Do we need to fix the anterior fracture component in insufficiency fractures of the pelvis? A biomechanical comparison on an FFP type IIIc fracture in an osteoporotic pelvic bone model.

There is a growing understanding of the specific characteristics of insufficiency fractures of the pelvis and of general requirements for the treatment of affected patients with focus on early mobilization and effective pain reduction as the main goals of therapy. While there is consensus on the significance of achieving stability of the dorsal pelvic ring structures there is still an open discussion about the potential benefits of additional stabilization of an anterior fracture component. Within a biomechanical test setup, two established methods of dorsal fracture fixation were tested under axial loading (25-1200 N; 1000 test cycles) on an explicit osteoporotic bone model (n = 32) with a standardized FFP type IIIc fracture with and without additional fixation of the anterior fracture component. Dorsal fixation was performed with and long and a short 7.3 mm cannulated screw in S1 in one group (n = 16), and a trans sacral bar with an additional short 7.3 mm cannulated screw in S1 in the other group (n = 16). Half of the samples received a 7.3 mm cannulated retrograde transpubic screw for anterior fixation. The fixation with the trans sacral bar and the additional anterior screw fixation showed the highest rate of stability (p = 0.0014), followed by the double SI-screw fixation with stabilization of the anterior fracture (p = 0.0002). During testing, we observed the occurrence of new sacral fractures contralateral to the initial fracture in 22/32 samples. The results let us assume that stabilization of an additional anterior fracture component relevantly improves the stability of the entire ring construct and might prevent failure of the dorsal stabilization or further fracture progression.

Diabetes, but Not Hypertension and Obesity, Is Associated with Postoperative Cognitive Dysfunction.

BACKGROUND/AIMS: Older people undergoing surgery are at risk of developing postoperative cognitive dysfunction (POCD), but little is known of risk factors predisposing patients to POCD. Our objective was to estimate the risk of POCD associated with exposure to preoperative diabetes, hypertension, and obesity. METHODS: Original data from 3 randomised controlled trials (OCTOPUS, DECS, SuDoCo) were obtained for secondary analysis on diabetes, hypertension, baseline blood pressure, obesity (BMI ≥30 kg/m2), and BMI as risk factors for POCD in multiple logistic regression models. Risk estimates were pooled across the 3 studies. RESULTS: Analyses totalled 1,034 patients. POCD occurred in 5.2% of patients in DECS, in 9.4% in SuDoCo, and in 32.1% of patients in OCTOPUS. After adjustment for age, sex, surgery type, randomisation, obesity, and hypertension, diabetes was associated with a 1.84-fold increased risk of POCD (OR 1.84; 95% CI 1.14, 2.97; p = 0.01). Obesity, BMI, hypertension, and baseline blood pressure were each not associated with POCD in fully adjusted models (all p > 0.05). CONCLUSION: Diabetes, but not obesity or hypertension, is associated with increased POCD risk. Consideration of diabetes status may be helpful for risk assessment of surgical patients.

Association of obesity, diabetes and hypertension with cognitive impairment in older age.

BACKGROUND: Age-related cognitive impairment is rising in prevalence but is not yet fully characterized in terms of its epidemiology. Here, we aimed to elucidate the role of obesity, diabetes and hypertension as candidate risk factors. METHODS: Original baseline data from 3 studies (OCTOPUS, DECS, SuDoCo) were obtained for secondary analysis of cross-sectional associations of diabetes, hypertension, blood pressure, obesity (body mass index [BMI] ≥30 kg/m2) and BMI with presence of cognitive impairment in log-binomial regression analyses. Cognitive impairment was defined as scoring more than 2 standard deviations below controls on at least one of 5-11 cognitive tests. Underweight participants (BMI<18.5 kg/m2) were excluded. Results were pooled across studies in fixed-effects inverse variance models. RESULTS: Analyses totaled 1545 participants with a mean age of 61 years (OCTOPUS) to 70 years (SuDoCo). Cognitive impairment was found in 29.0% of participants in DECS, 8.2% in SuDoCo and 45.6% in OCTOPUS. In pooled analyses, after adjustment for age, sex, diabetes and hypertension, obesity was associated with a 1.29-fold increased prevalence of cognitive impairment (risk ratio [RR] 1.29; 95% CI 0.98, 1.72). Each 1 kg/m2 increment in BMI was associated with 3% increased prevalence (RR 1.03; 95% CI 1.00, 1.06). None of the remaining risk factors were associated with impairment. CONCLUSION: Our results show that older people who are obese have higher prevalence of cognitive impairment compared with normal weight and overweight individuals, and independently of co-morbid hypertension or diabetes. Prospective studies are needed to investigate the temporal relationship of the association.

A Guinea pig cytomegalovirus resistant to the DNA maturation inhibitor BDCRB.

Herpesvirus DNA packaging is an essential step in virion morphogenesis and an important target for antiviral development. The halogenated benzimidazole 2-bromo-5,6-dichloro-1-ß-d-ribofuranosyl-1H-benzimidazole (BDCRB) was the first compound found to selectively disrupt DNA packaging. It has activity against human cytomegalovirus as well as guinea pig cytomegalovirus. The latter provides a useful small animal model for congenital cytomegalovirus infection. To better understand the mechanism by which BDCRB acts, a guinea pig cytomegalovirus resistant to BDCRB was derived and characterized. An L406P substitution occurred within GP89, a subunit of the complex that cleaves and packages DNA, but transfer of this mutation to an otherwise wild type genetic background did not confer significant BDCRB resistance. The resistant virus also had a 13.4-kb deletion that also appeared to be unrelated to BDCRB-resistance as a virus with a similar spontaneous deletion was sensitive to BDCRB. Lastly, the BDCRB-resistant virus exhibited a dramatic increase in the number of reiterated terminal repeats at both genomic termini. The mechanism that underlies this change in genome structure is not known but may relate to the duplication of terminal repeats that is associated with DNA cleavage and packaging. A model is presented in which BDCRB impairs the ability of terminase to recognize cleavage site sequences, but repeat arrays overcome this impairment by presenting terminase with multiple opportunities to recognize the correct cleavage site sequences that lie within the repeats. Further elucidation of this phenomenon should prove valuable for understanding the molecular basis of herpesvirus DNA maturation and the mechanism of action of this class of drugs.

Effects of dexamethasone on cognitive decline after cardiac surgery: a randomized clinical trial.

BACKGROUND: Cardiac surgery can be complicated by postoperative cognitive decline (POCD), which is characterized by impaired memory function and intellectual ability. The systemic inflammatory response that is induced by major surgery and cardiopulmonary bypass may play an important role in the etiology of POCD. Prophylactic corticosteroids to attenuate the inflammatory response may therefore reduce the risk of POCD. The authors investigated the effect of intraoperative high-dose dexamethasone on the incidence of POCD at 1 month and 12 months after cardiac surgery. METHODS: This multicenter, randomized, double-blind, placebo-controlled trial is a preplanned substudy of the DExamethasone for Cardiac Surgery trial. A total of 291 adult patients undergoing cardiac surgery with cardiopulmonary bypass were recruited in three hospitals and randomized to receive dexamethasone 1 mg/kg (n = 145) or placebo (n = 146). The main outcome measures were incidence of POCD at 1- and 12-month follow-up, defined as a decline in neuropsychological test performance beyond natural variability, as measured in a control group. RESULTS: At 1-month follow-up, 19 of 140 patients in the dexamethasone group (13.6%) and 10 of 138 patients in the placebo group (7.2%) fulfilled the diagnostic criteria for POCD (relative risk, 1.87; 95% CI, 0.90 to 3.88; P = 0.09). At 12-month follow-up, 8 of 115 patients in the dexamethasone group (7.0%) and 4 of 114 patients (3.5%) in the placebo group had POCD (relative risk, 1.98; 95% CI, 0.61 to 6.40; P = 0.24). CONCLUSION: Intraoperative high-dose dexamethasone did not reduce the risk of POCD after cardiac surgery.

Intraoperative dexamethasone and delirium after cardiac surgery: a randomized clinical trial.

BACKGROUND: Delirium is common after cardiac surgery and may be partly related to the systemic inflammatory response triggered by the surgery and the use of cardiopulmonary bypass. We hypothesized that intraoperative administration of high-dose dexamethasone, a drug with potent anti-inflammatory effects, would reduce the incidence of delirium at any time point during the first 4 postoperative days after cardiac surgery. METHODS: This was a single-center substudy within a larger, multicenter placebo-controlled randomized clinical trial, the Dexamethasone for Cardiac Surgery (DECS) trial that randomized patients ≥18 years, undergoing cardiac surgery with cardiopulmonary bypass, to receive, in a double-blind fashion, either dexamethasone 1 mg/kg or placebo at the induction of anesthesia. Over the first 4 postoperative days, we compared between groups the incidence of delirium (based on the Confusion Assessment Method adapted for the intensive care unit, or after intensive care unit discharge, by the Confusion Assessment Method, accompanied by chart review), restraint use, and administered haloperidol, benzodiazepines, and opioids. Data were analyzed according to the intention-to-treat principle. The proportion of patients with delirium in the dexamethasone versus the placebo group was compared using the odds ratio (OR) with a 95% confidence interval (CI). The proportion also was compared using logistic regression to adjust for common baseline variables that might confound the presence of delirium between the 2 groups. RESULTS: Of 768 eligible patients, 737 subjects (96.0%) had complete data. The incidence of delirium was similar between the dexamethasone (14.2%) and placebo (14.9%) groups (crude OR = 0.95, 95% CI, 0.63-1.43; adjusted OR = 0.85, 95% CI, 0.55-1.31). Among patients who developed delirium, the median (interquartile range) duration of delirium was similar between the dexamethasone and placebo groups (2 [1-3] vs 2 [1-2] days, respectively, P = 0.45; WMWodds 0.98, 95% CI, 0.83-1.17). Restraint use and the administration of haloperidol, benzodiazepines, and opioids were also similar between the 2 groups. CONCLUSIONS: The intraoperative administration of dexamethasone did not reduce the incidence or duration of delirium in the first 4 days after cardiac surgery.

Characterization of the sialic acid binding activity of influenza A viruses using soluble variants of the H7 and H9 hemagglutinins.

Binding of influenza viruses to target cells is mediated by the viral surface protein hemagglutinin. To determine the presence of binding sites for influenza A viruses on cells and tissues, soluble hemagglutinins of the H7 and H9 subtype were generated by connecting the hemagglutinin ectodomain to the Fc portion of human immunoglobulin G (H7Fc and H9Fc). Both chimeric proteins bound to different cells and tissues in a sialic acid-dependent manner. Pronounced differences were observed between H7Fc and H9Fc, in the binding both to different mammalian and avian cultured cells and to cryosections of the respiratory epithelium of different virus host species (turkey, chicken and pig). Binding of the soluble hemagglutinins was similar to the binding of virus particles, but showed differences in the binding pattern when compared to two sialic acid-specific plant lectins. These findings were substantiated by a comparative glycan array analysis revealing a very narrow recognition of sialoglycoconjugates by the plant lectins that does not reflect the glycan structures preferentially recognized by H7Fc and H9Fc. Thus, soluble hemagglutinins may serve as sialic acid-specific lectins and are a more reliable indicator of the presence of binding sites for influenza virus HA than the commonly used plant lectins.

Cognitive outcomes 7.5 years after angioplasty compared with off-pump coronary bypass surgery.

BACKGROUND: Off-pump coronary artery bypass grafting and percutaneous coronary intervention are both associated with cognitive decline, but limited data are available on long-term outcomes. This study compared long-term cognitive outcomes between patients managed with percutaneous coronary intervention and off-pump coronary artery bypass grafting. METHODS: A multicenter trial in the Netherlands randomized 280 patients to percutaneous coronary intervention or off-pump coronary artery bypass grafting. Cognitive performance 7.5 years after randomization was assessed through a battery of 9 neuropsychologic tests and summarized into a combined Z-score. RESULTS: After 7.5 years, cognitive assessment could be performed in 81% of the 249 surviving patients. Better cognitive performance was observed in the off-pump coronary artery bypass grafting group (combined Z-score 0.11 for off-pump coronary artery bypass grafting versus -0.17 for percutaneous coronary intervention; difference 0.28, 95% confidence interval 0.08 to 0.47, p < 0.01). However, this difference became nonsignificant (Z-score difference 0.14, 95% confidence interval -0.01 to 0.29, p = 0.08) after multivariable adjustment for potential confounders. CONCLUSIONS: At 7.5 years follow-up, off-pump coronary artery bypass grafting patients had a similar or perhaps even better cognitive performance compared with percutaneous coronary intervention patients.

The effects of risk-glorifying media exposure on risk-positive cognitions, emotions, and behaviors: a meta-analytic review.

In recent years, there has been a surge in the quantity of media content that glorifies risk-taking behavior, such as risky driving, extreme sports, or binge drinking. The authors conducted a meta-analysis involving more than 80,000 participants and 105 independent effect sizes to examine whether exposure to such media depictions increased their recipients' risk-taking inclinations. A positive connection was found for overall, combined risk taking (g=.41); as well as its underlying dimensions: risk-taking behaviors (g=.41), risk-positive cognitions and attitudes (g=.35), and risk-positive emotions (g=.56). This effect was observed across varying research methods (experimental, correlational, longitudinal); types of media (video games, movies, advertising, TV, music); and differing risk-related outcome measures (e.g., smoking, drinking, risky driving, sexual behavior). Multiple moderator analyses revealed 2 theoretically new boundary conditions for sociocognitive models. First, the effect was stronger for active (i.e., video games) than for passive (e.g., film, music) exposure to risk-glorifying media content. Second, the effect was stronger when there was a high degree of contextual fit between the media content and type of risk-taking measure. The theoretical, practical, and societal implications of the present research synthesis are discussed.

Peptides from cytomegalovirus UL130 and UL131 proteins induce high titer antibodies that block viral entry into mucosal epithelial cells.

Cytomegalovirus infections are an important cause of disease for which no licensed vaccine exists. Recent studies have focused on the gH/gL/UL128-131 complex as antibodies to gH/gL/UL128-131 neutralize viral entry into epithelial cells. Prior studies have used cells from the retinal pigment epithelium, while to prevent transmission, vaccine-induced antibodies may need to block viral infection of epithelial cells of the oral or genital mucosa. We found that gH/gL/UL128-131 is necessary for efficient viral entry into epithelial cells derived from oral and genital mucosa, that short peptides from UL130 and UL131 elicit high titer neutralizing antibodies in rabbits, and that such antibodies neutralize viral entry into epithelial cells derived from these relevant tissues. These results suggest that single subunits or peptides may be sufficient to elicit potent epithelial entry neutralizing responses and that secretory antibodies to such neutralizing epitopes have the potential to provide sterilizing immunity by blocking initial mucosal infection.

Structural requirements for repellency: norsesquiterpenes and sesquiterpenoid derivatives of nootkatone against the Formosan subterranean termite (Isoptera: Rhinotermitidae).

BACKGROUND: Research has shown that the family of grapefruit flavors called nootkatones have significant repellant and toxic effects to Formosan subterranean termites (Coptotermes formosanus Shiraki). RESULTS: Nineteen synthetic nootkatone derivatives, along with three commercially available nootkatone derivatives, were tested for repellent activity against C. formosanus by a choice assay in a petri dish with a two-step triage procedure. Based on the repellency threshold value, the relationships between structure and activity are discussed. CONCLUSION: Four derivatives of nootkatone have very high repellency and toxicity to C. formosanus, 9 times the potency of the primary compound nootkatone. Four other compounds have between 2 and 3 times the repellency of nootkatones, and three compounds are equal in their repellency to nootkatone.

A human cytomegalovirus deleted of internal repeats replicates with near wild type efficiency but fails to undergo genome isomerization.

The class E genome of human cytomegalovirus (HCMV) contains long and short segments that invert due to recombination between flanking inverted repeats, causing the genome to isomerize into four distinct isomers. To determine if isomerization is important for HCMV replication, one copy of each repeat was deleted. The resulting virus replicated in cultured human fibroblasts with only a slight growth impairment. Restriction and Southern analyses confirmed that its genome is locked in the prototypic arrangement and unable to isomerize. We conclude that efficient replication of HCMV in fibroblasts does not require (i) the ability to undergo genome isomerization, (ii) genes that lie partially within the deleted repeats, or (iii) diploidy of genes that lie wholly within repeats. The simple genomic structure of this virus should facilitate studies of genome circularization, latency or persistence, and concatemer packaging as such studies are hindered by the complexities imposed by isomerization.

Ethyl 2-(2,3,4,5,6-Penta-bromo-phen-yl)acetate.

The title compound PBPEA, C(10)H(7)Br(5)O(2), has its ethyl acetate portion nearly orthogonal to the benzene ring, with a C-C-C-C torsion angle of 88.3 (5)°. The packing involves an inter-molecular contact with a Br⋯Br distance of 3.491 (1) Å, having C-Br⋯Br angles of 173.4 (2) and 106.0 (2)°. The crystal studied was an inversion twin.

An efficient and economic asymmetric synthesis of (+)-nootkatone, tetrahydronootkatone, and derivatives.

A facile route to enantiomerically pure (+)-nootkatone and derivatives has been established through conjunctive stereoselective Grignard/anionic oxy-Cope (AOC) reactions.

Inactivation of Escherichia coli ATCC 25922 and Escherichia coil O157:H7 in apple juice and apple cider, using pulsed light treatment.

The main objective of this work was to evaluate the effectiveness of pulsed light (PL) treatment for the inactivation of Escherichia coli in liquids with different levels of clarity. Nonpathogenic E. coli ATCC 25922 and pathogenic E. coli O157: H7 were used as challenge organisms. Butterfield's phosphate buffer (BPB), tryptic soy broth (TSB), apple juice, and apple cider were used as substrates. The inoculated liquids were placed in a thin layer (1.3 mm) into glass chambers (23 by 53 by 11 mm) and exposed to PL doses of up to 13.1 J/cm2. PL treatments were performed in a Xenon RS-3000C PL unit, both in static mode and under turbulence. Survivors were determined by standard plate counting or the most-probable-number technique. For static treatments, reduction levels exceeding 8.5 log were obtained in BPB for all strains and reduction levels of about 3.5 log were obtained in TSB. For apple juice, inactivation levels of 2.66 +/- 0.10 log were obtained for E. coli ATCC 25922 and 2.52 +/- 0.19 log for E. coli O157:H7. In cider, inactivation levels of 2.32 +/- 0.16 log and 3.22 +/- 0.29 log were obtained for the nonpathogenic and pathogenic strains, respectively. Inactivation kinetics was characterized using the Weibull model. Turbulent treatments resulted in 5.76 +/- 0.06 log reduction in cider and 7.15 +/- 0.22 log reduction in juice, which satisfies the U.S. Food and Drug Administration requirement of 5-log reduction of E. coli. These results show promise for the use of PL for the effective reduction of E. coli in apple juice and cider.

Postoperative cognitive decline.

Memory loss and lack of concentration are symptoms that frequently occur in patients who have undergone a surgical procedure. Although cognitive function can be assessed using neuropsychological tests, reliable diagnosis of postoperative cognitive decline (POCD) appears to be difficult. Therefore, the true incidence of POCD is unknown. Severe POCD, which is apparent even without neuropsychological testing, is reported most frequently after cardiac and hip-replacement surgery. In these cases, POCD probably reflects microembolic brain injury. Apart from the nature of the surgical procedure, advanced age is the most important risk factor for POCD. The anesthetic technique is not a determinant of POCD: the risk of POCD appears to be similar after both general and regional anesthesia.

Presence of coronary collaterals is associated with a decreased incidence of cognitive decline after coronary artery bypass surgery.

OBJECTIVE: Coronary artery bypass grafting (CABG) is associated with significant cerebral morbidity, usually manifested as cognitive decline or stroke. The underlying mechanism leading to cognitive decline is still unclear. Presence of coronary collateral arteries, which may reflect an overall better cardiovascular condition, recently appeared to relate to a better cardiac outcome after CABG. In this study, we investigated the hypothesis that presence of coronary collaterals is associated with less cognitive decline after coronary artery bypass grafting. METHODS: Data from 281 patients undergoing first-time coronary artery bypass grafting were used. Presence of coronary collaterals was determined on the preoperative angiogram. Cognitive function was evaluated before the operation, at 3 and 12 months and 5 years thereafter by standardised neuropsychological assessment. Cognitive decline in individuals was determined by calculating the reliable change score, a cognitive change score corrected for natural testing variability and practice effects. RESULTS: Cognitive decline was found in 19 (8%) patients at 3 months, in 31 (12%) patients at 12 months and in 82 (34%) at 5 years follow-up. Presence of coronary collaterals was independently associated with a better cognitive outcome at both 3 months (odds ratio (OR) 0.30; 95% confidence interval (CI) 0.09-0.95; p=0.04) and 12 months (OR 0.42; 95% CI 0.18-0.97; p=0.04) after coronary artery bypass grafting. At 5 years, the OR was 0.57 (95% CI 0.31-1.05; p=0.07). CONCLUSIONS: In patients undergoing first-time coronary artery bypass grafting, presence of coronary collaterals is associated with a decreased risk of cognitive decline at both 3 and 12 months of follow-up. This trend persists at 5-year follow-up. Preoperative differences in the cardiac vascular condition may therefore predict cognitive outcome in patients undergoing coronary artery bypass grafting.

The sesquiterpenoid nootkatone and the absolute configuration of a dibromo derivative.

Nootkatone, or (4R,4aS,6R)-4,4a,5,6,7,8-hexahydro-4,4a-dimethyl-6-(1-methylethenyl)naphthalen-2(3H)-one, C(15)H(22)O, a sesquiterpene with strong repellent properties against Formosan subterranean termites and other insects, has the valencene skeleton. The dibromo derivative (1S,3R,4S,4aS,6R,8aR)-1,3-dibromo-6-isopropyl-4,4a-dimethyl-1,2,3,4,5,6,7,8-octahydronaphthalen-2-one, C(15)H(24)Br(2)O, has two independent molecules in the asymmetric unit, which differ in the rotation of the isopropyl group with respect to the main skeleton. The C-Br distances are in the range 1.950 (4)-1.960 (4) A. Both independent molecules form zigzag chains, with very short intermolecular carbonyl-carbonyl interactions, having the perpendicular motif and O...C distances of 2.886 (6) and 2.898 (6) A. These chains are flanked by intermolecular Br...Br interactions of distances in the range 4.067 (1)-4.218 (1) A. The absolute configuration of the dibromo derivative was determined, from which that of nootkatone was inferred.

Structure-activity of valencenoid derivatives and their repellence to the Formosan subterranean termite.

Eight valencenoid derivatives were evaluated for their repelling activity against Formosan subterranean termites, Coptotermes formosanus Shiraki. Among them, 1,10-dihydronootkatone was the strongest repellent, and valencene was the weakest. Results of the structure-repellency relationships indicated (1) reduction of the ketone group to the alcohol on position 2 of nootkatone curtailed the activity; (2) because of the low activity of valencene relative to nootkatone that the ketone group was essential for repellent activity; (3) reduction of the 1,10 double bond (1,10-dihydronootkatone and tetrahydronootkatone) produced compounds more repellent than nootkatone; (4) the isopropenyl group probably does not participate in binding as evidenced by no significant difference in the repellent activity among nootkatone (double bond between position 11 and 12), isonootkatone (double bond between position 7 and 11), and 11,12-dihydronootkatone.