Real time monitoring of screw insertion using acoustic emission can predict screw stripping in human cancellous bone.

BACKGROUND: To develop experience, orthopaedic surgeons train their own proprioception to detect torque during screw insertion. This experience is acquired over time and when implanting conventional/non-locked screws in osteopenic cancellous bone the experienced surgeon still strips between 38 and 45%. Technology needs to be investigated to reduce stripping rates. Acoustic-Emission technology has the ability to detect stress wave energy transmitted through a screw during insertion into synthetic bone. Our hypothesis is Acoustic-Emission waves can be detected through standard orthopaedic screwdrivers while advancing screws through purchase and overtightening in cancellous human bone with different bone mineral densities replicating the clinical state. METHODS: 77 non-locking 4 mm and 6.5 mm diameter cancellous bone screws were inserted through to stripping into the lateral condylar area of 6 pairs of embalmed distal femurs. Specimens had varying degrees of bone mineral density determined by quantitative CT. Acoustic-Emission energy and axial force were detected for each test. RESULTS: The tests showed a significant high correlation between bone mineral density and Acoustic-Emission energy with R = 0.74. A linear regression model with the mean stripping load as the dependent variable and mean Acoustic-Emission energy, bone mineral densities and screw size as the independent variables resulted in r2 = 0.94. INTERPRETATION: This experiment succeeded in testing real time Acoustic-Emission monitoring of screw purchase and overtightening in human bone. Acoustic-Emission energy and axial compressive force have positive high correlation to bone mineral density. The purpose is to develop a known technology and apply it to improve the bone-metal construct strength by reducing human error of screw overtightening.

Erratum to: Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

[This corrects the article DOI: 10.1186/s13017-016-0089-y.].

Calorie restriction increases lipopolysaccharide-induced neuropeptide Y immunolabeling and reduces microglial cell area in the arcuate hypothalamic nucleus.

Calorie restriction (CR) increases longevity and elicits many health promoting benefits including delaying immunosenescence and reducing the incidence of age-related diseases. Although the mechanisms underlying the health-enhancing effects of CR are not known, a likely contributing factor is alterations in immune system functioning. CR suppresses lipopolysaccharide (LPS)-induced release of pro-inflammatory cytokines, blocks LPS-induced fever, and shifts hypothalamic signaling pathways to an anti-inflammatory bias. Furthermore, we have recently shown that CR attenuates LPS-stimulated microglial activation in the hypothalamic arcuate nucleus (ARC), a brain region containing neurons that synthesize neuropeptide Y (NPY), an orexigenic neuropeptide that is upregulated by a CR diet and has anti-inflammatory properties. To determine if increased NPY expression in the ARC following CR was associated with changes in microglial activation, a set of brain sections from mice that were exposed to 50% CR or ad libitum feeding for 28 days before being injected with LPS were immunostained for NPY. The density of NPY-immunolabeling was assessed across the rostrocaudal extent of the ARC and hypothalamic paraventricular nucleus (PVN). An adjacent set of sections were immunostained for ionized calcium-binding adapter molecule-1 (Iba1) and immunostained microglia in the ARC were digitally reconstructed to investigate the effects of CR on microglial morphology. We demonstrated that exposure to CR increased NPY expression in the ARC, but not the PVN. Digital reconstruction of microglia revealed that LPS increased Iba1 intensity in ad libitum fed mice but had no effect on Iba1 intensity in CR mice. CR also decreased the size of ARC microglial cells following LPS. Correlational analyses revealed strong associations between NPY and body temperature, and body temperature and microglia area. Together these results suggest that CR-induced changes in NPY are not directly involved in the suppression of LPS-induced microglial activation, however, NPY may indirectly affect microglial morphology through changes in body temperature.

Whole-genome sequencing of bladder cancers reveals somatic CDKN1A mutations and clinicopathological associations with mutation burden.

Bladder cancers are a leading cause of death from malignancy. Molecular markers might predict disease progression and behaviour more accurately than the available prognostic factors. Here we use whole-genome sequencing to identify somatic mutations and chromosomal changes in 14 bladder cancers of different grades and stages. As well as detecting the known bladder cancer driver mutations, we report the identification of recurrent protein-inactivating mutations in CDKN1A and FAT1. The former are not mutually exclusive with TP53 mutations or MDM2 amplification, showing that CDKN1A dysfunction is not simply an alternative mechanism for p53 pathway inactivation. We find strong positive associations between higher tumour stage/grade and greater clonal diversity, the number of somatic mutations and the burden of copy number changes. In principle, the identification of sub-clones with greater diversity and/or mutation burden within early-stage or low-grade tumours could identify lesions with a high risk of invasive progression.

The impact of agglomeration and storage on flavor and flavor stability of whey protein concentrate 80% and whey protein isolate.

The impact of agglomeration on flavor and flavor stability of whey protein concentrates 80% (WPC80) and whey protein isolates (WPI) has not been widely addressed. This study examined the impact of agglomeration on the flavor and flavor stability of commercial WPC80 and WPI across 18 mo of storage. Duplicate agglomerated and nonagglomerated WPC80 and WPI were collected from 4 facilities and stored at 21 degrees C, 50% relative humidity. Volatile analysis using solid phase microextraction (SPME) with gas chromatography-mass spectrometry (GC-MS) and descriptive sensory analysis were conducted every 2 mo. Solubility index, bulk volume, dispersibility, moisture, and color (L, a, b) were tested every 3 or 6 mo. Consumer acceptance testing with protein beverages was conducted with fresh and stored whey proteins. Higher intensities and more rapid development of lipid oxidation flavors (cardboard, raisin/brothy, cucumber, and fatty) were noted in agglomerated powders compared to nonagglomerated powders (P < 0.05). Volatile analysis results confirmed sensory results, which indicated increased formation of aldehydes and ketones in agglomerated products compared to nonagglomerated powders (P < 0.05). Consumer acceptance scores for protein beverages were lower for beverages made with agglomerated WPC80 stored for 12 mo and agglomerated or nonagglomerated WPI stored for 18 mo compared to fresh products while trained panelists detected differences among beverages and rehydrated proteins earlier. Agglomeration with or without lecithin decreased the storage stability of whey proteins. These results indicate that the optimum shelf life at 21 degrees C for nonagglomerated whey proteins is 12 to 15 mo and 8 to 12 mo for agglomerated whey proteins.

Effectiveness of computer-assisted instruction in increasing the rate of universal precautions--related behaviors.

BACKGROUND: With widespread noncompliance to universal precautions well established, an experimental study was designed to compare the rate of universal precautions--related behaviors between nurses who participate in computer-assisted instruction. This study also explored the relationship between rates of universal precautions--related behaviors and subjects' demographic and experiential characteristics and history of occupational blood-borne exposure. METHODS: Data were collected by using a questionnaire to elicit information as to subjects' demographic and experiential characteristics and history of occupational blood-borne exposure. The Universal Precautions Assessment Tool was used to gather data on rates of universal precautions--related behaviors on two groups of registered nurses with 30 subjects per group. RESULTS: By using analysis of variance, the null hypothesis was rejected. The intervention used in this study did increase universal precautions--related behaviors. Multiple regression was used to analyze the research question and none of the variables were significant. Forty (67.8%) subjects reported receiving a needlestick or cut caused by a needle or sharp that was actually or potentially contaminated with blood or body fluids. Of these exposures, only one patient was known to be HIV antibody positive. CONCLUSION: Replication studies using computer-assisted instruction interventions are needed as are studies aimed at exploring other potentially effective interventions.

Effect of physical exercise on the performance of cognitive tasks.

This experiment examined the effect of physical exercise on measures of cognitive performance, Raven's Matrices, and an adaptation of the revised WAIS arithmetic subtest. We also tested the inverted-U hypothesis of an interactive relation between exercise-induced arousal and cognitive performance. 50 physically active men were assigned to five groups (n = 10) of equal physical fitness based on predicted maximum oxygen uptake. Three exercise groups undertook bench stepping at mean power outputs of either 47, 75, or 120 watts. One control group played Bingo and another control had no activity. There was no change in the Raven's Matrices scores pre- to posttest intervention, neither were there any between-group differences either pre- or posttest. The arithmetic scores were significantly higher over-all (p < .05) on the posttest, but there were no reliable differences between groups either pre- or posttest. These results suggest that short duration (6 min.) aerobic exercise has no effect on cognitive performance. This finding supports the majority of previous studies that used step-up tasks to examine the relation between physical exercise and cognitive performance.

Degree of ethoxyquin-induced nephrotoxicity in rat is dependent on age and sex.

The toxicity of ethoxyquin (EQ) to rat kidney was examined in males which were either weanling or adult at the beginning of the experiment, and also in adult females. Female rats were much less susceptible to the toxic effects of EQ than males of the same age. In males damage to the cortex, mainly as an acceleration of the normal ageing process, was similar in both age groups, but rats exposed to EQ as weanlings also suffered from extensive papillary necrosis. Male rats were more prone than females to proteinuria, which was greatly exacerbated by EQ in both age groups. Thus there is very little evidence of nephrotoxicity in adult female rats on exposure to EQ at 0.5% in the diet for 26 weeks. In males, the initial age of the animal, as well as the length of treatment, influences the extent of damage.

Protection by WR-151327 against late-effect damage from fission-spectrum neutrons.

The mutagenic and carcinogenic properties of fission-spectrum neutrons (KERMA-weighted mean energy of 0.85 MeV) from Argonne National Laboratory's JANUS reactor are substantially greater than those of low-LET radiation sources such as X-ray and 60Co photons. However, in contrast to the vast amount of work focused on chemical protection against damage induced by low-LET radiation, studies on the prevention of carcinogenic damage induced by fission neutrons have been limited. We have investigated the protective properties of the thiophosphorate compound S-3-(3-methylaminopropylamino)propylphosphorothioic acid (WR-151327) against carcinogenesis and life shortening in the B6CF1 hybrid mouse strain. Male and female mice, 200 of each sex per experimental group, were irradiated individually at 110 days of age. WR-151327 was administered intraperitoneally at a dose of 580 mg/kg 30 min prior to irradiation with a dose of 10 cGy. Animals were housed five to a cage; cage locations in holding rooms were controlled by computer and randomized. Mice were checked daily and all deceased animals were necropsied. A neutron dose of 10 cGy significantly altered the patterns of death of male and female animals compared to corresponding unirradiated control groups (logrank P values of 0.01 and 0.07, respectively). This was evidenced by a shortening of the life span due to tumor induction in the irradiated groups. WR-151327, when administered 30 min prior to irradiation, effectively protected both male and female animals from these effects. The life curves of irradiated male and female animals and those of corresponding unirradiated control groups were not significantly different (logrank P values of 0.63 and 0.25, respectively).

Effects of rat strain, diet composition, and phenobarbital on hepatic gamma-glutamyl transpeptidase histochemistry and on the induction of altered hepatocyte foci and hepatic tumors by diethylnitrosamine.

To extend our ongoing characterization of modulatory influences on hepatic tumorigenesis, we examined effects of rat strain (Sprague-Dawley versus Fischer), diet composition (semipurified diet versus standard nonpurified laboratory chow), and dietary phenobarbital on the production of gamma-glutamyl transpeptidase (GGT)-positive hepatocyte foci and hepatic tumors initiated by diethylnitrosamine. In addition to GGT-positive foci, we observed, under certain conditions, the appearance of extensive hepatic GGT staining not associated with focal lesions. This elevated nonfocal GGT was found in rats of both strains fed the nonpurified rather than the purified diet, but the level of staining was higher in Fischer than in Sprague-Dawley rats. Enhancement of this nonfocal staining by dietary phenobarbital appeared insignificant. By comparison, frequencies of GGT-positive foci were generally higher in rats fed the semipurified rather than the nonpurified diet, and the frequencies of GGT-positive foci were invariably higher in Sprague-Dawley than in Fischer rats. Moreover, dietary phenobarbital generally enhanced focus production. Assessments of focus and tumor yields among these experimental groups showed that differences in focus frequencies did not correspond closely to differences in subsequent tumor formation. These results document the need to consider the influences of diet and rat strain on experimental end points in designing protocols for hepatocarcinogenesis studies, especially those involving GGT histochemistry. The data also raise questions about the mechanistic relevance of GGT induction to hepatocarcinogenesis and support our prior evidence against the putative lineal relationship between foci and tumors.

Improvement of iron removal from the reticuloendothelial system by liposome encapsulation of N,N'-bis[2-hydroxybenzyl]-ethylenediamine-N,N'-diacetic acid (HBED). Comparison with desferrioxamine.

An iron chelator of low water solubility, HBED, has been encapsulated in the lipid bilayers of unilamellar and multilamellar liposomes. The effectiveness of liposome-encapsulated HBED for removing excess iron burden from the RE system of the mouse liver (i.e., Kupffer cells) has been compared to that of the most commonly used iron chelator, DF, a water-soluble drug. We report the following: (1) At a single dose of 25 mg/kg, HBED in liposomes is more effective in removing excess iron than free nonencapsulated HBED. (2) HBED is a more potent iron chelator than DF; after a single dose of 25 mg/kg, about 25% of the originally injected iron is excreted within 7 days from mice given HBED either in small unilamellar or in large multilamellar liposomes, whereas about 18% is excreted from mice given the same dose of liposome-encapsulated DF. (3) Although the iron burden is introduced into the Kupffer cells, liposome-encapsulated HBED promotes iron excretion mainly via the bile and feces, whereas liposome-encapsulated DF promotes iron excretion through the kidney. (4) Cell fractionation studies show that encapsulation of HBED in the lipid bilayers of liposomes does not alter the uptake pattern of liposomes by the Kupffer and parenchymal cells of the liver; in other words, Kupffer cells are more effective in taking up large-sized multilamellar liposomes while parenchymal cells take up small-sized unilamellar liposomes more effectively. (5) Electron microscopic studies demonstrate that the liver biliary canaliculi are enlarged and filled with vesicular materials in mice given liposome-encapsulated HBED and that this condition does not occur in control mice or mice given liposome-encapsulated DF. Our results have thus demonstrated that liposomes could be very useful as injection vehicles for metal chelators that are not readily soluble in water. HBED is also demonstrated to be far superior to DF, the iron chelator of choice for therapy of transfusional iron overload.

Differential uptake of liposomes varying in size and lipid composition by parenchymal and kupffer cells of mouse liver.

Using liposomes differing in size and lipid composition, we have studied the uptake characteristics of the liver parenchymal and Kupffer cells. Desferal labeled with iron-59 was chosen as a radiomarker for the liposomal content, because Desferal in its free form does not cross cellular membranes. At various time intervals after an intravenous injection of liposomes into mice, the liver was perfused with collagenase, and the cells were separated in a Percoll gradient. It was found that large multilamellar liposomes (diameter of about 0.5 micron) were mainly taken up by the Kupffer cells. For these large liposomes, the rate of uptake by Kupffer cells was rapid, with maximum uptake at around 2 hours after liposome injection. Unexpectedly, small unilamellar liposomes (diameter of about 0.08 micron) were less effectively taken up by Kupffer cells, and the rate of uptake was slow, with a maximum uptake at about 10 hours after liposome injection. In contrast, parenchymal cells were more effective in taking up small liposomes and the uptake of large liposomes was negligible. In addition, liposomes made with a galactolipid as part of the lipid constituents appeared to have higher affinity to parenchymal cells than liposomes made without the galactolipid. These findings should be of importance in designing suitable liposomes for drug targeting.

The labelling of dispensed medicines for the elderly patient: a pilot survey.

The problems that elderly patients encounter when managing their own drugs were approached from the point of view of the understanding that these patients have of the labels on dispensed medicines. Thirty medically qualified volunteers at Burton District Hospital Centre were used to evaluate the adequacy of the present handwritten, labelling system for elderly out-patients by the use of a questionnaire. Further, by means of structured interviews with thirty elderly out-patients and a discriminating test procedure, the proposed, new, typed, labelling system was compared with two other labelling systems, the ability of the patients to understand the labels determined and the efficiency of the proposed, new system tested. The trends indicated by this pilot survey are that the present system of handwritten labels is inadequate and inefficient. Medical staff may repeatedly go over instructions and patients identify their drugs by means other than the label. Regardless of the quality of the label the regimen for a particular patient often determines the necessity for repeat instructions. Further, the proposed, typed, labelling system was ranked last by staff and patients when compared with two other systems (Ladywell and Thomas). The ability of patients to understand typed labels was very low. A new labelling system based on these trends is proposed.

Preparation and observation by SEM of hemopoietic cells cloned in soft agar.

A method is described to prepare clones of hemopoietic cells grown in soft agar for scanning electron microscopy (SEM). A critical modification of the otherwise quite standard SEM processing procedure for biological samples involved the use of silver micropore disks as an adherent substrate to support the highly labile, deformable agar slabs. This support allows maintenance of the normal flat pancake shape of the specimen through the thiocarbohydrazide osmium ligand binding steps, dehydration, and critical point drying. With this support and careful dissection of the surface agar with a fine steel needle using a stereomicroscope, selected areas and depths within the colony can be exposed and examined by SEM. Surface topography of cloned cells can be correlated with intracellular cytological features by excising areas of interest and directly embedding them in plastic for thin-section preparation and viewing by transmission electron microscopy (TEM). The dried-specimen-teasing method appears useful, because of the ease of preparation of the specimens, its reproducibility, and the degree of visibility and preservation of cell surface structures and intraclonal relationships. Our initial observations, using combined EM techniques, indicate that clonal cell topography is highly variable and that this variability appears to be related both to the relative age and proliferative status of the colony. Based on work to date, we suggest that topographical and spatial analysis, in vitro of cloned, agar-embedded hemopoietic stem cells is possible with simple modifications of conventional SEM preparative techniques.

Correlation of plasma cholinesterase activity and duration of action of succinylcholine during pregnancy.

Correlation between plasma cholinesterase activity and duration of neuromuscular blockade following succinylcholine (SCh) was studied in 30 healthy women undergoing laparoscopic tubal coagulation and 20 pregnany women indergoing elective repeat cesarean section. All patients received N2O-thiopental anesthesia. Cholinesterase activity in nonpregnant patients was significantly greater than in pregnant patients. Time to 90 percent recovery of control twitch height following 40 or 80 mg/m2 BSA of SCh was not significantly different in pregnant versus nonpregnant patients. There also was no correlation between plasma cholinesterase activity and duration of paralysis from SCh. The authors conclude that pregnant patients have lower cholinesterase activity, but prolonged neuromuscular blockade from SCh should not occur unless the patient is grossly overdosed with SCh. Routine use of a peripheral nerve stimulator is recommended to avoid such overdosage.