Objectives　To assess the preliminary clinical results of implantation of dual chamber pacemaker defibrillator and to evaluate the safety and effectiveness of placement of endocardial leads in the axillary vein. Methods　Seven patients with ventricular tachycardia and/or ventricular fibrillation (VT/VF), associated with bradyarrhythmia received implantation of a dual chamber pacemaker defibrillator, including 5 patients with coronary artery disease and 2 patients with dilated cardiomyopathy.The atrial and ventricular leads were introduced via the axillary vein under venographic guidance. Results　Dual chamber pacemaker defibrillators were successfully implanted in the left chest subcutaneous pocket in 5 patients and the left pectoral muscular pocket in 2 patients. All the VT/VF occurring either inducibly during the procedure or spontanuously during follow-up were detected promptly and treated successfully. Both the pacing and sensing functions were satisfactory. The endocardial leads required were successfully introduced via the axillary vein without major complications. Conclusion　Dual chamber pacemaker defibrillators can provide reliable therapy for VT/VF and the dual chamber pacing function. Placement of endocardial leads via the axillary vein under venographic guidance is safe and effective.

Adjuvants improve the adaptive immune response to a vaccine antigen by modulating innate immunity or facilitating transport and presentation. The selection of an appropriate adjuvant has become vital as new vaccines trend toward narrower composition, expanded application, and improved safety. Functionally, adjuvants act directly or indirectly on antigen presenting cells (APCs) including dendritic cells (DCs) and are perceived as having molecular patterns associated either with pathogen invasion or endogenous cell damage (known as pathogen associated molecular patterns [PAMPs] and damage associated molecular patterns [DAMPs]), thereby initiating sensing and response pathways. PAMP-type adjuvants are ligands for toll-like receptors (TLRs) and can directly affect DCs to alter the strength, potency, speed, duration, bias, breadth, and scope of adaptive immunity. DAMP-type adjuvants signal via proinflammatory pathways and promote immune cell infiltration, antigen presentation, and effector cell maturation. This class of adjuvants includes mineral salts, oil emulsions, nanoparticles, and polyelectrolytes and comprises colloids and molecular assemblies exhibiting complex, heterogeneous structures. Today innovation in adjuvant technology is driven by rapidly expanding knowledge in immunology, cross-fertilization from other areas including systems biology and materials sciences, and regulatory requirements for quality, safety, efficacy and understanding as part of the vaccine product. Standardizations will aid efforts to better define and compare the structure, function and safety of adjuvants. This article briefly surveys the genesis of adjuvant technology and then re-examines polyionic macromolecules and polyelectrolyte materials, adjuvants currently not known to employ TLR. Specific updates are provided for aluminum-based formulations and polyelectrolytes as examples of improvements to the oldest and emerging classes of vaccine adjuvants in use.
Adaptive Immunity ; Adjuvants, Immunologic ; Allergy and Immunology ; Aluminum Hydroxide ; Aluminum* ; Antigen Presentation ; Antigen-Presenting Cells ; Bias (Epidemiology) ; Chitosan ; Colloids ; Dendritic Cells ; Emulsions ; Immunity, Innate ; Ligands ; Nanoparticles ; Polymers ; Receptors, Pattern Recognition ; Salts* ; Systems Biology ; Toll-Like Receptors ; Vaccines

Whilst Ecological momentary assessment (EMA) can provide important insights over time and across contexts among rotation workers whose work periods alternate with leave at home, it can also be challenging to implement in the resources and construction sectors. This review aimed to provide a summary of the methodological characteristics of EMA studies assessing health outcomes and related behaviors in rotation workers. Systematic searches in PubMed, Medline, EMBASE, CINAHL, PsycINFO, and Scopus were done to include 23 studies using EMA methods in assessing health-related outcomes and behaviors. EMA designs included daily diary: assessments once per day typically fixed at the end of day (47.8%), within day fixed interval time-based design: assessments on multiple times per day at certain times of day (17.4%) and combination of both designs (34.8%). Studies employed paper and pencil diaries (73.9%) and one or more electronic methods (60.9%): wrist-worn actigraphy device (52.2%) and online-based diaries (26.1%) for data collection. Most of the studies (91.3%) did not report prompting -EMAs by schedule alerts or compliance. Daily diary and within day fixed interval dairies designs are common, with the increasing use of electronic EMA delivery techniques. It is unclear how well participants adhere to assessment schedules, as these are inadequately reported. Researchers should report compliance-related information.

Tumors often have DNA repair defects, suggesting additional inhibition of other DNA repair pathways in tumors may lead to synthetic lethality. Accumulating data demonstrate that DNA repair-defective tumors, in particular homologous recombination (HR), are highly sensitive to DNA-damaging agents. Thus, HR-defective tumors exhibit potential vulnerability to the synthetic lethality approach, which may lead to new therapeutic strategies. It is well known that poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitors show the synthetically lethal effect in tumors defective in BRCA1 or BRCA2 genes encoded proteins that are required for efficient HR. In this review, we summarize the strategies of targeting DNA repair pathways and other DNA metabolic functions to cause synthetic lethality in HR-defective tumor cells.
Animals ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; genetics ; DNA Repair ; drug effects ; genetics ; Gene Expression Regulation, Neoplastic ; drug effects ; Genes, Lethal ; genetics ; Genes, Tumor Suppressor ; drug effects ; Genes, cdc ; drug effects ; Humans ; Mutagenesis ; Poly(ADP-ribose) Polymerase Inhibitors ; Rad52 DNA Repair and Recombination Protein ; antagonists & inhibitors ; Recombination, Genetic ; drug effects ; genetics

Surgical treatment of obstructive sleep apnea syndrome (OSAS) has been available in some form for greater than three decades. Early management for airway obstruction during sleep relied on tracheotomy which although life saving was not well accepted by patients. In the early eighties two new forms of treatment for OSAS were developed. Surgically a technique described as a uvulopalatopharyngoplasty (UPPP) was used to treat the retropalatal region for snoring and sleep apnea. Concurrently sleep medicine developed a nasal continuous positive airway pressure (CPAP) device to manage nocturnal airway obstruction. Both of these measures were used to expand and stabilize the pharyngeal airway space during sleep. The goal for each technique was to limit or alleviate OSAS. Almost 30 yr later these two treatment modalities continue to be the mainstay of contemporary treatment. As expected, CPAP device technology improved over time along with durable goods. Surgery followed suit and additional techniques were developed to treat soft and bony structures of the entire upper airway (nose, palate and tongue base). This review will only focus on the contemporary surgical methods that have demonstrated relatively consistent positive clinical outcomes. Not all surgical and medical treatment modalities are successful or even partially successful for every patient. Advances in the treatment of OSAS are hindered by the fact that the primary etiology is still unknown. However, both medicine and surgery continue to improve diagnostic and treatment methods. Methods of diagnosis as well as treatment regimens should always include both medical and surgical collaborations so the health and quality of life of our patients can best be served.
Airway Obstruction ; Continuous Positive Airway Pressure ; Cooperative Behavior ; Humans ; Palate ; Quality of Life ; Sleep Apnea Syndromes ; Sleep Apnea, Obstructive ; Snoring ; Tongue ; Tracheotomy

The present study was performed to observe histopathological effects of Oculotrema hippopotami Stunkard, 1924 infection in the eye of Hippopotamus amphibius, as well as to reveal new details of morphology and structural features of this monogenean and its comparison between 2 age stages of the parasite. This was done using both light and scanning electron microscopy, energy dispersive X-ray analysis (EDXA) and histopathology. The presence of a mixture of different generations (adult and sub-adult) in one host individual is common for Oculotrema Stunkard, 1924 in contrast to Polystoma Zeder, 1800. New metrical and graphical information obtained for adults and sub-adults compared with the previous studies. Here we show the presence of genital papillae in adults, metrical data on the distal part of the vas deferens. SEM micrographs of sperm ejaculatory structures and information about the flattened dorsal side of the body provided for the first time. Histopathological changes, such as necrosis and hemorrhage in host tissues as a result of O. hippopotami attachment structures are described. Structural analysis of different body parts of O. hippopotami of both age groups are also included. We show qualitative differences in the presence of hardening ions (S, P, Ca) in attachment structures (oral and haptor suckers) that increase with the age of the worm. The presence of sub-adults and adults on the same host, together with high levels of infection without high pathogenicity may account for Oculotrema being one of the most successful parasites among the Monogenea.
Adult ; Family Characteristics ; Hemorrhage ; Human Body ; Humans ; Ions ; Microscopy, Electron, Scanning ; Necrosis ; Parasites ; Spermatozoa ; Vas Deferens ; Virulence

Tissue fibrosis, characterized by excessive accumulation of aberrant extracellular matrix (ECM) produced by myofibroblasts, is a growing cause of mortality worldwide. Understanding the factors that induce myofibroblastic differentiation is paramount to prevent or reverse the fibrogenic process. Integrin-mediated interaction between the ECM and cytoskeleton promotes myofibroblast differentiation. In the present study, we explored the significance of integrin alpha 11 (ITGA11), the integrin alpha subunit that selectively binds to type I collagen during tissue fibrosis in the liver, lungs and kidneys. We showed that ITGA11 was co-localized with α-smooth muscle actin-positive myofibroblasts and was correlatively induced with increasing fibrogenesis in mouse models and human fibrotic organs. Furthermore, transcriptome and protein expression analysis revealed that ITGA11 knockdown in hepatic stellate cells (liver-specific myofibroblasts) markedly reduced transforming growth factor β-induced differentiation and fibrotic parameters. Moreover, ITGA11 knockdown dramatically altered the myofibroblast phenotype, as indicated by the loss of protrusions, attenuated adhesion and migration, and impaired contractility of collagen I matrices. Furthermore, we demonstrated that ITGA11 was regulated by the hedgehog signaling pathway, and inhibition of the hedgehog pathway reduced ITGA11 expression and fibrotic parameters in human hepatic stellate cells in vitro, in liver fibrosis mouse model in vivo and in human liver slices ex vivo. Therefore, we speculated that ITGA11 might be involved in fibrogenic signaling and might act downstream of the hedgehog signaling pathway. These findings highlight the significance of the ITGA11 receptor as a highly promising therapeutic target in organ fibrosis.
Animals ; Collagen ; Collagen Type I ; Cytoskeleton ; Extracellular Matrix ; Fibrosis ; Hedgehogs ; Hepatic Stellate Cells ; Humans ; In Vitro Techniques ; Kidney ; Liver ; Liver Cirrhosis ; Lung ; Mice ; Mortality ; Myofibroblasts* ; Phenotype* ; Transcriptome ; Transforming Growth Factors

Brain metastasis (BM) is the leading cause of mortality in lung cancer patients. The process of BM (from initial primary tumor development, migration and intravasation, dissemination and survival in the bloodstream, extravasation, to colonization and growth to metastases) is a complex process for which few tumor cells complete the entire process. Recent research on BM of lung cancer has recently stressed the essential role of tumor microenvironment (TME) in assisting tumor cells in the completion of each BM step. This review summarizes recent studies regarding the effects of TME on tumor cells in the entire process of BM derived from lung cancer. The identification of vulnerable targets in the TME and their prospects to provide novel therapeutic opportunities are also discussed.
Brain Neoplasms/pathology* ; Humans ; Lung Neoplasms/drug therapy* ; Neoplasm Metastasis ; Tumor Microenvironment