Combined open maxillectomy and endoscopic endonasal resection of a giant V2 trigeminal schwannoma.

BACKGROUND: Trigeminal schwannoma is a rare type of tumor that arises from the Schwann cells of the trigeminal nerve. METHOD: We present a case of a patient with a giant V2 trigeminal schwannoma with painful swelling in the left maxilla. A complete resection using a combined open maxillectomy and endoscopic endonasal approach was performed. CONCLUSION: This case highlights the importance of a multidisciplinary approach to perform a combined open and endoscopic approach for safe resection while preserving adequate speech and swallowing.

Flowers vs. Devils: plants used against witchcraft in the urbanized Sonora Market, Mexico City / Flores vs Demonios: plantas usadas contra la brujería en el urbanizado Mercado de Sonora, Ciudad de México

Mexican markets embody cultural diversity and offer a wide range of products, serving as hubs for local exchange.In our study at Mexico City's Sonora Market, the country's prominent medicinal market, we explored the use of plant remedies against witchcraft in an urban environment. Through interviews with plant vendors and extensive data collection, we identified 21 plant species from 16 botanical families renowned for their effectiveness in combating sorcery, attracting good luck, and promoting success. Additionally, we documented 14 ailments associated with envy and negative emotions. These remedies involved practices and applications such as cleansings, decoctions, baths, and incense burning, aimed at alleviating afflictions and fostering positive outcomes. Notably, the Sonora Market continues to uphold the tradition of using plant remedies against witchcraft, even in the bustling setting of one of the world's largest cities. This highlights the enduring significance of these practices within Mexican society

Los mercados mexicanos encarnan diversidad cultural y ofrecen numerosos productos, sirviendo como centros de intercambio local. En nuestro estudio en el Mercado de Sonora en la Ciudad de México, el sitio de plantas medicinales más relevante del país, exploramos el uso de plantas contra la brujería en un entorno urbano. A través de entrevistas con locatarios, identificamos 21 especies de plantas pertenecientes a 16 familias botánicas usadas en la lucha contra la brujería, atrayendo buena suerte y promoviendo el éxito. Además, documentamos 14 enfermedades asociadas con la envidia y emociones negativas. Los remedios involucraban prácticas y aplicaciones como limpias, decocciones, baños, incienso, con el objetivo de aliviar dolencias y fomentar resultados positivos. En el Mercado deSonora persiste la tradición de utilizar plantas contra la brujería, incluso en el marco de una de las mayores ciudades del mundo, resaltando la importancia de estas prácticas dentro de la sociedad mexicana.

Nissen Fundoplication in Infants With Severe Bronchopulmonary Dysplasia: A Propensity-Matched Analysis.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is a common respiratory morbidity among premature infants. Nissen fundoplication may be performed on infants with BPD to protect the lungs from gastroesophageal reflux-related aspiration, but the indications and benefits associated with fundoplication are not well-defined. This study evaluated associations of Nissen with clinical outcomes in infants with severe BPD (sBPD), using propensity score matching to minimize bias and confounding. METHODS: Infants ≤31 wk gestational age with sBPD (grade 2-3) admitted to a single neonatal intensive care unit (NICU) between January 2016 and October 2021 were included. Patients with sBPD who underwent Nissen fundoplication during initial NICU admission were propensity score-matched at a 1:2 ratio with control patients who did not undergo Nissen (no-Nissen). Outcomes were compared, including time to freedom from respiratory support (defined as ≤2 L nasal cannula), time to initial NICU discharge, and incidence of hospital readmission or death within 1 y postdischarge. RESULTS: After propensity score matching, 18 Nissen infants were compared with 30 no-Nissen infants. The Nissen group trended toward longer time to freedom from respiratory support (median 105 versus 70 d, P = 0.09), and had longer initial hospital stays (188 versus 111 d, P = 0.002), more 1-y hospital readmissions (83% versus 50%, P = 0.04), and more tracheostomies (28% versus 0%, P = 0.005). Mortality during first-year postdischarge was similar (6% versus 10%, P = 1.0). CONCLUSIONS: Despite adjustment for confounding variables, Nissen fundoplication was associated with prolonged support and greater resource utilization among infants with sBPD. Prospective studies are needed to clarify indications for fundoplication in this population.

(F)utility of preoperative pulmonary function testing in pectus excavatum to assess severity.

PURPOSE: The utility of pulmonary function testing (PFT) in pectus excavatum (PE) has been subject to debate. Although some evidence shows improvement from preoperative to postoperative values, the clinical significance is uncertain. A high failure-to-completion rate for operative PFT (48%) was identified in our large institutional cohort. With such a high non-completion rate, we questioned the overall utility of PFT in the preoperative assessment of PE and sought to evaluate if other measures of PE severity or cardiopulmonary function could explain this finding. METHODS: Demographics, clinical findings, and results from cardiac MRI, PFT (spirometry and plethysmography), and cardiopulmonary exercise tests (CPET) were reviewed in 270 patients with PE evaluated preoperatively between 2015 and 2018. Regression modeling was used to measure associations between PFT completion and cardiopulmonary function. RESULTS: There were no differences in demographics, symptoms, connective tissue disorders, or multiple indices of pectus severity and cardiac deformation in PFT completers versus non-completers. While regression analysis revealed higher RVEF, LVEF, and LVEF-Z scores, lower RV-ESV/BSA, LV-ESV/BSA, and LV-ESV/BSA-Z scores, and abnormal breathing reserve in PFT completers vs. non-completers, these findings were not consistent across continuous and binary analyses. CONCLUSIONS: We found that PFT completers were not significantly different from non-completers in most structural and functional measures of pectus deformity and cardiopulmonary function. Inability to complete PFT is not an indicator of pectus severity.

Isolation and Bioactivity Evaluation of Sesquiterpenes from an Alcyonarian of the Genus Lemnalia from the Saudi Arabian Red Sea.

Over the last decades, soft corals have been proven a rich source of biologically active compounds, featuring a wide range of chemical structures. Herein, we investigated the chemistry of an alcyonarian of the genus Lemnalia (Neptheidae), specimens of which were collected from the coral reefs near Al Lith, on the south-west coast of Saudi Arabia. A series of chromatographic separations led to the isolation of 31 sesquiterpenes, featuring mainly the nardosinane and neolemnane carbon skeletons, among which three (13, 14 and 28) are new natural products. The metabolites isolated in sufficient amounts were evaluated in vitro in human tumor and non-cancerous cell lines for a number of biological activities, including their cytotoxic, anti-inflammatory, anti-angiogenic, and neuroprotective activities, as well as for their effect on androgen receptor (AR)-regulated transcription. Among the tested metabolites, compound 12 showed comparable neuroprotective activity to the positive control N-acetylcysteine, albeit at a 10-fold lower concentration.

A Fulminant Case of Adenovirus Genotype C108 Infection in a Pediatric Stem Cell Transplant Recipient with x-Linked Lymphoproliferative Syndrome Type 1.

A 3-year-old male with X-linked lymphoproliferative syndrome type 1 underwent an unrelated umbilical cord blood transplant (UUCBT). The week prior to transplant the patient tested positive for adenovirus (HAdV) with a viral load of <190 copies/mL and was started on cidofovir. UUCBT proceeded as scheduled, and the patient engrafted on day +19. The patient's HAdV load in serum continued to rise with resulting hepatic dysfunction, despite ongoing therapy with cidofovir and HAdV specific T-cell infusions. The patient died 6 months after transplantation having never cleared the virus. Next generation whole genome sequencing and sequence data analyses identified an intertypic recombinant HAdV-C P1H2F2 closely related (99.6% similarity) to genotype C108 in the isolates from three blood specimens obtained during the last week of life. Incidentally, the de novo assembly strategy enabled the detection of an adeno-associated virus type 2 (AAV2) genome in the DNA purified from the plasma isolates. Proteotyping analysis revealed minor differences in the predicted amino acid sequences for E1A, E1B 19K, E1B 55K, DNA polymerase, penton base, and fiber. None of the mutations previously described for HAdV-C5 variants resistant to cidofovir were identified. In silico restriction enzyme analysis revealed a distinct Sac I profile for the identified virus, supporting its designation as a C108 variant.

Trombosis venosa y de senos cerebrales en recién nacidos y niños / Venous and cerebral sinus thrombosis in newborns and children

Resumen Introducción : La trombosis de venas y senos venosos cerebrales (TVSC) constituye una causa conocida, aun que subestimada de ictus en la infancia. Su diagnóstico requiere un alto índice de sospecha, una correcta in terpretación de la neuroimagen e interrelación entre el clínico y el radiólogo. Objetivo : Analizar las manifestaciones clínicas, fac tores de riesgo y neuroimagen de recién nacidos (RN) y niños menores de 15 años con TVSC. Métodos: Estudio descriptivo, retrospectivo, multi céntrico, de una serie consecutiva de casos de menores de 15 años que ingresaron por TVSC entre el 1 de enero del 2010 y el 1 de marzo de 2022. Resultados : El estudio incluyó 51 pacientes: 39% con síntomas agudos y 59% subagudos. En los RN predomi naron síntomas encefalopáticos y convulsiones, mien tras en los niños elementos de hipertensión endocranea na (HTEC). Se identificaron factores de riesgo en el 90% de los casos. La resonancia magnética con angiografía en tiempo venoso confirmó el diagnóstico en el 80%, siendo el seno recto el más afectado en RN y el seno lateral en niños. Se encontraron complicaciones hemorrágicas en 30.5%, siendo más frecuentes en los RN. Se inició anti coagulación en el 82% sin complicaciones. Las secuelas estuvieron presentes en 44.4% de RN y 37.9% de niños, siendo más frecuentes y graves en los RN. Conclusiones : Para realizar un diagnóstico precoz es fundamental pensar en TVSC en RN con síntomas en cefalopáticos y/o convulsiones y en mayores con clínica de HTEC en presencia de enfermedades predisponentes o desencadenantes.

Abstract Introduction : Cerebral venous sinus thrombosis (CVST) is a well-known, although underestimated, cause of stroke in childhood. Its diagnosis requires a high index of suspicion, a correct interpretation of neuroim aging studies and an interrelation between clinicians and radiologists. The clinical features, risk factors and neuroimaging of children under 15 years of age with CVST were analyzed. Methods : multicenter, retrospective, descriptive, study of a consecutive series of cases of children under 15 years of age, who were admitted due to CVST between January 1st, 2010, and March 1st, 2022. Results : The study included 51 patients: 39% with acute symptoms and 59% with subacute symptoms. Newborns predominantly presented encephalopathic symptoms and seizures, while children exhibited signs of intracranial hypertension (ICH). Risk factors were 96 identified in 90% of the cases. Magnetic resonance with angiography in venous time confirmed the diagnosis in 80% of the patients, with the straight sinus being the most affected in newborns and the lateral sinus in chil dren. Hemorrhagic complications were found in 30.5%, being more frequent in newborns. Anticoagulation was initiated in 82% without complications. Sequelae were present in 44.4% of newborns and 37.9% of children, being more frequent and severe in newborns. Conclusions : To make an early diagnosis, it is essen tial to consider CVST in newborns with encephalopathic symptoms and/or seizures, and in children with signs of ICH in the presence of predisposing or triggering conditions.

Programmed cell death ligand 1 expression associated with subtypes of post-transplant lymphoproliferative disorder among pediatric kidney transplant recipients.

BACKGROUND: Programmed cell death ligand 1 (PD-L1) expression on tumor cells engages the PD-1 receptor on T cells, inhibiting anti-tumor responses. PD-L1 has been detected in cases of post-transplant lymphoproliferative disorder (PTLD) but reports are limited. Here we examine PD-L1 expression and evaluate for clinical correlations. METHODS: Twenty-one cases of PTLD were identified among pediatric kidney transplant recipients at our institution from February 1996 to April 2017. Using paraffin-embedded tissue biopsies, we examined 21 primary tumors for expression using PD-L1 monoclonal antibody performed with PAX5 as a double stain. We scored expression of PD-L1 on lesional B-cells as a percentage of positive cells. Clinical course and outcome were obtained from retrospective chart review. RESULTS: Applying revised 2017 WHO PTLD classification showed five non-destructive, nine polymorphic, and seven monomorphic cases. Average PD-L1 expression based upon PTLD subtype was: non-destructive 11%, polymorphic 43%, and monomorphic 73% (p = .01). Two patients transferred shortly after diagnosis, five received chemotherapy, and three died from PTLD. Among the fatalities, all showed monomorphic PTLD and 90% of lesional B-cells expressed PD-L1. CONCLUSION: In this case series, significant differences in PD-L1 expression were seen among different subtypes, and monomorphic PTLD demonstrated the highest expression. Study of a larger cohort is needed, and if the correlation of PD-L1 expression and PTLD subtype is confirmed, this may highlight the potential utility of checkpoint inhibitor therapy in cases of severe or refractory disease among kidney transplant recipient in whom the risk of allograft loss is acceptable given the option of chronic dialysis.

Language Differences by Race on Letters of Recommendation for the Pediatric Surgery Match.

OBJECTIVE: This study aims to evaluate if there is any significant linguistic difference in LoR based on applicant's race/ethnicity. DESIGN: Retrospective review of applications to pediatric surgery fellowship at a single institution (2016-2020). Race was self-reported by applicants. LoR were analyzed via the Linguistic Inquiry and Word Count (LIWC) software program. SETTING: Johns Hopkins All Children's Hospital, St. Petersburg, Florida USA. A free-standing tertiary pediatric hospital. PARTICIPANTS: Pediatric surgery fellowship applicants from 2016 to 2020. RESULTS: A total of 1086 LoR from 280 applicants (52% female) were analyzed. Racial distribution was Caucasians 62.1%, Asian 12.1%, Hispanics 7.1%, multiracial 6.4% African Americans 5%, and other/unknown 7.1%. Letter writers were largely male (84%), pediatric surgeons (63%) and professors (57%). There was no difference in LoR word count across races. LoR for female multiracial candidates contained higher use of affiliation and negative emotion terms compared to Hispanic females (p = 0.002 and 0.048, respectively), and past focus terms when compared to Caucasian and Asian female applicants (p < 0.001 and p = 0.003, respectively). Religion terms were more common in LoR for Asian females when compared to Caucasian females (p < 0.001). CONCLUSION: This study demonstrates linguistic differences in LoR for pediatric surgery training programs based on applicant race/ethnicity. While differences are present, these do not suggest overt bias based on applicants race or ethnicity.

Attitudes Toward Surgical Innovation Research in the Pediatric Surgery Fellowship Match.

INTRODUCTION: Pediatric surgery applicants are increasingly pursuing research in non-traditional fields including surgical innovation. This study aims to evaluate the relative value that pediatric surgeons involved in fellow selection place on innovation experience compared to traditional research. METHODS: A cross-sectional web-based survey of American Pediatric Surgical Association members involved in the selection of pediatric surgical fellows was conducted. Respondents reported their own innovation experience and were asked to identify valuable traits of applicants who completed an innovation fellowship. They rated the value of traditional research metrics including publications, presentations, and advanced degrees compared to patents and other innovation-related metrics. Comparisons were made between those with and without innovation experience with respect to gender, years in practice, and institutional role. RESULTS: One hundred thirty respondents were involved in pediatric surgery fellow selection. Innovation work was felt to be equal to or more valuable than basic science by 75% of respondents (84% vs. clinical/outcomes, 93% vs. other non-traditional, 72% vs. other clinical fellowships). Commonly cited concerns included "fewer publications" (21%) and "preoccupation with financial reward" (19%). The most valuable innovation-related metrics were "developing a novel surgical procedure" (67%) and "developing a novel device" (58%). When asked if the respondent would advise a junior resident to pursue an innovation fellowship, 49% would, 9% would not, and 43% were unsure. Seventeen percent expressed concern for match success. CONCLUSION: Innovation experience is generally viewed positively by pediatric surgeons involved in fellow selection. However, applicants and mentors would benefit from focusing on traditional academic outputs to ensure competitiveness. TYPE OF STUDY: Cross-sectional observational study. LEVEL OF EVIDENCE: III.

Effects of subconjunctival ropivacaine, liposomal bupivacaine, and mepivacaine on corneal sensitivity in healthy horses.

OBJECTIVE: To evaluate corneal sensitivity and adverse events following subconjunctival administration of three local anesthetics in horses. STUDY DESIGN: Randomized, masked, crossover study. ANIMALS: Twelve healthy adult mares. METHODS: The subconjunctival space of the treated eye was injected with 0.2 mL of liposomal bupivacaine (1.3%), ropivacaine (0.5%), or mepivacaine (2%). All horses received each medication once and the contralateral eye received saline (control). Corneal touch threshold (CTT) was measured using a Cochet-Bonnet esthesiometer before sedation, after sedation, and at specified intervals until it returned to baseline. Ocular examinations were performed at 24-, 72, and 168 h post-injection to monitor for adverse effects. RESULTS: The mean total time of anesthesia (TTA) was 168.3 min for ropivacaine, 169.2 min for liposomal bupivacaine, 103.3 min for mepivacaine and 30.7 min for the control. TTA for liposomal bupivacaine (p < .001) and ropivacaine (p = .001) was longer than the control. TTA for mepivacaine was not different from the control (p = .138), liposomal bupivacaine (p = .075) or ropivacaine (p = .150). Injection site hemorrhage reduced TTA regardless of treatments (p = .047). No adverse effects attributed to injections were noted. CONCLUSION: All three medications were well tolerated. Subconjunctival administration of ropivacaine and liposomal bupivacaine resulted in longer TTAs compared to the control; however, their TTAs were not different from that of mepivacaine. CLINICAL SIGNIFICANCE: Subconjunctivally administered liposomal bupivacaine and ropivacaine are viable options to provide prolonged corneal analgesia in horses. Future studies are needed to assess the efficacy in diseased eyes.

Dysregulated early transcriptional signatures linked to mast cell and interferon responses are implicated in COVID-19 severity.

Background: Dysregulated immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are thought to underlie the progression of coronavirus disease 2019 (COVID-19) to severe disease. We sought to determine whether early host immune-related gene expression could predict clinical progression to severe disease. Methods: We analysed the expression of 579 immunological genes in peripheral blood mononuclear cells taken early after symptom onset using the NanoString nCounter and compared SARS-CoV-2 negative controls with SARS-CoV-2 positive subjects with mild (SARS+ Mild) and Moderate/Severe disease to evaluate disease outcomes. Biobanked plasma samples were also assessed for type I (IFN-α2a and IFN-ß), type II (IFN-γ) and type III (IFN-λ1) interferons (IFNs) as well as 10 additional cytokines using multiplex immunoassays. Results: We identified 19 significantly deregulated genes in 62 SARS-CoV-2 positive subject samples within 5 days of symptom onset and 58 SARS-CoV-2 negative controls and found that type I interferon (IFN) signalling (MX1, IRF7, IFITM1, IFI35, STAT2, IRF4, PML, BST2, STAT1) and genes encoding proinflammatory cytokines (TNF, TNFSF4, PTGS2 and IL1B) were upregulated in both SARS+ groups. Moreover, we found that FCER1, involved in mast cell activation, was upregulated in the SARS+ Mild group but significantly downregulated in the SARS+ Moderate/Severe group. In both SARS+ groups we discovered elevated interferon type I IFN-α2a, type II IFN and type III IFN λ1 plasma levels together with higher IL-10 and IL-6. These results indicate that those with moderate or severe disease are characterised by deficiencies in a mast cell response together with IFN hyper-responsiveness, suggesting that early host antiviral immune responses could be a cause and not a consequence of severe COVID-19. Conclusions: This study suggests that early host immune responses linking defects in mast cell activation with host interferon responses correlates with more severe outcomes in COVID-19. Further characterisation of this pathway could help inform better treatment for vulnerable individuals.

Características de la trombosis venosa cerebral en pacientes de dos hospitales universitarios de Colombia en el período 2018-2020 / Characteristics of cerebral venous thrombosis in patients from two university hospitals in Colombia between 2018-2020

Introducción. La trombosis venosa cerebral es una causa infrecuente de enfermedad cerebrovascular que viene en aumento a nivel mundial. A pesar de ello, actualmente, en Colombia no se cuenta con estudios suficientes que nos permitan caracterizar epidemiológicamente la enfermedad en nuestra población para identificar los factores de riesgo y las complicaciones más frecuentes en nuestro medio. Objetivo. Describir las características clínicas, demográficas y radiológicas, y los factores de riesgo de una serie de pacientes con trombosis venosa cerebral de dos hospitales de Colombia. Materiales y métodos. Es un estudio descriptivo retrospectivo de pacientes hospitalizados, atendidos en el servicio de neurología de dos hospitales de Bogotá desde diciembre de 2018 hasta diciembre del 2020. Resultados. Se incluyeron 33 pacientes. Las frecuencias más altas correspondieron a mujeres en edad fértil, en puerperio (n=7; 33,3 %) y pacientes con patologías autoinmunes (n=10; 30,3 %). El síntoma inicial más común fue la cefalea (n=31; 93,9 %), seguido de focalización neurológica (n=9; 27,2%) y crisis epiléptica (n=8; 24,2 %). El 51 % (n=17) de los pacientes tuvo un examen físico normal. El infarto venoso cerebral se presentó en el 21,1 % (n=7), la hemorragia subaracnoidea en el 12,1 % (n=4) y el hematoma intraparenquimatoso en el 9 % (n=3) del total de pacientes. El 60,6 % (n=20) quedó con nivel independiente en la escala funcional de Barthel. Ningún paciente falleció. Conclusiones. Se encontraron características sociodemográficas, clínicas y radiológicas similares a lo reportado en la literatura mundial. Con respecto a las diferencias, se encontró en nuestro estudio compromiso de la circulación venosa cerebral profunda en un porcentaje ligeramente mayor a lo descrito, pero sin aumento de complicaciones, ni mortalidad.

Introduction. Cerebral venous thrombosis is an uncommon cause of cerebrovascular disease, which has been increasing worldwide. In Colombia, there are not enough recent studies that allow us to determine epidemiological characteristics of the disease in our population to identify more frequent risk factors and complications according to our living conditions. Objective. To describe clinical, demographic, and radiographic characteristics, and risk factors in a cohort of patients with cerebral venous thrombosis attended at two hospitals in Colombia. Materials and methods. Retrospective descriptive study with patients treated in the hospitalization neurology service of two hospitals in Bogotá, Colombia from December 2018 to December 2020. Results. Thirty-three patients were included. There was a higher incidence of cerebral venous thrombosis in women of childbearing age in the puerperium (n=7; 33.3%) and associated with autoimmune diseases (n=10; 30.3%). The most common initial symptom was headache (n=31; 93.9 %), followed by neurological focal signs (n=9; 27.2%) and seizures (n=8; 24.2%). Fifty-one percent (n=17) of the patients had a normal physical examination. Cerebral venous infarction occurred in 21.1 % (n=7), subarachnoid hemorrhage in 12.1 % (n=4), and intraparenchymal hematoma in 9 % (n=3) of all the patients. Sixty-point six percent (n=20) of the patients had a total independent Barthel functional scale. None of those died. Conclusions. We found similar sociodemographic, clinical, and radiography characteristics to those reported in the world literature. Regarding the differences, deep cerebral venous circulation was higher than that described in previous studies but without complications increase or mortality.

Elevated APE1 Dysregulates Homologous Recombination and Cell Cycle Driving Genomic Evolution, Tumorigenesis, and Chemoresistance in Esophageal Adenocarcinoma.

BACKGROUND & AIMS: The purpose of this study was to identify drivers of genomic evolution in esophageal adenocarcinoma (EAC) and other solid tumors. METHODS: An integrated genomics strategy was used to identify deoxyribonucleases correlating with genomic instability (as assessed from total copy number events in each patient) in 6 cancers. Apurinic/apyrimidinic nuclease 1 (APE1), identified as the top gene in functional screens, was either suppressed in cancer cell lines or overexpressed in normal esophageal cells and the impact on genome stability and growth was monitored in vitro and in vivo. The impact on DNA and chromosomal instability was monitored using multiple approaches, including investigation of micronuclei, acquisition of single nucleotide polymorphisms, whole genome sequencing, and/or multicolor fluorescence in situ hybridization. RESULTS: Expression of 4 deoxyribonucleases correlated with genomic instability in 6 human cancers. Functional screens of these genes identified APE1 as the top candidate for further evaluation. APE1 suppression in EAC, breast, lung, and prostate cancer cell lines caused cell cycle arrest; impaired growth and increased cytotoxicity of cisplatin in all cell lines and types and in a mouse model of EAC; and inhibition of homologous recombination and spontaneous and chemotherapy-induced genomic instability. APE1 overexpression in normal cells caused a massive chromosomal instability, leading to their oncogenic transformation. Evaluation of these cells by means of whole genome sequencing demonstrated the acquisition of changes throughout the genome and identified homologous recombination as the top mutational process. CONCLUSIONS: Elevated APE1 dysregulates homologous recombination and cell cycle, contributing to genomic instability, tumorigenesis, and chemoresistance, and its inhibitors have the potential to target these processes in EAC and possibly other cancers.

First detection and genome analysis of simple nosed bat polyomaviruses in Central Europe.

Polyomaviruses (PyVs) are known to infect a diverse range of vertebrate host species. We report the discovery of PyVs in vesper bats (family Vespertilionidae) from sampling in Central Europe. Seven partial VP1 sequences from different PyVs were detected in samples originating from six distinct vesper bat species. Using a methodology based on conserved segments within the major capsid virus protein 1 (VP1) among known PyVs, the complete genomes of two different novel bat PyVs were determined. The genetic distances of the large T antigen coding sequences from these PyVs compared to previously-described bat PyVs exceeded 15% meriting classification as representatives of two novel PyV species: Alphapolyomavirus epserotinus and Alphapolyomavirus myodaubentonii. Phylogenetic analysis revealed that both belong to the genus Alphapolyomavirus and clustered together with high confidence in clades including other bat alphapolyomaviruses reported from China, South America and Africa. In silico protein modeling of the VP1 subunits and capsid pentamers, and electrostatic surface potential comparison of the pentamers showed significant differences between the reference template (murine polyomavirus) and the novel bat PyVs. An electrostatic potential difference pattern between the two bat VP1 pentamers was also revealed. Disaccharide molecular docking studies showed that the reference template and both bat PyVs possess the typical shallow sialic acid-binding site located between two VP1 subunits, with relevant oligosaccharide-binding affinities. The characterisation of these novel bat PyVs and the reported properties of their capsid proteins will potentially contribute in the elucidation of the conditions creating the host-pathogen restrictions associated with these viruses.

Two novel recombinant human mastadenovirus D genotypes associated with acute respiratory illness.

Two novel genotypes of species human mastadenovirus D designated 109 and 110 were isolated from three epidemiologically unrelated cases of acute respiratory disease detected in January 2018 by surveillance efforts at the California/Mexico border. Both genotypes represent examples of intertypic recombination. Genotype D109 is most closely related to genotype D56 (97.68% genomic similarity) and features a type D22-like penton base, a type D19-like hexon gene, and a type D9-like fiber [P22/H19/F9]. On the other hand, genotype D110 is most closely related to type D22 (96.94% genomic similarity) and features a type D67-like penton base, a novel hexon gene, and a type D9-like fiber [P67/H110/F9]. Importantly, the fibers of both novel genotypes are highly similar to those of genotypes D56 and D59, which have also been isolated from a few cases of respiratory infections. The present report shows data contributing to the understanding of the molecular determinants of the expanded tissue tropism of certain members of species HAdV-D.

Adeno-Associated Virus 2 and Human Adenovirus F41 in Wastewater during Outbreak of Severe Acute Hepatitis in Children, Ireland.

During April-July 2022, outbreaks of severe acute hepatitis of unknown etiology (SAHUE) were reported in 35 countries. Five percent of cases required liver transplantation, and 22 patients died. Viral metagenomic studies of clinical samples from SAHUE cases showed a correlation with human adenovirus F type 41 (HAdV-F41) and adeno-associated virus type 2 (AAV2). To explore the association between those DNA viruses and SAHUE in children in Ireland, we quantified HAdV-F41 and AAV2 in samples collected from a wastewater treatment plant serving 40% of Ireland's population. We noted a high correlation between HAdV-F41 and AAV2 circulation in the community and SAHUE clinical cases. Next-generation sequencing of the adenovirus hexon in wastewater demonstrated HAdV-F41 was the predominant HAdV type circulating. Our environmental analysis showed increased HAdV-F41 and AAV2 prevalence in the community during the SAHUE outbreak. Our findings highlight how wastewater sampling could aid in surveillance for respiratory adenovirus species.

Does age matter? Cardiopulmonary profiles of adolescents versus adults with pectus excavatum presenting for surgical evaluation.

PURPOSE: We sought to analyze differences in presentation and cardiopulmonary function between those referred for surgical consultation as adolescents (11-17 years) versus adults (18 + years). METHODS: Presenting symptoms, past medical history, and results from cardiac MRI (CMR), pulmonary function testing (PFT), and cardiopulmonary exercise testing (CPET) were reviewed in 329 patients evaluated preoperatively between 2015 and 2018. Adjusted regression modeling was used to measure associations between pectus indices and clinical endpoints of cardiopulmonary function. RESULTS: Our sample included 276 adolescents and 53 adults. Adults presented more frequently with chest pain (57% vs. 38%, p = 0.01), shortness of breath (76% vs. 59%, p = 0.02), palpitations (21% vs. 11%, p = 0.04), and exercise intolerance (76% vs. 59%, p = 0.02). Their Haller indices (5.2 [4.2, 7.0] vs. 4.7 [4.0, 5.7], p = 0.05) and cardiac asymmetry (1.8 [0.5] vs. 1.6 [0.5], p = 0.02) were also higher. In continuous outcome analysis, adolescents had higher FEV1/FVC on PFT and higher work on CPET (p < 0.01). CONCLUSIONS: Adults with pectus excavatum were more symptomatic than adolescents with deeper, more asymmetric deformities, decreased FEV1/FVC and exercise capacity. These findings may support earlier versus later repair to prevent age-related decline. Further studies are warranted.

Hipermedia Cardiología II para la enseñanza-aprendizaje de las arritmias cardiacas en las ciencias médicas

Introducción: Debido a dificultades detectadas en el desempeño sobre el diagnóstico de las arritmias cardiacas de los estudiantes de pregrado y postgrado de la carrera de medicina y por lo necesario que es el dominio de estos conocimientos para el perfil del graduado de algunas de las especialidades de ciencias médicas se hace necesario y pertinente desarrollar herramientas educativas que contribuyan a resolver ese problema. Teniendo como antecedente el curso a distancia sobre arritmias cardíacas basado en una hipermedia del mismo nombre, que actualmente no es utilizable por obsolescencia tecnológica y que el uso de software educativo constituye una alternativa que contribuye a elevar la calidad de la docencia se realizó este proyecto. Objetivo: Elaborar una versión actualizada de la hipermedia Arritmias Cardíacas desde el punto de vista tecnológico. Métodos: Se realizó un proyecto de innovación tecnológica. Para la construcción de la hipermedia se siguió la guía cubana de migración a software libre; se utilizaron HTML5, hojas de estilo en cascada y JavaScript versión 1.5 Resultados: Se desarrolló una nueva versión de la hipermedia Arritmias Cardíacas sobre tecnología WEB, multiplataforma y de código abierto que podrá ser utilizada en el proceso de enseñanza-aprendizaje de las disciplinas médicas que tratan la entidad. Conclusiones: La Hipermedia Arritmias Cardíacas es un material de apoyo a la docencia, tecnológicamente actualizado, para que los estudiantes de pregrado y postgrado desarrollen habilidades en el diagnóstico de las arritmias cardiacas pues sus contenidos abordan características, conducta a seguir, electrocardiogramas y sonidos de las arritmias cardiacas.

Introduction: Due to the difficulties detected in the performance of undergraduate and postgraduate medical students in the diagnosis of cardiac arrhythmias and the need to master this knowledge for the graduate profile of some of the medical science specialties, it is necessary and pertinent to develop educational tools that contribute to solve this problem. This project was carried out, taking as a background the distance course on cardiac arrhythmias based on a hypermedia of the same name, which is currently unusable due to technological obsolescence and that the use of educational software constitutes an alternative that contributes to raise the quality of teaching. Objective: To develop an updated version of the hypermedia Cardiac Arrhythmias from a technological point of view. Methods: A technological innovation project was carried out. For the construction of the hypermedia, the Cuban guide for migration to free software was followed; HTML5, cascading style sheets and JavaScript version 1.5 were used. Results: A new version of the Cardiac Arrhythmias hypermedia was developed on WEB technology, multiplatform and open source that can be used in the teaching-learning process of the medical disciplines that deal with this entity. Conclusions: The Cardiac Arrhythmias Hypermedia is a technologically updated teaching support material for undergraduate and postgraduate students to develop skills in the diagnosis of cardiac arrhythmias as its contents address characteristics, conduct to follow, electrocardiograms and sounds of cardiac arrhythmias.

Hemicraniectomía endonasal por estesioneuroblastoma: informe de un caso / Endonasal hemicraniectomy by esthesioneuroblastoma: report of a case

El estesioneuroblastoma es una neoplasia maligna que se origina del epitelio olfatorio. El tratamiento se establece de acuerdo con su extensión y el grado histológico de atipia y puede incluir cirugía, cirugía más radioterapia o más radioquimioterapia. Se han utilizado diferentes abordajes quirúrgicos que incluyeron incisiones faciales y craneotomía pero, con la mayor experiencia adquirida en cirugía endoscópica de senos paranasales y el trabajo en equipo con el neurocirujano, se han desarrollado técnicas endonasales que posibilitan realizar resecciones oncológicas en pacientes seleccionados, con menos morbilidad, internación breve y sin comprometer el control local de la enfermedad. Describimos el caso clínico de una paciente con un estesioneuroblastoma con invasión intracraneal, que fue tratada con éxito mediante una hemicraniectomía endonasal preservando el bulbo olfatorio contralateral. (AU)

Esthesioneuroblastoma is a malignant neoplasm that originates from the olfactory epithelium. Treatment is established according to its extension and the histological degree of atypia and may include surgery, surgery more radiotherapy or more chemoradiation therapy. Different surgical approaches have been used, including facial incisions and craniotomy, but with the greater experience acquired with endoscopic sinus surgery and teamwork with the neurosurgeon, endonasal techniques have been developed that make it possible to perform oncological resections in selected patients, with less morbidity, brief hospitalization and without compromising local control of the disease. We describe the clinical case of a patient with an esthesioneuroblastoma with intracranial invasion who was successfully treated by endonasal hemicraniectomy preserving the contralateral olfactory bulb. (AU)