential to survive in an extremely As toxic condition and it potentially aids to improve the tolerance level of host plants.

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Environmental and Experimental Botany

Título del artículo:

Drop jump neuromuscular performance qualities associated with maximal horizontal deceleration ability in team sport athletes

The purpose of this study was to investigate associations between, and within, drop jump (DJ) neuromuscular performance (NMP) qualities and maximal horizontal deceleration ability. We also compared DJ NMP qualities in “high” versus “low” horizontal deceleration ability athletes. Twenty-nine university athletes performed: (1) DJs on force plates from 20 (DJ20) and 40 cm (DJ40) heights and (2) maximal horizontal deceleration, measured using radar, following a 20 m acceleration. Maximal horizontal deceleration was evaluated using deceleration (HDEC; m·s−2), across the entire deceleration phase and during early and late deceleration sub-phases. Of the DJ variables assessed, DJ20 and DJ40 reactive strength index (RSI) and concentric mean force had the largest correlations with HDEC (r = −0.54 to −0.61) and the largest differences between high and low HDEC groups (d = 1.20 to 1.40). These correlations were stronger with the early than late HDEC sub-phase (r = −0.54 to −0.66 vs. r = −0.24 to −0.40). Notably, eccentric mean force in DJ40 had large correlations with both DJ20 and DJ40 concentric mean force (r = 0.67 to 0.77), whereas at DJ20 these correlations were small (r = 0.22 to 0.40). Similarly, DJ40 eccentric mean force had a much larger difference between the high and low HDEC groups than DJ20 (d = 1.11 vs. 0.51). These findings suggest DJ RSI from either height may be used as a proxy for HDEC ability, while DJ kinetic analyses should use a higher height to distinguish those with a better capacity to generate eccentric braking forces under increased eccentric loading demands. HIGHLIGHTS Players with greater drop jump reactive strength index (RSI) demonstrated superior horizontal deceleration ability. Drop jump RSI had a greater association with the early compared to the late horizontal deceleration sub-phase. Of the drop jump kinetic variables examined, concentric mean force had the largest associations with horizontal deceleration ability.

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European Journal of Sport Science

Título del artículo:

Psychometric performance of the brief Francis scale of attitude towards Christianity (Francis-4) in Mexican university students

The brief Francis scale of attitude towards Christianity (Francis-4) psychometric performance in Mexico is unknown. The objective was to evaluate the dimensionality, homogeneity, gender differential item functioning (DIF), and nomological validity of Francis-4. 1,108 university students between 18 and 60 years of age were evaluated; 80.4% were women (n = 891). CFA was performed with the following fit indicators: chi-square, RMSEA, CFI, TLI, and McDonald’s omega were calculated. For nomological validity, the mean and standard deviation according to gender were compared with Student’s t-test. Gender DIF was quantified with Kendall’s tau-b. The CFA revealed the following goodness-of-fit coefficients: chi-square = 25.45, df = 2, p = .001, RMSEA = .10, 90% CI.07 –.14, CFI = .99, TLI = .99, and SRMR = .01. Cronbach’s alpha of.97 and McDonald’s omega were.97. Scores were significantly higher in women than in men (M = 8.9, SD = 5.4 versus M = 7.6, t = 3.15, p = .002). Kendall’s tau ranged from.07 to.09 indicating absence of gender DIF. Francis-4 is a unidimensional instrument with nomological validity, high internal consistency, and absence of gender DIF. It is recommended to evaluate its performance in other populations.

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Journal of Beliefs and Values

Título del artículo:

Validity of the Hospital Anxiety and Depression Scale (HADS) in primary care patients in Colombia

Objective: To assess the validity of the Hospital Anxiety and Depression Scale (HADS) for depression and anxiety screening in primary care patients in Colombia. Methods: A criterion validity study was conducted with 243 adults that had completed the HADS and were later assessed using the MINI as a gold standard. Cronbach\'s alpha, McDonald\'s omega and factor structure were applied through confirmatory factor analysis (CFA). ROC curve analysis and Youden\'s statistic were used to determine the cut-off point. Results: Cronbach\'s α was reported to be 0.85 and 0.82 for McDonalds\' ω. CFA supported a two-factor solution demonstrating satisfactory fit. Root mean square error of approximation = 0.04, Comparative Fix Index (CFI) and Tucker-Lewis Index (TLI) = 0.97. For HADS-A, the cut-off point was determined as 6 associated with a sensitivity of 0.76, a specificity of 0.72 and Youden\'s index of 0.50. The ABC was 0.81. For HADS-D, the cut-off point was determined as 4 associated with a sensitivity of 0.78, a specificity of 0.74 and Youden\'s index of 0.53. The ABC was 0.82. Conclusion: The HADS is a valid and reliable instrument for anxiety and depression screening in adult patients of primary healthcare services in Colombia.

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General Hospital Psychiatry

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Phytochemical characterisation and in vivo antilithiatic activity of the stems of Caesalpinia bahamensis (Brasilete)

The aim of this work was to identify the main chemical constituents and to evaluate the antilithiatic activity of the aqueous and hydroalcoholic extracts of stems of Caesalpinia bahamensis Lam. Fractionation and isolation of constituents from the hydroalcoholic extract was carried out by flash chromatography and semi-preparative liquid chromatography. The antilithiatic activity of the aqueous and hydroalcoholic extracts was evaluated in Wistar rats, where kidney stones were induced by ethylene glycol and ammonium chloride. Creatinine, calcium, and oxalate levels were evaluated and histological analysis was carried out. The homoisoflavonoids protosappanin B, 10-methyl-protosappanin B and brazilin were isolated and the antilithiatic activity of the aqueous and hydroalcoholic extracts was demonstrated by the reduction of the concentration of calcium and oxalate in urine compared to the lithiasis group. It was corroborated by histological analysis. Brazilin and protosappanin B were proposed as chemical markers for this plant species.

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Natural Product Research

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Adaptation and psychometric evaluation of the Fear of COVID-19 Scale in the general Colombian population

The study aimed to adapt and explore the psychometric performance of the Fear of COVID-19 Scale (FCV-19S) in the general Colombian population. The original FCV-19S is a 7-item scale that underwent an adaptation (Item 1 and 5 were deleted). From an online sample of 1,687 adults (59% female), exploratory and confirmatory factor analyses were performed for versions of the scale with 6 and 5 items. Cronbach\'s alpha and McDonald\'s omega were calculated. The confirmatory factor analysis showed that the 5-item scale (Fear of COVID-5) presented better indicators. In conclusion, the Fear of COVID-5 has acceptable performance in the Colombian population.

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Death Studies

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Proposal of a method to evaluate the in-situ oxidation of polyphenolic during the cocoa drying

In this work, the oxidation of polyphenols during drying of cocoa beans by using microwaves (MWs), applied in an ON-OFF mode, was studied. Phenolic compounds were quantified in cocoa beans before and after drying. Total phenolics content was analyzed by using some analytical techniques such as Fourier transform infrared (FTIR) spectroscopy, and high-performance liquid chromatography (HPLC). To study the oxidation process in-situ, an innovative methodology was proposed based on the counting of the coloring of the polyphenols contained in the parenchyma cells of the cocoa beans (cotyledon). The level of coloration in the inner zone and the surface of the dried cocoa beans showed that degradation of polyphenol compounds during the drying does not obey to a transport mechanism (diffusion), but in-situ oxidative processes.

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Drying Technology

Título del artículo:

Psychosocial Risk Factors and Cardiovascular Disease and Death in a Population-Based Cohort from 21 Low-, Middle-, and High-Income Countries

Importance: Stress may increase the risk of cardiovascular disease (CVD). Most studies on stress and CVD have been conducted in high-income Western countries, but whether stress is associated with CVD in other settings has been less well studied. Objective: To investigate the association of a composite measure of psychosocial stress and the development of CVD events and mortality in a large prospective study involving populations from 21 high-, middle-, and low-income countries across 5 continents. Design, Setting, and Participants: This population-based cohort study used data from the Prospective Urban Rural Epidemiology study, collected between January 2003 and March 2021. Participants included individuals aged 35 to 70 years living in 21 low-, middle-, and high-income countries. Data were analyzed from April 8 to June 15, 2021. Exposures: All participants were assessed on a composite measure of psychosocial stress assessed at study entry using brief questionnaires concerning stress at work and home, major life events, and financial stress. Main Outcomes and Measures: The outcomes of interest were stroke, major coronary heart disease (CHD), CVD, and all-cause mortality. Results: A total of 118706 participants (mean [SD] age 50.4 [9.6] years; 69842 [58.8%] women and 48864 [41.2%] men) without prior CVD and with complete baseline and follow-up data were included. Of these, 8699 participants (7.3%) reported high stress, 21797 participants (18.4%) reported moderate stress, 34958 participants (29.4%) reported low stress, and 53252 participants (44.8%) reported no stress. High stress, compared with no stress, was more likely with younger age (mean [SD] age, 48.9 [8.9] years vs 51.1 [9.8] years), abdominal obesity (2981 participants [34.3%] vs 10599 participants [19.9%]), current smoking (2319 participants [26.7%] vs 10477 participants [19.7%]) and former smoking (1571 participants [18.1%] vs 3978 participants [7.5%]), alcohol use (4222 participants [48.5%] vs 13222 participants [24.8%]), and family history of CVD (5435 participants [62.5%] vs 20255 participants [38.0%]). During a median (IQR) follow-up of 10.2 (8.6-11.9) years, a total of 7248 deaths occurred. During the course of follow-up, there were 5934 CVD events, 4107 CHD events, and 2880 stroke events. Compared with no stress and after adjustment for age, sex, education, marital status, location, abdominal obesity, hypertension, smoking, diabetes, and family history of CVD, as the level of stress increased, there were increases in risk of death (low stress: hazard ratio [HR], 1.09 [95% CI, 1.03-1.16]; high stress: 1.17 [95% CI, 1.06-1.29]) and CHD (low stress: HR, 1.09 [95% CI, 1.01-1.18]; high stress: HR, 1.24 [95% CI, 1.08-1.42]). High stress, but not low or moderate stress, was associated with CVD (HR, 1.22 [95% CI, 1.08-1.37]) and stroke (HR, 1.30 [95% CI, 1.09-1.56]) after adjustment. Conclusions and Relevance: This cohort study found that higher psychosocial stress, measured as a composite score of self-perceived stress, life events, and financial stress, was significantly associated with mortality as well as with CVD, CHD, and stroke events..

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JAMA Network Open

Título del artículo:

Definitions and Risk Factors for Drug-Resistant Epilepsy in an Adult Cohort

Background: Less than one-third of people with epilepsy will develop drug-resistant epilepsy (DRE). Establishing the prognosis of each unique epilepsy case is an important part of evaluation and treatment.Most studies on DRE prognosis have been based on a pooled, heterogeneous group, including children, adults, and older adults, in the absence of clear recognition and control of important confounders, such as age group. Furthermore, previous studies were done before the 2010 definition of DRE by the International League Against Epilepsy (ILAE), so data based on the current definitions have not been entirely elucidated. This study aimed to explore the difference between 3 definitions of DRE and clinical predictors of DRE in adults and older adults. Methods: Patients with a new diagnosis of epilepsy ascertained at a Single Seizure Clinic (SSC) in Saskatchewan, Canada were included if they had at least 1 year of follow-up. The first study outcome was the diagnosis of DRE epilepsy at follow-up using the 2010 ILAE definition. This was compared with 2 alternative definitions of DRE by Kwan and Brodie and Camfield and Camfield. Finally, risk factors were analyzed using the ILAE definition. Results: In total, 95 patients with a new diagnosis of epilepsy and a median follow-up of 24 months were included. The median age of patients at the diagnosis of epilepsy was 33 years, and 51% were men. In the cohort, 32% of patients were diagnosed with DRE by the Kwan and Brodie definition, 10% by Camfield and Camfield definition, and 15% by the ILAE definition by the end of follow-up. The only statistically significant risk factor for DRE development was the failure to respond to the first anti-seizure medication (ASM). Conclusion: There were important differences in the percentage of patients diagnosed with DRE when using 3 concurrent definitions. However, the use of the ILAE definition appeared to be the most consistent through an extended follow-up. Finally, failure to respond to the first ASM was the sole significant risk factor for DRE in the cohort after considering the age group.

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Frontiers in Neurology

Título del artículo:

Antiproliferative, Antiangiogenic, and Antimetastatic Therapy Response by Mangiferin in a Syngeneic Immunocompetent Colorectal Cancer Mouse Model Involves Changes in Mitochondrial Energy Metabolism

In spite of the current advances and achievements in cancer treatments, colorectal cancer (CRC) persists as one of the most prevalent and deadly tumor types in both men and women worldwide. Drug resistance, adverse side effects and high rate of angiogenesis, metastasis and tumor relapse remain one of the greatest challenges in long-term management of CRC and urges need for new leads of anticancer drugs. We demonstrate that CRC treatment with the phytopharmaceutical mangiferin (MGF), a glucosylxanthone present in Mango tree stem bark and leaves (Mangifera Indica L.), induces dose-dependent tumor regression and decreases lung metastasis in a syngeneic immunocompetent allograft mouse model of murine CT26 colon carcinoma, which increases overall survival of mice. Antimetastatic and antiangiogenic MGF effects could be further validated in a wound healing in vitro model in human HT29 cells and in a matrigel plug implant mouse model. Interestingly, transcriptome pathway enrichment analysis demonstrates that MGF inhibits tumor growth, metastasis and angiogenesis by multi-targeting of mitochondrial oxidoreductase and fatty acid β-oxidation metabolism, PPAR, SIRT, NFκB, Stat3, HIF, Wnt and GP6 signaling pathways. MGF effects on fatty acid β-oxidation metabolism and carnitine palmitoyltransferase 1 (CPT1) protein expression could be further confirmed in vitro in human HT29 colon cells. In conclusion, antitumor, antiangiogenic and antimetastatic effects of MGF treatment hold promise to reduce adverse toxicity and to mitigate therapeutic outcome of colorectal cancer treatment by targeting mitochondrial energy metabolism in the tumor microenvironment.

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Frontiers in Pharmacology

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Computational study, synthesis and evaluation of active peptides derived from Parasporin-2 and spike protein from Alphacoronavirus against colorectal cancer cells

Parasporin-2Aa1 (PS2Aa1) is a toxic protein of 37 KDa (30 kDa, activated form produced by proteolysis) that was shown to be cytotoxic against specific human cancer cells, although its mechanism of action has not been elucidated yet. In order to study the role of some native peptide fragments of proteins on anticancer activity, here we investigated the cytotoxic effect of peptide fragments from domain-1 of PS2Aa1 and one of the loops present in the binding region of the virus spike protein from Alphacoronavirus (HCoV-229E), the latter according to scientific reports, who showed interaction with the human APN (h-APN) receptor, evidence corroborated through computational simulations, and thus being possible active against colon cancer cells. Peptides namely P264-G274, Loop1-PS2Aa, and Loop2-PS2Aa were synthesized using the Fmoc solid-phase synthesis and characterized by mass spectrometry (MS). Additionally, one region from loop 1 of HCoV-229E, Loop1-HCoV-229E, was also synthesized and characterized. The A4W-GGN5 anticancer peptide and 5-fluorouracil (5-FU) were taken as a control in all experiments. Circular dichroism revealed an α-helix structure for the peptides derived from PS2Aa1 (P264-G274, Loop1-PS2Aa, and Loop2-PS2Aa) and β-laminar structure for the peptide derived from Alphacoronavirus spike protein Loop1-HCoV-229E. Peptides showed a hemolysis percentage of less than 20% at 100 μM concentration. Besides, peptides exhibited stronger anticancer activity against SW480 and SW620 cells after exposure for 48 h. Likewise, these compounds showed significantly lower toxicity against normal cells CHO-K1. The results suggest that native peptide fragments from Ps2Aa1 may be optimized as a novel potential cancer-therapeutic agents.

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Bioscience Reports

Título del artículo:

Genetic modification approaches for parasporins bacillus thuringiensis proteins with anticancer activity

Bacillus thuringiensis (Bt) is a bacterium capable of producing Cry toxins, which are recognized for their bio-controlling actions against insects. However, a few Bt strains encode proteins lacking insecticidal activity but showing cytotoxic activity against different cancer cell lines and low or no cytotoxicity toward normal human cells. A subset of Cry anticancer proteins, termed parasporins (PSs), has recently arisen as a potential alternative for cancer treatment. However, the molecular receptors that allow the binding of PSs to cells and their cytotoxic mechanisms of action have not been well established. Nonetheless, their selective cytotoxic activity against different types of cancer cell lines places PSs as a promising alternative treatment modality. In this review, we provide an overview of the classification, structures, mechanisms of action, and insights obtained from genetic modification approaches for PS proteins.

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Molecules

Título del artículo:

Health problems and the use of medications and traditional therapies among chinese immigrants living in Spain

In this study, we investigate the health problems and the use of medications and traditional therapies among Chinese immigrants in the Southern region of Spain. A qualitative study using semi-structured interviews and including 133 immigrants and 7 stakeholders was conducted in 2017. Transcription, literal reading, and theoretical categorization were performed, and a narrative content analysis was carried out. The most common health problems were musculoskeletal (28.6%) and allergies (25.6%) related to work activity and unhealthy lifestyles. Key informants also reported gastric problems, stress, and changes in eating habits, mostly related to their work activity. For these problems, a large number of traditional remedies (herbs, diet therapy, acupuncture, vitamins, etc.) were used, usually combined with pharmaceutical drugs used for colds, flu, general malaise (29%), pain and fever (23%), and allergy drugs (9.2%). Chinese immigrants reported health conditions associated with their working conditions and life habits in Spain, using Traditional Chinese Medicine instead of pharmacological drugs. Understanding these health problems and promoting awareness towards traditional therapies in the healthcare system may help to design public policies and Health Promotion strategies targeting this group.

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Healthcare (Switzerland)

Título del artículo:

Patient-important outcomes reported in randomized controlled trials of pharmacologic treatments for COVID-19: a protocol of a META-epidemiological study

Background: The coronavirus disease 19 (covid-19) pandemic has underscored the need to expedite clinical research, which may lead investigators to shift away from measuring patient-important outcomes (PIO), limiting research applicability. We aim to investigate if randomized controlled trials (RCTs) of covid-19 pharmacological therapies include PIOs. Methods: We will perform a meta-epidemiological study of RCTs that included people at risk for, or with suspected, probable, or confirmed covid-19, examining any pharmacological treatment or blood product aimed at prophylaxis or treatment. We will obtain data from all RCTs identified in a living network metanalysis (NMA). The main data sources are the living WHO covid-19 database up to 1 March 2021 and six additional Chinese databases up to 20 February 2021. Two reviewers independently will review each citation, full-text article, and abstract data. To categorize the outcomes according to their importance to patients, we will adapt a previously defined hierarchy: a) mortality, b) quality of life/ functional status/symptoms, c) morbidity, and d) surrogate outcomes. Outcomes within the category a) and b) will be considered critically important to patients, and outcomes within the category c) will be regarded as important. We will use descriptive statistics to assess the proportion of studies that report each category of outcomes. We will perform univariable and multivariable analysis to explore associations between trial characteristics and the likelihood of reporting PIOs. Discussion: The findings from this meta-epidemiological study will help health care professionals and researchers understand if the current covid-19 trials are effectively assessing and reporting the outcomes that are important to patients. If a deficiency in capturing PIOs is identified, this information may help inform the development of future RCTs in covid-19. Systematic review registrations: Open Science Framework registration: osf.io/6xgjz.

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Systematic Reviews

Título del artículo:

Mental health benefits of a 1-week intensive multimodal group program for adolescents with multiple adverse childhood experiences

Background: Adverse childhood experiences (ACEs) are associated with a wide range of diseases, unsafe behavior and shorter life expectancy. However, there is scarce evidence on effective interventions for children or adolescents who report multiple ACEs, including abuse, neglect and household dysfunction. Objective: The aim of this study was to evaluate the mental health outcomes of a multimodal program designed for adolescents with multiple ACEs. Participants: Forty-four girls (aged 13–16 years, mean ACE score > 5) were randomized to an intervention group or a care-as-usual control group. Methods: The intervention included mindfulness-based practices, expressive arts and EMDR (Eye Movement Desensitization and Reprocessing Integrative) group treatment. We used questionnaires for adolescents to assess trauma (SPRINT, CPSS) and attention/awareness-related outcomes (MAAS-A) at baseline (T1), post-intervention (T2) and two-months post-discharge (T3). Results: Linear mixed effects model analyses showed significant Group by Time interactions on all the scales (F = 11.0, p = 0.015; F = 12.5 p < 0.001; and F = 6.4, p = 0.001, for SPRINT, CPSS and MAAS-A, respectively). After completing the program, the intervention group showed significant reduction in trauma-related outcomes (SPRINT, Δ%(T2-T1) = −73%, p < 0.001; CPSS, Δ%(T2-T1) = −26%, p < 0.001) while attention/awareness-related outcomes were improved by 57% (p < 0.001). These changes remained stable two months after discharge. SPRINT and CPSS scales were highly correlated (r = 0.833, p < 0.001) and outcomes from both trauma-related scales negatively correlated with mindfulness scores (MAAS-A/SPRINT, r = −0.515, p = 0.007; MAAS-A/CPSS, r = −0.553, p < 0.001). Conclusions: Results presented here support this multimodal group intervention as a feasible and promising program for reducing the psychological burden in adolescents with a history of multiple ACEs.

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Child Abuse and Neglect

Título del artículo:

Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer

Background: In an effort to contribute to overcoming the platinum resistance exhibited by most solid tumors, we performed an array of epigenetic approaches, integrating next-generation methodologies and public clinical data to identify new potential epi-biomarkers in ovarian cancer, which is considered the most devastating of gynecological malignancies. Methods: We cross-analyzed data from methylome assessments and restoration of gene expression through microarray expression in a panel of four paired cisplatin-sensitive/cisplatin-resistant ovarian cancer cell lines, along with publicly available clinical data from selected individuals representing the state of chemoresistance. We validated the methylation state and expression levels of candidate genes in each cellular phenotype through Sanger sequencing and reverse transcription polymerase chain reaction, respectively. We tested the biological role of selected targets using an ectopic expression plasmid assay in the sensitive/resistant tumor cell lines, assessing the cell viability in the transfected groups. Epigenetic features were also assessed in 189 primary samples obtained from ovarian tumors and controls. Results: We identified PAX9 and FKBP1B as potential candidate genes, which exhibited epigenetic patterns of expression regulation in the experimental approach. Re-establishment of FKBP1B expression in the resistant OVCAR3 phenotype in which this gene is hypermethylated and inhibited allowed it to achieve a degree of platinum sensitivity similar to the sensitive phenotype. The evaluation of these genes at a translational level revealed that PAX9 hypermethylation leads to a poorer prognosis in terms of overall survival. We also set a precedent for establishing a common epigenetic signature in which the validation of a single candidate, MEST, proved the accuracy of our computational pipelines. Conclusions: Epigenetic regulation of PAX9 and FKBP1B genes shows that methylation in non-promoter areas has the potential to control gene expression and thus biological consequences, such as the loss of platinum sensitivity. At the translational level, PAX9 behaves as a predictor of chemotherapy response to platinum in patients with ovarian cancer. This study revealed the importance of the transcript-specific study of each gene under potential epigenetic regulation, which would favor the identification of new markers capable of predicting each patient’s progression and therapeutic response.

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Clinical Epigenetics

Título del artículo:

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.

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BMC Complementary Medicine and Therapies

Título del artículo:

In favor of the concept of reasonable person: Analysis based on the innominate contract of logistics services

The atypical logistics services contract contains complex services designed according to commercial traffic. However, when interpretative conflicts arise, the judges resort to criteria external to the initial economic equation. This can lead to unintended consequences. This investigation investigated the limits of Kantian philosophy to solve the problem. It is concluded that equality may be a non-utilitarian basis for interpretation, but it continues to resort to more than just the will. Finally, the concept of reasonable person is proposed, since it respects the commercial logic of the business and at the same time is a hermeneutical method that is effective.

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Revista de Derecho Privado

Título del artículo:

Glutathione-related genetic polymorphisms are associated with mercury retention and nephrotoxicity in gold-mining settings of a Colombian population

Mercury (Hg) vapor can produce kidney injury, where the proximal tubule region of the nephron is the main target of the Hg-induced oxidative stress. Hg is eliminated from the body as a glutathione conjugate. Thus, single nucleotide polymorphisms (SNPs) in glutathione-related genes might modulate the negative impact of this metal on the kidneys. Glutathione-related SNPs were tested for association with levels of Hg and renal function biomarkers between occupationally exposed (n = 160) and non-exposed subjects (n = 121). SNPs were genotyped by TaqMan assays in genomic DNA samples. Total mercury concentration was measured in blood, urine and hair samples. Regression analyses were performed to estimate the effects of SNPs on quantitative traits. Alleles GCLM rs41303970-T and GSTP1 rs4147581-C were significantly overrepresented in the exposed compared with the non-exposed group (P < 0.01). We found significant associations for GCLM rs41303970-T with higher urinary clearance rate of Hg (β = 0.062, P = 0.047), whereas GCLC rs1555903-C was associated with lower levels of estimated glomerular filtration rate in the non-exposed group (eGFR, β = − 3.22, P = 0.008) and beta-2-microglobulin in the exposed group (β-2MCG, β = − 19.32, P = 0.02). A SNP-SNP interaction analysis showed significant epistasis between GSTA1 rs3957356-C and GSS rs3761144-G with higher urinary levels of Hg in the exposed (β = 0.13, P = 0.04) but not in the non-exposed group. Our results suggest that SNPs in glutathione-related genes could modulate the pathogenesis of Hg nephrotoxicity in our study population by modulating glutathione concentrations in individuals occupationally exposed to this heavy metal.

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Scientific Reports

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The prediction of Metabolic Syndrome alterations is improved by combining waist circumference and handgrip strength measurements compared to either alone

Background: Adiposity is a major component of the metabolic syndrome (MetS), low muscle strength has also been identified as a risk factor for MetS and for cardiovascular disease. We describe the prevalence of MetS and evaluate the relationship between muscle strength, anthropometric measures of adiposity, and associations with the cluster of the components of MetS, in a middle-income country. Methods: MetS was defined by the International Diabetes Federation criteria. To assess the association between anthropometric variables (waist circumference (WC), waist-to-hip ratio (W/H), body mass index (BMI)), strength (handgrip/kg bodyweight (HGS/BW)) and the cluster of MetS, we created a MetS score. For each alteration (high triglycerides, low HDLc, dysglycemia, or high blood pressure) one point was conferred. To evaluate the association an index of fat:muscle and MetS score, participants were divided into 9 groups based on combinations of sex-specific tertiles of WC and HGS/BW. Results: The overall prevalence of MetS in the 5,026 participants (64% women; mean age 51.2 years) was 42%. Lower HGS/BW, and higher WC, BMI, and W/H were associated with a higher MetS score. Amongst the 9 HGS/BW:WC groups, participants in the lowest tertile of HGS/BW and the highest tertile of WC had a higher MetS score (OR = 4.69 in women and OR = 8.25 in men;p < 0.01) compared to those in the highest tertile of HGS/BW and in the lowest tertile of WC. Conclusion: WC was the principal risk factor for a high MetS score and an inverse association between HGS/BW and MetS score was found. Combining these anthropometric measures improved the prediction of metabolic alterations over either alone.

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Cardiovascular Diabetology

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Study of heart rate recovery and cardiovascular autonomic modulation in healthy participants after submaximal exercise

Heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) provide important information on cardiovascular autonomic control. However, little is known about the reorganization of HRV, BPV, and BRS after aerobic exercise. While there is a positive relationship between heart rate (HR) recovery rate and cardiorespiratory fitness, it is unclear whether there is a relationship between cardiorespiratory fitness and reorganization of cardiovascular autonomic modulation during recovery. Thus, this study aimed to investigate whether cardiorespiratory fitness influences the cardiovascular autonomic modulation recovery, after a cardiopulmonary exercise test. Sixty men were assigned into groups according to their cardiorespiratory fitness: low cardiorespiratory fitness (LCF = VO2: 22–38 mL kg−1 min−1), moderate (MCF = VO2: 38–48 mL kg−1 min−1), and high (HCF = VO2 > 48 mL kg−1 min−1). HRV (linear and non-linear analysis) and BPV (spectral analysis), and BRS (sequence method) were performed before and after a cardiopulmonary exercise test. The groups with higher cardiorespiratory fitness had lower baseline HR values and HR recovery time after the cardiopulmonary exercise test. On comparing rest and recovery periods, the spectral analysis of HRV showed a decrease in low-frequency (LF) oscillations in absolute units and high frequency (HF) in absolute and normalized units. It also showed increases in LF oscillations of blood pressure. Nonlinear analysis showed a reduction in approximate entropy (ApEn) and in Poincare Plot parameters (SD1 and SD2), accompanied by increases in detrended fluctuation analysis (DFA) parameters α1 and α2. However, we did not find differences in cardiovascular autonomic modulation parameters and BRS in relation to cardiorespiratory fitness neither before nor after the cardiopulmonary test. We concluded that cardiorespiratory fitness does not affect cardiovascular autonomic modulations after cardiopulmonary exercise test, unlike HR recovery.

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Scientific Reports

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A novel method for isolation and culture of primary swine gastric epithelial cells

Background: Culturing primary epithelial cells has a major advantage over tumor-derived or immortalized cell lines as long as their functional phenotype and genetic makeup are mainly maintained. The swine model has shown to be helpful and reliable when used as a surrogate model for human diseases. Several porcine cell lines have been established based on a variety of tissues, which have shown to extensively contribute to the current understanding of several pathologies, especially cancer. However, protocols for the isolation and culture of swine gastric epithelial cells that preserve cell phenotype are rather limited. We aimed to develop a new method for establishing a primary epithelial cell culture from the fundic gland region of the pig stomach. Results: Mechanical and enzymatic dissociation of gastric tissue was possible by combining collagenase type I and dispase II, protease inhibitors and antioxidants, which allowed the isolation of epithelial cells from the porcine fundic glands showing cell viability > 90% during the incubation period. Gastric epithelial cells cultured in RPMI 1640, DMEM-HG and DMEM/F12 media did not contribute enough to cell adhesion, cluster formation and cell proliferation. By contrast, William’s E medium supplemented with growth factors supports confluency and proliferation of a pure epithelial cell monolayer after 10 days of incubation at 37 °C, 5% CO2. Mucin-producing cell phenotype of primary isolates was confirmed by PAS staining, MUC1 by immunohistochemistry, as well as the expression of MUC1 and MUC20 genes by RT-PCR and cDNA sequencing. Swine gastric epithelial cells also showed origin-specific markers such as cytokeratin cocktail (AE1/AE3) and cytokeratin 18 (CK-18) using immunohistochemical and immunofluorescence methods, respectively. Conclusions: A new method was successfully established for the isolation of primary gastric epithelial cells from the fundic gland zone through a swine model based on a combination of tissue-specific proteases, protease inhibitors and antioxidants after mechanical cell dissociation. The formulation of William’s E medium with growth factors for epithelial cells contributes to cell adhesion and preserves functional primary cells phenotype, which is confirmed by mucin production and expression of typical epithelial markers over time.

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BMC Molecular and Cell Biology