Diagnostic significance and cytological features of NUT carcinoma by EBUS-FNA, a case report and literature review.

Cytomorphological features of NUT carcinoma include sheets or discrete nests of primitive, monotonous, round to oval shaped tumour cells with high N/C ratio and brisk mitotic figures. Abrupt squamous differentiation might be a diagnostic hint. More than 50% positivity of NUT immunohistochemistry staining is diagnostic. NUT carcinoma represents a poorly differentiated malignancy by extremely aggressive clinical course and poor prognosis. It frequently manifests in midline organs, notably in the mediastinum and lung. The rising preferences for utilizing the EBUS-FNA procedure in diagnosing thoracic and lung lesions stems from its high diagnostic yield. Hence, recognizing the cytomorphological features of NUT carcinoma is crucial for timely treatment and improved patient survival.

In Silico Discovery of Potential Inhibitors Targeting the RNA Binding Loop of ADAR2 and 5-HT2CR from Traditional Chinese Natural Compounds.

Adenosine deaminase acting on RNA 2 (ADAR2) is an important enzyme involved in RNA editing processes, particularly in the conversion of adenosine to inosine in RNA molecules. Dysregulation of ADAR2 activity has been implicated in various diseases, including neurological disorders (including schizophrenia), inflammatory disorders, viral infections, and cancers. Therefore, targeting ADAR2 with small molecules presents a promising therapeutic strategy for modulating RNA editing and potentially treating associated pathologies. However, there are limited compounds that effectively inhibit ADAR2 reactions. This study therefore employed computational approaches to virtually screen natural compounds from the traditional Chinese medicine (TCM) library. The shortlisted compounds demonstrated a stronger binding affinity to the ADAR2 (<-9.5 kcal/mol) than the known inhibitor, 8-azanebularine (-6.8 kcal/mol). The topmost compounds were also observed to possess high binding affinity towards 5-HT2CR with binding energies ranging from -7.8 to -12.9 kcal/mol. Further subjecting the top ADAR2-ligand complexes to molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations revealed that five potential hit compounds comprising ZINC000014637370, ZINC000085593577, ZINC000042890265, ZINC000039183320, and ZINC000101100339 had favorable binding free energies of -174.911, -137.369, -117.236, -67.023, and -64.913 kJ/mol, respectively, with the human ADAR2 protein. Residues Lys350, Cys377, Glu396, Cys451, Arg455, Ser486, Gln488, and Arg510 were also predicted to be crucial in ligand recognition and binding. This finding will provide valuable insights into the molecular interactions between ADAR2 and small molecules, aiding in the design of future ADAR2 inhibitors with potential therapeutic applications. The potential lead compounds were also profiled to have insignificant toxicities. A structural similarity search via DrugBank revealed that ZINC000039183320 and ZINC000014637370 were similar to naringin and naringenin, which are known adenosine deaminase (ADA) inhibitors. These potential novel ADAR2 inhibitors identified herein may be beneficial in treating several neurological disorders, cancers, viral infections, and inflammatory disorders caused by ADAR2 after experimental validation.

Molecular Docking and Dynamics Simulation Studies Predict Potential Anti-ADAR2 Inhibitors: Implications for the Treatment of Cancer, Neurological, Immunological and Infectious Diseases.

Altered RNA editing has been linked to several neurodevelopmental disorders, including autism spectrum disorder (ASD) and intellectual disability, in addition to depression, schizophrenia, some cancers, viral infections and autoimmune disorders. The human ADAR2 is a potential therapeutic target for managing these various disorders due to its crucial role in adenosine to inosine editing. This study applied consensus scoring to rank potential ADAR2 inhibitors after performing molecular docking with AutoDock Vina and Glide (Maestro), using a library of 35,161 compounds obtained from traditional Chinese medicine. A total of 47 compounds were predicted to be good binders of the human ADAR2 and had insignificant toxicity concerns. Molecular dynamics (MD) simulations, including the molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) procedure, also emphasized the binding of the shortlisted compounds. The potential compounds had plausible binding free energies ranging from -81.304 to -1068.26 kJ/mol from the MM/PBSA calculations. ZINC000085511995, a naphthoquinone had more negative binding free energy (-1068.26 kJ/mol) than inositol hexakisphosphate (IHP) [-873.873 kJ/mol], an agonist and a strong binder of ADAR2. The potential displacement of IHP by ZINC000085511995 in the IHP binding site of ADAR2 could be explored for possible deactivation of ADAR2. Bayesian-based biological activity prediction corroborates the neuropharmacological, antineoplastic and antiviral activity of the potential lead compounds. All the potential lead compounds, except ZINC000014612330 and ZINC000013462928, were predicted to be inhibitors of various deaminases. The potential lead compounds also had probability of activity (Pa) > 0.442 and probability of inactivity (Pi) < 0.116 values for treating acute neurologic disorders, except for ZINC000085996580 and ZINC000013462928. Pursuing these compounds for their anti-ADAR2 activities holds a promising future, especially against neurological disorders, some cancers and viral infections caused by RNA viruses. Molecular interaction, hydrogen bond and per-residue decomposition analyses predicted Arg400, Arg401, Lys519, Trp687, Glu689, and Lys690 as hot-spot residues in the ADAR2 IHP binding site. Most of the top compounds were observed to have naphthoquinone, indole, furanocoumarin or benzofuran moieties. Serotonin and tryptophan, which are beneficial in digestive regulation, improving sleep cycle and mood, are indole derivatives. These chemical series may have the potential to treat neurological disorders, prion diseases, some cancers, specific viral infections, metabolic disorders and eating disorders through the disruption of ADAR2 pathways. A total of nine potential lead compounds were shortlisted as plausible modulators of ADAR2.

Ovarian Mixed Epithelial Carcinoma With Extensive Bilateral Fallopian Tubes Metastases by the Low-grade Serous Carcinoma Component Mimicking Serous Tubal Intraepithelial Carcinoma: Case Presentation and Literature Review.

Seromucinous carcinoma of the ovary was a newly defined category in the revised 2014 World Health Organization Classification of Tumors of Female Reproductive Organs. It was defined as a carcinoma composed of predominantly of serous and endocervical-type mucinous epithelium. Foci containing clear cells, and areas of endometrioid and squamous differentiation are not uncommon. It is a rare entity with morphologic and immunophenotypic features overlapping other types of ovarian carcinoma. There are different opinions as to whether it is a distinct entity or a histologic variant of well-established entities. Subsequent, to the writing of this manuscript the WHO 2020 reclassified this tumor as a type of endometrioid carcinoma. Here we present a case of seromucinous carcinoma of bilateral ovaries that had variable differentiation and morphology at different sites. Tumor in the fallopian tubes, ovarian surfaces, omentum, and peritoneal surfaces displayed predominant features of low-grade serous carcinoma, while the tumor in the ovaries had predominant mucinous carcinoma morphology with a confluent/expansile growth pattern. The mucosal involvement of the fallopian tubes morphologically mimicked serous tubal intraepithelial carcinoma.

Clinicopathologic features and prognostic significance of CD30 expression in de novo diffuse large B-cell lymphoma (DLBCL): results in a homogeneous series from a single institution.

Introduction: The present study evaluates CD30 expression by immunohistochemistry (IHQ) in 216 patients with de novo DLBCL.Methods: CD30 expression was assessed retrospectively in all cases by IHQ. More than >0% and >20% of CD30 expression in the malignant cells were used as a cut-off for positivity. Survival was analysed in 176 patients treated with R-CHOP/R-CHOP-like regimens.Results: CD30 expression >0% was found in 66 (31%) patients, and >20% in 41 (19%). Younger patients <60 years (p = 0.03), good performance status (p = 0.04), and non-GCB subtype (p = 0.004) correlated with CD30 expression. No significant differences were found in overall survival and progression-free survival (PFS), although there was a trend towards better PFS in CD30-positive patients (p = 0.07). Among 7 patients with Epstein-Barr virus (EBV)-positive-DLBCL, CD30 was expressed in 71%, and 2-year PFS significantly inferior compared with CD30-positive EBV-negative-DLBCL patients (p = 0.01).Conclusion: CD30 is expressed in 30% of DLBCL patients, in whom targeted therapy with an anti-CD30 monoclonal antibody could be explored. CD30 is expressed more frequently younger patients, with better performance status and in the non-GCB subtype and its expression trends towards a better PFS. No significant differences regarding characteristics at diagnosis or prognosis were found between groups with different cut-off for positivity.

Response duration and survival shorten after each relapse in patients with follicular lymphoma treated in the rituximab era.

Follicular lymphoma (FL) is an indolent disease characterized by long survival but frequent relapses. Before the introduction of rituximab, the clinical course of these patients showed a shorter response duration (RD) after each relapse. In this study, we analysed if this pattern of shortened responses remains in patients treated in the rituximab era. We selected 348 patients newly diagnosed with FL in two institutions between 2001 and 2014 that received chemoimmunotherapy. After a median follow-up of 6·3 years, 10-year progression-free and overall survivals were 53% and 72%, respectively. All patients received first-line, 111 second-line and 41 third-line treatments, with a 5-year RD of 62%, 39% and 24%, respectively (P < 0·0001). Variables predicting longer RD after first-line treatment were normal ß2microglobulin, complete remission achievement and maintenance with rituximab. Patients with longer RD after first-line showed significantly longer RD after second-line therapy. Autologous stem-cell transplantation after second-line therapy did not significantly impact RD. Median survival after first, second and third therapies was not reached, 7·6 and 4·8 years, respectively, whereas relative survival with respect to a sex- and age-matched Spanish population, the decrease in the life expectancy at 10 years was 17%, 45% and 79%, respectively. Thus, RD still shortens after each relapse in patients with FL treated in first line with rituximab combinations.

Changes in the socio-demographics, risk behaviors, clinical and immunological profile of a cohort of the Puerto Rican population living with HIV: an update of the Retrovirus Research Center (1992-2008).

OBJECTIVES: We describe the changes in the socio demographic, risk behavior, immunological and clinical trends profiles of a cohort HIV patients followed at the Retrovirus Research Center, at baseline and study periods interval by periods intervals: 1992-1997, 1998-2003, and 2004-2008. METHODS: This is a cross-sectional study of a longitudinal cohort comprised of 4016 HIV/AIDS patients admitted to the RRC since January 1992. Data collected include socio-demographic variables; risk related variables; psychological variables; and clinical variable by periods of study. RESULTS. The most common AIDS defining conditions observed in patients were: Pneumocistis Cariini pneumonia (PCP), toxoplasmosis of brain (TP), and wasting syndrome (WS). Chronic conditions are more prevalent than AIDS-defining conditions in the cohort of patients. CONCLUSIONS: Understanding the socio demographic, HIV risk behavior profile; and the immunological and clinical trends among HIV patients is critical for redesigning services and programs oriented in HIV patient care.

iNOS-derived nitric oxide mediates the increase in TFF2 expression associated with gastric damage: role of HIF-1.

Trefoil (TFF) peptides are involved in gastrointestinal mucosal restitution. An hypoxia inducible factor 1 (HIF-1)-dependent induction of TFF genes has been reported in gastric epithelial cells. Nitric oxide (NO) is associated with mucosal damage and modulates HIF-1 activity. The aim of the present study was to analyze the role of iNOS-derived NO in HIF-1alpha stabilization and TFF gene expression in damaged gastric mucosa. Aspirin caused gastric injury that peaked 6 h after dosing and returned to normality at 24 h. iNOS mRNA expression occurs in the corpus in parallel with damage. Blockade of iNOS activity did not modify gastric lesions induced by aspirin but delayed mucosal healing. Aspirin induced HIF-1alpha stabilization and TFF2 mRNA up-regulation in the mucosa, but these effects were diminished when iNOS activity was inhibited. Results obtained using a coculture setup showed that iNOS-derived NO from activated macrophages induced HIF-1alpha stabilization, TFF gene expression, and accelerated wound healing in cultured epithelial cells. Finally, transient silencing of endogenous HIF-1alpha in epithelial cells significantly undermined activated macrophage-induced TFF gene expression. Evidence suggests that the iNOS-derived NO associated with NSAID-induced gastric injury is implicated in mucosal restitution via the HIF-1-mediated induction of TFF genes.

Trends in the HIV and AIDS epidemic in a Puerto Rican cohort of patients: 1992-2005.

The HIV epidemic is a significant global health care issue. With increasing knowledge and improved therapeutics the natural history of the infection has been modified. In this paper we aim to present the general socio-demographic profile and the clinical and therapeutic spectrum of patients with HIV infection who have visited the Bayamón Health Care facilities over the last 12 years and who are part of the Retrovirus Research Center (RRC). The objectives of the study are: 1) describe changes in the demographic, risk factors and clinical stage of patients with HIV infection initially seen in our center; 2) assess changing trends from the clinical and immunological perspective across time; 3) describe mortality risk of patients particularly after the introduction of antiretroviral therapy (ART). This is a cross-sectional study of 3,569 patients admitted to the RRC at the Universidad Central del Caribe between years 1992 through 2005. The variables studied were demographic, risk factors exposure, HIV status at baseline, clinical and immunological parameters, ART and the mortality risk. Chi square with Cramer's coefficient, Kaplan Meier and Cox proportional hazard ratio analysis were performed. The study revealed that individuals presenting at our health care facilities are older and that the proportion of females has increased. The risk factor profile shows increase in heterosexual contact with the disease. The study found that patients treated with ART had significantly lower mortality risk than those without ART. Patients who arrive to RRC with AIDS and Intravenous Drug Users (IDU) had a higher mortality risk than participants with HIV. The analysis of the trends showed changes in the demographic and clinical profile of patients across the years. HIV/AIDS prevention programs and policies need to be continued in Puerto Rico in order to better control the spread of the epidemic.

A comparison of the sociodemographic, risk-behavior, and substance-abuse profile of young vs older HIV-infected Puerto Rican patients.

INTRODUCTION: As of May 2003, 17% of all reported AIDS cases in Puerto Rico had occurred among those 20-29 years of age. These individuals were likely initially infected with HIV in adolescence. The objectives of this study are to describe and compare the prevalence of the sociodemographic, risk-behavior, and substance-use profile among patients infected with HIV during their adolescence (early) and compare them with patients infected at an older age (non-early). METHODS: This is a cross-sectional study of 3151 HIV/AIDS patients admitted to the retrovirus research center of our institution between 1992 and 2002. The variables we studied include the presence or absence of early infection, sociodemographic variables, risk-behavior variables, and substance-use variables. An early-infected patient was defined as a patient with HIV/AIDS that reported his or her first positive HIV test result before the age of 21 years. Descriptive and differential analyses were performed. RESULTS: Five percent of our patients were early-infected (157/3151). A significantly higher proportion (P < or = .05) among the early-infected patients as compared to the older group was females, required inpatient hospital care at the time of study entry, and had less than a 12th-grade education. In the interview a significantly higher proportion had antisocial behavior, had been in prison at some point in their life, and had used crack-cocaine. CONCLUSIONS: The early HIV-infected patients showed a different sociodemographic, risk-behavior, and substance-use profile. Knowledge of the specific characteristics of early HIV-infected patients could be used to develop primary prevention programs directed toward reducing HIV infection among young Puerto Ricans.

Trabajo de investigación en psicoprofilaxis quirúrgica pediátrica. Primera experiencia nacional / Research on preoperative pediatric surgical psychoprophylasis. First national experience

Introducción: las ideas que las personas tienen de la cirugía están impregnadas de fantasías con una excesiva carga de ansiedad que impiden un control emocional y recuperación adecuados. La hipótesis del presente trabajo es demostrar que la psicoprofilaxis quirúrgica permite poner en funcionamiento mecanismos defensivos que amortiguan el impacto que implica la cirugía. Objetivo: demostrar el beneficio de la psicoprofilaxis quirúrgica en niños de edad escolar enfrentados a una cirugía de coordinación. Material y métodos: se estudiaron 30 pacientes del Centro Hospitalario Pereira Rossell (CHPR) con edades entre 5 y 12 años divididos en dos grupos de 15 niños: un grupo testigo, que recibió información básica, sin intervención psicológica; y un grupo muestra, que recibió información detallada, con intervención psicológica. El estudio comparativo entre ambos grupos se realizó a través de la valoración psicológica y de la variación de parámetros biológicos. Resultados y conclusiones: la psicoprofilaxis quirúrgica facilitó en este grupo de niños la creación de defensas eficaces permitiendo una conducta adaptativa con un monto de ansiedad que el Yo pudo controlar, disminuyendo el potencial efecto traumático de la vivencia, demostrando ser efectiva para disminuir el impacto psicobiológico y sus efectos deletéreos en la etapa de superación postoperatoria inmediata.

Changes in the AIDS epidemiologic situation in Puerto Rico following health care reform and the introduction of HAART.

OBJECTIVES: To compare the occurrence of AIDS as well as the sociodemographic and clinical profiles of AIDS patients in Puerto Rico before and after the introduction of highly active antiretroviral therapy (HAART) and the privatization of the island's public health care system. METHODS: We compared the incident AIDS cases for two three-year periods, 1992-1994 and 1998-2000, in four populations: (1) entire United States, (2) Puerto Rico, (3) Bayamón Health Region (located in north-central Puerto Rico, it includes 11 of the island's 78 municipalities), and (4) an HIV cohort enrolled at the Universidad Central del Caribe (UCC) School of Medicine. The UCC is located in Bayamón, Puerto Rico, within an academic medical complex that houses the teaching hospital (Ramón Ruíz Arnaú University Hospital), the ambulatory health care facilities (Immunology Clinics) for patients with HIV, and administrative buildings. This represents the major government-sponsored health care infrastructure within the Bayamón Health Region. RESULTS: Incident AIDS declined substantially between the two periods in each of the four populations studied. The 48.1% decline in Puerto Rico exceeded the 40.9% decline in the United States. The decline in Puerto Rico likely resulted from increased availability and implementation of HAART and the delivery of health care to HIV/AIDS patients in an integrated fashion within each regional ambulatory clinic. In spite of this improvement, the absolute number of patients with AIDS on the island remains high. Substantial resources for treatment and prevention are required. The proportion of new AIDS cases was lower among women, persons 40 years of age or older, the less educated, and those living alone. Injection drug use remains the predominant mode of transmission in Puerto Rico. CONCLUSIONS: Further gains in Puerto Rico's fight against AIDS will depend on the island's ability to reduce the transmission that occurs through injection drug use; the use of HAART on a larger number of vulnerable patients, particularly intravenous drug users; educational interventions to improve medication compliance in certain risk groups; and specific measures aimed at decreasing the rate of injection drug use.