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Abstract: Epidote etching anisotropy has been studied through step etching of 86Kr (300 MeV) ion tracks. A slice of epidote natural monocrystal was taken from the (010) plane and then divided into five pieces. Each piece was then irradiated with ions whose incidence angles (zenith angles) were of 15°, 30°, 45°, 60° and 75° with respect to y-axis. The azimuthal angle of incidence of the ions was the same for the pieces 15°, 60°, 75° and 180° apart for the pieces 30° and 45°. Etching times were of 10, 20, 30, 40 and 50 min (HF 40%, 35 °C). The results show that etching velocities of ion tracks are higher in directions closer to the y-axis. The mean lengths of the ion tracks, regarding the angles, were of 23.14 ± 0.21 (15°); 19.89 ± 0.08 (30°); 19.39 ± 0.04 (45°) and 16.59 ± 0.10 μm (60°). Since no tracks were identified in the 75° aliquot it was assumed that the epidote has a critical angle, for recording of ion tracks with this mass/energy ratio, between 60° and 75°. [Copyright &y& Elsevier]

Background and Aims: Interstitial lung diseases (ILDs), encompassing both pediatric and adult cases, present a diverse spectrum of chronic conditions with variable prognosis. Despite limited therapeutic options beyond antifibrotic drugs and immunosuppressants, accurate diagnosis is challenging, often necessitating invasive procedures that may not be feasible for certain patients. Drawn against this background, experts across pediatric and adult ILD fields have joined forces in the RARE-ILD initiative to pioneer novel non-invasive diagnostic algorithms and biomarkers. Collaborating with the RARE-ILD consortium, the eurILDreg aims to comprehensively describe different ILDs, analyze genetically defined forms across age groups, create innovative diagnostic and therapeutic biomarkers, and employ artificial intelligence for data analysis., Methods: The foundation of eurILDreg is built on a comprehensive parameter list developed and adopted by clinical experts, encompassing over 1,800 distinct parameters related to patient history, clinical examinations, diagnosis, lung function and biospecimen collection. This robust dataset is further enriched with daily assessments captured through the patientMpower app, including handheld spirometry and exercise tests, conducted on approximately 350 patients over the course of a year. This approach involves app-based daily assessments of quality of life, symptom tracking, handheld spirometry, saturation measurement, and the 1-min sit-to-stand test (1-STST). Additionally, pediatric data from the ChILD-EU registry will be integrated into the RARE-ILD Data Warehouse, with the ultimate goal of including a total of 4.000 ILD patients and over 100.000 biospecimen., Discussion: The collaborative efforts within the consortium are poised to streamline research endeavors significantly, promising to advance patient-centered care, foster innovation, and shape the future landscape of interstitial lung disease research and healthcare practices., Trial Registration: EurILDreg is registered in the German Clinical Trials Register (DRKS 00028968, 26.07.2022), and eurIPFreg is registered in ClinicalTrials.gov (NCT02951416)., Competing Interests: Declarations Ethics approval and consent to participate The ethics committee of the Justus Liebig University of Giessen has approved the eurILDreg as extension of eurIPFreg under protocol reference number 111/08. Additionally, approval from the medical ethics committee at each participating site will be obtained prior to patient inclusion. Written informed consent will be obtained from all participants. The study will be conducted in accordance with the Declaration of Helsinki. Consent for publication All authors gave their consent for publication. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The biotechnological development of monoclonal antibodies and their immunotherapeutic use in oncology have grown exponentially in the last decade, becoming the first-line therapy for some types of cancer. Their mechanism of action is based on the ability to regulate the immune system or by interacting with targets that are either overexpressed in tumor cells, released into the extracellular milieu or involved in processes that favor tumor growth. In addition, the intrinsic characteristics of each subclass of antibodies provide specific effector functions against the tumor by activating antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis, among other mechanisms. The rational design and engineering of monoclonal antibodies have improved their pharmacokinetic and pharmacodynamic features, thus optimizing the therapeutic regimens administered to cancer patients and improving their clinical outcomes. The selection of the immunoglobulin G subclass, modifications to its crystallizable region (Fc), and conjugation of radioactive substances or antineoplastic drugs may all improve the antitumor effects of therapeutic antibodies. This review aims to provide insights into the immunological and pharmacological aspects of therapeutic antibodies used in oncology, with a rational approach at molecular modifications that can be introduced into these biological tools, improving their efficacy in the treatment of cancer., (© 2024. The Author(s).)

Impulsivity has been proposed to have an impact on glycemic dysregulation. However, it remains uncertain whether an unfavorable glycemic status could also contribute to an increase in impulsivity levels. This study aims to analyze associations of baseline and time-varying glycemic status with 3-year time-varying impulsivity in older adults at high risk of cardiovascular disease. A 3-year prospective cohort design was conducted within the PREDIMED-Plus-Cognition substudy. The total population includes 487 participants (mean age = 65.2 years; female = 50.5%) with overweight or obesity and metabolic syndrome. Insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), presence of type 2 diabetes mellitus, and type 2 diabetes control were evaluated. Impulsivity was measured using the Impulsive Behavior Scale questionnaire and various cognitive measurements. Impulsivity z-scores were generated to obtain Global, Trait, and Behavioral Impulsivity domains. Linear mixed models were used to study the longitudinal associations across baseline, 1-year, and 3-year follow-up visits. HOMA-IR was not significantly related to impulsivity. Participants with higher HbA1c levels, type 2 diabetes, and poor control of diabetes showed positive associations with the Global Impulsivity domain over time, and those with higher HbA1c levels were further related to increases in the Trait and Behavioral Impulsivity domains over the follow-up visits. These results suggest a potential positive feedback loop between impulsivity and glycemic-related dysregulation., (© 2024 The Author(s). Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of The New York Academy of Sciences.)

This project aims to establish the acceptability and satiety of a hybrid snack containing plant protein and a small percentage of animal protein compared to a meat-based snack., Design: Randomised, crossover, double-blind, controlled post-prandial trial involving 24 participants (18-30 years), with two interventions: (a) a hybrid snack containing plant protein derived from chickpeas and 6.6% lean high-quality pork meat; and (b) a meat-based snack containing 90% lean pork meat., Methods: General, life-style, sensory acceptability questionnaire, and the following laboratory analyses were performed: lipid profile, endocannabinoids, and related compounds., Results: Sensory questionnaires showed in general good acceptability for both bars. Additionally, there was a greater increase in glycemia at 30, 60, and 90 min after consuming the hybrid snack compared to the meat-based snack, with no changes in the lipid profile. Regarding the endocannabinoid compounds and related compounds, the compound N-palmitoleoyl ethanolamine in the acylethanolamide group showed higher levels overall following the consumption of the hybrid snack compared to the meat-based snack, particularly at 2 h., Conclusions: The hybrid snack was associated with changes in endocannabinoid-like compounds. Therefore, it may provide a lasting satiating effect, while complementing the protein profile of plant-based foods with the quality of animal protein.

Objectives: This study evaluated the efficacy of an ultra-low-dose 0.005 % estriol vaginal gel in the prevention of urinary tract infections in postmenopausal women with genitourinary syndrome of menopause., Study Design: Randomized, double-blind, placebo-controlled, multicenter clinical trial conducted across 28 Spanish sites involving specialists in gynecology, urology, and primary care. A total of 108 postmenopausal women were randomly assigned in a 1:1 ratio to receive 1 g of vaginal gel with 50 micrograms of estriol or an identical moisturizing vaginal gel without estriol., Main Outcome Measures: The primary outcome was the number of episodes of urinary tract infection by the end of the 24-week treatment. Secondary measures encompassed percentage of patients without recurrence, time to first recurrence, use of antibiotic treatment, vaginal pH, safety, and tolerability, among others., Results: The incidence rate of urinary tract infections (new cases per 100 women-year) was 26 % lower in the group that received estriol vs. the group that received placebo (32.34 vs. 43.76 (RR = 0.74) p < 0.001). The frequency of urinary tract infections fell during treatment in all patients in the estriol group. Favorable pH changes from baseline were observed in the estriol arm at all follow-up visits., Conclusions: Ultra-low-dose 0.005 % estriol vaginal gel is safe and effective in preventing recurrent urinary tract infections in postmenopausal women with genitourinary syndrome of menopause, reducing the incidence and potentially decreasing the susceptibility to urogenital infections by improving vaginal pH. Study registration N°: 2018-001481-42. Date of registration: 09-04-2018., Competing Interests: Declaration of competing interest Susana Duce Tello declares to have received payments or fees for lectures, presentations, manuscript writing or educational events from Novartis, Pfizer. Payment for expert testimony from Italfarmaco, and support for attending meetings and/or travel from Viatris. Milagros González has been sponsored in communications at conferences and training courses by Chiesi, Menarini, GSK, Pfizer, Daichi Sankio, Alter, Astra Zeneca and Zentivia. Javier Rosado declares to have received fees for lectures and as a consultant from Astra-Zéneca, Boehringer Ingelgheim, Chiesi, Italfármaco, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi-Aventis, Recordati, Daichi-Sankyo, Almirall, Servier, Medtronic. Laura Noguera, Ana Doyle Sanchez, Amelia Rodríguez and Eva Aguilar are full time employees at ITF Research Pharma. All other authors declare that they have no competing of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: The current literature provides limited guidance on the best diuretic strategy post-hospitalization for acute heart failure (AHF). It is postulated that the efficacy and safety of the outpatient diuretic regimen may be significantly influenced by the degree of fluid overload (FO) encountered during hospitalization. We hypothesize that in patients with more pronounced FO, reducing their regular oral diuretic dosage might be associated with an elevated risk of unfavourable clinical outcomes., Methods and Results: It was a retrospective observational study of 410 patients hospitalized for AHF in which the dose of furosemide at admission and discharge was collected. Patients were categorized across diuretic dose status into two groups: (i) the down-titration group and (ii) the stable/up-titration group. FO status was evaluated by a clinical congestion score and circulating biomarkers. The endpoint of interest was the composite of time to all-cause death and/or heart failure readmission. A multivariable Cox proportional hazard regression model was constructed to analyse the endpoints. The median age was 86 (78-92) years, 256 (62%) were women, and 80% had heart failure with preserved ejection fraction. After multivariate adjustment, the down-titration furosemide equivalent dose remained not associated with the risk of the combined endpoint in the whole sample (hazard ratio 1.34, 95% confidence interval 0.86-2.06, P = 0.184). The risk of the combination of death and/or worsening heart failure associated with the diuretic strategy at discharge was significantly influenced by FO status, including clinical congestion scores and circulating proxies of FO like BNP and cancer antigen 125., Conclusions: In patients hospitalized for AHF, furosemide down-titration does not imply an increased risk of mortality and/or heart failure readmission. However, FO status modifies the effect of down-titration on the outcome. In patients with severe congestion or residual congestion at discharge, down-titration was associated with an increased risk of mortality and/or heart failure readmission., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Previous studies on the distribution of mycetoma globally have failed to identify Ecuador as an endemic country., Methods: We present data on 35 cases of mycetoma in Ecuador between 1955 and 2021: 5 cases from our experience and 30 cases from the literature., Results: Eight cases of eumycetoma (23%) and 27 cases of actinomycetoma (77%) were diagnosed. Most cases originated from the coastal region of Ecuador., Conclusions: For the first time in an English-language publication, this communication confirms the presence of mycetoma in Ecuador, securing Ecuador's position on the global mycetoma map., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: The coronavirus disease 2019 (COVID-19) has serious physiological and psychological consequences. The long-term (>12 weeks post-infection) impact of COVID-19 on mental health, specifically in older adults, is unclear. We longitudinally assessed the association of COVID-19 with depression symptomatology in community-dwelling older adults with metabolic syndrome within the framework of the PREDIMED-Plus cohort., Methods: Participants ( n = 5486) aged 55-75 years were included in this longitudinal cohort. COVID-19 status (positive/negative) determined by tests (e.g. polymerase chain reaction severe acute respiratory syndrome coronavirus 2, IgG) was confirmed via event adjudication (410 cases). Pre- and post-COVID-19 depressive symptomatology was ascertained from annual assessments conducted using a validated 21-item Spanish Beck Depression Inventory-II (BDI-II). Multivariable linear and logistic regression models assessed the association between COVID-19 and depression symptomatology., Results: COVID-19 in older adults was associated with higher post-COVID-19 BDI-II scores measured at a median (interquartile range) of 29 (15-40) weeks post-infection [fully adjusted β = 0.65 points, 95% confidence interval (CI) 0.15-1.15; p = 0.011]. This association was particularly prominent in women ( β = 1.38 points, 95% CI 0.44-2.33, p = 0.004). COVID-19 was associated with 62% increased odds of elevated depression risk (BDI-II ≥ 14) post-COVID-19 when adjusted for confounders (odds ratio; 95% CI 1.13-2.30, p = 0.008)., Conclusions: COVID-19 was associated with long-term depression risk in older adults with overweight/obesity and metabolic syndrome, particularly in women. Thus, long-term evaluations of the impact of COVID-19 on mental health and preventive public health initiatives are warranted in older adults.

Introduction: Albuminuria is prevalent in patients with chronic heart failure and is a risk factor for disease progression. However, its clinical meaning in acute heart failure remains elusive. This study analyzed the trajectory of urine albumin to creatinine ratio (UACR) between admission and discharge and its association with decongestion., Methods: In this prospective observational study, 63 patients were enrolled. UACR, B-type natriuretic peptide (BNP), and clinical congestion score (CCS) were obtained at admission and discharge. We used linear mixed regression analysis to compare changes in the natural logarithm of UACR (logUACR) and its association with changes in markers of decongestion. Estimates were reported as least squares mean with their respective 95% CIs., Results: The median age of the study population was 87 years, 68.5% were women, and 69.8% had a left ventricular ejection fraction &gt;50%. LogUACR at discharge significantly decreased in the overall population compared to admission (Δ -0.47, 95% CI: -0.78 to -0.15, p value = 0.003). The magnitude of UACR drop at discharge was associated with changes in surrogate markers of decongestion. Patients who showed a greater reduction in BNP at discharge exhibited a greater reduction in UACR (p = 0.016). The same trend was also found with clinical decongestion, as assessed by changes in CCS, however, without achieving statistical significance (p = 0.171). UACR change at discharge was not associated with changes in serum creatinine (p value = 0.923)., Conclusion: In elderly patients with AHF and volume overload, the level of UACR significantly decreased upon discharge compared to admission. This reduction in UACR was closely linked to decreases in BNP., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

MicroRNAs (miRNAs) are small non-coding RNAs that participate as powerful genetic regulators. MiRNAs can interfere with cellular processes by interacting with a broad spectrum of target genes under physiological and pathological states, including cancer development and progression. Major histocompatibility complex major histocompatibility complex class I-related chain A (MICA) belongs to a family of proteins that bind the natural-killer group 2, member D (NKG2D) receptor on Natural Killer cells and other cytotoxic lymphocytes. MICA plays a crucial role in the host's innate immune response to several disease settings, including cancer. MICA harbors various single nucleotide polymorphisms (SNPs) located in its 3'-untranslated region (3'UTR), a characteristic that increases the complexity of MICA regulation, favoring its post-transcriptional modulation by miRNAs under physiological and pathological conditions. Here, we conducted an in-depth analysis of MICA 3'UTR sequences according to each MICA allele described to date using NCBI database. We also systematically evaluated interactions between miRNAs and their putative targets on MICA 3'UTR containing SNPs using in silico analysis. Our in silico results showed that MICA SNPs rs9266829, rs 1880, and rs9266825, located in the target sequence of miRNAs hsa-miR-106a-5p, hsa-miR-17-5p, hsa-miR-20a-5p, hsa-miR-20b-5p, hsa-miR-93, hsa-miR-1207.5p, and hsa-miR-711 could modify the binding free energy between -8.62 and -18.14 kcal/mol, which may affect the regulation of MICA expression. We believe that our results may provide a starting point for further exploration of miRNA regulatory effects depending on MICA allelic variability; they may also be a guide to conduct miRNA in silico analysis for other highly polymorphic genes., 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 © 2023 Toledo-Stuardo, Ribeiro, Campos, Tello, Latorre, Altamirano, Dubois-Camacho and Molina.)

The aim of this study was to evaluate and compare the fracture resistance of a single-unit fixed prosthesis, using a CAD/CAM PMMA material and two printed materials (3DPPa and 3DPPb). A typodont with a specific preparation for a full crown was used; a digital impression was made with a state-of-the-art scanner (PrimeScan TM , Dentsply-Sirona TM , New York, NY, USA), and a full coverage restoration was designed using a biogeneric design proposal by means of specific software (InLAB 22.1, Dentsply-Sirona, NY, USA). Sixty crowns were prepared, divided into three groups according to the material: 3DPPa ( n = 20), 3DPPb ( n = 20), both 3D-printed from the .STL file with a resolution of 50 μm, and PMMA ( n = 20) milled-derived, which were subjected to a thermocycling process. A universal testing machine (Universal/Tensile Testing Machine, Autograph AGS-X Series) with integrated software (TRAPEZIUM LITE X) equipped with a 20 kN load cell was used to determine the fracture resistance. Significant differences were found by Kruskal-Wallis test and multiple comparisons ( p < 0.05) in fracture resistance between materials. The fracture resistance for the PMMA material was higher, and the standard deviation was lower (x = 1427.9; sd = 36.9 N) compared to the 3DPPa (x = 1231; sd = 380.1 N) and 3DPPb (x = 1029.9; sd = 166.46 N) prints. The restorations from the milled-derived group showed higher average fracture resistance than the provisional restorations obtained from the printed groups. However, the results demonstrated that all three materials analyzed in single-unit restorations are capable of withstanding the average masticatory forces.

Aims: Previous studies demonstrated the relationship between hypochloraemia and poor prognosis in patients hospitalized for acute heart failure (AHF). However, the usefulness of chloride in clinical practice remains uncertain, notably in very old patients with predominantly heart failure (HF) with preserved ejection fraction (HFpEF). We aimed to evaluate the prognostic impact of chloride in a cohort of very aged patients with AHF and the possible existence of different phenotypes of hypochloraemia with distinct clinical significance., Methods and Results: It was an observational study of 429 patients hospitalized for AHF in which chloraemia was measured. Two different phenotypes of hypochloraemia were identified by their relationship with estimated plasma volume status (ePVS) as a proxy of intravascular congestion. The endpoint of interest was time to all-cause mortality and the composite of death and/or HF readmission. A multivariable Cox proportional hazard regression model was constructed to analyse the endpoints. The median age was 85 (78-92) years, 266 (62%) were women, and 80% had HFpEF. After multivariable analysis, chloraemia, but not natraemia, was associated with the risk of death and HF readmission in a U-shaped pattern. The phenotype characterized by hypochloraemia and low ePVS (depletional) was associated with an increased risk of mortality when compared with patients with normochloraemia [hazard ratio (HR) 1.86, P = 0.008]. In contrast, hypochloraemia with high ePVS (dilutional) had no prognostic significance (HR 0.94, P = 0.855)., Conclusions: In very old patients hospitalized with AHF, plasma chloride was associated with the risk of death and HF readmission in a U-shaped pattern and could potentially be used for congestion phenotyping., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The perception of time depends on the rhythmicity of internal and external synchronizers. One external synchronizer that affects time estimation is music. This study aimed to analyze the effects of musical tempi on EEG spectral dynamics during subsequent time estimation. Participants performed a time production task after (i) silence and (ii) listening to music at different tempi -90, 120, and 150 bpm- while EEG activity was recorded. While listening, there was an increase in alpha power at all tempi compared to the resting state and an increase of beta at the fastest tempo. The beta increase persisted during the subsequent time estimations, with higher beta power during the task after listening to music at the fastest tempo than task performance without music. Spectral dynamics in frontal regions showed lower alpha activity in the final stages of time estimations after listening to music at 90- and 120-bpm than in the silence condition and higher beta in the early stages at 150 bpm. Behaviorally, the 120 bpm musical tempo produced slight improvements. Listening to music modified tonic EEG activity that subsequently affected EEG dynamics during time production. Music at a more optimal rate could have benefited temporal expectation and anticipation. The fastest musical tempo may have generated an over-activated state that affected subsequent time estimations. These results emphasize the importance of music as an external stimulus that can affect brain functional organization during time perception even after listening., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Studying functional connectivity may generate clues to the maturational changes that occur in children, expressed by the dynamical organization of the functional network assessed by electroencephalographic recordings (EEG). In the present study, we compared the EEG functional connectivity pattern estimated by linear cross-correlations of the electrical brain activity of three groups of children (6, 8, and 10 years of age) while performing odd-ball tasks containing facial stimuli that are chosen considering their importance in socioemotional contexts in everyday life. On the first task, the children were asked to identify the sex of faces, on the second, the instruction was to identify the happy expressions of the faces. We estimated the stable correlation pattern (SCP) by the average cross-correlation matrix obtained separately for the resting state and the task conditions and quantified the similarity of these average matrices comparing the different conditions. The accuracy improved with higher age. Although the topology of the SCPs showed high similarity across all ages, the two older groups showed a higher correlation between regions associated with the attentional and face processing networks compared to the youngest group. Only in the youngest group, the similarity metric decreased during the sex condition. In general, correlation values strengthened with age and during task performance compared to rest. Our findings indicate that there is a spatially extended stable brain network organization in children like that reported in adults. Lower similarity scores between several regions in the youngest children might indicate a lesser ability to cope with tasks. The brain regions associated with the attention and face networks presented higher synchronization across regions with increasing age, modulated by task demands., 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 © 2022 Ramos-Loyo, Olguín-Rodríguez, Espinosa-Denenea, Llamas-Alonso, Rivera-Tello and Müller.)

Despite the benefits of abdominal normothermic regional perfusion (A-NRP) for abdominal grafts in controlled donation after circulatory death (cDCD), there is limited information on the effect of A-NRP on the quality of the cDCD lungs. We aimed to study the effect of A-NRP in lungs obtained from cDCD and its impact on recipients´ outcomes. This is a study comparing outcomes of lung transplants (LT) from cDCD donors (September 2014 to December 2021) obtained using A-NRP as the abdominal preservation method. As controls, all lung recipients transplanted from donors after brain death (DBD) were considered. The primary outcomes were lung recipient 3-month, 1-year, and 5-year survival. A total of 269 LT were performed (60 cDCD and 209 DBD). There was no difference in survival at 3 months (98.3% cDCD vs. 93.7% DBD), 1 year (90.9% vs. 87.2%), and 5 years (68.7% vs. 69%). LT from the cDCD group had a higher rate of primary graft dysfunction grade 3 at 72 h (10% vs. 3.4%; p <  .001). This is the largest experience ever reported with the use of A-NRP combined with lung retrieval in cDCD donors. This combined method is safe for lung grafts presenting short-term survival outcomes equivalent to those transplanted through DBD., (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Systemic histoplasmosis is a disease of high morbidity and mortality in immunocompromised patients. Patients with AIDS get the infection through inhalation of spores, triggering a primary lung infection with a subsequent hematogenous spread to multiple organs, including the skin. Tissue necrosis have been documented in cutaneous histoplasmosis with multiple clinical manifestations that mimic other diseases., Case Presentation: We report the case of nasal cartilage destruction associated to cutaneous histoplasmosis in AIDS. A 24-year-old man, resident in Ecuadorian coast, with a history of HIV for 7 years without any treatment. In the last 3 months, he has been presenting a molluscum-like lesions on his nasal bridge with subsequent dissemination to the trunk and extremities. He was admitted to the emergency department for dyspnoea, cough, and malaise. Due to his respiratory failure, he was admitted to the intensive care unit (ICU) with mechanical ventilation. Physical examination reveals a crusted surface ulcer that involves the nose and cheeks, associated with erythematous papules, some with a crusted surface which are spread to the face, trunk, and upper limbs. The patient has a specific skin involvement with a butterfly-like ulcer appearance and destruction of the upper and lower lateral cartilage of the nose. At admission CD4 cell count was 11/mm 3 with a HIV viral load of 322,908 copies. Mycological cultures identified Histoplasma capsulatum. A treatment with highly active antiretroviral therapy (HAART) was stablished, associated with liposomal amphotericin B at a dose of 3 mg/kg/day and itraconazole 200 mg twice a day for 12 months., Conclusions: Cutaneous histoplasmosis is a rare manifestation of pulmonary histoplasmosis in patients with AIDS. The cutaneous manifestations included papules, nodules, plaques, and ulcers. A histology examination is required to rule out other fungal or parasitic infections. Treatment includes highly active antiretroviral therapy (HAART), amphotericin B liposomal and itraconazole, the latest for at least 12 months., (© 2022. The Author(s).)

Objectives: Acute myeloid leukemia (AML) is a heterogeneous disease, characterized by clonal expansion of undifferentiated myeloid precursors, leading to alterations in hematopoiesis and bone marrow failure. Characteristic chromosomal abnormalities in AML are translocations t(8;21), inv(16), t(15;17), t(9;22), as well as mutations of genes that regulate proliferation and survival (FLT 3, PTPN 11, ETV 6/PDGFB), or genes responsible for differentiation and apoptosis (RUNX-1/RUNX1T1, PML/RARA, KMT2A, CEBPA and CBFB). Amplification of RUNX1 is a rare event in AML. Herein we described a 60-year-old patient that was admitted to the hospital due to a clinical picture of symptoms of acute anemia, thrombocytopenia, leukocytosis, and profuse nasal bleeding, hepatomegaly, splenomegaly, and gallstones. The blood cell count indicated the presence of 72% blasts. The bone marrow also showed 97% of blasts of myeloid lineage. The flow cytometry study also showed findings compatible with AML (MPOneg/+, CD34+, CD19neg /+d, CD117+, CD38neg /+, HLA-DR ++, CD13neg /+, CD33neg, CD15neg, D56neg, CD123+, CD7neg, CD11bneg, CD64neg, CD41aneg, which represented 68% of the pathological cellularity). Chromosome analysis showed additional copies of an isochromosome 21q. FISH studies revealed five copies of RUNX1. Amplification of RUNX1 is a rare event in AML with only a few cases reported in the literature (mainly therapy related AML) and it is usually associated with poor prognosis., (Copyright© by the Association of Genetic Technologists.)

Purpose: We examined the relationships between pattern electroretinogram and optical coherence tomography derived optic nerve head measurements, after controlling for disc area., Methods: Thirty-two eyes from 20 subjects with preperimetric glaucoma underwent pattern electroretinogram and optical coherence tomography. Pattern electroretinogram parameters (Magnitude, MagnitudeD, and MagnitudeD/Magnitude ratio) and optic nerve head measurements (rim area, average cup to disc ratio, vertical cup to disc ratio, cup volume, retinal nerve fiber layer thickness sectors, and Bruch's membrane opening-minimum rim width thickness sectors) were analyzed after controlling for disc area., Results: Magnitude and MagnitudeD were significantly associated with rim area ( r   ≥  0.503, p ≤ 0.004). All pattern electroretinogram parameters significantly correlated with Bruch's membrane opening-minimum rim width sectors-temporal superior and nasal inferior ( r   =  0.400, p =0.039)-and retinal nerve fiber layer sectors-superior, nasal superior, and inferior ( r  ≥ 0.428, p ≤ 0.026). Magnitude and MagnitudeD explained an additional 26.8% and 25.2% of variance in rim area ( B   =  0.174 (95% CI: 0.065, 0.283), p =0.003, and B   =  0.160 (95% CI: 0.056, 0.265), p =0.004), respectively. MagnitudeD and MagnitudeD/Magnitude ratio explained an additional 13.4% and 12.8% of the variance in Bruch's membrane opening-minimum rim width global ( B   =  38.921 [95% CI: 3.872, 73.970], p =0.031, and B   =  129.024 (95% CI: 9.589, 248.460), p =0.035), respectively. All Bruch's membrane opening-minimum rim width sectors and retinal nerve fiber layer sectors (nasal superior, nasal inferior, and inferior) were significantly correlated with rim area ( r   ≥  0.389, p ≤ 0.045)., Conclusion: PERG abnormalities can predict rim area loss in preperimetric glaucoma after controlling for disc area. We recommend controlling for disc area to increase diagnostic accuracy in early glaucoma., Competing Interests: All authors declare no conflict of interest, except for Peter Derr, who is an employee for Diopsys, Inc, and Celso Tello a consultant., (Copyright © 2021 Andrew Tirsi et al.)

Background: Hypovitaminosis D has been linked to deterioration in clinical parameters and lung function in COPD. As a response to low levels of vitamin D serum Parathyroid Hormone (iPTH) is increased in some, but not all, patients. The aim of this study was to determine whether COPD patients with elevated PTH levels are at higher risk of COPD exacerbations and hospitalizations., Methods: 166 COPD outpatients were randomly preselected. Clinical and analytical characteristics were assessed at baseline. After excluding patients with other conditions known to disturb calcium metabolism 141 patients were identified. Except one, all patients were prospectively followed for 12 months after obtaining the blood samples. Hypovitaminosis D was considered when serum 25(OH)D < 30 ng/mL. Secondary hyperparathyroidism was considered when serum iPTH was higher than normal (50 pg/mL) in patients with hypovitaminosis D. COPD exacerbations and hospital admissions were recorded during the follow-up., Results: Prevalence of hypovitaminosis D in COPD patients was 89.3%, prevalence of secondary hyperparathyroidism associated with hypovitaminosis D was 22,9%. Cox proportional risk analysis showed that patients belonging to the high iPTH-low 25(OH)D group were at a higher risk of moderate COPD exacerbations (HR 1.81 (CI95% 1.043-3.127), p = 0.035) and hospital admissions (HR 5.45 (CI95% 2.018-14.720), p = 0.002) as compared with those with normal iPTH-low 25(OH)D levels., Conclusions: COPD patients with hypovitaminosis D and elevated iPTH have higher risk of moderate exacerbations and hospitalizations than those with hypovitaminosis D and normal iPTH., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Pirfenidone has been shown to slow disease progression in patients with idiopathic pulmonary fibrosis (IPF). However, there are few treatment options for progressive fibrotic interstitial lung diseases (ILDs)) other than IPF. In view of the pathomechanistic and clinical similarities between IPF and other progressive fibrotic ILDs, we aimed to assess the efficacy and safety of pirfenidone in patients with four non-IPF progressive fibrotic ILDs., Methods: We did a multicentre, double-blind, randomised, placebo-controlled, parallel phase 2b trial (RELIEF) in 17 centres with expertise in ILD in Germany. Eligible participants were patients aged 18-80 years with progressive fibrotic ILD due to four diagnoses: collagen or vascular diseases (ie, connective tissue disease-associated ILDs), fibrotic non-specific interstitial pneumonia, chronic hypersensitivity pneumonitis, or asbestos-induced lung fibrosis. Other eligibility criteria included a forced vital capacity (FVC) of 40-90% predicted, a diffusing capacity of the lung for carbon monoxide of 10-90% predicted, and an annual decline of FVC of at least 5% predicted despite conventional therapy, based on at least three measurements within 6-24 months before enrolment. Patients who had received any previous antifibrotic therapy were excluded. We randomly assigned patients (1:1) to either oral pirfenidone (267 mg three times per day in week 1, 534 mg three times per day in week 2, and 801 mg three times per day thereafter) or matched placebo, added to their ongoing medication. Randomisation was done centrally using permuted block randomisation with varying block sizes stratified by the four diagnostic groups. Patients, investigators, statisticians, monitors, and the study coordinator were masked to treatment assignment until database closure. The placebo-controlled study period was 48 weeks (including up-titration). The primary endpoint was absolute change in percentage of predicted FVC (FVC % predicted) from baseline to week 48 in the intention-to-treat population, with imputation of missing data by the smallest sum of squared differences and attribution of deceased patients to the lowest rank in a rank ANCOVA model. Additionally, we did linear mixed-model repeated measures slope analyses of FVC % predicted longitudinal data over the course of the study as a prespecified sensitivity analysis and post-hoc sensitivity analyses of the primary endpoint in the intention-to-treat population using imputation methods of last observation carried forward [LOCF] and a regression-based multiple imputation procedure. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered with EudraCT 2014-000861-32; DRKS00009822 and is no longer recruiting., Findings: Between April 5, 2016, and Oct 4, 2018, we randomly assigned 127 patients to treatment: 64 to pirfenidone, 63 to placebo. After 127 patients had been randomised, the study was prematurely terminated on the basis of an interim analysis for futility triggered by slow recruitment. After 48 weeks and in the overall population of 127 patients, rank ANCOVA with diagnostic group included as a factor showed a significantly lower decline in FVC % predicted in the pirfenidone group compared with placebo (p=0·043); the result was similar when the model was stratified by diagnostic group (p=0·042). A significant treatment effect was also observed when applying the LOCF and multiple imputation methods to analyses of the primary endpoint. The median difference (Hodges-Lehmann estimate) between pirfenidone and placebo groups for the primary endpoint was 1·69 FVC % predicted (95% CI -0·65 to 4·03). In the linear mixed-model repeated measures slope analysis of FVC % predicted, the estimated difference between treatment and placebo groups from baseline to week 48 was 3·53 FVC % predicted (95% CI 0·21 to 6·86) with imputation of deaths as prespecified, or 2·79 FVC % predicted (95% CI 0·03 to 5·54) without imputation. One death (non-respiratory) occurred in the pirfenidone group (2%) and five deaths (three of which were respiratory) occurred in the placebo group (8%). The most frequent serious adverse events in both groups were infections and infestations (five [8%] in the pirfenidone group, ten [16%] in the placebo group); general disorders including disease worsening (two [3%] in the pirfenidone group, seven [11%] in the placebo group); and cardiac disorders (one ([2%] in the pirfenidone group, 5 [8%] in the placebo group). Adverse events (grade 3-4) of nausea (two patients on pirfenidone, two on placebo), dyspnoea (one patient on pirfenidone, one on placebo), and diarrhoea (one patient on pirfenidone) were also observed., Interpretation: In view of the premature study termination, results should be interpreted with care. Nevertheless, our data suggest that in patients with fibrotic ILDs other than IPF who deteriorate despite conventional therapy, adding pirfenidone to existing treatment might attenuate disease progression as measured by decline in FVC., Funding: German Center for Lung Research, Roche Pharma., Competing Interests: Declaration of interests JB reports personal fees from Boehringer Ingelheim, Bristol Myers Squibb, Biogen, Galapagos, Promedior, Roche, and the German Center for Lung Research (DZL). SB reports personal fees and non-financial support from Roche, Bayer, Novartis, and Boehringer Ingelheim; personal fees from Merck Serono; and non-financial support from Teva, Gilead, Lucane Pharma, Actelion, CSL Behring, and Vertex. FB reports personal fees for consultancy, lecturing, and travel support from Boehringer Ingelheim and Roche. MC reports grants from DZL. JHF reports personal fees, grants, and non-financial support from Roche; and personal fees and non-financial support from Boehringer Ingelheim. AG reports grants from DZL, Boehringer Ingelheim, and Roche. MH reports grants from Actelion; honoraria for lectures from Actelion, Bayer Healthcare, Berlin Chemie, Boehringer Ingelheim, GlaxoSmithKline (GSK), Merck Sharp & Dohme (MSD), Novartis, OMT, Pfizer, and Roche; honoraria for advisory boards from Actelion, Bayer, Boehringer Ingelheim, GSK, MSD, and Roche; and honoraria for clinical trials from Actelion, Bayer, GSK, Pfizer, and United Therapeutics. NKn reports personal fees from Roche. DK reports personal fees from Roche; and personal fees and non-financial support from Boehringer Ingelheim. MK reports grants from DZL; and grants and personal fees from Boehringer Ingelheim and Roche. AP reports grants from DZL; grants, personal fees, and non-financial support from Boehringer Ingelheim and AstraZeneca; personal fees and non-financial support from Roche, Pliant, Chiesi Pharmaceuticals, and Nitto Denko; personal fees from Amgen; and non-financial support from Galapagos. KFR reports grants and personal fees from Boehringer Ingelheim and AstraZeneca; and personal fees from Novartis, Sanofi, Regeneron, Roche, and Chiesi Pharmaceuticals. TW reports grants from Roche; and personal fees from Boehringer Ingelheim, Roche, and Novartis. HWil reports personal fees for lectures or consultations from Actelion–Janssen, Bayer, Biotest, Boehringer Ingelheim, GSK, Pfizer, and Roche. HWir reports lecture fees from Roche. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The commercialization of medical devices and biotechnology products is characterized by high failure rates and long development lead times particularly among start-up enterprises. To increase the success rate of these high-risk ventures, the University of Massachusetts Lowell (UML) and University of Massachusetts Medical School (UMMS) partnered to create key academic support centers with programs to accelerate entrepreneurship and innovation in this industry. In 2008, UML and UMMS founded the Massachusetts Medical Device Development Center (M2D2), which is a business and technology incubator that provides business planning, product prototyping, laboratory services, access to clinical testing, and ecosystem networking to medical device and biotech start-up firms. M2D2 has three physical locations that encompass approximately 40,000 square feet. Recently, M2D2 leveraged these resources to expand into new areas such as health security, point of care technologies for heart, lung, blood, and sleep disorders, and rapid diagnostics to detect SARS-CoV-2. Since its inception, M2D2 has vetted approximately 260 medical device and biotech start-up companies for inclusion in its programs and provided active support to more than 80 firms. This manuscript describes how two UMass campuses leveraged institutional, state, and Federal resources to create a thriving entrepreneurial environment for medical device and biotech companies., Competing Interests: The authors have no conflicts of interest to declare., (© The Association for Clinical and Translational Science 2021.)

Gastric cancer (GC) is the fifth most prevalent type of cancer worldwide. Gastric tumor cells express MICA protein, a ligand to NKG2D receptor that triggers natural killer (NK) cells effector functions for early tumor elimination. MICA gene is highly polymorphic, thus originating alleles that encode protein variants with a controversial role in cancer. The main goal of this work was to study MICA gene polymorphisms and their relationship with the susceptibility and prognosis of GC. Fifty patients with GC and 50 healthy volunteers were included in this study. MICA alleles were identified using Sanger sequencing methods. The analysis of MICA gene sequence revealed 13 MICA sequences and 5 MICA-short tandem repeats (STR) alleles in the studied cohorts We identified MICA * 002 ( * A9) as the most frequent allele in both, patients and controls, followed by MICA * 008 allele ( * A5.1). MICA * 009/049 allele was significantly associated with increased risk of GC (OR: 5.11 [95% CI: 1.39-18.74], p = 0.014). The analysis of MICA-STR alleles revealed a higher frequency of MICA * A5 in healthy individuals than GC patients (OR = 0.34 [95% CI: 0.12-0.98], p = 0.046). Survival analysis after gastrectomy showed that patients with MICA * 002/002 or MICA * 002/004 alleles had significantly higher survival rates than those patients bearing MICA * 002/008 ( p = 0.014) or MICA * 002/009 (MICA * 002/049) alleles ( p = 0.040). The presence of threonine in the position MICA-181 (MICA * 009/049 allele) was more frequent in GC patients than controls ( p = 0.023). Molecular analysis of MICA-181 showed that the presence of threonine provides greater mobility to the protein than arginine in the same position (MICA * 004), which could explain, at least in part, some immune evasion mechanisms developed by the tumor. In conclusion, our findings suggest that the study of MICA alleles is crucial to search for new therapeutic approaches and may be useful for the evaluation of risk and prognosis of GC and personalized therapy., 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 Toledo-Stuardo, Ribeiro, Canals, Morales, Gárate, Rodríguez-Siza, Tello, Bustamante, Armisen, Matthies, Zapata-Torres, González-Hormazabal and Molina.)

Objectives: In idiopathic pulmonary fibrosis (IPF), alterations in the pulmonary surfactant system result in an increased alveolar surface tension and favor repetitive alveolar collapse. This study aimed to assess the usefulness of electrical impedance tomography (EIT) in characterization of regional ventilation in IPF., Materials and Methods: We investigated 17 patients with IPF and 15 healthy controls from the University of Giessen and Marburg Lung Center (UGMLC), Germany, for differences in the following EIT parameters: distribution of ventilation (TID), global inhomogeneity index (GI), regional impedance differences through the delta of end-expiratory lung impedance (dEELI), differences in surface of ventilated area (SURF), as well as center of ventilation (CG) and intratidal gas distribution (ITV). These parameters were assessed under spontaneous breathing and following a predefined escalation protocol of the positive end-expiratory pressure (PEEP), applied through a face mask by an intensive care respirator (EVITA, Draeger, Germany)., Results: Individual slopes of dEELI over the PEEP increment protocol were found to be highly significantly increased in both groups ( p < 0.001) but were not found to be significantly different between groups. Similarly, dTID slopes were increasing in response to PEEP, but this did not reach statistical significance within or between groups. Individual breathing patterns were very heterogeneous. There were no relevant differences of SURF, GI or CGVD over the PEEP escalation range. A correlation of dEELI to FVC, BMI, age, or weight did not forward significant results., Conclusions: In this study, we did see a significant increase in dEELI and a non-significant increase in dTID in IPF patients as well as in healthy controls in response to an increase of PEEP under spontaneous breathing. We propose the combined measurements of EIT and lung function to assess regional lung ventilation in spontaneously breathing subjects.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic pulmonary disease with rising incidence. In this study the effectiveness of pirfenidone, as measured by longitudinal change in individual slope of forced vital capacity (FVC) prior to and after initiating pirfenidone treatment, was evaluated in IPF patients recruited into the European registry for idiopathic pulmonary fibrosis (eurIPFreg). Secondary variables were the evaluation of the change in individual slope of diffusion capacity of the lungs for carbon monoxide (DLco), the Borg dyspnea scale, and six-minute walking distance (6MWD), as well as survival analyses., Results: Data of 122 eurIPFreg patients, who had at least two pulmonary function tests (PFTs) prior to or under treatment with pirfenidone, were analyzed by calculating slope-changes. The global analysis revealed an average slope change of +1.48 ± 0.28 (% per annum (p.a)) after start of treatment ( p < 0.001), reflecting a reduction in annual FVC decline of approx. 50% under pirfenidone; it also showed a reduction in DLco, and increase in 6MWD (both p < 0.0001), as well as a flattening of the Borg dyspnea scale ( p = 0.02). The median survival under treatment was 4.82 years. Patients with a more restrictive disease (FVC < 80% pred.), with a rapid progression (FVC decline >10% pred. p.a.), previous smokers and patients > 60 years of age seemed to profit more from pirfenidone treatment., Conclusions: We report the effectiveness of pirfenidone in a European "real world" IPF cohort with outcome data extending up to 9 years. Global analyses demonstrated a positive effect of pirfenidone on the decline of the lung function over time. Survival was dependent on Gender-Age-Physiology (GAP) score and age prior to therapy.

(1) Aim of the study: In spite of extensive research, up to 20% of interstitial lung diseases (ILD) patients cannot be safely classified. We analyzed clinical features, progression factors, and outcomes of unclassifiable ILD (uILD). (2) Methods: A total of 140 uILD subjects from the University of Giessen and Marburg Lung Center (UGMLC) were recruited between 11/2009 and 01/2019 into the European Registry for idiopathic pulmonary fibrosis (eurIPFreg) and followed until 01/2020. The diagnosis of uILD was applied only when a conclusive diagnosis could not be reached with certainty. (3) Results: In 46.4% of the patients, the uILD diagnosis was due to conflicting clinical, radiological, and pathological data. By applying the diagnostic criteria of usual interstitial pneumonia (UIP) based on computed tomography (CT), published by the Fleischner Society, 22.2% of the patients displayed a typical UIP pattern. We also showed that forced vital capacity (FVC) at baseline ( p = 0.008), annual FVC decline ≥10% ( p < 0.0001), smoking ( p = 0.033), and a diffusing capacity of the lung for carbon monoxide (DLco) ≤55% of predicted value at baseline ( p < 0.0001) were significantly associated with progressive disease. (4) Conclusions: The most important prognostic factors in uILD are baseline level and decline in lung function and smoking. The use of Fleischner diagnostic criteria allows further differentiation and accurate diagnosis.

Our knowledge about the structure and function of Andean forests at regional scales remains limited. Current initiatives to study forests over continental or global scales still have important geographical gaps, particularly in regions such as the tropical and subtropical Andes. In this study, we assessed patterns of structure and tree species diversity along ~ 4000 km of latitude and ~ 4000 m of elevation range in Andean forests. We used the Andean Forest Network (Red de Bosques Andinos, https://redbosques.condesan.org/) database which, at present, includes 491 forest plots (totaling 156.3 ha, ranging from 0.01 to 6 ha) representing a total of 86,964 identified tree stems ≥ 10 cm diameter at breast height belonging to 2341 identified species, 584 genera and 133 botanical families. Tree stem density and basal area increases with elevation while species richness decreases. Stem density and species richness both decrease with latitude. Subtropical forests have distinct tree species composition compared to those in the tropical region. In addition, floristic similarity of subtropical plots is between 13 to 16% while similarity between tropical forest plots is between 3% to 9%. Overall, plots ~ 0.5-ha or larger may be preferred for describing patterns at regional scales in order to avoid plot size effects. We highlight the need to promote collaboration and capacity building among researchers in the Andean region (i.e., South-South cooperation) in order to generate and synthesize information at regional scale., Competing Interests: The authors have declared that no competing interests exist.

Prenatal stress (PNS) can influence behaviors associated with cognition, reward and emotional regulation, which are controlled by brain areas such as the cortex, hippocampus, hypothalamus, midbrain and cerebellum. Allopregnanolone in these regions modulates behavioral and parasympathetic effects. The current study tested whether exposing pregnant dams to 5 days of resident-intruder stress on prenatal days 15-20 for 10 min altered the levels of allopregnanolone in cortex, hypothalamus, hippocampus, midbrain, and cerebellum of male and female juvenile offspring. In cortex, hypothalamus, and midbrain of male rats exposed to prenatal stress, levels of allopregnanolone were significantly lower compared to all other groups. In the hippocampus and cerebellum, among females exposed to prenatal stress levels were significantly higher compared to all other groups. These differences in allopregnanolone levels varying by prenatal stress, sex and brain regions provide insight in potential mechanism of stress regulation and etiopathophysiology of stress-related disorders., Competing Interests: No conflicts of interest declared., (© 2020 The Authors.)

Based on molecular phylogenetic analyses of a multigene matrix of partial nuSSU-ITS-LSU rDNA, RPB1 , RPB2 and TEF1 sequences and by morphological evidence, the genus Mycosphaerangium is shown to be the closest relative of Neomelanconium , and confirmed to be a member of the Cenangiaceae (Leotiomycetes). While Mycosphaerangium and Neomelanconium share many traits like similar conidia, conidiogenesis, asci and ascospores, their apothecia differ particularly in excipular features and are therefore recognized as distinct genera. Mycosphaerangium tiliae , described from North America, is excluded from the genus but shown to represent the sexual morph of the European Neomelanconium gelatosporum , and it is therefore synonymized with the latter. Based on morphology, Neomelanconium deightonii is assumed to be congeneric with Neomelanconium gelatosporum , and it is lectotypified. Dermatea tetraspora and Phaeangium magnisporum , the basionyms of Mycosphaerangium tetrasporum and M. magnisporum , respectively, are lectotypified as well, and for M. tetrasporum , the asexual morph is recorded for the first time. Mycosphaerangium quercinum sp. nov. is described as a new species from various Quercus hosts in Europe, where it is shown to be widely distributed. It morphologically and ecologically closely resembles the North American M. tetrasporum , but differs in paraphysis and ascospore morphology and by croziers at its ascus base. The three accepted species of Mycosphaerangium and the two of Neomelanconium are described and illustrated. Mycosphaerangium magnisporum , M. quercinum and M. tetrasporum are recorded to be constantly associated with species of Coryneum , indicating a fungicolous habit, but no evidence for fungal associations has been found in Neomelanconium deightonii and N. gelatosporum ., (© The Author(s) 2020.)

The aim of this study was to compare a reconfigurable mobile electroencephalography (EEG) system (M-EMOTIV) based on the Emotiv Epoc® (which has the ability to record up to 14 electrode sites in the 10/20 International System) and a commercial, clinical-grade EEG system (Neuronic MEDICID-05®), and then validate the rationale and accuracy of recordings obtained with the prototype proposed. In this approach, an Emotiv Epoc® was modified to enable it to record in the parieto-central area. All subjects (15 healthy individuals) performed a visual oddball task while connected to both devices to obtain electrophysiological data and behavioral responses for comparative analysis. A Pearson's correlation analysis revealed a good between-devices correlation with respect to electrophysiological measures. The present study not only corroborates previous reports on the ability of the Emotiv Epoc® to suitably record EEG data but presents an alternative device that allows the study of a wide range of psychophysiological experiments with simultaneous behavioral and mobile EEG recordings.

Recombinant protein expression for structural and therapeutic applications requires the use of systems with high expression yields. Escherichia coli is considered the workhorse for this purpose, given its fast growth rate and feasible manipulation. However, bacterial inclusion body formation remains a challenge for further protein purification. We analyzed and optimized the expression conditions for three different proteins: an anti-MICA scFv, MICA, and p19 subunit of IL-23. We used a response surface methodology based on a three-level Box-Behnken design, which included three factors: post-induction temperature, post-induction time and IPTG concentration. Comparing this information with soluble protein data in a principal component analysis revealed that insoluble and soluble proteins have different optimal conditions for post-induction temperature, post-induction time, IPTG concentration and in amino acid sequence features. Finally, we optimized the refolding conditions of the least expressed protein, anti-MICA scFv, using a fast dilution protocol with different additives, obtaining soluble and active scFv for binding assays. These results allowed us to obtain higher yields of proteins expressed in inclusion bodies. Further studies using the system proposed in this study may lead to the identification of optimal environmental factors for a given protein sequence, favoring the acceleration of bioprocess development and structural studies.

Background: The aim of this study was to analyze the relative frequency, clinical characteristics, disease onset and progression in f-IPF vs. sporadic IPF (s-IPF)., Methods: Familial IPF index patients and their family members were recruited into the European IPF registry/biobank (eurIPFreg) at the Universities of Giessen and Marburg (UGMLC). Initially, we employed wide range criteria of f-IPF (e.g. relatives who presumably died of some kind of parenchymal lung disease). After narrowing down the search to occurrence of idiopathic interstitial pneumonia (IIP) in at least one first grade relative, 28 index patients were finally identified, prospectively interviewed and examined. Their family members were phenotyped with establishment of pedigree charts., Results: Within the 28 IPF families, overall 79 patients with f-IPF were identified. In the same observation period, 286 f-IIP and s-IIP patients were recruited into the eurIPFreg at our UGMLC sites, corresponding to a familial versus s-IPF of 9.8%. The both groups showed no difference in demographics (61 vs. 79% males), smoking history, and exposure to any environmental triggers known to cause lung fibrosis. The f-IPF group differed by an earlier age at the onset of the disease (55.4 vs. 63.2 years; p < 0.001). On average, the f-IPF patients presented a significantly milder extent of functional impairment at the time point of inclusion vs. the s-IPF group (FVC 75% pred. vs. FVC 62% pred., p = 0.011). In contrast, the decline in FVC was found to be faster in the f-IPF vs. the s-IPF group (4.94% decline in 6 months in f-IPF vs. 2.48% in s-IPF, p = 0.12). The average age of death in f-IPF group was 67 years vs. 71.8 years in s-IPF group (p = 0.059). The f-IIP group displayed diverse inheritance patterns, mostly autosomal-dominant with variable penetrance. In the f-IPF, the younger generations showed a tendency for earlier manifestation of IPF vs. the older generation (58 vs. 66 years, p = 0.013)., Conclusions: The 28 f-IPF index patients presented an earlier onset and more aggressive natural course of the disease. The disease seems to affect consecutive generations at a younger age., Trial Registration: Nr. NCT02951416 http://www.www.clinicaltrials.gov.

Background: Since 2009, IPF patients across Europe are recruited into the eurIPFreg, providing epidemiological data and biomaterials for translational research., Methods: The registry data are based on patient and physician baseline and follow-up questionnaires, comprising 1700 parameters. The mid- to long-term objectives of the registry are to provide clues for a better understanding of IPF phenotype sub-clusters, triggering factors and aggravating conditions, regional and environmental characteristics, and of disease behavior and management., Results: This paper describes baseline data of 525 IPF subjects recruited from 11/2009 until 10/2016. IPF patients had a mean age of 68.1 years, and seeked medical advice due to insidious dyspnea (90.1%), fatigue (69.2%), and dry coughing (53.2%). A surgical lung biopsy was performed in 32% in 2009, but in only 8% of the cases in 2016, possibly due to increased numbers of cryobiopsy. At the time of inclusion in the eurIPFreg, FVC was 68.4% ± 22.6% of predicted value, DLco ranged at 42.1% ± 17.8% of predicted value (mean value ± SD). Signs of pulmonary hypertension were found in 16.8%. Steroids, immunosuppressants and N-Acetylcysteine declined since 2009, and were replaced by antifibrotics, under which patients showed improved survival (p = 0.001)., Conclusions: Our data provide important insights into baseline characteristics, diagnostic and management changes as well as outcome data in European IPF patients over time., Trial Registration: The eurIPFreg and eurIPFbank are listed in ClinicalTrials.gov( NCT02951416 ).

The discovery of a second species of Bicornispora in Spain, B. seditiosa, which is closely related to B. exophiala but has smaller ascospores, narrower asci and different ecology, gave us the opportunity to culture and sequence the fungus. Phylogenetic analyses of rDNA regions including partial nuc 28S rDNA (28S) and ITS1-5.8S-ITS2 (ITS) supported a close relationship with species of the genus Lambertella (Rutstroemiaceae), placing Bicornispora, previously ascribed to Coryneliales, within Helotiales. This result confirmed an evolutionary linkage between certain inoperculate discomycetes such as Lambertella palmeri and derived cleistothecial forms (Bicornispora spp.). Based on analyses of morphological study and molecular phylogenetic analyses, a new combination Rutstroemia asphodeli is proposed for Ciboria asphodeli., (© 2015 by The Mycological Society of America.)

Objective: Chronic disease is the main epidemic of the 21st century. It takes up a large part of the social-health budgets that are dedicated to its care. The aim of this study is to analyze if the welfare quality in the management of the chronic patients improves by implementing non-contact care time., Material and Methods: Intervention study conducted in the health care center of Orcasitas (January 2012 - September 2013) in patients with hypertension (357), diabetes (180) and/or ischemic heart disease (60). Health care quality was analyzed through the effectiveness in the program, Tracking Objectives in Primary Care. The intervention group had four physical 10minute consultations/year and three non-physical 10minute consultations/year. The patients in the control group were seen as usual. The data were compared using the McNemar test, chi-square and Cochran's Q test., Results: In the intervention group, the effectiveness increased in the analyzed period by 46%, 54% and 55.9%, respectively, for processes of hypertension, diabetes and dyslipidemia control in ischemic heart disease, whereas in the control group (community of Madrid) it was 2.54%, 1.78%, and 5.44%, respectively, for these processes (statistically significant differences [χ(2)=24.78; χ(2)=39.9 y χ(2)=67.3, P<.0001])., Conclusions: Thirty minutes/year of non-presential care represents a significant change in the level of control of chronic patients. These results should be considered in the approach strategies to chronic diseases., (Copyright © 2014 SECA. Published by Elsevier Espana. All rights reserved.)

Unlabelled: Occupational musculoskeletal disorders in the upper limbs and its consequences on the impact and prevalence in the work force are subject of many investigations in almost all the production fields. However, the exposure to this kind of risk factor on urban gardeners has not been well studied so far. The kind of plant varieties used in the parks, the tools that they use, as much as the necessary actions for the maintenance of the park, have an impact on the biomechanical overload of the upper limbs. Additionally, the analysis of the exposure to the biomechanical overload on upper limbs in gardening work is a complex task, mainly because it is an activity highly variable and of annual cycle. For this reason an analytical model for risk exposure evaluation is necessary. During this research the work activity of 29 gardeners in 3 urban parks of Barcelona has been analyzed. Each park has a specific acting plan, in relation with the quantity and the typology of vegetal species, its classification and the season of the year. Work and observation and video recording sessions on-site were conducted. The video-graphic registration was done on workers without any prior musculoskeletal disorder and with a minimum labour experience of 5 years. Moreover, the analysis of saturation time, considered as the relation of the repetitive working hours in reference with the hours of effective work was done. Using the registered tasks on video, the biomechanical overload on upper limbs applying the OCRA Checklist method was analyzed., Results: A methodological procedure to analyze the risk exposure in annual working cycle has been proposed. The results that we got allow us to get information that can help in the assignment of the tasks and in the training of staff, as well as in the recommendations of the urban landscape's design. All these aspects have the goal to decrease the risk to develop work-related musculoskeletal disorders.

The performance of the LightCycler SeptiFast (SF) assay was compared to that of culture methods in the detection of microorganisms in 43 purulent fluids from patients with pyogenic infections. The SF assay was more sensitive than the culture methods (86% versus 61%, respectively), irrespective of whether the infections were mono- or polymicrobial.

Arapaima gigas is an air-breathing giant fish of Amazonian rivers. Given its great economic and cultural importance, the aquaculture development of this species represents an evident solution to face the decline of wild populations. In captivity, reproduction occurs generally in large earthen ponds where stocks of a few tens of brooders are maintained together at the beginning of the rainy season (December-March in the Peruvian Amazon). Fry production relies on the spontaneous formation of male and female pairs, which build a nest, delimit a territory and guard the offspring for at least 20 days from other congeners and predators. However, as sex determination of A. gigas is not possible by morphological criteria, it is very difficult to optimize reproduction conditions and fry production in each pond, which seriously hampers the culture of this species. This situation prompted us to develop sexing methodologies based on (1) the detection of female specific plasma Vitellogenin (Vtg) using an enzyme immuno assay (EIA), and (2) the determination of plasma 17beta-estradiol and 11-ketotestosterone levels for immature specimens. The Vtg purification was performed by electro-elution after polyacrilamide gel electrophoresis (PAGE) from plasma of 17beta-estradiol treated A. gigas juveniles. Two different Vtg molecules were isolated, (Vtg(1) and Vtg(2)) with 184 and 112 kDa apparent molecular masses, respectively, and two antibodies were raised in rabbits for each Vtg molecule. Adult fish were 100% accurately sexed by Vtg EIA, while 100% of immature fish and 95% of adults were accurately sexed by 17beta-Estradiol and 11-Ketestosterone ratios. We also observed different color pattern development in male and female adult fish (6-year-olds) around the reproductive period.