First-in-human trial evaluating safety and pharmacokinetics of AT-752, a novel nucleotide prodrug with pan-serotype activity against dengue virus.

AT-752 is a novel guanosine nucleotide prodrug inhibitor of the dengue virus (DENV) polymerase with sub-micromolar, pan-serotype antiviral activity. This phase 1, double-blind, placebo-controlled, first-in-human study evaluated the safety, tolerability, and pharmacokinetics of ascending single and multiple oral doses of AT-752 in healthy subjects. AT-752 was well tolerated when administered as a single dose up to 1,500 mg or when administered as multiple doses up to 750 mg three times daily (TID).

Oral bemnifosbuvir (AT-527) vs placebo in patients with mild-to-moderate COVID-19 in an outpatient setting (MORNINGSKY).

This phase III study assessed the efficacy/safety/antiviral activity/pharmacokinetics of bemnifosbuvir, a novel, oral nucleotide analog to treat COVID-19. Outpatient adults/adolescents with mild-to-moderate COVID-19 were randomized 2:1 to bemnifosbuvir/placebo. Time to symptom alleviation/improvement (primary outcome), risk of hospitalization/death, viral load and safety were evaluated.

Disease causing mutation (P178L) in mitochondrial transcription factor A results in impaired mitochondrial transcription initiation.

Mitochondrial transcription factor A (TFAM) is essential for the maintenance, expression, and packaging of mitochondrial DNA (mtDNA). Recently, a pathogenic homozygous variant in TFAM (P178L) has been associated with a severe mtDNA depletion syndrome leading to neonatal liver failure and early death. We have performed a biochemical characterization of the TFAM variant P178L in order to understand the molecular basis for the pathogenicity of this mutation.

Humeral Shaft Fracture Sustained During Arm Wrestling with Review of Factors Contributing to its Causation.

Introduction: Humeral shaft fractures are the most common injury sustained in arm wrestling, and its various biomechanical, anatomical, kinematic and electromyographic aspects have been studied and reported. We present a series of six cases of humeral shaft fractures in the arm wrestlers and a review of basic science studies to determine the factors contributing to their causation.

Materials And Methods: Six humeral shaft fractures associated with arm wrestling were treated between December 2018 and January 2020.

A first-in-human study of BLZ-100 (tozuleristide) demonstrates tolerability and safety in skin cancer patients.

BLZ-100 (tozuleristide) is an intraoperative fluorescent imaging agent that selectively detects malignant tissue and can be used in real time to guide tumor resection. The purpose of this study was to assess the safety, tolerability, and pharmacokinetics of BLZ-100 and to explore the pharmacodynamics of fluorescence imaging of skin tumors. In this first-in-human study, BLZ-100 was administered intravenously to 21 adult patients 2 days before excising known or suspected skin cancers.

Phase 1 Safety, Pharmacokinetics, and Fluorescence Imaging Study of Tozuleristide (BLZ-100) in Adults With Newly Diagnosed or Recurrent Gliomas.

Background: Fluorescence-guided surgery (FGS) can improve extent of resection in gliomas. Tozuleristide (BLZ-100), a near-infrared imaging agent composed of the peptide chlorotoxin and a near-infrared fluorophore indocyanine green, is a candidate molecule for FGS of glioma and other tumor types.

Objective: To perform a phase 1 dose-escalation study to characterize the safety, pharmacokinetics, and fluorescence imaging of tozuleristide in adults with suspected glioma.

Real-time Visualization of Breast Carcinoma in Pathology Specimens From Patients Receiving Fluorescent Tumor-Marking Agent Tozuleristide.

Context.—: Resection of breast carcinoma with adequate margins reduces the risk of local recurrence and reoperation. Tozuleristide (BLZ-100) is an investigational peptide-fluorophore agent that may aid in intraoperative tumor detection and margin assessment.

Autophagy controls the pathogenicity of OPA1 mutations in dominant optic atrophy.

Optic Atrophy 1 (OPA1) gene mutations cause diseases ranging from isolated dominant optic atrophy (DOA) to various multisystemic disorders. OPA1, a large GTPase belonging to the dynamin family, is involved in mitochondrial network dynamics. The majority of OPA1 mutations encodes truncated forms of the protein and causes DOA through haploinsufficiency, whereas missense OPA1 mutations are predicted to cause disease through deleterious dominant-negative mechanisms.

A comprehensive approach to determining BER capacities and their change with aging in Drosophila melanogaster mitochondria by oligonucleotide microarray.

DNA repair mechanisms are key components for the maintenance of the essential mitochondrial genome. Among them, base excision repair (BER) processes, dedicated in part to oxidative DNA damage, are individually well known in mitochondria. However, no large view of these systems in differential physiological conditions is available yet.

Synmastia: prevention and correction.

Synmastia is a condition of aberrant communication of the breasts. Apart from the rare congenital cases, this is usually a result of technical complications during breast augmentation surgery caused by an overdissection at the medial side of the pocket, over the sternum, in the subglandular plane; or overdivision of the major pectoralis muscle insertion along the sternum, in the submuscular plane. A multidatabase search about synmastia has been performed.

Time and motion in cosmetic surgery.

Time and motion studies have been used to analyze performance and improve outcomes. This prospective study evaluated a typical operating day at a surgical facility in the United Kingdom by recording admitting time into the hospital, entrance and exit times from theatre, and length of surgical time. The same surgical team performed 10 breast augmentations in less than 10 hr, with a mean preparation time of 9 min 20 s and a mean surgical time (from incision to closure) of 32 min.

Safety and pharmacokinetics of recombinant factor XIII-A2 administration in patients with congenital factor XIII deficiency.

Congenital factor XIII (FXIII) deficiency is associated with a tendency for severe bleeding, a risk for spontaneous abortion, and a high rate of spontaneous intracranial hemorrhage. This phase 1 escalating-dose study was developed to evaluate the safety and pharmacokinetics of a single administration of human recombinant FXIII-A2 (rFXIII-A2) homodimer in adults with congenital FXIII deficiency. Pharmacokinetics and activity of rXIII and changes in endogenous B subunit levels were assessed.

The BTA stat test: a tumor marker for the detection of upper tract transitional cell carcinoma.

Objectives: To conduct a prospective evaluation to determine the utility of the BTA stat test in the detection of upper tract transitional cell carcinoma (UTTCC). Monitoring for UTTCC currently relies on invasive procedures such as upper tract imaging, ureteral washing cytology (UWC) and/or ureteroscopy, or voided urine cytology (VUC). The BTA stat test is a sensitive qualitative immunoassay that detects human complement factor H-related protein in voided urine.

Evaluation of the BTA tests for the detection of bilharzial related bladder cancer: the Cairo experience.

Objective: To evaluate the clinical performance of the BTA stat test and the BTA TRAK assay in the diagnosis of bilharzia-related bladder cancer and to calculate a new 'Egyptian' cut-off value for the BTA TRAK (quantitative) assay.

Methods: Urine samples of 149 individuals were tested for the presence of the human complement factor H-related protein, the antigen detected by the BTA stat and BTA TRAK tests. The group consisted of 53 healthy volunteers, 20 patients with active bilharziasis, 11 patients with other urologic disorders including prostate cancer, and 65 patients with histologically proven bladder cancer.

Multicenter trial of the quantitative BTA TRAK assay in the detection of bladder cancer.

Background: Human complement factor H-related protein (hCFHrp) is produced by several bladder cancer cell lines and may be useful as a cancer marker. The aim of this study was to compare urinary hCFHrp and cytology for the detection of bladder cancer found by cystoscopy in patients with suggestive signs, symptoms, or preliminary test results.

Methods: The BTA TRAK assay, a quantitative enzyme immunoassay for the bladder tumor-associated antigen in urine, was compared with exfoliative cytology in 220 patients (155 men, 65 women; mean age, 64.

The relationship between serial measurements of the level of a bladder tumor associated antigen and the potential for recurrence.

Purpose: We evaluate the relationship between a serially assessed quantitative diagnostic marker (QDM) and the hazard function for the diagnosis of recurrence of bladder cancer. The marker is based on a bladder tumor associated antigen (BTA TRAK) assay. We present a rigorous approach to the evaluation of diagnostic markers to be used for recurrence monitoring.

Comparison of the BTA stat test with voided urine cytology and bladder wash cytology in the diagnosis and monitoring of bladder cancer.

Objective: To compare the BTA stat test (BTA stat), a new one-step immunochromatographic assay that can be performed in the urologist's office or in the laboratory, to voided urine cytology and bladder wash cytology (cytology) in the diagnosis and monitoring of cancer of the bladder (BC).

Methods: BTA stat and cytology were performed in a double-blinded, prospective, clinical study on specimens from 240 subjects (68 females; mean age of subjects: 64 years) suspected of having BC.

Results: In 107 subjects with final diagnoses of BC confirmed by cystoscopy or cystoscopy and biopsy, the overall sensitivities of BTA stat and cytology were 65 and 33%, respectively.

Clinical evaluation of the BTA TRAK assay and comparison to voided urine cytology and the Bard BTA test in patients with recurrent bladder tumors. The Multi Center Study Group.

Objectives: To assess the clinical performance of the BTA TRAK assay and to compare it with that of voided urine cytology (VUC) and the Bard BTA test (BTA) in the detection of recurrent bladder cancer (BC).

Methods: The study was performed on randomly selected archival voided urine samples for many of which VUC and/or BTA information was available. Sensitivity was determined in samples from patients with histologically confirmed recurrent BC.