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Sickle cell disease (SCD) and systemic lupus erythematosus (SLE) are two uncommon disorders each characterized by multisystemic manifestations. Individuals with SCD exhibit abnormalities in the complement pathway, which may predispose patients to develop autoimmune disorders such as SLE. As many manifestations of SLE mimic those of SCD, diagnosis and therapeutic management of SLE in a patient with known SCD may be delayed. In this study, we describe our institutional experience of diagnosing and managing concomitant SCD and SLE. We offer insights into the complex interplay between these conditions to enhance early recognition and effective management of concurrent SCD and SLE., (© 2024 Wiley Periodicals LLC.)

Background: Comprehensive guidelines for the management of iron deficiency anemia (IDA) in adolescents with heavy menstrual bleeding (HMB) presenting to the emergency department (ED) are lacking, leading to variability in care. We aimed to standardize the evaluation and management of these patients through the development and implementation of an evidence-based algorithm using quality improvement methodology., Methods: Baseline data of the target population identified variability across four key measures of clinical management: therapy choice and administration, laboratory evaluation, hematology service consultation, and patient disposition. Literature review and consensus from pediatric hematology and gynecology providers informed a draft algorithm that was refined in an iterative multidisciplinary process. From December 2022 to July 2023, we aimed to achieve a 25% relative increase in patients to receive optimal management per the algorithm, while using sequential Plan-Do-Study-Act (PDSA) cycles. Process measures focusing on provider documentation and balancing measures, such as ED length of stay, were assessed concurrently., Results: Forty-nine patients were evaluated during four PDSA cycles. Improvement of ≥40% above baseline regarding recommended therapy administration was achieved across four PDSA cycles. Adherence to recommended therapy choice improved from 57% (baseline) to 100%, minimal laboratory evaluation from 14% to 83%, hematology consultation from 36% to 100%, and appropriate disposition from 71% to 100%. ED length of stay remained stable., Conclusion: Implementation of a standardized algorithm for management of IDA secondary to HMB in adolescents in the ED increased adherence to evidence-based patient care., (© 2024 Wiley Periodicals LLC.)

The intricate composition of microalgal pigments plays a crucial role in various biological processes, from photosynthesis to biomarker identification. Traditional pigment analysis methods involve complex extraction techniques, posing challenges in maintaining analyte integrity. In this study, we employ Electron Transfer Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (ET-MALDI-MS) to compare the pigmentary profiles of Chlorella vulgaris intact cells, chloroplasts, and solvent extracts. We aim to obtain comprehensive extracts rich in polar and non-polar compounds using ultrasound-assisted and supercritical fluid extraction methods. Additionally, intact chloroplasts are isolated using a lysis buffer and sucrose density gradient centrifugation. Our ET-MALDI-MS analysis reveals distinct compositional differences, highlighting the impact of extraction protocols on microalgal pigment identification. We observe prominent signals corresponding to radical cations of key pigments, including chlorophylls and carotenoids, which are crucial for C. vulgaris identification. Furthermore, ET-MALDI-MS facilitates the identification of specific lipids within chloroplast membranes and other organelles. This study underscores the rapid and precise nature of ET-MALDI-MS in microalgal biomarker analysis, providing valuable insights into phytoplankton dynamics, trophic levels, and environmental processes. C. vulgaris emerges as a promising model for studying pigment composition and membrane lipid diversity, enhancing our understanding of microalgal ecosystems.

Therapeutic options for sickle cell disease (SCD) have increased recently as well as the development of updated national guidelines. It is not known how these options are being offered or to what degree guidelines are incorporated into clinical practice. This study aimed to describe practice patterns for pediatric hematologists regarding the use of disease-modifying and potentially curative therapies for SCD. A 9-section, cross-sectional electronic survey was disseminated during a 3-month period via SurveyMonkey, to members of the American Society of Pediatric Hematology/Oncology Hemoglobinopathy Special Interest Group (ASPHO HSIG). A total of 88 physician members of the ASPHO HSIG were surveyed. Ninety percent of respondents (72/80) start hydroxyurea routinely in patients with HbSS and HbSβ 0 thalassemia, regardless of disease severity. Laboratory monitoring was recommended every 3 months for stable dosing in 63.8% (51/80). New therapies were recommended for patients on hydroxyurea who were still experiencing SCD complications: L-glutamine 68.5% (37/54) or crizanlizumab 93.1% (54/58). Voxelotor was recommended for patients on hydroxyurea with low hemoglobin in 65.1% (43/66) of cases. Matched sibling transplant was considered for any disease severity by 55.1% (38/69). Gene therapy trials are offered on-site by 29% (20/69). Our study demonstrated the enhanced utilization of hydroxyurea while revealing the unexplored potential of other disease-modifying therapies in SCD. These findings underscore the importance of continued knowledge acquisition about the long-term efficacy of new medical therapies and addressing barriers to the use of proven therapies and guide the development of future studies of optimal SCD management., Competing Interests: T.A.F. served as a consultant for Forma Therapeutics, Novartis, and Global Blood Therapeutics (all completed). The remaining authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pompe Disease (PD) is a metabolic myopathy caused by variants in the GAA gene, resulting in deficient enzymatic activity. We aimed to characterize the clinical features and related genetic variants in a series of Mexican patients., Methods: We performed a retrospective study of clinical records of patients diagnosed with LOPD, IOPD or pseudodeficiency., Results: Twenty-nine patients were included in the study, comprising these three forms. Overall, age of symptom onset was 0.1 to 43 years old. The most frequent variant identified was c.-32-13T>G, which was detected in 14 alleles. Among the 23 different variants identified in the GAA gene, 14 were classified as pathogenic, 5 were likely pathogenic, and 1 was a variant of uncertain significance. Two variants were inherited in cis arrangement and 2 were pseudodeficiency-related benign alleles. We identified two novel variants (c.1615 G>A and c.1076-20_1076-4delAAGTCGGCGTTGGCCTG)., Conclusion: To the best of our knowledge, this series represent the largest phenotypic and genotypic characterization of patients with PD in Mexico. Patients within our series exhibited a combination of LOPD and IOPD associated variants, which may be related to genetic diversity within Mexican population. Further population-wide studies are required to better characterize the incidence of this disease in Mexican population., (© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

While matched related donor (MRD) allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for transfusion-dependent beta-thalassemia (TDT), the use of alternative sources has increased, resulting in the exploration of novel transplant-conditioning regimens to reduce the contribution of graft-versus-host disease (GVHD) and graft failure (GF) to transplant-related morbidity and mortality. Alemtuzumab is a CD52 monoclonal antibody that has been successfully incorporated into myeloablative conditioning regimens for other hematologic conditions, yet there have been limited studies regarding the use of alemtuzumab in HSCT for TDT. The purpose of this study was to evaluate engraftment, incidence of GVHD, and transplant related morbidity and mortality in patients with TDT who received alemtuzumab in addition to standard busulfan-based conditioning. The primary endpoint was severe GVHD-free, event-free survival (GEFS). Our cohort included 24 patients with a median age of 6.8 years (range 1.5-14.9). Eleven patients received a 10/10 MRD HSCT, eleven 10/10 unrelated donor (UD), and two mismatched UD. All patients achieved primary engraftment. For all patients, 5-year GEFS was 77.4% and 5-year overall survival (OS) was 91%. The 5-year cumulative incidence of GF (attributed to poor graft function) without loss of donor chimerism was 13.8% (95% CI: 4.5, 35.3). We report low rates of significant acute GVHD grade II-IV (12.5%) and chronic GVHD (4.4%). Younger age and MRD were associated with significantly improved GEFS, OS and EFS. Our results show that the use of alemtuzumab promotes stable engraftment, may reduce rates of severe GVHD, and results in acceptable GEFS, OS, and EFS.

Pesticide contamination in emerging foods and supplements is currently a topic of great interest. This study focused on the evaluation of pesticide residues in commercial bee pollen samples to evaluate the risk associated with their consumption. To this end, an automated clean-up method for the pesticide extracts of bee pollen was developed. An LC-MS/MS and a GC-MS/MS method were validated for the analysis of 353 pesticides in 80 bee pollen samples purchased from different countries. The results showed the presence of 77 different pesticide residues in bee pollen, including plant protection chemicals and veterinary treatments. 85 % of the samples were contaminated with pesticides and no relevant differences were found between conventional and organic samples. Pesticide concentrations exceeding the imposed MRL were found in 40 % of the samples, but the risk assessment showed that consumers are not exposed to an unacceptable risk when consuming the evaluated bee pollen., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In Latin America, asthma is a public health problem with a significant impact on both patients and health systems. The greater understanding of the pathophysiology and the recognition of the central role that inflammation has in the severity of asthma has favored the development of monoclonal antibodies that have IL-5, IL-4, IL-13 and IgE as therapeutic targets. Although these therapeutic alternatives promote better control of the disease, not all patients respond favorably to these treatments. Therefore, it is of particular interest to explore monoclonal antibodies such as Tezepelumab, directed against thymic stromal lymphopoietin (TSLP), an alarmin (epithelial cytokine) that participates in the initiation and perpetuation of inflammation in Asthma. Therefore, in this review, we will show the clinical efficacy of tezepelumab in reducing the annual rate of exacerbations, improving lung function, and reducing bronchial hyperreactivity, regardless of the patient's baseline biomarker levels. Therefore, this new molecule is a highly effective therapeutic option for patients with severe asthma., (Licencia CC 4.0 (BY-NC-ND) © 2023 Revista Médica del Instituto Mexicano del Seguro Social.)

Background: Anti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life., Methods: In this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies., Results: A total of 162 patients were included, median age 68 years (range 65-87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.1 ± 7.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days ≥ 30%, ≥ 50%, ≥ 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%)., Conclusions: Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice., (© 2023. The Author(s).)

Objectives: Hexavalent chromium (CrVI)-exposure of suckling rats has been shown to delay tooth eruption. However, the effects of CrVI-exposure on bone formation at the base of the alveolus, which provides a motive force for tooth eruption in the early stages of the process, remain unknown. The present work sought to evaluate the effect of CrVI-exposure on bone formation at the base of the alveolus during the intraosseous stage of tooth eruption in suckling rats, using histomorphometric and immunohistochemical studies., Methods: Experimental animals received 12.5 mg/kg-bw/day of potassium dichromate dissolved in saline solution by gavage starting on day 4 of the experiment; controls similarly received an equivalent volume of saline. All the animals were euthanized at the age of 9 days. The base of the developing alveolus at the level of the mesial root of the first lower molar was analyzed histomorphometrically and immunohistochemically. Data were statistically analyzed using student's t-test, with statistical significance set at p < 0.05., Results: CrVI-exposed animals showed lower bone volume and height at the base of the alveolus, a significant preponderance of bone rest on the surface adjacent to the dental follicle, and a significantly lower percentage of positive Runt-related transcription factor-2 (RUNX2+) osteoblasts and a significantly higher number of mesenchymal-like RUNX2+ cells at the latter site., Conclusion: CrVI-exposure during lactation affects bone formation at the base of the developing alveolus, delaying tooth eruption. These findings underscore the importance of controlling drinking water levels of toxic substances since their effects can alter the growth and development of individuals exposed during early childhood., Competing Interests: Conflict of interest The authors declare no potential conflict of interest regarding the research, authorship and publication of this article., (Copyright © 2023 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

Cacao pod husks (CHs), the most abundant by-product of cacao beans production, can potentially become a source of functional ingredients for the food, cosmetic, and pharmaceutical industries. Three pigment samples (yellow, red, and purple) from lyophilized and ground cacao pod husk epicarp (CHE), were isolated by ultrasound-assisted solvent extraction, with yields between 11 and 14 wt%. The pigments exhibited UV-Vis flavonoid-related absorption bands at 283 nm and 323 nm and, only for the purple extract, reflectance bands in the 400-700 nm range. As per the Folin-Ciocalteu method, the CHE extracts contain high yields of antioxidant phenolic compounds amounting to 161.6, 153.9, and 167.9 mg GAE per g extract for the yellow, red, and purple samples, respectively. Phloretin, quercetin, myricetin, jaceosidin, and procyanidin B1 were among the main flavonoids identified by MALDI-TOF MS. A biopolymeric bacterial-cellulose matrix can effectively retain up to 541.8 mg of CHE extract per g of cellulose in dry weight. Also, MTT assays revealed that CHE extracts are non-toxic and increase viability in cultured VERO cells., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The method describes pigment analysis from microalgae/phytoplankton extracts using electron-transfer Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (ET MALDI MS). Current microalgae/phytoplankton pigment analysis requires resource- and time-intensive chromatographic methods due to the broad polarity range of the target analytes. On the other hand, traditional MALDI MS chlorophyll analysis, using proton-transfer matrices such as 2,5-dihydroxybenzoic acid (DHB) or α-cyano-4-hydroxycinnamic acid (CHCA), results in central metal loss and phytol-ester cleavage. ET MALDI MS is an alternative for the rapid screening and detection of pigments in microalgae extracts.•MALDI matrices with ionization energies above 8.0 eV guarantee electron-transfer processes from photosynthetic and photoprotective pigments whose ionization energies lay below 7.5 eV.•ET MALDI MS pigment analysis agrees with data gathered from conventional chromatographic techniques (HPLC) and optical microscopy for pigment extracts from C. vulgaris cultures and freshwater phytoplankton samples.•The ET MALDI MS method allows fast and reliable detection of pigments in microalgae cultures and freshwater phytoplankton samples ., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier B.V.)

Objective: We aimed to investigate estradiol (E2) as a therapeutic drug for spinal cord injury (SCI) and elucidate the disagreement in the field about the use of this hormone after an injury., Methods: Eleven animals underwent surgery (laminectomy at the T9-T10 levels) followed by an intravenous injection (100 μg) of an E2 bolus and the implantation of 0.5cm of Silastic tubing containing 3 mg of E2 (sham E2 + E2 bolus) immediately after the laminectomy. The SCI control animals received a moderate contusion using the Multicenter Animal SCI Study impactor device over the exposed spinal cord followed by an intravenous bolus injection of sesame oil and were implanted with empty Silastic tubing (injury SE + vehicle); treated rats received a bolus of E2 and a Silastic implant with 3 mg of E2 (injury E2 + E2 bolus). Functional locomotor recovery and fine motor coordination were assessed by the Basso, Beattie, and Bresnahan (BBB) open field test and grid-walking tests, respectively, from the acute (7 days post-injury [DPI]) to the chronic stages (35 DPI). Anatomical studies of the cord were performed using Luxol fast blue staining followed by densitometric analysis., Results: As observed in the BBB open field and the grid-walking tests, E2 post-SCI did not improve locomotor function but instead increased spared white matter tissue, in the rostral region., Conclusion: Estradiol post-SCI, at the dose and route of administration used in this study, failed to promote locomotor recovery but partially restored spared white matter tissue.

Introduction: Pompe disease (PD) is a rare metabolic myopathy with an ample and heterogeneous clinical spectrum, particularly late onset PD (LOPD), which is characterized by appearance at older age and slower disease progression, leading to diagnostic confirmation difficulty and delay., Aim: To describe the genotype and clinical characteristics of Mexican patients with LOPD., Material and Methods: Clinical information from 19 Mexican patients with LOPD confirmed with enzyme activity and GAA gene analysis was reviewed. Genetic information of our population was crossed with international genetic databases., Results: Median age between onset of symptoms and diagnosis was 19 years (range 2-43) and diagnostic confirmation 36 years (range 9-52). Most frequently referred symptoms were proximal axial weakness (n = 17; 89.5%), waddling gait (n = 17; 89.5%) and hyperlordosis (n = 7; 36.8%). Sixteen patients (84.2%) were evaluated with electromyography; a myopathic pattern was reported in 11 (57.8%), but only in 5 patients (26%) paraspinal muscle evaluation was included. The most pathogenic mutations in our group were c.-32-13T>G, c.1799G>A and c.1082C>T., Conclusions: Similar to other international publications, LOPD in Mexico is clinically heterogeneous; patients may delay years before diagnosis is established. Axial and proximal weakness is the most frequent clinical feature; thus, electromyography with paraspinal muscle evaluation is essential. Except for one, the mutations found in our patients have been previously reported in PD genetic databases.

Objectives: The estimates of biological variation (BV) have traditionally been determined using direct methods, which present limitations. In response to this issue, two papers have been published addressing these limitations by employing indirect methods. Here, we present a new procedure, based on indirect methods that analyses data collected within a multicenter pilot study. Using this method, we obtain CV I estimates and calculate confidence intervals (CI), using the EFLM-BVD CV I estimates as gold standard for comparison., Methods: Data were collected over a 18-month period for 7 measurands, from 3 Spanish hospitals; inclusion criteria: patients 18-75 years with more than two determinations. For each measurand, four different strategies were carried out based on the coefficient of variation ratio (rCoeV) and based on the use of the bootstrap method (OS1, RS2 and RS3). RS2 and RS3 use symmetry reference change value (RCV) to clean database., Results: RS2 and RS3 had the best correlation for the CV I estimates with respect to EFLM-BVD. RS2 used the symmetric RCV value without eliminating outliers, while RS3 combined RCV and outliers. When using the rCoeV and OS1 strategies, an overestimation of the CV I value was obtained., Conclusions: Our study presents a new strategy for obtaining robust CV I estimates using an indirect method together with the value of symmetric RCV to select the target population. The CV I estimates obtained show a good correlation with those published in the EFLM-BVD database. Furthermore, our strategy can resolve some of the limitations encountered when using direct methods such as calculating confidence intervals., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Primary screening with Human Papilloma Virus (HPV) testing was introduced in Colombia in 2014 for individuals between 30 and 65 years of age. When the result is positive, cytology triage is performed for colposcopy referral. The convenience of initiating HPV-DNA testing for screening at 25 years of age is currently a subject of discussion. Therefore, the objective of this health technology assessment (HTA) is to analyze the available evidence regarding safety, efficacy, cost-effectiveness, values and preferences, ethical dilemmas and considerations pertaining to the implementation of the HPV-DNA test as a cervical screening strategy in women under 30 years of age in the Colombian context., Domains to Be Assessed: Clinical efficacy and safety 1. Cumulative rate of cervical intraepithelial neoplasia (CIN) grade 2 or high-er after 2 screening rounds. 2. Cumulative rates of invasive cancer of the uterine cervix after 2 screening rounds. 3. Safety: referral to colposcopy. Cost-effectiveness Cost-effectiveness for Colombia. Other domains considered Ethical considerations associated with cervical screening in women under 30 years of age. Organizational and individual considerations. Barriers and facilitators pertaining to the implementation of cervical screening in women under 30 years of age in the Colombian context., Methods: Clinical efficacy and safety assessment A systematic literature search of systematic reviews and clinical trials was conducted in MEDLINE, Embase and CENTRAL. The body of evidence was rated using the GRADE approach. An interdisciplinary team was then convened to create a working group to review the retrieved evidence. This led to the discussion and construction of the conclusions following the guidelines of a formal consensus in accordance with the RAND/UCLA methodology. Economic study Systematic literature research of studies that had assessed cost-effectiveness for Colombia., Results: Clinical outcomes An integrative analysis of 5 randomized clinical trials that met the inclusion critera was performed. Compared with cytology, primary HPV-DNA testing in women under 30 years of age could be associated with a lower frequency of CIN+2 lesions during the first screening round (RR: 1.57; CI: 1.20 to 2.04; low evidence certainty), and a lower incidence of CIN+2 (RR: 0.67; CI: 0.48 to 0.92; low evidence certainty). Moreover, it is associated with a lower frequency of invasive carcinoma at the end of follow-up (RR: 0.19; CI: 0.07 to 0.53; high evidence certainty). Economic results From the financial point of view, the use of HPVDNA testing plus cytology-based triage starting at 25 years of age is perhaps the most cost-effective option for Colombia (incremental cost-effectiveness ratio, COP 8,820,980 in 2013). Other implications Two studies suggest that barriers to implementation attributable to intermediation, public unrest and geographic considerations could be overcome with the use of new screening technologies or strategies. It is important to consider administration and service provision alternatives in order to overcome some acceptability and access barriers. Any cervical screening program must take into consideration ethical principles of nonmaleficence, beneficence, autonomy and equity. Future studies should focus on analyzing new screening techniques with emphasis on the population under 30 years of age., Conclusions: The use of HPV-DNA testing as a screening strategy in women under 30 years of age is a potentially efficacious and cost-effective intervention for Colombia. Future studies should focus on analyzing new screening technologies, with emphasis on the population under 30 years of age.

Introduction: For many patients with primary immune deficiency (PID), stem-cell transplantation (SCT) may be life-saving., Objective: To review our experience of 11 years transplanting children with PID in Mexico., Methods: Chart review of patients who underwent SCT from 2008 to 2018, to describe their diagnoses, time to transplant, conditioning regime, survival rate and outcomes. All patients received post-transplant cyclophosphamide as graft-versus-host-disease (GVHD) prophylaxis., Results: 19 patients with combined, phagocytic or syndromic PID from 5 states. Twelve of them were male (58%) and 14 survive (79%). Mean age at HSCT was 41.9 months; mean time from diagnosis was 31.2 months. Seven grafts were umbilical cord and 12 haploidentical. The conditioning regime was myeloablative, with five primary graft failures. Two patients had partial and 10 full chimerism. Five patients died within 2 months after transplant. Immune reconstitution was complete in 11 of 19 patients. We found a prevalence of 21% GVHD., Discussion: We describe 19 patients from Mexico with 8 PID diagnoses who underwent allogenic HSCT over a period of 11 years. Survival rate and other outcomes compare well with industrialized countries. We recommend the use of post-transplant cyclophosphamide to prevent GVHD in scenarios of resource scarcity and a lack of HLA-identical donors., (© 2022 The Scandinavian Foundation for Immunology.)

Introduction: Pompe disease (PD) is a rare form of metabolic myopathy; the classic infantile presentation is severe, with death occurring before reaching one year of life, and the non-classical form is of slower progression and survival can exceed one year., Objective: To describe the genotype and characteristics of Mexican patients with infantile-onset PD., Methods: Seven patients with PD confirmed by enzymatic activity determination and GAA gene molecular analysis were included. Mutations were reviewed in genomic databases., Results: Median age at symptom onset was four months (1-12 months) and age at diagnosis was eight months (4-16 months). All patients had cardiomyopathy: four who died before one year of age had mutations that predicted severe disease (c.2431dup, c.2560C>T, c.655G>A, c.1987delC) and were negative for cross-reactive immunologic material (CRIM). Three patients survived after one year of age with enzyme replacement therapy; one survived almost five years, another 18 months, and one girl was almost three years of age at the time of this report; their pathogenic variants predicted potentially less severe disease (c.1979G>A, c.655G>A, c.1447G>A) and they were positive for CRIM., Conclusion: There was a good correlation between genotype and phenotype in children with Pompe disease., (Copyright: © 2022 Permanyer.)

Psychophysical methods allow us to measure the relationship between stimuli and sensory perception. Of these, Detection Threshold (DT) allows us to know the minimum concentration to produce taste identification. Given this, we wonder whether, for example, wine tasting experts are more capable of perceiving their sensory properties than other people, or whether they can distinguish them because they are better able to "describe" them. To verify this, this study analyses the influence of having prior knowledge of the name astringency and, failing that, to detect it and distinguish it between the four basic tastes. One-hundred-and-sixty-two university students with an average age of 19.43 (SD = 2.55) years were assigned to three experimental conditions: an experimental group (G.2) without previous knowledge of the name astringency and with alimentary satiety, and two control groups, both with previous knowledge of the name, these being G.1, with satiety, and G.3, with hunger. DT was collected for the four basic tastes and astringencies. Results showed significant differences in the identification of astringency, being the least identified experimental group with respect to the control groups. It is striking that G.2, without prior knowledge of the name, identified astringency as a bitter taste in most cases. This supports our hypothesis of the importance of attending to linguistic cognitive processes when psychophysically estimating taste in humans.

Oat, Avena sativa , is an important crop traditionally grown in cool-temperate regions. However, its cultivated area in the Mediterranean rim steadily increased during the last 20 years due to its good adaptation to a wide range of soils. Nevertheless, under Mediterranean cultivation conditions, oats have to face high temperatures and drought episodes that reduce its yield as compared with northern regions. Therefore, oat crop needs to be improved for adaptation to Mediterranean environments. In this work, we investigated the influence of climatic and edaphic variables on a collection of 709 Mediterranean landraces and cultivars growing under Mediterranean conditions. We performed genotype-environment interaction analysis using heritability-adjusted genotype plus genotype-environment biplot analyses to determine the best performing accessions. Further, their local adaptation to different environmental variables and the partial contribution of climate and edaphic factors to the different agronomic traits was determined through canonical correspondence, redundancy analysis, and variation partitioning. Here, we show that northern bred elite cultivars were not among the best performing accessions in Mediterranean environments, with several landraces outyielding these. While all the best performing cultivars had early flowering, this was not the case for all the best performing landraces, which showed different patterns of adaption to Mediterranean agroclimatic conditions. Thus, higher yielding landraces showed adaptation to moderate to low levels of rain during pre- and post-flowering periods and moderate to high temperature and radiation during post-flowering period. This analysis also highlights landraces adapted to more extreme environmental conditions. The study allowed the selection of oat genotypes adapted to different climate and edaphic factors, reducing undesired effect of environmental variables on agronomic traits and highlights the usefulness of variation partitioning for selecting genotypes adapted to specific climate and edaphic conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Canales, Montilla-Bascón, Gallego-Sánchez, Flores, Rispail and Prats.)

Introduction: Patients with inborn errors of immunity (IEI) have a compromised or inappropriate immune response. Although they might be considered a high-risk group for severe SARS-CoV-2 infection, the reported impact of COVID-19 in these patients has been reassuring, while the differential susceptibility of distinct types of IEI remains unclear., Objective: We aimed to describe the findings and outcomes of our known patients with IEI who were diagnosed with COVID-19., Methods: In a retrospective study from March 2020 to February 2021, four centers in Mexico collected clinical, laboratory, and genetic data from pediatric and adult patients with known diagnoses of IEI who presented with COVID-19, based on compatible symptoms and positive SARS-CoV-2 testing or known household exposure., Results: We report 31 patients with known IEI from Mexico who presented with SARS-CoV-2 infection. Seventy-four percent were male, 52% were pediatric, and 81% survived. Their ages ranged from 5 months to 56 years, with a median of 17 years. Sixty-five percent had predominant antibody deficiencies, 48% were hospitalized, and 26% required ICU. Pediatric patients had a higher hospital admission rate than adults. Inpatient mortality was 40%, and ICU mortality rate was 63%. Forty-eight percent developed pneumonia, while 36% had evidence of hyperinflammation (4 adults and 7 children). Predominant laboratory features were lymphopenia and thrombocytopenia, seen in 70 and 44% of patients, respectively. The serum D-dimer median value was 2.6 (0.5-20.6) μg/mL, and the median highest ferritin value was 1015 (32-10,303) ng/mL. Intravenous immunoglobulin was used in 80% of patients. Other treatments included macrolides (39%) and corticosteroids (29%). Six patients died from secondary infection or uncontrolled systemic inflammation., Discussion: Although impaired immunity due to IEI may be a predisposing factor for severe COVID-19, most of our patients with IEI who acquired the SARS-CoV-2 infection developed a well-tolerated infection and survived, as have more than 80% of worldwide reported patients to date. An impaired immune or inflammatory response may be a predisposing factor for some and a protective factor for others. A systematic review of the literature could help identify those patients at risk of severe disease and complications. Healthcare-associated infections should be aggressively prevented., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The shape and dimensions of a micromixer are key elements in the mixing process. Accurately quantifying the mixing efficiency enables the evaluation of the performance of a micromixer and the selection of the most suitable one for specific applications. In this paper, two methods are investigated to evaluate the mixing efficiency: a numerical model and an experimental model with a software image processing technique. Using two methods to calculate the mixing efficiency, in addition to corroborating the results and increasing their reliability, creates various possible approaches that can be selected depending on the circumstances, resources, amount of data to be processed and processing time. Image processing is an easy-to-implement tool, is applicable to different programming languages, is flexible, and provides a quick response that allows the calculation of the mixing efficiency using a process of filtering of images and quantifying the intensity of the color, which is associated with the percentage of mixing. The results showed high similarity between the two methods, with a difference ranging between 0 and 6% in all the evaluated points.

Although it has been demonstrated that exposure of lactating rats to CrVI delays tooth eruption, the effects of CrVI exposure on bone remodeling in the developing alveolus during tooth eruption remain unknown. Our purpose was to analyze the effect of CrVI in the alveolus of the first lower molar of rats. Thirty-two suckling Wistar rats were divided into two groups. The experimental group received 12.5 mg/kg body weight/day of potassium dichromate dissolved in saline solution by oral gavage as of day 4 of the experiment; the control group received an equal dose of saline solution. Each group was divided into two sub-sets and euthanized at the ages of 9 and 15 days, respectively. Histochemical and histomorphometric studies of the bone surfaces of the developing tooth alveolus were performed. The percentage of bone formation surfaces was lower in experimental animals than in age-matched controls. The percentage of bone resorption surfaces was significantly lower in 9-day-old experimental rats than in controls and significantly higher in 15-day-old experimental rats than in controls. Exposure to CrVI during lactation alters the sequence of bone resorption and formation in the walls of the developing alveolus, both of which are necessary for tooth eruption, thus causing a delay., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article, (Sociedad Argentina de Investigación Odontológica.)

Liposomes encapsulate different substances ranging from drugs to genes. Control over the average size and size distribution of these nanoparticles is vital for biomedical applications since these characteristics determine to a high degree where liposomes will accumulate in the human body. Micromixers enable the continuous flow synthesis of liposomes, improving size control and reproducibility. Recently, Dean flow dynamics-based micromixers, such as the periodic disturbance mixer (PDM), have been shown to produce controlled-size liposomes in a scalable and reproducible way. However, contrary to micromixers based on molecular diffusion or chaotic advection, their production factors and their influence over liposome properties have not yet been addressed thoroughly. In this work, we present a comprehensive parametric study of the effects of flow conditions and molecular changing factors such as concentration, lipid type, and temperature on the physicochemical characteristics of liposomes. Numerical models and confocal images are used to quantitatively and qualitatively evaluate mixing performance under different liposome production conditions and their relationship with vesicle properties. The total flow rate (TFR) and, to a lesser extent, the flow rate ratio (FRR) control the liposome size and size distribution. Effects on liposome size are also observed by changing the molecular factors. Moreover, the liposome ζ potential is independent of the factors studied here. The micromixer presented in this work enables the production of liposomes as small as 24 nm, with monodispersed to low or close to low polydispersed liposome populations as well as a production rate as high as 41 mg/h.

The assessment and treatment of emotional variables is a priority in the rehabilitation of offenders. Although theoretical proposals suggest a clear relationship between violence and self-esteem, attachment, and empathy, the research carried out to date has reached contradictory results due mainly to differences in the measurements used, the reliability of self-reports, or even to problems with the definition of the constructs. The present study analyzed these three variables in a prison sample of sexual offenders ( n = 48) and partner-violent men ( n = 68), using the Interpersonal Reactivity Index , the Rape Empathy Measure , the Rosenberg Self-Esteem Scale , and the Adult Attachment Questionnaire . Results confirmed the low utility of nonspecific empathy, the predominance of high self-esteem, and the difficulty of identifying an insecure attachment. The implications of the use of these variables in the treatment of offenders, and the need to improve the assessment tools, are discussed.

Cancer stem cells (CSCs) are involved in the resistance of estrogen (ER)-positive breast tumors against endocrine therapy. On the other hand, nitric oxide (NO) plays a relevant role in CSC biology, although there are no studies addressing how this important signaling molecule may contribute to resistance to antihormonal therapy in ER + breast cancer. Therefore, we explored whether targeting NO in ER + breast cancer cells impacts CSC subpopulation and sensitivity to hormonal therapy with tamoxifen. NO was targeted in ER + breast cancer cells by specific NO depletion and NOS2 silencing and mammosphere formation capacity, stem cell markers and tamoxifen sensitivity were analyzed. An orthotopic breast tumor model in mice was also performed to analyze the efficacy of NO-targeted therapy plus tamoxifen. Kaplan-Meier curves were made to analyze the association of NOS2 gene expression with survival of ER + breast cancer patients treated with tamoxifen. Our results show that targeting NO inhibited mamosphere formation, CSC markers expression and increased the antitumoral efficacy of tamoxifen in ER + breast cancer cells, whereas tamoxifen-resistant cells displayed higher expression levels of NOS2 and Notch-1 compared with parental cells. Notably, NO-targeted therapy plus tamoxifen was more effective than either treatment alone in an orthotopic breast tumor model in immunodeficient mice. Furthermore, low NOS2 expression was significantly associated with a higher metastasis-free survival in ER + breast cancer patients treated with tamoxifen. In conclusion, our data support that NO-targeted therapy in ER + breast cancer may contribute to increase the efficacy of antihormonal therapy avoiding the development of resistance to these treatments.

Introduction: Knee dislocation is a rare injury but considered serious clinically since it can be accompanied by vascular and neurological injuries that if they do not have a timely diagnosis and treatment can lead to the loss of the limb. Regarding vascular injury, the optimal diagnostic method for the identification of this type of lesion is of the utmost importance., Objective: To present the literature review on the epidemiology, classification and diagnostic approach of knee dislocation with or without associated vascular injury., Methods: Report of the literature found in databases and analyses based on clinical experience and synthesis of these documents., Conclusion: Vascular injury is not an uncommon finding in the context of knee dislocation, with a high risk of complications and even amputation if an early diagnosis is not made, the authors recommend angio-CT to confirm the suspected diagnosis and not delay treatment.

This study represents a novel proof of concept of the clinical utility of miRNAs from exhaled breath condensate (EBC) as biomarkers of lung cancer (LC). Genome-wide miRNA profiling and machine learning analysis were performed on EBC from 21 healthy volunteers and 21 LC patients. The levels of 12 miRNAs were significantly altered in EBC from LC patients where a specific signature of miR-4507, miR-6777-5p and miR-451a distinguished these patients with high accuracy. Besides, a distinctive miRNA profile between LC adenocarcinoma and squamous cell carcinoma was observed, where a combined panel of miR-4529-3p, miR-8075 and miR-7704 enabling discrimination between them. EBC levels of miR-6777-5p, 6780a-5p and miR-877-5p predicted clinical outcome at 500 days. Two additional miRNA signatures were also associated with other clinical features such as stage and invasion status. Dysregulated EBC miRNAs showed potential target genes related to LC pathogenesis, including CDKN2B, PTEN, TP53, BCL2, KRAS and EGFR. We conclude that EBC miRNAs might allow the identification, stratification and monitorization of LC, which could lead to the development of precision medicine in this and other respiratory diseases.

Liposomes are versatile particles used in the biomedical field as drug delivery systems (DDS). Liposome production using micromixers have shown to yield nanoparticles for DDS in a single step with a controllable size by changing flow conditions. Nonetheless, other factors such as the organic solvent, play a crucial role in the liposome formation process. Furthermore, drug solubility and toxicity are pivotal when deciding which organic solvent to choose. In this work, liposomes were produced in a periodic disturbance mixer (PDM). We investigated three conventional organic solvents: ethanol, methanol, and isopropanol as well as Transcutol®. We assessed the organic solvent influence on liposome characteristics (size, size distribution and zeta potential). Among the four organic solvents, Transcutol® yielded the smallest liposomes, which ranged from 80 nm to 160 nm. Moreover, a more in-depth investigation showed that Transcutol® produced smaller or similar-sized particles under different temperature and lipid concentration conditions, compared with ethanol. Furthermore, we proved that particles zeta potential was not influenced by the organic solvent, production temperature, or lipid concentration. This work results show that Transcutol® could replace the conventional alcohol-based solvents and can potentially avoid filtration steps due to its low toxicity. Therefore, the present approach is appealing for DDS development., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Recently, phenotyping has become one of the main bottlenecks in plant breeding and fundamental plant science. This is particularly true for plant disease assessment, which has to deal with time-consuming evaluations and the subjectivity of visual assessments. In this work, we have developed an open source Robust, User-friendy Script Tool (RUST) for semi-automated evaluation of leaf rust diseases. RUST runs under the free Fiji imaging software (developed from ImageJ), which is a well-recognized software among the scientific community. The script enables the evaluation of leaf rust diseases using a color transformation tool and provides three different automation modes. The script opens images sequentially and records infection frequency (pustules per area) (semi-)automatically for high-throughput analysis. Furthermore, it can manage several scanned leaf segments in the same image, consecutively selecting the desired segments. The script has been validated with nearly 900 samples from 80 oat genotypes ranging from resistant to susceptible and from very light to heavily infected leaves showing a high accuracy with a Lin's concordance correlation coefficient of 0.99. The analysis show a high repeatability as indicated by the low variation coefficients obtained when repeating the measurement of the same samples. The script also has optional steps for calibration and training to ensure accuracy, even in low-resolution images. This script can evaluate efficiently hundreds of leaves facilitating the screening of novel sources of resistance to this important cereal disease.

Tumor budding has been found to be of prognostic significance for several cancers, including colorectal cancer (CRC). Additionally, the molecular classification of CRC has led to the identification of different immune microenvironments linked to distinct prognosis and therapeutic response. However, the association between tumor budding and the different molecular subtypes of CRC and distinct immune profiles have not been fully elucidated. This study focused, firstly, on the validation of derived xenograft models (PDXs) for the evaluation of tumor budding and their human counterparts and, secondly, on the association between tumor budding and the immune tumor microenvironment by the analysis of gene expression signatures of immune checkpoints, Toll-like receptors (TLRs), and chemokine families. Clinical CRC samples with different grades of tumor budding and their corresponding PDXs were included in this study. Tumor budding grade was reliably reproduced in early passages of PDXs, and high-grade tumor budding was intimately related with a poor-prognosis CMS4 mesenchymal subtype. In addition, an upregulation of negative regulatory immune checkpoints (PDL1, TIM-3, NOX2, and IDO1), TLRs (TLR1, TLR3, TLR4, and TLR6), and chemokine receptors and ligands (CXCR2, CXCR4, CXCL1, CXCL2, CXCL6, and CXCL9) was detected in high-grade tumor budding in both human samples and their corresponding xenografts. Our data support a close link between high-grade tumor budding in CRC and a distinctive immune-suppressive microenvironment promoting tumor invasion, which may have a determinant role in the poor prognosis of the CMS4 mesenchymal subtype. In addition, our study demonstrates that PDX models may constitute a robust preclinical platform for the development of novel therapies directed against tumor budding in CRC., (Copyright © 2020 Guil-Luna, Mena, Navarrete-Sirvent, López-Sánchez, Khouadri, Toledano-Fonseca, Mantrana, Guler, Villar, Díaz, Medina-Fernández, De la Haba-Rodríguez, Aranda and Rodríguez-Ariza.)

Nitric oxide (NO) has been highlighted as an important agent in tumor processes. However, a complete understanding of the mechanisms by which this simple diatomic molecule contributes in tumorigenesis is lacking. Evidence is rapidly accumulating that metabolic reprogramming is a major new aspect of NO biology and this review is aimed to summarize recent research progress on this novel feature that expands the complex and multifaceted role of NO in cancer. Therefore, we discuss how NO may influence glucose and glutamine utilization by tumor cells, and its participation in the regulation of mitochondrial function and dynamics, that is an important mechanism through which cancer cells reprogram their metabolism to meet the biosynthetic needs of rapid proliferation. Finally, we also discuss the NO-related metabolic rewiring involved in the modification of the tumor microenvironment to support cancer invasion and the escape from immune system-mediated recognition. Protein S-nitrosylation appears as a common mechanism by which NO signaling reprograms metabolism. Hence, future research is needed on dysregulated S-nitrosylation/denitrosylation in cancer to comprehend the NO-induced metabolic changes in tumor cells and the role of NO in the metabolic crosstalk within tumor microenvironment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

To evaluate the level of adherence to antidepressant therapies and associated factors in patients with depressive disorders. a cross-sectional analytical study was conducted in patients diagnosed with depressive disorders. The sample was for convenience, and a survey including sociodemographic, clinical, and therapeutic variables was designed. The Morisky-Green test, Beliefs about Medicines Questionnaire, and Simplified Medication Adherence Questionnaire were also used, all of which have been validated for assessing adherence in patients with depression. The qualitative variables were evaluated with absolute and relative frequencies, and a bivariate analysis was performed. This study included 54 patients with an average age of 49.5 ± 13.7 years, and 83.3% were women. All patients were diagnosed with major depression, and 9.25% also had an anxiety disorder. According to the Morisky-Green test, only 37% of patients were compliant with the drug therapy, although this was not statistically significant. Women were less compliant than men (33.3% versus 55.6%; p = 0.21). The beliefs that patients have regarding medication do not have a great impact on adherence to antidepressant therapy. However, it was evidenced that adherent patients had less doubts about the medication administered in comparison to non-adherent patients.

Liposomes nanoparticles (LNPs) are vesicles that encapsulate drugs, genes, and imaging labels for advanced delivery applications. Control and tuning liposome physicochemical characteristics such as size, size distribution, and zeta potential are crucial for their functionality. Liposome production using micromixers has shown better control over liposome characteristics compared with classical approaches. In this work, we used our own designed and fabricated Periodic Disturbance Micromixer (PDM). We used Design of Experiments (DoE) and Response Surface Methodology (RSM) to statistically model the relationship between the Total Flow Rate (TFR) and Flow Rate Ratio (FRR) and the resulting liposomes physicochemical characteristics. TFR and FRR effectively control liposome size in the range from 52 nm to 200 nm. In contrast, no significant effect was observed for the TFR on the liposomes Polydispersity Index (PDI); conversely, FRR around 2.6 was found to be a threshold between highly monodisperse and low polydispersed populations. Moreover, it was shown that the zeta potential is independent of TFR and FRR. The developed model presented on the paper enables to pre-establish the experimental conditions under which LNPs would likely be produced within a specified size range. Hence, the model utility was demonstrated by showing that LNPs were produced under such conditions.

Background: Heavy metals including Cr VI are present in inadequately treated effluents that contaminate drinking water. Hence, Cr VI exposure can affect children through intake of breast milk from an exposed mother or bottle-feeding formula prepared with contaminated water. To date, there are no reports on the effects of Cr VI exposure on tooth formation processes concomitant to tooth eruption., Aim: To study the effect of Cr VI exposure on tooth tissue formation in suckling Wistar rats by assessing dental tissues at different stages of tooth eruption., Design: Experimental animals received 12.5 mg/kg body weight/day of a potassium dichromate solution by gavage; control animals were similarly administered an equivalent volume of saline solution. Each group was divided into three subsets according to age at euthanasia: 9, 15, and 23 days. Dental formation was analysed histologically and histomorphometrically., Statistical Analysis: Student's t test; P < .05., Results: Cr VI-exposed animals showed a delay in mineralized crown and root tissue formation. These findings are directly associated with the observed delay in tooth eruption., Conclusion: Our findings show the importance of monitoring drinking water levels of toxic substances, since exposure during early childhood can alter tooth formation, growth, and development., (© 2019 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Newly emerged proteomic methodologies, particularly data-independent acquisition (DIA) analysis-related approaches, would improve current gene expression-based classifications of colorectal cancer (CRC). Therefore, this study was aimed to identify protein expression signatures using SWATH-MS DIA and targeted data extraction, to aid in the classification of molecular subtypes of CRC and advance in the diagnosis and development of new drugs. For this purpose, 40 human CRC samples and 7 samples of healthy tissue were subjected to proteomic and bioinformatic analysis. The proteomic analysis identified three different molecular CRC subtypes: P1, P2 and P3. Significantly, P3 subtype showed high agreement with the mesenchymal/stem-like subtype defined by gene expression signatures and characterized by poor prognosis and survival. The P3 subtype was characterized by decreased expression of ribosomal proteins, the spliceosome, and histone deacetylase 2, as well as increased expression of osteopontin, SERPINA 1 and SERPINA 3, and proteins involved in wound healing, acute inflammation and complement pathway. This was also confirmed by immunodetection and gene expression analyses. Our results show that these tumours are characterized by altered expression of proteins involved in biological processes associated with immune evasion and metastasis, suggesting new therapeutic options in the treatment of this aggressive type of CRC., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Reduced bone quality or mineral density predict susceptibility to fracture and also attenuate subsequent repair. Bone regrowth is also compromised by bacterial infection, which exacerbates fracture site inflammation. Because of the cellular complexity of fracture repair, as well as genetic and environmental influences, there is a need for models that permit visualisation of the fracture repair process under clinically relevant conditions. To characterise the process of fracture repair in zebrafish, we employed a crush fracture of fin rays, coupled with histological and transgenic labelling of cellular responses; the results demonstrate a strong similarity to the phased response in humans. We applied our analysis to a zebrafish model of osteogenesis imperfecta (OI), which shows reduced bone quality, spontaneous fractures and propensity for non-unions. We found deficiencies in the formation of a bone callus during fracture repair in our OI model and showed that clinically employed antiresorptive bisphosphonates can reduce spontaneous fractures in OI fish and also measurably reduce fracture callus remodelling in wild-type fish. The csf1ra mutant, which has reduced osteoclast numbers, also showed reduced callus remodelling. Exposure to excessive bisphosphonate, however, disrupted callus repair. Intriguingly, neutrophils initially colonised the fracture site, but were later completely excluded. However, when fractures were infected with Staphylococcus aureus , neutrophils were retained and compromised repair. This work elevates the zebrafish bone fracture model and indicates its utility in assessing conditions of relevance to an orthopaedic setting with medium throughput.This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

Spa mineral waters are used for the treatment of chronic diseases' symptoms. Anti-inflammatory, analgesic, anti-ageing and tissue repair effects have been attributed to them. This work seeks to improve knowledge about the effect of spa mineral waters on human cells. For this, human lung fibroblasts were treated with mineral waters from Ledesma, Paracuellos and Archena spas, three Spanish health resorts with different water chemical composition. A significant increase of cell proliferation together with an enhanced antioxidant capacity (reactive oxygen and nitrogen species, glutathione levels and superoxide dismutase activity) in mineral water-treated fibroblasts compared to control fibroblasts was observed. Moreover, cytokine profiling revealed an increase in the release of MIF, IL-6, CL-1, CCL-5 and ICAM-1, which are described as mediators in proliferation, wound healing and cell migration processes. In conclusion, our results could be in line with the effects attributed to spa mineral waters in wound healing strategies and oxidative damage protection.

Objectives: Lung metastasizing leiomyomatosis (LML) is an infrequently diagnosed pathology developed after sexual maturation, commonly preceded by uterine myomas. Symptoms can include difficulties to breathe, cough, dyspnea and pain, because of mechanical obstruction exerted by expanding local growing leiomyomas. Lung leiomyomas are normally detected by imaging studies, but nowadays the precise diagnosis demands histological characterization of biopsies obtained from the affected tissues. The purpose of the present study was to determine the presence of genomic alterations in circulating cells of LML., Methods: Immunohistochemical characterization of a lung biopsy extracted by thoracoscopy was performed. Pathologic proliferative smooth muscle cells were observed in a major lung metastasizing nodule, with a growing pattern similar to a uterine myoma. The presence of cellular linages different to smooth muscle cells was discarded by testing the presence of a battery of molecular markers. Also, a normal karyotype was determine by GTG-banding cytogenetic study, but a high density microarray analysis revealed six submicroscopic chromosomal regions displaying genomic abnormalities: microduplications were detected on chromosomes 4, 14, 17 and 22; and microdeletions on chromosomes 8 and 10., Conclusion: This study remarks the relevance of submicroscopic chromosomal analysis of unusual pathologic conditions such as Benign Metastasizing Leiomyomatosis. This propitiate a better understanding of the molecular basis on the development of the pathology, in order to reckon on minimally invasive diagnostic methods, and to design appropriate treatments., (© 2018 John Wiley & Sons Ltd.)

The treatment of refractory terminal heart failure has been heart transplantation. However, there are limitations with regard to clinical conditions of the recipient and availability of donors, and ventricular support has therefore been alternatively used as destination therapy. We describe the case is of a female patient with ischemic cardiomyopathy-associated heart failure who had a left ventricular assist device successfully implanted and at eight months of the procedure was at functional class I, with no complications., (Copyright: © 2019 SecretarÍa de Salud.)