PET/CT guided tuberculosis treatment shortening: a randomized trial.

Six months of chemotherapy using current agents is standard of care for pulmonary, drug-sensitive tuberculosis (TB), even though some are believed to be cured more rapidly and others require longer therapy. Understanding what factors determine the length of treatment required for durable cure in individual patients would allow individualization of treatment durations, provide better clinical tools to determine the of appropriate duration of new regimens, as well as reduce the cost of large Phase III studies to determine the optimal combinations to use in TB control programs. We conducted a randomized clinical trial in South Africa and China that recruited 704 participants with newly diagnosed, drug-sensitive pulmonary tuberculosis and stratified them based on radiographic disease characteristics as assessed by FDG PET/CT scan readers.

High resolution imaging and five-year tuberculosis contact outcomes.

Background: The evolution of tuberculosis (TB) disease during the clinical latency period remains incompletely understood.

Methods: 250 HIV-uninfected, adult household contacts of rifampicin-resistant TB with a negative symptom screen underwent baseline F-Fluorodeoxyglucose positron emission and computed tomography (PET/CT), repeated in 112 after 5-15 months. Following South African and WHO guidelines, participants did not receive preventive therapy.

A retrospective review of CT pulmonary angiogram confirmed pulmonary emboli in COVID-19 patients admitted to Groote Schuur Hospital, Cape Town.

Background: A high incidence of thromboembolic phenomena has been widely reported in patients with coronavirus disease 2019 (COVID-19) pneumonia. There is, however, a paucity of data detailing the incidence and characteristics of pulmonary emboli (PE) in COVID-19 patients in the South African setting.

Objectives: To describe the incidence and characteristics of PE confirmed by CT pulmonary angiogram (CTPA) in patients with COVID-19 pneumonia admitted to a tertiary hospital in the Western Cape, South Africa.

Infraspinatus shift for massive, posterosuperior tears yields good clinical outcome.

Aim: To evaluate the functional outcome of partial reconstruction margin convergence in the treatment of massive, irreparable posterosuperior rotator cuff tear (RCT).

Methods: This retrospective, single-center study included all patients that were operated by means of a partial repair and infraspinatus shift for a massive, posterosuperior cuff tear between 2009 and 2016, either in arthroscopic or mini-open technique. Outcome measures included sex- and age-adapted Constant Score (saCS), Western Ontario Rotator Cuff (WORC) Index, Disabilities of Arm, Shoulder and Hand Scores (DASH), and relative effect per patient (REPP).

Lipid Bilayer Interactions of Peptidic Supramolecular Polymers and Their Impact on Membrane Permeability and Stability.

The synthesis and physicochemical characterization of supramolecular polymers with tunable assembly profiles offer exciting opportunities, involving the development of new biomedical carriers. Because synthetic nanocarriers aim to transport substances across or toward cellular membranes, we evaluated the interactions of amphiphilic peptide-based supramolecular polymers with lipid bilayers. Here, we focused on nanorod-like supramolecular polymers, obtained from two -symmetric dendritic peptide amphiphiles with alternating Phe/His sequences, equipped with a peripheral tetraethylene glycol dendron (C3-PH) or charged ethylenediamine end groups (C3-PH+).

Prospective evaluation of host biomarkers other than interferon gamma in QuantiFERON Plus supernatants as candidates for the diagnosis of tuberculosis in symptomatic individuals.

Background: There is an urgent need for new tools for the diagnosis of TB. We evaluated the usefulness recently described host biomarkers in supernatants from the newest generation of the QuantiFERON test (QuantiFERON Plus) as tools for the diagnosis of active TB.

Methods: We recruited individuals presenting at primary health care clinics in Cape Town, South Africa with symptoms requiring investigation for TB disease, prior to the establishment of a clinical diagnosis.

Impact of Branching on the Solution Behavior and Serum Stability of Starlike Block Copolymers.

The size control of nanomedicines for tumor diagnosis and therapy is of high importance, since it enables or disables deep and sufficient tumor penetration. Amphiphilic star-shaped block copolypept(o)ides offer substantial promise to precisely adjust the hydrophobic core and the hydrophilic corona, independent of each other, and therefore simultaneously control the size dimension in the interesting size range from 10 to 30 nm. To gain access to core-shell structures of such sizes, 3-arm and 6-arm PeptoStars, based on poly(γ- tert-butyloxycarbonyl-l-glutamate)- b-polysarcosine (pGlu(O tBu)- b-pSar), were prepared via controlled living ring-opening polymerization (ROP) of the corresponding N-carboxyanhydrides.

A semi-automatic technique to quantify complex tuberculous lung lesions on F-fluorodeoxyglucose positron emission tomography/computerised tomography images.

Background: There is a growing interest in the use of F-FDG PET-CT to monitor tuberculosis (TB) treatment response. However, TB causes complex and widespread pathology, which is challenging to segment and quantify in a reproducible manner. To address this, we developed a technique to standardise uptake (Z-score), segment and quantify tuberculous lung lesions on PET and CT concurrently, in order to track changes over time.

Tuning the pH-Switch of Supramolecular Polymer Carriers for siRNA to Physiologically Relevant pH.

The preparation of histidine enriched dendritic peptide amphiphiles and their self-assembly into multicomponent pH-switchable supramolecular polymers is reported. Alternating histidine and phenylalanine peptide synthons allow the assembly/disassembly to be adjusted in a physiologically relevant range of pH 5.3-6.

The synthesis of dendritic EDOT-peptide conjugates and their multistimuli-responsive self-assembly into supramolecular nanorods and fibers in water.

We report the synthesis of amphiphilic dendritic EDOT-peptide conjugates and discuss their stimuli-responsive self-assembly into polyanionic nanorods in water. In order to expand the general concept of frustrated growth, whereby attractive supramolecular interactions within the enlarged π-system of the hydrophobic core of a dendritic peptide are hampered by repulsive interactions in the hydrophilic periphery, we show that changes in the pH and ionic strength are both able to independently trigger the self-assembly of the dendritic monomers into supramolecular nanorods and nanofibers. These transitions are analyzed using circular dichroism and fluorescence spectroscopic methods, and the resulting supramolecular polymers are characterized by transmission electron microscopy.

Endothelial progenitor cells correlate with endothelial function in patients with coronary artery disease.

Endothelial progenitor cells (EPC) predict morbidity and mortality in patients at cardiovascular risk.Patients with low EPC counts and impaired endothelial colony forming activity have a higher incidence for cardiovascular events compared to patients with high EPC counts and favorable colony forming activity. The pathophysiological basis for this finding may be an insufficient endothelial cell repair by EPC.

Circulating CD31+/annexin V+ apoptotic microparticles correlate with coronary endothelial function in patients with coronary artery disease.

Objective: Endothelial dysfunction predicts morbidity and mortality in patients at cardiovascular risk. Endothelial function may be decisively influenced by the degree of endothelial cell apoptosis.

Methods And Results: To test this hypothesis in humans, endothelial-dependent vasodilatation was invasively assessed in 50 patients with coronary artery disease (CAD) by quantitative coronary angiography during intracoronary acetylcholine infusion.

Circulating endothelial progenitor cells and cardiovascular outcomes.

Background: Endothelial progenitor cells derived from bone marrow are believed to support the integrity of the vascular endothelium. The number and function of endothelial progenitor cells correlate inversely with cardiovascular risk factors, but the prognostic value associated with circulating endothelial progenitor cells has not been defined.

Methods: The number of endothelial progenitor cells positive for CD34 and kinase insert domain receptor (KDR) was determined with the use of flow cytometry in 519 patients with coronary artery disease as confirmed on angiography.

Application of the obligate aerobic yeast Yarrowia lipolytica as a eucaryotic model to analyse Leigh syndrome mutations in the complex I core subunits PSST and TYKY.

We have used the obligate aerobic yeast Yarrowia lipolytica to reconstruct and analyse three missense mutations in the nuclear coded subunits homologous to bovine TYKY and PSST of mitochondrial complex I (proton translocating NADH:ubiquinone oxidoreductase) that have been shown to cause Leigh syndrome (MIM 25600), a severe progressive neurodegenerative disorder. While homozygosity for a V122M substitution in NDUFS7 (PSST) has been found in two siblings with neuropathologically proven Leigh syndrome (R. Triepels et al.

Function of conserved acidic residues in the PSST homologue of complex I (NADH:ubiquinone oxidoreductase) from Yarrowia lipolytica.

Proton-translocating NADH:ubiquinone oxidoreductase (complex I) is the largest and least understood enzyme of the respiratory chain. Complex I from bovine mitochondria consists of more than forty different polypeptides. Subunit PSST has been suggested to carry iron-sulfur center N-2 and has more recently been shown to be involved in inhibitor binding.

The cost of auditing outpatient records.

When patient records are to be auditied in a program designed to assess the quality of medical care rendered, careful consideration must be given to the cost of the system implemented. Structured data collection and a defined treatment plan are advantageous in facilitating the use of nonphysicians for the majority of the audit. A system using checklists to ensure adequate recording of subjective and objective data and a defined treatment plan for a common symptom complex were implemented by physicians and physician's assistants with a patient load averaging more than 1,000 patient contacts per week in a general medical clinic at Duke University Medical Center.