Visible light units (LCU) used in routine dentistry to cure light activated materials may become contaminated with oral micro-organisms. This pilot study was designed to investigate whether the fan, ...handle and base unit mains on/off button areas of three different designs of quartz tungsten halogen LCUs (3M Unitek 2500, Elipar Highlight, Demetron Optilux 401) were effectively disinfected after use in a dental teaching hospital. Over a period of seven days 52 LCUs were swabbed before clinics in the morning and 28 were swabbed again after clinics in the afternoon. Bacterial contamination was detected on approximately 40% (20/52) of units before use and 64% (18/28) after use: few viable organisms were detected on the fan or handle areas, but many were isolated from the mains button, including Staphylococus aureus. These findings highlight the need for greater awareness of the potential risk of contamination of the base unit and compliance with recommendations to clean and disinfect all areas of the units.
Many naturally occurring mineralisation processes yield hydroxyapatite (HA) or related salts, but biological routes to calcification have not generally been exploited for production of hydroxyapatite ...for clinical and industrial applications. Serratia sp. NCIMB 40259 is a non-pathogenic Gram-negative bacterium which is capable of growing as a biofilm on many surfaces and can be used to form HA coatings on a variety of polymeric and metallic materials, including titanium. Here we review previous work and report the results of more recent studies on the influence of titanium compositional and surface properties on Serratia adherence and proliferation and biomineralisation on commercially pure titanium (cp Ti) discs and a Ti mesh. Bacterial adherence was equivalent on cpTi and Ti6Al4V, and biofilms formed on both rough and mirror-polished cpTi surfaces. Embedded alumina particles and alkali treatment did not noticeably alter the precipitation of Serratia HA, nor the structure of the coating in comparison with non-treated substrates. Coatings were retained after sintering at 800°C in argon, although the original curved plate-like crystals changed to nano-scale β-tricalcium phosphate particles. A phosphorous-rich diffusion zone formed at the coating-titanium interface. Bacterial mineralisation may have applications as a method for producing coatings on implants in non load-bearing sites, and non-clinical applications where a high surface area is the major concern.
The worldwide outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Alongside vaccines, antiviral therapeutics are an important ...part of the healthcare response to countering the ongoing threat presented by COVID-19. Here, we report the discovery and characterization of PF-07321332, an orally bioavailable SARS-CoV-2 main protease inhibitor with in vitro pan-human coronavirus antiviral activity and excellent off-target selectivity and in vivo safety profiles. PF-07321332 has demonstrated oral activity in a mouse-adapted SARS-CoV-2 model and has achieved oral plasma concentrations exceeding the in vitro antiviral cell potency in a phase 1 clinical trial in healthy human participants.
A species of Serratia bacteria produces nano-crystalline hydroxyapatite (HA) crystals by use of a cell-bound phosphatase enzyme, located both periplasmically and within extracellular polymeric ...materials. The enzyme functions in resting cells by cleaving glycerol-2-phosphate (G-2-P) to liberate free phosphate ions which combine with calcium in solution to produce a cell-bound calcium phosphate material. Bacteria grown as a biofilm on polyurethane reticulated foam cubes were challenged with calcium and G-2-P in a bioreactor to produce a 3-D porous bone-substitute material. The scaffold has 1 mm macropores and 1 microm micropores. XRD showed the crystallites to be 25-28 nm in size, resembling HA before sintering and beta-tricalcium phosphate (beta-TCP, whitlockite) after. When biofilm was grown on titanium discs and challenged with calcium and G-2-P, a calcium phosphate layer formed on the discs. Biomineralisation is therefore a potential route to production of precursor nanophase HA, which has the potential to improve strength. The scaffold material produced by this method could be used as a bone-filler or as an alternative method for coating implants with a layer of HA.
A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on ...Clostridium difficile infection (CDI) in adults. The update, which has incorporated recommendations for children (following the adult recommendations for epidemiology, diagnosis, and treatment), includes significant changes in the management of this infection and reflects the evolving controversy over best methods for diagnosis. Clostridium difficile remains the most important cause of healthcare-associated diarrhea and has become the most commonly identified cause of healthcare-associated infection in adults in the United States. Moreover, C. difficile has established itself as an important community pathogen. Although the prevalence of the epidemic and virulent ribotype 027 strain has declined markedly along with overall CDI rates in parts of Europe, it remains one of the most commonly identified strains in the United States where it causes a sizable minority of CDIs, especially healthcare-associated CDIs. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, infection prevention, and environmental management.
The herbicide glyphosate became widely used in the United States and other parts of the world after the commercialization of glyphosate-resistant crops. These crops have constitutive overexpression ...of a glyphosate-insensitive form of the herbicide target site gene, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). Increased use of glyphosate over multiple years imposes selective genetic pressure on weed populations. We investigated recently discovered glyphosate-resistant Amaranthus palmeri populations from Georgia, in comparison with normally sensitive populations. EPSPS enzyme activity from resistant and susceptible plants was equally inhibited by glyphosate, which led us to use quantitative PCR to measure relative copy numbers of the EPSPS gene. Genomes of resistant plants contained from 5-fold to more than 160-fold more copies of the EPSPS gene than did genomes of susceptible plants. Quantitative RT-PCR on cDNA revealed that EPSPS expression was positively correlated with genomic EPSPS relative copy number. Immunoblot analyses showed that increased EPSPS protein level also correlated with EPSPS genomic copy number. EPSPS gene amplification was heritable, correlated with resistance in pseudo-F₂ populations, and is proposed to be the molecular basis of glyphosate resistance. FISH revealed that EPSPS genes were present on every chromosome and, therefore, gene amplification was likely not caused by unequal chromosome crossing over. This occurrence of gene amplification as an herbicide resistance mechanism in a naturally occurring weed population is particularly significant because it could threaten the sustainable use of glyphosate-resistant crop technology.
Blocking Programmed Death-1 (PD-1) can reinvigorate exhausted CD8 Tcells (TEX) and improve control of chronic infections and cancer. However, whether blocking PD-1 can reprogram TEX into durable ...memory Tcells (TMEM) is unclear. We found that reinvigoration of TEX in mice by PD-L1 blockade caused minimal memory development. After blockade, reinvigorated TEX became reexhausted if antigen concentration remained high and failed to become TMEM upon antigen clearance. TEX acquired an epigenetic profile distinct from that of effector Tcells (TEFF) and TMEM cells that was minimally remodeled after PD-L1 blockade. This finding suggests that TEX are a distinct lineage of CD8 T cells. Nevertheless, PD-1 pathway blockade resulted in transcriptional rewiring and reengagement of effector circuitry in the TEX epigenetic landscape. These data indicate that epigenetic fate inflexibility may limit current immunotherapies.
3,5,3'-Tri-iodothyronine (T3), 1 alpha,25(OH)2-vitamin D3 (D3) and retinoids activate related nuclear receptors which interact by heterodimerisation to regulate gene expression. Actions of each ...hormone are discrete and may be specified by changes in the relative concentrations of their receptors (T3R, vitamin D receptor (VDR), retinoic acid receptor (RAR), retinoid X receptor (RXR)). T3, D3 and retinoids are essential for skeletal development and maintenance and we have previously shown complex interactions amongst their signalling pathways in osteosarcoma cells. In these studies we demonstrate that similar T3R, VDR, RAR and RXR proteins are co-expressed in both osteoblast lineage cell primary cultures and osteosarcoma cells by Western blotting. We investigated whether hormone interactions in bone result from changes in receptor stoichiometry. Cells were treated with combinations of T3, D3, 9-cis retinoic acid (9-cis RA) and all-trans retinoic acid (RA) that are known from previous studies to produce complex cell specific responses. No alteration in expression of any receptor protein was seen in response to any hormone combination in three phenotypically distinct osteosarcoma cell lines. Thus, in contrast to studies of overexpressed receptors in vitro, changes in the physiological concentrations of endogenous T3R, VDR, RAR and RXR do not specify discrete hormone actions in osteoblastic cells. Other unidentified factors are likely to modulate hormone action in these bone cells.
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