Project description:BackgroundMitral valve prolapse (MVP) is a common valvular heart disease and has often been associated with an increased risk of sudden cardiac death (SCD). This underlines the pressing need for the establishment of consistent tools for arrhythmic risk prediction.Case summaryA 73-year-old man with previous diagnosis of MVP was referred to the cardiology outpatient consult for a 1-month history of near-syncope and light-headedness. He had no family history of SCD. Physical examination was unremarkable. Holter monitoring recorded frequent and multiple long episodes of non-sustained ventricular tachycardia (VT) and paroxysmal atrial fibrillation with controlled ventricular response. Echocardiogram revealed mitral bileaflet billowing, systolic curling, and annular disjunction, as well as increased peak systolic strain dispersion with two-dimensional speckle tracking. Cardiac magnetic resonance disclosed additional tricuspid annular dilatation and disjunction, as non-ischaemic late gadolinium enhancement on the left ventricular basal inferolateral wall. The Heart Team decided to implant a defibrillator as primary prevention for SCD due to arrhythmogenic mitral valve disease (AMVD) with high-risk features. The patient remained asymptomatic over the next 2 years, when he suffered an appropriate shock due to VT at 200 b.p.m.DiscussionHere, we present a case of a patient with AMVD with classic features of high arrhythmic risk but also with some unusual characteristics such as older age, male gender, and only little pronounced mitral valve billowing, emphasizing the wide heterogeneity and lack of knowledge surrounding this entity.
Project description:Zika virus (ZIKV) is a mosquito-borne flavivirus that spread throughout the American continent in 2015 causing considerable worldwide social and health alarm due to its association with ocular lesions and microcephaly in newborns, and Guillain-Barré syndrome (GBS) cases in adults. Nowadays, no licensed vaccines or antivirals are available against ZIKV, and thus, in this very short time, the scientific community has conducted enormous efforts to develop vaccines and antivirals. So that, different platforms (purified inactivated and live attenuated viruses, DNA and RNA nucleic acid based candidates, virus-like particles, subunit elements, and recombinant viruses) have been evaluated as vaccine candidates. Overall, these vaccines have shown the induction of vigorous humoral and cellular responses, the decrease of viremia and viral RNA levels in natural target organs, the prevention of vertical and sexual transmission, as well as that of ZIKV-associated malformations, and the protection of experimental animal models. Some of these vaccine candidates have already been assayed in clinical trials. Likewise, the search for antivirals have also been the focus of recent investigations, with dozens of compounds tested in cell culture and a few in animal models. Both direct acting antivirals (DAAs), directed to viral structural proteins and enzymes, and host acting antivirals (HAAs), directed to cellular factors affecting all steps of the viral life cycle (binding, entry, fusion, transcription, translation, replication, maturation, and egress), have been evaluated. It is expected that this huge collaborative effort will produce affordable and effective therapeutic and prophylactic tools to combat ZIKV and other related still unknown or nowadays neglected flaviviruses. Here, a comprehensive overview of the advances made in the development of therapeutic measures against ZIKV and the questions that still have to be faced are summarized.
Project description:Brugada syndrome (BrS) is an arrhythmogenic disorder which was first described in 1992. This disease is a channelopathy characterized by ST-segment elevations in the right precordial leads and is susceptible to sudden death. BrS is a fatal disease with gender and age preferences. It occurs mainly in young male subjects with a structurally normal heart and silently progresses to sudden death with no significant symptoms. The prevalence of BrS has been reported in the ranges of 5-20 per 10 000 people. The disease is more prevalent in Asia. Nowadays, numerous variations in 23 genes have been linked to BrS since the first gene SCN5A has been associated with BrS in 1998. Not only can clinical specialists apply these discoveries in risk assessment, diagnosis and personal medicine, but also forensic pathologists can make full use of these variations to conduct death cause identification. However, despite the progress in genetics, these associated genes can only account for approximately 35% of the BrS cases while the etiology of the remaining BrS cases is still unexplained. In this review, we discussed the prevalence, the genes associated with BrS and the application of molecular autopsy in forensic pathology. We also summarized the present obstacles, and provided a new insight into the genetic basis of BrS.
Project description:Obesity is a disease rather than a state, and metabolic bariatric surgery (MBS) is its most effective treatment. Body contouring surgery (BCS) is an integral part of the continuum of care following MBS, provided that the body mass index (BMI) has stabilized for an adequate period. This study is an attempt to capture the current status of BCS following MBS in Greece, based on data from one of the country's highest-volume hospitals. We recruited patients from the Bariatric and Plastic-Reconstructive Surgery registries who had undergone both MBS and BCS and invited them to answer a structured questionnaire with components on demographics, safety and effectiveness of previous operations, quality of life (QoL), body image, social activity, sexual activity, and doctor-patient communication. Twenty-four patients participated in the survey (response rate 88.1%). The mean BMI pre-MBS was 43.8 kg/m2 and that pre-BCS was 28.6 kg/m2. Based on the Bariatric sub-cohort, only 2.5% of post-bariatric patients underwent BCS. The mean interval between MBS and BCS was 2.9 years. The distribution of patients by MBS was as follows: sleeve gastrectomy 8 (33.3%), gastric band 7 (29.2%), gastric bypass 5 (20.8%), and gastric plication 2 (8.3%). The distribution of patients by BCS was as follows: abdominoplasty 23 (94.7%), breast contouring 8 (33.3%), thigh contouring 3 (12.5%), and arm contouring 5 (20.8%). Most positive components (70.6%) regarding QoL were appraised by >80% of the participants, indicating overall satisfaction after BCS. Conversely, only 12.5% of negative components were endorsed by >20% of patients. In conclusion, BCS has a low prevalence after MBS, although it is related to an improved quality of life and body image.
Project description:Hepatitis C virus (HCV) is a major global health problem with high morbidity and mortality. About 185 million people are living with HCV, of which 80% are living in low and middle income countries. With the development of new highly effective treatments for HCV, it is considered that the eradication of HCV may only be one step away. The major problem with new treatment options is its high price. The price of sofosbuvir-based treatment for one patient in the United States is US$85000-110000, while the actual production cost of a 12 wk direct-acting antiviral regimen is less than US$250. Another major hindrance in HCV eradication is the lack of quality management of blood transfusion screens. Due to the lack of HCV screening, 75% of people in the United States with HCV infection are unaware of their positive HCV status. The control of massive HCV pandemic will require a significant financial investment, political will, and support from medical, pharmaceutical, and civil organizations around the globe.
Project description:Caspases are an evolutionary conserved family of cysteine-dependent proteases that are involved in many vital cellular processes including apoptosis, proliferation, differentiation and inflammatory response. Dysregulation of caspase-mediated apoptosis and inflammation has been linked to the pathogenesis of various diseases such as inflammatory diseases, neurological disorders, metabolic diseases, and cancer. Multiple caspase inhibitors have been designed and synthesized as a potential therapeutic tool for the treatment of cell death-related pathologies. However, only a few have progressed to clinical trials because of the consistent challenges faced amongst the different types of caspase inhibitors used for the treatment of the various pathologies, namely an inadequate efficacy, poor target specificity, or adverse side effects. Importantly, a large proportion of this failure lies in the lack of understanding various caspase functions. To overcome the current challenges, further studies on understanding caspase function in a disease model is a fundamental requirement to effectively develop their inhibitors as a treatment for the different pathologies. Therefore, the present review focuses on the descriptive properties and characteristics of caspase inhibitors known to date, and their therapeutic application in animal and clinical studies. In addition, a brief discussion on the achievements, and current challenges faced, are presented in support to providing more perspectives for further development of successful therapeutic caspase inhibitors for various diseases.
Project description:Mammalian cell surfaces are modified with complex arrays of glycans that play major roles in health and disease. Abnormal glycosylation is a hallmark of cancer; terminal sialic acid and fucose in particular have high levels in tumor cells, with positive implications for malignancy. Increased sialylation and fucosylation are due to the upregulation of a set of sialyltransferases (STs) and fucosyltransferases (FUTs), which are potential drug targets in cancer. In the past, several advances in glycostructural biology have been made with the determination of crystal structures of several important STs and FUTs in mammals. Additionally, how the independent evolution of STs and FUTs occurred with a limited set of global folds and the diverse modular ability of catalytic domains toward substrates has been elucidated. This review highlights advances in the understanding of the structural architecture, substrate binding interactions, and catalysis of STs and FUTs in mammals. While this general understanding is emerging, use of this information to design inhibitors of STs and FUTs will be helpful in providing further insights into their role in the manifestation of cancer and developing targeted therapeutics in cancer.