Uncommon Hepatic Sequelae from an Acute Sickle Cell Crisis

Background Sickle cell crises are commonly treated at our institution given its large sickle cell patient population and well-established hematology department. While pain management is a crucial aspect to these patients\u27 care, it is important to remember that a vasa-occlusive crisis can be life threatening. Many organs can be at risk, including the lungs (acute chest syndrome), brain (stroke), eyes (retinopathy) and as in our case, the liver. We hope this case report can become incorporated in future differential diagnoses pertaining to sickle cell crises. Case Presentation A 48-year-old black female with a past medical history of sickle cell anemia, HIV on antiretroviral therapy, pulmonary hypertension on 4L of home oxygen, lymphocytic interstitial pneumonitis, chronic obstructive pulmonary disease, remote history of deep vein thrombosis, and pulmonary embolism, presented to the emergency department with complaints of shortness of breath, increased abdominal girth and lower extremity swelling for four days. She also complained of lower back and leg pain typical of her sickle cell crises. Her prescribed medications included tenofovir/emtricitabine, atazanavir, ritonavir, folic acid, oxycodone/acetaminophen, oral hydromorphone, and furosemide. Her social history was significant for smoking one fourth of a pack of cigarettes daily

“You Have to Be Strong and Struggle”: Stigmas as a Determinants of Inequality for Female Survivors of Sex Trafficking in Cambodia

Across the globe, human trafficking survivors have reported facing stigma and discrimination after reintegrating into communities. What makes stigma particularly dangerous is that it threatens what is “most at stake” in our lives, our close personal relationships and our personal life values. This paper explores longitudinal data from the Chab Dai Butterfly Longitudinal Research Project to document and describe forms of stigma and discrimination faced by survivors of sexual exploitation and trafficking living in Cambodian communities. Our research suggests stigmas associated with sex trafficking are a “fundamental determinant” of social inequality for many female survivors following reintegration. In this study, 56 women survivors discussed their encounters with stigma and discrimination interspersed with coping strategies and resilience attributes used to navigate life experiences. The majority (70%) spoke about contending with cultural stigma together with stigma from human trafficking experiences. Four main stigma causes dominated survivor narratives: gender, sex work, socioeconomic status, and marriageability. We use these causes, in combination with the voices of survivors, to develop a conceptual model of cohort experiences with stigma in Cambodia. Many survivors are conscious of negative stereotypes in their home communities before trafficking and discuss their struggles with self-stigmatizing thoughts and labels as they reintegrate back into their communities. Survivor discussions regarding stigmas associated with sex work show intense and persistent stigma layered over existing cultural stigmas and connected with a wide variety of societal discrimination and negative outcomes. This assessment identifies multiple disadvantaged outcomes for survivors in education, relationships, marital rights, and gender-based violence. We argue that these outcomes impact survivors\u27 access/barriers to resources and life conditions related to job skills, employment opportunities, improving their socioeconomic status, mental and physical health, and other perceptions of family harmony, societal honor, and personal well-being

Iterative in Situ Click Chemistry Assembles a Branched Capture Agent and Allosteric Inhibitor for Akt1

We describe the use of iterative in situ click chemistry to design an Akt-specific branched peptide triligand that is a drop-in replacement for monoclonal antibodies in multiple biochemical assays. Each peptide module in the branched structure makes unique contributions to affinity and/or specificity resulting in a 200 nM affinity ligand that efficiently immunoprecipitates Akt from cancer cell lysates and labels Akt in fixed cells. Our use of a small molecule to preinhibit Akt prior to screening resulted in low micromolar inhibitory potency and an allosteric mode of inhibition, which is evidenced through a series of competitive enzyme kinetic assays. To demonstrate the efficiency and selectivity of the protein-templated in situ click reaction, we developed a novel QPCR-based methodology that enabled a quantitative assessment of its yield. These results point to the potential for iterative in situ click chemistry to generate potent, synthetically accessible antibody replacements with novel inhibitory properties

Genomics-based re-examination of the taxonomy and phylogeny of human and simian Mastadenoviruses: an evolving whole genomes approach, revealing putative zoonosis, anthroponosis, and amphizoonosis

With the advent of high-resolution and cost-effective genomics and bioinformatics tools and methods contributing to a large database of both human (HAdV) and simian (SAdV) adenoviruses, a genomics-based re-evaluation of their taxonomy is warranted. Interest in these particular adenoviruses is growing in part due to the applications of both in gene transfer protocols, including gene therapy and vaccines, as well in oncolytic protocols. In particular, the re-evaluation of SAdVs as appropriate vectors in humans is important as zoonosis precludes the assumption that human immune system may be na€ıve to these vectors. Additionally, as impor- tant pathogens, adenoviruses are a model organism system for understanding viral pathogen emergence through zoonosis and anthroponosis, particularly among the primate species, along with recombination, host adaptation, and selection, as evidenced by one long-standing human respiratory pathogen HAdV-4 and a recent re-evaluation of another, HAdV-76. The latter reflects the insights on amphizoonosis, defined as infections in both directions among host species including “other than human”, that are pos- sible with the growing database of nonhuman adenovirus genomes. HAdV-76 is a recombinant that has been isolated from human, chimpanzee, and bonobo hosts. On-going and potential impacts of adenoviruses on public health and translational medicine drive this evaluation of 174 whole genome sequences from HAdVs and SAdVs archived in GenBank. The conclusion is that rather than separate HAdV and SAdV phylogenetic lineages, a single, intertwined tree is observed with all HAdVs and SAdVs forming mixed clades. Therefore, a single designation of “primate adenovirus” (PrAdV) superseding either HAdV and SAdV is proposed, or alter- natively, keeping HAdV for human adenovirus but expanding the SAdV nomenclature officially to include host species identifica- tion as in ChAdV for chimpanzee adenovirus, GoAdV for gorilla adenovirus, BoAdV for bonobo adenovirus, and ad libitum

Virtual Dissection of White Matter Tracts in a Human brain using applied Game Design and Virtual Reality imaging

Visualisation of neural tracts in the human brain has previously been accomplished using two dimensional (2D) representational formats. In most cases, pre-operative visualisation is through the medium of 2D MRI image slices, representing coordinates in the brain through a combination of axial, sagittal, and coronal orthographic viewpoints. Software such as ExploreDTI can visualise off-axis viewpoints, however this method is limited to 2.5D image representations. The use of such 2D representations can require significant training in order to contextualise real-world 3D positions and accurately locate and identify neural tract pathways in the brain. Utilising anonymised tract data and advanced neuroimaging technologies pioneered by Trinity College Institute of Neuroscience (TCIN), the Technological University Dublin (TU Dublin) School of Media created an interactive visualisation environment using the Unity 3D game engine. This virtual reality visualisation utilises the Oculus Rift Virtual Reality (VR) peripheral to realise the first ever virtual dissection of the fornix in-vivo in a highly interactive full 3D environment. Ethical approval was granted by St James/Tallaght Research & Ethics Committee. MRI tract coordinate data in the form of .wrl format 3D objects were converted to game-engine ready formats such as .obj through a 3D editing program (3DS Max) then imported into Unity. A virtual representation of a human brain was created, and scale, position, and rotation manipulation of the VR environment implemented, using natural motion tracking and minimal button usage. Isolation of individual or groups of neural tracts was achieved using hand tracking and spatial selection. Positional data was mapped to MRI image planes in order to overlay traditional MRI images at each position to aid diagnostic accuracy. In summary, virtual dissection of the fornix pathway in the human brain, first individuated by TCIN was transcribed into a 3D VR gaming environment for spatially intuitive visualisation, manipulation, and analysis

Multi-setting Bell inequality for qudits

We propose a generalized Bell inequality for two three-dimensional systems with three settings in each local measurement. It is shown that this inequality is maximally violated if local measurements are configured to be mutually unbiased and a composite state is maximally entangled. This feature is similar to Clauser-Horne-Shimony-Holt inequality for two qubits but is in contrast with the two types of inequalities, Collins-Gisin-Linden-Massar-Popescu and Son-Lee-Kim, for high-dimensional systems. The generalization to aribitrary prime-dimensional systems is discussed.Comment: Accepted for publication in Phys. Rev.

In situ click chemistry: from small molecule discovery to synthetic antibodies

Advances in the fields of proteomics, molecular imaging, and therapeutics are closely linked to the availability of affinity reagents that selectively recognize their biological targets. Here we present a review of Iterative Peptide In Situ Click Chemistry (IPISC), a novel screening technology for designing peptide multiligands with high affinity and specificity. This technology builds upon in situ click chemistry, a kinetic target-guided synthesis approach where the protein target catalyzes the conjugation of two small molecules, typically through the azide–alkyne Huisgen cycloaddition. Integrating this methodology with solid phase peptide libraries enables the assembly of linear and branched peptide multiligands we refer to as Protein Catalyzed Capture Agents (PCC Agents). The resulting structures can be thought of as analogous to the antigen recognition site of antibodies and serve as antibody replacements in biochemical and cell-based applications. In this review, we discuss the recent progress in ligand design through IPISC and related approaches, focusing on the improvements in affinity and specificity as multiligands are assembled by target-catalyzed peptide conjugation. We compare the IPISC process to small molecule in situ click chemistry with particular emphasis on the advantages and technical challenges of constructing antibody-like PCC Agents

Emerging biomarkers in psoriatic arthritis

Psoriasis is an immuneâ mediated skin disease which affects 2â 4% of the worldwide population. Approximately 20â 30% of patients with psoriasis develop psoriatic arthritis (PsA), a frequently destructive and disabling condition. As skin manifestations precede joint symptoms in nearly all patients with PsA, identification of biomarkers for early prediction of joint damage is an important clinical need. Because not all patients with PsA respond to treatment in the same fashion, identification of biomarkers capable of predicting therapeutic response is also imperative. Here, we review existing literature and discuss current investigations to identify potential biomarkers for PsA disease activity, with particular emphasis on microRNAs as novel markers of interest. Serum (soluble) biomarkers, peripheral osteoclast precursor as cellular biomarkers, and genetic loci associated with skin and joint disease are also reviewed. © 2015 IUBMB Life, 67(12):923â 927, 2015Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136299/1/iub1453.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136299/2/iub1453_am.pd