[Trauma Injuries Associated with Rope Bullfights in the Azores: A Cross-Sectional Study]. / Trauma Associado às Touradas à Corda nos Açores: Um Estudo Transversal.

INTRODUCTION: The aim of the study was to describe trauma injuries associated with rope bullfights in the Azores, Portugal, regarding the cause of the incident, trauma mechanism, most affected anatomical areas, and injury severity. METHODS: Two-year cross-sectional study in the local hospital with prospective data collection. Patients who were consecutively admitted to the local hospital's emergency department with trauma injuries from the bull's direct impact or from falls either during the bull's escape or when handling the rope, were included. Data on general demographics, lesion characteristics, treatments, need for hospitalization and mortality were collected. RESULTS: Fifty-six incidents and 80 trauma injuries were identified. The main cause of trauma was the bull's direct impact (37; 66.07%) and the mechanism of injury was blunt trauma in all patients (100%; 56). Head and neck injuries (27; 33.75%) were the most common. The median Injury Severity Score at the emergency department admission was 4. Major trauma was noted in five patients (8.92%). Ten patients (17.85%) needed hospitalization with a median hospital stay of seven days. Three of the 10 hospitalized patients (30%) were previously admitted to the intensive care unit. Surgery was performed in six patients (10.71%). CONCLUSION: The main cause of trauma was the bull's direct impact, and the mechanism of injury was blunt trauma. The most affected anatomical areas were the head and neck. These findings are a wake-up call to the impact of these events regarding the economic costs they entail, the costs for the health of the local population, the safety measures currently implemented and the availability of the necessary means to treat these patients.

Introdução: O objetivo deste estudo foi caracterizar as lesões traumáticas tauromáquicas ocorridas nas touradas à corda nos Açores no que diz respeito à causa do incidente, mecanismo de trauma, área anatómica mais afetada e gravidade das lesões. Métodos: Estudo unicêntrico, transversal, com a colheita prospetiva de dados realizada durante dois anos. Foram incluídos os doentes que consecutivamente recorreram ao serviço de urgência do hospital local por lesões traumáticas ocorridas por trauma direto com o animal ou quedas aquando da fuga ou manuseio da corda. Foram colhidos dados demográficos gerais, características da lesão, tratamentos efetuados, necessidade de internamento hospitalar e mortalidade. Foi realizada uma análise estatística descritiva com recurso ao software estatístico SPSS. Resultados: Registaram-se 56 admissões hospitalares e 80 lesões traumáticas. A principal causa de traumatismo foi o trauma direto com o animal (37; 66,07%) e o mecanismo de lesão foi o trauma fechado (56; 100%). As áreas anatómicas mais afetadas foram a cabeça e pescoço (27; 33,75%). A mediana de Injury Severity Score foi de 4 à admissão hospitalar. Cinco doentes (8,92%) apresentaram trauma major. Dez doentes (17,85%) necessitaram de internamento hospitalar com uma mediana de dias de internamento de sete (IIQ 4,5 dias). Três (30%) dos doentes internados necessitaram de internamento em unidade de cuidados intensivos. Seis doentes (10,71%) foram submetidos a cirurgia. Conclusão: A principal causa de traumatismo foi o trauma direto com o animal e o mecanismo de lesão foi o trauma fechado. As áreas anatómicas mais afetadas foram a cabeça e pescoço. Estes dados constituem um alerta para o impacto destes eventos no que diz respeito aos custos económicos que acarretam, aos custos para a saúde da população local, às medidas de segurança atualmente implementadas e à disponibilidade dos meios necessários para tratar estes doentes.

VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway.

Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed. Mechanistically, we unveil that VEGF-B binds to FGFR1, induces FGFR1/VEGFR1 complex formation, and suppresses FGF2-induced Erk activation, and inhibits FGF2-driven angiogenesis and tumor growth. Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway. Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels, caution is warranted when modulating VEGF-B activity to treat neovascular diseases.

A Comparison of Cell-Cell Interaction Prediction Tools Based on scRNA-seq Data.

Computational prediction of cell-cell interactions (CCIs) is becoming increasingly important for understanding disease development and progression. We present a benchmark study of available CCI prediction tools based on single-cell RNA sequencing (scRNA-seq) data. By comparing prediction outputs with a manually curated gold standard for idiopathic pulmonary fibrosis (IPF), we evaluated prediction performance and processing time of several CCI prediction tools, including CCInx, CellChat, CellPhoneDB, iTALK, NATMI, scMLnet, SingleCellSignalR, and an ensemble of tools. According to our results, CellPhoneDB and NATMI are the best performer CCI prediction tools, among the ones analyzed, when we define a CCI as a source-target-ligand-receptor tetrad. In addition, we recommend specific tools according to different types of research projects and discuss the possible future paths in the field.

Epidemiological study of vaccination against SARS-CoV-2 and its impact on COVID-19 progression in a cohort of patients in gran Canaria.

Objectives. We analyzed the impact of age, sex, vaccination against COVID-19, immunosuppressive treatment, and comorbidities on patients' risk of requiring hospital admission or of death. Methods. Population-based observational retrospective study conducted on a cohort of 19,850 patients aged 12 years or more, who were diagnosed with COVID-19 between June 1st and December 31st, 2021, in the island of Gran Canaria. Results. Hypertension (18.5%), asthma (12.8%) and diabetes (7.2%) were the most frequent comorbidities; 147 patients died (0.7%). The combination of advanced age, male sex, cancer, coronary heart disease, immunosuppressive treatment, hospital admission, admission to the intensive care unit, mechanical ventilation and lack of complete COVID-19 vaccination or booster dose was strongly predictive of mortality (p < 0.05); 831 patients required hospital admission and it was more frequent in men, older age groups, and patients with cancer, diabetes, arterial hypertension, chronic obstructive pulmonary disease, congestive heart failure or immunosuppressive treatment. The COVID-19 vaccine booster dose was associated with a lower risk of death ([OR] 0.11, 95% CI 0.06-0.21, p < 0.05) or hospital admission ([OR] 0.36, 95% CI 0.29-0.46, p < 0.05). Conclusions. Cancer, coronary heart disease, and immunosuppressive treatment were associated with increased COVID-19 mortality. More complete vaccination was associated with lower risk of hospital admission or death. Three doses of the SARS-CoV-2 vaccine were highly associated with the prevention of death and hospital admission in all age groups. These findings suggest that COVID-19 vaccination can help bring the pandemic under control.

Objetivos. Analizamos el impacto de la edad, el sexo, la vacunación frente a la COVID-19, el tratamiento inmunosupresor y las comorbilidades en el riesgo de los pacientes de precisar ingreso hospitalario o de fallecer.Métodos. Estudio retrospectivo observacional de base poblacional realizado sobre una cohorte de 19.850 pacientes de 12 años o más, que fueron diagnosticados de COVID-19 entre el 1 de junio y el 31 de diciembre de 2021, en la isla de Gran Canaria.Resultados. La hipertensión arterial (18,5%), el asma (12,8%) y la diabetes (7,2%) fueron las comorbilidades más frecuentes; Fallecieron 147 pacientes (0,7%). La combinación de edad avanzada, sexo masculino, cáncer, cardiopatía coronaria, tratamiento inmunosupresor, ingreso hospitalario, ingreso en unidad de cuidados intensivos, ventilación mecánica y la falta de vacunación completa contra el COVID-19 o dosis de refuerzo fue fuertemente predictiva de mortalidad (p < 0,05); 831 pacientes requirieron ingreso hospitalario y fue más frecuente en hombres, grupos de mayor edad y pacientes con cáncer, diabetes, hipertensión arterial, enfermedad pulmonar obstructiva crónica, insuficiencia cardiaca congestiva o tratamiento inmunosupresor. La dosis de refuerzo contra la vacuna del COVID-19 se asoció con un menor riesgo de muerte ([OR] 0.11, IC 95% 0.06­0.21, p < 0,05) o ingreso hospitalario ([OR] 0.36, IC 95% 0.29­0.46; p < 0,05).Conclusiones. El cáncer, la enfermedad coronaria y el tratamiento inmunosupresor se asociaron con una mayor mortalidad por COVID-19. Una vacunación más completa se asoció con un menor riesgo de hospitalización o muerte. Tres dosis de la vacuna contra el SARS-CoV-2 se asociaron a una mayor prevención de la muerte y el ingreso hospitalario relacionados con la COVID-19 en todos los grupos de edad. Estos hallazgos sugieren que la vacunación contra el COVID-19 puede ayudar a controlar la pandemia.

Assessment of SARS-CoV-2 Infection According to Previous Metabolic Status and Its Association with Mortality and Post-Acute COVID-19.

Background. SARS-CoV-2 infection was analyzed according to previous metabolic status and its association with mortality and post-acute COVID-19. Methods. A population-based observational retrospective study was conducted on a cohort of 110,726 patients aged 12 years or more who were diagnosed with COVID-19 infection between June 1st, 2021, and 28 February 2022 on the island of Gran Canaria, Spain. Results. In the 347 patients who died, the combination of advanced age, male sex, cancer, immunosuppressive therapy, coronary heart disease, elevated total cholesterol and reduced high-density lipoprotein cholesterol (HDL-C) was strongly predictive of mortality (p < 0.05). In the 555 patients who developed post-acute COVID-19, the persistence of symptoms was most frequent in women, older subjects and patients with obstructive sleep apnea syndrome, asthma, elevated fasting glucose levels or elevated total cholesterol (p < 0.05). A complete vaccination schedule was associated with lower mortality (incidence rate ratio (IRR) 0.5, 95%CI 0.39−0.64; p < 0.05) and post-acute COVID-19 (IRR 0.37, 95%CI 0.31−0.44; p < 0.05). Conclusions. Elevated HDL-C and elevated total cholesterol were significantly associated with COVID-19 mortality. Elevated fasting glucose levels and elevated total cholesterol were risk factors for the development of post-acute COVID-19.

PDGFD switches on stem cell endothelial commitment.

The critical factors regulating stem cell endothelial commitment and renewal remain not well understood. Here, using loss- and gain-of-function assays together with bioinformatic analysis and multiple model systems, we show that PDGFD is an essential factor that switches on endothelial commitment of embryonic stem cells (ESCs). PDGFD genetic deletion or knockdown inhibits ESC differentiation into EC lineage and increases ESC self-renewal, and PDGFD overexpression activates ESC differentiation towards ECs. RNA sequencing reveals a critical requirement of PDGFD for the expression of vascular-differentiation related genes in ESCs. Importantly, PDGFD genetic deletion or knockdown increases ESC self-renewal and decreases blood vessel densities in both embryonic and neonatal mice and in teratomas. Mechanistically, we reveal that PDGFD fulfills this function via the MAPK/ERK pathway. Our findings provide new insight of PDGFD as a novel regulator of ESC fate determination, and suggest therapeutic implications of modulating PDGFD activity in stem cell therapy.

Up to half of patients diagnosed with chronic lymphocytic leukemia in México may not require treatment.

Introduction: Although therapeutic choices for patients with chronic lymphocytic leukemia (CLL) were once limited, treatment of this disease has vastly improved in the last decades.Patients and methods: Consecutive CLL patients diagnosed in a single institution were analyzed. Treatment was withheld in persons with CLL Rai stage 0 or 1, until progression and in persons with stages 2-4, with a negative expression of ZAP-70 until progression. Between 1983 and 1991, patients were give chlorambucil and prednisone (CP); after 1991 fludarabine and cyclophosphamide (FC) and after 1998, rituximab and FC (FCR).Results: 98 patients with CLL were identified; 49 were followed for >3 months. 21 persons (43%) did not require treatment nor progressed; 14 received CP, 6 FC, 7 FCR and one rituximab. Median overall survival (OS) has not been reached, being above 247 months; median OS for patients given CP was 115 months, for FC above 132 months and for FCR above 136 months (p > 0.5).Conclusion: CLL seems to be less aggressive in Mexican mestizos than in Caucasians; 43% of patients do not need treatment at all.

GREG-studying transcriptional regulation using integrative graph databases.

A gene regulatory process is the result of the concerted action of transcription factors, co-factors, regulatory non-coding RNAs (ncRNAs) and chromatin interactions. Therefore, the combination of protein-DNA, protein-protein, ncRNA-DNA, ncRNA-protein and DNA-DNA data in a single graph database offers new possibilities regarding generation of biological hypotheses. GREG (The Gene Regulation Graph Database) is an integrative database and web resource that allows the user to visualize and explore the network of all above-mentioned interactions for a query transcription factor, long non-coding RNA, genomic range or DNA annotation, as well as extracting node and interaction information, identifying connected nodes and performing advanced graphical queries directly on the regulatory network, in a simple and efficient way. In this article, we introduce GREG together with some application examples (including exploratory research of Nanog's regulatory landscape and the etiology of chronic obstructive pulmonary disease), which we use as a demonstration of the advantages of using graph databases in biomedical research. Database URL: https://mora-lab.github.io/projects/greg.html, www.moralab.science/GREG/.

Treatment of Persons with Multiple Myeloma in Underprivileged Circumstances: Real-World Data from a Single Institution.

BACKGROUND: The treatment of patients with multiple myeloma (MM) has evolved in recent years, and the disease-associated prognosis has improved substantially. This improvement has been driven largely by the approval of novel agents, many of which are expensive and not universally available. Less expensive but effective approaches would be of value globally. PATIENTS AND METHODS: All consecutive MM patients diagnosed in the Centro de Hematología y Medicina Interna de Puebla after 1993 were included in this study. Patients were given oral thalidomide (100 mg/day), oral dexamethasone (36-40 mg/week), and aspirin 100 mg/day. Bor-tezomib (1.75 mg s.c. every week) was administered to those who could afford it. After 4-6 weeks of treatment, patients were offered an outpatient-based hematopoietic cell transplant (HCT). After the recovery of granulocytes following HCT, patients continued indefinitely on thalidomide; those who failed to tolerate thalidomide were switched to lenalidomide (25 mg/day). RESULTS: The median overall survival (OS) for all patients has not been reached and is >157 months. Median follow-up of the patients lasted 14 months (range 1.3-157). The median OS of patients with and without HCT was similar. The response rate (complete remission or very good partial remission) was 72% for those given thalidomide plus dexamethasone versus 88% for those given bortezomib, thalidomide, and dexamethasone before HCT, but OS was not different. As post-HCT maintenance, 37 patients received thalidomide; 26 of those (70%) could be maintained indefinitely on thalidomide, whereas 11 were switched to lenalidomide after a median of 7 months; median OS of patients maintained on thalidomide or lenalidomide after HCT was not different. CONCLUSION: In this series, a regimen incorporating low-cost novel agents and outpatient HCT was associated with excellent long-term survival in the treatment of MM patients. This approach may be a model for MM treatment in underprivileged circumstances.

Nonalcoholic Fatty Liver Disease and Thrombocytopenia III: Its Association With Insulin Resistance.

Thrombocytopenia (less than 100 × 109/L platelets) presents in around one quarter of patients with nonalcoholic fatty liver disease (NAFLD), the hepatic component of insulin resistance (IR). It is unknown whether IR, by itself, associates with thrombocytopenia. Persons with NAFLD and/or IR were prospectively accrued in the study after February 2018. Insulin resistance was defined by assessing α hydroxybutyrate, lynoleoyl glycerolphosphocoline, oleic acid, and insulin (Quantose IR), whereas the presence of NAFLD was defined by serologic determinations (Fibromax) and liver transient elastography (Fibroscan). In 78 patients with NAFLD, thrombocytopenia was identified in 22 (28%), whereas in 19 persons with IR, 14 (73%) were found to have NAFLD. In persons with IR + NAFLD, thrombocytopenia presented in 9 (64%). In the subset of patients with IR, the prevalence of thrombocytopenia was 52%. There was only 1 patient with IR/without NAFLD who displayed thrombocytopenia. Significant statistical association between NAFLD and thrombocytopenia was found (odds ratio [OR]: = 13, confidence interval [CI]: 1.5-162, P = .05), whereas there was no association between IR and thrombocytopenia (OR = 0.38, CI: 0.06-2.3, P = .61). Insulin resistance, by itself, was not found to be associated with diminished platelet counts. The presence of NAFLD, one of the consequences of IR, seems to be required to lead into thrombocytopenia.

Separate and combined effects of DNMT and HDAC inhibitors in treating human multi-drug resistant osteosarcoma HosDXR150 cell line.

Understanding the molecular mechanisms underlying multi-drug resistance (MDR) is one of the major challenges in current cancer research. A phenomenon which is common to both intrinsic and acquired resistance, is the aberrant alteration of gene expression in drug-resistant cancers. Although such dysregulation depends on many possible causes, an epigenetic characterization is considered a main driver. Recent studies have suggested a direct role for epigenetic inactivation of genes in determining tumor chemo-sensitivity. We investigated the effects of the inhibition of DNA methyltransferase (DNMT) and hystone deacethylase (HDAC), considered to reverse the epigenetic aberrations and lead to the re-expression of de novo methylated genes in MDR osteosarcoma (OS) cells. Based on our analysis of the HosDXR150 cell line, we found that in order to reduce cell proliferation, co-treatment of MDR OS cells with DNMT (5-Aza-dC, DAC) and HDAC (Trichostatin A, TSA) inhibitors is more effective than relying on each treatment alone. In re-expressing epigenetically silenced genes induced by treatments, a very specific regulation takes place which suggests that methylation and de-acetylation have occurred either separately or simultaneously to determine MDR OS phenotype. In particular, functional relationships have been reported after measuring differential gene expression, indicating that MDR OS cells acquired growth and survival advantage by simultaneous epigenetic inactivation of both multiple p53-independent apoptotic signals and osteoblast differentiation pathways. Furthermore, co-treatment results more efficient in inducing the re-expression of some main pathways according to the computed enrichment, thus emphasizing its potential towards representing an effective therapeutic option for MDR OS.

Effects of protein interaction data integration, representation and reliability on the use of network properties for drug target prediction.

BACKGROUND: Previous studies have noted that drug targets appear to be associated with higher-degree or higher-centrality proteins in interaction networks. These studies explicitly or tacitly make choices of different source databases, data integration strategies, representation of proteins and complexes, and data reliability assumptions. Here we examined how the use of different data integration and representation techniques, or different notions of reliability, may affect the efficacy of degree and centrality as features in drug target prediction. RESULTS: Fifty percent of drug targets have a degree of less than nine, and ninety-five percent have a degree of less than ninety. We found that drug targets are over-represented in higher degree bins - this relationship is only seen for the consolidated interactome and it is not dependent on n-ary interaction data or its representation. Degree acts as a weak predictive feature for drug-target status and using more reliable subsets of the data does not increase this performance. However, performance does increase if only cancer-related drug targets are considered. We also note that a protein's membership in pathway records can act as a predictive feature that is better than degree and that high-centrality may be an indicator of a drug that is more likely to be withdrawn. CONCLUSIONS: These results show that protein interaction data integration and cleaning is an important consideration when incorporating network properties as predictive features for drug-target status. The provided scripts and data sets offer a starting point for further studies and cross-comparison of methods.

The neurofibromin 1 type I isoform predominance characterises female population affected by sporadic breast cancer: preliminary data.

AIMS: Neurofibromin 1 (NF1) as a tumour suppressor gene can give rise to several transcripts by an alternative splicing event, generated at least for CELF cofactors. At present, the NF1 isoforms and CELF splicing transcripts in sporadic breast cancer are unknown. The aim of the authors was to detect NF1 gene expression, the NF1 isoform ratio and the CELF transcripts present in sporadic breast cancer. METHODS: Neurofibromin and RAS expression were analysed on tissue microarrays containing sporadic breast cancer (n=22), benign lesions (n=18, including six fibroadenomas, six fibrocystic changes and six ductal hyperplasias) and normal breast tissue (n=6) by immunohistochemistry assay. NF1 and CELF 3-6 RNA expression was performed by end point reverse transcription-PCR in the breast samples. RESULTS: NF1 and RAS expression in breast tissues showed no differential expression by immunohistochemistry results. Interestingly, the authors observed a shift transition in the isoform transcripts, from type II in normal breast tissue to type I isoform in breast carcinomas. CELF cofactor expression failed to be related with the shift transition of NF1 in breast tissues. CONCLUSIONS: These data suggest that there is a tendency for an NF1 expression shift transition from type II to type I isoform, which could comprise a significant event in the development and progression of sporadic breast cancer. This shift transition may not be related with CELF cofactors.

Poststapedectomy hearing gain: comparison of a Teflon (fluoroplastic ASTM F 754) prosthesis with a Schuknecht-type wire/Teflon prosthesis.

We conducted a retrospective study to compare poststapedectomy hearing gain in study-eligible patients who had received a Teflon (fluoroplastic ASTM F 754) prosthesis (study group; n = 76) with hearing gain achieved in a matched group (by age, sex, and degree of hypoacusis) of patients who had received a Schuknecht-type wire/Teflon prosthesis (control group; n = 70). All procedures had been performed by the authors at our institution between Jan. 2, 1994, and Dec. 31, 1997. Airway averages at low, medium, and high frequencies were estimated on the basis ofpre- and postoperative audiologic evaluations, as were total air-bone gaps at 7 frequencies between 125 and 8, 000 Hz. We found that the study group achieved a significantly greater degree of hearing gain at 125 and 250 Hz and significantly better closure of the air-bone gap at 250, 500, 1,000, 2,000, and 4,000 Hz. The hearing outcomes among patients in the study group were excellent.

Timpanoplastia en otitis media crónica y su relación con la trompa de Eustaquio / Tympanoplasty in chronic otitis media and its relations to the Eustachian tube

Objetivo: identificar la relación de la función de la trompa de Eustaquio con los resultados anatómicos y funcionales de timpanoplastia efectuada a pacientes con otitis media crónica. Diseño: estudio prospectivo, longitudinal, clínico controlado, comparativo, no cegado. Material y métodos: se estudiaron 55 pacientes en el Departamento de Otorrinolaringología del Hospital General, Centro Médico Nacional La Raza. Se les practicó estudio audiométrico con logoaudiometría, valoración de la función de la trompa de Eusaquio mediante impedanciometría, y timpanoplastia retroauricular. Resultados: se trató de 19 pacientes masculinos y 36 femeninos, promedio de edad 32 años. La función posoperatoria de la trompa de Eustaquio cambió en 29.1 por ciento y se mantuvo igual en 69.1 por ciento. La integración del injerto se logró en 26 casos (96.3 por ciento) del grupo con buena función tubaria y en 28 (100 por ciento) del grupo con mala función tubaria. La movilidad del injerto fue normal en 80 por ciento y anormal en 18.2 por ciento. Se obtuvo ganancia auditiva en 89.1 por ciento (siendo mayor en frecuencias bajas sobre todo en 250 Hz), 9.1 por ciento sin ganancia y no hubo casos con pérdida autidiva. Conclusión: la función de la rompa de Eustauio no influye en el resultado de la timpanoplastia y es posible continuar con las intervenciones quirúrgicas en pacientes con mala función tubaria preoperatoria, ya que su condición no modifica los resultados

Quiste dermoide mastoideo, reporte de un caso / Dermoid cyst in the mastoid process. case report

Se reporta el caso de paciente femenino de 34 años de edad, con historia de otitis media crónica y cirugía mastoidea en su infancia que en su vida adulta presenta hipoacusia conductiva unilateral progresiva, sintomatología vestibular, acúfeno y otalgia ipsilateral de un año de evolución. Los hallazgos tanto en estudios de imagen como trans operatorio fueron de una neoformación que ocupaba y ampliaba antro y mastoides con un defecto óseo hacia fosa posterior. La lesión fue resecada vía transmastoidea. El reporte histopatológico señalaba quiste dermoide mastoideo