Rapid Development and Validation of a Novel Laboratory-Derived Test for the Detection of SARS-CoV-2.

Objectives: To increase testing capability for SARS-CoV-2 during a rapidly evolving public health emergency, we aimed to deploy a validated laboratory-developed real-time reverse transcription polymerase chain reaction (RT-PCR) diagnostic test for SARS-CoV-2 on an accelerated timeline and using reagent supply chains that were not constrained.

Methods: A real-time RT-PCR assay that detects the structural envelope ( gene of SARS-CoV-2 was developed and validated on the Roche cobas 6800 instrument platform with the omni Utility channel reagents, which performs automated nucleic acid extraction and purification, PCR amplification, and detection. analysis was performed for both inclusivity of all SARS-CoV-2 variants and cross reactivity with other pathogenic organisms.

Summary from Advanced Manufacturing Technology Workshop Held at 6th Accelerating Biopharmaceutical Development Meeting.

A workshop was held at the 6 Accelerating Biopharmaceutical Development meeting in Carlsbad, CA on February 18, 2019. An anonymous survey was sent to all industry participants before the meeting to identify their top technological barriers to achieving a future manufacturing state and a real-time polling tool was used to collect live feedback during the meeting. Senior leaders from across the biopharmaceutical industry discussed the top technology opportunities to enable high-throughput, flexible manufacturing capabilities and business drivers for the industry.

NIIMBL-Facilitated Active Listening Meeting between Industry and FDA Identifies Common Challenges for Adoption of New Biopharmaceutical Manufacturing Technologies.

The National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) piloted a forum to encourage an exchange of information between the biopharmaceutical industry and the U.S. Food and Drug Administration (FDA).

Cyberbiosecurity for Biopharmaceutical Products.

Cyberbiosecurity is an emerging discipline that addresses the unique vulnerabilities and threats that occur at the intersection of cyberspace and biotechnology. Advances in technology and manufacturing are increasing the relevance of cyberbiosecurity to the biopharmaceutical manufacturing community in the United States. Threats may be associated with the biopharmaceutical product itself or with the digital thread of manufacturing of biopharmaceuticals, including those that relate to supply chain and cyberphysical systems.

Immunoglobulin G transport increases in an in vitro blood-brain barrier model with amyloid-β and with neuroinflammatory cytokines.

Immunotherapies are a promising strategy for the treatment of neurological diseases such as Alzheimer's disease (AD), however, transport of antibodies to the brain is severely restricted by the blood-brain barrier (BBB). Furthermore, molecular transport at the BBB is altered in disease, which may affect the mechanism and quantity of therapeutic antibody transport. To better understand the transport of immunotherapies at the BBB in disease, an in vitro BBB model derived from human induced pluripotent stem cells (iPSCs) was used to investigate the endocytic uptake route of immunoglobulin G (IgG).

A differentiating neural stem cell-derived astrocytic population mitigates the inflammatory effects of TNF-α and IL-6 in an iPSC-based blood-brain barrier model.

Inflammation can be a risk factor for neurodegenerative diseases such as Alzheimer's disease (AD) and may also contribute to the progression of AD. Here, we sought to understand how inflammation affects the properties of the brain microvascular endothelial cells (BMECs) that compose the blood-brain barrier (BBB), which is impaired in AD. A fully human in vitro BBB model with brain microvascular endothelial cells derived from induced pluripotent stem cells and differentiating neural stem cell (NSC)-derived astrocytic cells was used to investigate the effects of neuroinflammation on barrier function.

Minimum Transendothelial Electrical Resistance Thresholds for the Study of Small and Large Molecule Drug Transport in a Human in Vitro Blood-Brain Barrier Model.

A human cell-based in vitro model that can accurately predict drug penetration into the brain as well as metrics to assess these in vitro models are valuable for the development of new therapeutics. Here, human induced pluripotent stem cells (hPSCs) are differentiated into a polarized monolayer that express blood-brain barrier (BBB)-specific proteins and have transendothelial electrical resistance (TEER) values greater than 2500 Ω·cm. By assessing the permeabilities of several known drugs, a benchmarking system to evaluate brain permeability of drugs was established.

Fabrication of 3D Biomimetic Microfluidic Networks in Hydrogels.

A laser-based hydrogel degradation technique is developed that allows for local control over hydrogel porosity, fabrication of 3D vascular-derived, biomimetic, hydrogel-embedded microfluidic networks, and generation of two intertwining, yet independent, microfluidic networks in a single construct.

A prospective observational trial of pelvic floor muscle training for female stress urinary incontinence.

Objective: To assess the impact of pelvic floor muscle training (PFMT) on bladder neck mobility in a prospective observational study, and to correlate any observed changes with objective, standardized outcome measures of the severity of stress urinary incontinence (SUI).

Patients And Methods: Women with the symptom of SUI were recruited prospectively over a 3-year period from a tertiary referral urogynaecology clinic in a teaching hospital. A group of 97 treatment-naive women complaining of SUI and confirmed as having urodynamic SUI on video-urodynamic assessment agreed to participate.

Weighted vaginal cones for urinary incontinence.

Background: Pelvic floor muscle training has long been the most common form of conservative treatment for stress urinary incontinence. Weighted vaginal cones can be used to help women to train their pelvic floor muscles. Cones are inserted into the vagina and the pelvic floor is contracted to prevent them slipping out.

Weighted vaginal cones for urinary incontinence.

Background: Pelvic floor muscle training has long been the most common form of conservative treatment for stress urinary incontinence. Many people have trouble identifying their pelvic floor, and thus difficulty training it. One aid to help with training the pelvic floor in women is weighted vaginal cones.

Home self-assessment of obsessive-compulsive disorder. Use of a manual and a computer-conducted telephone interview: two UK-US studies.

Background: Two studies tested whether subjects with obsessive-compulsive disorder could successfully use BT STEPS, a computer-aided system, to perform self-assessment for self-treatment of obsessive-compulsive disorder by exposure and ritual prevention.

Method: Subjects were given a self-guiding manual and could use a touch-tone telephone to access computer-controlled Interactive Voice Response interviews at their convenience from home. Using the BT STEPS system, patients rated themselves and worked out a plan for individually tailored self-exposure therapy.

Self-treatment for obsessive compulsive disorder using a manual and a computerized telephone interview: a U.S.-U.K. study.

Bt steps is a patient-centered behavioral therapy program that uses a manual and a computer-driven interactive voice response system to assess and treat obsessive compulsive disorder. This nine-step program contains a self-assessment module and a self-treatment module that provides teaching on exposure and ritual prevention. The patient reads about the steps in a manual and then uses a touch-tone telephone to contact the program, in which a recorded voice conducts the interview.

Administration of the Hamilton Depression Rating Scale using interactive voice response technology.

We compared the reliability and equivalence of scores on the Hamilton rating scale for depression obtained by an interactive voice response (IVR) system and by human raters among 367 subjects 18 to 79 years old. Structured clinical interviews indicated that 93 of these subjects met the DSM-IV criteria for current major depression. We also examined short forms using the IVR data.

A computer-administered telephone interview to identify mental disorders.

Context: Common mental disorders are often not identified in primary care settings.

Objective: To evaluate the validity and clinical utility of a telephone-assisted computer-administered version of Primary Care Evaluation of Mental Disorders (PRIME-MD), a brief questionnaire and interview instrument designed to identify psychiatric disorders in primary care patients.

Design: Comparison of diagnoses obtained by computer over the telephone using interactive voice response (IVR) technology vs those obtained by a trained clinician over the telephone using the Structured Clinical Interview for DSM-IV [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition] Diagnosis (SCID).

Sertraline for social phobia: a double-blind, placebo-controlled crossover study.

Objective: The authors examined the efficacy of sertraline in the treatment of social phobia.

Method: In a double-blind crossover study, 12 outpatients were randomly assigned to 10 weeks of sertraline (50-200 mg/day, flexible dosing) and 10 weeks of placebo.

Results: A statistically significant improvement in scores on the Liebowitz Social Anxiety Scale was found with sertraline but not with placebo.

Physiotherapy for stress urinary incontinence: a national survey.

Objective: To study the physiotherapeutic treatment of urinary stress incontinence in England.

Design: Postal questionnaire survey.

Setting: All 192 English district health authorities.

Return of left ventricular function after reperfusion in patients with myocardial infarction: importance of subtotal stenoses or intact collaterals.

To determine whether subsequent improvement in left ventricular ejection fraction can be predicted from preintervention coronary arteriograms, we divided 63 patients with acute myocardial infarction into two groups based on findings at emergency coronary arteriography at a mean of 7 hr after onset of symptoms: (1) a "no-flow" group with an occluded infarct-related artery and no easily visible collaterals (n = 36) and (2) a "limited-flow" group with either subtotal stenosis or total occlusion of the infarct-related vessel with intact collaterals (n = 27). Of the 63 patients, 61 underwent emergency procedures to establish reperfusion. At follow-up angiography (contrast or radionuclide) performed 12 +/- 7 days after infarction, global ejection fraction had increased significantly in patients with limited flow to the infarct zone and "successful" early reperfusion intervention due primarily to a significant increase in the regional ejection fraction in the infarct zone.

Anthracycline-induced cardiomyopathy in children: a report of six cases.

Although anthracycline antibiotics are among the most useful chemotherapy agents, the risk of producing cardiomyopathy and the absence of a reliable noninvasive technique to predict subclinical cardiomyopathy remain a major problem. We retrospectively reviewed our experience with anthracyclines over a 5-year period. Cardiomyopathy developed in 6 of 112 patients (5.

The relationship between cardiac output and effective renal plasma flow in patients with cardiac disease.

The relationship between effective renal plasma flow (ERPF) and cardiac output was examined in 46 patients (22 with congestive heart failure and 24 following cardiac surgical procedures) by simultaneously measuring the global ERPF by the single-injection method and cardiac output by the thermodilution method. Of the patients in the heart-failure group, 21 also had pulmonary artery end diastolic pressure (PAEDP) recorded at the same time. ERPF and cardiac output were found to be related by the regression equation: cardiac output = 2.

Prospective randomized trial of intravenous and intracoronary streptokinase in acute myocardial infarction.

To evaluate the relative thrombolytic efficacy and complications of intracoronary vs high-dose, short-term intravenous streptokinase infusion in patients with acute myocardial infarction, we performed baseline coronary arteriography and then randomly allocated 51 patients with acute myocardial infarction to receive either intracoronary (n = 25) or intravenous (n = 26) streptokinase. Patients getting the drug by the intracoronary route received 240,000 IU of streptokinase into the infarct-related artery over 1 hr, whereas those getting the drug by the intravenous route received either 500,000 IU of streptokinase over 15 min (n = 10) or 1 million IU of streptokinase over 45 min (n = 16). Angiographically observed thrombolysis occurred in 76% (19/25) of the patients receiving intracoronary streptokinase, in 10% (1/10) of the patients receiving 500,000 IU of streptokinase intravenously, and in 44% (7/16) of the patients receiving 1 million IU of streptokinase intravenously.