Sustaining global partnerships for simulation integration: lessons from the field.

AIM: A reciprocal partnership between two World Health Organization Collaborating Centers in the Americas region aimed to strengthen nursing and midwifery education through innovative integration of high-fidelity simulation. METHODS/IMPLEMENTATION: Immersion of a visiting scholar in six-week training within a North American nursing school (host) solidified simulation champion designation, upon return at the home institution. Next, two expert nursing faculty implemented a train-the-trainer simulation course on-site. Following evaluation and virtual debriefing, a midwifery faculty visited the host institution for second-round training. CONCLUSION: This ongoing program targets faculty development needs through a strong academic partnership, built upon global awareness and sustainable engagement.

Hearing Loss and Urinary trans,trans-Muconic Acid (t,t-MA) in 6- to 19-Year-Old Participants of NHANES 2017-March 2020.

Hearing loss (HL) is associated with poorer language development and school performance. Ototoxic substances such as metals and solvents, including benzene, are a risk factor associated with HL. This study examines potential associations between the benzene metabolite trans,trans-muconic acid (t,t-MA) and HL in youth of the National Health and Nutrition Examination Survey (NHANES). Logistic regression calculated adjusted odds ratio (aOR) associations between HL and urinary t,t-MA quartiles, natural-log transformed, and doubled urinary t,t-MA. Hearing threshold pure-tone average (PTA) at speech frequencies (SF) 0.5, 1, 2, and 4 kHz and high frequencies (HF) 3, 4, and 6 kHz were analyzed for slight HL (PTA > 15 dB) and mild HL (PTA > 20 dB). Urinary t,t-MA was statistically significantly associated with both slight SF and HF HL. For each doubling of t,t-MA there were increased odds of having slight SFHL (aOR = 1.42; 95% CI: 1.05, 1.92), slight HFHL (aOR = 1.31; 95% CI: 1.03, 1.66), mild SFHL (aOR = 1.60; 95% CI: 1.10, 2.32), and mild HFHL (aOR = 1.45; 95% CI: 1.03, 2.04). To our knowledge, this is the first population-based report of an association between SFHL, HFHL, and the benzene metabolite t,t-MA in youth 6 to 19 years old.

Continuous dental eruption identifies Sts 5 as the developmentally oldest fossil hominin and informs the taxonomy of Australopithecus africanus.

The relatively small Australopithecus africanus specimen Sts 5 has figured prominently in taxonomic debates, and the determination of this specimen as a young male or an elderly female has the potential to offer a great deal of resolution on this question. Sts 5 has been argued to be either a small, immature male or a mature female based on a variety of characters. A proposed model of continuous root remodeling and angular change for heavily worn dentition may account for the extremely short tooth roots, particularly for the anterior dentition, that Sts 5 demonstrates. The anterior tooth roots of Sts 5 are oriented vertically (relative to the alveolar plane), unlike those found in most other apes, humans, and fossil specimens, in which the tooth roots are roughly parallel with the plane of the nasoalveolar clivus. Computed tomography (CT) data of adult apes were examined and a relationship between the angle of the anterior tooth roots and their length was discovered, caused by heavily worn anterior dentition continuing to erupt to maintain occlusion. The extremely short and vertically oriented anterior roots observed in Sts 5 thus suggest that the specimen represents an aged female specimen with extremely worn dentition. Interestingly, this reorientation of anterior tooth roots helps account for the unusual nasoalveolar contour of Sts 5. The remodeling associated with the heavily worn teeth and reoriented roots thus resolves the taxonomic question raised by analyses identifying unusual prognathism of this small specimen.

The costs incurred by the NHS in England due to the unnecessary prescribing of dependency-forming medications.

This cross-sectional study estimates the costs incurred by the National Health Service (NHS) in England as a consequence of the unnecessary prescribing (i.e. non-indicated or dispensable) of dependency-forming medicines (antidepressants, opioids, gabapentinoids, benzodiazepines, Z-drugs). It assesses prescribing in primary care from April 2015-March 2018. Analyses were based upon the following data sets: the number of adults continuously prescribed dependency forming medications and the duration of prescriptions (obtained from Public Health England); the Net Ingredient Cost (NIC) and the dispensing costs for each medicine (obtained from the NHS Business Service Authority [NHSBSA]). Consultation costs were calculated based on guideline recommendations and the number of consultations evidenced in prior research for long-term medication monitoring. Across opioids, gabapentinoids, benzodiazepines, Z-drugs the total estimated unnecessary cost over three years (April 2015-March 2018) was £1,367,661,104 to £1,555,234,627. For antidepressants the total estimated unnecessary cost for one year was £37,321,783 to £45,765,504. The data indicate that the NHS in England may incur a significant estimated mean annual loss of £455,887,035 to £518,411,542 for opioids, gabapentinoids, benzodiazepines, Z-drugs and an estimated annual loss of £37,321,783 to £45,765,504 for antidepressants. Combined, this gives an estimated annual loss of £493,208,818 to £564,177,046 as a result of non-indicated or dispensable prescribing of dependency-forming medicines. Estimates are conservative and figures could be higher.

Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase.

The copper chaperone for the superoxide dismutase (CCS) gene is necessary for expression of an active, copper-bound form of superoxide dismutase (SOD1) in vivo in spite of the high affinity of SOD1 for copper (dissociation constant = 6 fM) and the high intracellular concentrations of both SOD1 (10 microM in yeast) and copper (70 microM in yeast). In vitro studies demonstrated that purified Cu(I)-yCCS protein is sufficient for direct copper activation of apo-ySOD1 but is necessary only when the concentration of free copper ions ([Cu]free) is strictly limited. Moreover, the physiological requirement for yCCS in vivo was readily bypassed by elevated copper concentrations and abrogation of intracellular copper-scavenging systems such as the metallothioneins. This metallochaperone protein activates the target enzyme through direct insertion of the copper cofactor and apparently functions to protect the metal ion from binding to intracellular copper scavengers. These results indicate that intracellular [Cu]free is limited to less than one free copper ion per cell and suggest that a pool of free copper ions is not used in physiological activation of metalloenzymes.

Debromination of polybrominated diphenyl ether-99 (BDE-99) in carp (Cyprinus carpio) microflora and microsomes.

Based on previous findings in dietary studies with carp (Cyprinus carpio), we investigated the mechanism of 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) debromination to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) using liver and intestinal components. In vitro aerobic and anaerobic experiments tested the ability of carp intestinal microflora to debrominate BDE-99. No debromination of BDE-99 to BDE-47 was observed in microfloral samples; therefore, carp enzymatic pathways were assessed for debromination ability. After sixty-min incubation, intestine and liver microsomes exhibited 83+/-34% and 106+/-18% conversions, respectively, of BDE-99 to BDE-47; with no significant (p>0.05) difference between organ debromination capabilities. Microsomal incubations with BDE-99, enzyme cofactors and competing substrates assessed the potential mechanisms of debromination. The presence of NADPH in the microsomal assay did not significantly (p>0.05) affect BDE-99 debromination, which suggest that cytochrome P450 enzymes are not the main debrominating pathway for BDE-99. Co-incubation of BDE-99 spiked microsomes with reverse thyronine (rT3) significantly (p<0.05) decreased the debromination capacity of intestinal microsomes indicating the potential of catalytic mediation via thyroid hormone deiodinases. The significant findings of this study are that intestinal microflora are not responsible for BDE-99 debromination, however, it is an endogenous process which occurs with approximately equal activity in intestine and liver microsomes and it can be inhibited by rT3.

The action of cobalt, nickel and chromium on phagocytosis and bacterial killing by human polymorphonuclear leucocytes; its relevance to infection after total joint arthroplasty.

Infection after total joint arthroplasty is a serious clinical complication. The accumulation of metallic wear and corrosion products may cause a localized reduction in the defense process, which may be particularly relevant in the cause of late infections. This hypothesis has been tested by exposing human polymorphonuclear leucocytes (PMN) in vitro to cobalt, nickel and chromium at various concentrations. The ability of PMNs to phagocytose and kill Staphylococcus epidermidis was measured. Nickel and cobalt reduced the number of bacteria phagocytosed by about 50% at a concentration of 0.05 and 0.01 mumol ml-1 respectively over an 18 h incubation period. Neither metal affected the rate at which S. epidermidis was killed. Chromium had no effect. All metals were used at sub-toxic levels.

The biological response to titanium and titanium-aluminium-vanadium alloy particles. II. Long-term animal studies.

The long-term tissue reactions to particulate titanium and titanium-aluminium-vanadium alloy were investigated by the intra-articular injection of material into the knee joints of mice. The tissue response was studied over a period of 2 to 52 weeks. In general, both materials were well tolerated, there was no evidence of necrosis and only a slight thickening of the synovium occurred around particles. Multinucleated giant cells were only rarely seen and no palpable tumours formed in any animal at any site.

The biological response to titanium and titanium-aluminium-vanadium alloy particles. I. Tissue culture studies.

One aspect of the biological response to titanium and titanium-aluminium-vanadium alloy was investigated by exposing primary cultures of human synovial fibroblasts and mouse peritoneal macrophages to particulate preparations of these materials. Both cell types appeared to be unaffected by either material as judged by microscopical examination. A small but significant release of lactate dehydrogenase was detected from both cell types in response to their exposure to the particulate material indicating that some cell damage occurred. Macrophages also exhibited a small release of the two lysosomal enzyme markers beta-glucuronidase and N-acetyl-beta-D-glucosaminidase. This indicates that these materials may have a mild inflammatory potential. No soluble metal could be shown to have dissolved from the particulate alloy or from pure titanium.

The intra-articular response to particulate carbon fibre reinforced high density polyethylene and its constituents: an experimental study in mice.

Carbon fibre reinforced high density polyethylene (CFRHDP) Meuller acetabular cups are available for total hip replacement. Despite the improved mechanical properties of CFRHDP over high density polyethylene (HDP) the wear characteristics of CFRHDP are a contentious issue. The biocompatibility of CFRHDP wear debris was investigated by intra-articular injection into mice and compared with that induced by HDP and carbon fibres. The response to CFRHDP was identical to that seen with HDP: the carbon fibre component did not appear to modify the response. From the biological point of view, therefore, the wear properties of CFRHDP must be better than those of HDP to offer a significant advantage.

Pelvic congestion in women: evaluation with transvaginal ultrasound and observation of venous pharmacology.

Fourteen women with chronic pelvic pain due to congestion underwent transvaginal ultrasound scanning to observe changes in the diameters of dilated pelvic veins. Spontaneous fluctuations were observed, and intravenous dihydroergotamine resulted in a consistent venoconstrictor response (p = 0.0021) during 20 min observation. Transvaginal ultrasound is useful for imaging dilated pelvic veins and for the study of venous pharmacology.

A study on the effects of particulate metals of orthopaedic interest on murine macrophages in vitro.

This is part of a larger study designed to investigate the action of particulate metals of orthopaedic interest on tissues. Damaging effects were determined by cytological examination and the assay of two enzymes. Lactic dehydrogenase (LDH) if released into the supernatant indicates a damaged cell membrane; decreased intracellular levels of glucose-6-phosphate dehydrogenase (G6PD) indicates a lowered phagocytic capacity of the cells. Soluble and wear products around implanted prostheses could facilitate late infections by impairing local reactions to bacteria. Particulate cobalt, nickel and cobalt-chromium alloy were found to damage the cells and to cause LDH release. G6PD was found to have a lower activity in the cells exposed to these materials. In contrast, titanium, chromium and molybdenum were well tolerated by macrophages and had no effect on the distribution and activity of either enzyme. The solubility of these metals in the culture medium was also measured.

The toxicity of metals used in orthopaedic prostheses. An experimental study using cultured human synovial fibroblasts.

Some of the component metals of the alloys used for total joint prostheses are toxic and dissolve in the body fluids. It is important to establish how toxic these metals are and to assess the risk of localised tissue necrosis around the prostheses. This has been investigated by incubating primary monolayer cultures of human synovial fibroblasts with various preparations of metals for periods up to 18 days. Morphological changes were evident after exposure to cobalt chloride at a concentration of 50 nanomoles per millilitre and to nickel chloride at 200 nanomoles per millilitre. Chromic chloride, ammonium molybdate and ferric chloride produced no changes up to 500 nanomoles per millilitre. Cultures exposed to particulate pure metals were poisoned by cobalt and vanadium but were not affected under the same conditions by nickel, chromium, molybdenum, titanium or aluminium. Particulate cobalt and vanadium were probably toxic due to their relatively high solubility (four and one micromoles per millilitre respectively after seven days incubation). Particulate nickel also dissolved (three nanomoles per millilitre after seven days) but not in sufficient quantities to be toxic. It appears, therefore, that potentially the most harmful components are cobalt from cobalt-chromium alloy, nickel from stainless steel, and vanadium from titanium alloy. As far as can be estimated, the only combination of materials which is likely to give rise to toxic levels of metal under clinical conditions, is cobalt-chromium alloy articulating against itself to produce relatively high levels of cobalt.

The influence of the surface energy and roughness of implants on bone resorption.

We investigated the possibility that the macrophages which are seen around implants may stimulate bone resorption and cause loosening. We found that macrophages release mediators that stimulate bone resorption, and that the amount of resorption increased by between 2.5 and 10 times when the macrophages adhered to a foreign surface. This bone resorption depended on the surface energy and roughness of the foreign surface, varying with these physical properties rather than with the chemical nature of the material. It is concluded that loosening of orthopaedic implants is likely to be influenced by the surface energy and roughness of the implant.

Carbon fibre composite bone plates. Development, evaluation and early clinical experience.

We compared the mechanical properties of carbon fibre composite bone plates with those of stainless steel and titanium. The composite plates have less stiffness with good fatigue properties. Tissue culture and small animal implantation confirmed the biocompatibility of the material. We also present a preliminary report on the use of the carbon fibre composite plates in 40 forearm fractures. All fractures united, 67% of them showing radiological remodelling within six months. There were no refractures or mechanical failures, but five fractures showed an unexpected reaction; this is discussed.

Influence of craniofacial morphology on primate paranasal pneumatization.

In order to test the hypothesis that variation in the maxillary sinus volume (MSV) of anthropoid primates is related to skull architecture, a mixed sex sample of adult primate crania covering Hominoidea, Cercopithecoidea and Ceboidea was examined using CT scans. MSV was regressed against basicranial length, using reduced major axis analysis. 2 distinct scaling patterns emerged: while a large MSV seems to be a primitive condition of Anthropoidea, it is clearly reduced in Cercopithecoidea. Although some correlations exist between MSV and different indices of the facial skeleton, they are relatively weak and differed among the 3 groups. A full appreciation of epigenetic factors and the relation of the paranasal sinuses to different cranial components is necessary to highlight the biological role of skull pneumatization.

The effect of starch glove powder on joint and other tissues.

The purpose of this research was to establish the possible role of starch glove powder in complications following orthopaedic surgery using in vivo and in vitro techniques. Exposure of primary mouse peritoneal macrophages to starch glove powder caused 10% release of prostaglandin E2 (0.1 mg/ml, 16 h) but no increased release of lactate dehydrogenase, demonstrating that cell integrity had not been compromised. Long-term tissue reaction to starch glove powder was investigated in vivo by injection into mouse knee joints. Over a period of 52 weeks no inflammatory response was elicited, no starch was observed in the regional lymph nodes and none was found in joints after the 8th week. Starch glove powder appeared to be innocuous in the joint and although prostaglandin E2 release was stimulated in vitro, this had no apparent effect on joints in vivo.

The haemolytic action of particulate metals (Cd, Cr, Co, Fe, Mo, Ni, Ta, Ti, Zn, Co-Cr alloy).

The haemolytic action of particulate cadmium, chromium, cobalt, iron, molybdenum, nickel, tantalum, titanium, zinc and cobalt-chromium alloy is described. Cobalt, nickel and cobalt-chromium alloy were found to be the most active and were also the most toxic for other cells in tissue culture. In contrast the other particulate metals produced only low levels of haemolysis and in general, were well tolerated by cells in culture. A dual effect of particulate metals is described due firstly to a direct interaction between the particle surface and cell membrane and secondly to the possible toxic effects of dissolved metal.

Tolerance of mouse macrophages in vitro to barium sulfate used in orthopedic bone cement.

Barium sulfate, used as a radio-opaque marker in some orthopedic bone cements, has been shown to escape into the surrounding tissues. This may present a potential hazard. In particular, phagocytic cells may be exposed to relatively high internal levels of barium once the particles have been phagocytosed. Mouse peritoneal macrophages exposed to barium sulfate for periods up to 144 hr showed a marked cytoplasmic vacuolization from which they recovered only partially. Barium sulfate did not appear to damage the cell membrane as judged by lactice dehydrogenase release. In the relatively low doses and with the periods of exposure described here, barium sulfate does not appear to present a serious toxic hazard in the short term. It is possible, however, that longer exposures and larger doses may result in the death of phagocytic cells which have ingested barium sulfate.

Mosaic evolution in the origin of the Hominoidea.

The initial appearance of hominoids, or apes, and the selective pressures that led to their emergence are currently disputed. Central to the argument are the proconsulids, variously described as the earliest apes or as stem catarrhines, based on facial and postcranial data, respectively. The present paper reports on incongruence and parsimony analyses applied to a combined data set. The results demonstrate that proconsulids are cladistic hominoids, and that the apparent incongruence between the data sets is due to mosaic evolution; the earliest changes in Hominoidea occurred in the face. These results suggest that the initial divergence of hominoids involved selection for an ape-like face, and was not driven by an adaptive shift to below-branch locomotion.