Phenotypic hypersusceptibility to multiple protease inhibitors and low replicative capacity in patients who are chronically infected with human immunodeficiency virus type 1

Increased susceptibility to the protease inhibitors saquinavir and amprenavir has been observed in human immunodeficiency virus type 1 (HIV-1) with specific mutations in protease (V82T and N88S). Increased susceptibility to ritonavir has also been described in some viruses from antiretroviral agent-naïve patients with primary HIV-1 infection in association with combinations of amino acid changes at polymorphic sites in the protease. Many of the viruses displaying increased susceptibility to protease inhibitors also had low replication capacity. In this retrospective study, we analyze the drug susceptibility phenotype and the replication capacity of virus isolates obtained at the peaks of viremia during five consecutive structured treatment interruptions in 12 chronically HIV-1-infected patients. Ten out of 12 patients had at least one sample with protease inhibitor hypersusceptibility (change ≤0.4-fold) to one or more protease inhibitor. Hypersusceptibility to different protease inhibitors was observed at variable frequency, ranging from 38% to amprenavir to 11% to nelfinavir. Pairwise comparisons between susceptibilities for the protease inhibitors showed a consistent correlation among all pairs. There was also a significant relationship between susceptibility to protease inhibitors and replication capacity in all patients. Replication capacity remained stable over the course of repetitive cycles of structured treatment interruptions. We could find no association between in vitro replication capacity and in vivo plasma viral load doubling time and CD4(+) and CD8(+) T-cell counts at each treatment interruption. Several mutations were associated with hypersusceptibility to each protease inhibitor in a univariate analysis. This study extends the association between hypersusceptibility to protease inhibitors and low replication capacity to virus isolated from chronically infected patients and highlights the complexity of determining the genetic basis of this phenomenon. The potential clinical relevance of protease inhibitor hypersusceptibility and low replication capacity to virologic response to protease inhibitor-based therapies deserves to be investigated further

Synthesis of Rutile Nb: TiO2 Free-Standing Thin Film at the Liquid-Air Interface

One‐step hydrothermal synthesis of the niobium doped rutile TiO2 free standing film at the liquid–air interface without the use of a template is presented. Film is flexible within first few minutes of removal from the solution and allows application on various shaped objects and substrates

Structure of Gold - Silver Nanoparticles

Nanoparticles with nominal structures of Au@Ag (core@shell) and Au@Ag@Au (core@shell@shell) were prepared using the sequential citrate reduction technique and characterized using routine characterization techniques, including transmission electron microscopy. X-ray absorption spectroscopy was then carried out on the samples, and extended X-ray absorption fine structure (EXAFS) analysis was used to determine the structure of the systems. The results of the routine techniques and the X-ray absorption spectroscopy were then compared. EXAFS analysis of the nanoparticles with the Au@Ag structure revealed very limited bimetallic interactions, supporting the assignment of a core@shell structure. EXAFS analysis of the nanoparticles with Au@Ag@Au structure showed an increased proportion of bimetallic interactions. Based on the colloid composition, the other characterization techniques and the chemistry of the system, these nanoparticles were interpreted as having an Au@Au/Ag-alloy structure. The EXAFS analyses corroborated the other characterization techniques and enabled the determination of the average-structure of the entire sample

Controlling and modelling the wetting properties of III-V semiconductor surfaces using re-entrant nanostructures

Inorganic semiconductors such as III-V materials are very important in our everyday life as they are used for manufacturing optoelectronic and microelectronic components with important applications span from energy harvesting to telecommunications. In some applications, these components are required to operate in harsh environments. In these cases, having waterproofng capability is essential. Here we demonstrate design and control of the wettability of indium phosphide based multilayer material (InP/InGaAs/InP) using re-entrant structures fabricated by a fast electron beam lithography technique. This patterning technique enabled us to fabricate highly uniform nanostructure arrays with at least one order of magnitude shorter patterning times compared to conventional electron beam lithography methods. We reduced the surface contact fraction signifcantly such that the water droplets may be completely removed from our nanostructured surface. We predicted the wettability of our patterned surface by modelling the adhesion energies between the water droplet and both the patterned surface and the dispensing needle. This is very useful for the development of coating-free waterproof optoelectronic and microelectronic components where the coating may hinder the performance of such devices and cause problems with semiconductor fabrication compatibility

Ultra high molecular weight polyethylene with incorporated crystal violet and gold nanoclusters is antimicrobial in low intensity light and in the dark

Antibiotics lose their effectiveness over time due to antimicrobial resistance. The increasing risk of hospital-acquired infections from contaminated surfaces and medical interventions requires the development of new antimicrobial materials. We report the first example of a modified ultra high molecular weight polyethylene that showed good antibacterial properties on light activation. Its efficacy was due to the production of reactive oxygen species under low-intensity white light sources (ca. 375 lux). Crystal violet and cysteine capped gold nanoclusters were successfully incorporated into the polymer using a readily available solvent as a dispersing agent followed by the process of compression moulding at 200 °C, 4.5 MPa for 1 min. This modified ultra-high molecular weight polyethylene demonstrates excellent robustness with regards to dye and metal leaching as well as photostability. Despite incorporating antimicrobial agents, the modified ultra-high molecular weight polyethylene retained its mechanical properties and showed >99% reduction in bacterial numbers against Escherichia coli and. To our knowledge, this paper reports the first use of compression moulding to create a light-activated antimicrobial surface which has distinct processing advantages over the widely used “swell-encapsulation-shrink” method and is potentially scalable

White light-activated antimicrobial surfaces: effect of nanoparticles type on activity

Toluidine blue O (TBO) dye together with either silver (Ag) nanoparticles (NPs), gold (Au) NPs, or a mixture of Ag and Au NPs (Mix Ag–Au NPs) were incorporated into polyurethane to make antimicrobial surfaces using a swell-encapsulation-shrink process. Antimicrobial testing against Escherichia coli showed that inclusion of the NPs significantly enhanced the antimicrobial activities of the TBO polyurethane samples. In particular, samples containing Ag NPs exhibited potent antimicrobial activity under white light and surprisingly, also in the dark. The numbers of viable bacteria decreased below the detection limit on the TBO/Ag NPs incorporated samples within 3 h and 24 h under white light and dark conditions. A mechanistic study using furfuryl alcohol indicated that the enhanced photobactericidal activity was most likely due to a type I photochemical reaction. To the best of our knowledge, this is the first report of an antimicrobial surface comprised of a combination of Ag NPs and a light activated agent to provide a dual kill mechanism. These surfaces are promising candidates for use in healthcare environments to reduce the incidence of hospital-acquired infections

Synthesis of PEG-PPG-PEG templated polydopamine nanoparticles under intensified conditions: Kinetics investigation, continuous process design and demonstration for photothermal application

Polydopamine is a nature inspired functional material with promising applications in a plethora of fields due to its structural, chemical, and optical properties. While there is significant interest in the preparation of polydopamine based nanomaterials that take advantage of its properties, less attention has been given to the optimisation of the synthetic process, which typically involves the oxidative self-polymerisation of dopamine under basic pH and requires 24–72 h for reaction completion. The present work investigated the kinetics of polydopamine formation in the presence of Pluronic P-123 (PEG-PPG-PEG) micelles acting as a soft template, in low monomer concentrations (that promote particle growth instead of nucleation) as a function of temperature and pressure. Simultaneous increase of pressure and temperature (up to 50 °C and 5 bar O2) was found to significantly reduce the reaction time to 20–40 min without compromising the particle quality. Based on the results of the kinetic investigation, the polydopamine synthesis was translated into a continuous process utilising a millifluidic co-axial membrane reactor with a focus on ease of use, process conditions’ reproducibility and safety of operation. The reactor produced nanoparticles similar to the batch synthesis and resisted fouling (which is generally expected in a compact flow reactor) due to the action of the P-123 surfactant. Due to the nontoxic process that utilises only biocompatible materials and oxygen as the oxidising agent, and the melanin-like structure of polydopamine, photothermal heating of the synthesised nanoparticles under concentrated IR irradiation at 808 nm light was studied, as this can potentially be used for photo-induced hyperthermia. The hyperthermia threshold of 10 °C temperature increase at relatively low laser power settings (fluence 1.77 W/cm2) was achieved, making it a promising candidate for this application

Long-term effects of once-only flexible sigmoidoscopy screening after 17 years of follow-up: the UK Flexible Sigmoidoscopy Screening randomised controlled trial

National Institute for Health Research Efficacy and Mechanism Evaluation

Schistosomiasis and Urinary Bladder Cancer in North Western Tanzania: A Retrospective Review of 185 Patients.

Worldwide, cancers of the urinary bladder are well known to be associated with environmental chemical carcinogens such as smoking and occupational exposure to polycyclic aromatic hydrocarbons. These cancers are typically transitional cell carcinoma (urothelial carcinoma). In areas where schistosomiasis is endemic there is a high incidence of squamous cell carcinoma of the urinary bladder. Schistosomiasis causes chronic granulomatous cystitis leading to squamous metaplasia of transitional epithelium, and subsequently development of squamous cell carcinoma. The western part of Tanzania on the shores of Lake Victoria is such an endemic area. This study was done to document the burden of urinary bladder cancer associated with schistosomiasis in this region. This was a descriptive retrospective study of histologically confirmed cases of urinary bladder cancer seen at the Department of Pathology Bugando Medical Centre (BMC) over a period of 10 years. Data were retrieved from the records of the Departments of Pathology, Medical Records and Surgery. Data were analyzed by the use of contingency tables. A total of 185 patients were diagnosed with cancer of the urinary bladder during the study period, where as 90 (48.6%) were males and 95 (51.4) were females. The mean age at diagnosis was 54.3 years. Squamous cell carcinoma was the most frequent histological type (55.1%), followed by conventional transitional cell carcinoma (40.5%). Eighty three of all cancer cases (44.9%) were found to have schistosomal eggs. Schistosomiasis was commonly associated with squamous cancers compared to non squamous cancers. Most of the cancers associated with schistosomiasis had invaded the muscularis propria of the urinary bladder at the time of diagnosis (p<0.001) and such cancers were frequent below 50 years of age with a significant statistical difference (p<0.001). Poorly differentiated tumors were more frequent in females than males with a significant statistical difference (p=0.006). The majority of urinary bladder cancers seen in the Lake Region were squamous cell carcinoma associated with schistosomiasis. These cancers showed an aggressive behavior and were commonly seen in the younger age groups. Effective control of schistosomiasis in this region should significantly reduce the burden of urinary bladder cancer

Photobactericidal activity activated by thiolated gold nanoclusters at low flux levels of white light

The emergence of antibiotic resistant bacteria is a major threat to the practice of modern medicine. Photobactericidal agents have obtained significant attention as promising candidates to kill bacteria, and they have been extensively studied. However, to obtain photobactericidal activity, an intense white light source or UV-activation is usually required. Here we report a photobactericidal polymer containing crystal violet (CV) and thiolated gold nanocluster ([Au25(Cys)18]) activated at a low flux levels of white light. It was shown that the polymer encapsulated with CV do not have photobactericidal activity under white light illumination of an average 312 lux. However, encapsulation of [Au25(Cys)18] and CV into the polymer activates potent photobactericidal activity. The study of the photobactericidal mechanism shows that additional encapsulation of [Au25(Cys)18] into the CV treated polymer promotes redox reactions through generation of alternative electron transfer pathways, while it reduces photochemical reaction type-ІІ pathways resulting in promotion of hydrogen peroxide (H2O2) production