Focused Cardiac Ultrasonography: Current Applications and Future Directions

Focused cardiac ultrasonography is performed by clinicians at the bedside and is used in time‐sensitive scenarios to evaluate a patient's cardiovascular status when comprehensive echocardiography is not immediately available. This simplified cardiac ultrasonography is often performed by noncardiologists using small, portable devices to augment the physical examination, triage patients, and direct management in both critical care and outpatient settings. However, as the use of focused cardiac ultrasonography continues to expand, careful consideration is required regarding training, scope of practice, impact on patient outcomes, and medicolegal implications. In this review, we examine some of the challenges with rapid uptake of this technique and explore the benefits and potential risk of focused cardiac ultrasonography. We propose possible mechanisms for cross‐specialty collaboration, quality improvement, and oversight.     

Occurrence and distribution of antibiotics in surface water

Ecotoxicology - The concentrations, distribution, and ecological risks of 24 typical antibiotics in Hong Kong rivers and seawater were investigated using high-performance liquid chromatography...     

The Amsterdam Sexual Abuse Case: What Scars did it Leave? Long-Term Course of Psychological Problems for Children Who have been Sexually Abused at a Very Young Age,and their Parents

Child Psychiatry & Human Development - Longitudinal research of CSA in infancy and early childhood is scarce. The current study examined the long-term course of psychological outcomes (PTSD,...     

The generation and analyses of a novel combination of recombinant adenovirus vaccines targeting three tumor antigens as an immunotherapeutic

Phenotypic heterogeneity of human carcinoma lesions, including heterogeneity in expression of tumor-associated antigens (TAAs), is a well-established phenomenon. Carcinoembryonic antigen (CEA), MUC1, and brachyury are diverse TAAs, each of which is expressed on a wide range of human tumors. We have previously reported on a novel adenovirus serotype 5 (Ad5) vector gene delivery platform (Ad5 [E1-, E2b-]) in which regions of the early 1 (E1), early 2 (E2b), and early 3 (E3) genes have been deleted. The unique deletions in this platform result in a dramatic decrease in late gene expression, leading to a marked reduction in host immune response to the vector. Ad5 [E1-, E2b-]-CEA vaccine (ETBX-011) has been employed in clinical studies as an active vaccine to induce immune responses to CEA in metastatic colorectal cancer patients. We report here the development of novel recombinant Ad5 [E1-, E2b-]-brachyury and-MUC1 vaccine constructs, each capable of activating antigen-specific human T cells in vitro and inducing antigen-specific CD4⁺ and CD8⁺ T cells in vaccinated mice. We also describe the use of a combination of the three vaccines (designated Tri-Ad5) of Ad5 [E1-, E2b-]-CEA, Ad5 [E1-, E2b-]-brachyury and Ad5 [E1-, E2b-]-MUC1, and demonstrate that there is minimal to no “antigenic competition” in in vitro studies of human dendritic cells, or in murine vaccination studies. The studies reported herein support the rationale for the application of Tri-Ad5 as a therapeutic modality to induce immune responses to a diverse range of human TAAs for potential clinical studies.     

CAPN5 genetic inactivation phenotype supports therapeutic inhibition trials

Small molecule pharmacological inhibition of dominant human genetic disease is a feasible treatment that does not rely on the development of individual, patient‐specific gene therapy vectors. However, the consequences of protein inhibition as a clinical therapeutic are not well‐studied. In advance of human therapeutic trials for CAPN5 vitreoretinopathy, genetic inactivation can be used to infer the effect of protein inhibition in vivo. We created a photoreceptor‐specific knockout (KO) mouse for Capn5 and compared the retinal phenotype to both wild‐type and an existing Capn5 KO mouse model. In humans, CAPN5 loss‐of‐function (LOF) gene variants were ascertained in large exome databases from 60,706 unrelated subjects without severe disease phenotypes. Ocular examination of the retina of Capn5 KO mice by histology and electroretinography showed no significant abnormalities. In humans, there were 22 LOF CAPN5 variants located throughout the gene and in all major protein domains. Structural modeling of coding variants showed these LOF variants were nearby known disease‐causing variants within the proteolytic core and in regions of high homology between human CAPN5 and 150 homologs, yet the LOF of CAPN5 was tolerated as opposed to gain‐of‐function disease‐causing variants. These results indicate that localized inhibition of CAPN5 is a viable strategy for hyperactivating disease alleles.