Privacy-Preserving Breast Cancer Classification: A Federated Transfer Learning Approach.

Breast cancer is deadly cancer causing a considerable number of fatalities among women in worldwide. To enhance patient outcomes as well as survival rates, early and accurate detection is crucial. Machine learning techniques, particularly deep learning, have demonstrated impressive success in various image recognition tasks, including breast cancer classification. However, the reliance on large labeled datasets poses challenges in the medical domain due to privacy issues and data silos. This study proposes a novel transfer learning approach integrated into a federated learning framework to solve the limitations of limited labeled data and data privacy in collaborative healthcare settings. For breast cancer classification, the mammography and MRO images were gathered from three different medical centers. Federated learning, an emerging privacy-preserving paradigm, empowers multiple medical institutions to jointly train the global model while maintaining data decentralization. Our proposed methodology capitalizes on the power of pre-trained ResNet, a deep neural network architecture, as a feature extractor. By fine-tuning the higher layers of ResNet using breast cancer datasets from diverse medical centers, we enable the model to learn specialized features relevant to different domains while leveraging the comprehensive image representations acquired from large-scale datasets like ImageNet. To overcome domain shift challenges caused by variations in data distributions across medical centers, we introduce domain adversarial training. The model learns to minimize the domain discrepancy while maximizing classification accuracy, facilitating the acquisition of domain-invariant features. We conducted extensive experiments on diverse breast cancer datasets obtained from multiple medical centers. Comparative analysis was performed to evaluate the proposed approach against traditional standalone training and federated learning without domain adaptation. When compared with traditional models, our proposed model showed a classification accuracy of 98.8% and a computational time of 12.22 s. The results showcase promising enhancements in classification accuracy and model generalization, underscoring the potential of our method in improving breast cancer classification performance while upholding data privacy in a federated healthcare environment.

Advances in Cardiac Electrophysiology.

Despite the global COVID-19 pandemic, during the past 2 years, there have been numerous advances in our understanding of arrhythmia mechanisms and diagnosis and in new therapies. We increased our understanding of risk factors and mechanisms of atrial arrhythmias, the prediction of atrial arrhythmias, response to treatment, and outcomes using machine learning and artificial intelligence. There have been new technologies and techniques for atrial fibrillation ablation, including pulsed field ablation. There have been new randomized trials in atrial fibrillation ablation, giving insight about rhythm control, and long-term outcomes. There have been advances in our understanding of treatment of inherited disorders such as catecholaminergic polymorphic ventricular tachycardia. We have gained new insights into the recurrence of ventricular arrhythmias in the setting of various conditions such as myocarditis and inherited cardiomyopathic disorders. Novel computational approaches may help predict occurrence of ventricular arrhythmias and localize arrhythmias to guide ablation. There are further advances in our understanding of noninvasive radiotherapy. We have increased our understanding of the role of His bundle pacing and left bundle branch area pacing to maintain synchronous ventricular activation. There have also been significant advances in the defibrillators, cardiac resynchronization therapy, remote monitoring, and infection prevention. There have been advances in our understanding of the pathways and mechanisms involved in atrial and ventricular arrhythmogenesis.

Fucoidan-Incorporated Composite Scaffold Stimulates Osteogenic Differentiation of Mesenchymal Stem Cells for Bone Tissue Engineering.

Globally, millions of bone graft procedures are being performed by clinicians annually to treat the rising prevalence of bone defects. Here, the study designed a fucoidan from Sargassum ilicifolium incorporated in an osteo-inductive scaffold comprising calcium crosslinked sodium alginate-nano hydroxyapatite-nano graphene oxide (Alg-HA-GO-F), which tends to serve as a bone graft substitute. The physiochemical characterization that includes FT-IR, XRD, and TGA confirms the structural integration between the materials. The SEM and AFM reveal highly suitable surface properties, such as porosity and nanoscale roughness. The incorporation of GO enhanced the mechanical strength of the Alg-HA-GO-F. The findings demonstrate the slower degradation and improved protein adsorption in the fucoidan-loaded scaffolds. The slow and sustained release of fucoidan in PBS for 120 h provides the developed system with an added advantage. The apatite formation ability of Alg-HA-GO-F in the SBF solution predicts the scaffold's osteointegration and bone-bonding capability. In vitro studies using C3H10T1/2 revealed a 1.5X times greater cell proliferation in the fucoidan-loaded scaffold than in the control. Further, the results determined the augmented alkaline phosphatase and mineralization activity. The physical, structural, and enriching osteogenic potential results of Alg-HA-GO-F indicate that it can be a potential bone graft substitute for orthopedic applications.

Exploration of mercaptoacetamide-linked pyrimidine-1,3,4-oxadiazole derivatives as DNA intercalative topo II inhibitors: Cytotoxicity and apoptosis induction.

The design and synthesis of a new series of mercaptoacetamide-linked pyrimidine-1,3,4-oxadiazole hybrids was accomplished. The in vitro cytotoxic potential of these new compounds was evaluated against lung cancer (A549), prostate cancer (PC-3, DU-145) and human embryonic kidney (HEK) cell lines. Compound 9p showed the highest potency on A549 cells with an IC50 value of 3.8 ± 0.02 µM. Moreover, 9p was found to be 25-fold more selective towards cancer cell lines than the non-cancerous (HEK) cell line. The target-based assay revealed the inhibition of the topoisomerase II enzyme by compound 9p. UV-visible spectroscopy, fluorescence, circular dichroism (CD), and viscosity studies inferred the intercalative property and effective binding of compound 9p with CT-DNA. Apoptosis induced by the compound 9p was observed by various morphological staining assays, i.e, DAPI, EtBr/AO. Further, the molecular modeling studies revealed the binding of compound 9p at the active site of the DNA-topoisomerase II complex while the physicochemical properties were in the recommended range. Finally, mercaptoacetamide-linked pyrimidine-1,3,4-oxadiazole derivatives can be considered as a promising scaffold for development as effective anticancer agents and topoisomerase II inhibitors.

Disseminated histoplasmosis as a presenting manifestation in an HIV patient - A case report from South India.

Histoplasmosis has heterogenous clinical presentation ranging from mild and self-limiting respiratory disease to disseminated forms with high mortality. In progressive disseminated histoplasmosis (PDH), patient presents with fever, lymphadenopathy, hepatosplenomegaly, adrenal enlargement, hemophagocytic lymphohistiocytosis and non-specific mucocutaneous lesions, usually in late stage of HIV. Cutaneous involvement is upto 25% in PDH which are papules, plaques, nodules and ulcers. Forty-two year old male, recently diagnosed as HIV positive presented with complaints of multiple painful ulcerated lesions over face, neck, tongue, arms, trunk & genitalia. Skin Biopsy was suggestive of histoplasmosis. Patient showed excellent response with amphotericin B and itraconazole. Since histoplasmosis is relatively uncommon, there should be a high-index of suspicion when an HIV patient presents with disseminated skin lesions.

Synthesis and biological evaluation of novel imidazo[1,2-a]pyridine-oxadiazole hybrids as anti-proliferative agents: Study of microtubule polymerization inhibition and DNA binding.

Efforts towards the development of potential anticancer agents, a new series of imidazo[1,2-a]pyridine-oxadiazole hybrids were synthesized and evaluated for their in vitro anticancer activity against lung cancer (A549) and prostate cancer (PC-3, DU-145) cell lines. Amongst the compounds tested, 6d showed the highest potency on A549 cells with an IC50 value of 2.8 ± 0.02 µM. Flow cytometric analysis of compound 6d treated A549 cells showed apoptosis induction by annexin-v/PI dual staining assay and the effect of 6d on different phases of cell cycle was also analyzed. Target based studies demonstrated the inhibition of tubulin polymerization by 6d at an IC50 value of 3.45 ± 0.51 µM and its effective binding with CT-DNA. Further, the molecular modelling studies revealed that 6d has a prominent binding affinity towards α/ß-tubulin receptor with admirable physico-chemical properties.

Prescripción y beneficios de la rehabilitación cardiovascular en pacientes con cardiopatías congénitas: Análisis de varios estudios

RESUMEN Introducción: Las cardiopatías congénitas son consideradas de gran importancia debido a que pertenecen a las enfermedades cardiovasculares con alto índice de mortalidad. Objetivo: Determinar los beneficios de la rehabilitación cardiovascular en las cardiopatías congénitas e identificar cuáles son los parámetros adecuados a la hora de prescribir estos programas en pacientes con este tipo de afecciones. Método: Revisión sistemática en combinación con un análisis descriptivo y cronología retrospectiva de artículos científicos publicados en bases de datos indexadas entre los años 2004 a 2019, con la finalidad de obtener un panorama más amplio de los programas de rehabilitación. Los datos extraídos fueron: tipo de población, grupos de intervención y control, tipos de cardiopatías congénitas, plazo del programa de rehabilitación cardíaca y frecuencia de la intervención. Resultados: De los 53528 documentos encontrados en las bases de datos mediante los descriptores médicos empleados, se seleccionaron 13, 5 de carácter experimental y 8 de revisión. En estos se encontraron aspectos relacionados con la mejoría de la calidad de vida y cuestiones psicológicas, entre otros efectos importantes a tener en cuenta en pacientes con cardiopatías congénitas que asisten a algún tipo de programa de rehabilitación cardíaca. Conclusiones: La promoción e implementación de programas seguros, consensos y guías de rehabilitación cardíaca, enfocados en pacientes que presenten alguna cardiopatía congénita, con una prescripción detallada de los ejercicios implementados, son necesarios en la actualidad, de manera tal que los pacientes perciban que no presentan complicaciones, si se llevan adecuadamente.

ABSTRACT Introduction: Congenital heart diseases are considered of great importance because they belong to the cardiovascular diseases leading to a high mortality rate. Objective: To determine the benefits of cardiovascular rehabilitation in congenital heart disease and to identify which parameters are appropriate when prescribing cardiovascular rehabilitation programs in patients with congenital heart disease. Method: Systematic review in combination with a descriptive analysis and retrospective chronology of scientific articles published in indexed databases from 2004 to 2019, aiming to obtain a broader picture of the rehabilitation programs. The data extracted included the type of population, intervention and control groups, types of congenital heart disease, time frame of the cardiac rehabilitation program, and frequency of intervention. Results: A total of 53,528 papers were found in databases after placing medical descriptors. At the end, 13 articles were selected, 5 experimental and 8 review articles. In these articles, improvements in quality of life, psychological aspects, among other effects were found, as well as data of importance to take into account in patients with congenital heart disease who are attending some type of cardiac rehabilitation program. Conclusions: There is a current need for the promotion and implementation of cardiac rehabilitation programs, consensuses and guidelines, focused on patients with congenital heart disease with a detailed prescription of the exercises implemented; as well as the patient being aware that the programs are safe and they do not present complications if properly developed.

Hearing Loss-a Camouflaged Manifestation of COVID 19 Infection.

The symptomatology of novel Severe Acute Respiratory Syndrome Corona virus type 2 infection runs the entire gamut of mild to moderate and serious illness among the affected individuals. As listed in recent literature, respiratory, cardiovascular, gastrointestinal, olfactory and gustatory systems are commonly involved. With the growing knowledge about the disease, varied manifestations have been identified and lately, otorhinolaryngology dysfunctions in COVID 19 have been described. Hearing loss in COVID era is one of the emerging areas of concern and calls for further research in the field for the better understanding and treatment of this entity. This study was designed to assess the audiological profile among 100 mild to moderately affected COVID-19 individuals, so as to make a contribution to the emerging literature on otologic manifestations in COVID 19. In our case series, high frequency hearing loss and referred OAE was noted among significant number of COVID 19 positive patients. This was even observed in patients without any otologic symptoms. Hence, early identification and intervention if required helps to give a better quality of life to the patient.

Primary Outcome Evaluation of a Next-Generation Left Atrial Appendage Closure Device: Results From the PINNACLE FLX Trial.

BACKGROUND: Left atrial appendage (LAA) occlusion provides an alternative to oral anticoagulation for thromboembolic risk reduction in patients with nonvalvular atrial fibrillation. Since regulatory approval in 2015, the WATCHMAN device has been the only LAA closure device available for clinical use in the United States. The PINNACLE FLX study (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the Watchman FLX LAA Closure Technology) evaluated the safety and effectiveness of the next-generation WATCHMAN FLX LAA closure device in patients with nonvalvular atrial fibrillation in whom oral anticoagulation is indicated, but who have an appropriate rationale to seek a nonpharmaceutical alternative. METHODS: This was a prospective, nonrandomized, multicenter US Food and Drug Administration study. The primary safety end point was the occurrence of one of the following events within 7 days after the procedure or by hospital discharge, whichever was later: death, ischemic stroke, systemic embolism, or device- or procedure-related events requiring cardiac surgery. The primary effectiveness end point was the incidence of effective LAA closure (peri-device flow ≤5 mm), as assessed by the echocardiography core laboratory at 12-month follow-up. RESULTS: A total of 400 patients were enrolled. The mean age was 73.8±8.6 years and the mean CHA2DS2-VASc score was 4.2±1.5. The incidence of the primary safety end point was 0.5% with a 1-sided 95% upper CI of 1.6%, meeting the performance goal of 4.2% (P<0.0001). The incidence of the primary effectiveness end point was 100%, with a 1-sided 95% lower CI of 99.1%, again meeting the performance goal of 97.0% (P<0.0001). Device-related thrombus was reported in 7 patients, no patients experienced pericardial effusion requiring open cardiac surgery, and there were no device embolizations. CONCLUSIONS: LAA closure with this next-generation LAA closure device was associated with a low incidence of adverse events and a high incidence of anatomic closure. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02702271.

Clinical implications in orbital and pterional flap surgeries as well as radioimaging studies to determine topographical prevalence and characterization of meningo-orbital foramen in orbits of the Indian population / Implicaciones clínicas en cirugías de colgajo orbitario y pterional, así como estudios de radioimagen para determinar la prevalencia topográfica y la caracterización del foramen meningoorbitario en órbitas de la población india

SUMMARY: The pear-shaped bony orbit connects with intracranial cavity via foramina's and fissures. The Meningo-orbital Foramen (MOF) is usually present in greater wing of sphenoid close to lateral edge of Superior orbital fissure. It provides a route for an anastomosis between the orbital branch of the middle meningeal artery (MMA) and recurrent meningeal branch of Ophthalmic Artery (OA) and hence, risk of damage during surgeries can occur. To verify occurrence and location, with morphology of MOF in dry orbits and the impending clinical hazards in surgeries pertaining to the orbit, document and analysis it to determine a standardized guideline. The presence for MOF was studied in 446 dry orbits with its location from the supra orbital margin (SOM), front zygomatic suture (FZS), the lateral tubercle of Whitnall (WT)and the lateral end of superior orbital fissure (SOF) along with its patency, laterality and number of foramina's present. Nylon probes, long divider/pins, compass and Vernier callipers was used to check the patency and various parameters. The study noted the percentage prevalence of MOF as 69 % with communication with middle cranial fossa (MCF) being 76 % of 69 % and the average distance from SOM, FZS, WT and lateral end of SOF being 35.58 mm, 24.9 mm, 26.6 mm and 0.92 mm. On comparison with various population studies, certain similarities and differences with regards to different parameters were noted. Prevalence of MOF was mostly unilateral and showed multiple foramina, that can act as channels for arteries, a variant of MMA or OA, that supply orbital structures or tumour growths. Thus, awareness of this variation is of prime importance to ophthalmologists and neurosurgeons as well as interventional radiologists, in preventing haemorrhagic condition which could further raise the difficulties in operative procedures and surgical outcomes.

RESUMEN: La órbita ósea en forma de pera se conecta con la cavidad intracraneal a través de forámenes y fisuras. El foramen meningoorbitario (MOF) suele estar presente en el ala mayor del esfenoides cerca del margen lateral de la fisura orbitaria superior. Proporciona una ruta para una anastomosis entre la rama orbitaria de la arteria meníngea media (MMA) y la rama meníngea recurrente de la arteria oftálmica (OA) y, por lo tanto, puede ocurrir riesgo de daño durante las cirugías. Para verificar la ocurrencia y ubicación, con la morfología de MOF en órbitas secas y los peligros clínicos inminentes en cirugías de la órbita, documentarlo y analizarlo para determinar una pauta estandarizada. Se estudió la presencia de MOF en 446 órbitas secas desde el margen supraorbitario (MOS), sutura cigomática frontal (FZS), el tubér- culo lateral de Whitnall (WT) y el extremo lateral de la fisura orbitaria superior (SOF) junto con su permeabilidad, lateralidad y número de forámenes presentes. Se utilizaron sondas de nailon, divisores / pasadores largos, brújula y calibradores Vernier para comprobar la permeabilidad. En el estudio se pudo observar que la prevalencia porcentual de MOF era del 69 %, siendo la comunica- ción con la fosa craneal media (MCF) del 76 % del 69 % y la distancia promedio desde SOM, FZS, WT y el extremo lateral de SOF era de 35,58 mm, 24,9 mm, 26,6 mm y 0,92 mm. En comparación con varios estudios de población, se observaron ciertas similitudes y diferencias con respecto a diferentes parámetros. La prevalencia de MOF fue mayoritariamente unilateral y mostró múltiples forámenes, que pueden actuar como canales para las arterias, una variante de MMA u OA, que irrigan estructuras orbitarias o crecimientos tumorales. Por lo tanto, la conciencia de esta variación es de primordial importancia para los oftalmólogos y neurocirujanos, así como para los radiólogos intervencionistas, en la prevención de una enfermedad hemorrágica que podría aumentar aún más las dificultades en los procedimientos y los resultados quirúrgicos.

Immunohistochemical and Molecular Characterization of Endometrial Stromal Sarcomas.

INTRODUCTION: Endometrial stromal sarcomas (ESSs) are rare and characterized by translocations t(7;17)(p15;q11.2) and t(10;17)(q22;p13), resulting in JAZF1-SUZ12 and YWHAE-FAM22 gene fusions used for defining low-grade (LG-ESS) and high-grade (HG-ESS) tumours. AIM: The objective of the study was to characterize ESSs using immunohistochemical and molecular markers. MATERIAL AND METHODS: Patients diagnosed as having ESSs between January 2014 and December 2018 were included in the study. The slides were reviewed along with a panel of immunohistochemical markers, CD10, cyclin D1, oestrogen receptor (ER) and progesterone receptor (PR), Ki67, and vimentin and classified according to World Health Organization (2014) criteria into LG-ESS, HG-ESS, and undifferentiated uterine sarcoma (UUS). Molecular characterization was performed by fluorescence in situ hybridization using relevant probes. RESULTS: Over a 4-year period, 552 cases of endometrial malignancies were reported, 10 of which were ESS (1.8%). Of these, 5 were LG-ESS, 3 HG-ESS, and 2 UUS. CD10 was 100% sensitive and 75% specific for LG-ESS. Oestrogen receptor and PR were 100% specific but less sensitive (80%) for LG-ESS. Forty per cent (2/5) of LG-ESS demonstrated JAZF1-SUZ12 gene rearrangement. All 3 cases of HG-ESS showed diffuse strong cyclin D1 (>70% nuclei) positivity and were negative for cluster differentiation 10, ER, and PR and demonstrated YWHAE gene rearrangement. None of the UUS cases demonstrated this gene rearrangement. CONCLUSION: Endometrial stromal sarcomas are rare tumours (1.8% in this study). JAZF1-SUZ12 and YWHAE-FAM22 gene rearrangement helps in accurate characterization of ESS and can be used as diagnostic tools especially when the diagnosis is unclear or difficult. Cyclin D1 can be used as an adjuvant immunomarker for YWHAE gene-rearranged HG-ESS.

Respuestas cardiovasculares de pacientes con obesidad en la prueba de esfuerzo / Cardiovascular responses of obese patients to exercise stress test

RESUMEN Introducción: La obesidad es una enfermedad multisistémica que constituye un factor de riesgo coronario y se asocia frecuentemente a otros, como la hipertensión arterial, la diabetes y la dislipidemia, todo lo cual aumenta el riesgo de enfermedad cardiovascular. Objetivo: Determinar la respuesta cardiovascular de los pacientes con obesidad durante una prueba de esfuerzo. Método: Estudio observacional, descriptivo y transversal con 67 participantes obesos (45 mujeres y 22 hombres), con promedio de edad de 35±12,6 años. Para el desarrollo de esta investigación se obtuvieron variables antropométricas, signos vitales, escala de Borg, cuestionario para factores de riesgo cardiovascular, y se realizó una prueba de esfuerzo en tapiz rodante con protocolo de Bruce. Resultados: Los principales factores de riesgo cardiovascular encontrados fueron el sedentarismo (100%) y los antecedentes patológicos familiares (76%). Se obtuvo una frecuencia cardíaca máxima promedio de 172,82±18,81 latidos por minuto, que fue superior en las mujeres (173,9±17,5 vs. 168,9±22,1) y al asociarla con los factores de riesgo cardiovascular se encontró que fue mayor en los pacientes con menos de 4 factores de este tipo (179,4±17,7 vs. 167,1±18,6). Conclusiones: Se encontró una disminución de la respuesta cardiovascular en relación con el esfuerzo esperado para la prueba de esfuerzo. A mayor número de factores de riesgo cardiovascular presentes, menor fue la frecuencia cardíaca máxima alcanzada.

ABSTRACT Introduction: Obesity is a multisystemic disease and a coronary risk factor that is frequently associated with others, such as high blood pressure, diabetes and dyslipidemia. These all increase the risk of heart disease. Objective: We aimed to determine the cardiovascular response of obese patients during a stress test. Methods: An observational, descriptive and cross-sectional study was conducted with 67 obese participants (45 women and 22 men) aged 35±12.6 years on average. To develop our research, we analyzed anthropometric variables and vital signs. The Borg scale, a cardiovascular risk factor interview and a Bruce treadmill stress test protocol were also applied. Results: The main cardiovascular risk factors found were sedentary lifestyle (100%) and family history of disease (76%). An average maximum heart rate of 172.82±18.81 beats per minute was obtained, which was higher in women (173.9±17.5 vs. 168.9±22.1). It was found to be higher in patients with less than four cardiovascular risk factors (179.4±17.7 vs. 167.1±18.6) when associated with cardiovascular risk factors. Conclusions: A decrease in cardiovascular response was found in relation to the expected test effort. The greater the number of cardiovascular risk factors, the lower the maximum heart rate achieved.

Genetic analysis of SLC26A4 gene (pendrin) related deafness among a cohort of assortative mating families from southern India.

PURPOSE: Assortative mating (AM) or preferential mating is known to influence the genetic architecture of the hearing-impaired (HI) population. AM is now seen as a universal phenomenon with individuals seeking partners based on quantitative, qualitative, and behavioral phenotypes. However, the molecular genetic dynamics of AM among the HI tested in real time are limited to the DFNB1 locus. METHODS: A total of 113 HI partners from 82 South Indian families (52 deaf marrying deaf and 30 deaf marrying normal), previously excluded for DFNB1 (GJB2/6) etiology, were screened for SLC26A4 gene (DFNB4) variants. RESULTS: A spectrum of seven pathogenic variants viz., p.S90L, p.V239D, p.V359E, p.Gly389Trpfs*79 (novel), p.T410M, p.N457K and p.K715N were identified. The pathogenic allele frequency of SLC26A4 variants identified in this study was 3.98% (9/226). CONCLUSION: We recommend a preliminary screening of mutational hotspots for future investigations to rapidly test for its recurrence among South Indian HI population. This will be the first study to comprehensively account for the incidence of SLC26A4 gene variants and the real-time dynamics of DFNB4 variants among this type of a HI cohort.

Novel diindoloazepinone derivatives as DNA minor groove binding agents with selective topoisomerase I inhibition: Design, synthesis, biological evaluation and docking studies.

We present here-in the molecular design and chemical synthesis of a novel series of diindoloazepinone derivatives as DNA minor groove binding agents with selective topoisomerase I inhibition. The in vitro cytotoxicity of the synthesized compounds was evaluated against four human cancer cell lines including DU143, HEPG2, RKO and A549 in addition to non-cancerous immortalized human embryonic kidney cells (HEK-293). Compound 11 showed significant cytotoxicity against all the four human cancer cell lines with IC50 values ranging from 4.2 to 6.59 µM. 11 was also found to display 13-fold selective cytotoxicity towards A549 cancerous cells compared to the non-cancerous cell lines (HEK-293). The decatenation, DNA relaxation and intercalation assays revealed that the investigational compounds 10 and 11 act as highly selective inhibitors of Topo-I with DNA minor groove binding ability which was also supported by the results obtained from circular dichroism (CD), UV-visible spectroscopy and viscosity studies. Apoptosis induced by the lead 11 was observed using morphological observations, AO/EB and DAPI staining procedures. Further, dose-dependent increase in the depolarization of mitochondrial membrane was also observed through JC-1 staining. Annexin V-FITC/PI assay confirmed that 11 induced early apoptosis. Additionally, cell cycle analysis indicated that the cells were arrested at sub-G1 phase. Gratifyingly, in silico studies demonstrated promising interactions of 11 with the DNA and Topo I, thus supporting their potential DNA minor groove binding property with relatively selective Topo I inhibition compared to Topo II.

Depresión y ansiedad y su relación con el perfil antropométrico de los pacientes en rehabilitación cardíaca fases I y II / Depression and anxiety and their relationship with the anthropometric profile of patients in Cardiac Rehabilitation Phases I and II

RESUMEN Introducción: La depresión es una alteración del estado mental que afecta a muchas personas alrededor del mundo y que, junto con la ansiedad, constituye un problema a nivel mundial que puede afectar a los pacientes en el período posquirúrgico cardiovascular. Objetivo: Determinar los niveles de depresión y ansiedad, y su relación con el sobrepeso y la obesidad, en pacientes que asisten a rehabilitación cardíaca fases I y II. Método: Se hizo la selección de 50 participantes de rehabilitación cardíaca (25 de fase I y 25 en fase II). Se utilizó la Hospital Anxiety and Depression Scale (HADS) para la detección de trastornos de ansiedad y depresión. Además, se valoró la antropometría de los participantes y se realizaron pruebas de normalidad de Kolmogorov-Smirnov y Shapiro-Wilk; como también, la media, desviación estándar y el coeficiente de correlación de Pearson con un grado significativo de p<0,05. Resultados: Los 50 participantes (66% hombres) tenían una edad promedio de 63,86±10,99, con diagnósticos posoperatorios de revascularización miocárdica (44%), angioplastia coronaria (40%), enfermedad aterosclerótica (4%), reemplazo de válvula aórtica (4%), cierre de comunicación interauricular (4%), marcapasos implantado (2%) y desacondicionamiento físico (2%). Se encontró una depresión de 36% y ansiedad de 30%. Conclusiones: Existe una alta prevalencia de depresión y ansiedad en los programas de rehabilitación cardíaca, su frecuencia es mayor en la fase I en comparación con la II. Además, se encontró que existe una correlación moderada leve entre la ansiedad y el normopeso y la obesidad, al igual que entre la depresión frente al sobrepeso.

ABSTRACT Introduction: Depression is a mental state disorder that affects a good number of people around the world and that, along with anxiety, is a wide-reaching problem that can strike patients after undergoing heart surgery. Objective: To determine the levels of depression and anxiety, and their relationship with overweight and obesity, in patients attending cardiac rehabilitation phases I and II. Method: Fifty patients receiving cardiac rehabilitation (25 in phase I and 25 in phase II) were selected. The Hospital Anxiety and Depression Scale (HADS) was used to screen anxiety and depression disorders. In addition, the anthropometry of the participants was examined and Kolmogorov-Smirnov and Shapiro-Wilk normality tests were performed. Mean, standard deviation and Pearson correlation coefficient with a significant degree of p<0.050 were also applied. Results: The 50 participants (66% men) had an average age of 63.86±10.99, with postoperative diagnosis of coronary-artery bypass grafting (44%), coronary angioplasty (40%), atherosclerotic disease (4%), aortic valve replacement (4%), atrial septal defect closure (4%), implanted pacemaker (2%) and physical deconditioning (2%). Depression was found at 36% and anxiety at 30%. Conclusions: There is a high prevalence of depression and anxiety in cardiac rehabilitation programs; its frequency is higher in phase I compared to phase II. Moreover, we found that there is a slight-mild correlation between anxiety versus normal weight and obesity, as well as depression versus overweight.

Early barriers to neonatal porcine islet engraftment in a dual transplant model.

Porcine islet xenografts have the potential to provide an inexhaustible source of islets for ß cell replacement. Proof-of-concept has been established in nonhuman primates. However, significant barriers to xenoislet transplantation remain, including the poorly understood instant blood-mediated inflammatory reaction and a thorough understanding of early xeno-specific immune responses. A paucity of data exist comparing xeno-specific immune responses with alloislet (AI) responses in primates. We recently developed a dual islet transplant model, which enables direct histologic comparison of early engraftment immunobiology. In this study, we investigate early immune responses to neonatal porcine islet (NPI) xenografts compared with rhesus islet allografts at 1 hour, 24 hours, and 7 days. Within the first 24 hours after intraportal infusion, we identified greater apoptosis (caspase 3 activity and TUNEL [terminal deoxynucleotidyl transferase dUTP nick end labeling])-positive cells) of NPIs compared with AIs. Macrophage infiltration was significantly greater at 24 hours compared with 1 hour in both NPI (wild-type) and AIs. At 7 days, IgM and macrophages were highly specific for NPIs (α1,3-galactosyltransferase knockout) compared with AIs. These findings demonstrate an augmented macrophage and antibody response toward xenografts compared with allografts. These data may inform future immune or genetic manipulations required to improve xenoislet engraftment.

Th1/Th2 immune responses and oxidative stress in caprine flea allergy dermatitis.

Flea allergy dermatitis (FAD) is the common, often neglected skin disease of goats caused mainly by Ctenocephalides felis. This study aimed to evaluate the immuno-oxidative pathobiology of FAD in goats. Twelve goats from the same herd were divided into two groups of six animals each. The group I (FAD) included animals with natural flea infestation and severe dermatitis lesions. The group II (Healthy control) animals were free from any parasitic infestation. To assess the pathological changes, the markers of oxidative stress (lipid peroxidation, reduced glutathione and total antioxidant capacity), and immune status (Tumour necrosis factor alpha, Interleukin 10, Transforming growth factor beta 1 and Th1/Th2 cytokine ratio) were evaluated from the blood and the serum samples. Remarkable oxidative stress and severe inflammatory response with Th2 cytokine dominance were observed in flea infested animals. Highly antigenic agents of fleas, either secretory or excretory or structural, induced severe inflammatory responses and significant oxidative stress in caprine FAD. Massive release of cytokines may be responsible for severe skin inflammation and lesions in FAD in contrast to other Th2 dominant ectoparasitic skin conditions of goats'.

X-linked inhibitor of apoptosis protein mediates tumor cell resistance to antibody-dependent cellular cytotoxicity.

Inflammatory breast cancer (IBC) is the deadliest, distinct subtype of breast cancer. High expression of epidermal growth factor receptors [EGFR or human epidermal growth factor receptor 2 (HER2)] in IBC tumors has prompted trials of anti-EGFR/HER2 monoclonal antibodies to inhibit oncogenic signaling; however, de novo and acquired therapeutic resistance is common. Another critical function of these antibodies is to mediate antibody-dependent cellular cytotoxicity (ADCC), which enables immune effector cells to engage tumors and deliver granzymes, activating executioner caspases. We hypothesized that high expression of anti-apoptotic molecules in tumors would render them resistant to ADCC. Herein, we demonstrate that the most potent caspase inhibitor, X-linked inhibitor of apoptosis protein (XIAP), overexpressed in IBC, drives resistance to ADCC mediated by cetuximab (anti-EGFR) and trastuzumab (anti-HER2). Overexpression of XIAP in parental IBC cell lines enhances resistance to ADCC; conversely, targeted downregulation of XIAP in ADCC-resistant IBC cells renders them sensitive. As hypothesized, this ADCC resistance is in part a result of the ability of XIAP to inhibit caspase activity; however, we also unexpectedly found that resistance was dependent on XIAP-mediated, caspase-independent suppression of reactive oxygen species (ROS) accumulation, which otherwise occurs during ADCC. Transcriptome analysis supported these observations by revealing modulation of genes involved in immunosuppression and oxidative stress response in XIAP-overexpressing, ADCC-resistant cells. We conclude that XIAP is a critical modulator of ADCC responsiveness, operating through both caspase-dependent and -independent mechanisms. These results suggest that strategies targeting the effects of XIAP on caspase activation and ROS suppression have the potential to enhance the activity of monoclonal antibody-based immunotherapy.

A Case of AML-M2 with Sole Interstitial Deletion in 9q Without AML1-ETO/Inv 16 Rearrangement and FLT3/NPMI Mutations.

Conventional/molecular cytogenetics is important in identification of genomic abnormalities, for prognostication and in risk stratification of de novo patients with acute myeloid leukemias (AML). Here we present an AML M2 case showing the sole karyotypic abnormality, the rare interstitial deletion in the long arm of chromosome 9 with the loss of segment q12-q13.

A case report of a urothelial carcinoma arising in the renal pelvis with exuberant chondrosarcomatous element associated with adrenal metastasis.

Sarcomatoid carcinoma is a rare malignant tumor that has both malignant epithelial and mesenchymal components. We describe a sarcomatoid carcinoma arising in the left renal pelvis of a 49-year-old man. The dominant component of the tumor was chondrosarcomatous, but there were also focal carcinomatous areas. The carcinomatous tumor cells consisted of papillary urothelial carcinoma. Immunohistochemical assay showed that the sarcomatous tumor cells were positive for vimentin and S 100 and negative for cytokeratin. The papillary urothelial carcinoma was positive for cytokeratin and negative for vimentin. The patient underwent neoadjuvant chemotherapy and after downsizing the tumor, radical nephrectomy was performed with excision of the cuff of bladder.