Abstract: Systems, kits, and related methods of making fecal transplants are described. In an embodiment, the system comprises a sample collector defining a sample collection chamber shaped to collect a fecal sample from fecal matter; a sample processing module defining a sample port shaped to receive the sample collector and comprising: a channel positioned to receive at a proximal end of the channel the fecal sample from the sample collection chamber when the sample collector is received by the sample port; and a capsule fluidically coupled to a distal end of the channel adapted to receive a portion of the fecal sample passed therethrough; and a sample processing unit comprising: a housing defining an opening shaped to receive the sample processing module; and an actuator disposed in the housing and configured to urge the sample from the sample collection chamber through the channel to the capsule.

Abstract: An IV system can include a first flow regulator configured to restrict flow through a tube and a second flow regulator configured to restrict flow through the tube downstream of the first flow regulator. The first flow regulator can compress the tube a fixed amount to set an initial flow rate through the tube, while the second flow regulator includes a user-adjustable mechanical compression device that compresses the tube to a variable degree to fine-tune the flow rate through to a more precise flow rate that is lower than the initial flow rate. The flow regulators can utilize a purely mechanical means such that electricity is not required. Such systems can provide a simple, low-cost, and low-power way to provide precise flow control to patients, especially neonatal patient, in any environment. Systems can also include flow rate monitoring, alerting, and shutoff components.

Abstract: Methods of reducing or inhibiting Clostridium infection, treating intestinal dysbiosis associated with Clostridium infection, and preventing Clostridium colonization or Clostridium recolonization in a subject are disclosed. The methods include administering to the subject a whole foods exclusionary diet, such as a diet that excludes grains, sugars other than honey, and milk products other than hard cheeses and yogurt fermented for greater than 24 hours.

Abstract: Transcutaneous, ultrasound-mediated methods for administering compound(s) to subject tissue(s) are provided. Examples involve positioning an occluding device in a vessel such that the blockage is adjacent to target tissue; engaging the device to occlude outflow from a region adjacent to the tissue; administering compound(s) to the vessel such that it is substantially retained adjacent to the target tissue; determining the location of the compound and/or a detectable adjunct compound optionally administered with the compound, using diagnostic ultrasound, radiography, or fluorography; administering therapeutic ultrasound energy transcutaneously to mediate delivery of the compound across the vessel wall and into adjacent target tissue.

Abstract: Artificial expression constructs for selectively modulating gene expression in selected central nervous system cell types are described. The artificial expression constructs can be used to selectively express synthetic genes or modify gene expression in GABAergic interneurons.

Abstract: Newborn screening for primary immunodeficiencies, cystinosis, and Wilson disease is described. The newborn screening can detect these disorders from dried blood spots already routinely collected at the time of birth. Early detection of these disorders will greatly improve patient outcome as each of them can be fatal once symptoms emerge.

Abstract: The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.

Abstract: Early detection of lysosomal storage diseases (LSDs) including Mucopolysaccharidosis Type I (MPS I) and Pompe Disease can greatly improve patient outcome as each disease can be fatal once symptoms emerge. Screening for MPS I and Pompe Disease using biological samples including dried blood spots (DBS), buccal swab, peripheral blood mononuclear cells (PBMCs), or white blood cells (WBCs) is described. The disclosed methods and assays provide a robust way to screen newborns for LSDs. The disclosed methods and assays can also allow rapid prediction of whether a patient with LSD will develop an immune response to enzyme replacement therapy (ERT), thus improving treatment for patients with LSDs. The disclosed methods and assays can also further reduce the number of false positives caused by pseudo deficiency cases of LSD, such as MPS I and Pompe Disease.

Abstract: Clinical diagnosis and newborn screening for primary immunodeficiencies (PIDDs) is described. The PIDDs include X-linked chronic granulomatous disease (X-CGD), X-linked lymphoproliferative syndrome (XLP1; SH2D1A deficiency), familial hemophagocytic lymphohistiocytosis 2 (FHL2), ataxia telangiectasia (AT), common variable immunodeficiency (CVID; B-cell dysfunctions), severe combined immunodeficiency (SCID), adenosine deaminase (ADA) deficiency, and dedicator of cytokinesis 8 (DOCKS) deficiency. Additionally, cell specific markers for platelets (CD42), natural killer (NK) cells (CD56), and T cells (CD3epsilon and CD3delta) can be used as secondary markers to provide support for diagnosis of disease.

Abstract: Methods, compositions, and systems for treating subject(s) in need of plasma Factor VIII, particularly a subject having preexisting anti-FVIII inhibitory antibodies, are provided. The methods involve administering to the subject a therapeutically effective amount of an inflammation suppressor, a therapeutically effective amount of a CD8+ T cell depleting agent, and a therapeutically effective amount of a composition comprising a lentiviral vector (LV) comprising an optimized FVIII expression cassette expressibly linked to a megakaryocyte-specific promoter. Such methods, compositions, and systems are useful to treat subjects with blood clotting disorder(s), such as hemophilia A.

Abstract: Selectively providing voltage-gated sodium channel function sufficient to rescue impaired Nav1.1 function to inhibitory neurons is described. Provided voltage-gated sodium channel function sufficient to rescue impaired Nav1.1 function in inhibitory neurons can be used to treat disorders such as epilepsy, and more particularly, Dravet Syndrome.

Abstract: In vivo gene therapies for immune deficiencies are described. The in vivo gene therapies utilize a foamy viral vector including a PGK promoter with a therapeutic gene. The foamy viral vector can be beneficially administered with cell mobilization into the peripheral blood.

Abstract: The disclosure relates to doubly attenuated malaria parasites that have had the functionality of LISP 2 and PlasMei2 genes interrupted through genetic manipulation. The double attenuated malaria parasites disclosed herein are useful for methods and compositions for stimulating of vertebrate host immune systems because of the complete cessation of lifecycle progression in the late liver stage, while providing a comprehensive antigenic presentation representing wildtype liver stage parasites. The disclosure also relates to the additional blood stage and gametocyte antigens to compositions of genetically attenuated malaria parasites (GAPs) to enhance efficient immune stimulation and prevention of disease and transmission related to the presence of blood stage parasites.

Abstract: Provided herein are methods of sorting antigen-specific IgM memory B cells (MBCs), compositions and methods comprising such antigen-specific IgM MBCs, and recombinant antibody or antigen-binding fragments isolated from such antigen-specific IgM MBCs. As demonstrated herein, IgM and IgD MBCs are unique populations of cells with distinct phenotypic, functional and survival properties. Accordingly, the antigen-specific IgM MBCs and antibodies and antigen-binding fragments derived from these cells described herein are useful in therapeutic applications in vaccine strategies and treatment of infectious diseases.

Abstract: The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.

Abstract: The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.

Abstract: It has been discovered that high amplitude, low frequency, broadband spectrum pressure oscillations of sufficient time duration can help stabilize lung volumes and improve gas exchange in a patient receiving ventilation assistance by helping to recruit and stabilize alveoli. A novel device is presented which can produce pressure oscillations having high amplitudes, a low broad-band frequency spectrum and long time duration. Additionally, the device can maintain a patient's mean airway pressure at one or more controlled levels. The device can control the oscillatory amplitude, frequency range and composition, time duration, and mean airway pressure levels by adjusting certain device parameters, such as the angle and depth of the device in a fluid. A device and mechanical system for remotely adjusting and measuring the angle of the device in a fluid are also disclosed.

Abstract: It has been discovered that high amplitude, low frequency, broadband spectrum pressure oscillations of sufficient time duration can help stabilize lung volumes and improve gas exchange in a patient receiving ventilation assistance by helping to recruit and stabilize alveoli. A novel device is presented which can produce pressure oscillations having high amplitudes, a low broad-band frequency spectrum and long time duration. Additionally, the device can maintain a patient's mean airway pressure at one or more controlled levels. The device can control the oscillatory amplitude, frequency range and composition, time duration, and mean airway pressure levels by adjusting certain device parameters, such as the angle and depth of the device in a fluid. A device and mechanical system for remotely adjusting and measuring the angle of the device in a fluid are also disclosed.