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Abstract Background/objectives Adherence to dietary recommendations is a critical component in the management of type 1 diabetes (T1D). Taste and flavor significantly influence food choices. The aim of this study was to investigate taste sensitivity and flavor recognition ability in adults with T1D compared to healthy individuals. Subjects/methods Seventy-two people with T1D and 72 matched healthy controls participated in the study. Participants underwent the gustometry test for sweet, sour, salty, and bitter tastes and the flavor test, which consisted of oral administration of aqueous aromatic solutions identifying 21 different compounds. Results Participants with T1D had significantly lower flavor scores and gustometry scores than controls (p

Abstract Objective Biallelic mutations in PRDX3 have been linked to autosomal recessive spinocerebellar ataxia type 32. In this study, which aims to contribute to the growing body of knowledge on this rare disease, we identified two unrelated patients with mutations in PRDX3. We explored the impact of PRDX3 mutation in patient skin fibroblasts and the role of the gene in neurodevelopment. Methods We performed trio exome sequencing that identified mutations in PRDX3 in two unrelated patients. We also performed functional studies in patient skin fibroblasts and generated a “crispant” zebrafish (Danio rerio) model to investigate the role of the gene during nervous system development. Results Our study reports two additional patients. Patient 1 is a 19‐year‐old male who showed a novel homozygous c.525_535delGTTAGAAGGTT (p. Leu176TrpfsTer11) mutation as the genetic cause of cerebellar ataxia. Patient 2 is a 20‐year‐old male who was found to present the known c.425C>G/p. Ala142Gly variant in compound heterozygosity with the p. Leu176TrpfsTer11 one. While the fibroblast model failed to recapitulate the pathological features associated with PRDX3 loss of function, our functional characterization of the prdx3 zebrafish model revealed motor defects, increased susceptibility to reactive oxygen species‐triggered apoptosis, and an impaired oxygen consumption rate. Conclusions We identified a new variant, thereby expanding the genetic spectrum of PRDX3‐related disease. We developed a novel zebrafish model to investigate the consequences of prdx3 depletion on neurodevelopment and thus offered a potential new tool for identifying new treatment opportunities.

Abstract Background In Ecuador, cervical cancer is the third most common cancer among women and the second most common cause of cancer-related death in women. Although HPV represents a serious public health problem worldwide, the information about its prevalence and genotypes in remote communities of Ecuador is limited. The aim of this study was to determine the distribution of HPV genotypes among ethnic minority women from two remote communities of the northwestern region of Ecuador: Afro-Ecuadorians and Chachis (Amerindian group). Methods We included 291 women who responded to a short survey and were screened for HPV by the amplification of the L1 gene and a nested multiplex PCR to detect 14 high risk (HR) genotypes. A survey collected information on ethnicity, age, community access, and sexual and gynecological history. We identified risk factors associated with HPV infection and co-infection using multivariate logistic regression to calculate odds ratio (OR) and Wald 95% confidence intervals (CI). Results Overall, HPV prevalence in the study cohort was 56%, and the five most common HR-HPV genotypes were HPV-58, -16, -68, -39, and -43; however, the distribution of HPV genotypes varied according to ethnicity. We identified lineage A (European variant) for HPV-16 and sublineage A2 for HPV-58 in both ethnic groups. Adjusting for ethnicity, age, community access, and number of sexual partners, we found that Afro-Ecuadorian women were less likely to have an HPV infection than Chachi women (OR: 0.49, 95% CI: 0.25, 0.96), and that participants in communities only accessible by river had 64% less chances of an HPV infection when compared to women in communities accessible by road (OR: 0.36, 95% CI: 0.19, 0.71), and women with 2 to 3 sexual partners had 2.47 times the odds of HPV infection than participants with 0–1 partners (OR: 2.47, 95% CI: 1.32, 4.6). Similar associations were observed with prevalence of co-infection. Conclusions This study provides baseline knowledge regarding the prevalence and distribution of HPV genotypes in ethnic groups of the northwestern coastal Ecuador and essential information for the implementation of appropriate HPV testing and vaccination program to prevent cervical cancer.

Purpose CHEK2 c.1100delC is associated with an increased breast cancer risk in women. While this variant is prevalent in the Netherlands (1% in the general population), knowledge of aetiology and prognosis of breast cancer and other tumours in CHEK2 c.1100delC carriers is lacking. The nationwide HEreditary Breast and Ovarian cancer study the Netherlands (Hebon) cohort aims to answer study questions in families with an increased risk of breast cancer and ovarian cancer. While initially focusing on BRCA1/2-variant families, Hebon gradually expanded to include pathogenic variants in other genes associated with breast and/or ovarian cancer over time. This provides an excellent setting to establish a cohort to ultimately study the impact of CHEK2 c.1100delC on cancer risk prediction and surveillance, breast cancer treatment and prognosis.Participants We invited all heterozygous and homozygous CHEK2 c.1100delC indexes and tested female relatives. 1802 women were included, of whom 1374 were heterozygotes and 938 were breast cancer cases. Pedigrees were collected from all clinical genetic departments. Furthermore, participants completed a detailed questionnaire on hormonal and lifestyle factors, family history, cancer diagnosis and treatment.Findings to date Mean age at study inclusion was 53 years. Linkage with the Netherlands Cancer Registry showed a younger age at diagnosis in homozygotes (mean age 41.7 years) and heterozygotes (47.9 years) than non-carriers (51.2 years). Furthermore, carriers were more often diagnosed with grade 2, oestrogen receptor-positive breast cancer and more often developed contralateral breast cancer than non-carriers. Most women consumed alcohol regularly and about half never smoked.Future plans Further data linkages with the Netherlands Cancer Registry will allow prospective follow-up and breast cancer risk assessment in unaffected women at the time of genetic testing, risk of contralateral breast cancer and survival in patients with breast cancer. Also, linkage with the nationwide network and registry of histopathology and cytopathology in The Netherlands (PALGA) allows us to retrieve tumour samples to study tumourigenesis.

Abstract Background Conventional, non-specific preventive migraine treatments often demonstrate low rates of treatment persistence due to poor efficacy or tolerability. Effective, well-tolerated preventive treatments are needed to reduce migraine symptoms, improve function, and enhance quality of life. Atogepant is a migraine-specific oral calcitonin gene–related peptide receptor antagonist that is indicated for the preventive treatment of migraine in adults. This analysis evaluated the safety and tolerability profile of atogepant for the preventive treatment of migraine, including adverse events (AEs) of interest, such as constipation, nausea, hepatic safety, weight changes, and cardiac disorders. Methods This post hoc analysis was performed using data pooled from 2 (12-week) randomized, double-blind, placebo-controlled trials (RCTs) and 2 (40- and 52-week) open-label long-term safety (LTS) trials of oral atogepant for episodic migraine (EM). Results The safety population included 1550 participants from the pooled RCTs (atogepant, n = 1142; placebo, n = 408) and 1424 participants from the pooled LTS trials (atogepant, n = 1228; standard care [SC], n = 196). In total, 643/1142 (56.3%) atogepant participants and 218/408 (53.4%) placebo participants experienced ≥ 1 treatment-emergent AEs (TEAEs) in the RCTs. In the LTS trials, 792/1228 (64.5%) of atogepant participants and 154/196 (78.6%) of SC participants experienced ≥ 1 TEAEs. The most commonly reported TEAEs (≥ 5%) in participants who received atogepant once daily were upper respiratory tract infection (5.3% in RCTs, 7.7% in LTS trials), constipation (6.1% in RCTs, 5.0% in LTS trials), nausea (6.6% in RCTs, 4.6% in LTS trials), and urinary tract infection (3.4% in RCTs, 5.2% in LTS trials). Additionally, weight loss appeared to be dose- and duration-dependent. Most TEAEs were considered unrelated to study drug and few led to discontinuation. Conclusions Overall, atogepant is safe and well tolerated in pooled RCTs and LTS trials for the preventive treatment of EM in adults. Trial registration ClinicalTrials.gov identifiers: NCT02848326 (MD-01), NCT03777059 (ADVANCE), NCT03700320 (study 302), NCT03939312 (study 309). Graphical Abstract

Adoptive transfer of tumor infiltrating lymphocytes (TIL therapy) has proven highly effective for treating solid cancers, including non-small cell lung cancer (NSCLC). However, not all patients benefit from this therapy for yet unknown reasons. Defining markers that correlate with high tumor-reactivity of the autologous TIL products is thus key for achieving better tailored immunotherapies. We questioned whether the composition of immune cell infiltrates correlated with the tumor-reactivity of expanded TIL products. Unbiased flow cytometry analysis of immune cell infiltrates of 26 early-stage and 20 late-stage NSCLC tumor lesions was used for correlations with the T cell differentiation and activation status, and with the expansion rate and anti-tumor response of generated TIL products. The composition of tumor immune infiltrates was highly variable between patients. Spearman’s Rank Correlation revealed that high B cell infiltration negatively correlated with the tumor-reactivity of the patient’s expanded TIL products, as defined by cytokine production upon exposure to autologous tumor digest. In-depth analysis revealed that tumor lesions with high B cell infiltrates contained tertiary lymphoid structure (TLS)-related immune infiltrates, including BCL6+ antibody-secreting B cells, IgD+BCL6+ B cells and CXCR5+BLC6+ CD4+ T cells, and higher percentages of naïve CD8+ T cells. In conclusion, the composition of immune cell infiltrates in NSCLC tumors associates with the functionality of the expanded TIL product. Our findings may thus help improve patient selection for TIL therapy.

AbstractPurpose As reported in most European countries, the percentage of treated hypertensive patients achieving a well-controlled blood pressure (e.g. < 140/90 mmHg) is insufficient. This represents a major health concern particularly in countries with a high prevalence of cardiovascular events such as stroke. Therefore, there is a need to develop national programs to increase not only the awareness regarding elevated blood pressure but also the percentage of treated patients achieving recommended blood pressure targets. The present paper describes the new initiative of the Portuguese Society of Hypertension (PSH) to achieveat least 70% of controlled hypertensive patients, followed in primary care, in 2026.Materials and Methods The strategies used to improve blood pressure control are aimed at healthcare professionals and general population and include governmental and organizational interventions. To be able to analyze the control rate of HTN patients, and using BI-CSP reports (the Primary Care health unit platform), every six months, we will be addressing the proportion of HTN patients (age: 18-65 years) with BP < 140/90 mmHg and the proportion of HTN patients with at least one blood pressure recorded in the last semester.Conclusion With Mission 70/26, the PHS aims to improve awareness among all health professionals and community alike about the problem of uncontrolled HTN and its role in the consequent disability and high mortality rate from cardiovascular causes.

Objective: To obtain insights into parents' information needs during the first year at home with their very preterm (VP) born infant. Methods: We conducted semi-structured interviews with parents of VP infants participating in a post-discharge responsive parenting intervention (TOP program). Online interviews were audiotaped and transcribed verbatim. Inductive thematic analysis was performed by two independent coders. Results: Ten participants were interviewed and had various and changing information needs during the developmental trajectory of their infant. Three main themes emerged; (1) Help me understand and cope, (2) Be fully responsible for my baby, and (3) Teach me to do it myself. Available and used sources, such as the Internet, did not meet their information needs. Participants preferred their available and knowledgeable healthcare professionals for reassurance, tailored information, and practical guidance. Conclusion: This study identified parents' information needs during the first year at home with their VP infant and uncovered underlying re-appearing needs to gain confidence in child-caring abilities and autonomy in decision-making about their infants' care. Innovation: This study provides valuable information for healthcare professionals and eHealth developers to support parental self-efficacy during the first year after preterm birth.

Background: This study aims to describe post-chikungunya complications chronically developed cases in returning travelers from some epidemic/endemic regions, and the variables that are associated with the progression of acute or subacute cases to the chronic phase. Methods: This single-center retrospective cohort study included chikungunya fever cases treated at La Paz-Carlos III University Hospital in Madrid, Spain, April 2014 to September 2016, when the chikungunya outbreak in Latin America started through the time of its greatest impact. Results: The analysis included 119 cases. Of these, 67.2 % were male, with a median age of 41.0 years [IQR 16.0 to 76.0] years. Only 25.6 % of the patients attended a pre-travel advice consultation. Most patients reported arthralgias, which significantly impacted their daily quality of life (86 %). The mean duration of joint symptoms was 129.4 days, with a median of 90 days [IQR 0 to 715]. Factors found to be associated with chronic arthralgia include female sex, country of infection, age at diagnosis, previous diseases, symptoms during the acute phase, pain in previously injured tendons/joints, acute phase severity, and various laboratory markers such as hemoglobin, hematocrit, total serum bilirubin, and creatinine. Progression to chronic arthralgia significantly increased the need for changes in daily activity. Furthermore, 42.6 % of patients with chronic arthralgia reported recurrence of symptoms once they felt they had disappeared. Targeted treatment regimens led to significant improvements in these patients. Conclusions: The results of this study underscore the need for: (1) comprehensive pre-travel advice; (2) effective management of patients in specialized units, alongside early diagnosis and treatment, to prevent trivialization of these viral infections; and (3) the development of interdisciplinary recommendations to assist physicians in treating patients and enhancing outcomes.

Acute myeloid leukemia (AML) is a heterogeneous malignancy that requires further therapeutic improvement, especially for the elderly and for subgroups with poor prognosis. A recently discovered T cell receptor (TCR) targeting mutant nucleophosmin 1 (ΔNPM1) presents an attractive option for the development of a cancer antigen-targeted cellular therapy. Manufacturing of TCR-modified T cells, however, is still limited by a complex, time-consuming, and laborious procedure. Therefore, this study specifically addressed the requirements for a scaled manufacture of ΔNPM1-specific T cells in an automated, closed, and good manufacturing practice-compliant process. Starting from cryopreserved leukapheresis, 2E8 CD8-positive T cells were enriched, activated, lentivirally transduced, expanded, and finally formulated. By adjusting and optimizing culture conditions, we additionally reduced the manufacturing time from 12 to 8 days while still achieving a clinically relevant yield of up to 5.5E9 ΔNPM1 TCR-engineered T cells. The cellular product mainly consisted of highly viable CD8-positive T cells with an early memory phenotype. ΔNPM1 TCR CD8 T cells manufactured with the optimized process showed specific killing of AML in vitro and in vivo. The process has been implemented in an upcoming phase 1/2 clinical trial for the treatment of NPM1-mutated AML.

Yessy Novianti,1 Wahyu Hidayat,2 Desi Elvhira Rosa1 1Oral Medicine Residency Program, Faculty of Dentistry, Universitas Padjadjaran, Bandung, Indonesia; 2Department of Oral Medicine, Faculty of Dentistry, Universitas Padjadjaran, Bandung, IndonesiaCorrespondence: Yessy Novianti, Faculty of Dentistry, Universitas Padjadjaran, Sekeloa Selatan Street No. 1, Bandung, 40132, Indonesia, Tel +6281368429045, Email yessy21001@mail.unpad.ac.idIntroduction: Psoriasis is a complex autoimmune disease associated with chronic systemic keratinization and inflammation, which can affect the skin, joints, and oral cavity. Xerostomia is a subjective feeling of oral dryness that impairs patient comfort and lowers the quality of life. The aim of this case report is to describe the clinical mechanism of xerostomia in a psoriasis patient with multiple systemic diseases.Case Report: A 51-year-old inpatient man with psoriasis vulgaris was referred to the Oral Medicine Department with complaints of difficulty swallowing due to a sore throat and dry tongue since last week. The patient had psoriasis vulgaris 15 years ago, chronic adrenal insufficiency, psoriatic arthritis, acute circulatory collapse, anemia of inflammation, acute kidney injury, dehydration, gastritis, urinary tract infections, and malnutrition. A complete anamnesis and oral examination were done. The patient was diagnosed with severe xerostomia, a fissured tongue, exfoliative cheilitis, angular cheilitis, and gingivitis by the Oral Medicine Department.Case Management: The patient was treated with petroleum jelly, chlorine dioxide mouthwash, miconazole cream, and benzydamine HCl lozenges.Conclusion: Based on case reports and reviews, multiple systemic diseases may not only increase the risk of xerostomia but also aggravate its severity.Keywords: acute kidney injury, inflammation, nitrogen oxide, psoriasis arthritis, SXI-ID

Introduction: Detecting imported diseases by migrants and individuals visiting friends and relatives (VFR) is key in the prevention and management of emergent infectious diseases acquired abroad. Methods: Retrospective descriptive study on migrants and VFR from Central and South America between 2017 and 2022 attended at a National Referral Centre for Tropical Diseases in Madrid, Spain. Demographic characteristics, syndromes and confirmed travel-related diagnoses were obtained from hospital patient medical records. Results: 1654 cases were registered, median age of 42 years, 69.1% were female, and 55.2% were migrants. Most cases came from Bolivia (49.6%), followed by Ecuador (12.9%). Health screening while asymptomatic (31.6%) was the main reason for consultation, followed by Chagas disease follow-up (31%). Of those asymptomatic at screening, 47,2% were finally diagnosed of any disease, mainly Chagas disease (19,7%) and strongyloidiasis (10,2%) Conclusion: Our study emphasizes the importance of proactive health screening to detect asymptomatic conditions in migrants and VFR, enabling timely intervention and improved health outcomes. By understanding the unique health profiles of immigrant populations, targeted public health interventions can be devised to safeguard the well-being of these vulnerable groups.

Carbapenem-resistant Acinetobacter spp. is associated with nosocomial infections in intensive care unit patients, resulting in high mortality. Although Acinetobacter spp. represent a serious public health problem worldwide, there are a few studies related to the presence of carbapenemases in health care facilities and other environmental settings in Ecuador. The main aim of this study was to characterize the carbapenem-resistant Acinetobacter spp. isolates obtained from four hospitals (52) and from five rivers (27) close to Quito. We used the disc diffusion and EDTA sinergy tests to determine the antimicrobial susceptibility and the production of metallo β-lactamases, respectively. We carried out a multiplex PCR of gyrB gene and the sequencing of partial rpoB gene to bacterial species identification. We performed molecular screening of nine carbapenem-resistant genes (blaSPM, blaSIM, blaGIM, blaGES, blaOXA-23, blaOXA-24, blaOXA-51, blaOXA-58, and blaOXA-143) by multiplex PCR, followed by identification using sequencing of blaOXA genes. Our findings showed that carbapenem-resistant A. baumannii were the main species found in health care facilities and rivers. Most of the clinical isolates came from respiratory tract samples and harbored blaOXA-23, blaOXA-366, blaOXA-72, blaOXA-65, blaOXA-70, and blaOXA-143-like genes. The river isolates harbored only the blaOXA-51 and probably blaOXA-259 genes. We concluded that the most predominant type of carbapenem genes among isolates were both blaOXA-23 and blaOXA-65 among A. baumannii clinical isolates.

O objetivo deste trabalho é abordar a situação da filosofia da educação na pós-modernidade, para isto dividimos o trabalho levantando desafios epistemológicos e éticos, num segundo momento o papel da filosofia da educação para uma educação libertadora e por último o papel da estética para atingir o desafio ético da solidariedade. O trabalho justifica-se porque observa a crise atual da educação, depois da pandemia de COVID-19 através de manifestações de totalitarismo, intolerância e anticiência na população e o papel da filosofia da educação para poder fortalecer a democracia. A pesquisa é bibliográfico e tem como principais referenciais teóricos a Theodor Adorno (1998), Zygmunt Bauman (1997), Karl Popper (1972) e Richard Rorty (1992). Como resultados esperados acreditamos que este trabalho possa servir para refletir sobre a crise da educação e fomentar o diálogo, que nos leve a propor alternativas para aliviar a situação crítica da educação.

Desi Elvhira Rosa,1 M Hasan Hapid,1 Wahyu Hidayat2 1Oral Medicine Residency Program, Faculty of Dentistry, Universitas Padjadjaran, Bandung, Indonesia; 2Oral Medicine Department, Faculty of Dentistry, Universitas Padjadjaran, Bandung, IndonesiaCorrespondence: Desi Elvhira Rosa, Oral Medicine Residency Program, Faculty of Dentistry, Universitas Padjadjaran, Jalan Sekeloa Selatan I, Bandung, 40132, Indonesia, Tel +62 852 6725 5596, Email desi20004@mail.unpad.ac.idIntroduction: Traumatic ulcer commonly occurs in the oral cavity, resulting in the loss of the entire epithelium. Traumatic ulcers often appear to mimic other lesions of the oral mucosa but the causative factors and other characteristic features rule out the differential diagnosis. It may have a similar appearance to some oral ulcer lesions such as traumatic ulcer granuloma with stromal eosinophilia (TUGSE) and oral squamous cell carcinoma (OSCC).Objective: To identify traumatic ulcers from other chronic lesions such as TUGSE and OSCC.Case: First case, a 63-year-old female complained of pain on the right side of the tongue for 4 months. Intraoral examination showed a painful single ulcer, mild keratosis white halo, and induration on the right lateral of the tongue. The second case, a 38-year-old male complained of pain on the left side of the tongue for 2 months. Intraoral examination showed a painful single ulcer, mild keratosis white halo, and induration on the left lateral of the tongue. In both cases, there were some retained roots where the ulcer was located, and due to its contact with lateral of the tongue and the appearance of the lesion, we got a provisional diagnosis of traumatic ulcer.Case Management: These ulcers had a visual appearance similar to OSCC and TUGSE, so eliminating etiological factors and a comprehensive treatment plan were needed. We planned to extract teeth close to the lesion that was suspected to be the etiology of traumatic ulcer. We also prescribed 0.1% triamcinolone acetonide in orabase to improve healing. One week later, the ulcer in both patients had healed.Conclusion: Recognition of traumatic ulcer characteristics is crucial in eliminating local factors to get rid of any differential diagnosis.Keywords: characteristic, local factor, traumatic ulcer

Alzheimer’s disease (AD) may manifest retinal changes preceding brain pathology. A transversal case-control study utilized spectral-domain OCT angiography (SD-OCTA) and Angio-Tool software 0.6a to assess retinal vascular structures and OCT for inner and outer retina thickness in the APPNL-F/NL-F AD model at 6, 9, 12, 15, 17, and 20 months old. Comparisons to age-matched wild type (WT) were performed. The analysis focused on the three vascular plexuses using AngiooTool and on retinal thickness, which was represented with the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Compared to WT, the APPNL-F/NL-F group exhibited both vascular and structural changes as early as 6 months persisting and evolving at 15, 17, and 20 months. Significant vascular alterations, principally in the superficial vascular complex (SVC), were observed. There was a significant decrease in the vessel area and the total vessel length in SVC, intermediate, and deep capillary plexus. The inner retina in the APPNL-F/NL-F group predominantly decreased in thickness while the outer retina showed increased thickness in most analyzed time points compared to the control group. There are early vascular and structural retinal changes that precede the cognitive changes, which appear at later stages. Therefore, the natural history of the APPNL-F/NL-F model may be more similar to human AD than other transgenic models.

To better address mechanical behavior, it is necessary to make use of modern tools through which it is possible to run predictions, simulate scenarios, and optimize decisions. sources integration. This will increase the capability of detecting material modifications that forerun damage and/or to forecast the stage in the future when very likely fatigue is initiating and propagating cracks. Early warning outcomes obtained by the synergetic implementation of NDE-based protocols for studying mechanical and fatigue and fracture behavior will enhance the preparedness toward economically sustainable future damage control scenarios. Specifically, these early warning outcomes will be developed in the form of retopologized models to be used coupled with FEA. This paper presents the first stage of calibration and the combination of a system of different sensors (photogrammetry, laser scanning and strain gages) for the creation of volumetric models suitable for the prediction of failure of FEA software. The test objects were two components of car suspension to which strain gauges were attached to measure its deformation under cyclic loading. The calibration of the methodology was carried out using models obtained from photogrammetry and experimental strain gauge measurements.

Introducción/objetivo: la innovación y el emprendimiento son factores importantes para el crecimiento económico a largo plazo. Las universidades proporcionan investigación y conocimientos básicos que forman la base para futuras innovaciones. Estudios previos han examinado la alianza entre la universidad y la industria en términos de la difusión del conocimiento, las actividades empresariales, así como la competitividad regional. Sin embargo, no se ha explorado el rol que específicamente tienen las universidades en Ecuador en cuanto a las colaboraciones universidad-industria. Metodología: se utilizó como estudio de caso la contribución de la Universidad de Guayaquil (UG) al entorno empresarial de su ciudad. Manteniendo un enfoque cualitativo se detallaron los registros de propiedad intelectual de cada facultad para compararlos con las actuales áreas de trabajo de los distintos centros de emprendimiento en la ciudad. Resultados: con base en los datos de la propiedad intelectual, se identificó el surgimiento de innovaciones en el campo de la arquitectura, odontología, sistemas computacionales, ciencias de la educación e ingeniería industrial. Conclusiones: esta investigación no solo satisface una brecha en la investigación, sino que también trae ramificaciones prácticas para las empresas y constituye un insumo directo para la toma de decisiones al interior de la UG. Introduction/objective: Innovation and entrepreneurship are important factors for long-term economic growth. Universities provide basic research and knowledge that form the basis for future innovations. Previous studies have examined the university-industry alliance in terms of knowledge diffusion, entrepreneurial activities, as well as regional competitiveness. However, the role that universities specifically have in Ecuador in terms of university-industry collaborations has not been explored. Methods: The contribution of the University of Guayaquil (UG) to the business environment of its city has been used as a case study. A qualitative research method was chosen in order to provide details about the intellectual property records of each faculty and compare them with the current work areas of the different entrepreneurship centers in the city. Results: Based on intellectual property data, the emergence of innovations in the field of architecture, dentistry, computer systems, educational sciences and industrial engineering was identified. Thus, there is a need to strengthen the efforts of the INNOVUG business incubator in these fields of study. Conclusions: This research not only satisfies a gap in the research, but also becomes a direct input for decision-making within the UG and brings practical ramifications for companies, and those responsible for evaluating the impact of education. superior in collaboration between university and industry.

Abstract Introduction Advanced neuroimaging techniques have extensively contributed to elucidate the complex mechanisms underpinning the pathophysiology of migraine, a neurovascular disorder characterized by episodes of headache associated with a constellation of non-pain symptoms. The present manuscript, summarizing the most recent progresses of the arterial spin labelling (ASL) MRI techniques and the most significant findings from ASL studies conducted in migraine, is aimed to clarify how ASL investigations are contributing to the evolving insight on migraine pathophysiology and their putative role in migraine clinical setting. ASL techniques, allowing to quantitatively demonstrate changes in cerebral blood flow (CBF) both during the attacks and in the course of interictal period, could represent the melting point between advanced neuroimaging investigations, conducted with pure scientific purposes, and conventional neuroimaging approaches, employed in the diagnostic decision-making processes. Main body Converging ASL evidences have demonstrated that abnormal CBF, exceeding the boundaries of a single vascular territory, with biphasic trend dominated by an initial hypoperfusion (during the aura phenomenon but also in the first part of the headache phase) followed by hyperperfusion, characterizes migraine with aura attack and can represent a valuable clinical tool in the differential diagnosis from acute ischemic strokes and epileptic seizures. Studies conducted during migraine without aura attacks are converging to highlight the involvement of dorsolateral pons and hypothalamus in migraine pathophysiology, albeit not able to disentangle their role as “migraine generators” from mere attack epiphenomenon. Furthermore, ASL findings tend to support the presence of perfusion abnormalities in brain regions known to be involved in aura ignition and propagation as well as in areas involved in multisensory processing, in both patients with migraine with aura and migraine without aura. Conclusion Although ASL studies have dramatically clarified quality and timing of perfusion abnormalities during migraine with aura attacks, the same cannot be said for perfusion changes during migraine attacks without aura and interictal periods. Future studies with more rigorous methodological approaches in terms of study protocol, ASL technique and sample selection and size are mandatory to exploit the possibility of better understanding migraine pathophysiology and identifying neuroimaging biomarkers of each migraine phase in different migraine phenotypes.

Abstract Space experiments are a technically challenging but a scientifically important part of astrobiology and astrochemistry research. The International Space Station (ISS) is an excellent example of a highly successful and long-lasting research platform for experiments in space, that has provided a wealth of scientific data over the last two decades. However, future space platforms present new opportunities to conduct experiments with the potential to address key topics in astrobiology and astrochemistry. In this perspective, the European Space Agency (ESA) Topical Team Astrobiology and Astrochemistry (with feedback from the wider scientific community) identifies a number of key topics and summarizes the 2021 “ESA SciSpacE Science Community White Paper” for astrobiology and astrochemistry. We highlight recommendations for the development and implementation of future experiments, discuss types of in situ measurements, experimental parameters, exposure scenarios and orbits, and identify knowledge gaps and how to advance scientific utilization of future space-exposure platforms that are either currently under development or in an advanced planning stage. In addition to the ISS, these platforms include CubeSats and SmallSats, as well as larger platforms such as the Lunar Orbital Gateway. We also provide an outlook for in situ experiments on the Moon and Mars, and welcome new possibilities to support the search for exoplanets and potential biosignatures within and beyond our solar system.

Glaucoma is a neurodegenerative disease of the retina characterized by the irreversible loss of retinal ganglion cells (RGCs) leading to visual loss. Degeneration of RGCs and loss of their axons, as well as damage and remodeling of the lamina cribrosa are the main events in the pathogenesis of glaucoma. Different molecular pathways are involved in RGC death, which are triggered and exacerbated as a consequence of a number of risk factors such as elevated intraocular pressure (IOP), age, ocular biomechanics, or low ocular perfusion pressure. Increased IOP is one of the most important risk factors associated with this pathology and the only one for which treatment is currently available, nevertheless, on many cases the progression of the disease continues, despite IOP control. Thus, the IOP elevation is not the only trigger of glaucomatous damage, showing the evidence that other factors can induce RGCs death in this pathology, would be involved in the advance of glaucomatous neurodegeneration. The underlying mechanisms driving the neurodegenerative process in glaucoma include ischemia/hypoxia, mitochondrial dysfunction, oxidative stress and neuroinflammation. In glaucoma, like as other neurodegenerative disorders, the immune system is involved and immunoregulation is conducted mainly by glial cells, microglia, astrocytes, and Müller cells. The increase in IOP produces the activation of glial cells in the retinal tissue. Chronic activation of glial cells in glaucoma may provoke a proinflammatory state at the retinal level inducing blood retinal barrier disruption and RGCs death. The modulation of the immune response in glaucoma as well as the activation of glial cells constitute an interesting new approach in the treatment of glaucoma.

The prevalence of hypertension is rising, and the majority of patients are managed by General Physicians (GPs). GPs workload influences their capacity to follow and implement hypertension guidelines adequately. The time needed to treat (TNT) each patient at the GP level should be taken into consideration in hypertension practice guidelines.

Este artigo tem como objetivo analisar a política de acesso para refugiados aos cursos de graduação da Universidade Federal do ABC (UFABC) entre 2019 e 2022. Trata-se de uma investigação exploratória, de natureza aplicada e viés qualitativo, usando o método hipotético-dedutivo, o procedimento de estudo de caso e as técnicas de revisão bibliográfica e análise documental. Conclui-se que a política da UFABC representa um avanço quanto às alternativas de inserção socioeconômica e acadêmica deste público no Brasil, e reafirma a diferença como uma medida política de reconhecimento de identidades. Contudo, refugiados ocuparam menos da metade das vagas destinadas para si.

Neurodegenerative diseases include a heterogeneous group of conditions that pose a growing challenge to public health and the scientific community [...]

Introdução: Luanda é a capital de Angola, um país, que se situa no sudoeste africano. Os médicos, enfrentavam o problema do atendimento de inúmeros casos de síndromes febris de uma série de potenciais etiologias. O pacote de testes laboratorial, não incluía a avaliação de rotina da presença do vírus da dengue. A descoberta da circulação do vírus em Angola data de 1973, porém continuou sem registo até 2013. O objectivo do presente estudo foi, avaliar a consideração da probabilidade da infecção pelo vírus da dengue pela equipa de médicos, a frequência da infecção, o perfil sócio-demográfico, referente a idade, sexo, e os principais sintomas relacionados a infecção pela dengue, no período de Abril à Julho de 2022, para a produção de evidências científicas que possam mostrar a necessidade de colocar a dengue dentro da importância, no quadro nosológico de doenças transmissíveis em Angola. Métodos: Após assinatura de um documento de consentimento livre e esclarecido, foram analisadas clinicamente 140 pacientes adultos com síndromes febril e laboratorialmente as respectivas amostras de soro, colhidas em consultas, nas secções de Medicina Interna dos Hospitais dos Cajueiros e Américo Boavida, localizados em áreas sub-urbanas de Luanda. O diagnóstico laboratorial foi feito por testes seroimunológicos imunocromatográficos de diagnóstico rápido (TDRs), da marca SD Bioline, para a pesquisa de antigénios NS1, e paralelamente outro teste da presença de anticorpos IgM/IgG específicos contra o vírus da Dengue. Resultados: No total de 140 pacientes avaliados nas consultas, a dengue não foi considerada como hipótese diagnóstica, 35% (49/140) apresentaram infecções pelo vírus da dengue, detectada em indivíduos nas idades de 18 à 58 anos, tendo se constatado maior predominância de infecção em indivíduos mais jovens, de 18 à 28 anos, representando 40.81% (20/49) anos dos indivíduos, 57% e 43% foram do sexo masculino e feminino, respectivamente. Os sintomas mais frequentes, da dengue foram: febre (100% (49/49), dor retro-orbitrária (90% (44/49), cefaleias (100% (49/49), artralgias (100% (49/49), geralmente nos membros superiores, mialgias (41% (20/49). Conclusão: O vírus da dengue, pode ser o agente etiológico de inúmeros síndromes febris, que desafiam diariamente os médicos. O estudo epidemiológico da Dengue, envolvendo um maior é um necessidade prioritária para colocar a dengue na devida importância no quadro de doenças das doenças transmissíveis em Luanda, Angola.

Oceanic energy, such as offshore wind energy and various marine energy sources, holds significant potential for generating green hydrogen through water electrolysis. Offshore-generated hydrogen has the potential to be transported through standard pipelines and stored in diverse forms. This aids in mitigating the variability of renewable energy sources in power generation and, consequently, holds the capacity to reshape the framework of electrical systems. This research provides a comprehensive review of the existing state of investigation and technological advancement in the domain of offshore wind energy and other marine energy sources for generating green hydrogen. The primary focus is on technical, economic, and environmental issues. The technology's optimal features have been pinpointed to achieve the utmost capacity for hydrogen production, providing insights for potential enhancements that can propel research and development efforts forward.The objective of this study is to furnish valuable information to energy companies by presenting multiple avenues for technological progress. Concurrently, it strives to expand its technical and economic outlook within the clean fuel energy sector. This analysis delivers insights into the best operating conditions for an offshore wind farm, the most suitable electrolyzer for marine environments and the most economical storage medium. The green hydrogen production process from marine systems has been found to be feasible and to possess a reduced ecological footprint compared to grey hydrogen production.

Patients with Parkinson’s disease (PD), often elderly with various comorbidities, may require a continuous intestinal infusion of carbidopa/levodopa gel by the placement of a percutaneous endoscopic gastrostomy (PEG) with a jejunal tube (PEG-J) to improve their motor outcome and quality of life. However, it is unclear what is the best procedural sedation protocol for PEG-J procedures. Fifty patients with PD and indication for PEG-J procedure (implantation, replacement, removal) underwent, from 2017 to 2022, a sedation protocol characterized by premedication with atropine (0.01 mg/Kg i.v.), midazolam (0.015–0.03 mg/Kg i.v.) and induction with bolus propofol (0.5–1 mg/Kg i.v.) as well as, finally, sedation with continuous infusion propofol (2–5 mg/Kg/h i.v.) by Target Controlled Infusion (TCI) technique. Ninety-eight per cent of patients experienced no intraprocedural or peri-procedural adverse events. All the procedures were technically successful. A good discharge time was recorded. The vital parameters recorded during the procedure did not vary significantly. A PEG-J procedure conducted within 30 min showed a significant advantage over end-tidal carbon dioxide (EtCO2). Indeed, the latter showed some predictive behavior (OR: 1.318, 95% CI 1.075–1.615, p = 0.008). In the real world, this sedation protocol showed a good safety and effectiveness profile, even with reduced doses of midazolam and a TCI propofol technique in moderate sedation.

Summary: Background: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. Methods: We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. Findings: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio

Desi Elvhira Rosa,1 Irna Sufiawati2 1Oral Medicine Residency Program, Faculty of Dentistry, Universitas Padjadjaran, Bandung, Indonesia; 2Oral Medicine Department, Faculty of Dentistry, Universitas Padjadjaran, Bandung, IndonesiaCorrespondence: Desi Elvhira Rosa, Oral Medicine Residency Program, Faculty of Dentistry, Universitas Padjadjaran, Jalan Sekeloa Selatan I, Bandung, 40132, Indonesia, Tel +62 852 6725 5596, Email desi20004@mail.unpad.ac.idIntroduction: The coronavirus disease 2019 (COVID-19) pandemic has a serious impact on HIV-infected individuals due to limited access to treatment services. This report aimed to describe four cases of oral lesions in HIV-infected antiretroviral-naive patients found during the COVID-19 pandemic.Case: Four patients, males, with an age ranged from 29 to 53 years, came to Oral Medicine Department with chief complaints of lesions on their mouth. They had postponed their visit to healthcare services due to limited access during pandemic. Three patients had just been diagnosed with HIV and had not yet received anti-retrovirus, while 1 patient had not yet been detected with HIV. From the clinical examination and laboratory findings, we diagnosed the lesions with mucous patches, chronic atrophic candidiasis, angular cheilitis, necrotizing ulcerative gingivitis, linear gingival erythema, cytomegalovirus-associated ulcers, and oral hairy leukoplakia.Case Management: We gave chlorhexidine gluconate 0.2% mouthwash for mucous patches, nystatin oral suspension for chronic atrophic candidiasis, miconazole cream 2% for angular cheilitis, debridement with hydrogen peroxide 1.5% and rinsed with normal saline for necrotizing ulcerative gingivitis, and diphenhydramine hydrochloride and 0.2% chlorhexidine gluconate for CMV ulcers. All patients showed good clinical improvement after the treatments.Conclusion: Oral lesions are still commonly found in HIV-infected patients during COVID-19 pandemic. Dentists remain to have a crucial role in the early diagnosis and treatment of HIV-associated oral lesions during COVID-19 pandemic that will have an impact on HIV treatments, also in implementing the Bali Declaration on oral health in HIV/AIDS 2019 to support UNAIDS goal to end AIDS by 2030.Keywords: ARV-naive patients, COVID-19 pandemic, HIV, oral lesions

Abstract Background The earliest pathological features of Alzheimer’s disease (AD) appear decades before the clinical symptoms. The pathology affects the brain and the eye, leading to retinal structural changes and functional visual alterations. Healthy individuals at high risk of developing AD present alterations in these ophthalmological measures, as well as in resting-state electrophysiological activity. However, it is unknown whether the ophthalmological alterations are related to the visual-related electrophysiological activity. Elucidating this relationship is paramount to understand the mechanisms underlying the early deterioration of the system and an important step in assessing the suitability of these measures as early biomarkers of disease. Methods In total, 144 healthy subjects: 105 with family history of AD and 39 without, underwent ophthalmologic analysis, magnetoencephalography recording, and genotyping. A subdivision was made to compare groups with less demographic and more risk differences: 28 high-risk subjects (relatives/APOEɛ4 +) and 16 low-risk (non-relatives/APOEɛ4 −). Differences in visual acuity, contrast sensitivity, and macular thickness were evaluated. Correlations between each variable and visual-related electrophysiological measures (M100 latency and time–frequency power) were calculated for each group. Results High-risk groups showed increased visual acuity. Visual acuity was also related to a lower M100 latency and a greater power time–frequency cluster in the high-risk group. Low-risk groups did not show this relationship. High-risk groups presented trends towards a greater contrast sensitivity that did not remain significant after correction for multiple comparisons. The highest-risk group showed trends towards the thinning of the inner plexiform and inner nuclear layers that did not remain significant after correction. The correlation between contrast sensitivity and macular thickness, and the electrophysiological measures were not significant after correction. The difference between the high- and low- risk groups correlations was no significant. Conclusions To our knowledge, this paper is the first of its kind, assessing the relationship between ophthalmological and electrophysiological measures in healthy subjects at distinct levels of risk of AD. The results are novel and unexpected, showing an increase in visual acuity among high-risk subjects, who also exhibit a relationship between this measure and visual-related electrophysiological activity. These results have not been previously explored and could constitute a useful object of research as biomarkers for early detection and the evaluation of potential interventions’ effectiveness.

BackgroundTo date, there are no large studies delineating the clinical correlates of “pure” essential tremor (ET) according to its new definition.MethodsFrom the ITAlian tremor Network (TITAN) database, we extracted data from patients with a diagnosis of “pure” ET and excluded those with other tremor classifications, including ET-plus, focal, and task-specific tremor, which were formerly considered parts of the ET spectrum.ResultsOut of 653 subjects recruited in the TITAN study by January 2022, the data of 208 (31.8%) “pure” ET patients (86M/122F) were analyzed. The distribution of age at onset was found to be bimodal. The proportion of familial cases by the age-at-onset class of 20 years showed significant differences, with sporadic cases representing the large majority of the class with an age at onset above 60 years. Patients with a positive family history of tremor had a younger onset and were more likely to have leg involvement than sporadic patients despite a similar disease duration. Early-onset and late-onset cases were different in terms of tremor distribution at onset and tremor severity, likely as a function of longer disease duration, yet without differences in terms of quality of life, which suggests a relatively benign progression. Treatment patterns and outcomes revealed that up to 40% of the sample was unsatisfied with the current pharmacological options.DiscussionThe findings reported in the study provide new insights, especially with regard to a possible inversed sex distribution, and to the genetic backgrounds of “pure” ET, given that familial cases were evenly distributed across age-at-onset classes of 20 years. Deep clinical profiling of “pure” ET, for instance, according to age at onset, might increase the clinical value of this syndrome in identifying pathogenetic hypotheses and therapeutic strategies.

IntroductionAlzheimer’s disease (AD) is the most common form of dementia affecting the central nervous system, and alteration of several visual structures has been reported. Structural retinal changes are usually accompanied by changes in visual function in this disease. The aim of this study was to analyse the differences in visual function at different stages of the pathology (family history group (FH+), mild cognitive impairment (MCI), mild AD and moderate AD) in comparison with a control group of subjects with no cognitive decline and no family history of AD.MethodsWe included 53 controls, 13 subjects with FH+, 23 patients with MCI, 25 patients with mild AD and, 21 patients with moderate AD. All were ophthalmologically healthy. Visual acuity (VA), contrast sensitivity (CS), colour perception, visual integration, and fundus examination were performed.ResultsThe analysis showed a statistically significant decrease in VA, CS and visual integration score between the MCI, mild AD and moderate AD groups compared to the control group. In the CS higher frequencies and in the colour perception test (total errors number), statistically significant differences were also observed in the MCI, mild AD and moderate AD groups with respect to the FH+ group and also between the control and AD groups. The FH+ group showed no statistically significant difference in visual functions compared to the control group. All the test correlated with the Mini Mental State Examination score and showed good predictive value when memory decline was present, with better values when AD was at a more advanced stage.ConclusionAlterations in visual function appear in subjects with MCI and evolve when AD is established, being stable in the initial stages of the disease (mild AD and moderate AD). Therefore, visual psychophysical tests are a useful, simple and complementary tool to neuropsychological tests to facilitate diagnosis in the preclinical and early stages of AD.

The murine models of Alzheimer’s disease (AD) have advanced our understanding of the pathophysiology. In vivo studies of the retina using optical coherence tomography (OCT) have complemented histological methods; however, the lack of standardisation in OCT methodologies for murine models of AD has led to significant variations in the results of different studies. A literature search in PubMed and Scopus has been performed to review the different methods used in these models using OCT and to analyse the methodological characteristics of each study. In addition, some recommendations are offered to overcome the challenges of using OCT in murine models. The results reveal a lack of consensus on OCT device use, retinal area analysed, segmentation techniques, and analysis software. Although some studies use the same OCT device, variations in other parameters make the direct comparison of results difficult. Standardisation of retinal analysis criteria in murine models of AD using OCT is crucial to ensure consistent and comparable results. This implies the application of uniform measurement and segmentation protocols. Despite the absence of standardisation, OCT has proven valuable in advancing our understanding of the pathophysiology of AD.

In the original publication [...]

Background: To date, little and discordant data still exists on the management of cervical cancer (CC) during pregnancy. In this paper, we report our experience of the treatment of these patients analyzing the oncologic, obstetric, and neonatal outcomes. Methods: Between January 2010 and December 2021, 13 patients were diagnosed with CC during pregnancy. All patients underwent platinum-based neoadjuvant chemotherapy (NACT) and 11/13 patients underwent a cesarean radical hysterectomy (CRH). Results: All 13 patients were diagnosed with squamous-cell carcinoma, FIGO-2018 stage between IB2-IIIC1. The majority of patients had a partial (61.5%) or complete (15.4%) response to NACT. Most patients had a regular course of pregnancy and the obstetric complications observed were gestational diabetes mellitus in 23.1% and IUGR in 15.4% of cases. CRH was performed in the absence of major complications. Only 2 patients (15.4%) had disease recurrence and only 1 patient (7.7%) died of disease. All children are currently healthy. At birth, we observed mainly prematurity-related complications (38.5% respiratory distress syndrome and 7.7% neonatal jaundice) and only a case of congenital malformation (hypospadias). In our pediatric population, we reported a case of malignancy (acute myeloid leukemia). Conclusion: NACT seems to be safe and efficacious in controlling tumor burden during pregnancy. CRH following NACT appears to be feasible, avoiding repeated surgery and treatment delays. This approach is also reasonably safe from a maternal, obstetric, and neonatal point of view.

Objective: To characterize different provenances of Jatropha curcas L., introduced and collected, through morphoagronomic indicators, in order to select those with the best performance. Materials and Methods: The study was conducted during one year (2019) in areas of the Pastures and Forages Research Station Indio Hatuey. The work was done with plant material from Paraguay, Ecuador and eastern Cuba. The different Jatropha curcas L. provenances were propagated by seeds. The indicators height, number of branches, stem diameter, quantity of racemes and their length, quantity and length of inflorescences, quantity of fruits and their sizes, were measured, among other variables. The data were processed through the principal component (PCA), cluster and correlation analyses. Results: Of the variability, 96,8 % was explained through four components. The fruit quantity, length and width, quantity of seeds and their sizes, as well as quantity of inflorescences and stem diameter were the indicators with which 55,6 % of the variability was explained in the first two components. Five groups were formed. The second was the one with the best performance in six of the evaluated indicators. Conclusions: There is variability for the evaluated morphoagronomic traits. The provenance Ecuador 2 was the one with the best performance in six of the evaluated indicators. It was followed by Paraguay 2 in four indicators, for which both were selected and turned out to be promising for their study in future breeding programs.

Abstract Background Two main genetic risks for sporadic Alzheimer’s disease (AD) are a family history and ɛ4 allele of apolipoprotein E. The brain and retina are part of the central nervous system and share pathophysiological mechanisms in AD. Methods We performed a cross-sectional study with 30 participants without a family history of sporadic AD (FH−) and noncarriers of ApoE ɛ4 (ApoE ɛ4−) as a control group and 34 participants with a family history of sporadic AD (FH+) and carriers of at least one ɛ4 allele (ApoE ɛ4+). We analyzed the correlations between macular volumes of retinal layers and thickness of the peripapillary retinal nerve fiber layer (pRNFL) measured by optical coherence tomography (OCT) with the brain area parameters measured by magnetic resonance imaging (MRI) in participants at high genetic risk of developing AD (FH+ ApoE ɛ4+). Results We observed a significant volume reduction in the FH+ ApoE ɛ4+ group compared with the control group in some macular areas of (i) macular RNFL (mRNFL), (ii) inner plexiform layer (IPL), (iii) inner nuclear layer (INL), and (iv) outer plexiform layer (OPL). Furthermore, in the FH+ ApoE ɛ4+ group, the retinal sectors that showed statistically significant volume decrease correlated with brain areas that are affected in the early stages of AD. In the same group, the peripapillary retinal nerve fiber layer (pRNFL) did not show statistically significant changes in thickness compared with the control group. However, correlations of these sectors with the brain areas involved in this disease were also found. Conclusions In cognitively healthy participants at high genetic risk of developing sporadic forms of AD, there are significant correlations between retinal changes and brain areas closely related to AD such as the entorhinal cortex, the lingual gyrus, and the hippocampus.

Abstract Background Clinical trials have demonstrated galcanezumab as safe and effective in migraine prevention. However, real-life data are still lacking and overlook the impact of galcanezumab on those different migraine facets strongly contributing to migraine burden. Herein we report the clinical experience from an Italian real-world setting using galcanezumab in patients with migraine experiencing previous unsuccessful preventive treatments. Methods Forty-three patients with migraine and failure of at least 3 migraine preventive medication classes received monthly galcanezumab 120 mg s.c. At the first administration and after 3 and 6 months, patients underwent extensive interviews to assess clinical parameters of disease severity. Furthermore, validated questionnaires were administered to explore migraine-related disability, impact, and quality of life as well as symptoms of depression or anxiety, pain catastrophizing, sleep quality and the ictal cutaneous allodynia. Results After the third and the sixth administration of monthly galcanezumab 120 mg s.c., headache attacks frequency reduced from 20.56 to 7.44 and 6.37 headache days per month, respectively. Moreover, a significant improvement in headache pain intensity (from 8.95 to 6.84 and 6.21) and duration (from 9.03 to 3.75 and 2.38) as well as in scores assessing migraine related disability and impact, depressive and anxious symptoms, and pain catastrophizing was observed. Furthermore, we demonstrated a significant reduction in the values of “whole pain burden”, a composite score derived from the product of the average of headache frequency, intensity, and duration in the last three months. Conclusion Real-world data support monthly galcanezumab 120 mg s.c. as a safe and effective preventive treatment in reducing headache frequency, intensity, and duration as well as comorbid depressive or anxious symptoms, pain catastrophizing and quality of life in both episodic and chronic migraine patients with previous unsuccessful preventive treatments. Furthermore, we demonstrated that monthly galcanezumab 120 mg s.c. is able to induce a significant improvement in the scores of “whole pain burden”. The latter is a reliable and easy-to-handle tool to be employed in clinical setting to evaluate the effectiveness of preventive drugs (in this case, galcanezumab) or when the decision of continuing the treatment with anti-CGRP mAbs is mandatory.

Dance is a high demanding discipline that involves physiological and psychological pressures. The pressure increases when dancers perform in front of an audience that, on a physiological level, can generate hormonal responses similar to those of an athlete before a competition for social status. Low levels of testosterone (T) and high levels of cortisol (C) are related to a decrease in performance and an increase in the risk of injury. Therefore, this study sets out to analyse hormone response patterns in professional flamenco dance performances depending on whether the performances are completed successfully and whether there are differences by sex and professional category. Saliva specimens (2–5 ml) were taken from the participants before and after the performance. Samples were immunoassayed by duplicate to analyze momentary fluctuations in two hormones regularly used in studies with professional athletes. The results showed significant differences in solo dancers’ T responses before and after the performance (p < 0.01), suggesting that the dancing role in the show (soloist or corps the ballet) and responsibility over the performance were important modulators to the hormone responses observed.

Introdução: Cuidado paliativo é uma abordagem que busca compreender e auxiliar pacientes com comorbidades que ameaçam a vida. O fonoaudiólogo paliativista atua na interação entre paciente e familiar por meio da reabilitação da comunicação e manutenção da alimentação por via oral. Manter os pacientes, cuidadores e a própria equipe de saúde informados sobre os cuidados com a alimentação e prevenção do risco de broncoaspiração é de extrema importância, e a utilização de materiais impressos, como cartilhas educativas, é uma grande aliada na educação em saúde. Objetivo: Elaborar e avaliar uma cartilha educativa sobre os cuidados para realizar uma alimentação segura para cuidadores de pacientes em cuidados paliativos. Método: Pesquisa de campo com a participação de dez cuidadores/acompanhantes de pacientes em cuidados paliativos e dez profissionais de saúde de um hospital oncológico que trabalham nas clínicas de cuidados paliativos. Para a avaliação da cartilha proposta, todos os participantes responderam a questionários que continham perguntas referentes ao entendimento, linguagem utilizada, compreensão dos cuidados com a alimentação, entre outras informações pertinentes para sua avaliação. Em seguida, realizou-se a estatística descritiva para tratamento dos dados obtidos. Resultados: A média de aprovação da cartilha foi de 9,65 para o grupo de profissionais de saúde e 10,00 para os cuidadores/acompanhantes. Conclusão: A cartilha intitulada “Guia de Cuidados para Realizar uma Alimentação Segura” obteve alta aprovação pelo público pesquisado e foi considerada válida para ser utilizada pela população.

Introduction: Telemedicine was leveraged for its contribution to mitigate the impact of COVID-19 in Brazil and worldwide. Objective: We aim to evaluate the acceptability of incorporating teleconsultation through synchronized videoconference by users and professionals in a service specialized in the prevention and treatment of the human immunodeficiency virus and other sexually transmitted infections, and to identify associated factors. Methods: This is a cross-sectional study with 410 users and 57 professionals who answered a category-standardized questionnaire. Predictors of acceptability were assessed using logistic regression model. Results: A total of 364 (88.8%) users said they would accept the modality. The factors positively associated with the odds of acceptance were the self-assessment of having favorable conditions to participate in a teleconsultation (aOR 54.8; 95%CI 12.4–242.1; p

Stimulated thermography is a very common non-destructive testing (NDT) technique used for a wide range of applications and materials. An external excitation source is required to stimulate the component and detect defects. Electric currents can be used in this sense adopting two different approaches: induction thermography and conduction thermography. In this work, a preliminary investigation to evaluate the influence of some test parameters during experiments of conduction thermography, for the detection of short fatigue cracks, induced in thin specimens of different materials, is presented. The capability of the technique and crack detectability have been analysed and compared with the Thermoelastic Stress Analysis (TSA) considered as a well-established technique capable of quantifying short fatigue cracks in metal materials.

Presently, composites are one of the top-of-the-range materials used in different industrial sectors and represent the best alternative to metal alloys in those applications where higher mechanical properties and lower weights are required [...]

(1) Background: Lichens, as an important part of the terrestrial ecosystem, attract the attention of various research disciplines. To elucidate their ultrastructure, transmission electron microscopy of resin-embedded samples is indispensable. Since most observations of lichen samples are generated via chemical fixation and processing at room temperature, they lack the rapid immobilization of live processes and are prone to preparation artefacts. To improve their preservation, cryoprocessing was tested in the past, but never widely implemented, not least because of an extremely lengthy protocol. (2) Methods: Here, we introduce an accelerated automated freeze substitution protocol with continuous agitation. Using the example of three lichen species, we demonstrate the preservation of the native state of algal photobionts and mycobionts in association with their extracellular matrix. (3) Results: We bring to attention the extent and the structural variability of the hyphae, the extracellular matrix and numerous crystallized metabolites. Our findings will encourage studies on transformation processes related to the compartmentation of lichen thalli. They include cryopreserved aspects of algal photobionts and observations of putative physiological relevance, such as the arrangement of numerous mitochondria within chloroplast pockets. (4) Conclusions: In summary, we present accelerated freeze substitution as a very useful tool for systematic studies of lichen ultrastructures.

Reverse electrodialysis (RED), an emerging membrane-based technology, harnesses salinity gradient energy for sustainable power generation. Accurate characterization of electrical parameters in RED stacks is crucial to monitoring its performance and exploring possible applications. In this study, a DC electronic load module (DCELM) is implemented in a constant current condition (CC mode) for characterization of lab scale RED process, using a RED prototype in-house designed and manufactured (RU1), at different data capture setups (DCS), on which the total number of steps for data capture (NS) and the number of measurements per step (ρ) are the parameters that were modified to study their effect on obtained electrical parameters in RED. NS of 10, 50, and 100 and ρ of 10 and 20 were used with this purpose. The accuracy of resulting current and voltage steps can be enhanced by increasing NS and ρ values, and according to obtained results, the higher accuracy of resulting output current and voltage steps, with low uncertainty of the average output steps (AOS) inside the operational region of power curve, was obtained using a DCS of NS = 100 and ρ = 20. The developed DCELM is a low-cost alternative to commercial electronic load devices, and the proposed methodology in this study represents an adaptative and optimizable CC mode characterization of RED process. The results obtained in this study suggest that data capture conditions have a direct influence of RED performance, and the accuracy of electrical parameters can be improved by optimizing the DCS parameters, according to the required specifications and the scale of RED prototypes.

Indonesia is a multicultural country that has a variety of cultures. This is due to the geographical location of Indonesia which is an archipelagic country that stretches from the western end of Sabang Island to the eastern end of Merauke Island. So in conditions like this, various tribes, customs, ethnic cultures and beliefs emerged in Indonesia. This diversity has both positive and negative impacts. The positive impact is that diversity can strengthen unity, but the negative impact is that it can lead to division. One of the problems that can lead to the division of the Indonesian nation is the intolerant behavior of the people. Intolerant behavior often occurs in people's lives in various fields. The fields of politics, economics, religion, social and culture are always inseparable from intolerant attitudes, especially in the development of the flow of information in the current era of globalization. There are many cases that trigger inter-ethnic divisions that circulate in the mass media, especially social media. Therefore, a guide for the Indonesian people is needed to deal with the issue of division, namely Pancasila. Pancasila which is the nation's ideology has values ​​that become the view of life of the Indonesian people which are always relevant to the times, especially in the current era of globalization. By implementing and preserving Pancasila in all areas of people's lives, it means that we are trying to realize a common life that is conditional on the values ​​of unity, kinship, justice, tolerance and humanity.

Background: Percentage and speed of germination are crucial factors that can restrict processes involved in plant succession during ecological restoration. Pre-germination treatments and the effect of storage time on germination percentage and mean germination time were investigated in nine native herbaceous plants of the La Primavera Flora and Fauna Protection Area. Question: Do the seeds of the studied species go dormant, and can storage time affect germination percentage and mean germination time? Species studied: Aeschynomene villosa var. longifolia (Micheli) Rudd, Crotalaria pumila Ort., Dalea leporina (Ait.) Bullock, D. foliolosa (Ait.) Barneby, Desmodium aparines (Link) DC., D. distortum (Aubl.) JF Macbr., D. tortuosum (Sw.) DC., Paspalum notatum Flüggé, and Zornia reticulata I. E. Smith. Place and dates of study: Area of Protection of Flora and Fauna La Primavera. From 2019 to 2020 Methods: Under greenhouse conditions, four treatments were applied prior to germination: scarification with a tweezer pliers, immersion in water at 40 ᵒC for 24 and 48 h, and control. Results: Seven species had highly viable (≥ 90 %) seeds after 12 months of storage. Five species with seed dormancy reached germination above 80 % after 24 months of storage and scarification with a tweezer pliers. Mean germination time for most species decreased with the scarification treatment. Conclusion: Our findings provide basic information on the germination of native species that could help restore degraded sites in the La Primavera Flora and Fauna Protection Area.

Abstract ABBV‐47D11 is a neutralizing monoclonal antibody that targets a mutationally conserved hydrophobic pocket distal to the ACE2 binding site of SARS‐CoV‐2. This first‐in‐human safety, pharmacokinetics, and antiviral pharmacodynamic assessment in patients with COVID‐19 provide an initial evaluation of this antibody that may allow further development. This multicenter, randomized, double‐blind, and placebo‐controlled single ascending dose study of ABBV‐47D11 (180, 600, or 2400 mg) as an intravenous infusion, was in hospitalized and non‐hospitalized (confined) adults with mild to moderate COVID‐19. Primary outcomes were grade 3 or higher study drug‐related adverse events and infusion‐related reactions. Secondary outcomes were pharmacokinetic parameters and concentration‐time profiles to Day 29, immunogenicity (anti‐drug antibodies), and antiviral activity (change in RT‐PCR viral load) from baseline to Days 15 and 29. ABBV‐47D11 single doses up to 2400 mg were safe and tolerated and no safety signals were identified. The pharmacokinetics of ABBV‐47D11 were linear and showed dose‐proportional increases in serum concentrations with ascending doses. The exploratory anti‐SARS‐CoV‐2 activity revealed a reduction of viral load at and above the 600 mg dose of ABBV‐47D11 regardless of patient demographics and baseline characteristics, however; because of the high inter‐individual variability and small sample size a statistical significance was not reached. There is potential for anti‐SARS‐CoV‐2 activity with ABBV‐47D11 doses of 600 mg or higher, which could be evaluated in future clinical trials designed and powered to assess viral load reductions and clinical benefit.

Summary: Background: Previous epigenome-wide association studies have shown that HIV infection can disrupt the host DNA methylation landscape. However, it remains unclear how antiretroviral therapy (ART) affects the HIV-induced epigenetic modifications. Methods: 184 individuals with HIV from the NEAT001/ANRS143 clinical trial (with pre-ART and post-ART samples [96 weeks of follow-up]) and 44 age-and-sex matched individuals without HIV were included. We compared genome-wide DNA methylation profiles in whole blood between groups adjusting for age, sex, batch effects, and DNA methylation-based estimates of leucocyte composition. Findings: We identified 430 differentially methylated positions (DMPs) between HIV+ pre-ART individuals and HIV-uninfected controls. In participants with HIV, ART initiation modified the DNA methylation levels at 845 CpG positions and restored 49.3% of the changes found between HIV+ pre-ART and HIV-uninfected individuals. We only found 15 DMPs when comparing DNA methylation profiles between HIV+ post-ART individuals and participants without HIV. The Gene Ontology enrichment analysis of DMPs associated with untreated HIV infection revealed an enrichment in biological processes regulating the immune system and antiviral responses. In participants with untreated HIV infection, DNA methylation levels at top HIV-related DMPs were associated with CD4/CD8 ratios and viral loads. Changes in DNA methylation levels after ART initiation were weakly correlated with changes in CD4+ cell counts and the CD4/CD8 ratio. Interpretation: Control of HIV viraemia after 96 weeks of ART initiation partly restores the host DNA methylation changes that occurred before antiretroviral treatment of HIV infection. Funding: NEAT-ID Foundation and Instituto de Salud Carlos III, co-funded by European Union.