Ultraclean air systems and the claim that laminar airflow systems fail to prevent deep infections after total joint arthroplasty.

The World Health Organization published guidelines in 2016 for preventing surgical site infections. The guidelines contained a conditional recommendation that laminar airflow (LAF) ventilation systems should not be used to reduce the risk of infection after total joint arthroplasty (TJA). This recommendation was largely based on a systematic review and meta-analysis of information from hospital infection surveillance registries. The recommendation contradicts information published in earlier major studies carried out by Charnley and the UK Medical Research Council (MRC). The first aim of this article is to revisit and explain the MRC study, and reply to criticisms of it. The second aim is to suggest reasons why some recent studies have failed to demonstrate that ultraclean air (UCA) systems reduce deep joint infection after TJA. It demonstrates that if a UCA system establishes average airborne concentrations of microbe-carrying particles (MCPs) <10/m3, and preferably <1/m3, then deep joint infection after TJA will be lower than in conventionally ventilated operating theatres.

An actuatable soft reservoir modulates host foreign body response.

The performance of indwelling medical devices that depend on an interface with soft tissue is plagued by complex, unpredictable foreign body responses. Such devices-including breast implants, biosensors, and drug delivery devices-are often subject to a collection of biological host responses, including fibrosis, which can impair device functionality. This work describes a milliscale dynamic soft reservoir (DSR) that actively modulates the biomechanics of the biotic-abiotic interface by altering strain, fluid flow, and cellular activity in the peri-implant tissue. We performed cyclical actuation of the DSR in a preclinical rodent model. Evaluation of the resulting host response showed a significant reduction in fibrous capsule thickness (P = 0.0005) in the actuated DSR compared with non-actuated controls, whereas the collagen density and orientation were not changed. We also show a significant reduction in myofibroblasts (P = 0.0036) in the actuated group and propose that actuation-mediated strain reduces differentiation and proliferation of myofibroblasts and therefore extracellular matrix production. Computational models quantified the effect of actuation on the reservoir and surrounding fluid. By adding a porous membrane and a therapy reservoir to the DSR, we demonstrate that, with actuation, we could (i) increase transport of a therapy analog and (ii) enhance pharmacokinetics and time to functional effect of an inotropic agent. The dynamic reservoirs presented here may act as a versatile tool to further understand, and ultimately to ameliorate, the host response to implantable biomaterials.

Tough adhesives for diverse wet surfaces.

Adhesion to wet and dynamic surfaces, including biological tissues, is important in many fields but has proven to be extremely challenging. Existing adhesives are cytotoxic, adhere weakly to tissues, or cannot be used in wet environments. We report a bioinspired design for adhesives consisting of two layers: an adhesive surface and a dissipative matrix. The former adheres to the substrate by electrostatic interactions, covalent bonds, and physical interpenetration. The latter amplifies energy dissipation through hysteresis. The two layers synergistically lead to higher adhesion energies on wet surfaces as compared with those of existing adhesives. Adhesion occurs within minutes, independent of blood exposure and compatible with in vivo dynamic movements. This family of adhesives may be useful in many areas of application, including tissue adhesives, wound dressings, and tissue repair.

Use of a real-time microbial air sampler for operational cleanroom monitoring.

A sampler that detects and counts viable particles in the air of cleanrooms in real-time was studied. It was found that when the sampler was used to monitor airborne particles dispersed from a number of materials used in cleanrooms, including garments, gloves, and skin, the number of viable particles dispersed from these materials was greater than anticipated. It was concluded that a substantial proportion of these viables were of a non-microbiological origin. When the sampler was used to monitor a non-unidirectional airflow cleanroom occupied by personnel wearing cleanroom garments, it was found that the airborne viable concentrations were unrealistically high and variable in comparison to microbe-carrying particles simultaneously measured with efficient microbial air samplers. These results confirmed previously reported ones obtained from a different real-time sampler. When the real-time sampler was used in a workstation within the same cleanroom, the recorded viables gave results that suggest that the sampler may provide an effective airborne monitoring method, but more investigations are required. LAY ABSTRACT: The airborne concentrations measured by a real-time microbial air sampler within an operational, non-unidirectional airflow cleanroom were found to be unrealistically high due to a substantial numbers of particles of non-microbiological origin. These particles, which resulted in false-positive microbial counts, were found to be associated with a number of materials used in cleanrooms. When the sampler was used within a cleanroom workstation, the counts appeared to be more realistic and suggest that this type of real-time airborne microbial counter may provide a useful monitoring method in such workstations, but further investigations are required.

Sacroiliac joint syndrome.

The sacroiliac joint has long been considered to be a potential source of low back and/or buttock pain with or without lower extremity symptoms. Until recently, supportive evidence for this disorder has been empirical as it was solely derived from information garnered from patients who obtained successful treatment for a constellation of signs, symptoms and examination findings believed to be indicative of sacroiliac joint syndrome. Due to this fallacious reasoning, successful treatment denotes a correct diagnosis; many of the concepts espoused during the past few decades have been predicated upon spurious data. With the advent of and systematic utilization of fluoroscopically guided diagnostic sacroiliac joint blockade specific epidemiologic, symptomatic, examination, diagnostic, and outcome data have been derived. This review describes current concepts and provides information that expounds and, in some instances, supplants prior held notions about this disorder.

Isolators and barrier devices in pharmaceutical manufacturing.

The use of isolators and barrier technology in pharmaceutical manufacturing may cause design problems, some of them unrecognised. These design problems are highlighted in this paper and, where possible, solutions are given.

Airborne contamination during blow-fill-seal pharmaceutical production.

The routes of airborne contamination, during Blow-Fill-Seal (BFS) production, were studied using tracer gas, particles and bacteria. The prevention of airborne contamination, by the air shower at the point of fill, was effective (> 99.2% efficient). However, microbe-carrying particles could gain access, by deposition or air exchange, when the containers were cut open and before they shuttled under the protection of the air shower. The use of SF6 tracer gas demonstrated that when the air shower was not on, 50% of the air within the containers came from the area round the machine. When the air shower was switched on, only about 5% of the air came from the surroundings. Airborne microbial contamination of containers is in proportion to: the number of airborne microbes around the machine, the time the container is open, the neck area and the amount of air left within the container. The likely microbial contamination rate can be calculated from a model incorporating these variables. Microbial contamination of containers during BFS manufacturing is normally very low, but by increasing the naturally occurring bacteria in the air of the production rooms by about 100-fold, it was possible to verify the accuracy of this model. The contamination model agrees well with the observation that microbial contamination levels of between 1 in 10(5) and in 10(7) will be found when small containers (< 10 ml) are filled in conventionally ventilated rooms. To achieve similar contamination rates when filling of larger bottles, it is likely that unidirectional flow, or barrier technology will be required.

Ischemic preconditioning.

It has been shown that repeated brief coronary occlusions increase myocardial resistance towards prolonged episodes of ischemia. This phenomenon, which renders the heart more tolerant to ischemia with subsequent limitation of infarct size, has been termed ischemic preconditioning and has been described in a variety of species. Preconditioning may also protect the heart against postischemic dysfunction and ventricular arrhythmias. Although the beneficial effects seem to be transient, they re-appear at 24 hours, representing a "second window of protection." Ischemia-induced activation of adenosine receptors and opening of ATP-sensitive potassium channels appear to play a role in the acute cardioprotection. For the late protection, stress protein synthesis may play a role. There is experimental and clinical evidence that preconditioning effects may also exist in the human heart. If so, the mechanisms of ischemic preconditioning might be applied to future therapy.

In support of settle plates.

During pharmaceutical production the quality of the air in manufacturing areas is monitored by volumetric samplers and settle plates. Settle plates are often assigned a secondary role, their usefulness in predicting airborne contamination of containers not being fully recognised. In this paper criticisms of settle plates are answered and the advantages of settle plates explained. It is concluded that using settle plates is the best method of quantifying the likely airborne microbial contamination of containers filled in pharmaceutical production areas.

The genetic analysis of achiasmate segregation in Drosophila melanogaster. III. The wild-type product of the Axs gene is required for the meiotic segregation of achiasmate homologs.

The regular segregation of achiasmate chromosomes in Drosophila melanogaster females is ensured by two distinct segregational systems. The segregation of achiasmate homologs is assured by the maintenance of heterochromatic pairing; while the segregation of heterologous chromosomes is ensured by a separate mechanism that may not require physical association. AxsD (Aberrant X segregation) is a dominant mutation that specifically impairs the segregation of achiasmate homologs; heterologous achiasmate segregations are not affected. As a result, achiasmate homologs frequently participate in heterologous segregations at meiosis I. We report the isolation of two intragenic revertants of the AxsD mutation (Axsr2 and Axsr3) that exhibit a recessive meiotic phenotype identical to that observed in AxsD/AxsD females. A third revertant (Axsr1) exhibits no meiotic phenotype as a homozygote, but a meiotic defect is observed in Axsr1/Axsr2 females. Therefore mutations at the AxsD locus define a gene necessary and specific for homologous achiasmate segregation during meiosis. We also characterize the interactions of mutations at the Axs locus with two other meiotic mutations (ald and ncd). Finally, we propose a model in which Axs+ is required for the normal separation of paired achiasmate homologs. In the absence of Axs+ function, the homologs are often unable to separate from each other and behave as a single segregational unit that is free to segregate from heterologous chromosomes.

The relative importance of the routes and sources of wound contamination during general surgery. II. Airborne.

The influence of airborne bacteria on wound contamination during biliary surgery was studied. When bacteria grew in the bile they accounted for most of the bacteria in the wound but when the wounds were free of bile bacteria many of the bacteria came from the patient's skin. It was only in wounds with little contamination from non-airborne routes that it was possible to demonstrate an effect of airborne contamination. In such a situation it was estimated that a reduction in the airborne bacteria in the operating room of about 13-fold would reduce the wound contamination by about 50%. The contamination of patient drapes from various sources and its relationship to wound contamination was studied. It was demonstrated that in areas away from the wound, the bacterial concentration on the drape surface was significantly affected only by airborne bacteria. In the area close to the wound, airborne bacteria and bacteria from the wound significantly affected drape contamination. However, it was found that more bacteria transferred from the wound to the drape surface than vice versa. Punctured gloves, impervious gowns and the number of bacteria on the patient's skin did not significantly affect the counts on the drapes' surfaces.

The relative importance of routes and sources of wound contamination during general surgery. I. Non-airborne.

A study was undertaken to determine the relative importance of some sources, routes of transmission, and measures to prevent bacteria entering the wound during biliary tract surgery. When bacteria were growing in the bile they accounted for the majority (greater than 99%) of the bacteria found in the wound. However, when the bile was sterile the skin bacteria at the incision site were found to make a substantial contribution to the wound flora. The difference in the total wound contamination between a patient who had practically no skin bacteria and one who had an average amount was in the region of 17-fold. No transfer of skin bacteria from the surgical team through perforated gloves or by direct contact from the surface of operating gowns was demonstrated. Ten of the patients studied had septic wounds. Five of these were infected by bacteria from the bile.

Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: isolation, characterization and regulation of the SPO7 sporulation gene.

SPO7 is one of several previously identified genes from the yeast Saccharomyces cerevisiae that is required for sporulation but not for vegetative growth. The SPO7 gene has been cloned by functional complementation and physically mapped 15-16 kb to the left of CEN1. Gene-disruption experiments confirmed that the cloned gene was the bona fide SPO7 gene. SPO7 codes for a 0.95-kb transcript that is expressed at approximately the same level in both vegetative and sporulating cells. The gene was sequenced and has the capacity to encode a 259-amino acid protein that does not appear to be related to other known proteins.

Skin sampling-validation of a pad method and comparison with commonly used methods.

Two types of pad were tested for sampling bacteria from the skin. One pad was made of 85% viscose and a 15% mixture of polyester and polyamide fibres, the other was made of polyvinyl-alcohol foam. The efficiency was calculated using double samples and 8 consecutive samples. The two pads were equally efficient and more efficient when moist. Their efficiency was compared with that of the bud swab, the Rodac plate and the scrub cylinder method. Using the double sample method for calculation, the scrub cylinder method and the pads were equally efficient, around 50%. As calculated from consecutive samples the efficiency of the pads was about 45%, the efficiency of the cylinder scrub method 29%, and that of the bud swab and Rodac plate 16% and 5% respectively. The low efficiency of the Rodac plate may be partly explained by the fact that microcolonies and not bacterial cells are sampled with this method.

An investigation of occlusive polyester surgical clothing.

The bacterial dispersion rate of people wearing operating room clothing made from several types of polyester fabric was compared to conventional cotton clothing, total-body exhaust gowns and disposable clothing. Airborne bacteria were measured in a chamber, three ultra-clean air operating rooms and a conventionally ventilated operating room. The polyester clothing was demonstrated to be much superior to conventional cotton clothing and at least as good as the total-body exhaust gowns and disposable clothing.

Biliary tract surgery: a bacteriologic and epidemiologic study.

The sources and routes of postoperative wound infections were prospectively studied in 440 patients undergoing biliary tract surgery. The overall infection rate was 7.3%. Specimens for culture were taken peroperatively from bile, liver bed and subcutaneous fat in 402 patients and also from skin in 64. Of the 126 patients with positive bile culture (31%), all but one had bacteria in the other intraoperative cultures, with high counts of bile bacteria in liver bed and transfer of such bacteria to subcutaneous fat in 81.2%. The wound infection rate in this group was 12.8%. Of the 276 patients with sterile bile, more than 90% had bacteria in the other intraoperative cultures. The degree of contamination was low, with dominance of typical skin bacteria, and the group wound infection rate was 3.2%. In 19 postoperative wound infections intraoperative cultures were available for comparison. Eleven of these infections were classified as endogenous, six as exogenous and two as of uncertain origin. S. aureus was uncommon in bile and intraoperative wound cultures, but was almost as common as E. coli in the etiology of postoperative wound infections, indicating high pathogenicity.

Continuous stressing of mouse interparietal suture fibroblasts in vitro.

The morphological and biochemical response of sutural fibroblasts in vitro to continuous force was examined. Cells from mouse interparietal sutures were grown and subcultured on glass slides. Titanium disks coated with collagen were allowed to attach to the cellular multilayers. Four of the glass slides were then placed at an angle of 75 degrees for a period of three days so that continuous stress would be created, while four others were left flat. Also, four glass slides were left flat with no disk. Following the incubation period, the dishes were labeled with 14C-glycine for 15 h. The cells and medium were then collected for collagen extraction followed by SDS-polyacrylamide gel electrophoresis. Dried gels impregnated with fluor were exposed to x-ray films that were then scanned densitometrically for collagen types I and III. It was found that the proportion of newly-synthesized type III collagen increased significantly with the application of continuous stress. A second set of experimental and control glass slides was fixed in glutaraldehyde and post-fixed in osmium tetroxide. Following critical-point drying and coating, the glass slides were examined under a scanning electron microscope. The scanning images showed the formation of a ligament-like structure between the disk and the glass slide. Moreover, mitotic activity, as evidenced by spheroidal cells, was stimulated in the areas previously adjacent to the disc, which had since moved away. This system offers a standardized continuous force system that can stress cells in a ligament-like structure and thus provides an in vitro model analogous to clinical orthodontic and orthopedic stress.