Abstract: Compounds, compositions, and methods of treatment and prevention of HIV, including HIV-1 and HIV-2, Dengue, and Chikungunya infection are disclosed. The compounds are TREM-1 inhibitors. Combinations of these TREM-1 inhibitors and additional antiretroviral compounds, such as NRTI, NNRTI, integrase inhibitors, entry inhibitors, protease inhibitors, JAK inhibitors, macrophage depleting agents, and the like, are also disclosed. In one embodiment, the combinations include a combination of adenine, cytosine, thymidine, and guanine nucleoside antiviral agents, optionally in further combination with at least one additional antiviral agent that works via a different mechanism than a nucleoside analog. This combination has the potential to eliminate the presence of HIV, Dengue, or Chikungunya virus in an infected patient.

Abstract: The present invention is directed to compounds, compositions and methods for treating or preventing Zika virus. The compounds include pyrimidine and purine nucleosides and prodrugs thereof, including certain N4-hydroxycytidine nucleoside derivatives, sulfasalazine, and various entry inhibitors.

Abstract: The devices and methods can provide short-term strength and rigidity and long-term stability and support after a bone and/or ligament injury in a single procedure. An orthopedic fixation device may include a body having a first end, a second end, and a length therebetween. The body may include a first portion, a second portion and a shaft portion disposed between the first portion and the second portion. The shaft portion may include one or more bioabsorbable materials. The body may include an internal channel disposed along the length. The device may also include a suture being disposed within the internal channel.

Abstract: Methods for controlling brain activity in a subject are described herein. An example method can include delivering a stimulus to the subject, wherein the stimulus induces neural activity in the subjects brain and modulates expression of at least one soluble mediator of cellular activity (such as, for example, a cytokine, chemokine, and/or growth factor) within the subject, and the stimulus is delivered to the subject for less than one hour.

Abstract: It is disclosed herein that ssAAV and scAAV vectors of the same serotype administered by injection into the cerebrospinal fluid (CSF) via the intracerebroventricular (ICV) or intrathecal (cisternal or lumbar) route exhibit different cellular tropisms in the central nervous system. Thus, a subject can be treated by injection into the CSF of ssAAV or scAAV vector encoding a therapeutic protein, such as an ssAAV9 or scAAV9 vector. The therapeutic protein can be targeted to specific cells using these vectors. In some embodiments, scAAV9 is utilized to achieve superior transduction in the hippocampus, cerebellum and cerebral cortex where both neurons, particularly Purkinje neurons, and glial cells (such as astrocytes) are transduced. In other embodiments, ssAAV9 is utilized to minimize transduction of astrocytes. In further embodiments, an immunosuppressive agent is also administered to the subject.

Abstract: A nanostructured cross-wire memory architecture is provided that can interface with conventional semiconductor technologies and be electrically accessed and read. The architecture links lower and upper sets of generally parallel nanowires oriented crosswise, with a memory element that has a characteristic conductance. Each nanowire end is attached to an electrode. Conductance of the linkages in the gap between the wires encodes the information. The nanowires may be highly-conductive, self-assembled, nucleic acid-based nanowires enhanced with dopants including metal ions, carbon, metal nanoparticles and intercalators. Conductance of the memory elements can be controlled by sequence, length, conformation, doping, and number of pathways between nanowires. A diode can also be connected in series with each of the memory elements. Linkers may also be redox or electroactive switching molecules or nanoparticles where the charge state changes the resistance of the memory element.

Abstract: As an IV infiltration occurs and fluid leaks into surrounding tissues, several physiological changes are expected locally. The systems and methods described herein provide a scalable automated IV infiltration detection device to provide medical staff an early warning of a possible infiltration such that they can respond accordingly. The systems and methods capture the physiological state of the user at or around a peripheral catheter insertion site by incorporating one or more modalities of wearable sensing, processing the data collected from these wearable sensors, detecting the presence of extravascular fluid, and providing an indication to a medical professional.

Abstract: This disclosure relates to certain N4-hydroxycytidine derivatives, pharmaceutical compositions, and methods related thereto. In certain embodiments, the disclosure relates to the treatment or prophylaxis of viral infections, such as Eastern, Western, and Venezuelan Equine Encephalitis (EEE, WEE and VEE, respectively), Chikungunya fever (CHIK), Ebola, Influenza, RSV, and Zika virus infection with the disclosed compounds.

Abstract: This disclosure relates to recombinant or chimeric FVIII proteins, variants, and vectors encoding the proteins containing one or more ancestral mutations. In certain embodiments, one or more protein domains comprise amino acid sequences that are derived from ancestrally reconstructed amino acid sequences. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising the proteins or vectors and related methods of inducing blood clotting.

Abstract: Disclosed are 5?-substituted nucleoside monophosphates, which contain 5-fluorouracil or 5-fluorothiouracil as the nucleobase. In general, the 5?-substituted nucleoside monophosphates disclosed herein can inhibit human thymidylate synthase and thereby possess anti-cancer therapeutic effects. The 5?-substitution in these nucleoside monophosphates can prevent metabolic cleavage of the monophosphate group, mediated by enzymes such as 5?-nucleotidases, phospholipase D, etc. This feature can improve metabolic profiles, enhance target specificity, and/or reduce side effects of these compounds, compared to their corresponding unsubstituted analogs. Also disclosed are prodrugs of these 5?-substituted nucleoside monophosphates. After administration, the prodrugs can be metabolized to release their corresponding 5?-substituted nucleoside monophosphates. Methods of treating cancer using the 5?-substituted nucleoside monophosphates and prodrugs thereof are disclosed.

Abstract: This disclosure relates DNA based movement of objects. In certain embodiments, particles, pairs of particles, or rods are conjugated with single stranded DNA that hybridizes to a single stranded RNA that is conjugated to a substrate. When the DNA particle, pair of particles, or rod interacts with the surface RNA in the presence of an endonuclease, such as RNase H and the DNA hybridizes to the RNA, then the particle, pair of particles, or rod moves along the surface. The complementarity of the DNA and RNA affect the velocity.

Abstract: This disclosure relates to methods of using beneficial bacterial such as, a Lactococcus lactis strain, to manage, treat, or prevent obesity, fatty liver disease, harmful ionizing radiation, and other conditions or aliments. In certain embodiments, the subject is at risk or, susceptible to, exhibiting symptoms of, or diagnosed with a disease or conditions disclosed herein. In certain embodiments, methods comprise administering an effective amount of a Lactococcus lactis strain to a subject in need thereof. In certain embodiments, the Lactococcus lactis strain is Lactococcus lactis subsp. cremoris ATCC® 19257 or a mutant thereof.

Abstract: Systems and methods are configured to treat a tissue by automatically linearly oscillating an instrument into a target site. A system may include a body having a length and configured to receive a portion of the instrument guide member having an exposed end and/or an instrument. The system may further include an actuator member disposed within the body and configured to linearly oscillate the instrument within the instrument guide member a fixed distance past the exposed end. The systems and methods can increase patient comfort while empowering clinicians by simplifying interventions for musculoskeletal disorders.

Abstract: This disclosure relates to managing conditioned fear and conditions induced by experiencing or witnessing an extreme traumatic event using neurokinin receptor antagonists. In certain embodiments, the disclosure relates to methods of treating or preventing conditioned fear comprising administering an effective about neurokinin 3 receptor antagonist to a subject in need thereof. In certain embodiments, the subject is diagnosed with Post-Traumatic Stress Disorder.

Abstract: The devices and methods can prevent pulmonary aspiration thereby allowing for procedures, such as an endoscopic procedure, to be performed under sedation without general anesthesia. The device may include a first end, a second end, and a length therebetween. The body may have a central lumen along the length. The device may include a first base member fixedly disposed at the first end and a second base member fixedly disposed at the second end. The device may also include an expandable assembly movable along the length of the body with respect to the first base member. The expandable assembly may be configured to move between a collapsed configuration and an expanded configuration. The expandable assembly may also be configured to expand radially with respect to the body when in the expanded configuration.

Abstract: This disclosure relates to boosting the immunogenicity of vaccines using an adjuvant combination comprising a saponin and an agonist of the intracellular stimulator of interferon genes pathway. In certain embodiments, the vaccine comprises an inactivated virus, attenuated virus, virus protein, virus like particle, or virosome. In certain embodiments, the human subject is of advanced age or elderly. In certain embodiments, the viral vaccine is an influenza vaccine.

Abstract: The present invention is directed to compounds, compositions and methods for preventing, treating or curing Norovirus infection in human subjects or other animal hosts.

Abstract: This disclosure relates to compositions and methods of reversing senescence in T cells by interrupting vasoactive intestinal peptide (VIP) signaling and/or inhibiting phosphatidylinositol-3-kinase (PI3 kinase) inhibitor signaling and uses in managing cancer and chronic viral infections. In certain embodiments, the disclosure contemplates methods of reversing T cell senescence by mixing T cell in vitro with an agent that prevents VIP from interacting with VIP receptors and/or a PI3 Kinase inhibitor. In certain embodiments, the disclosure contemplates the expansion of senescent T cells by mixing with a PI3 kinase inhibitor, an agent that block VIP and VIP receptor signaling, a VIP degrading enzyme, and combinations thereof.

Abstract: This disclosure relates therapeutic compositions containing a compound of Formula Im: or a pharmaceutically acceptable salt thereof, wherein R1 is as defined herein.