Failure of non-vacuum steam sterilization processes for dental handpieces

Background: Dental handpieces are used in critical and semi-critical operative interventions. Although a number of dental professional bodies recommend that dental handpieces are sterilized between patient use there is a lack of clarity and understanding of the effectiveness of different steam sterilization processes. The internal mechanisms of dental handpieces contain narrow lumens (0·8-2·3mm) which can impede the removal of air and ingress of saturated steam required to achieve sterilization conditions. Aim: To identify the extent of sterilization failure in dental handpieces using a non-vacuum process. Methods: In-vitro and in-vivo investigations were conducted on commonly used UK benchtop steam sterilizers and three different types of dental handpieces. The sterilization process was monitored inside the lumens of dental handpieces using thermometric (TM) methods (dataloggers), chemical indicators (CI) and biological indicators (BI). Findings: All three methods of assessing achievement of sterility within dental handpieces that had been exposed to non-vacuum sterilization conditions demonstrated a significant number of failures (CI=8/3,024(fails/n tests); BI=15/3,024; TM=56/56) compared to vacuum sterilization conditions (CI=2/1,944; BI=0/1,944; TM=0/36). The dental handpiece most likely to fail sterilization in the non-vacuum process was the surgical handpiece. Non-vacuum sterilizers located in general dental practice had a higher rate of sterilization failure (CI=25/1,620; BI=32/1,620; TM=56/56) with no failures in vacuum process. Conclusion: Non-vacuum downward/gravity displacement, type-N steam sterilizers are an unreliable method for sterilization of dental handpieces in general dental practice. The handpiece most likely to fail sterilization is the type most frequently used for surgical interventions

Investigating steam penetration using thermometric methods in dental handpieces with narrow internal lumens during sterilizing processes with non-vacuum or vacuum processes

Background: Dental handpieces are required to be sterilized between patient use. Vacuum steam sterilization processes with fractionated pre/post-vacuum phases or unique cycles for specified medical devices, are required for hollow instruments with internal lumens to assure successful air removal. Entrapped air will compromise achievement of required sterilization conditions. Many countries and professional organisations still advocate non-vacuum sterilization processes for these devices. Aim: To investigate non-vacuum downward/gravity displacement, type-N steam sterilization of dental handpieces, using thermometric methods to measure time to achieve sterilization temperature at different handpiece locations. Methods: Measurements at different positions within air turbines were undertaken with thermocouples and dataloggers. Two examples of commonly used UK benchtop steam sterilizers were tested; a non-vacuum benchtop sterilizer (Little Sister 3, Eschmann, UK) and a vacuum benchtop sterilizer (Lisa, W&H, Austria). Each sterilizer cycle was completed with three handpieces and each cycle in triplicate. Findings: A total of 140 measurements inside dental handpiece lumens were recorded. We demonstrate that the non-vacuum process fails (time range 0-150 seconds) to reliably achieve sterilization temperatures within the time limit specified by the International standard (15 seconds equilibration time). The measurement point at the base of the handpiece failed in all test runs (n=9) to meet the standard. No failures were detected with the vacuum steam sterilization type B process with fractionated pre-vacuum and post-vacuum phases. Conclusion: Non-vacuum downward/gravity displacement, type-N steam sterilization processes are unreliable in achieving sterilization conditions inside dental handpieces and the base of the handpiece is the site most likely to fail

Aspergillus fumigatus enhances elastase production in pseudomonas aeruginosaco-cultures

In the cystic fibrosis (CF) lung the presence of bacteria and fungi in the airways promotes an inflammatory response causing progressive lung damage, ultimately leading to high rates of morbidity and mortality. We hypothesized that polymicrobial interactions play an important role in promoting airway pathogenesis. We therefore examined the interplay between the most commonly isolated bacterial CF pathogen, Pseudomonas aeruginosa, and the most prevalent filamentous fungi, Aspergillus fumigatus, to test this. Co-culture experiments showed that in the presence of A. fumigatus the production of P. aeruginosa elastase was enhanced. This was confirmed by the presence of zones of clearance on Elastin-Congo Red (ECR) agar, which was identified as elastase by mass spectrometry. When P. aeruginosa were grown in a co-culture model with mature A. fumigatus biofilms, 60% of isolates produced significantly more elastase in the presence of the filamentous fungi than in its absence (P < .05). The expression of lasB also increased when P. aeruginosa isolates PA01 and PA14 were grown in co-culture with A. fumigatus. Supernatants from co-culture experiments were also significantly toxic to a human lung epithelial cell line (19–38% cell cytotoxicity) in comparison to supernatants from P. aeruginosa only cultures (P < .0001). Here we report that P. aeruginosa cytotoxic elastase is enhanced in the presence of the filamentous fungi A. fumigatus, suggesting that this may have a role to play in the damaging pathology associated with the lung tissue in this disease. This indicates that patients who have a co-colonisation with these two organisms may have a poorer prognosis

HOX GENES: Seductive Science, Mysterious Mechanisms

HOX genes are evolutionarily highly conserved. The HOX proteins which they encode are master regulators of embryonic development and continue to be expressed throughout postnatal life. The 39 human HOX genes are located in four clusters (A-D) on different chromosomes at 7p15, 17q21.2, 12q13, and 2q31 respectively and are assumed to have arisen by duplication and divergence from a primordial homeobox gene. Disorders of limb formation, such as hand-foot-genital syndrome, have been traced to mutations in HOXA13 and HOXD13. Evolutionary conservation provides unlimited scope for experimental investigation of the functional control of the Hox gene network which is providing important insights into human disease. Chromosomal translocations involving the MLL gene, the human homologue of the Drosophila gene trithorax, create fusion genes which exhibit gain of function and are associated with aggressive leukaemias in both adults and children. To date 39 partner genes for MLL have been cloned from patients with leukaemia. Models based on specific translocations of MLL and individual HOX genes are now the subject of intense research aimed at understanding the molecular programs involved, and ultimately the design of chemotherapeutic agents for leukaemia. Investigation of the role of HOX genes in cancer has led to the concept that oncology may recapitulate ontology, a challenging postulate for experimentalists in view of the functional redundancy implicit in the HOX gene network

Photocatalytic reactions of a nickel(II) annulene complex incorporated in polymeric structures

The photochemical reactions of the Ni(II) annulene complex, [NiII([5,7,12,14]-tetra methyl dibenzo[2,3- b:2,3-b,i][1,4,8,11]tetraaza[14]annulenate)], grafted into a poly(isobutylene-alt-maleate) backbone were investigated in aqueous media. The grafted Ni(II) complex becomes soluble in aqueous and organic solvents where the strands form aggregates with medium-dependent shapes. Irradiation of the polymer at 532 or 351 nm produce charge-separated macrocyclic pendants, CS, with a lifetime s 30 ns. CS reacts with electron donors and acceptors before it decays with a lifetime s 1 ms. In parallel to the decay of CS, an excited state-excited state annihilation process gives rise to luminescence whose spectrum spans wavelengths shorter than the wavelength of the irradiation, lex > 500 nm. Theoretical calculations were carried out with the aim of understanding the morphology and structures of strand aggregates, to confirm the nature of reaction products and to account for the spectroscopic and photochemical properties of the Ni(II) pendants. The endothermic reduction of CO2 to CO by S(IV) species was used as a test of the Ni(II) complex´s ability to photocatalyze the reaction. In the photoprocess, the Ni(II) complex fulfills the double role of antenna and catalyst.Fil: Estiu, G.. University Of Notre Dame-indiana; Estados UnidosFil: Ferraudi, G.. University Of Notre Dame-indiana; Estados UnidosFil: Lappin, A. G.. University Of Notre Dame-indiana; Estados UnidosFil: Ruiz, Gustavo Teodosio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina. Universidad Nacional de La Plata; ArgentinaFil: Vericat, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina. Universidad Nacional de La Plata; ArgentinaFil: Costamagna, J.. Universidad de Santiago de Chile; ChileFil: Villagrán, M.. Universidad de Santiago de Chile; Chil

GPR35 as a Novel Therapeutic Target

G protein-coupled receptors (GPCRs) remain the best studied class of cell surface receptors and the most tractable family of proteins for novel small molecule drug discovery. Despite this, a considerable number of GPCRs remain poorly characterized and in a significant number of cases, endogenous ligand(s) that activate them remain undefined or are of questionable physiological relevance. GPR35 was initially discovered over a decade ago but has remained an “orphan” receptor. Recent publications have highlighted novel ligands, both endogenously produced and synthetic, which demonstrate significant potency at this receptor. Furthermore, evidence is accumulating which highlights potential roles for GPR35 in disease and therefore, efforts to characterize GPR35 more fully and develop it as a novel therapeutic target in conditions that range from diabetes and hypertension to asthma are increasing. Recently identified ligands have shown marked species selective properties, indicating major challenges for future drug development. As we begin to understand these issues, the continuing efforts to identify novel agonist and antagonist ligands for GPR35 will help to decipher its true physiological relevance; translating multiple assay systems in vitro, to animal disease systems in vivo and finally to man

Photophysical properties of [(norharmane)Re(CO)3 (L)]+ complexes (L = bpy, phen or dppz). Redox behavior of the excited states and their interaction with Calf Thymus DNA

The photochemical and photophysical properties of [(nHo)Re(CO)3(L)]+ complexes, where nHo = 9H-pyrido[3,4-b]indole and L = 2,2′ bipyridine (bpy), 1,10 phenantroline (phen) or dipyridil[3,2-a:2′3′-c]phenazine (dppz) were investigated by Laser Flash Photolysis (LFF) and Pulse Radiolysis (PR) techniques. While complexes with L = bpy or phen show absorption transients compatible with MLCTRe→L excited states, [(nHo)Re(CO)3(dppz)]+ showed an excited state assignable to a dppz-centered, 3ππ*dppz. In aqueous solutions, the last complex does not generate any absorption transient. However, when Calf thymus DNA was added, the same absorption spectrum was obtained. These results suggest that this complex can intercalate into DNA. The species generated in either reductive or oxidative conditions in LFF experiments were compared with those obtained in PR. Also, the quenching rate constants (kq) of the excited states with MV2+ were calculated. The intercalation of the [(nHo)Re(CO)3(dppz)]+ into DNA, increases kq ∼100 times. This result is rationalized in terms of the conditions created by the intercalation using the biopolymer as a well-organized matrix.Fil: Maisuls, Iván. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Cabrerizo, Franco Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Lappin, Alexander G.. University of Notre Dame-Indiana; Estados UnidosFil: Ruiz, Gustavo Teodosio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Ferraudi, Guillermo J.. University of Notre Dame-Indiana; Estados Unido

Prevalence and Characteristics Associated with Chronic Noncancer Pain in Suicide Decedents: A National Study

Objective: The aims were to estimate the prevalence of CNCP in suicide decedents, and compare sociodemographic and clinical characteristics of people who die by suicide (i) with and without a history of CNCP and (ii) among decedents with CNCP who are younger (<65 years) and older (65 + years). Method: We examined all closed cases of intentional deaths in Australia in 2014, utilizing the National Coronial Information System. Results: We identified 2,590 closed cases of intentional deaths in Australia in 2014 in decedents over 18 years of age. CNCP was identified in 14.6% of cases. Decedents with CNCP were more likely to be older, have more mental health and physical health problems, and fewer relationship problems, and were more likely to die by poisoning from drugs, compared with decedents without CNCP. Comparisons of older and younger decedents with CNCP found that compared to younger (<65 years) decedents with CNCP, older decedents (65 + years) were less likely to have mental health problems. Conclusions: This is the first national study to examine the characteristics of suicide deaths with a focus on people with CNCP. Primary care physicians should be aware of the increased risk for suicide in people living with CNCP, and it may be useful for clinicians to screen for CNCP among those presenting with suicidal behaviors

Microdosing and other phase 0 clinical trials: facilitating translation in Drug Development

Increasing costs of drug development and ethical concernsabout the risks of exposing humans and animals to novelchemical entities favor limited exposure clinical trials suchas microdosing and other phase 0 trials. An increasing bodyof research supports the validity of extrapolation from thelimited drug exposure of phase 0 approaches to the full,therapeutic exposure. An increasing number of applicationsand design options demonstrate the versatility and exibilitythese approaches offer to drug developers

Development of an in vitro periodontal biofilm model for assessing antimicrobial and host modulatory effects of bioactive molecules

Background: Inflammation within the oral cavity occurs due to dysregulation between microbial biofilms and the host response. Understanding how different oral hygiene products influence inflammatory properties is important for the development of new products. Therefore, creation of a robust host-pathogen biofilm platform capable of evaluating novel oral healthcare compounds is an attractive option. We therefore devised a multi-species biofilm co-culture model to evaluate the naturally derived polyphenol resveratrol (RSV) and gold standard chlorhexidine (CHX) with respect to anti-biofilm and anti-inflammatory properties.&lt;p&gt;&lt;/p&gt; Methods: An in vitro multi-species biofilm containing &lt;i&gt;S. mitis, F. nucleatum, P. Gingivalis&lt;/i&gt; and &lt;i&gt;A. Actinomycetemcomitans&lt;/i&gt; was created to represent a disease-associated biofilm and the oral epithelial cell in OKF6-TERT2. Cytotoxicity studies were performed using RSV and CHX. Multi-species biofilms were either treated with either molecule, or alternatively epithelial cells were treated with these prior to biofilm co-culture. Biofilm composition was evaluated and inflammatory responses quantified at a transcriptional and protein level.&lt;p&gt;&lt;/p&gt; Results: CHX was toxic to epithelial cells and multi-species biofilms at concentrations ranging from 0.01-0.2%. RSV did not effect multi-species biofilm composition, but was toxic to epithelial cells at concentrations greater than 0.01%. In co-culture, CHX-treated biofilms resulted in down regulation of the inflammatory chemokine IL-8 at both mRNA and protein level. RSV-treated epithelial cells in co-culture were down-regulated in the release of IL-8 protein, but not mRNA.&lt;p&gt;&lt;/p&gt; Conclusions: CHX possesses potent bactericidal properties, which may impact downstream inflammatory mediators. RSV does not appear to have bactericidal properties against multi-species biofilms, however it did appear to supress epithelial cells from releasing inflammatory mediators. This study demonstrates the potential to understand the mechanisms by which different oral hygiene products may influence gingival inflammation, thereby validating the use of a biofilm co-culture model.&lt;p&gt;&lt;/p&gt