Merkel Cell Polyomavirus targets SET/PP2A complex to promote cellular proliferation and migration.

Merkel Cell Carcinoma (MCC) is a rare neuroendocrine skin cancer. In our previous work, we decoded genes specifically deregulated by MCPyV early genes as opposed to other polyomaviruses and established functional importance of NDRG1 in inhibiting cellular proliferation and migration in MCC. In the present work, we found the SET protein, (I2PP2A, intrinsic inhibitor of PP2A) upstream of NDRG1 which was modulated by MCPyV early genes, both in hTERT-HK-MCPyV and MCPyV-positive (+) MCC cell lines. Additionally, MCC dermal tumour nodule tissues showed strong SET expression. Inhibition of the SET-PP2A interaction in hTERT-HK-MCPyV using the small molecule inhibitor, FTY720, increased NDRG1 expression and inhibited cell cycle regulators, cyclinD1 and CDK2. SET inhibition by shRNA and FTY720 also decreased cell proliferation and colony formation in MCPyV(+) MCC cells. Overall, these results pave a path for use of drugs targeting SET protein for the treatment of MCC.

The pharmacoepigenetic paradigm in cancer treatment.

Epigenetic modifications, characterized by changes in gene expression without altering the DNA sequence, play a crucial role in the development and progression of cancer by significantly influencing gene activity and cellular function. This insight has led to the development of a novel class of therapeutic agents, known as epigenetic drugs. These drugs, including histone deacetylase inhibitors, histone acetyltransferase inhibitors, histone methyltransferase inhibitors, and DNA methyltransferase inhibitors, aim to modulate gene expression to curb cancer growth by uniquely altering the epigenetic landscape of cancer cells. Ongoing research and clinical trials are rigorously evaluating the efficacy of these drugs, particularly their ability to improve therapeutic outcomes when used in combination with other treatments. Such combination therapies may more effectively target cancer and potentially overcome the challenge of drug resistance, a significant hurdle in cancer therapy. Additionally, the importance of nutrition, inflammation control, and circadian rhythm regulation in modulating drug responses has been increasingly recognized, highlighting their role as critical modifiers of the epigenetic landscape and thereby influencing the effectiveness of pharmacological interventions and patient outcomes. Epigenetic drugs represent a paradigm shift in cancer treatment, offering targeted therapies that promise a more precise approach to treating a wide spectrum of tumors, potentially with fewer side effects compared to traditional chemotherapy. This progress marks a step towards more personalized and precise interventions, leveraging the unique epigenetic profiles of individual tumors to optimize treatment strategies.

Gastric cancer actionable genomic alterations across diverse populations worldwide and pharmacogenomics strategies based on precision oncology.

Introduction: Gastric cancer is one of the most prevalent types of cancer worldwide. The World Health Organization (WHO), the International Agency for Research on Cancer (IARC), and the Global Cancer Statistics (GLOBOCAN) reported an age standardized global incidence rate of 9.2 per 100,000 individuals for gastric cancer in 2022, with a mortality rate of 6.1. Despite considerable progress in precision oncology through the efforts of international consortia, understanding the genomic features and their influence on the effectiveness of anti-cancer treatments across diverse ethnic groups remains essential. Methods: Our study aimed to address this need by conducting integrated in silico analyses to identify actionable genomic alterations in gastric cancer driver genes, assess their impact using deleteriousness scores, and determine allele frequencies across nine global populations: European Finnish, European non-Finnish, Latino, East Asian, South Asian, African, Middle Eastern, Ashkenazi Jewish, and Amish. Furthermore, our goal was to prioritize targeted therapeutic strategies based on pharmacogenomics clinical guidelines, in silico drug prescriptions, and clinical trial data. Results: Our comprehensive analysis examined 275,634 variants within 60 gastric cancer driver genes from 730,947 exome sequences and 76,215 whole-genome sequences from unrelated individuals, identifying 13,542 annotated and predicted oncogenic variants. We prioritized the most prevalent and deleterious oncogenic variants for subsequent pharmacogenomics testing. Additionally, we discovered actionable genomic alterations in the ARID1A, ATM, BCOR, ERBB2, ERBB3, CDKN2A, KIT, PIK3CA, PTEN, NTRK3, TP53, and CDKN2A genes that could enhance the efficacy of anti-cancer therapies, as suggested by in silico drug prescription analyses, reviews of current pharmacogenomics clinical guidelines, and evaluations of phase III and IV clinical trials targeting gastric cancer driver proteins. Discussion: These findings underline the urgency of consolidating efforts to devise effective prevention measures, invest in genomic profiling for underrepresented populations, and ensure the inclusion of ethnic minorities in future clinical trials and cancer research in developed countries.

Mortalidad infantil en la provincia de Santiago de Cuba durante el período 2008-2022

Introducción: La tasa de mortalidad infantil es un indicador importante y sensible del bienestar y la calidad de vida de una población, muy usado para medir su estado de salud. Objetivo: Caracterizar la mortalidad infantil según semestres en la provincia de Santiago de Cuba durante 2008-2022. Métodos: Se realizó un estudio observacional descriptico y transversal sobre la mortalidad infantil en la provincia de Santiago de Cuba durante los años 2008-2022. Para ello se analizó la relación existente entre los semestres de cada año respecto a los nacimientos, las defunciones y su incidencia en la tasa del país. Resultados: Se observó una disminución de los nacimientos y un incremento de las defunciones en cada quinquenio estudiado respecto al anterior. El número de fallecidos menores de un año fluctuó, con una tendencia al aumento a partir del 2019; asimismo, los indicadores de mortalidad infantil fueron inestables, con propensión al incremento, sobre todo en el segundo semestre, y peores resultados en el 2021 y 2022. Existió un descenso mantenido de los nacimientos a partir del 2011, que alcanzó 25,6 % en el 2022. Respecto a los semestres, en el segundo hubo mayor número de nacimientos, defunciones y tasas. Conclusiones: La provincia de Santiago de Cuba influye de forma directa en los resultados de la mortalidad infantil nacional, con una tasa superior a la exhibida por el país. El segundo semestre es el período en el que se incrementan los nacimientos y las defunciones, lo que incide en la elevación de las tasas respectivas.

Introduction: The infant mortality rate is an important and sensitive indicator of the well-being and life quality of a population, very used to measure the health state. Objective: To characterize the infant mortality in Santiago de Cuba province during the period 2008-2022. Methods: An observational descriptive and cross-sectional study about the infant mortality was carried out in Santiago de Cuba during the years 2008-2022. The existent relationship among the semesters of every year regarding births, deaths and their incidence in the country rate was analyzed. Results: A decrease of births and an increment of deaths were observed in each five year period studied regarding the previous one. The number of deceased children under one year fluctuated, with a tendency to the increase starting from 2019; also, the indicators of infant mortality were unstable, with tendency to the increment, mainly in the second semester, and worse results in 2021 and 2022. There was a maintained decrease of births since 2011 that reached 25.6% in 2022. In relation to semesters, in the second one there was a higher number of births, deaths and rates. Conclusions: Santiago de Cuba province influences in a direct way on the results of national infant mortality, with a superior rate to the one exhibited by the country. The second semester is the period in which births and deaths are increased, what impacts in the elevation of the respective rates.

High-risk HPV prevalence and vaccination coverage among Indigenous women in the Colombian Amazon: Implications for cervical cancer prevention. Cross-sectional study.

Cervical cancer, primarily caused by Human Papillomavirus (HPV) transmission through sexual contact, necessitates comprehensive strategies to combat its impact on women's health. Yet, certain underserved populations, such as low socioeconomic and ethnic minority groups, encounter barriers in accessing timely interventions and early diagnosis. This cross-sectional study was conducted with the aim of assessing HPV prevalence, genotype distribution, and co-infections among 280 adult women residing in a Colombian Indigenous Reserve within the Amazon region. The research adhered to a community-centric approach that respected cultural norms, native languages, and Indigenous authorities' permission. The study revealed an overall HPV infection prevalence of 31.1% (n = 87, 95% CI 25.7-36.8), with 22.5% (n = 63, 95% CI 17.7-27.8) of women infected by at least one high-risk HPV genotype and 15.0% (n = 42, 95% CI 11-19.7) infected by at least one LR genotype. These results align with the findings of other Colombian studies. Notable high-frequency genotypes included 16, 52, 66, 56, and 68, with the most common combinations being [66-52] and [66-58]. The study also assessed the prevalence of HPV vaccination, revealing a rate of 22.9%, lower than the national average. In vaccinated women, the prevalence of genotypes 16 and 18 was significantly reduced, as anticipated. Importantly, it was observed that 57.1% of all high-risk HPV infections could have been prevented with the use of the nonavalent vaccine. These findings underscore the critical need to enhance adherence to early cervical cancer detection and monitor positive cases to evaluate high-risk HPV persistence. Efforts should be directed toward continuing vaccination coverage against high-risk HPV 16 and 18 with the quadrivalent vaccine, while also striving to make the nonavalent vaccine accessible for inclusion in large-scale public health programs. Additionally, the study did not identify a specific pattern of co-infection. The study emphasizes the significance of adopting a locally tailored epidemiological approach to guide and promote cervical cancer prevention efforts in Indigenous communities.

Necrotizing external otitis: diagnostic clues in the emergency department.

PURPOSE: The assessment of necrotizing external otitis requires a high index of suspicion by the attending physician. The purpose of the study is to determine the accuracy of parameters available at the Emergency Department for the diagnosis of this pathology. METHODS: Retrospective diagnostic accuracy study. Patients consulting at the Emergency Department for longstanding ear swelling, severe otalgia, and failure to respond to topical treatment were included. Otoscopy, physical examination, CT appearance, and analytical results were tested for the diagnosis of necrotizing external otitis, using nuclear imaging as gold standard. Sensitivity, specificity, likelihood ratios and ROC curves were calculated. RESULTS: 24 patients were included; 13 cases were necrotizing external otitis, and 11 cases were other external ear pathologies. Erythrocyte sedimentation rate and C-reactive protein levels were significantly associated with necrotizing external otitis (AUC 0.92 p < 0.001, and 0.8 p < 0.001). Positive likelihood ratios were 10.15 for values of erythrocyte sedimentation rate over 26 mm/h, and 8.25 for C-reactive protein levels over 10 mg/L. Negative likelihood ratios were 0.08 and 0.28, respectively. These results were significant. The rest of clinical and radiological parameters were less accurate. CONCLUSIONS: Erythrocyte sedimentation rate and C-reactive protein are useful parameters in the evaluation of a case of longstanding otitis with clinical suspicion of necrotizing external otitis. If any of them is elevated, the probability of suffering this condition is significantly increased. If they are within normal ranges, an alternative diagnosis should be sought.

Asociación entre la salud oral y el deterioro cognitivo leve en adultos mayores / Association between Oral Health and Mild Cognitive Impairment in Older Adults

Introducción: En la medida que se incrementa la población de adultos mayores, aumenta la prevalencia, aumenta la prevalencia del deterioro cognitivo. Recientemente, se ha introducido la mala salud oral entre los factores de riesgo potenciales. Objetivo: Determinar la asociación entre la salud oral y el deterioro cognitivo leve en adultos mayores de una comunidad de la provincia de Santiago de Cuba. Métodos: Se realizó un estudio observacional, analítico y retrospectivo, de tipo casos y controles en el período comprendido entre enero y julio del año 2023. La población de estudio estuvo constituida por 257 adultos mayores que vivían en esta comunidad, de los cuales se escogieron 40 casos con diagnóstico de deterioro cognitivo leve, según los criterios de Petersen. Se seleccionaron tres controles por cada caso, 120 adultos mayores con aproximadamente las mismas características que el caso. Se precisó la fuerza de asociación de cada factor de riesgo. Resultados: Se halló una asociación significativa entre padecer deterioro cognitivo leve y presentar un número de 1 a 9 dientes. El dolor oral se presentó con mayor frecuencia en el 72,5 por ciento de los casos. No recordar la última visita al estomatólogo fue causa de deterioro cognitivo leve en el 42,5 por ciento. Cepillarse irregularmente se asoció 4,1 veces más con el riesgo de desarrollar esta afección. Conclusiones : Existe una asociación entre la salud oral y el deterioro cognitivo leve en los adultos mayores. Tener menos dientes y referir dolor oral fueron factores de riesgo importantes para presentar deterioro cognitivo. La visita al estomatólogo y el cepillado de dientes irregular influyeron negativamente en la enfermedad. Sin embargo, el uso de prótesis dentales fue un factor protector para el deterioro cognitivo leve(AU)

Introduction: Along with the increase in the population of older adults, the prevalence of cognitive impairment is increasing. Recently, poor oral health has been introduced among potential risk factors. Objective: To determine the association between oral health and mild cognitive impairment in older adults in a community in the province of Santiago de Cuba. Methods: An observational, analytical and retrospective case-control study was carried out from January to July 2023. The study population consisted of 257 older adults living in this community, from which 40 cases were selected with a diagnosis of mild cognitive impairment, according to Petersen's criteria. Three controls were selected for each case, 120 older adults with approximately the same characteristics as the case. The strength of association of each risk factor was determined. Results: A significant association was found between having mild cognitive impairment and having 1 to 9 teeth. Oral pain was more frequent in 72.5 percent of the cases. Not remembering the last visit to the dentist was a cause of mild cognitive impairment in 42.5 percent. Irregular brushing was 4.1 times more associated with the risk of developing this condition. Conclusions: There is an association between oral health and mild cognitive impairment in older adults. Having fewer teeth and reporting oral pain were important risk factors for cognitive impairment. Visiting the dentist and irregular tooth brushing had a negative influence on the disease. However, the use of dental prosthetics was a protective factor for mild cognitive impairment(AU)

HPV38 impairs UV-induced transcriptional activation of the IL-18 pro-inflammatory cytokine.

IMPORTANCE: Here, we demonstrate that the direct binding of p53 on the IL-18 promoter region regulates its gene expression. However, the presence of E6 and E7 from human papillomavirus type 38 impairs this mechanism via a new inhibitory complex formed by DNA methyltransferase 1 (DNMT1)/PKR/ΔNp73α, which binds to the region formerly occupied by p53 in primary keratinocytes.

Pesticides in rice-based products commercialised in Argentina.

People with coeliac disease have a limited diet. Therefore, rice-based products are an ideal alternative. Highlighting this import item, an analytical methodology was validated to determine pesticides in rice-based product samples. The precision was satisfactory for all pesticides since the RSD did not exceed 13% in any case. Regarding recovery, the method had values close to 100%. The limit of quantification was established at 10 µg/kg and the expanded uncertainty was less than 20%. After validation, 80 samples of toasts and rice crackers were analysed. All samples were compliant with the national regulations for dichlorvos and tebuconazole. The pesticide that was present in the highest number of samples was pirimiphos - methyl, but all below the maximum residue limit. From all samples analysed, 38 were positive for at least one pesticide and only one contained four pesticides simultaneously: deltamethrin, pirimiphos-methyl, kresoxim-methyl and epoxiconazole.

Integrated multi-omics analysis reveals the molecular interplay between circadian clocks and cancer pathogenesis.

Circadian rhythms (CRs) are fundamental biological processes that significantly impact human well-being. Disruption of these rhythms can trigger insufficient neurocognitive development, insomnia, mental disorders, cardiovascular diseases, metabolic dysfunctions, and cancer. The field of chronobiology has increased our understanding of how rhythm disturbances contribute to cancer pathogenesis, and how circadian timing influences the efficacy of cancer treatments. As the circadian clock steadily gains recognition as an emerging factor in tumorigenesis, a thorough and comprehensive multi-omics analysis of CR genes/proteins has never been performed. To shed light on this, we performed, for the first time, an integrated data analysis encompassing genomic/transcriptomic alterations across 32 cancer types (n = 10,918 tumors) taken from the PanCancer Atlas, unfavorable prognostic protein analysis, protein-protein interactomics, and shortest distance score pathways to cancer hallmark phenotypes. This data mining strategy allowed us to unravel 31 essential CR-related proteins involved in the signaling crossroad between circadian rhythms and cancer. In the context of drugging the clock, we identified pharmacogenomic clinical annotations and drugs currently in late phase clinical trials that could be considered as potential cancer therapeutic strategies. These findings highlight the diverse roles of CR-related genes/proteins in the realm of cancer research and therapy.

Colocolic intussusception by lipoma in transverse colon. A cause of intestinal obstruction.

Lipomas in the colon usually present as sessile polypoid masses, rarely pedunculated, with variable dimensions. They are generally asymptomatic and diagnosed incidentally although occasionally they may debut with symptoms. We present the case of a 48-year-old male with intestinal obstruction secondary to colonic lipoma causing invagination at the level of the transverse colon.

Darolutamide in Spanish patients with nonmetastatic castration-resistant prostate cancer: ARAMIS subgroup analysis.

Aim: Darolutamide significantly prolonged metastasis-free survival (MFS) versus placebo in the Phase III ARAMIS study. We analyzed outcomes in Spanish participants in ARAMIS. Patients & methods: Patients with high-risk nonmetastatic castration-resistant prostate cancer were randomized 2:1 to darolutamide 600 mg twice daily or placebo, plus androgen-deprivation therapy. The primary end point was MFS. Descriptive statistics are reported for this post hoc analysis. Results: In Spanish participants, darolutamide (n = 75) prolonged MFS versus placebo (n = 42): hazard ratio 0.345, 95% confidence interval 0.175-0.681. The incidence and type of treatment-emergent adverse events were comparable between treatment arms. Conclusion: For Spanish participants in ARAMIS, efficacy outcomes favored darolutamide versus placebo, with a similar safety profile, consistent with the overall ARAMIS population. Clinical Trials Registration: NCT02200614 (ClinicalTrials.gov).

Darolutamide is an oral treatment for a type of prostate cancer that has stopped responding to other treatments and is at risk of spreading to other parts of the body (termed "nonmetastatic castration-resistant prostate cancer" or "nmCRPC"). In the international ARAMIS study, patients treated with darolutamide lived longer without their cancer spreading than patients who were given placebo (sugar) pills. We wanted to know whether Spanish patients in ARAMIS had similar characteristics and treatment outcomes to other patients in the study. We found that the 75 Spanish patients who were treated with darolutamide had a significantly lower risk of their cancer spreading than the 42 Spanish patients who received placebo. The two groups of Spanish patients had similar side effects.

Incidence of Acute Neurological Events in Neonates and Infants Undergoing Cardiac Surgery Using a High-Hematocrit/ High-Flow Bypass Strategy.

Background: The incidence of new acute neurological injury occurring in neonates and infants during cardiac surgery utilizing cardiopulmonary bypass is reportedly 3% to 5%. In 2013, we adopted a high flow rate, and high hematocrit bypass strategy, and sought to assess the incidence of early neurological injuries associated with this strategy. Methods: Neonates and infants undergoing cardiopulmonary bypass between January 2013 and December 2019 (n = 714) comprise the study. Adverse neurological events (ANEs) were defined as any abnormality of pupils, delayed awakening, seizures, focal neurological deficits, concerns prompting neurological consultation, or any abnormality on neurological imaging in the postoperative period. Our bypass strategy included a high flow rate (150-200 mL/kg/min), without reduction of flow rates during cooling and maintaining a target hematocrit on bypass > 32% with a terminal hematocrit of > 42%. Results: Median weight at the time of the procedure was 4.6 kg (IQR 3.6-6.1 kg) with the smallest patient weighing 1.36 kg. There were 46 premature patients (6.4%). There were 149 patients (20.9%) patients who underwent deep hypothermic circulatory arrest with a median time of 26 min (IQR 21-41 min). Hospital mortality was 3.5% (24/714, 95% CI: 2.28-5.13). The incidence of neurological events as defined above was 0.84% (6/714, 95% CI: 0.31-1.82). Neurological imaging identified ischemic injury in 4 patients and intraventricular hemorrhage in 2. Conclusions: High flow/high hematocrit bypass strategy was associated with a low incidence of ANE in this vulnerable population.

The E2F4/p130 Repressor Complex Cooperates with Oncogenic ΔNp73α To Inhibit Gene Expression in Human Papillomavirus 38 E6/E7-Transformed Keratinocytes and in Cancer Cells.

Tumor suppressor p53 and its related proteins, p63 and p73, can be synthesized as multiple isoforms lacking part of the N- or C-terminal regions. Specifically, high expression of the ΔNp73α isoform is notoriously associated with various human malignancies characterized by poor prognosis. This isoform is also accumulated by oncogenic viruses, such as Epstein-Barr virus (EBV), as well as genus beta human papillomaviruses (HPV) that appear to be involved in carcinogenesis. To gain additional insight into ΔNp73α mechanisms, we have performed proteomics analyses using human keratinocytes transformed by the E6 and E7 proteins of the beta-HPV type 38 virus as an experimental model (38HK). We find that ΔNp73α associates with the E2F4/p130 repressor complex through a direct interaction with E2F4. This interaction is favored by the N-terminal truncation of p73 characteristic of ΔNp73 isoforms. Moreover, it is independent of the C-terminal splicing status, suggesting that it could represent a general feature of ΔNp73 isoforms (α, ß, γ, δ, ε, ζ, θ, η, and η1). We show that the ΔNp73α-E2F4/p130 complex inhibits the expression of specific genes, including genes encoding for negative regulators of proliferation, both in 38HK and in HPV-negative cancer-derived cell lines. Such genes are not inhibited by E2F4/p130 in primary keratinocytes lacking ΔNp73α, indicating that the interaction with ΔNp73α rewires the E2F4 transcriptional program. In conclusion, we have identified and characterized a novel transcriptional regulatory complex with potential implications in oncogenesis. IMPORTANCE The TP53 gene is mutated in about 50% of human cancers. In contrast, the TP63 and TP73 genes are rarely mutated but rather expressed as ΔNp63 and ΔNp73 isoforms in a wide range of malignancies, where they act as p53 antagonists. Accumulation of ΔNp63 and ΔNp73, which is associated with chemoresistance, can result from infection by oncogenic viruses such as EBV or HPV. Our study focuses on the highly carcinogenic ΔNp73α isoform and uses a viral model of cellular transformation. We unveil a physical interaction between ΔNp73α and the E2F4/p130 complex involved in cell cycle control, which rewires the E2F4/p130 transcriptional program. Our work shows that ΔNp73 isoforms can establish interactions with proteins that do not bind to the TAp73α tumor suppressor. This situation is analogous to the gain-of-function interactions of p53 mutants supporting cellular proliferation.

Aplasia cutis congénita: a propósito de un caso / Aplasia cutis congenita: case report / Aplasia congênita da cútis: relato do caso

La aplasia cutis congénita es una patología rara caracterizada por la ausencia de desarrollo de piel. Aunque puede localizarse en diferentes áreas del cuerpo, mayormente afecta el cuero cabelludo y puede extenderse a tejidos subyacentes. Presentamos aquí un caso clínico que se destaca por la extensión de la lesión. Se incluye la descripción del tratamiento y seguimiento del paciente.

Aplasia Cutis Congenita is a rare pathology characterized by the absence of development of the epidermis, and even though it can compromise any area of the body, it usually affects the scalp and it can be extended to the underlying tissues. We present a particular case due to the lesion size. It includes treatment description and follow-up.

A Aplasia Congênita da Cútis é uma patologia rara caracterizada pela ausência de desenvolvimento das epidermes, e embora possa se localizar em diferentes áreas do corpo, acomete principalmente o couro cabeludo e pode se espalhar para os tecidos subjacentes. Apresentamos aqui um caso clínico que se destaca pela extensão da lesão. Incluímos a descrição do tratamento e acompanhamento do paciente.

Efecto de la dibucaína sobre la SERCA del músculo pterigoideo interno / Drug action of dibucaine on the SERCA from medial pterygoid muscle

Objetivo: Determinar el efecto del anestésico local di-bucaína sobre las principales isoformas de la SERCA (calcio ATPasa de retículo sarco-endoplásmico) pre-sentes en músculo pterigoideo interno. Métodos: Se aislaron por centrifugación diferencial membranas de retículo sarcoplásmico de pterigoideo interno de conejo neozelandés macho (n=5). Se separaron las isoformas SERCA1a, 2a y 2b por cromatografía de afinidad. Se determinó in vitro la actividad enzimá-tica en presencia de diferentes concentraciones de dibucaína (0-90 mM) por el método de Fiske y Subba-row, realizando 5 experimentos por duplicado y en paralelo para cada isoforma. Se calculó la media y ES de la CI50 (mM) del anestésico para cada isofor-ma y éstas se compararon por ANOVA de una vía (p<0,05), y prueba Student-Newman-Keuls de com-paraciones múltiples. Resultados: Dibucaína inhibió la actividad enzimática en función de su concentra-ción en las tres isoformas en estudio. Las CI50 fueron: SERCA1a 20,02 ± 0,64 mM, SERCA2a 15,03 ± 0,52 mM y SERCA2b 16,00 ± 0,51 mM y resultaron signi-ficativamente diferentes (F2,27 = 11,08, p<0,001). La prueba post hoc identificó diferencias significativas entre SERCA1a y 2a, 1a y 2b. El efecto inhibitorio re-sultó significativamente mayor sobre las isoformas 2a y 2b, cuya presencia es sustancialmente mayor en músculos masticadores. Conclusión: La dibucaína inhibe a la SERCA de pterigoideo interno a concen-traciones menores que las usadas en clínica médica (29 mM). Es un anestésico local con potencial efecto miotóxico derivado de la inhibición de la SERCA (AU)

Aim: To test the effect of the local anesthetic dibu-caine on the main isoforms of the SERCA (sarco-endosplasmic reticulum calcium-ATPase) in medial pterygoid muscle. Methods: Sarcoplasmic reticulum membranes from male New Zealand rabbits (n=5) were isolated from medial pterygoid muscle by ul-tracentrifugation. The isoforms SERCA1a, 2a and 2b were separated using high affinity chromatography. In vitro enzymatic activity determinations were per-formed in the presence of different dibucaine con-centrations (0-90 mM) using the colorimetric method described by Fiske & Subbarow. Five assays in dupli-cate and run in parallel were performed for each of the isoforms. Mean and SEM of the IC50 (mM) for the effect of the anesthetic on each isoform were calcu-lated and compared by one-way ANOVA (p<0.05), and Student-Newman-Keuls multiple comparisons test. Results: Dibucaine inhibited the enzymatic activity in a concentration-dependent manner for the three studied isoforms. The IC50 values were: SERCA1a 20.02 ± 0.64 mM, SERCA2a 15.03 ± 0.52 mM and SER-CA2b 16.00 ± 0.51 mM. The values were significantly different (F2.27 = 11.08, p<0.001). The post hoc test revealed significant differences between SERCA1a and 2a, 1a and 2b. The inhibitory effect was signifi-cantly higher on 2a and 2b isoforms, whose presence is substantially higher in masticatory muscles. Con-clusion: Dibucaine inhibits SERCA in medial pterygoid muscle at concentrations lower than those used in clinical medicine (29 mM). It is a potentially myotoxic local anesthetic whose toxic effect may derive from SERCA inhibition (AU)

Asociación de hemangioma en zona cérvico facial y hemangioma subglótico en un neonato / Association of cervical-facial and subglottic hemangioma in neonates / Associação de hemangioma cervicofacial e subglótico em neonatos

Se presenta un neonato con hemangioma cérvico facial y posterior diagnóstico de hemangioma subglótico. Los hemangiomas en el período neonatal y los primeros meses de vida requieren una atención cuidadosa. Debido a su patrón de crecimiento y la futura aparición de nuevas lesiones, son considerados imprevisibles en esta etapa. Se encontró una fuerte asociación entre los hemangiomas difusos de localización cérvico facial y los hemangiomas sintomáticos de la vía aérea alta. El riesgo está relacionado con el grado de extensión de la afectación cutánea en un área que incluye la piel de la región mandibular, el mentón, el labio inferior y la parte anterior del cuello. Los hemangiomas infantiles requieren tratamiento cuando presentan riesgo vital y alteraciones funcionales, como compromiso de la vía aérea.

This is the case of a newborn with cervical hemangioma and a subsequent diagnosis of subglottic hemangioma. Hemangiomas in neonates and infants require careful attention. Due to their growth pattern and the potential appearance of new lesions, they are considered unpredictable at this stage. A strong link was found between diffuse cervical-facial and symptomatic upper airway hemangiomas. The risk is related to the extent of skin involvement in a given area, which might include the jaw, chin, lower lip, and front of the neck skin. Infant hemangiomas require treatment when they present life-threatening and functional alterations, such as airway compromise.

Relatamos o caso de um recém-nascido com hemangioma cervical com diagnóstico posterior de hemangioma subglótico. Hemangiomas em recém-nascidos e lactentes requerem atenção cuidadosa. Devido ao seu padrão de crescimento e ao potencial aparecimento de novas lesões, são considerados imprevisíveis nessa fase. Uma forte associação foi encontrada entre hemangiomas cervicofaciais difusos e hemangiomas sintomáticos das vias aéreas superiores. O risco está relacionado à extensão do envolvimento da pele da mandíbula, o queixo, o lábio inferior e a pele da frente do pescoço. Os hemangiomas infantis necessitam de tratamento quando apresentam alterações funcionais ou risco de vida, como comprometimento das vias aéreas.

Brachiocephalic Vein and Superior Vena Cava Reconstruction with a Superficial Femoral Vein Graft

Abstract Superior vena cava syndrome (SVCS) is an entity that has become more frequent due to the increasing use of indwelling central venous catheters. Surgical management is considered in patients with extensive venous thrombosis and when endovascular therapy is not feasible. The use of superficial femoral vein is an excellent technique for reconstruction of the brachiocephalic vein and superior vena cava (SVC) in cases with benign and malignant etiologies. We describe two cases of SVCS that were managed surgically at our institution with replacement of the SVC and brachiocephalic veins with a superficial femoral vein graft technique.

Catarata bilateral congénita en recién nacido con síndrome de Down / Congenital bilateral cataract in a newborn with Down syndrome / Catarata congênita bilateral em recém-nascido com síndrome de Down

Las cataratas son una causa importante de discapacidad visual en la población pediátrica en todo el mundo y pueden afectar significativamente el neurodesarrollo de un niño. Constituyen un problema fundamental en cuanto a su manejo y una de las causas más relevantes de ceguera tratable en los países desarrollados y en vías de desarrollo. La trisomía 21 es la cromosomopatía más frecuente, de características fenotípicas determinadas con un 60% de anormalidades oculares, entre las que se destacan las ametropías, queratocono y las cataratas. El diagnóstico clínico y la identificación temprana del tipo de cataratas, junto con intervenciones clínicas y tratamientos precoces, son claves para lograr resultados óptimos. Se presenta el caso de un recién nacido con síndrome de Down y catarata congénita bilateral y su manejo inicial.

Cataracts are a major cause of visual impairment in the pediatric population worldwide and can significantly affect a child's neurobiological development. Congenital cataract management can become a very important problem and is one of the most important causes of blindness in developed and developing countries. Trisomy 21 is the most common chromosomal disease and it has certain phenotypic characteristics and 60% ophthalmic abnormalities, such as, ametropia, keratoconus and cataracts. The diagnosis is fundamentally clinical. Early identification, diagnosis, and appropriate clinical care are key to achieve optimal results. We present the case of a newborn with Down syndrome who was diagnosed with an early bilateral congenital cataract.

A catarata é uma das principais causas de deficiência visual na população pediátrica no mundo e pode afetar significativamente o neurodesenvolvimento de uma criança, além de constituir um problema fundamental em termos de sua gestão e é uma das causas mais relevantes de cegueira tratável em países desenvolvidos e em desenvolvimento. Trissomia 21 é a cromossomopatia mais frequente e tem determinadas características fenotípicas com 60% de alterações oculares, como a ametropia, ceratocone e catarata. O diagnóstico clínico e a identificação precoce do tipo de catarata, juntamente com intervenções clínicas e tratamento precoces, são fundamentais para alcançar os melhores resultados. Apresentamos o caso de um recém-nascido com síndrome de Down e catarata congênita bilateral e seu manejo inicial.